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  1. Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells.

    PubMed

    Tsuneki, Hiroshi; Sekizaki, Naoto; Suzuki, Takashi; Kobayashi, Shinjiro; Wada, Tsutomu; Okamoto, Tadashi; Kimura, Ikuko; Sasaoka, Toshiyasu

    2007-07-02

    Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis of vascular complications in diabetes. Although some clinical evidences suggest the use of an antioxidant reagent coenzyme Q10 in diabetes with hypertension, the direct effect of coenzyme Q10 on the endothelial functions has not been examined. In the present study, we therefore investigated the protective effect of coenzyme Q10 against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVEC). HUVEC exposed to high glucose (30 mM) exhibited abnormal properties, including the morphological and biochemical features of apoptosis, overproduction of reactive oxygen species, activation of protein kinase Cbeta2, and increase in endothelial nitric oxide synthase expression. Treatment with coenzyme Q10 strongly inhibited these changes in HUVEC under high glucose condition. In addition, coenzyme Q10 inhibited high glucose-induced cleavage of poly(ADP-ribose) polymerase, an endogenous caspase-3 substrate. These results suggest that coenzyme Q10 prevents reactive oxygen species-induced apoptosis through inhibition of the mitochondria-dependent caspase-3 pathway. Moreover, consistent with previous reports, high glucose caused upregulation of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in HUVEC, and promoted the adhesion of U937 monocytic cells. Coenzyme Q10 displayed potent inhibitory effects against these endothelial abnormalities. Thus, we provide the first evidence that coenzyme Q10 has a beneficial effect in protecting against the endothelial dysfunction by high glucose-induced oxidative stress in vitro.

  2. Proanthocyanidins Prevent High Glucose-Induced Eye Malformation by Restoring Pax6 Expression in Chick Embryo

    PubMed Central

    Tan, Rui-Rong; Zhang, Shi-Jie; Li, Yi-Fang; Tsoi, Bun; Huang, Wen-Shan; Yao, Nan; Hong, Mo; Zhai, Yu-Jia; Mao, Zhong-Fu; Tang, Lu-Ping; Kurihara, Hiroshi; Wang, Qi; He, Rong-Rong

    2015-01-01

    Gestational diabetes mellitus (GDM) is one of the leading causes of offspring malformations, in which eye malformation is an important disease. It has raised demand for therapy to improve fetal outcomes. In this study, we used chick embryo to establish a GDM model to study the protective effects of proanthocyanidins on eye development. Chick embryos were exposed to high glucose (0.2 mmol/egg) on embryo development day (EDD) 1. Proanthocyanidins (1 and 10 nmol/egg) were injected into the air sac on EDD 0. Results showed that both dosages of proanthocyanidins could prevent the eye malformation and rescue the high glucose-induced oxidative stress significantly, which the similar effects were showed in edaravone. However, proanthocyanidins could not decrease the glucose concentration of embryo eye. Moreover, the key genes regulating eye development, Pax6, was down-regulated by high glucose. Proanthocyanidins could restore the suppressed expression of Pax6. These results indicated proanthocyanidins might be a promising natural agent to prevent high glucose-induced eye malformation by restoring Pax6 expression. PMID:26262640

  3. Proanthocyanidins Prevent High Glucose-Induced Eye Malformation by Restoring Pax6 Expression in Chick Embryo.

    PubMed

    Tan, Rui-Rong; Zhang, Shi-Jie; Li, Yi-Fang; Tsoi, Bun; Huang, Wen-Shan; Yao, Nan; Hong, Mo; Zhai, Yu-Jia; Mao, Zhong-Fu; Tang, Lu-Ping; Kurihara, Hiroshi; Wang, Qi; He, Rong-Rong

    2015-08-07

    Gestational diabetes mellitus (GDM) is one of the leading causes of offspring malformations, in which eye malformation is an important disease. It has raised demand for therapy to improve fetal outcomes. In this study, we used chick embryo to establish a GDM model to study the protective effects of proanthocyanidins on eye development. Chick embryos were exposed to high glucose (0.2 mmol/egg) on embryo development day (EDD) 1. Proanthocyanidins (1 and 10 nmol/egg) were injected into the air sac on EDD 0. Results showed that both dosages of proanthocyanidins could prevent the eye malformation and rescue the high glucose-induced oxidative stress significantly, which the similar effects were showed in edaravone. However, proanthocyanidins could not decrease the glucose concentration of embryo eye. Moreover, the key genes regulating eye development, Pax6, was down-regulated by high glucose. Proanthocyanidins could restore the suppressed expression of Pax6. These results indicated proanthocyanidins might be a promising natural agent to prevent high glucose-induced eye malformation by restoring Pax6 expression.

  4. A novel antioxidant peptide derived from wheat germ prevents high glucose-induced oxidative stress in vascular smooth muscle cells in vitro.

    PubMed

    Chen, Siyuan; Lin, Dingbo; Gao, Yulong; Cao, Xiaozhou; Shen, Xinchun

    2017-01-25

    The ingestion of whole wheat products is responsible for the prevention of a number of chronic diseases. The aim of this study is to characterize the molecular properties of a novel wheat germ-derived antioxidant peptide (AOP) in protection against high glucose-induced oxidative stress in vascular smooth muscle cells (VSMCs). AOP (amino acid sequence AREGETVVPG) was isolated from wheat germ albumin using dual-enzymatic hydrolysis/separation, followed by MS/MS. The in vitro IC50 value for Fe(2+) chelation was 0.77 mM. The stability of purified AOP was confirmed by hydrolyzation in a simulated gastrointestinal (GI) digestion system in vitro. Furthermore, AOP significantly prevented high glucose-induced cell growth by 37.4 ± 2.7%, decreased the generation of intracellular reactive oxygen species (ROS) by 22.3 ± 4.6%, suppressed the phosphorylation of PKCζ, AKT and Erk1/2, and inhibited Nox4 protein expression. Our findings suggested that AOP exerted a protective role against high glucose-induced oxidative stress through the inhibition of the PKCζ/Nox4 signaling pathway in VSMCs.

  5. The antioxidant silybin prevents high glucose-induced oxidative stress and podocyte injury in vitro and in vivo

    PubMed Central

    Khazim, Khaled; Gorin, Yves; Cavaglieri, Rita Cassia; Abboud, Hanna E.

    2013-01-01

    Podocyte injury, a major contributor to the pathogenesis of diabetic nephropathy, is caused at least in part by the excessive generation of reactive oxygen species (ROS). Overproduction of superoxide by the NADPH oxidase isoform Nox4 plays an important role in podocyte injury. The plant extract silymarin is attributed antioxidant and antiproteinuric effects in humans and in animal models of diabetic nephropathy. We investigated the effect of silybin, the active constituent of silymarin, in cultures of mouse podocytes and in the OVE26 mouse, a model of type 1 diabetes mellitus and diabetic nephropathy. Exposure of podocytes to high glucose (HG) increased 60% the intracellular superoxide production, 90% the NADPH oxidase activity, 100% the Nox4 expression, and 150% the number of apoptotic cells, effects that were completely blocked by 10 μM silybin. These in vitro observations were confirmed by similar in vivo findings. The kidney cortex of vehicle-treated control OVE26 mice displayed greater Nox4 expression and twice as much superoxide production than cortex of silybin-treated mice. The glomeruli of control OVE26 mice displayed 35% podocyte drop out that was not present in the silybin-treated mice. Finally, the OVE26 mice experienced 54% more pronounced albuminuria than the silybin-treated animals. In conclusion, this study demonstrates a protective effect of silybin against HG-induced podocyte injury and extends this finding to an animal model of diabetic nephropathy. PMID:23804455

  6. Punicalagin exerts protective effect against high glucose-induced cellular stress and neural tube defects.

    PubMed

    Zhong, Jianxiang; Reece, E Albert; Yang, Peixin

    2015-11-13

    Maternal diabetes-induced birth defects remain a significant health problem. Studying the effect of natural compounds with antioxidant properties and minimal toxicities on diabetic embryopathy may lead to the development of new and safe dietary supplements. Punicalagin is a primary polyphenol found in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumorigenic properties, suggesting a protective effect of punicalagin on diabetic embryopathy. Here, we examined whether punicalagin could reduce high glucose-induced neural tube defects (NTDs), and if this rescue occurs through blockage of cellular stress and caspase activation. Embryonic day 8.5 (E8.5) mouse embryos were cultured for 24 or 36 h with normal (5 mM) glucose or high glucose (16.7 mM), in presence or absence of 10 or 20 μM punicalagin. 10 μM punicalagin slightly reduced NTD formation under high glucose conditions; however, 20 μM punicalagin significantly inhibited high glucose-induced NTD formation. Punicalagin suppressed high glucose-induced lipid peroxidation marker 4-hydroxynonenal, nitrotyrosine-modified proteins, and lipid peroxides. Moreover, punicalagin abrogated endoplasmic reticulum stress by inhibiting phosphorylated protein kinase ribonucleic acid (RNA)-like ER kinase (p-PERK), phosphorylated inositol-requiring protein-1α (p-IRE1α), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP) and x-box binding protein 1 (XBP1) mRNA splicing. Additionally, punicalagin suppressed high glucose-induced caspase 3 and caspase 8 cleavage. Punicalagin reduces high glucose-induced NTD formation by blocking cellular stress and caspase activation. These observations suggest punicalagin supplements could mitigate the teratogenic effects of hyperglycemia in the developing embryo, and possibly prevent diabetes-induced NTDs.

  7. Punicalagin exerts protective effect against high glucose-induced cellular stress and neural tube defects

    PubMed Central

    Zhong, Jianxiang; Reece, E. Albert; Yang, Peixin

    2015-01-01

    Maternal diabetes-induced birth defects remain a significant health problem. Studying the effect of natural compounds with antioxidant properties and minimal toxicities on diabetic embryopathy may lead to the development of new and safe dietary supplements. Punicalagin is a primary polyphenol found in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumorigenic properties, suggesting a protective effect of punicalagin on diabetic embryopathy. Here, we examined whether punicalagin could reduce high glucose-induced neural tube defects (NTDs), and if this rescue occurs through blockage of cellular stress and caspase activation. Embryonic day 8.5 (E8.5) mouse embryos were cultured for 24 or 36 hours with normal (5 mM) glucose or high glucose (16.7 mM), in presence or absence of 10 or 20 µM punicalagin. 10 µM punicalagin slightly reduced NTD formation under high glucose conditions; however, 20 µM punicalagin significantly inhibited high glucose-induced NTD formation. Punicalagin suppressed high glucose-induced lipid peroxidation marker 4-hydroxynonenal, nitrotyrosine-modified proteins, and lipid peroxides. Moreover, punicalagin abrogated endoplasmic reticulum stress by inhibiting phosphorylated protein kinase ribonucleic acid (RNA)-like ER kinase (p-PERK), phosphorylated inositol-requiring protein-1α (p-IRE1α), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP) and x-box binding protein 1 (XBP1) mRNA splicing. Additionally, punicalagin suppressed high glucose-induced caspase 3 and caspase 8 cleavage. Punicalagin reduces high glucose-induced NTD formation by blocking cellular stress and caspase activation. These observations suggest punicalagin supplements could mitigate the teratogenic effects of hyperglycemia in the developing embryo, and possibly prevent diabetesinduced NTDs. PMID:26453010

  8. Ethanol extract of Moringa oliefera prevents in vitro glucose induced cataract on isolated goat eye lens

    PubMed Central

    Kurmi, Raghvendra; Ganeshpurkar, Aditya; Bansal, Divya; Agnihotri, Abhishek; Dubey, Nazneen

    2014-01-01

    Aim of Study: The aim of current work was to evaluate in vitro anticataract potential of Moringa oliefera extract. Materials and Methods: Goat eye lenses were divided into 4 groups; Group served as control, Group II as toxic control, Group III and Group IV were incubated in extract (250 μg/ml and 500 μg/ml of extract of M. oliefera) Group II, III and IV were incubated in 55 mM glucose in artificial aqueous humor to induce lens opacification. Estimation of total, water soluble protein, catalase, glutathione and malondialdehyde along with photographic evaluation of lens was done. Results: Group II (toxic control) lenses showed high amount of MDA (Malondialdehyde), soluble, insoluble protein, decreased catalase and glutathione levels, while lenses treated with Moringa oliefera extract (Group III and Group IV) showed significant (* P < 0.05) reduction in MDA and increased level of catalase, glutathione, total and soluble protein. Conclusion: Results of present findings suggest protective effect of Moringa oliefera in prevention of in vitro glucose induced cataract. PMID:24008789

  9. Nanoceria Attenuated High Glucose-Induced Oxidative Damage in HepG2 Cells

    PubMed Central

    Shokrzadeh, Mohammad; Abdi, Hakimeh; Asadollah-Pour, Azin; Shaki, Fatemeh

    2016-01-01

    Objective Hyperglycemia, a common metabolic disorder in diabetes, can lead to oxidative damage. The use of antioxidants can benefit the control and prevention of diabetes side effects. This study aims to evaluate the effect of nanoceria particles, as an antioxidant, on glucose induced cytotoxicity, reactive oxygen species (ROS), lipid peroxidation (LPO) and glutathione (GSH) content in a human hepatocellular liver carcinoma cell line (HepG2) cell line. Materials and Methods In this experimental study, we divided HepG2 cells into these groups: i. Cells treated with 5 mM D-glucose (control), ii. Cells treated with 45 mM D- mannitol+5 mM D-glucose (osmotic control), iii. Cells treated with 50 mM D-glucose (high glucose), and iv. Cells treated with 50 mM D-glucose+nanoceria. Cell viability, ROS formation, LPO and GSH were measured and analyzed statistically. Results High glucose (50 mM) treatment caused significant cell death and increased oxidative stress markers in HepG2 cells. Interestingly, nanoceria at a concentration of 50 mM significantly decreased the high glucose-induced cytotoxicity, ROS formation and LPO. This concentration of nanoceria increased the GSH content in HepG2 cells (P<0.05). Conclusion The antioxidant feature of nanoceria particles makes it an attractive candidate for attenuation of hyperglycemia oxidative damage in different organs. PMID:27054124

  10. Thymol, a monoterpene, inhibits aldose reductase and high-glucose-induced cataract on isolated goat lens

    PubMed Central

    Kanchan, Divya M.; Kale, Smita S.; Somani, Gauresh S.; Kaikini, Aakruti A.; Sathaye, Sadhana

    2016-01-01

    Background: Overactivation of aldose reductase (AR) enzyme has been implicated in the development of various diabetic complications. In the present study, the inhibitory effect of thymol was investigated on AR enzyme and its anti-cataract activity was also examined on isolated goat lens. Materials and Methods: Various concentrations of thymol were incubated with AR enzyme prepared from isolated goat lens. Molecular docking studies were carried out using Schrodinger software to verify the binding of thymol with AR as well as to understand their binding pattern. Further, thymol was evaluated for its anti-cataract activity in high-glucose-induced cataract in isolated goat lens in vitro. Quercetin was maintained as standard (positive control) throughout the study. Results: Thymol showed potent inhibitory activity against goat lens AR enzyme with an IC50 value of 0.65 μg/ml. Docking studies revealed that thymol binds with AR in similar binding pattern as that of quercetin. The high–glucose-induced cataract in isolated goat lens was also improved by thymol treatment. Thymol was also able to significantly (P < 0.001) reduce the oxidative stress associated with cataract. Conclusion: The results suggest that thymol may be a potential therapeutic approach in the prevention of diabetic complications through its AR inhibitory and antioxidant activities. PMID:28216950

  11. Activation of Na+/K+-ATPase attenuates high glucose-induced H9c2 cell apoptosis via suppressing ROS accumulation and MAPKs activities by DRm217.

    PubMed

    Yan, Xiaofei; Xun, Meng; Li, Jing; Wu, Litao; Dou, Xiaojuan; Zheng, Jin

    2016-10-01

    Hyperglycemia is one of the major factors responsible for the myocardial apoptosis and dysfunction in diabetes. Many studies have proved that there is a close relationship between decreased Na(+)/K(+)-ATPase activity and diabetic cardiomyopathy. However, the effect of directly activated Na(+)/K(+)-ATPase on high glucose-induced myocardial injury is still unknown. Here we found that DRm217, a Na(+)/K(+)-ATPase's DR-region specific monoclonal antibody and direct activator, could prevent high glucose-induced H9c2 cell injury, reactive oxygen species (ROS) release, and mitochondrial dysfunction. High glucose-treatment decreased Na(+)/K(+)-ATPase activity and increased intracellular Ca(2+) level, whereas DRm217 increased Na(+)/K(+)-ATPase activity and alleviated Ca(2+) overload. Inhibition of Ca(2+) overload or closing sodium calcium exchanger (NCX channel) could reverse high glucose-induced ROS increasing and cell injury. In addition, DRm217 could significantly attenuate high glucose-induced p38, JNK and ERK1/2 phosphorylation, which were involved in high glucose-induced cell injury and ROS accumulation. Our findings suggest that DRm217 may protect against the deleterious effects of high glucose in the heart. Prevention of high glucose-induced myocardial cell injury by specific Na(+)/K(+)-ATPase activator may be an attractive therapeutic option.

  12. Erythropoietin (EPO) protects against high glucose-induced apoptosis in retinal ganglional cells.

    PubMed

    Wang, Yunxiao; Zhang, Hui; Liu, Yanping; Li, Ping; Cao, Zhihong; Cao, Yu

    2015-03-01

    The aim of this study was to investigate the protective effect and mechanism of EPO on the apoptosis induced by high levels of glucose in retinal ganglial cells (RGCs). High glucose-induced apoptosis model was established in RGCs isolated from SD rats (1-3 days old) and identified with Thy1.1 mAb and MAP-2 pAb. The apoptosis was determined by Hochest assay. The levels of ROS were quantitated by staining the cells with dichloro-dihydro-fluorescein diacetate (DCFH-DA) and measure by flow cytometry. The SOD, GSH-Px, CAT activities, and levels of T-AOC and MDA were determined by ELISA. Change in mitochondrial membrane potential (Δψm) was also assessed by flow cytometry, and expressions of Bcl-2, Bax, caspase-3, caspase-9, and cytochrome C were assessed by western blotting. The RGCs treated with high glucose levels exhibited significantly increased apoptotic rate and concentrations of ROS and MDA. Pretreatment of the cells with EPO caused a significant blockade of the high glucose-induced increase in ROS and MDA levels and apoptotic rate. EPO also increased the activities of SOD, GSH-Px, and CAT, and recovered the levels of T-AOC levels. As a consequence, the mitochondrial membrane potential was improved and Cyt c release into the cytoplasm was prevented which led to significantly suppressed up-regulation of Bax reducing the Bax/Bcl-2 ratio. The expressions of caspase-3 and caspase-9 induced by high glucose exposure were also ameliorated in the RGCs treated with EPO. The protective effect of EPO against apoptosis was mediated through its antioxidant action. Thus, it blocked the generation of pro-apoptotic proteins and apoptotic degeneration of the RGCs by preventing the mitochondrial damage.

  13. NLRP3 Inflammasome Expression and Signaling in Human Diabetic Wounds and in High Glucose Induced Macrophages

    PubMed Central

    Zhang, Xiaotian; Dai, Jiezhi; Li, Li

    2017-01-01

    Introduction. To investigate the contribution and mechanism of NLRP3 inflammasome expression in human wounds in diabetes mellitus and in high glucose induced macrophages. Methods. In the present study, we compared the expression of NLRP3 inflammasome in debridement wound tissue from diabetic and nondiabetic patients. We also examined whether high glucose induces NLRP3 inflammasome expression in cultures THP-1-derived macrophages and the influence on IL-1β expression. Results. The expressions of NLRP3, caspase1, and IL-1β, at both the mRNA and protein level, were significantly higher in wounds of diabetic patients compared with nondiabetic wounds (P < 0.05). High glucose induced a significant increase in NLRP3 inflammasome and IL-1β expression in THP-1-derived macrophages. M1 macrophage surface marker with CCR7 was significantly upregulated after high glucose stimulation. SiRNA-mediated silencing of NLRP3 expression downregulates the expression of IL-1β. Conclusion. The higher expression of NLRP3, caspase1, and secretion of IL-1β, signaling, and activation might contribute to the hyperinflammation in the human diabetic wound and in high glucose induced macrophages. It may be a novel target to treat the DM patients with chronic wound. PMID:28164132

  14. Theophylline prevents the inhibitory effect of prostaglandin E2 on glucose-induced insulin secretion in man.

    PubMed

    Giugliano, D; Cozzolino, D; Salvatore, T; Giunta, R; Torella, R

    1988-06-01

    This study was undertaken to assess the mechanism by which prostaglandins of the E series inhibit glucose-induced insulin secretion in man. Acute insulin response (mean change 3-10 min) to iv glucose (0.33 g/kg) was decreased by 40% during the infusion of prostaglandin E2 (10 micrograms/min) and glucose disappearance rates were reduced (P less than 0.05). Insulin response to arginine (5 g iv) and tolbutamide (1 g iv) were not affected by the same rate of prostaglandin E2 infusion. The inhibitory effect of prostaglandin E2 on glucose-induced insulin secretion was prevented by theophylline (100 mg as a loading dose followed by a 5 mg/min infusion), a drug that increases the intracellular cAMP concentrations by inhibiting phosphodiesterase activity. Our data suggest the involvement of the adenylate cyclase system in the inhibitory action of prostaglandin E2 on glucose-induced insulin secretion in man.

  15. Pioglitazone inhibits high glucose-induced expression of receptor for advanced glycation end products in coronary artery smooth muscle cells

    PubMed Central

    DI, BEI-BING; LI, HONG-WEI; LI, WEI-PING; SHEN, XU-HUA; SUN, ZHI-JUN; WU, XING

    2015-01-01

    Receptor for advanced glycation end products (RAGE) is critical in inflammatory diseases, including diabetes and atherosclerosis. The mechanism underlying the effect of peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone (PIO) on RAGE expression in coronary artery smooth muscle cells (SMCs) stimulated by high glucose concentrations remains to be elucidated. In the present study, the effect and mechanism of action of PIO on RAGE expression in SMCs was investigated following treatment with high glucose concentrations. Rat coronary artery SMCs were pretreated with PIO alone, PIO and GW9662 (a PPARγ antagonist), diphenyleneiodonium (DPI; a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor) or the antioxidant pyrrolidine dithiocarbamate (PDTC; a nuclear factor-κB (NF-κB) inhibitor), followed by treatment with high glucose. RAGE mRNA and protein expression, reactive oxygen species (ROS) production and NF-κB nuclear translocation were investigated. Glucose induced RAGE expression in a dose-dependent manner, with maximal effect at a concentration of 25 mmol/l following treatment for 48 h. PIO, DPI and PDTC reduced high glucose-induced increases in RAGE protein and mRNA expression. PIO prominently downregulated RAGE expression and inhibited high glucose-induced increases in ROS production and NF-κB activation (P<0.05). Pretreatment with PIO and GW9662 did not exhibit this inhibitory effect. High glucose may stimulate RAGE expression in coronary artery SMCs through NADPH oxidase-mediated ROS generation and NF-κB activation. PIO downregulated RAGE expression and inhibited ROS production and NF-κB activation via PPARγ activation, which may prevent the inflammatory effect of AGE/RAGE system in diabetes. PMID:25523934

  16. Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells

    SciTech Connect

    Ryu, Gyeong Ryul; Lee, Esder; Chun, Hyun-Ji; Yoon, Kun-Ho; Ko, Seung-Hyun; Ahn, Yu-Bae; Song, Ki-Ho

    2013-09-20

    Highlights: •High glucose increased production of reactive oxygen species in cultured pancreatic stellate cells. •High glucose facilitated the activation of these cells. •Antioxidant treatment attenuated high glucose-induced activation of these cells. -- Abstract: The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2–5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation.

  17. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes.

    PubMed

    He, Xiaoqing; Kan, Hong; Cai, Lu; Ma, Qiang

    2009-01-01

    Exposure to high levels of glucose induces the production of reactive oxygen species (ROS) in cardiomyocytes that may contribute to the development of cardiomyopathy in diabetes. Nuclear factor erythroid 2-related factor 2 (Nrf2) controls the antioxidant response element (ARE)-dependent gene regulation in response to oxidative stress. The role of Nrf2 in defense against high glucose-induced oxidative damage in cardiomyocytes was investigated. Glucose at high concentrations induced ROS production in both primary neonatal and adult cardiomyocytes from the Nrf2 wild type (WT) mouse heart, whereas, in Nrf2 knockout (KO) cells, ROS was significantly higher under basal conditions and high glucose markedly further increased ROS production in concentration and time-dependent manners. Concomitantly, high glucose induced significantly higher levels of apoptosis at lower concentrations and in shorter time in Nrf2 KO cells than in WT cells. Primary adult cardiomyocytes from control and diabetic mice also showed dependence on Nrf2 function for isoproterenol-stimulated contraction. Additionally, cardiomyocytes from Nrf2 KO mice exhibited increased sensitivity to 3-nitropropionic acid, an inhibitor of mitochondrial respiratory complex II, for both ROS production and apoptosis compared with Nrf2 WT cells, further emphasizing the role of Nrf2 in ROS defense in the cells. Mechanistically, Nrf2 was shown to mediate the basal expression and induction of ARE-controlled cytoprotective genes, Nqo1 and Ho1, at both mRNA and protein levels in cardiomyocytes, as both the basal and inducible expressions of the genes were lost in Nrf2 KO cells or largely reduced by Nrf2 SiRNA. The findings, for the first time, established Nrf2 as a critical regulator of defense against ROS in normal and diabetic hearts.

  18. High glucose-induced cytoplasmic translocation of Dnmt3a contributes to CTGF hypo-methylation in mesangial cells

    PubMed Central

    Zhang, Hao; Li, Aimei; Zhang, Wei; Huang, Zhijun; Wang, Jianwen; Yi, Bin

    2016-01-01

    Connective tissue growth factor (CTGF) plays an essential role in the pathogenesis of diabetic nephropathy and we have previously identified that high glucose induced the expression of CTGF by decreasing DNA methylation. The aim of the present study was to investigate the underlying mechanisms of the high glucose-induced CTGF hypo-methylation. Human glomerular mesangial cells (hMSCs) were treated with low glucose (5 mM), mannitol (30 mM) or high glucose (30 mM) respectively. Immunofluorescence staining, real-time quantitative PCR and western blotting were performed to determine the subcellular distribution and expression of CTGF and Dnmt3a. ChIP-PCR assay was applied to investigate the capability of Dnmt3a to bind the CpG island of CTGF. Our results showed that high glucose induced both mRNA and protein expressions of CTGF, and led to increased cytoplasmic translocation of Dnmt3a in cultured hMSCs. The nuclear Dnmt3a protein was significantly reduced after high glucose treatment, although the expression of total Dnmt3a protein was not altered. We further discovered that ERK/MAPK signalling contributed to the high glucose-induced cytoplasmic translocation of Dnmt3a. Consequently, less Dnmt3a protein was bound to the CpG island of CTGF promoter, which induced an increase in CTGF expression by epigenetic regulation in the presence of high glucose. In conclusion, high glucose induces cytoplasmic translocation of Dnmt3a, possibly through activating ERK/MAPK signalling pathway, which contributes to the decreased binding of Dnmt3a on CTGF promoter and the subsequent CTGF hypo-methylation in diabetic nephropathy. PMID:27364355

  19. Effects of hydrogen sulfide on high glucose-induced glomerular podocyte injury in mice.

    PubMed

    Liu, Ye; Zhao, Huichen; Qiang, Ye; Qian, Guanfang; Lu, Shengxia; Chen, Jicui; Wang, Xiangdong; Guan, Qingbo; Liu, Yuantao; Fu, Yuqin

    2015-01-01

    The aim of this study was to assess the effects of hydrogen sulfide on high glucose-induced mouse podocyte (MPC) injury and the underlying mechanisms. Mouse podocytes were randomly divided into 4 groups, including high glucose (HG), normal glucose (NG), normal glucose + DL-propargylglycine (PPG), and high glucose + NaHS (HG + NaHS) groups for treatment. Then, ZO-2, nephrin, β-catenin, and cystathionine γ-lyase (CSE) protein expression levels were determined by western blot. We found that high glucose significantly reduced nephrin, ZO-2, and CSE expression levels (P<0.05), and overtly elevated β-catenin amounts (P<0.05), in a time-dependent manner. Likewise, PPG at different concentrations in normal glucose resulted in significantly lower CSE, ZO-2, and nephrin levels (P<0.05), and increased β-catenin amounts (P<0.05). Interestingly, significantly increased ZO-2 and nephrin levels, and overtly reduced β-catenin amounts were observed in the HG + NaHS group compared with HG treated cells (P<0.01). Compared with NG treated cells, decreased ZO-2 and nephrin levels and higher β-catenin amounts were obtained in the HG + NaHS group. In conclusion,CSE downregulation contributes to hyperglycemia induced podocyte injury, which is alleviated by exogenous H2S possibly through ZO-2 upregulation and the subsequent suppression of Wnt/β-catenin pathway.

  20. Protective Role of Morin, a Flavonoid, against High Glucose Induced Oxidative Stress Mediated Apoptosis in Primary Rat Hepatocytes

    PubMed Central

    Kapoor, Radhika; Kakkar, Poonam

    2012-01-01

    Apoptosis is an early event of liver damage in diabetes and oxidative stress has been linked to accelerate the apoptosis in hepatocytes. Therefore, the compounds that can scavenge ROS may confer regulatory effects on high-glucose induced apoptosis. In the present study, primary rat hepatocytes were exposed to high concentration (40 mM) of glucose. At this concentration decreased cell viability and enhanced ROS generation was observed. Depleted antioxidant status of hepatocytes under high glucose stress was also observed as evident from transcriptional level and activities of antioxidant enzymes. Further, mitochondrial depolarisation was accompanied by the loss of mitochondrial integrity and altered expression of Bax and Bcl-2. Increased translocation of apoptotic proteins like AIF (Apoptosis inducing factor) & Endo-G (endonuclease-G) from its resident place mitochondria to nucleus was also observed. Cyt-c residing in the inter-membrane space of mitochondria also translocated to cytoplasm. These apoptotic proteins initiated caspase activation, DNA fragmentation, chromatin condensation, increased apoptotic DNA content in glucose treated hepatocytes, suggesting mitochondria mediated apoptotic mode of cell death. Morin, a dietary flavonoid from Psidium guajava was effective in increasing the cell viability and decreasing the ROS level. It maintained mitochondrial integrity, inhibited release of apoptotic proteins from mitochondria, prevented DNA fragmentation, chromatin condensation and hypodiploid DNA upon exposure to high glucose. This study confirms the capacity of dietary flavonoid Morin in regulating apoptosis induced by high glucose via mitochondrial mediated pathway through intervention of oxidative stress. PMID:22899998

  1. High glucose-induced, endothelin-dependent fibronectin synthesis is mediated via NF-kappa B and AP-1.

    PubMed

    Chen, Shali; Mukherjee, Suranjana; Chakraborty, Chandan; Chakrabarti, Subrata

    2003-02-01

    Human endothelial cells cultured under high glucose (HG) conditions were shown before to upregulate several basement membrane proteins, including fibronectin (FN), thus mimicking effects of diabetes. Using human macrovascular (HUVEC) and microvascular (HMEC) endothelial cell lines, we evaluated in the present study some of the key molecular signaling events involved in HG-induced FN overexpression. This expression was shown to be dependent on endogenous endothelin (ET) receptor-mediated signaling. We also examined the roles played by protein kinase C (PKC) and the transcription factors nuclear factor kappaB (NF-kappaB) and activating protein (AP)-1 with respect to such changes. HG, PKC activators, and ETs (ET-1 and ET-3) that increased FN expression also caused activation of NF-kappaB and AP-1. Inhibitors of both NF-kappaB and AP-1 prevented HG- and ET-induced FN production. ET receptor blockade also prevented these HG- and ET-mediated changes. The results of this study indicate that glucose-induced increased FN production in diabetes may be mediated via ET-dependent NF-kappaB and AP-1 activation.

  2. Proteasome Dysfunction Mediates High Glucose-Induced Apoptosis in Rodent Beta Cells and Human Islets

    PubMed Central

    Broca, Christophe; Varin, Elodie; Armanet, Mathieu; Tourrel-Cuzin, Cécile; Bosco, Domenico; Dalle, Stéphane; Wojtusciszyn, Anne

    2014-01-01

    The ubiquitin/proteasome system (UPS), a major cellular protein degradation machinery, plays key roles in the regulation of many cell functions. Glucotoxicity mediated by chronic hyperglycaemia is detrimental to the function and survival of pancreatic beta cells. The aim of our study was to determine whether proteasome dysfunction could be involved in beta cell apoptosis in glucotoxic conditions, and to evaluate whether such a dysfunction might be pharmacologically corrected. Therefore, UPS activity was measured in GK rats islets, INS-1E beta cells or human islets after high glucose and/or UPS inhibitor exposure. Immunoblotting was used to quantify polyubiquitinated proteins, endoplasmic reticulum (ER) stress through CHOP expression, and apoptosis through the cleavage of PARP and caspase-3, whereas total cell death was detected through histone-associated DNA fragments measurement. In vitro, we found that chronic exposure of INS-1E cells to high glucose concentrations significantly decreases the three proteasome activities by 20% and leads to caspase-3-dependent apoptosis. We showed that pharmacological blockade of UPS activity by 20% leads to apoptosis in a same way. Indeed, ER stress was involved in both conditions. These results were confirmed in human islets, and proteasome activities were also decreased in hyperglycemic GK rats islets. Moreover, we observed that a high glucose treatment hypersensitized beta cells to the apoptotic effect of proteasome inhibitors. Noteworthily, the decreased proteasome activity can be corrected with Exendin-4, which also protected against glucotoxicity-induced apoptosis. Taken together, our findings reveal an important role of proteasome activity in high glucose-induced beta cell apoptosis, potentially linking ER stress and glucotoxicity. These proteasome dysfunctions can be reversed by a GLP-1 analog. Thus, UPS may be a potent target to treat deleterious metabolic conditions leading to type 2 diabetes. PMID:24642635

  3. High Glucose-induced Retinal Pericyte Apoptosis Depends on Association of GAPDH and Siah1.

    PubMed

    Suarez, Sandra; McCollum, Gary W; Jayagopal, Ashwath; Penn, John S

    2015-11-20

    Diabetic retinopathy (DR) is a leading cause of blindness worldwide, and its prevalence is growing. Current therapies for DR address only the later stages of the disease, are invasive, and have limited effectiveness. Retinal pericyte death is an early pathologic feature of DR. Although it has been observed in diabetic patients and in animal models of DR, the cause of pericyte death remains unknown. A novel pro-apoptotic pathway initiated by the interaction between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the E3 ubiquitin ligase, seven in absentia homolog 1 (Siah1), was recently identified in ocular tissues. In this article we examined the involvement of the GAPDH/Siah1 interaction in human retinal pericyte (hRP) apoptosis. HRP were cultured in 5 mm normal glucose, 25 mm l- or d-glucose for 48 h (osmotic control and high glucose treatments, respectively). Siah1 siRNA was used to down-regulate Siah1 expression. TAT-FLAG GAPDH and/or Siah1-directed peptides were used to block GAPDH and Siah1 interaction. Co-immunoprecipitation assays were conducted to analyze the effect of high glucose on the association of GAPDH and Siah1. Apoptosis was measured by Annexin V staining and caspase-3 enzymatic activity assay. High glucose increased Siah1 total protein levels, induced the association between GAPDH and Siah1, and led to GAPDH nuclear translocation. Our findings demonstrate that dissociation of the GAPDH/Siah1 pro-apoptotic complex can block high glucose-induced pericyte apoptosis, widely considered a hallmark feature of DR. Thus, the work presented in this article can provide a foundation to identify novel targets for early treatment of DR.

  4. A catechin-enriched green tea extract prevents glucose-induced survival reduction in Caenorhabditis elegans through sir-2.1 and uba-1 dependent hormesis.

    PubMed

    Deusing, Dorothé Jenni; Winter, Sarah; Kler, Adolf; Kriesl, Erwin; Bonnländer, Bernd; Wenzel, Uwe; Fitzenberger, Elena

    2015-04-01

    Hyperglycemia is a hallmark of diabetes mellitus which leads to the onset of complications in the long term. Green tea through its high content of polyphenolic catechins, on the other hand, is suggested to prevent or at least delay such detrimental complications. In the present study we fed the nematode Caenorhabditis elegans on a liquid medium supplemented with 10mM glucose in the absence or presence of a catechin-enriched green tea extract (CEGTE). After exposure of young adults for 48h survival was subsequently measured under heat stress at 37°C. Whereas CEGTE at 0.01% did not affect the survival of wild type nematodes, it completely reversed the glucose-induced survival reduction. Those effects were not achieved through the monomeric catechins included in CEGTE. RNA interference (RNAi) for sir-2.1 not only prevented the survival extension by CEGTE under simultaneous glucose exposure but also caused a further reduction of survival. Likewise, the knockdown of uba-1, encoding the only E1-ubiquitin-activating enzyme in C. elegans, proved that UBA-1 is essential for the survival extension by CEGTE and that its loss of function changes CEGTE from a survival extending into a survival reducing extract. Stimulation of the proteasome by CEGTE was finally proven through measurements of the proteolytic cleavage of a fluorogenic peptide substrate. To conclude, our studies provide evidence that CEGTE reverses glucose-induced damage in C. elegans through activation of adaptive responses mediated by SIR-2.1 and proteasomal degradation. The hormetic mode of action is revealed by a reduction of survival once the adaptive processes were blocked.

  5. Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid.

    PubMed

    Tian, Rong; Ding, Yun; Peng, Yi-Yuan; Lu, Naihao

    2017-03-11

    Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H2O2), have emerged as important molecules in the pathogenesis of diabetic endothelial dysfunction. Additionally, neutrophils-derived myeloperoxidase (MPO) and MPO-catalyzed hypochlorous acid (HOCl) play important roles in the vascular injury. However, it is unknown whether MPO can use vascular-derived ROS to induce diabetic endothelial dysfunction. In the present study, we demonstrated that NADPH oxidase was the main source of ROS formation in high glucose-cultured human umbilical vein endothelial cells (HUVECs), and played a critical role in high glucose-induced endothelial dysfunction such as cell apoptosis, loss of cell viability and reduction of nitric oxide (NO). However, the addition of MPO could amplify the high glucose-induced endothelial dysfunction which was inhibited by the presence of apocynin (NADPH oxidase inhibitor), catalase (H2O2 scavenger), or methionine (HOCl scavenger), demonstrating the contribution of NADPH oxidase-H2O2-MPO-HOCl pathway in the MPO/high glucose-induced vascular injury. In high glucose-incubated rat aortas, MPO also exacerbated the NADPH oxidase-induced impairment of endothelium-dependent relaxation. Consistent with these in vitro data, in diabetic rat aortas, both MPO expresion and NADPH oxidase activity were increased while the endothelial function was simultaneously impaired. The results suggested that vascular-bound MPO could amplify high glucose-induced vascular injury in diabetes. MPO-NADPH oxidase-HOCl may represent an important pathogenic pathway in diabetic vascular diseases.

  6. NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression

    SciTech Connect

    Li, Ruizhao; Zhang, Li; Shi, Wei; Zhang, Bin; Liang, Xinling; Liu, Shuangxin; Wang, Wenjian

    2013-04-15

    Background: Hyperglycemia promotes podocyte apoptosis and plays a key role in the pathogenesis of diabetic nephropathy. However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis is still far from being fully understood. Recent studies reported that high glucose activate nuclear factor of activated T cells (NFAT) in vascular smooth muscle or pancreatic β-cells. Here, we sought to determine if hyperglycemia activates NFAT2 in cultured podocyte and whether this leads to podocyte apoptosis. Meanwhile, we also further explore the mechanisms of NFAT2 activation and NFAT2 mediates high glucose-induced podocyte apoptosis. Methods: Immortalized mouse podocytes were cultured in media containing normal glucose (NG), or high glucose (HG) or HG plus cyclosporine A (a pharmacological inhibitor of calcinerin) or 11R-VIVIT (a special inhibitor of NFAT2). The activation of NFAT2 in podocytes was detected by western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was further evaluated by observing the inhibition of NFAT2 activation by 11R-VIVIT using flow cytometer. Intracellular Ca{sup 2+} was monitored in HG-treated podcocytes using Fluo-3/AM. The mRNA and protein expression of apoptosis gene Bax were measured by real time-qPCR and western blotting. Results: HG stimulation activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. Pretreatment with cyclosporine A (500 nM) or 11R-VIVIT (100 nM) completely blocked NFAT2 nuclear accumulation. Meanwhile, the apoptosis effects induced by HG were also abrogated by concomitant treatment with 11R-VIVIT in cultured podocytes. We further found that HG also increased [Ca{sup 2+}]i, leading to activation of calcineurin, and subsequent increased nuclear accumulation of NFAT2 and Bax expression in cultured podocytes. Conclusion: Our results identify a new finding that HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway

  7. Berberine enhances the AMPK activation and autophagy and mitigates high glucose-induced apoptosis of mouse podocytes.

    PubMed

    Jin, Yingli; Liu, Shuping; Ma, Qingshan; Xiao, Dong; Chen, Li

    2017-01-05

    High glucose concentration can induce injury of podocytes and berberine has a potent activity against diabetic nephropathy. However, whether and how berberine can inhibit high glucose-mediated injury of podocytes have not been clarified. This study tested the effect of berberine on high glucose-mediated apoptosis and the AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) activation and autophagy in podocytes. The results indicated that berberine significantly mitigated high glucose-decreased cell viability, and nephrin and podocin expression as well as apoptosis in mouse podocytes. Berberine significantly increased the AMPK activation and mitigated high glucose and/or the AMPK inhibitor, compound C-mediated mTOR activation and apoptosis in podocytes. Berberine significantly enhanced the AMPK activation and protected from high glucose-induced apoptosis in the AMPK-silencing podocytes. Furthermore, berberine significantly increased the high glucose-elevated Unc-51-like autophagy-activating kinase 1 (ULK1) S317/S555 phosphorylation, Beclin-1 expression, the ratios of LC3II to LC3I expression and the numbers of autophagosomes, but reduced ULK1 S757 phosphorylation in podocytes. In addition, berberine significantly attenuated compound C-mediated inhibition of autophagy in podocytes. The protective effect of berberine on high glucose-induced podocyte apoptosis was significantly mitigated by pre-treatment with 3-methyladenine or bafilomycin A1. Collectively, berberine enhanced autophagy and protected from high glucose-induced injury in podocytes by promoting the AMPK activation. Our findings may provide new insights into the molecular mechanisms underlying the anti-diabetic nephropathy effect of berberine and may aid in design of new therapies for intervention of diabetic nephropathy.

  8. Spleen tyrosine kinase mediates high glucose-induced transforming growth factor-{beta}1 up-regulation in proximal tubular epithelial cells

    SciTech Connect

    Yang, Won Seok; Chang, Jai Won; Han, Nam Jeong; Lee, Sang Koo; Park, Su-Kil

    2012-09-10

    The role of spleen tyrosine kinase (Syk) in high glucose-induced intracellular signal transduction has yet to be elucidated. We investigated whether Syk is implicated in high glucose-induced transforming growth factor-{beta}1 (TGF-{beta}1) up-regulation in cultured human proximal tubular epithelial cells (HK-2 cell). High glucose increased TGF-{beta}1 gene expression through Syk, extracellular signal-regulated kinase (ERK), AP-1 and NF-{kappa}B. High glucose-induced AP-1 DNA binding activity was decreased by Syk inhibitors and U0126 (an ERK inhibitor). Syk inhibitors suppressed high glucose-induced ERK activation, whereas U0126 had no effect on Syk activation. High glucose-induced NF-{kappa}B DNA binding activity was also decreased by Syk inhibitors. High glucose increased nuclear translocation of p65 without serine phosphorylation of I{kappa}B{alpha} and without degradation of I{kappa}B{alpha}, but with an increase in tyrosine phosphorylation of I{kappa}B{alpha} that may account for the activation of NF-{kappa}B. Both Syk inhibitors and Syk-siRNA attenuated high glucose-induced I{kappa}B{alpha} tyrosine phosphorylation and p65 nuclear translocation. Depletion of p21-activated kinase 2 (Pak2) by transfection of Pak2-siRNA abolished high glucose-induced Syk activation. In summary, high glucose-induced TGF-{beta}1 gene transcription occurred through Pak2, Syk and subsequent ERK/AP-1 and NF-{kappa}B pathways. This suggests that Syk might be implicated in the diabetic kidney disease.

  9. Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

    PubMed Central

    Tsai, Hsiao-Ya; Lin, Chih-Pei; Huang, Po-Hsun; Li, Szu-Yuan; Chen, Jia-Shiong; Lin, Feng-Yen; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients. PMID:26682233

  10. Emodin attenuates high glucose-induced TGF-β1 and fibronectin expression in mesangial cells through inhibition of NF-κB pathway

    SciTech Connect

    Yang, Jie; Zeng, Zhi; Wu, Teng; Yang, Zhicheng; Liu, Bing; Lan, Tian

    2013-12-10

    The activation of nuclear factor-κB (NF-κB) and the subsequent overexpression of its downstream targets transforming growth factor-β1 (TGF-β1) and fibronectin (FN) are among the hallmarks for the progressive diabetic nephropathy. Our previous studies demonstrated that emodin ameliorated renal injury and inhibited extracellular matrix accumulation in kidney and mesangial cells under diabetic condition. However, the molecular mechanism has not been fully elucidated. Here, we showed that emodin significantly attenuated high glucose-induced NF-κB nuclear translocation in mesangial cells. Interestingly, emodin also inhibited the DNA-binding activity and transcriptional activity of NF-κB. Furthermore, NF-κB-mediated TGF-β1 and FN expression was significantly decreased by emodin. These results demonstrated that emodin suppressed TGF-β1 and FN overexpression through inhibition of NF-κB activation, suggesting that emodin-mediated inhibition of the NF-κB pathway could protect against diabetic nephropathy. - Highlights: • Emodin decreased high glucose-induced p65 phosphorylation in MCs. • Emodin decreased high glucose-induced IκB-α degradation in MCs. • Emodin decreased high glucose-induced p65 translocation in MCs. • Emodin blocked high glucose-induced NF-κB activity. • Emodin blocked high glucose-induced the expression of TGF-β1 and FN.

  11. Phytolacca americana inhibits the high glucose-induced mesangial proliferation via suppressing extracellular matrix accumulation and TGF-beta production.

    PubMed

    Jeong, Seung Il; Kim, Kang Ju; Choo, Yong Kug; Keum, Kyung Soo; Choi, Bong Kyu; Jung, Kyu Yong

    2004-02-01

    This study describes a potential of Phytolaccaceae (Phytolacca americana var.) as an inhibitor of high glucose-stimulated production of extracellular matrix (ECM) proteins and TGF-beta in cultured glomerular mesangial cells (GMCs). Raising the ambient glucose concentration for 24 hrs caused a dose-dependent increase in [3H]thymidine incorporation of GMCs, and the maximal response was achieved at 20 mM. Phytolaccaceae extracts (2.5-20 microg/ml) inhibited the high glucose-induced [3H]thymidine incorporation in a dose-dependent manner, and the concentrations tested here did not affect to the cell viability. Exposure of the GMCs to 20 mM glucose caused both ECM (collagen and fibronectin) accumulation and TGF-beta secretion, and these changes were significantly diminished by treatment of GMCs with Phytolaccaceae (10 microg/ml). Taken together, these results indicate that Phytolaccaceae inhibits the high glucose-induced GMCs proliferation partially through suppressing accumulation of ECM components and TGF-beta production, suggesting that Phytolaccaceae may be a promising agent for treating the development and progression of diabetic glomerulopathy.

  12. MicroRNA-34a regulates high glucose-induced apoptosis in H9c2 cardiomyocytes.

    PubMed

    Zhao, Fang; Li, Bo; Wei, Yin-zhi; Zhou, Bin; Wang, Han; Chen, Ming; Gan, Xue-dong; Wang, Zhao-hui; Xiong, Shi-xi

    2013-12-01

    Hyperglycemia is an important initiator of cardiovascular disease, contributing to the development of cardiomyocyte death and diabetic complications. The purpose of the present study was to investigate whether high glucose state could induce apoptosis of rat cardiomyocyte cell line H9c2 through microRNA-mediated Bcl-2 signaling pathway. The expression of miR-34a and Bcl-2 mRNA was detected by using real-time PCR. Western blotting was used to examine the changes in apoptosis-associated protein Bcl-2. Apoptosis of H9c2 cells was tested by using flow cytometry. The results showed that the expression of miR-34a was significantly elevated and that of Bcl-2 was strongly reduced, and apoptosis of cardiomyocytes was apparently increased in the high-glucose-treated H9c2 cells as compared with normal-glucose-treated controls. In addition, we identified Bcl-2 gene was the target of miR-34a. miR-34a mimics reduced the expression of Bcl-2 and increased glucose-induced apoptosis, but miR-34a inhibitor acted as the opposite mediator. Our data demonstrate that miR-34a contributes to high glucose-induced decreases in Bcl-2 expression and subsequent cardiomyocyte apoptosis.

  13. Tartary buckwheat flavonoids protect hepatic cells against high glucose-induced oxidative stress and insulin resistance via MAPK signaling pathways.

    PubMed

    Hu, Yuanyuan; Hou, Zuoxu; Liu, Dongyang; Yang, Xingbin

    2016-03-01

    Oxidative stress plays a crucial role in chronic complication of diabetes. In this study, the protective effect of purified tartary buckwheat flavonoids (TBF) fraction against oxidative stress induced by a high-glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells. Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs), nuclear factor E2 related factor 2 (Nrf2) and p-(Ser307)-IRS-1 expression, and glucose uptake were evaluated. Results suggest that treatment of HepG2 cells with TBF alone improved glucose uptake and antioxidant enzymes, and activated Nrf2, and attenuated the IRS-1 Ser307 phosphorylation, and enhanced total levels of IRS-1. Furthermore, the high glucose-induced changes in antioxidant defences, Nrf2, p-MAPKs, p-IRS1 Ser307, and IRS-1 levels, and glucose uptake were also significantly inhibited by pre-treatment with TBF. Interestingly, the selective MAPK inhibitors significantly enhanced the TBF-mediated protection by inducing changes in the redox status, glucose uptake, p-(Ser307) and total IRS-1 levels. This report firstly showed that TBF could recover the redox status of insulin-resistant HepG2 cells, suggesting that TBF significantly protected the cells against high glucose-induced oxidative stress, and these beneficial effects of TBF on redox balance and insulin resistance were mediated by targeting MAPKs.

  14. Renoprotective Effects of Aldose Reductase Inhibitor Epalrestat against High Glucose-Induced Cellular Injury

    PubMed Central

    Eid, Ali Hussein

    2017-01-01

    Diabetic nephropathy (DN) is the leading cause of end stage renal disease worldwide. Increased glucose flux into the aldose reductase (AR) pathway during diabetes was reported to exert deleterious effects on the kidney. The objective of this study was to investigate the renoprotective effects of AR inhibition in high glucose milieu in vitro. Rat renal tubular (NRK-52E) cells were exposed to high glucose (30 mM) or normal glucose (5 mM) media for 24 to 48 hours with or without the AR inhibitor epalrestat (1 μM) and assessed for changes in Akt and ERK1/2 signaling, AR expression (using western blotting), and alterations in mitochondrial membrane potential (using JC-1 staining), cell viability (using MTT assay), and cell cycle. Exposure of NRK-52E cells to high glucose media caused acute activation of Akt and ERK pathways and depolarization of mitochondrial membrane at 24 hours. Prolonged high glucose exposure (for 48 hours) induced AR expression and G1 cell cycle arrest and decreased cell viability (84% compared to control) in NRK-52E cells. Coincubation of cells with epalrestat prevented the signaling changes and renal cell injury induced by high glucose. Thus, AR inhibition represents a potential therapeutic strategy to prevent DN. PMID:28386557

  15. High glucose-induced barrier impairment of human retinal pigment epithelium is ameliorated by treatment with Goji berry extracts through modulation of cAMP levels.

    PubMed

    Pavan, Barbara; Capuzzo, Antonio; Forlani, Giuseppe

    2014-03-01

    Human retinal pigment epithelium cells were used to investigate the mechanisms underlying blood-retinal barrier disruption under conditions of chronic hyperglycemia. The treatment with 25 mM glucose caused a rapid drop in the transepithelial electrical resistance (TEER), which was reversed by the addition of either a methanolic extract from Goji (Lycium barbarum L.) berries or its main component, taurine. Intracellular cAMP levels increased concurrently with the high glucose-induced TEER decrease, and were correlated to an increased activity of the cytosolic isoform of the enzyme adenylyl cyclase. The treatment with plant extract or taurine restored control levels. Data are discussed in view of a possible prevention approach for diabetic retinopathy.

  16. Sequential signaling cascade of IL-6 and PGC-1α is involved in high glucose-induced podocyte loss and growth arrest

    SciTech Connect

    Kim, Dong Il; Park, Soo Hyun

    2013-06-14

    Highlights: •The pathophysiological role of IL-6 in high glucose-induced podocyte loss. •The novel role of PGC-1α in the development of diabetic nephropathy. •Signaling of IL-6 and PGC-1α in high glucose-induced dysfunction of podocyte. -- Abstract: Podocyte loss, which is mediated by podocyte apoptosis, is implicated in the onset of diabetic nephropathy. In this study, we investigated the involvement of interleukin (IL)-6 in high glucose-induced apoptosis of rat podocytes. We also examined the pathophysiological role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in this system. High glucose treatment induced not only podocyte apoptosis but also podocyte growth arrest. High glucose treatment also increased IL-6 secretion and activated IL-6 signaling. The high glucose-induced podocyte apoptosis was blocked by IL-6 neutralizing antibody. IL-6 treatment or overexpression induced podocyte apoptosis and growth arrest, and IL-6 siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Furthermore, high glucose or IL-6 treatment increased PGC-1α expression, and PGC-1α overexpression also induced podocyte apoptosis and growth arrest. PGC-1α siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Collectively, these findings showed that high glucose promoted apoptosis and cell growth arrest in podocytes via IL-6 signaling. In addition, PGC-1α is involved in podocyte apoptosis and cell growth arrest. Therefore, blocking IL-6 and its downstream mediators such as IL6Rα, gp130 and PGC-1α may attenuate the progression of diabetic nephropathy.

  17. Oleanolic acid ameliorates high glucose-induced endothelial dysfunction via PPARδ activation

    PubMed Central

    Zhang, Zihui; Jiang, Manli; Xie, Xinya; Yang, Haixia; Wang, Xinfeng; Xiao, Lei; Wang, Nanping

    2017-01-01

    Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid, OA) is a pentacyclic triterpenes widely distributed in food, medicinal plants and nutritional supplements. OA exhibits various pharmacological properties, such as hepatoprotective and anti-tumor effects. In this study, we analyzed the effect of OA on endothelial dysfunction induced by high glucose in human vascular endothelial cells (ECs). Western blotting showed that OA attenuated high glucose-reduced nitric production oxide (NO) as well as Akt-Ser473 and eNOS-Ser1177 phosphorylation in cultured human umbilical vein ECs (HUVECs). Next, luciferase reporter assay showed that OA activated peroxisome proliferators-activated receptor δ (PPARδ) activity. Quantitative reverse transcriptase PCR (qRT-PCR) demonstrated that OA increased the expressions of PPARδ target genes (PDK4, ADRP and ANGPTL4) in ECs. Meanwhile, the induced expressions of PDK4, ADRP and ANGPTL4 by OA were inhibited by GSK0660, a specific antagonist of PPARδ. In addition, inhibition of PPARδ abolished OA-induced the Akt-Ser473 and eNOS-Ser1177 phosphorylation, and NO production. Finally, by using Multi Myograph System, we showed that OA prevented high glucose-impaired vasodilation. This protective effect on vasodilation was inhibited in aortic rings pretreated with GSK0660. Collectively, we demonstrated that OA improved high glucose-impaired endothelial function via a PPARδ-mediated mechanism and through eNOS/Akt/NO pathway. PMID:28067284

  18. Pterostilbene attenuates high glucose-induced oxidative injury in hippocampal neuronal cells by activating nuclear factor erythroid 2-related factor 2.

    PubMed

    Yang, Yang; Fan, Chongxi; Wang, Bodong; Ma, Zhiqiang; Wang, Dongjin; Gong, Bing; Di, Shouyin; Jiang, Shuai; Li, Yue; Li, Tian; Yang, Zhi; Luo, Erping

    2017-04-01

    In the present study, neuroblastoma (SH-SY5Y) cells were used to investigate the mechanisms mediating the potential protective effects of pterostilbene (PTE) against mitochondrial metabolic impairment and oxidative stress induced by hyperglycemia for mimicking the diabetic encephalopathy. High glucose medium (100mM) decreased cellular viability after 24h incubation which was evidenced by: (i) reduced mitochondrial complex I and III activities; (ii) reduced mitochondrial cytochrome C; (iii) increased reactive oxygen species (ROS) generation; (iv) decreased mitochondrial membrane potential (ΔΨm); and (v) increased lactate dehydrogenase (LDH) levels. PTE (2.5, 5, and 10μM for 24h) was nontoxic and induced the nuclear transition of Nrf2. Pretreatment of PTE (2.5, 5, and 10μM for 2h) displayed a dose-dependently neuroprotective effect, as indicated by significantly prevented high glucose-induced loss of cellular viability, generation of ROS, reduced mitochondrial complex I and III activities, reduced mitochondrial cytochrome C, decreased ΔΨm, and increased LDH levels. Moreover, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and glutathione S-transferase (GST) were elevated after PTE treatment. In addition, the elevation of nuclear Nrf2 by PTE treatment (10μM for 2h) was abolished by Nrf2 siRNA. Importantly, Nrf2 siRNA induced the opposite changes in mitochondrial complex I and III activities, mitochondrial cytochrome C, reactive species generation, ΔΨm, and LDH. Overall, the present findings were the first to show that pterostilbene attenuated high glucose-induced central nervous system injury in vitro through the activation of Nrf2 signaling, displaying protective effects against mitochondrial dysfunction-derived oxidative stress.

  19. Volume-sensitive outwardly rectifying chloride channel blockers protect against high glucose-induced apoptosis of cardiomyocytes via autophagy activation.

    PubMed

    Wang, Lin; Shen, Mingzhi; Guo, Xiaowang; Wang, Bo; Xia, Yuesheng; Wang, Ning; Zhang, Qian; Jia, Lintao; Wang, Xiaoming

    2017-03-16

    Hyperglycemia is a well-characterized contributing factor for cardiac dysfunction and heart failure among diabetic patients. Apoptosis of cardiomyocytes plays a major role during the onset and pathogenesis of diabetic cardiomyopathy (DCM). Nonetheless, the molecular machinery underlying hyperglycemia-induced cardiac damage and cell death remains elusive. In the present study, we found that chloride channel blockers, 4,4'-diisothiocya-natostilbene-2,2'- disulfonic acid (DIDS) and 4-(2-butyl-6,7-dichlor-2-cyclopentyl-indan-1-on-5-yl) oxybutyric acid (DCPIB), inhibited high glucose-activated volume-sensitive outwardly rectifying (VSOR) Cl(-) channel and improved the viability of cardiomyocytes. High glucose induced cardiomyocyte apoptosis by suppressing the autophagic stress, which can be reversed via blockade of VSOR Cl(-) channel. VSOR activation in high glucose-treated cardiomyocytes was attributed to increased intracellular levels of reactive oxygen species (ROS). Taken together, our study unraveled a role of VSOR chloride currents in impaired autophagy and increased apoptosis of high glucose-exposed cardiomyocyte, and has implications for a therapeutic potential of VSOR chloride channel blockers in DCM.

  20. Effects of astragalosides from Radix Astragali on high glucose-induced proliferation and extracellular matrix accumulation in glomerular mesangial cells

    PubMed Central

    CHEN, XIAO; WANG, DONG-DONG; WEI, TONG; HE, SU-MEI; ZHANG, GUAN-YING; WEI, QUN-LI

    2016-01-01

    Diabetic nephropathy (DN) exhibits a deteriorating course that may lead to end-stage renal failure. Astragalosides have been clinically tested for the treatment of DN, but the mechanism is unclear at present. In this study, the effects of astragalosides were investigated on high glucose-induced proliferation and expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), type IV collagen (colIV) and fibronectin (FN) in glomerular mesangial cells (MCs). Cell proliferation was determined by 5-bromo-2′-deoxyuridine assay, and the expression of TGF-β1, CTGF, colIV and FN mRNA and proteins in MCs was detected by reverse transcription-polymerase chain reaction and ELISA assay, respectively. The results showed that high glucose clearly induced the proliferation of MCs and increased the expression of TGF-β1, CTGF, colIV and FN. Treatment with 50, 100, 200 µg/ml astragalosides inhibited cell proliferation and the expression of TGF-β1, CTGF, colIV and FN induced by high glucose. Thus, it is concluded that astragalosides inhibit the increased cell proliferation and expression of major extracellular matrix proteins that are induced by high glucose, indicating their value for the prophylaxis and therapy of DN. PMID:27313676

  1. Volume-sensitive outwardly rectifying chloride channel blockers protect against high glucose-induced apoptosis of cardiomyocytes via autophagy activation

    PubMed Central

    Wang, Lin; Shen, Mingzhi; Guo, Xiaowang; Wang, Bo; Xia, Yuesheng; Wang, Ning; Zhang, Qian; Jia, Lintao; Wang, Xiaoming

    2017-01-01

    Hyperglycemia is a well-characterized contributing factor for cardiac dysfunction and heart failure among diabetic patients. Apoptosis of cardiomyocytes plays a major role during the onset and pathogenesis of diabetic cardiomyopathy (DCM). Nonetheless, the molecular machinery underlying hyperglycemia-induced cardiac damage and cell death remains elusive. In the present study, we found that chloride channel blockers, 4,4′-diisothiocya-natostilbene-2,2′- disulfonic acid (DIDS) and 4-(2-butyl-6,7-dichlor-2-cyclopentyl-indan-1-on-5-yl) oxybutyric acid (DCPIB), inhibited high glucose-activated volume-sensitive outwardly rectifying (VSOR) Cl− channel and improved the viability of cardiomyocytes. High glucose induced cardiomyocyte apoptosis by suppressing the autophagic stress, which can be reversed via blockade of VSOR Cl− channel. VSOR activation in high glucose-treated cardiomyocytes was attributed to increased intracellular levels of reactive oxygen species (ROS). Taken together, our study unraveled a role of VSOR chloride currents in impaired autophagy and increased apoptosis of high glucose-exposed cardiomyocyte, and has implications for a therapeutic potential of VSOR chloride channel blockers in DCM. PMID:28300155

  2. Protective Effects of Panax notoginseng Saponins against High Glucose-Induced Oxidative Injury in Rat Retinal Capillary Endothelial Cells

    PubMed Central

    Fan, Yue; Qiao, Yuan; Huang, Jianmei

    2016-01-01

    Diabetic retinopathy, a leading cause of visual loss and blindness, is characterized by microvascular dysfunction. Hyperglycemia is considered the major pathogenic factor for diabetic retinopathy and is associated with increased oxidative stress in the retina. In this study, we investigated the potential protective effects of Panax notoginseng Saponins (PNS) in retinal capillary endothelial cells (RCECs) exposed to high glucose conditions. We found a pronounced increase in cell viability in rat RCECs incubated with both PNS and high glucose (30 mM) for 48 h or 72 h. The increased viability was accompanied by reduced intracellular hydrogen peroxide (H2O2) and superoxide (O2−), decreased mitochondrial reactive oxygen species (ROS), and lowered malondialdehyde (MDA) levels. PNS also increased the activities of total superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione peroxidase (GSH-PX). The glutathione (GSH) content also increased after PNS treatment. Furthermore, PNS reduced NADPH oxidase 4 (Nox4) expression. These results indicate that PNS exerts a protective effect against high glucose-induced injury in RCECs, which may be partially attributed to its antioxidative function. PMID:27019662

  3. H2 and H3 relaxin inhibit high glucose-induced apoptosis in neonatal rat ventricular myocytes.

    PubMed

    Zhang, Xiaohui; Ma, Xiao; Zhao, Meng; Zhang, Bo; Chi, Jinyu; Liu, Wenxiu; Chen, Wenjia; Fu, Yu; Liu, Yue; Yin, Xinhua

    2015-01-01

    High concentrations of glucose induce cardiomyocyte apoptosis, and contribute to diabetic cardiomyopathy. Relaxin-2 and relaxin-3 are two members of the relaxin peptide family that are cardioprotective. However, it remains unknown whether relaxin-2 or relaxin-3 can regulate apoptosis in high glucose treated-neonatal rat ventricular myocytes (NRVMs). In cultured NRVMs, 33 mmol/l high glucose (HG) increased apoptosis in a time-dependent manner. HG-increased the protein expression of cleaved caspase-8 and -9, two initiators of the extrinsic and intrinsic pathways of apoptosis, Caspase-3 was attenuated by human recombinant relaxin-2 (H2 relaxin) or relaxin-3 (H3 relaxin), indicating that H2 and H3 relaxin inhibited HG-induced apoptosis. Furthermore, endoplasmic reticulum stress (ERS) markers CHOP and caspase-12 were markedly increased in HG-treated NRVMs, leading to apoptosis; this effect was also effectively attenuated by H2 relaxin or H3 relaxin. Treatment of NRVMs with HG reduced autophagy which cannot be adjusted by H2 relaxin or H3 relaxin. In conclusion, HG-induced apoptosis in NRVMs was mediated, in part, by the activation of the extrinsic and intrinsic pathways of apoptosis and ERS, all inhibited by H2 relaxin or H3 relaxin.

  4. SIRT1 attenuates high glucose-induced insulin resistance via reducing mitochondrial dysfunction in skeletal muscle cells.

    PubMed

    Zhang, Hao-Hao; Ma, Xiao-Jun; Wu, Li-Na; Zhao, Yan-Yan; Zhang, Peng-Yu; Zhang, Ying-Hui; Shao, Ming-Wei; Liu, Fei; Li, Fei; Qin, Gui-Jun

    2015-05-01

    Insulin resistance is often characterized as the most critical factor contributing to the development of type 2 diabetes mellitus (T2DM). Sustained high glucose is an important extracellular environment that induces insulin resistance. Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial activity as a result of increased mitochondrial dysfunction. Silent information regulator 1 (SIRT1) is one member of the SIRT2 (Sir2)-like family of proteins involved in glucose homeostasis and insulin secretion in mammals. Although SIRT1 has a therapeutic effect on metabolic deterioration in insulin resistance, it is still not clear how SIRT1 is involved in the development of insulin resistance. Here, we demonstrate that pcDNA3.1 vector-mediated overexpression of SIRT1 attenuates insulin resistance in the high glucose-induced insulin-resistant skeleton muscle cells. These beneficial effects were associated with ameliorated mitochondrial dysfunction. Further studies have demonstrated that SIRT1 restores mitochondrial complex I activity leading to decreased oxidative stress and mitochondrial dysfunction. Furthermore, SIRT1 significantly elevated the level of another SIRT which is named SIRT3, and SIRT3 siRNA-suppressed SIRT1-induced mitochondria complex activity increments. Taken together, these results showed that SIRT1 improves insulin sensitivity via the amelioration of mitochondrial dysfunction, and this is achieved through the SIRT1-SIRT3-mitochondrial complex I pathway.

  5. High glucose induces inflammatory cytokine through protein kinase C-induced toll-like receptor 2 pathway in gingival fibroblasts

    SciTech Connect

    Jiang, Shao-Yun; Wei, Cong-Cong; Shang, Ting-Ting; Lian, Qi; Wu, Chen-Xuan; Deng, Jia-Yin

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer High glucose significantly induced TLR2 expression in gingival fibroblasts. Black-Right-Pointing-Pointer High glucose increased NF-{kappa}B p65 nuclear activity, IL-1{beta} and TNF-{alpha} levels. Black-Right-Pointing-Pointer PKC-{alpha}/{delta}-TLR2 pathway is involved in periodontal inflammation under high glucose. -- Abstract: Toll-like receptors (TLRs) play a key role in innate immune response and inflammation, especially in periodontitis. Meanwhile, hyperglycemia can induce inflammation in diabetes complications. However, the activity of TLRs in periodontitis complicated with hyperglycemia is still unclear. In the present study, high glucose (25 mmol/l) significantly induced TLR2 expression in gingival fibroblasts (p < 0.05). Also, high glucose increased nuclear factor kappa B (NF-{kappa}B) p65 nuclear activity, tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-l{beta} (IL-1{beta}) levels. Protein kinase C (PKC)-{alpha} and {delta} knockdown with siRNA significantly decreased TLR2 and NF-{kappa}B p65 expression (p < 0.05), whereas inhibition of PKC-{beta} had no effect on TLR2 and NF-{kappa}B p65 under high glucose (p < 0.05). Additional studies revealed that TLR2 knockdown significantly abrogated high-glucose-induced NF-{kappa}B expression and inflammatory cytokine secretion. Collectively, these data suggest that high glucose stimulates TNF-{alpha} and IL-1{beta} secretion via inducing TLR2 through PKC-{alpha} and PKC-{delta} in human gingival fibroblasts.

  6. High glucose-induced proteome alterations in hepatocytes and its possible relevance to diabetic liver disease.

    PubMed

    Chen, Jing-Yi; Chou, Hsiu-Chuan; Chen, You-Hsuan; Chan, Hong-Lin

    2013-11-01

    Hyperglycemia can cause several abnormalities in liver cells, including diabetic liver disease. Previous research has shown that high blood glucose levels can damage liver cells through glycoxidation. However, the detailed molecular mechanisms underlying the effects of high blood glucose on the development of diabetic liver disease have yet to be elucidated. In this study, we cultured a liver cell line (Chang liver cell) in mannitol-balanced 5.5 mM, 25 mM and 100 mM d-glucose media and evaluated protein expression and redox regulation. We identified 141 proteins that showed significant changes in protein expression and 29 proteins that showed significant changes in thiol reactivity, in response to high glucose concentration. Several proteins involved in transcription-control, signal transduction, redox regulation and cytoskeleton regulation showed significant changes in expression, whereas proteins involved in protein folding and gene regulation displayed changes in thiol reactivity. Further analyses of clinical plasma specimens confirmed that the proteins AKAP8L, galectin-3, PGK 1, syntenin-1, Abin 2, aldose reductase, CD63, GRP-78, GST-pi, RXR-gamma, TPI and vimentin showed type 2 diabetic liver disease-dependent alterations. In summary, in this study we used a comprehensive hepatocyte-based proteomic approach to identify changes in protein expression and to identify redox-associated diabetic liver disease markers induced by high glucose concentration. Some of the identified proteins were validated with clinical samples and are presented as potential targets for the prognosis and diagnosis of diabetic liver disease.

  7. Orientin inhibits high glucose-induced vascular inflammation in vitro and in vivo.

    PubMed

    Ku, Sae-Kwang; Kwak, Soyoung; Bae, Jong-Sup

    2014-12-01

    Vascular inflammation plays a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Orientin, a C-glycosyl flavonoid, is known to have anxiolytic and antioxidative activity. In this study, we assessed whether orientin can suppress vascular inflammation induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Our data indicate that HG markedly increased vascular permeability, monocyte adhesion, the expression of cell adhesion molecules (CAMs), the formation of reactive oxygen species (ROS), and the activation of nuclear factor kappa B (NF-κB). Remarkably, the vascular inflammatory effects of HG were attenuated by pretreatment with orientin. Since vascular inflammation induced by HG is critical in the development of diabetic complications, our results suggest that orientin may have significant benefits in the treatment of diabetic complications and atherosclerosis.

  8. Hyperoside inhibits high-glucose-induced vascular inflammation in vitro and in vivo.

    PubMed

    Ku, Sae-Kwang; Kwak, Soyoung; Kwon, O-Jun; Bae, Jong-Sup

    2014-10-01

    Hyperoside, an active compound from the genera of Hypericum and Crataegus, was reported to have antioxidant, antihyperglycemic, anticancer, anti-inflammatory, and anticoagulant activities. Vascular inflammatory process has been suggested to play a key role in initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether hyperoside can suppress vascular inflammatory processes induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Data showed that HG induced markedly increased vascular permeability, monocyte adhesion, expressions of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-κB. Remarkably, all of the above-mentioned vascular inflammatory effects of HG were attenuated by pretreatment with hyperoside. Vascular inflammatory responses induced by HG are critical events underlying development of various diabetic complications; therefore, our results suggest that hyperoside may have significant therapeutic benefits against diabetic complications and atherosclerosis.

  9. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    SciTech Connect

    Dong, Chenglong; Zheng, Haining; Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng; Ding, Dafa; Lu, Yibing

    2015-10-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK.

  10. Poria cocos inhibits high glucose-induced proliferation of rat mesangial cells.

    PubMed

    Yoon, Jung Joo; Lee, Yun Jung; Lee, So Min; Jin, Song Nan; Kang, Dae Gill; Lee, Ho Sub

    2013-01-01

    Mesangial cell proliferation is correlated with the progression of renal failure. The purpose of this study was to determine whether a water extract of Poria cocos Wolf (WPC), a well-known medicinal plant, regulates rat mesangial cell proliferation in the presence of high glucose (HG). HG significantly accelerated [(3)H]-thymidine incorporation, which was inhibited by WPC (1-50 μg/mL) in a dose-dependent manner. Cell migration and fibronectin mRNA expression data also supported the anti-proliferative effect of WPC. Western blot analysis revealed that pretreatment with WPC decreased the expression of cyclins and cyclin-dependent kinases (CDKs) and promoted the expression of p21(waf1/cip1) and p27(kip1). WPC also suppressed HG-induced p38 mitogen-activated protein kinase (p38 MAPK) and extracellular-signal-regulated kinase 1/2 (ERK 1/2) phosphorylation. Furthermore, WPC inhibited HG-induced production of dichlorofluorescein (DCF)-sensitive intracellular reactive oxygen species (ROS). In conclusion, HG promoted mesangial cell proliferation, and WPC inhibited this activity, at least in part, via induction of cell cycle arrest and activation of anti-oxidant properties. Taken together, these results suggest that P. cocos may be a potent regulator of HG-induced proliferation.

  11. Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts.

    PubMed

    Chao, Louis Kuoping; Chang, Wen-Teng; Shih, Yuan-Wei; Huang, Jau-Shyang

    2010-04-15

    Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and alpha-smooth muscle actin (alpha-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.

  12. Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption.

    PubMed

    Rajesh, Mohanraj; Mukhopadhyay, Partha; Bátkai, Sándor; Haskó, György; Liaudet, Lucas; Drel, Viktor R; Obrosova, Irina G; Pacher, Pál

    2007-07-01

    A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes. In this study we have investigated the effects of CBD on high glucose (HG)-induced, mitochondrial superoxide generation, NF-kappaB activation, nitrotyrosine formation, inducible nitric oxide synthase (iNOS) and adhesion molecules ICAM-1 and VCAM-1 expression, monocyte-endothelial adhesion, transendothelial migration of monocytes, and disruption of endothelial barrier function in human coronary artery endothelial cells (HCAECs). HG markedly increased mitochondrial superoxide generation (measured by flow cytometry using MitoSOX), NF-kappaB activation, nitrotyrosine formation, upregulation of iNOS and adhesion molecules ICAM-1 and VCAM-1, transendothelial migration of monocytes, and monocyte-endothelial adhesion in HCAECs. HG also decreased endothelial barrier function measured by increased permeability and diminished expression of vascular endothelial cadherin in HCAECs. Remarkably, all the above mentioned effects of HG were attenuated by CBD pretreatment. Since a disruption of the endothelial function and integrity by HG is a crucial early event underlying the development of various diabetic complications, our results suggest that CBD, which has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in humans, may have significant therapeutic benefits against diabetic complications and atherosclerosis.

  13. High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43.

    PubMed

    Yu, Hongmei; Yang, Juan; Zhou, Xiangdong; Xiao, Qian; Lü, Yang; Xia, Li

    2016-03-01

    The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases.

  14. High glucose induces rat mesangial cells proliferation and MCP-1 expression via ROS-mediated activation of NF-κB pathway, which is inhibited by eleutheroside E.

    PubMed

    Yang, Xiuqin; Wang, Yangang; Gao, Guanqi

    2016-01-01

    Glomerular hypertrophy and extracellular matrix accumulation are early features of diabetic nephropathy (DN). High glucose-induced oxidative stress is implicated in the etiology of DN. This study aims to investigate the effect of eleutheroside E (EE) on high glucose mediated rat mesangial cells (MCs) proliferation and monocyte chemoattractant protein-1 (MCP-1) expression and the underlying mechanism. MCs proliferation was assessed by MTT assay. Reactive oxygen species (ROS) level and MCP-1 expression were evaluated by ELISA kit. The protein expression of p47, NF-κB p65, p-NF-κB p65, IκBα, p-IκBα, IKKβ and p-IKKβ were determined by Western blot. The results showed that treatment with EE markedly attenuated high glucose induced MCs proliferation and in a dose-dependent manner. Intervention with EE also significantly blocked high glucose induced intracellular ROS production by decreasing NADPH oxidase activity. Meanwhile, EE administration could effectively alleviate the high glucose-stimulated activation of NF-κB, the degradation of IκBα and the expression of MCP-1. These results demonstrate that high glucose enhances MCs proliferation and MCP-1 expression by activating the ROS/NF-κB pathway and can be inhibited by EE. Our findings provide a new perspective for the clinical treatment of DN.

  15. High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells

    SciTech Connect

    Huang, Wei; Xu, Ling; Zhou, Xueqin; Gao, Chenlin; Yang, Maojun; Chen, Guo; Zhu, Jianhua; Jiang, Lan; Gan, Huakui; Gou, Fang; Feng, Hong; Peng, Juan; Xu, Yong

    2013-08-30

    Highlights: •The expression of SUMO1, SUMO2/3 under high glucose was obviously enhanced. •High glucose induced degradation of IκBα and activation of NF-κB pathway. •Sumoylation of IκBα in high glucose were significantly decreased. •The proteasome inhibitor MG132 could partially revert the degradation of IκBα. -- Abstract: The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor κB (NF-κB) pathway, which plays a critical role in the regulation of inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-κB signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6 mmol/L), high glucose groups (10, 20, and 30 mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30 mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, IκBα, NF-κBp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and IκBα was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently enhanced by high glucose (p < 0.05). However, the expression of IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p < 0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 and MCP-1 were increased under high glucose conditions, which

  16. Agmatine protects Müller cells from high-concentration glucose-induced cell damage via N-methyl-D-aspartic acid receptor inhibition.

    PubMed

    Han, Ning; Yu, Li; Song, Zhidu; Luo, Lifu; Wu, Yazhen

    2015-07-01

    Neural injury is associated with the development of diabetic retinopathy. Müller cells provide structural and metabolic support for retinal neurons. High glucose concentrations are known to induce Müller cell activity. Agmatine is an endogenous polyamine, which is enzymatically formed in the mammalian brain and has exhibited neuroprotective effects in a number of experimental models. The aims of the present study were to investigate whether agmatine protects Müller cells from glucose-induced damage and to explore the mechanisms underlying this process. Lactate dehydrogenase activity and tumor necrosis factor-α mRNA expression were significantly reduced in Müller cells exposed to a high glucose concentration, following agmatine treatment, compared with cells not treated with agmatine. In addition, agmatine treatment inhibited glucose-induced Müller cell apoptosis, which was associated with the regulation of Bax and Bcl-2 expression. Agmatine treatment suppressed glucose-induced phosphorylation of mitogen-activated protein kinase (MAPK) protein in Müller cells. The present study demonstrated that the protective effects of agmatine on Müller cells were inhibited by N-methyl-D-aspartic acid (NMDA). The results of the present study suggested that agmatine treatment protects Müller cells from high-concentration glucose-induced cell damage. The underlying mechanisms may relate to the anti-inflammatory and antiapoptotic effects of agmatine, as well as to the inhibition of the MAPK pathway, via NMDA receptor suppression. Agmatine may be of use in the development of novel therapeutic approaches for patients with diabetic retinopathy.

  17. Hydrophobic motif site-phosphorylated protein kinase CβII between mTORC2 and Akt regulates high glucose-induced mesangial cell hypertrophy.

    PubMed

    Das, Falguni; Ghosh-Choudhury, Nandini; Mariappan, Meenalakshmi M; Kasinath, Balakuntalam S; Choudhury, Goutam Ghosh

    2016-04-01

    PKCβII controls the pathologic features of diabetic nephropathy, including glomerular mesangial cell hypertrophy. PKCβII contains the COOH-terminal hydrophobic motif site Ser-660. Whether this hydrophobic motif phosphorylation contributes to high glucose-induced mesangial cell hypertrophy has not been determined. Here we show that, in mesangial cells, high glucose increased phosphorylation of PKCβII at Ser-660 in a phosphatidylinositol 3-kinase (PI3-kinase)-dependent manner. Using siRNAs to downregulate PKCβII, dominant negative PKCβII, and PKCβII hydrophobic motif phosphorylation-deficient mutant, we found that PKCβII regulates activation of mechanistic target of rapamycin complex 1 (mTORC1) and mesangial cell hypertrophy by high glucose. PKCβII via its phosphorylation at Ser-660 regulated phosphorylation of Akt at both catalytic loop and hydrophobic motif sites, resulting in phosphorylation and inactivation of its substrate PRAS40. Specific inhibition of mTORC2 increased mTORC1 activity and induced mesangial cell hypertrophy. In contrast, inhibition of mTORC2 decreased the phosphorylation of PKCβII and Akt, leading to inhibition of PRAS40 phosphorylation and mTORC1 activity and prevented mesangial cell hypertrophy in response to high glucose; expression of constitutively active Akt or mTORC1 restored mesangial cell hypertrophy. Moreover, constitutively active PKCβII reversed the inhibition of high glucose-stimulated Akt phosphorylation and mesangial cell hypertrophy induced by suppression of mTORC2. Finally, using renal cortexes from type 1 diabetic mice, we found that increased phosphorylation of PKCβII at Ser-660 was associated with enhanced Akt phosphorylation and mTORC1 activation. Collectively, our findings identify a signaling route connecting PI3-kinase to mTORC2 to phosphorylate PKCβII at the hydrophobic motif site necessary for Akt phosphorylation and mTORC1 activation, leading to mesangial cell hypertrophy.

  18. The dual targeting of EGFR and ErbB2 with the inhibitor Lapatinib corrects high glucose-induced apoptosis and vascular dysfunction by opposing multiple diabetes-induced signaling changes.

    PubMed

    Benter, Ibrahim F; Sarkhou, Fatima; Al-Khaldi, Abeer T; Chandrasekhar, Bindu; Attur, Sreeja; Dhaunsi, Gursev S; Yousif, Mariam H M; Akhtar, Saghir

    2015-01-01

    The epidermal growth factor receptors, EGFR and EGFR2 (ErbB2), appear important mediators of diabetes-induced vascular dysfunction. We investigated whether targeted dual inhibition of EGFR and ErbB2 with Lapatinib would be effective in treating diabetes-induced vascular dysfunction in a rat model of type 1 diabetes. In streptozotocin-induced diabetes, chronic 4-week oral or acute, ex vivo, administration of Lapatinib prevented the development of vascular dysfunction as indicated by the attenuation of the hyper-reactivity of the diabetic mesenteric vascular bed (MVB) to norephinephrine without correcting hyperglycemia. Chronic in vivo or acute ex vivo Lapatinib treatment also significantly attenuated diabetes-induced increases in phosphorylation of EGFR, ErbB2, ERK1/2, AKT, ROCK2 and IkB-alpha as well as normalized the reduced levels of phosphorylated FOXO3A, and eNOS (Ser1177) in the diabetic MVB. Similar results were observed in vascular smooth muscle cells (VSMCs) cultured in high glucose (25 mM) treated with Lapatinib or small interfering RNA (siRNA) targeting the ErbB2 receptor. Lapatinib also prevented high glucose-induced apoptosis in VSMC. Thus, Lapatinib corrects hyperglycemia-induced apoptosis and vascular dysfunction with concomitant reversal of diabetes or high glucose-induced signaling changes in EGFR/ErbB2 and downstream signaling pathways implying that targeted dual inhibition of EGFR/ErbB2 might be an effective vasculoprotective treatment strategy in diabetic patients.

  19. SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat

    PubMed Central

    Lee, Dongyeop; Jeong, Dae-Eun; Son, Heehwa G.; Yamaoka, Yasuyo; Kim, Hyunmin; Seo, Keunhee; Khan, Abdul Aziz; Roh, Tae-Young; Moon, Dae Won; Lee, Youngsook; Lee, Seung-Jae V.

    2015-01-01

    Glucose-rich diets shorten the life spans of various organisms. However, the metabolic processes involved in this phenomenon remain unknown. Here, we show that sterol regulatory element-binding protein (SREBP) and mediator-15 (MDT-15) prevent the life-shortening effects of a glucose-rich diet by regulating fat-converting processes in Caenorhabditis elegans. Up-regulation of the SREBP/MDT-15 transcription factor complex was necessary and sufficient for alleviating the life-shortening effect of a glucose-rich diet. Glucose feeding induced key enzymes that convert saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), which are regulated by SREBP and MDT-15. Furthermore, SREBP/MDT-15 reduced the levels of SFAs and moderated glucose toxicity on life span. Our study may help to develop strategies against elevated blood glucose and free fatty acids, which cause glucolipotoxicity in diabetic patients. PMID:26637528

  20. Asiaticoside protects cochlear hair cells from high glucose-induced oxidative stress via suppressing AGEs/RAGE/NF-κB pathway.

    PubMed

    Xing, Ying; Ji, Qiuhe; Li, Xiaomiao; Ming, Jie; Zhang, Nana; Zha, Dingjun; Lin, Ying

    2017-02-01

    Asiaticoside (AC) has been known to have anti-oxidative activity, however, the effect of AC on the progression of high glucose-induced hearing loss has not been studied. This study aims to analyze the effect of AC on cochlear hair cells under the treatment of high glucose in vitro and the hearing function in vivo. The results of MTT showed that high glucose decreased the activity of HEI-OC1 cells, but AC increased the activity of HEI-OC1 cells compared with high glucose group. The results of flow cytometry showed that AC decreased the degree of apoptosis induced by high levels of glucose. The results of DCFH-DA staining showed that AC inhibited the ROS production induced by high glucose levels. The results of JC-1 staining showed that AC inhibited the mitochondrial depolarization induced by high glucose levels. Furthermore, AC decreased the threshold, and protected inner and outer hair cells from damage in rats with hearing loss induced by diabetes mellitus. Moreover, AC decreased the activity of MDA, but, increased the activity of SOD, CAT and GSH-Px in vivo. AC also decreased the expression of AGEs, RAGE and NF-κB p65. Collectively, these results suggest that AC protects cochlear hair cells from high glucose-induced injury by increasing anti-oxidative activity and suppressing the AGEs/RAGE/NF-κB pathway.

  1. Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway

    PubMed Central

    Gao, Haiyang; Xu, Ruixia; Teng, Siyong; Wu, Yongjian

    2015-01-01

    Endothelial senescence plays crucial roles in diabetic vascular complication. Recent evidence indicated that transient hyperglycaemia could potentiate persistent diabetic vascular complications, a phenomenon known as “metabolic memory.” Although SIRT1 has been demonstrated to mediate high glucose-induced endothelial senescence, whether and how “metabolic memory” would affect endothelial senescence through SIRT1 signaling remains largely unknown. In this study, we investigated the involvement of SIRT1 axis as well as the protective effects of resveratrol (RSV) and metformin (MET), two potent SIRT1 activators, during the occurrence of “metabolic memory” of cellular senescence (senescent “memory”). Human umbilical vascular endothelial cells (HUVECs) were cultured in either normal glucose (NG)/high glucose (HG) media for 6 days, or 3 days of HG followed by 3 days of NG (HN), with or without RSV or MET treatment. It was shown that HN incubation triggered persistent downregulation of deacetylase SIRT1 and upregulation of acetyltransferase p300, leading to sustained hyperacetylation (at K382) and activation of p53, and subsequent p53/p21-mediated senescent “memory.” In contrast, senescent “memory” was abrogated by overexpression of SIRT1 or knockdown of p300. Interestingly, we found that SIRT1 and p300 could regulate each other in response to HN stimulation, suggesting that a delicate balance between acetyltransferases and deacetylases may be particularly important for sustained acetylation and activation of non-histone proteins (such as p53), and eventually the occurrence of “metabolic memory.” Furthermore, we found that RSV or MET treatment prevented senescent “memory” by modulating SIRT1/p300/p53/p21 pathway. Notably, early and continuous treatment of MET, but not RSV, was particularly important for preventing senescent “memory.” In conclusion, short-term high glucose stimulation could induce sustained endothelial senescence via SIRT

  2. Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts.

    PubMed

    Zhang, Yu; Yang, Jian-Hong

    2013-11-01

    Diabetes mellitus is associated with increased risk of osteopenia and bone fracture that may be related to hyperglycemia. However, the mechanisms accounting for diabetic bone disorder are unclear. Here, we showed that high glucose significantly promoted the production of reactive oxygen species (ROS) in rat primary osteoblasts. Most importantly, we reported for the first time that ROS induced by high glucose increased alkaline phosphatase activity, inhibited type I collagen (collagen I) protein level and cell mineralization, as well as gene expression of osteogenic markers including runt-related transcription factor 2 (Runx2), collagen I, and osteocalcin, but promoted lipid droplet formation and gene expression of adipogenic markers including peroxisome proliferator-activated receptor gamma, adipocyte fatty acid binding protein (aP2), and adipsin, which were restored by pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, high glucose-induced oxidative stress activated PI3K/Akt pathway to inhibited osteogenic differentiation but stimulated adipogenic differentiation. In contrast, NAC and a PI3K inhibitor, LY-294002, reversed the down-regulation of osteogenic markers and the up-regulation of adipogenic markers as well as the activation of Akt under high glucose. These results indicated that oxidative stress played a key role in high glucose-induced increase of adipogenic differentiation, which contributed to the inhibition of osteogenic differentiation. This process was mediated by PI3K/Akt pathway in rat primary osteoblasts. Hence, suppression of oxidative stress could be a potential therapeutic approach for diabetic osteopenia.

  3. Propolis, a Constituent of Honey, Inhibits the Development of Sugar Cataracts and High-Glucose-Induced Reactive Oxygen Species in Rat Lenses

    PubMed Central

    Shibata, Teppei; Shibata, Shinsuke; Shibata, Naoko; Kiyokawa, Etsuko; Singh, Dhirendra P.

    2016-01-01

    Purpose. This study investigated the effects of oral propolis on the progression of galactose-induced sugar cataracts in rats and the in vitro effects of propolis on high-glucose-induced reactive oxygen species (ROS) and cell death in cultured rat lens cells (RLECs). Methods. Galactose-fed rats and RLECs cultured in high glucose (55 mM) medium were treated with propolis or vehicle control. Relative lens opacity was assessed by densitometry and changes in lens morphology by histochemical analysis. Intracellular ROS levels and cell viability were measured. Results. Oral administration of propolis significantly inhibited the onset and progression of cataract in 15% and 25% of galactose-fed rats, respectively. RLECs cultured with high glucose showed a significant increase in ROS expression with reduced cell viability. Treatment of these RLECs with 5 and 50 μg/mL propolis cultured significantly reduced ROS levels and increased cell viability, indicating that the antioxidant activity of propolis protected cells against ROS-induced damage. Conclusion. Propolis significantly inhibited the onset and progression of sugar cataract in rats and mitigated high-glucose-induced ROS production and cell death. These effects may be associated with the ability of propolis to inhibit hyperglycemia-evoked oxidative or osmotic stress-induced cellular insults. PMID:27242920

  4. Protective effect of trans-δ-viniferin against high glucose-induced oxidative stress in human umbilical vein endothelial cells through the SIRT1 pathway.

    PubMed

    Zhao, Huijun; Ma, Ting; Fan, Boyi; Yang, Lei; Han, Chao; Luo, Jianguang; Kong, Lingyi

    2016-01-01

    Oxidative stress plays a critical role in the pathogenesis of diabetic vascular complications. Trans-δ-viniferin (TVN), a polyphenolic compound, has recently attracted much attention as an antioxidant exhibiting a hypoglycemic potential. In the present study, we aimed at investigating the protective effect of TVN against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVECs) and the potential mechanism involved. We found that TVN attenuated reactive oxygen species (ROS) production, increased catalase (CAT) activity and decreased malondialdehyde (MDA) levels to ameliorate cell survival induced by 35 mM glucose. Meanwhile, it inhibited high glucose-induced apoptosis by maintaining Ca(2+) and preserving mitochondrial membrane potential (MMP) levels. The immunoblot analysis indicated that TVN efficiently regulated the cleavage of caspase family, p53, Bax and Bcl-2, all mediated by SIRT1. Furthermore, the increased level of SIRT1 induced by TVN was inhibited by nicotinamide and siRNA-medicated SIRT1 silencing (si-SIRT1), thereby confirming the significant role of SIRT1 in these events. In conclusion, our results indicated that TVN efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in high glucose-treated HUVECs. It suggested that TVN is pharmacologically promising for treating diabetic cardiovascular complications.

  5. Irisin Promotes Human Umbilical Vein Endothelial Cell Proliferation through the ERK Signaling Pathway and Partly Suppresses High Glucose-Induced Apoptosis

    PubMed Central

    Song, Haibo; Wu, Fei; Zhang, Yuan; Zhang, Yuzhu; Wang, Fang; Jiang, Miao; Wang, Zhongde; Zhang, Mingxiang; Li, Shiwu; Yang, Lijun; Wang, Xing Li; Cui, Taixing; Tang, Dongqi

    2014-01-01

    Irisin is a newly discovered myokine that links exercise with metabolic homeostasis. It is involved in modest weight loss and improves glucose intolerance. However, the direct effects and mechanisms of irisin on vascular endothelial cells (ECs) are not fully understood. In the current study, we demonstrated that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) proliferation. It was further demonstrated that this pro-proliferation effect was mediated by irisin-induced activation of extracellular signal–related kinase (ERK) signaling pathways. Inhibition of ERK signaling with U0126 decreased the pro-proliferation effect of irisin on HUVECs. It was also demonstrated that irisin reduced high glucose-induced apoptosis by up-regulating Bcl-2 expression and down-regulating Bax, Caspase-9 and Caspase-3 expression. In summary, these results suggested that irisin plays a novel role in sustaining endothelial homeostasis by promoting HUVEC proliferation via the ERK signaling pathway and protects the cell from high glucose-induced apoptosis by regulating Bcl-2,Bax and Caspase expression. PMID:25338001

  6. The pivotal role of high glucose-induced overexpression of PKCβ in the appearance of glucagon-like peptide-1 resistance in endothelial cells.

    PubMed

    Pujadas, Gemma; De Nigris, Valeria; La Sala, Lucia; Testa, Roberto; Genovese, Stefano; Ceriello, Antonio

    2016-11-01

    Recently, it has been demonstrated that Glucagon-like peptide-1 (GLP-1) has a protective effect on endothelial cells. Our hypothesis is that this GLP-1 protective effect is partly lost when the cells are exposed to sustained high glucose concentrations. Human umbilical vein endothelial cells (HUVECs) were cultured for 21 days in normal glucose (5 mmol/L, NG) or high glucose (25 mmol/L glucose, HG). GLP-1 (7-37) and Ruboxistaurin were added at 50 and 500 nM, respectively, alone or in combination, 1 h before cell harvesting. Analysis of GLP-1 receptor protein levels, as well as of the gene expression of different ER stress-related genes, proliferation markers, antioxidant cell response-related genes, and PKA subunits, was performed. ROS production was also measured in HUVECs exposed to mentioned treatments. GLP-1 receptor expression was reduced in HUVECs exposed to chronic high glucose concentrations but was partially restored by a chemical PKCβ-specific inhibitor. GLP-1, added as an acute treatment in endothelial cells, had the capacity to induce the expression of Nrf2-detoxifying enzyme targets, to increase transcription levels of scavenger genes, to attenuate the expression of high glucose-induced PKA subunits, ER stress and also the apoptotic phenotype of HUVECs; these effects occured only when high glucose-induced PKCβ overexpression was reduced by Ruboxistaurin. In a similar manner, ROS production induced by high glucose was reduced by GLP-1 in the presence of PKCβ inhibitor. This study suggests that an increase in PKCβ, induced by high glucose, could have a role in endothelial GLP-1 resistance, reducing GLP-1 receptor levels and disrupting the GLP-1 canonical pathway.

  7. Tea polyphenols alleviate high fat and high glucose-induced endothelial hyperpermeability by attenuating ROS production via NADPH oxidase pathway

    PubMed Central

    2014-01-01

    Background Hyperglycemia-induced endothelial hyperpermeability is crucial to cardiovascular disorders and macro-vascular complications in diabetes mellitus. The objective of this study is to investigate the effects of green tea polyphenols (GTPs) on endothelial hyperpermeability and the role of nicotinamide adenine dinucleotide phosphate (NADPH) pathway. Methods Male Wistar rats fed on a high fat diet (HF) were treated with GTPs (0, 0.8, 1.6, 3.2 g/L in drinking water) for 26 weeks. Bovine aortic endothelial cells (BAECs) were treated with high glucose (HG, 33 mmol/L) and GTPs (0.0, 0.4, or 4 μg/mL) for 24 hours in vitro. The endothelial permeabilities in rat aorta and monolayer BAECs were measured by Evans blue injection method and efflux of fluorescein isothiocyanate (FITC)-dextran, respectively. The reactive oxygen species (ROS) levels in rat aorta and monolayer BAECs were measured by dihydroethidium (DHE) and 2′, 7′-dichloro-fluorescein diacetate (DCFH-DA) fluorescent probe, respectively. Protein levels of NADPH oxidase subunits were determined by Western-blot. Results HF diet-fed increased the endothelial permeability and ROS levels in rat aorta while HG treatments increased the endothelial permeability and ROS levels in cultured BAECs. Co-treatment with GTPs alleviated those changes both in vivo and in vitro. In in vitro studies, GTPs treatments protected against the HG-induced over-expressions of p22phox and p67phox. Diphenylene iodonium chloride (DPI), an inhibitor of NADPH oxidase, alleviated the hyperpermeability induced by HG. Conclusions GTPs could alleviate endothelial hyperpermeabilities in HF diet-fed rat aorta and in HG treated BAECs. The decrease of ROS production resulting from down-regulation of NADPH oxidase contributed to the alleviation of endothelial hyperpermeability. PMID:24580748

  8. Vaccarin attenuates high glucose-induced human EA•hy926 endothelial cell injury through inhibition of Notch signaling.

    PubMed

    Qiu, Yuyu; Du, Bin; Xie, Fengshan; Cai, Weiwei; Liu, Yanling; Li, Yue; Feng, Lei; Qiu, Liying

    2016-03-01

    Endothelial cell injury is a critical component of atherosclerosis and hypertension. Vaccarin is considered to be of potential benefit in the treatment of vascular diseases. The aim of the present study was to evaluate the possible effects of vaccarin in human EA·hy926 cells induced by high glucose, and to investigate its underlying mechanism in the prevention and treatment of high glucose‑induced injury. In the present study, EA·hy926 cells were exposed to 90, 180 and 270 mM high glucose for 24 h, and the induced cell injury was examined using a sulforhodamine B assay. Following treatment with high glucose, it was found that high glucose stimulated cell injury, resulting in reduced cell viability and migratory ability, increased lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity. High glucose further accelerated cell apoptosis via activating Notch1 and Hairy and enhancer of split 1. It was found that preincubation with vaccarin protected the EA·hy926 cells from high glucose‑induced cell injury, which promoted cell viability and migratory ability, inhibited the expression levels of LDH and MDA, and enhanced the activity of SOD. Cell migratory ability, LDH leakage, MDA levels and decreasing SOD activity were evaluated using a wound healing assay and corresponding assay kits. Cell apoptosis was detected by flow cytometry with an Annexin V‑fluorescein isothiocyanate/propidium iodide apoptosis detection kit and Hoechst staining. Furthermore, western blotting was used to detect the protein expression levels of Notch1, Hes1 and caspase‑3. In particular, in addition to inducing the downregulation of Notch signaling, vaccarin treatment downregulated the cell apoptotic pathway‑associated protein caspase 3. These findings suggested that vaccarin may be able to selectively protect the vascular endothelium from dysfunction induced by high glucose.

  9. Resveratrol inhibits high glucose induced collagen upregulation in cardiac fibroblasts through regulating TGF-β1-Smad3 signaling pathway.

    PubMed

    Liu, Junhui; Zhuo, Xiaozhen; Liu, Weimin; Wan, Zhaofei; Liang, Xiao; Gao, Shanshan; Yuan, Zuyi; Wu, Yue

    2015-02-05

    Cardiac fibrosis is a common pathological process presented in a variety of diseases, including hypertension and diabetes. Cardiac fibroblasts (CFs) have been identified as the most important participants in the development of cardiac fibrosis. Exposure of cultured CFs to high glucose (HG) or angiotensin II (Ang II) resulted in increased collagen synthesis. Resveratrol (Res) is a natural polyphenol exhibiting anti-fibrosis effects in a number of different organs fibrosis process, whether Res can prevent HG and Ang II induced fibrosis response in CFs remains unclear. The aim of this work was to evaluate the effects of Res in HG and Ang II induced fibrosis response in CFs. We cultured rat CFs in either normal glucose (5.6 mM) or HG (25 mM) media in the presence of Res or not and the changes in collagens synthesis and TGF-β1 production were assessed by Real-time PCR, Western blotting, and enzyme linked immunosorbent assay (ELISA). Furthermore, normal and diabetic mice (induced by single dose of streptozotocin (100 mg/kg) via tail vein) receiving Res (10 mg/kg) were used to explore the effects of Res on cardiac fibrosis in vivo. Masson staining and immunohistochemistry were performed to visualize cardiac collagen deposition. Results indicate that CFs exposed to HG condition shows enhanced proliferation rate. Furthermore, in the presence of HG or Ang II, CFs exhibited increased collagens synthesis and TGF-β1 production. And these effects were abolished by Res intervention. In vivo results show that diabetic mice exhibit increased collagen deposition in the cardiac compared with the normal mice. And this change was prevented by the treatment of Res. These results suggest that Res possesses a potential antifibrogenic effect in hypertension and diabetes-related cardiac fibrosis. Moreover, the action mechanism is probably associated with its ability to reduce TGF-β1 content in CFs.

  10. HGF alleviates high glucose-induced injury in podocytes by GSK3β inhibition and autophagy restoration.

    PubMed

    Zhang, Congying; Hou, Bo; Yu, Siying; Chen, Qi; Zhang, Nong; Li, Hui

    2016-11-01

    Podocyte injury or loss plays a major role in the pathogenesis of proteinuric kidney disease including diabetic nephropathy (DN). High basal level of autophagy is critical for podocyte health. Recent studies have revealed that hepatocyte growth factor (HGF) can ameliorate podocyte injury and proteinuria. However, little is known about the impact of HGF on podocyte autophagy. In this study, we investigated whether and how HGF affects autophagy in podocytes treated with high glucose (HG) conditions. HGF significantly diminishes apoptosis, oxidative stress and autophagy impairment inflicted by HG in podocytes. These beneficial effects of HGF disappear once HGF receptor is blocked by SU11274, a specific inhibitor of c-Met. Moreover, HGF markedly suppresses HG-stimulated glycogen synthase kinase 3beta (GSK3β) activity. Accordingly, exogenous constitutively-active GSK3β overexpression using an adenoviral vector system (Ad-GSK3β-S9A) abrogates the ability of HGF to ameliorate HG-mediated podocyte injury while neither adenoviral-mediated overexpression of wild-type GSK3β (Ad-GSK3β-WT) nor adenoviral transduction of inactive GSK3β mutant (Ad-GSK3β-K85A) can counteract the protective effects of HGF on HG-treated podocytes. Collectively, these results suggest that HGF prevents HG-induced podocyte injury via an autophagy-promoting mechanism, which involves GSK3β inhibition.

  11. High glucose-induced oxidative stress represses sirtuin deacetylase expression and increases histone acetylation leading to neural tube defects.

    PubMed

    Yu, Jingwen; Wu, Yanqing; Yang, Peixin

    2016-05-01

    Aberrant epigenetic modifications are implicated in maternal diabetes-induced neural tube defects (NTDs). Because cellular stress plays a causal role in diabetic embryopathy, we investigated the possible role of the stress-resistant sirtuin (SIRT) family histone deacetylases. Among the seven sirtuins (SIRT1-7), pre-gestational maternal diabetes in vivo or high glucose in vitro significantly reduced the expression of SIRT 2 and SIRT6 in the embryo or neural stem cells, respectively. The down-regulation of SIRT2 and SIRT6 was reversed by superoxide dismutase 1 (SOD1) over-expression in the in vivo mouse model of diabetic embryopathy and the SOD mimetic, tempol and cell permeable SOD, PEGSOD in neural stem cell cultures. 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a superoxide generating agent, mimicked high glucose-suppressed SIRT2 and SIRT6 expression. The acetylation of histone 3 at lysine residues 56 (H3K56), H3K14, H3K9, and H3K27, putative substrates of SIRT2 and SIRT6, was increased by maternal diabetes in vivo or high glucose in vitro, and these increases were blocked by SOD1 over-expression or tempol treatment. SIRT2 or SIRT6 over-expression abrogated high glucose-suppressed SIRT2 or SIRT6 expression, and prevented the increase in acetylation of their histone substrates. The potent sirtuin activator (SRT1720) blocked high glucose-increased histone acetylation and NTD formation, whereas the combination of a pharmacological SIRT2 inhibitor and a pan SIRT inhibitor mimicked the effect of high glucose on increased histone acetylation and NTD induction. Thus, diabetes in vivo or high glucose in vitro suppresses SIRT2 and SIRT6 expression through oxidative stress, and sirtuin down-regulation-induced histone acetylation may be involved in diabetes-induced NTDs. The mechanism underlying pre-gestational diabetes-induced neural tube defects (NTDs) is still elusive. Our study unravels a new epigenetic mechanism in which maternal diabetes-induced oxidative stress represses

  12. Quercetin and sesamin protect neuronal PC12 cells from high-glucose-induced oxidation, nitrosative stress, and apoptosis.

    PubMed

    Bournival, Julie; Francoeur, Marc-André; Renaud, Justine; Martinoli, Maria-Grazia

    2012-06-01

    Complications of diabetes are now well-known to affect sensory, motor, and autonomic nerves. Diabetes is also thought to be involved in neurodegenerative processes characteristic of several neurodegenerative diseases. Indeed, it has been acknowledged recently that hyperglycemia-induced oxidative stress contributes to numerous cellular reactions typical of central nervous system deterioration. The goal of the present study was to evaluate the effects of the polyphenol quercetin and the lignan sesamin on high-glucose (HG)-induced oxidative damage in an in vitro model of dopaminergic neurons, neuronal PC12 cells. When incubated with HG (13.5 mg/mL), neuronal PC12 cells showed a significant increase of cellular death. Our results revealed that quercetin and sesamin defend neuronal PC12 cells from HG-induced cellular demise. An elevated level of reactive oxygen and nitrogen species is a consequence of improved oxidative stress after HG administration, and we demonstrated that this production diminishes with quercetin and sesamin treatment. We also found that quercetin and sesamin elicited an increment of superoxide dismutase activity. DNA fragmentation, Bax/Bcl-2 ratio, nuclear translocation of apoptosis-inducing factor, as well as poly(adenosine diphosphate [ADP]-ribose) polymerase cleavage were significantly reduced by quercetin and sesamin administration, affirming their antiapoptotic features. Also, HG treatment impacted caspase-3 cleavage, supporting caspase-3-dependent pathways as mechanisms of apoptotic death. Our results indicate a powerful role for these natural dietary compounds and emphasize preventive or complementary nutritional strategies for diabetes control.

  13. Berberine attenuates high glucose-induced proliferation and extracellular matrix accumulation in mesangial cells: involvement of suppression of cell cycle progression and NF-κB/AP-1 pathways.

    PubMed

    Lan, Tian; Wu, Teng; Chen, Cheng; Chen, Xiaolan; Hao, Jie; Huang, Junying; Wang, Lijing; Huang, Heqing

    2014-03-25

    Berberine has been shown to have renoprotective effects on diabetes through attenuating TGF-β1 and fibronectin (FN) expression. However, how berberine regulates TGF-β1 and FN is not fully clear. Here we investigated whether berberine inhibited TGF-β1 and FN expression in high glucose-cultured mesangial cells. Berberine significantly inhibited mesangial cell proliferation and hypertrophy by increasing the cell population in G1-phase and reducing that in S-phase. In addition, berberine reversed high glucose-induced down-regulation of cyclin-dependent kinase inhibitor p21(Waf1)/(Cip1) and p27(Kip1). Berberine inhibited p65 translocation to the nucleus and c-jun phosphorylation induced by high glucose. Furthermore, berberine attenuated high glucose-induced expression of TGF-β1 and FN. Using a luciferase reporter assay, we found that high glucose-induced transcription activity of NF-κB and AP-1 was blocked by berberine. Electrophoretic mobility shift assay showed that high glucose increased that NF-κB and AP-1 DNA binding activity. These data indicate that berberine inhibited mesangial cell proliferation and hypertrophy by modulating cell cycle progress. In addition, berberine suppressed high glucose-induced TGF-β1 and FN expression by blocking NF-κB/AP-1 pathways.

  14. High glucose induces cell death of cultured human aortic smooth muscle cells through the formation of hydrogen peroxide

    PubMed Central

    Peiró, Concepción; Lafuente, Nuria; Matesanz, Nuria; Cercas, Elena; Llergo, José L; Vallejo, Susana; Rodríguez-Mañas, Leocadio; Sánchez-Ferrer, Carlos F

    2001-01-01

    Alterations of the vessel structure, which is mainly determined by smooth muscle cells through cell growth and/or cell death mechanisms, are characteristic of diabetes complications. We analysed the influence of high glucose (22 mM) on cultured human aortic smooth muscle cell growth and death, as hyperglycaemia is considered one of the main factors involved in diabetic vasculopathy. Growth curves were performed over 96 h in medium containing 0.5% foetal calf serum. Cell number increased by 2–4 fold over the culture period in the presence of 5.5 mM (low) glucose, while a 20% reduction in final cell number was observed with high glucose. Under serum-free conditions, cell number remained constant in low glucose cultures, but a 40% decrease was observed in high glucose cultures, suggesting that high glucose may induce increased cell death rather than reduced proliferation. Reduced final cell number induced by high glucose was also observed after stimulation with 5 or 10% foetal calf serum. The possible participation of oxidative stress was investigated by co-incubating high glucose with different reactive oxygen species scavengers. Only catalase reversed the effect of high glucose. Intracellular H2O2 content, visualized with 2′,7′-dichlorofluorescein and quantified by flow cytometry, was increased after high glucose treatment. To investigate the cell death mechanism induced by high glucose, apoptosis and necrosis were quantified. No differences were observed regarding the apoptotic index between low and high glucose cultures, but lactate dehydrogenase activity was increased in high glucose cultures. In conclusion, high glucose promotes necrotic cell death through H2O2 formation, which may participate in the development of diabetic vasculopathy. PMID:11487505

  15. High glucose induces the expression of osteopontin in blood vessels in vitro and in vivo.

    PubMed

    Li, Tianjia; Ni, Leng; Liu, Xinnong; Wang, Zhanqi; Liu, Changwei

    2016-11-11

    Osteopontin (OPN) is involved in mineral metabolism and the inflammatory response while diabetes mellitus is associated with severe and extensive vascular calcification. Therefore, we speculated that OPN could be a key factor in the calcification and dysfunction of blood vessels exposed to high glucose. To identify the relationship between high glucose and OPN, we used high glucose medium to stimulate smooth muscle cells (SMCs) and vascular endothelial cells (VECs) in vitro and diabetic rats for in vivo analyses. As assessed by flow cytometry and western blots, SMC and VEC apoptosis levels increased with high glucose. Potassium and calcium uptake by cells were also increased with high glucose. These findings demonstrated the relationship between mineral metabolism and high glucose. Western blot and quantitative real time polymerase chain reaction analyses demonstrated that OPN increased in vitro with high glucose stimulation. The inflammatory factor ICAM1 and the inhibitory phosphorylation of endothelial nitric-oxide synthase (eNOS) (Thr495) were also upregulated by high glucose. In contrast, the anti-inflammatory factor Nrf2 and the activating phosphorylation of eNOS (Ser1177) were downregulated. Similar to the change of OPN, phosphorylated P38 was increased with high glucose. SB203580, an inhibitor of P38 phosphorylation, downregulated the expression of OPN and related inflammatory factors. Additionally, OPN was increased in the aortas and plasma of diabetic rats. In conclusion, our findings demonstrate that high glucose can induce the expression of OPN, which may be a key factor in the calcification and dysfunction of the vascular wall in diabetes.

  16. Experimental study on apoptosis of TNFR1 receptor pro-endothelial progenitor cells activated by high glucose induced oxidative stress

    PubMed Central

    Liu, Yong; Xei, Fei; Xu, Xiong-Fei; Zeng, Hong; He, Hu-Qiang; Zhang, Lei; Zheng, Ying-Qiang; He, Yan-Zheng

    2015-01-01

    Objective: To investigate whether high glucose in vitro activating TNFR1 and further promote rat marrow endothelial progenitor cells (EPCs) apoptosis. Methods: Rat morrow endothelial progenitor cells were cultured and identified by Confocal Microscopy; then were treated with high glucose (5.5, 15, 30, 60 mmol/L), mannitol (15, 30, 60, 90 mmol/L), high glucose + Tempol and high glucose+ MAB430. Apoptosis rate of the above cells were detected by flow cytometry. ROS and MDA level and anti-O2- were detected by colorimetric technique; the expression level of TNFR1 induced signal pathway related proteins were detected by Western blotting. Results: High glucose can induce endothelial progenitor cells apoptosis, which is mostly in the later stage (72 h-96 h) instead of the earlier stage (24 h-48 h); high glucose can also induce oxidative stress reaction and the produces ROS and MDA increase significantly in the later stage (after 72 h), but anti-O2- decrease significantly. TNF apoptosis signal pathway related protein expression level not increase in the earlier stage (before 24 h) but increase significantly in the later stage (after 72 h). Tempol and MAB430 down-regulate TNF apoptosis signal pathway related protein expression and reduce EPCs apoptosis. Conclusion: High glucose activates the TNFR1 of TPCs through oxidative stress reaction and further induces cell apoptosis. PMID:26884909

  17. Synthesis and Characterization of Sygyzium cumini Nanoparticles for Its Protective Potential in High Glucose-Induced Cardiac Stress: a Green Approach.

    PubMed

    Atale, Neha; Saxena, Sharad; Nirmala, J Grace; Narendhirakannan, R T; Mohanty, Sujata; Rani, Vibha

    2017-03-01

    There exists a complex and multifactorial relationship between diabetes and cardiovascular disease. Hyperglycemia is an important factor imposing damage (glucose toxicity) on cardiac cell leading to diabetic cardiomyopathy. There are substantial clinical evidences on the adverse effects of conventional therapies in the prevention/treatment of diabetic cardiovascular complications. Currently, green-synthesized nanoparticles have emerged as a safe, efficient, and inexpensive alternative for therapeutic uses. The present study discloses the silver nanoparticle biosynthesizing capability and cardioprotective potential of Syzygium cumini seeds already reported to have antidiabetic properties. Newly generated silver nanoparticles S. cumini MSE silver nanoparticles (SmSNPs) were characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), zeta sizer, X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. Using methanolic extract of S. cumini seeds, an average size of 40-100-nm nanoparticles with 43.02 nm and -19.6 mV zeta potential were synthesized. The crystalline nature of SmSNPs was identified by using XRD. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays revealed the antioxidative potential to be 66.87 (±0.7) % and 86.07 (±0.92) % compared to 60.29 (±0.02) % and 85.67 (±1.27) % for S. cumini MSE. In vitro study on glucose-stressed H9C2 cardiac cells showed restoration in cell size, nuclear morphology, and lipid peroxide formation upon treatment of SmSNPs. Our findings concluded that S. cumini MSE SmSNPs significantly suppress the glucose-induced cardiac stress in vitro by maintaining the cellular integrity and reducing the oxidative damages therefore establishing its therapeutic potential in diabetic cardiomyopathy.

  18. Epigallocatechin gallate (EGCG) attenuates high glucose-induced insulin signaling blockade in human hepG2 hepatoma cells.

    PubMed

    Lin, Chih-Li; Lin, Jen-Kun

    2008-08-01

    Insulin resistance is the primary characteristic of type 2 diabetes which as a result of insulin signaling defects. It has been suggested that the tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) displays some antidiabetic effects, but the mechanism for EGCG insulin-enhancing effects is incompletely understood. In the present study, the investigations of EGCG on insulin signaling are performed in insulin-responsive human HepG2 cells cotreated with high glucose. We found that the high glucose condition causes significant increasing Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1), leading to reduce insulin-stimulated phosphorylation of Akt. As the results, the insulin metabolic effects of glycogen synthesis and glucose uptake are inhibited by high glucose. However, the treatment of EGCG improves insulin-stimulated downsignaling by reducing IRS-1 Ser307 phosphorylation. Furthermore, we also demonstrated these EGCG effects are essential depends on the 5'-AMP-activated protein kinase (AMPK) activation. Together, our data suggest a putative link between high glucose and insulin resistance in HepG2 cells, and the EGCG treatment attenuates insulin signaling blockade by reducing IRS-1 Ser307 phosphorylation through the AMPK activation pathway.

  19. High glucose-induced resistance to 5-fluorouracil in pancreatic cancer cells alleviated by 2-deoxy-D-glucose.

    PubMed

    Cheng, Yao; Diao, Dongmei; Zhang, Hao; Guo, Qi; Wu, Xuandi; Song, Yongchun; Dang, Chengxue

    2014-03-01

    Abnormal glucose metabolism from hyperglycemia or diabetes aggravates the progression of pancreatic cancer. It is unknown whether high glucose has an impact on the antitumor effect of 5-fluorouracil (5-Fu) and whether targeting aberrant glucose metabolism using 2-deoxy-D-glucose (2-DG) may reverse this effect in high-glucose microenvironments. The cell viability of AsPC-1 and Panc-1 was analyzed by MTT assay following 5-Fu treatment at different glucose concentrations. Altered sensitivity to 5-Fu by 2-DG was also analyzed. LY294002 was used to inhibit PI3K-Akt signaling to determine the mechanism involved. In response to glucose, 5-Fu-induced cell growth inhibition was attenuated in a dose-dependent manner, accompanied with activated p-Akt, while 2-DG enhanced 5-Fu-induced cell growth inhibition. Moreover, blocking the PI3K/Akt pathway by LY294002 effectively eliminated 2-DG-induced apoptosis. In conclusion, high glucose weakens the antitumor effect of 5-Fu via PI3K/Akt signaling. Using 2-DG in combination with 5-Fu significantly increased their therapeutic effectiveness in high-glucose microenvironments.

  20. Maresin 1 Mitigates High Glucose-Induced Mouse Glomerular Mesangial Cell Injury by Inhibiting Inflammation and Fibrosis

    PubMed Central

    Tang, Shi; Long, Yang; Huang, Wei; Chen, Jiao; Fan, Fang; Jiang, Chunxia

    2017-01-01

    Background. Inflammation and fibrosis are the important pathophysiologic processes in diabetic nephropathy (DN). Maresin 1 is a potential anti-inflammatory lipid mediator, which has displayed powerful proresolving activities. Aim. We determine whether maresin 1 has protective effect on mouse glomerular mesangial cells (GMCs) induced by high glucose. Methods. We cultured GMCs stimulated by high glucose and categorized as follows: normal glucose group (5.6 mmol/L), high glucose group (30 mmol/L), mannitol group, maresin 1 intervention group (1, 10, and 100 nmol/L), maresin 1 and normal glucose group, and the N-acetylcysteine (NAC) intervention group (10 μmol/L NAC). After 24 h, the expression of ROS, NLRP3, caspase-1, procaspase-1, IL-1β, and pro-IL-1β was detected by western-blot, RT-PCR, and immunofluorescence. After 48 h, the expression of TGF-β1 and FN was detected by RT-PCR and ELISA. Results. Compared with normal glucose group, the expression of ROS, NLRP3, caspase-1, IL-1β, TGF-β1, and FN increased in high glucose group (P < 0.05), but it decreased after the treatment of maresin 1 in different concentrations. On the contrary, the expression of procaspase-1 and pro-IL-1β protein was restrained by high glucose and enhanced by maresin 1 in a dose-dependent manner (P < 0.05). Conclusion. Maresin 1 can inhibit NLRP3 inflammasome, TGF-β1, and FN in GMCs; it may have protective effect on DN by mitigating the inflammation and early fibrosis. PMID:28182085

  1. Mechanical strain- and high glucose-induced alterations in mesangial cell collagen metabolism: role of TGF-beta.

    PubMed

    Riser, B L; Cortes, P; Yee, J; Sharba, A K; Asano, K; Rodriguez-Barbero, A; Narins, R G

    1998-05-01

    Cultured mesangial cells (MC) exposed to cyclic mechanical strain or high glucose levels increase their secretion of transforming growth factor-beta1 (TGF-beta1) and collagen, suggesting possible mechanisms for the development of diabetic renal sclerosis resulting from intraglomerular hypertension and/or hyperglycemia. This study examines whether glucose interacts with mechanical strain to influence collagen metabolism and whether this change is mediated by TGF-beta. Accordingly, rat MC were grown on flexible-bottom plates in 8 or 35 mM glucose media, subjected to 2 to 5 d of cyclic stretching, and assayed for TGF-beta1 mRNA, TGF-beta1 secretion, and the incorporation of 14C-proline into free or protein-associated hydroxyproline to assess the dynamics of collagen metabolism. Stretching or high glucose exposure increased TGF-beta1 secretion twofold and TGF-beta1 mRNA levels by 30 and 45%, respectively. However, the combination of these stimuli increased secretion greater than fivefold without further elevating mRNA. In 8 mM glucose medium, stretching significantly increased MC collagen synthesis and breakdown, but did not alter accumulation, whereas those stretched in 35 mM glucose markedly increased collagen accumulation. TGF-beta neutralization significantly reduced baseline collagen synthesis, breakdown, and accumulation in low glucose, but had no significant effect on the changes induced by stretch. In contrast, the same treatment of MC in high glucose medium greatly reduced stretch-induced synthesis and breakdown of collagen and totally abolished the increase in collagen accumulation. These results indicate that TGF-beta plays a positive regulatory role in MC collagen synthesis, breakdown, and accumulation. However, in low glucose there is no stretch-induced collagen accumulation, and the effect of TGF-beta is limited to basal collagen turnover. In high glucose media, TGF-beta is a critical mediator of stretch-induced collagen synthesis and catabolism, and

  2. MicroRNA-29 regulates high-glucose-induced apoptosis in human retinal pigment epithelial cells through PTEN.

    PubMed

    Lin, Xiaohui; Zhou, Xiyuan; Liu, Danning; Yun, Lixia; Zhang, Lina; Chen, Xiaohai; Chai, Qinghe; Li, Langen

    2016-04-01

    Hyperglycemia or high-glucose (HG)-induced apoptosis in human retinal pigment epithelial (RPE) cells is a characteristic process in diabetic retinopathy. In our study, we examined whether microRNA-29 (miR-29) may regulate HG-induced RPE cell apoptosis. Human RPE cell line, ARPE-19 cells, was treated with various high concentration of glucose in vitro. HG-induced RPE cell apoptosis was examined by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay and miR-29 gene expression by quantitative RT-PCR (qRT-PCR). miR-29 was then downregulated in RPE cells, and its effect on HG-induced apoptosis was examined by TUNEL assay and western blot assay on caspase-7 protein. Association of miR-29 on its downstream target, PTEN, in HG-induced RPE cell apoptosis was evaluated by dual-luciferase assay and qRT-PCR. PTEN was silenced in RPE cells. The effects of PTEN downregulation on miR-29-mediated HG-induced RPE cell apoptosis were also examined by TUNEL and western blot assays. HG induced significant apoptosis in RPE cells in a dose-dependent manner. miR-29 was upregulated by HG in RPE cells. miR-29 downregulation protected HG-induced apoptosis and reduced the production of caspase-7 protein in RPE cells. PTEN was shown to be directly downregulated by HG and then upregulated by miR-29 downregulation in RPE cells. Small interfering RNA (siRNA)-mediated PTEN downregulation reversed the protective effect of miR-29 downregulation on HG-induced RPE cell apoptosis. This study demonstrates that miR-29, through inverse association of PTEN, plays an important role in the process of HG-induced apoptosis in RPE cells.

  3. Aspalathin and Nothofagin from Rooibos (Aspalathus linearis) inhibits high glucose-induced inflammation in vitro and in vivo.

    PubMed

    Ku, Sae-Kwang; Kwak, Soyoung; Kim, Yaesol; Bae, Jong-Sup

    2015-02-01

    Vascular inflammation plays a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Aspalathin (Asp) and nothofagin (Not) are two major active dihydrochalcones found in green rooibos, which have been reported for their antioxidant activity. In this study, we assessed whether Asp or Not can suppress vascular inflammation induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. We monitored the effects of Asp or Not on HG-induced vascular hyperpermeability, expression of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-κB in vitro and in vivo. Our data indicate that HG markedly increased vascular permeability, monocyte adhesion, expression of CAMs, formation of ROS, and activation of NF-κB. Remarkably, treatment of Asp or Not inhibited HG-mediated vascular hyperpermeability, adhesion of monocytes toward HUVECs, and expression of CAMs. In addition, Asp or Not suppressed the formation of ROS and the activation of NF-κB. Since vascular inflammation induced by HG is critical in the development of diabetic complications, our results suggest that Asp or Not may have significant benefits in the treatment of diabetic complications.

  4. Suppression of ROS Production by Exendin-4 in PSC Attenuates the High Glucose-Induced Islet Fibrosis

    PubMed Central

    Kim, Ji-Won; Park, Shin-Young; You, Young-Hye; Ham, Dong-Sik; Lee, Seung-Hwan; Yang, Hae Kyung; Jeong, In-Kyung; Ko, Seung-Hyun

    2016-01-01

    Pancreatic stellate cells (PSCs) play a major role to fibrotic islet destruction observed in diabetic patients and animal model of diabetes. Exendin-4 (Ex-4) is a potent insulinotropic agent and has been approved for the treatment of type 2 diabetes. However, there have been no reports demonstrating the effects of Ex-4 on pancreatic islet fibrosis. In this study, Ex-4 treatment clearly attenuated fibrotic islet destruction and improved glucose tolerance and islet survival. GLP-1 receptor expression was upregulated during activation and proliferation of PSCs by hyperglycemia. The activation of PKA pathway by Ex-4 plays a role in ROS production and angiotensin II (Ang II) production. Exposure to high glucose stimulated ERK activation and Ang II-TGF- β1 production in PSCs. Interestingly, Ex-4 significantly reduced Ang II and TGF-β1 production by inhibition of ROS production but not ERK phosphorylation. Ex-4 may be useful not only as an anti-diabetic agent but also as an anti-fibrotic agent in type 2 diabetes due to its ability to inhibit PSC activation and proliferation and improve islet fibrosis in OLETF rats. PMID:27977690

  5. Anthocyanins inhibit high-glucose-induced cholesterol accumulation and inflammation by activating LXRα pathway in HK-2 cells.

    PubMed

    Du, Chunyang; Shi, Yonghong; Ren, Yunzhuo; Wu, Haijiang; Yao, Fang; Wei, Jinying; Wu, Ming; Hou, Yanjuan; Duan, Huijun

    2015-01-01

    The dysregulation of cholesterol metabolism and inflammation plays a significant role in the progression of diabetic nephropathy (DN). Anthocyanins are polyphenols widely distributed in food and exert various biological effects including antioxidative, anti-inflammatory, and antihyperlipidemic effects. However, it remains unclear whether anthocyanins are associated with DN, and the mechanisms involved in the reciprocal regulation of inflammation and cholesterol efflux are yet to be elucidated. In this study, we evaluated the regulation of cholesterol metabolism and the anti-inflammatory effects exerted by anthocyanins (cyanidin-3-O-β-glucoside chloride [C3G] or cyanidin chloride [Cy]) and investigated the underlying molecular mechanism of action using high-glucose (HG)-stimulated HK-2 cells. We found that anthocyanins enhanced cholesterol efflux and ABCA1 expression markedly in HK-2 cells. In addition, they increased peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptor alpha (LXRα) expression and decreased the HG-induced expression of the proinflammatory cytokines intercellular adhesion molecule-1 (ICAM1), monocyte chemoattractant protein-1 (MCP1), and transforming growth factor-β1 (TGFβ1), as well as NFκB activation. Incubation with the PPARα-specific inhibitor GW6471 and LXRα shRNA attenuated the anthocyanin-mediated promotion of ABCA1 expression and cholesterol efflux, suggesting that anthocyanins activated PPARα-LXRα-ABCA1-dependent cholesterol efflux in HK-2 cells. Moreover, the knockout of LXRα abrogated the anti-inflammatory effect of anthocyanins, whereas the PPARα antagonist GW6471 does not have this effect. Further investigations revealed that LXRα might interfere with anthocyanin-induced decreased ICAM1, MCP1, and TGFβ1 expression by reducing the nuclear translocation of NFκB. Collectively, these findings suggest that blocking cholesterol deposition and inhibiting the LXRα pathway-induced inflammatory response

  6. Overexpression of miR-34c inhibits high glucose-induced apoptosis in podocytes by targeting Notch signaling pathways.

    PubMed

    Liu, Xiang-Dong; Zhang, Lian-Yun; Zhu, Tie-Chui; Zhang, Rui-Fang; Wang, Shu-Long; Bao, Yan

    2015-01-01

    Recent findings have shown that microRNAs play critical roles in the pathogenesis of diabetic nephropathy. miR-34c has been found to inhibit fibrosis and the epithelial-mesenchymal transition of kidney cells. However, the role of miR-34c in diabetic nephropathy has not been well studied. The current study was designed to investigate the role and potential underlying mechanism of miR-34c in regulating diabetic nephropathy. After treating podocytes with high glucose (HG) in vitro, we found that miR-34c was downregulated and that overexpression of miR-34c inhibited HG-induced podocyte apoptosis. The direct interaction between miR-34c and the 3'-untranslated region (UTR) of Notch1 and Jagged1 was validated by dual-luciferase reporter assay. Moreover, Notch1 and Jagged1 as putative targets of miR-34c were downregulated by miR-34c overexpression in HG-treated podocytes. Overexpression of miR-34c inhibited HG-induced Notch signaling pathway activation, as indicated by decreased expression of the Notch intracellular domain (NICD) and downstream genes including Hes1 and Hey1. Furthermore, miR-34c overexpression increased the expression of the anti-apoptotic gene Bcl-2, and decreased the expression of the pro-apoptotic protein Bax and cleaved Caspase-3. Additionally, the phosphorylation of p53 was also downregulated by miR-34c overexpression. Taken together, our findings suggest that miR-34c overexpression inhibits the Notch signaling pathway by targeting Notch1 and Jaggged1 in HG-treated podocytes, representing a novel and potential therapeutic target for the treatment of diabetic nephropathy.

  7. Protective effect of hydrogen-rich medium against high glucose-induced apoptosis of Schwann cells in vitro.

    PubMed

    Yu, Yang; Ma, Xiaoye; Yang, Tao; Li, Bo; Xie, Keliang; Liu, Daquan; Wang, Guolin; Yu, Yonghao

    2015-09-01

    Diabetic peripheral neuropathy (DPN) is considered to be one of the most prevalent and life threatening microvascular diabetic complications. DPN affects up to 50% of patients with diabetes mellitus and there are currently no efficacious therapeutic strategies available for its treatment. Previous studies have reported that oxidative stress and poly(ADP‑ribose) polymerase‑1 (PARP‑1) may be unifying factors for hyperglycemic injury. The aim of the present study was to investigate the protective effects of hydrogen‑rich medium (HM) on high glucose (HG)‑mediated oxidative stress, PARP‑1 activation and the apoptosis of Schwann cells (SCs) in vitro. The cells were divided into different groups, and were treated for 48 h. Cell viability and apoptosis were evaluated using Cell Counting kit‑8 and annexin V/propidium iodide assays, respectively. The concentrations of 8‑hydroxy‑2‑deoxyguanosine (8‑OHdG) and peroxynitrite (ONOO‑) were detected using an enzyme‑linked immunosorbent assay. The presence of intracellular oxygen free radicals was confirmed using flow cytometric analysis. Colorimetric assays were performed to determine the activity of caspase‑3, and western blotting was performed to detect the protein expression levels of PARP‑1, cleaved PARP‑1, PAR, apoptosis‑inducing factor (AIF), B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein. HG was found to induce severe oxidative stress and promote the caspase‑dependent and caspase‑independent apoptosis of SCs. Treatment with HM inhibited HG‑induced oxidative stress by suppressing hydroxyl and ONOO‑ production, levels of 8‑OHdG, caspase‑3 activity and apoptosis in the SCs. Furthermore, treatment with HM downregulated the HG‑induced release of PAR, the activation of PARP‑1 and nuclear translocation of AIF, and upregulated the expression of Bcl‑2 in the SCs. These results indicated that HM inhibited the HG‑induced‑oxidative stress‑associated caspase

  8. Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure

    PubMed Central

    Di Filippo, C.; Ferraro, B.; Maisto, R.; Trotta, M. C.; Di Carluccio, N.; Sartini, S.; La Motta, C.; Ferraraccio, F.; Rossi, F.; D'Amico, M.

    2016-01-01

    This study investigated the effects of the new aldose reductase inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy)benzofuroxane (BF-5m) on the prolongation of cardiac QT interval and increase of coronary perfusion pressure (CPP) in isolated, high glucose (33.3 mM D-glucose) perfused rat hearts. BF-5m was dissolved in the Krebs solution at a final concentration of 0.01 μM, 0.05 μM, and 0.1 μM. 33.3 mM D-glucose caused a prolongation of the QT interval and increase of CPP up to values of 190 ± 12 ms and 110 ± 8 mmHg with respect to the values of hearts perfused with standard Krebs solution (11.1 mM D-glucose). The QT prolongation was reduced by 10%, 32%, and 41%, respectively, for the concentration of BF-5m 0.01 μM, 0.05 μM, and 0.1 μM. Similarly, the CPP was reduced by 20% for BF-5m 0.05 μM and by 32% for BF-5m 0.1 μM. BF-5m also increased the expression levels of sirtuin 1, MnSOD, eNOS, and FOXO-1, into the heart. The beneficial actions of BF-5m were partly abolished by the pretreatment of the rats with the inhibitor of the sirtuin 1 activity EX527 (10 mg/kg/day/7 days i.p.) prior to perfusion of the hearts with high glucose + BF-5m (0.1 μM). Therefore, BF-5m supplies cardioprotection from the high glucose induced QT prolongation and increase of CPP. PMID:26839893

  9. MiR-18b suppresses high-glucose-induced proliferation in HRECs by targeting IGF-1/IGF1R signaling pathways.

    PubMed

    Wu, Jin-hui; Wang, Yi-han; Wang, Wei; Shen, Wei; Sang, Yan-zhi; Liu, Lin; Chen, Cui-min

    2016-04-01

    MicroRNAs (miRNAs) are important for the proliferation of endothelial cells and have been shown to be involved in diabetic retinopathy (DR). In previous study, we found that miRNAs might play a critical role in hyperglycemia-induced endothelial cell proliferation based on miRNA expression profiling. Here, the roles of microRNA-18b (miR-18b) in the proliferation of human retinal endothelial cells (HRECs) were investigated in an in vitro model of HRECs grown in high glucose. We identified that levels of miR-18b were decreased in high-glucose-induced HRECs, compared with those in cells incubated in normal glucose. However, the reduction of miR-18b up-regulated vascular endothelial growth factor (VEGF) secretion and promoted effects on in vitro proliferation of HRECs. Mechanistically, insulin growth factor-1 (IGF-1) was identified as a target of miR-18b. IGF-1 simulation could antagonize the effect induced by miR-18b up-regulation, promoting cell proliferation and increasing VEGF production. In contrast, the opposite results were observed with silencing IGF-1, which was consistent with the effects of miR-18b overexpression. MiR-18b exerted its function on VEGF synthesis and cell proliferation by suppressing the IGF-1/insulin growth factor-1 receptor (IGF1R) pathway, consequently inhibiting the downstream phosphorylation of Akt, MEK, and ERK. Hence, this may provide a new insight into understanding the mechanism of DR pathogenesis, as well as a potential therapeutic target for proliferative DR.

  10. Establishment of in vitro model of erectile dysfunction for the study of high-glucose-induced angiopathy and neuropathy.

    PubMed

    Yin, G N; Park, S-H; Song, K-M; Limanjaya, A; Ghatak, K; Minh, N N; Ock, J; Ryu, J-K; Suh, J-K

    2017-03-01

    Penile erection requires complex interaction between vascular endothelial cells, smooth muscle cells, pericytes, and autonomic nerves. Diabetes mellitus is one of the most common causes of erectile dysfunction (ED) and multiple pathogenic factors, such as cavernous angiopathy and autonomic neuropathy, are associated with diabetic ED. Although a variety of animal models of diabetic ED play an important role in understanding pathophysiologic mechanisms of diabetes-induced ED, these animal models have limitations for addressing the exact cellular or molecular mechanisms involved in ED. Therefore, we established an in vitro model of ED for the study of high-glucose-induced angiopathy and neuropathy. We successfully isolated and cultivated mouse cavernous endothelial cells (MCECs) and mouse cavernous pericytes (MCPs). The cells were exposed to the normal-glucose (5 mmoL) or high-glucose (30 mmoL) condition for 48 h. In vitro matrigel assay revealed impairments in tube formation in primary cultured MCECs or MCPs exposed to high-glucose condition. To study cellular interaction between MCECs and MCPs, co-culture systems including indirect contact, indirect non-contact, and direct mixed co-culture system, were established. We observed impaired tube formation and increased permeability in MCECs-MCPs co-culture exposed to high-glucose condition. To evaluate the effect of high-glucose on neurite sprouting, the mouse major pelvic ganglion (MPG) tissue was harvested and cultivated in matrigel. Neurite outgrowth and nNOS-positive nerve fibers were significantly lower in MPG tissues exposed to the high-glucose condition than in the tissues exposed to the normal-glucose condition. We believe that in vitro model of ED will aid us to understand the role of each cellular component in the pathogenesis of diabetic ED, and also be a useful tool for determining the efficacy of candidate therapeutics targeting vascular or neuronal function. This model would present a new avenue for

  11. Glucose induces apoptosis of cardiomyocytes via microRNA-1 and IGF-1.

    PubMed

    Yu, Xi-Yong; Song, Yao-Hua; Geng, Yong-Jian; Lin, Qiu-Xiong; Shan, Zhi-Xin; Lin, Shu-Guang; Li, Yangxin

    2008-11-21

    Glucose toxicity is an important initiator of cardiovascular disease, contributing to the development of cardiomyocyte death and diabetic complications. The present study investigated whether high glucose state could induce apoptosis of rat cardiomyocyte cell line H9C2 through microRNA regulated insulin-like growth factor (IGF-1) signaling pathway. Our data showed that H9C2 cells exposed to high glucose have increased miR-1 expression level, decreased mitochondrial membrane potential, increased cytochrome-c release, and increased apoptosis. Glucose induced mitochondrial dysfunction, cytochrome-c release and apoptosis was blocked by IGF-1. Using prediction algorithms, we identified 3'-untranslated regions of IGF-1 gene are the target of miR-1. miR-1 mimics, but not mutant miR-1, blocked the capacity of IGF-1 to prevent glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis. In conclusion, our data demonstrate that IGF-1 inhibits glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis and IGF-1's effect is regulated by miR-1.

  12. Cocoa flavonoids attenuate high glucose-induced insulin signalling blockade and modulate glucose uptake and production in human HepG2 cells.

    PubMed

    Cordero-Herrera, Isabel; Martín, María Ángeles; Goya, Luis; Ramos, Sonia

    2014-02-01

    Insulin resistance is the primary characteristic of type 2 diabetes. Cocoa and its main flavanol, (-)-epicatechin (EC), display some antidiabetic effects, but the mechanisms for their preventive activities related to glucose metabolism and insulin signalling in the liver remain largely unknown. In the present work, the preventive effect of EC and a cocoa polyphenolic extract (CPE) on insulin signalling and on both glucose production and uptake are studied in insulin-responsive human HepG2 cells treated with high glucose. Pre-treatment of cells with EC or CPE reverted decreased tyrosine-phosphorylated and total levels of IR, IRS-1 and -2 triggered by high glucose. EC and CPE pre-treatment also prevented the inactivation of the PI3K/AKT pathway and AMPK, as well as the diminution of GLUT-2 levels induced by high glucose. Furthermore, pre-treatment of cells with EC and CPE avoided the increase in PEPCK levels and the diminished glucose uptake provoked by high glucose, returning enhanced levels of glucose production and decreased glycogen content to control values. These findings suggest that EC and CPE improved insulin sensitivity of HepG2 treated with high glucose, preventing or delaying a potential hepatic dysfunction through the attenuation of the insulin signalling blockade and the modulation of glucose uptake and production.

  13. High Blood Pressure Prevention

    MedlinePlus

    ... version of this page please turn Javascript on. High Blood Pressure Prevention Steps You Can Take You can take steps to prevent high blood pressure by adopting these healthy lifestyle habits. Follow a ...

  14. High glucose-induced mitochondrial respiration and reactive oxygen species in mouse cerebral pericytes is reversed by pharmacological inhibition of mitochondrial carbonic anhydrases: Implications for cerebral microvascular disease in diabetes.

    PubMed

    Shah, Gul N; Morofuji, Yoichi; Banks, William A; Price, Tulin O

    2013-10-18

    Hyperglycemia-induced oxidative stress leads to diabetes-associated damage to the microvasculature of the brain. Pericytes in close proximity to endothelial cells in the brain microvessels are vital to the integrity of the blood-brain barrier and are especially susceptible to oxidative stress. According to our recently published results, streptozotocin-diabetic mouse brain exhibits oxidative stress and loose pericytes by twelve weeks of diabetes, and cerebral pericytes cultured in high glucose media suffer intracellular oxidative stress and apoptosis. Oxidative stress in diabetes is hypothesized to be caused by reactive oxygen species (ROS) produced during hyperglycemia-induced enhanced oxidative metabolism of glucose (respiration). To test this hypothesis, we investigated the effect of high glucose on respiration rate and ROS production in mouse cerebral pericytes. Previously, we showed that pharmacological inhibition of mitochondrial carbonic anhydrases protects the brain from oxidative stress and pericyte loss. The high glucose-induced intracellular oxidative stress and apoptosis of pericytes in culture were also reversed by inhibition of mitochondrial carbonic anhydrases. Therefore, we extended our current study to determine the effect of these inhibitors on high glucose-induced increases in pericyte respiration and ROS. We now report that both the respiration and ROS are significantly increased in pericytes challenged with high glucose. Furthermore, inhibition of mitochondrial carbonic anhydrases significantly slowed down both the rate of respiration and ROS production. These data provide new evidence that pharmacological inhibitors of mitochondrial carbonic anhydrases, already in clinical use, may prove beneficial in protecting the brain from oxidative stress caused by ROS produced as a consequence of hyperglycemia-induced enhanced respiration.

  15. Hydrogen sulfide releasing aspirin, ACS14, attenuates high glucose-induced increased methylglyoxal and oxidative stress in cultured vascular smooth muscle cells.

    PubMed

    Huang, Qian; Sparatore, Anna; Del Soldato, Piero; Wu, Lingyun; Desai, Kaushik

    2014-01-01

    Hydrogen sulfide is a gasotransmitter with vasodilatory and anti-inflammatory properties. Aspirin is an irreversible cyclooxygenase inhibitor anti-inflammatory drug. ACS14 is a novel synthetic hydrogen sulfide releasing aspirin which inhibits cyclooxygenase and has antioxidant effects. Methylglyoxal is a chemically active metabolite of glucose and fructose, and a major precursor of advanced glycation end products formation. Methylglyoxal is harmful when produced in excess. Plasma methylglyoxal levels are significantly elevated in diabetic patients. Our aim was to investigate the effects of ACS14 on methylglyoxal levels in cultured rat aortic vascular smooth muscle cells. We used cultured rat aortic vascular smooth muscle cells for the study. Methylglyoxal was measured by HPLC after derivatization, and nitrite+nitrate with an assay kit. Western blotting was used to determine NADPH oxidase 4 (NOX4) and inducible nitric oxide synthase (iNOS) protein expression. Dicholorofluorescein assay was used to measure oxidative stress. ACS14 significantly attenuated elevation of intracellular methylglyoxal levels caused by incubating cultured vascular smooth muscle cells with methylglyoxal (30 µM) and high glucose (25 mM). ACS14, but not aspirin, caused a significant attenuation of increase in nitrite+nitrate levels caused by methylglyoxal or high glucose. ACS14, aspirin, and sodium hydrogen sulfide (NaHS, a hydrogen sulfide donor), all attenuated the increase in oxidative stress caused by methylglyoxal and high glucose in cultured cells. ACS14 prevented the increase in NOX4 expression caused by incubating the cultured VSMCs with MG (30 µM). ACS14, aspirin and NaHS attenuated the increase in iNOS expression caused by high glucose (25 mM). In conclusion, ACS14 has the novel ability to attenuate an increase in methylglyoxal levels which in turn can reduce oxidative stress, decrease the formation of advanced glycation end products and prevent many of the known deleterious effects

  16. Fagopyrum tataricum (buckwheat) improved high-glucose-induced insulin resistance in mouse hepatocytes and diabetes in fructose-rich diet-induced mice.

    PubMed

    Lee, Chia-Chen; Hsu, Wei-Hsuan; Shen, Siou-Ru; Cheng, Yu-Hsiang; Wu, She-Ching

    2012-01-01

    Fagopyrum tataricum (buckwheat) is used for the treatment of type 2 diabetes mellitus in Taiwan. This study was to evaluate the antihyperglycemic and anti-insulin resistance effects of 75% ethanol extracts of buckwheat (EEB) in FL83B hepatocytes by high-glucose (33 mM) induction and in C57BL/6 mice by fructose-rich diet (FRD; 60%) induction. The active compounds of EEB (100 μg/mL; 50 mg/kg bw), quercetin (6 μg/mL; 3 mg/kg bw), and rutin (23 μg/mL; 11.5 mg/kg bw) were also employed to treat FL83B hepatocytes and animal. Results indicated that EEB, rutin, and quercetin + rutin significantly improved 2-NBDG uptake via promoting Akt phosphorylation and preventing PPARγ degradation caused by high-glucose induction for 48 h in FL83B hepatocytes. We also found that EEB could elevate hepatic antioxidant enzymes activities to attenuate insulin resistance as well as its antioxidation caused by rutin and quercetin. Finally, EEB also inhibited increases in blood glucose and insulin levels of C57BL/6 mice induced by FRD.

  17. Glucose-Induced Acidification in Yeast Cultures

    ERIC Educational Resources Information Center

    Myers, Alan; Bourn, Julia; Pool, Brynne

    2005-01-01

    We present an investigation (for A-level biology students and equivalent) into the mechanism of glucose-induced extracellular acidification in unbuffered yeast suspensions. The investigation is designed to enhance understanding of aspects of the A-level curriculum that relate to the phenomenon (notably glucose catabolism) and to develop key skills…

  18. Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by activating AMP-activated protein kinase in renal epithelial cells.

    PubMed

    Lee, Hak Joo; Mariappan, Meenalakshmi M; Feliers, Denis; Cavaglieri, Rita C; Sataranatarajan, Kavithalakshmi; Abboud, Hanna E; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S

    2012-02-10

    Hydrogen sulfide, a signaling gas, affects several cell functions. We hypothesized that hydrogen sulfide modulates high glucose (30 mm) stimulation of matrix protein synthesis in glomerular epithelial cells. High glucose stimulation of global protein synthesis, cellular hypertrophy, and matrix laminin and type IV collagen content was inhibited by sodium hydrosulfide (NaHS), an H(2)S donor. High glucose activation of mammalian target of rapamycin (mTOR) complex 1 (mTORC1), shown by phosphorylation of p70S6 kinase and 4E-BP1, was inhibited by NaHS. High glucose stimulated mTORC1 to promote key events in the initiation and elongation phases of mRNA translation: binding of eIF4A to eIF4G, reduction in PDCD4 expression and inhibition of its binding to eIF4A, eEF2 kinase phosphorylation, and dephosphorylation of eEF2; these events were inhibited by NaHS. The role of AMP-activated protein kinase (AMPK), an inhibitor of protein synthesis, was examined. NaHS dose-dependently stimulated AMPK phosphorylation and restored AMPK phosphorylation reduced by high glucose. Compound C, an AMPK inhibitor, abolished NaHS modulation of high glucose effect on events in mRNA translation as well as global and matrix protein synthesis. NaHS induction of AMPK phosphorylation was inhibited by siRNA for calmodulin kinase kinase β, but not LKB1, upstream kinases for AMPK; STO-609, a calmodulin kinase kinase β inhibitor, had the same effect. Renal cortical content of cystathionine β-synthase and cystathionine γ-lyase, hydrogen sulfide-generating enzymes, was significantly reduced in mice with type 1 diabetes or type 2 diabetes, coinciding with renal hypertrophy and matrix accumulation. Hydrogen sulfide is a newly identified modulator of protein synthesis in the kidney, and reduction in its generation may contribute to kidney injury in diabetes.

  19. Connexin43 regulates high glucose-induced expression of fibronectin, ICAM-1 and TGF-β1 via Nrf2/ARE pathway in glomerular mesangial cells.

    PubMed

    Chen, Zhiquan; Xie, Xi; Huang, Junying; Gong, Wenyan; Zhu, Xiaoyu; Chen, Qiuhong; Huang, Jiani; Huang, Heqing

    2017-01-01

    Nrf2/ARE signaling pathway is a crucial cellular defense system to cope with oxidative stress, which is adaptively activated, in diabetic condition that is not efficient enough to resist the oxidative stress provoked by hyperglycemia. We have previously demonstrated that Connexin43 (Cx43) attenuates renal fibrosis through c-Src. However, the underlying mechanisms need to be further clarified. It has been reported that Cx43 possesses the ability of anti-oxidative. The current study aimed to determine if Cx43 exerts protective effects on renal fibrosis in diabetes via activation of Nrf2/ARE pathway and explore the underlying molecular mechanisms. The following findings were observed: (1) Cx43 expression decreased and c-Src activity increased in kidneys of diabetic animals; (2) Over-expressed Cx43 in high glucose treated GMCs inhibited protein levels of FN, ICAM-1 and TGF-β1; (3) Nrf2/ARE signaling adaptively responded to high glucose treatment in GMCs; (4) Cx43 reduced ROS generation by boost Nrf2/ARE signaling under high glucose condition; (5) Inhibition of c-Src activity promoted nucleus accumulation of Nrf2; (6) Over-expressed Cx43 inhibited c-Src activity and the interaction between c-Src and Nrf2 in GMCs cultured in high glucose. Thus we propose that Cx43 might enhance the activation of Nrf2/ARE pathway by means of inhibiting c-Src activity to hinder the nuclear export of Nrf2, and then reduce expression of FN, ICAM-1 and TGF-β1, ultimately attenuating renal fibrosis in diabetes.

  20. High glucose induces platelet-derived growth factor-C via carbohydrate response element-binding protein in glomerular mesangial cells.

    PubMed

    Kitsunai, Hiroya; Makino, Yuichi; Sakagami, Hidemitsu; Mizumoto, Katsutoshi; Yanagimachi, Tsuyoshi; Atageldiyeva, Kuralay; Takeda, Yasutaka; Fujita, Yukihiro; Abiko, Atsuko; Takiyama, Yumi; Haneda, Masakazu

    2016-03-01

    Persistent high concentration of glucose causes cellular stress and damage in diabetes via derangement of gene expressions. We previously reported high glucose activates hypoxia-inducible factor-1αand downstream gene expression in mesangial cells, leading to an extracellular matrix expansion in the glomeruli. A glucose-responsive transcription factor carbohydrate response element-binding protein (ChREBP) is a key mediator for such perturbation of gene regulation. To provide insight into glucose-mediated gene regulation in mesangial cells, we performed chromatin immunoprecipitation followed byDNAmicroarray analysis and identified platelet-derived growth factor-C (PDGF-C) as a novel target gene of ChREBP In streptozotocin-induced diabetic mice, glomerular cells showed a significant increase inPDGF-C expression; the ratio ofPDGF-C-positive cells to the total number glomerular cells demonstrated more than threefold increase when compared with control animals. In cultured human mesangial cells, high glucose enhanced expression ofPDGF-C protein by 1.9-fold. Knock-down of ChREBPabrogated this induction response. UpregulatedPDGF-C contributed to the production of typeIVand typeVIcollagen, possibly via an autocrine mechanism. Interestingly, urinaryPDGF-C levels in diabetic model mice were significantly elevated in a fashion similar to urinary albumin. Taken together, we hypothesize that a high glucose-mediated induction ofPDGF-C via ChREBPin mesangial cells contributes to the development of glomerular mesangial expansion in diabetes, which may provide a platform for novel predictive and therapeutic strategies for diabetic nephropathy.

  1. Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes.

    PubMed

    Negi, Geeta; Kumar, Ashutosh; Sharma, Shyam S

    2011-11-01

    High glucose driven reactive oxygen intermediates production and inflammatory damage are recognized contributors of nerve dysfunction and subsequent damage in diabetic neuropathy. Sulforaphane, a known chemotherapeutic agent holds a promise for diabetic neuropathy because of its dual antioxidant and anti-inflammatory activities. The present study investigated the effect of sulforaphane in streptozotocin (STZ) induced diabetic neuropathy in rats. For in vitro experiments neuro2a cells were incubated with sulforaphane in the presence of normal (5.5 mM) and high glucose (30 mM). For in vivo studies, sulforaphane (0.5 and 1 mg/kg) was administered six weeks post diabetes induction for two weeks. Motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and pain behavior were improved and malondialdehyde (MDA) level was reduced by sulforaphane. Antioxidant effect of sulforaphane is derived from nuclear erythroid 2-related factor 2 (Nrf2) activation as demonstrated by increased expression of Nrf2 and downstream targets hemeoxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1) in neuro2a cells and sciatic nerve of diabetic animals. Nuclear factor-kappa B (NF-κB) inhibition seemed to be responsible for antiinflammatory activity of sulforaphane as there was reduction in NF-κB expression and IκB kinase (IKK) phosphorylation along with abrogation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) levels. Here in this study we provide an evidence that sulforaphane is effective in reversing the various deficits in experimental diabetic neuropathy. This study supports the defensive role of Nrf2 in neurons under conditions of oxidative stress and also suggests that the NF-κB pathway is an important modulator of inflammatory damage in diabetic neuropathy.

  2. DANGER is involved in high glucose-induced radioresistance through inhibiting DAPK-mediated anoikis in non-small cell lung cancer.

    PubMed

    Kwon, TaeWoo; Youn, HyeSook; Son, Beomseok; Kim, Daehoon; Seong, Ki Moon; Park, Sungkyun; Kim, Wanyeon; Youn, BuHyun

    2016-02-09

    18F-labeled fluorodeoxyglucose (FDG) uptake during FDG positron emission tomography seems to reflect increased radioresistance. However, the exact molecular mechanism underlying high glucose (HG)-induced radioresistance is unclear. In the current study, we showed that ionizing radiation-induced activation of the MEK-ERK-DAPK-p53 signaling axis is required for anoikis (anchorage-dependent apoptosis) of non-small cell lung cancer (NSCLC) cells in normal glucose media. Phosphorylation of DAPK at Ser734 by ERK was essential for p53 transcriptional activity and radiosensitization. In HG media, overexpressed DANGER directly bound to the death domain of DAPK, thus inhibiting the catalytic activity of DAPK. In addition, inhibition of the DAPK-p53 signaling axis by DANGER promoted anoikis-resistance and epithelial-mesenchymal transition (EMT), resulting in radioresistance of HG-treated NSCLC cells. Notably, knockdown of DANGER enhanced anoikis, EMT inhibition, and radiosensitization in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that overexpression of DANGER and the subsequent inhibitory effect on DAPK kinase activity are critical responses that account for HG-induced radioresistance of NSCLC.

  3. MicroRNA-9 inhibits high glucose-induced proliferation, differentiation and collagen accumulation of cardiac fibroblasts by down-regulation of TGFBR2

    PubMed Central

    Li, Jiaxin; Dai, Yingnan; Su, Zhendong; Wei, Guoqian

    2016-01-01

    To investigate the effects of miR-9 on high glucose (HG)-induced cardiac fibrosis in human cardiac fibroblasts (HCFs), and to establish the mechanism underlying these effects. HCFs were transfected with miR-9 inhibitor or mimic, and then treated with normal or HG. Cell viability and proliferation were detected by using the Cell Counting Kit-8 (CCK-8) assay and Brdu-ELISA assay. Cell differentiation and collagen accumulation of HCFs were detected by qRT-PCR and Western blot assays respectively. The mRNA and protein expressions of transforming growth factor-β receptor type II (TGFBR2) were determined by qRT-PCR and Western blotting. Up-regulation of miR-9 dramatically improved HG-induced increases in cell proliferation, differentiation and collagen accumulation of HCFs. Moreover, bioinformatics analysis predicted that the TGFBR2 was a potential target gene of miR-9. Luciferase reporter assay demonstrated that miR-9 could directly target TGFBR2. Inhibition of TGFBR2 had the similar effect as miR-9 overexpression. Down-regulation of TGFBR2 in HCFs transfected with miR-9 inhibitor partially reversed the protective effect of miR-9 overexpression on HG-induced cardiac fibrosis in HCFs. Up-regulation of miR-9 ameliorates HG-induced proliferation, differentiation and collagen accumulation of HCFs by down-regulation of TGFBR2. These results provide further evidence for protective effect of miR-9 overexpression on HG-induced cardiac fibrosis. PMID:27756824

  4. Erianin inhibits high glucose-induced retinal angiogenesis via blocking ERK1/2-regulated HIF-1α-VEGF/VEGFR2 signaling pathway

    PubMed Central

    Yu, Zengyang; Zhang, Tianyu; Gong, Chenyuan; Sheng, Yuchen; Lu, Bin; Zhou, Lingyu; Ji, Lili; Wang, Zhengtao

    2016-01-01

    Erianin is a natural compound found in Dendrobium chrysotoxum Lindl. Diabetic retinopathy (DR) is a serious and common microvascular complication of diabetes. This study aims to investigate the inhibitory mechanism of erianin on retinal neoangiogenesis and its contribution to the amelioration of DR. Erianin blocked high glucose (HG)-induced tube formation and migration in choroid-retinal endothelial RF/6A cells. Erianin inhibited HG-induced vascular endothelial growth factor (VEGF) expression, hypoxia-inducible factor 1-alpha (HIF-1α) translocation into nucleus and ERK1/2 activation in RF/6A and microglia BV-2 cells. MEK1/2 inhibitor U0126 blocked HG-induced HIF-1α and ERK1/2 activation in both above two cells. In addition, erianin abrogated VEGF-induced angiogenesis in vitro and in vivo, and also inhibited VEGF-induced activation of VEGF receptor 2 (VEGFR2) and its downstream cRaf-MEK1/2-ERK1/2 and PI3K-AKT signaling pathways in RF/6A cells. Furthermore, erianin reduced the increased retinal vessels, VEGF expression and microglia activation in streptozotocin (STZ)-induced hyperglycemic and oxygen-induced retinopathy (OIR) mice. In conclusion, our results demonstrate that erianin inhibits retinal neoangiogenesis by abrogating HG-induced VEGF expression by blocking ERK1/2-mediated HIF-1α activation in retinal endothelial and microglial cells, and further suppressing VEGF-induced activation of VEGFR2 and its downstream signals in retinal endothelial cells. PMID:27678303

  5. Prevention of High Blood Pressure

    MedlinePlus

    ... the NHLBI on Twitter. Prevention of High Blood Pressure Healthy lifestyle habits, proper use of medicines, and ... blood pressure or its complications. Preventing High Blood Pressure Onset Healthy lifestyle habits can help prevent high ...

  6. Snf1-Dependent Transcription Confers Glucose-Induced Decay upon the mRNA Product

    PubMed Central

    Braun, Katherine A.; Dombek, Kenneth M.

    2015-01-01

    In the yeast Saccharomyces cerevisiae, the switch from respiratory metabolism to fermentation causes rapid decay of transcripts encoding proteins uniquely required for aerobic metabolism. Snf1, the yeast ortholog of AMP-activated protein kinase, has been implicated in this process because inhibiting Snf1 mimics the addition of glucose. In this study, we show that the SNF1-dependent ADH2 promoter, or just the major transcription factor binding site, is sufficient to confer glucose-induced mRNA decay upon heterologous transcripts. SNF1-independent expression from the ADH2 promoter prevented glucose-induced mRNA decay without altering the start site of transcription. SNF1-dependent transcripts are enriched for the binding motif of the RNA binding protein Vts1, an important mediator of mRNA decay and mRNA repression whose expression is correlated with decreased abundance of SNF1-dependent transcripts during the yeast metabolic cycle. However, deletion of VTS1 did not slow the rate of glucose-induced mRNA decay. ADH2 mRNA rapidly dissociated from polysomes after glucose repletion, and sequences bound by RNA binding proteins were enriched in the transcripts from repressed cells. Inhibiting the protein kinase A pathway did not affect glucose-induced decay of ADH2 mRNA. Our results suggest that Snf1 may influence mRNA stability by altering the recruitment activity of the transcription factor Adr1. PMID:26667037

  7. High Blood Cholesterol Prevention

    MedlinePlus

    ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

  8. Preventing High Blood Pressure

    MedlinePlus

    ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

  9. Paradoxical glucose-induced hyperkalemia. Combined aldosterone-insulin deficiency.

    PubMed

    Goldfarb, S; Strunk, B; Singer, I; Goldberg, M

    1975-11-01

    Severe hyperkalemia associated with spontaneous hyperglycemia as well as with the intravenous infusions of glucose occurred in an insulin-requiring diabetic patient in the absence of potassium administration, the use of diuretics which inhibit urinary potassium excretion or acidemia. Metabolic balance studies revealed, in addition to diabets, the presence of isolated aldosterone deficiency of the hyporeninemic type. Intravenous glucose infusions (0.5 g/kg body weight) produced significant hyperkalemia but desoxycortisone acetate (DOCA) therapy (10 mg/day) prevented the glucose-induced hyperkalemia. In this patient, the serum potassium concentration increases after the intravenous infusions of glucose because there is insufficient aldosterone and insulin to reverse the transfer of potassium to the extracellular fluid which normally occurs after hypertonic infusions of glucose. Although DOCA replacement modifies the distribution of potassium in the extracellular fluid and blunts the hyperkalemic effect of intravenous infusions of glucose, a rise in the insulin level is required for the usual hypokalemic response to intravenously administered glucose. These studies illustrate the risk of raising blood glucose levels in patients with combined aldosterone and insulin deficiency and the tendency towards hyperkalemia in diabetic patients under certain clinical conditions.

  10. Augmented glucose-induced insulin release in mice lacking G(o2), but not G(o1) or G(i) proteins.

    PubMed

    Wang, Ying; Park, Sangeun; Bajpayee, Neil S; Nagaoka, Yoshiko; Boulay, Guylain; Birnbaumer, Lutz; Jiang, Meisheng

    2011-01-25

    Insulin secretion by pancreatic β cells is a complex and highly regulated process. Disruption of this process can lead to diabetes mellitus. One of the various pathways involved in the regulation of insulin secretion is the activation of heterotrimeric G proteins. Bordetella pertussis toxin (PTX) promotes insulin secretion, suggesting the involvement of one or more of three G(i) and/or two G(o) proteins as suppressors of insulin secretion from β cells. However, neither the mechanism of this inhibitory modulation of insulin secretion nor the identity of the G(i/o) proteins involved has been elucidated. Here we show that one of the two splice variants of G(o), G(o2), is a key player in the control of glucose-induced insulin secretion by β cells. Mice lacking G(o2)α, but not those lacking α subunits of either G(o1) or any G(i) proteins, handle glucose loads more efficiently than wild-type (WT) mice, and do so by increased glucose-induced insulin secretion. We thus provide unique genetic evidence that the G(o2) protein is a transducer in an inhibitory pathway that prevents damaging oversecretion of insulin.

  11. Cardioprotective role of Syzygium cumini against glucose-induced oxidative stress in H9C2 cardiac myocytes.

    PubMed

    Atale, Neha; Chakraborty, Mainak; Mohanty, Sujata; Bhattacharya, Susinjan; Nigam, Darshika; Sharma, Manish; Rani, Vibha

    2013-09-01

    Diabetic patients are known to have an independent risk of cardiomyopathy. Hyperglycemia leads to upregulation of reactive oxygen species (ROS) that may contribute to diabetic cardiomyopathy. Thus, agents that suppress glucose-induced intracellular ROS levels can have therapeutic potential against diabetic cardiomyopathy. Syzygium cumini is well known for its anti-diabetic potential, but its cardioprotective properties have not been evaluated yet. The aim of the present study is to analyze cardioprotective properties of methanolic seed extract (MSE) of S. cumini in diabetic in vitro conditions. ROS scavenging activity of MSE was studied in glucose-stressed H9C2 cardiac myoblasts after optimizing the safe dose of glucose and MSE by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide. 2',7'-dichlorfluorescein diacetate staining and Fluorescence-activated cell sorting analysis confirmed the suppression of ROS production by MSE in glucose-induced cells. The intracellular NO and H2O2 radical-scavenging activity of MSE was found to be significantly high in glucose-induced cells. Exposure of glucose-stressed H9C2 cells to MSE showed decline in the activity of catalase and superoxide dismutase enzymes and collagen content. 4',6-diamidino-2-phenylindole, propidium iodide and 10-N-nonyl-3,6-bis (dimethylamino) acridine staining revealed that MSE protects myocardial cells from glucose-induced stress. Taken together, our findings revealed that the well-known anti-diabetic S. cumini can also protect the cardiac cells from glucose-induced stress.

  12. Icariin attenuates high glucose-induced type IV collagen and fibronectin accumulation in glomerular mesangial cells by inhibiting transforming growth factor-β production and signalling through G protein-coupled oestrogen receptor 1.

    PubMed

    Li, Yi-Chen; Ding, Xuan-Sheng; Li, Hui-Mei; Zhang, Cheng

    2013-09-01

    Icariin has been shown to attenuate diabetic nephropathy in rats by decreasing transforming growth factor-β (TGF-β) and type IV collagen expression, but its mode of action in glomerular mesangial cells is uncertain. The present study aimed to investigate the effect of icariin on excess mesangial type IV collagen and fibronectin accumulation induced by high glucose, and to determine the mechanism underlying its protective effects. Under high-glucose conditions, icariin diminished type IV collagen and fibronectin accumulation, as well as TGF-β production in human and rat mesangial cells. Mesangial cells treated with icariin after TGF-β1 exposure expressed less type IV collagen and fibronectin than those without icariin treatment, suggesting inhibition by icariin of TGF-β1 downstream pathways. On TGF-β1 stimulation, icariin inhibited TGF-β canonical Smad signalling and extracellular signal-regulated kinase (ERK)1/2 signalling by decreasing Smad2/3 and ERK1/2 phosphorylation in a dose-dependent manner. U0126, which blocked the ERK1/2 pathway, exerted an additive effect on the icariin suppression of type IV collagen and fibronectin expression, enhancing the beneficial effects of icariin. The G protein-coupled oestrogen receptor 1 (GPER) antagonist, G-15, abolished the icariin-induced inhibition of type IV collagen, and fibronectin overproduction and TGF-β signalling. Treatment of cells with fulvestrant, a downregulator of the oestrogen receptor, enhanced the action of icariin. In conclusion, icariin decreased type IV collagen and fibronectin accumulation induced by high glucose in mesangial cells by inhibiting TGF-β production, as well as Smad and ERK signalling in a GPER-dependent manner.

  13. TGR5 suppresses high glucose-induced upregulation of fibronectin and transforming growth factor-β1 in rat glomerular mesangial cells by inhibiting RhoA/ROCK signaling.

    PubMed

    Xiong, Fengxiao; Li, Xuejuan; Yang, Zhiying; Wang, Yu; Gong, Wenyan; Huang, Junying; Chen, Cheng; Liu, Peiqing; Huang, Heqing

    2016-12-01

    RhoA/ROCK can cause renal inflammation and fibrosis in the context of diabetes by activating nuclear factor-κB (NF-κB). TGR5 is known for its role in maintaining metabolic homeostasis and anti-inflammation, which is closely related to NF-κB inhibition. Given that TGR5 is highly enriched in kidney, we aim to investigate the regulatory role of TGR5 on fibronectin (FN) and transforming growth factor-β1 (TGF-β1) in high glucose (HG)-treated rat glomerular mesangial cells (GMCs). Both the factors are closely related to renal inflammations and mediated by NF-κB. Moreover, our study determines whether such regulation is achieved by the inhibition of RhoA/ROCK and the subsequent NF-κB suppression. Polymerase chain reaction was taken to test the mRNA level of TGR5. Western blot was used to measure the protein expressions of TGR5, FN, TGF-β1, p65, IκBα, phospho-MYPT1 (Thr853), and MYPT1. Glutathione S-transferase-pull down and immunofluorescence were conducted to test the activation of RhoA, the distribution of TGR5, and p65, respectively. Electrophoretic mobility shift assay was adopted to measure the DNA binding activity of NF-κB. In GMCs, TGR5 activation or overexpression significantly suppressed FN and TGF-β1 protein expressions, NF-κB, and RhoA/ROCK activation induced by HG or transfection of constitutively active RhoA. By contrast, TGR5 RNA interference caused enhancement of FN, TGF-β1 protein expressions, increase of RhoA/ROCK activation. However, TGR5 cannot suppress RhoA/ROCK activation when a selective Protein kinase A (PKA) inhibitor was used. This study suggests that in HG-treated GMCs, TGR5 significantly suppresses the NF-κB-mediated upregulation of FN and TGF-β1, which are hallmarks of diabetic nephropathy. These functions are closely related to the suppression of RhoA/ROCK via PKA.

  14. An inhibitor of thrombin activated fibrinolysis inhibitor (TAFI) can reduce extracellular matrix accumulation in an in vitro model of glucose induced ECM expansion.

    PubMed

    Atkinson, J M; Pullen, N; Johnson, T S

    2013-06-24

    Chronic kidney disease (CKD) is characterised by the pathological accumulation of extracellular matrix (ECM) proteins leading to progressive kidney scarring via glomerular and tubular basement membrane expansion. Increased ECM synthesis and deposition, coupled with reduced ECM breakdown contribute to the elevated ECM level in CKD. Previous pre-clinical studies have demonstrated that increased plasmin activity has a beneficial effect in the protein overload model of CKD. As plasmin activation is downregulated by the action of the thrombin activated fibrinolytic inhibitor (TAFI), we tested the hypothesis that inhibition of TAFI might increase plasmin activity and reduce ECM accumulation in an in vitro model of glucose induced ECM expansion. Treatment of NRK52E tubular epithelial cells with increasing concentrations of glucose resulted in a 40% increase in TAFI activity, a 38% reduction in plasmin activity and a subsequent increase in ECM accumulation. In this model system, application of the previously reported TAFI inhibitor UK-396082 [(2S)-5-amino-2-[(1-n-propyl-1H-imidazol-4-yl)methyl]pentanoic acid] caused a reduction in TAFI activity, increased plasmin activity and induced a parallel decrease in ECM levels. In contrast, RNAi knockdown of plasmin resulted in an increase in ECM levels. The data presented here indicate that high glucose induces TAFI activity, inhibiting plasmin activation which results in elevated ECM levels in tubular epithelial cells. The results support the hypothesis that UK-396082 is able to reduce TAFI activity, normalising plasmin activity and preventing excess ECM accumulation suggesting that TAFI inhibition may have potential as an anti-scarring strategy in CKD.

  15. Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets

    PubMed Central

    Maedler, Kathrin; Sergeev, Pavel; Ris, Frédéric; Oberholzer, José; Joller-Jemelka, Helen I.; Spinas, Giatgen A.; Kaiser, Nurit; Halban, Philippe A.; Donath, Marc Y.

    2002-01-01

    In type 2 diabetes, chronic hyperglycemia is suggested to be detrimental to pancreatic β cells, causing impaired insulin secretion. IL-1β is a proinflammatory cytokine acting during the autoimmune process of type 1 diabetes. IL-1β inhibits β cell function and promotes Fas-triggered apoptosis in part by activating the transcription factor NF-κB. Recently, we have shown that increased glucose concentrations also induce Fas expression and β cell apoptosis in human islets. The aim of the present study was to test the hypothesis that IL-1β may mediate the deleterious effects of high glucose on human β cells. In vitro exposure of islets from nondiabetic organ donors to high glucose levels resulted in increased production and release of IL-1β, followed by NF-κB activation, Fas upregulation, DNA fragmentation, and impaired β cell function. The IL-1 receptor antagonist protected cultured human islets from these deleterious effects. β cells themselves were identified as the islet cellular source of glucose-induced IL-1β. In vivo, IL-1β–producing β cells were observed in pancreatic sections of type 2 diabetic patients but not in nondiabetic control subjects. Similarly, IL-1β was induced in β cells of the gerbil Psammomys obesus during development of diabetes. Treatment of the animals with phlorizin normalized plasma glucose and prevented β cell expression of IL-1β. These findings implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and identify the IL-1β/NF-κB pathway as a target to preserve β cell mass and function in this condition. PMID:12235117

  16. Cysteine analogues potentiate glucose-induced insulin release in vitro

    SciTech Connect

    Ammon, H.P.; Hehl, K.H.; Enz, G.; Setiadi-Ranti, A.; Verspohl, E.J.

    1986-12-01

    In rat pancreatic islets, cysteine analogues, including glutathione, acetylcysteine, cysteamine, D-penicillamine, L-cysteine ethyl ester, and cysteine-potentiated glucose (11.1 mM) induced insulin secretion in a concentration-dependent manner. Their maximal effects were similar and occurred at approximately 0.05, 0.05, 0.1, 0.5, 1.0, 1.0 mM, respectively. At substimulatory glucose levels (2.8 mM), insulin release was not affected by these compounds. In contrast, thiol compounds, structurally different from cysteine and its analogues, such as mesna, tiopronin, meso-2,3-dimercaptosuccinic acid (DMSA), dimercaprol (BAL), beta-thio-D-glucose, as well as those cysteine analogues that lack a free-thiol group, including L-cystine, cystamine, D-penicillamine disulfide, S-carbocysteine, and S-carbamoyl-L-cysteine, did not enhance insulin release at stimulatory glucose levels (11.1 mM); cystine (5 mM) was inhibitory. These in vitro data indicate that among the thiols tested here, only cysteine and its analogues potentiate glucose-induced insulin secretion, whereas thiols that are structurally not related to cysteine do not. This suggests that a cysteine moiety in the molecule is necessary for the insulinotropic effect. For their synergistic action to glucose, the availability of a sulfhydryl group is also a prerequisite. The maximal synergistic action is similar for all cysteine analogues tested, whereas the potency of action is different, suggesting similarity in the mechanism of action but differences in the affinity to the secretory system.

  17. Fenofibrate Attenuated Glucose-Induced Mesangial Cells Proliferation and Extracellular Matrix Synthesis via PI3K/AKT and ERK1/2

    PubMed Central

    Zhu, Fengming; Ma, Zufu; Liao, Wenhui; He, Yong; He, JinSeng; Li, Wei; Yang, Juan; Lu, Qian; Xu, Gang; Yao, Ying

    2013-01-01

    Excess mesangial extracellular matrix (ECM) and mesangial cell proliferation is the major pathologic feature of diabetic nephropathy (DN). Fenofibrate, a PPARα agonist, has been shown to attenuate extracellular matrix formation in diabetic nephropathy. However, the mechanisms underlying this effect remain to be elucidated. In this study, the effect of fenofibrate on high-glucose induced cell proliferation and extracellular matrix exertion and its mechanisms were investigated in cultured rat mesangial cells by the methylthiazoletetrazolium (MTT) assay, flow cytometry and western blot. The results showed that treatment of mesangial cells (MCs) with fenofibrate repressed high-glucose induced up-regulation of extracellular matrix Collagen-IV, and inhibited entry of cell cycle into the S phase. This G1 arrest and ECM inhibition was caused by the reduction of phosphorylation and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and AKT. On the contrary, PPARα siRNA accelerated high glucose-induced cell cycle progression by ERK1/2 and AKT activation. Taken together, fenofibrate ameliorated glucose-induced mesangial cell proliferation and matrix production via its inhibition of PI3K/AKT and ERK1/2 signaling pathways. Such mechanisms may contribute to the favorable effects of treatment using fenofibrate in diabetic nephropathy. PMID:24130796

  18. The protective effect of magnesium lithospermate B against glucose-induced intracellular oxidative damage

    SciTech Connect

    Qu, Jian; Ren, Xian; Hou, Rui-ying; Dai, Xing-ping; Zhao, Ying-chun; Xu, Xiao-jing; Zhang, Wei; Zhou, Gan; Zhou, Hong-hao; Liu, Zhao-qian

    2011-07-22

    Highlights: {yields} LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. {yields} LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. {yields} LAB plays an important role against glucose-induced intracellular oxidative damage. {yields} The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway. -- Abstract: Objectives: To investigate the effects of magnesium lithospermate B (LAB) on intracellular reactive oxygen species (ROS) production induced by high dose of glucose or H{sub 2}O{sub 2}, we explored the influences of LAB on the expression of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf2) in HEK293T cells after treatment with high dose of glucose. Materials and methods: The total nuclear proteins in HEK293T cells were extracted with Cytoplasmic Protein Extraction Kit. The ROS level was determined by flow cytometry. The mRNA and protein expression of HO-1 and Nrf2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Results: LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. The amount of Nrf2 translocation was enhanced after cells were pretreated with 50 {mu}mol/L or 100 {mu}mol/L LAB. Silencing of Nrf2 gene eliminated the enhanced expression of HO-1 protein induced by high dose of glucose plus LAB. Conclusions: LAB plays an important role against glucose-induced intracellular oxidative damage. The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway.

  19. Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance

    PubMed Central

    Brandon, Amanda E.; Tid-Ang, Jennifer; Wright, Lauren E.; Stuart, Ella; Suryana, Eurwin; Bentley, Nicholas; Turner, Nigel; Cooney, Gregory J.; Ruderman, Neil B.; Kraegen, Edward W.

    2015-01-01

    SIRT1 is a NAD+-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 expression affect markers of muscle mitochondrial content and also determined whether SIRT1 influenced muscle insulin resistance induced by acute glucose oversupply. In male Wistar rats either SIRT1 or a deacetylase inactive mutant form (H363Y) was electroprated into the tibialis cranialis (TC) muscle. The other leg was electroporated with an empty control vector. One week later, glucose was infused and hyperglycaemia was maintained at ~11mM. After 5 hours, 11mM glucose induced significant insulin resistance in skeletal muscle. Interestingly, overexpression of either SIRT1 or SIRT1 (H363Y) for 1 week did not change markers of mitochondrial content or function. SIRT1 or SIRT1 (H363Y) overexpression had no effect on the reduction in glucose uptake and glycogen synthesis in muscle in response to hyperglycemia. Therefore we conclude that acute increases in SIRT1 protein have little impact on mitochondrial content and that overexpressing SIRT1 does not prevent the development of insulin resistance during hyperglycaemia. PMID:25798922

  20. Preventative effects of Ginkgo biloba extract (EGb761) on high glucose-cultured opacity of rat lens.

    PubMed

    Lu, Qian; Yang, Tingting; Zhang, Mingzhu; Du, Lei; Liu, Ling; Zhang, Nan; Guo, Hao; Zhang, Fan; Hu, Gang; Yin, Xiaoxing

    2014-05-01

    Diabetic cataract is one of the earliest secondary complications of diabetes, and it is characterized by opacification of the eye lens. In this study, we examined the protective effects of Ginkgo biloba extract (EGb761) on rat lenses cultured in high-glucose conditions. The cultured rat lenses were divided into six groups: normal group, high-glucose group, high glucose plus low, medium, and high concentrations of EGb761 groups, and a high glucose plus bendazac lysine group. The activities of antioxidases, aldose reductase, advanced glycosylation end products, transforming growth factor-β2, Smad2/3, E-cadherin, and α-smooth muscle actin were assessed by different methods. Compared with the levels in the high glucose group, EGb761 decreased the intensity of oxidative stress, decreased aldose reductase activation and the level of advanced glycosylation end products, and suppress the transforming growth factor-β2 or Smad pathway activation, further increase the expression of E-cadherin and decrease α-smooth muscle actin, and therefore, prevents the pathological changes of high glucose-induced lens epithelial cells and ameliorated lens opacity. These results suggest that EGb761 has protective effects on several pharmacological targets in the progress of diabetic cataract and is a potential drug for the prevention of diabetic cataract.

  1. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

    SciTech Connect

    Deusing, Dorothé Jenni Beyrer, Melanie Fitzenberger, Elena Wenzel, Uwe

    2015-05-08

    Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation.

  2. Succinate is a preferential metabolic stimulus-coupling signal for glucose-induced proinsulin biosynthesis translation.

    PubMed

    Alarcon, Cristina; Wicksteed, Barton; Prentki, Marc; Corkey, Barbara E; Rhodes, Christopher J

    2002-08-01

    The secondary signals emanating from increased glucose metabolism, which lead to specific increases in proinsulin biosynthesis translation, remain elusive. It is known that signals for glucose-stimulated insulin secretion and proinsulin biosynthesis diverge downstream of glycolysis. Consequently, the mitochondrial products ATP, Krebs cycle intermediates, glutamate, and acetoacetate were investigated as candidate stimulus-coupling signals specific for glucose-induced proinsulin biosynthesis in rat islets. Decreasing ATP levels by oxidative phosphorylation inhibitors showed comparable effects on proinsulin biosynthesis and total protein synthesis. Although it is a cofactor, ATP is unlikely to be a metabolic stimulus-coupling signal specific for glucose-induced proinsulin biosynthesis. Neither glutamic acid methyl ester nor acetoacetic acid methyl ester showed a specific effect on glucose-stimulated proinsulin biosynthesis. Interestingly, among Krebs cycle intermediates, only succinic acid monomethyl ester specifically stimulated proinsulin biosynthesis. Malonic acid methyl ester, an inhibitor of succinate dehydrogenase, also specifically increased glucose-induced proinsulin biosynthesis without affecting islet ATP levels or insulin secretion. Glucose caused a 40% increase in islet intracellular succinate levels, but malonic acid methyl ester showed no further effect, probably due to efficient conversion of succinate to succinyl-CoA. In this regard, a GTP-dependent succinyl-CoA synthetase activity was found in cytosolic fractions of pancreatic islets. Thus, succinate and/or succinyl-CoA appear to be preferential metabolic stimulus-coupling factors for glucose-induced proinsulin biosynthesis translation.

  3. Fructose impairs glucose-induced hepatic triglyceride synthesis.

    PubMed

    Huang, Danshan; Dhawan, Tania; Young, Stephen; Yong, William H; Boros, Laszlo G; Heaney, Anthony P

    2011-01-24

    Obesity, type 2 diabetes and hyperlipidemia frequently coexist and are associated with significantly increased morbidity and mortality. Consumption of refined carbohydrate and particularly fructose has increased significantly in recent years and has paralled the increased incidence of obesity and diabetes. Human and animal studies have demonstrated that high dietary fructose intake positively correlates with increased dyslipidemia, insulin resistance, and hypertension. Metabolism of fructose occurs primarily in the liver and high fructose flux leads to enhanced hepatic triglyceride accumulation (hepatic steatosis). This results in impaired glucose and lipid metabolism and increased proinflammatory cytokine expression. Here we demonstrate that fructose alters glucose-stimulated expression of activated acetyl CoA carboxylase (ACC), pSer hormone sensitive lipase (pSerHSL) and adipose triglyceride lipase (ATGL) in hepatic HepG2 or primary hepatic cell cultures in vitro. This was associated with increased de novo triglyceride synthesis in vitro and hepatic steatosis in vivo in fructose- versus glucose-fed and standard-diet fed mice. These studies provide novel insight into the mechanisms involved in fructose-mediated hepatic hypertriglyceridemia and identify fructose-uptake as a new potential therapeutic target for lipid-associated diseases.

  4. Working with Youth in High-Risk Environments: Experiences in Prevention. OSAP Prevention Monograph-12.

    ERIC Educational Resources Information Center

    Marcus, Carol E., Ed.; Swisher, John D., Ed.

    This report focuses on prevention programs developed with support from the Office for Substance Abuse Prevention's (OSAP) High-Risk Youth Demonstration Grant Program. Included are an Introduction (Eric Goplerud and others) and the following reports: (1) "Athletes Coaching Teens for Substance Abuse Prevention: Alcohol and Other Drug Use and Risk…

  5. Consumption of a glucose diet enhances the sensitivity of pancreatic islets from adrenalectomized genetically obese (ob/ob) mice to glucose-induced insulin secretion.

    PubMed

    Mistry, A M; Chen, N G; Lee, Y S; Romsos, D R

    1995-03-01

    Consumption of a glucose diet for 4 d markedly elevates plasma insulin concentrations in adrenalectomized ob/ob mice. The present study examined regulation of insulin secretion from perifused pancreatic islets of female adrenalectomized genetically obese (ob/ob) and lean mice fed a glucose diet for 4 d. These mice were fed a high carbohydrate commercial diet for 21 d, or the high carbohydrate commercial diet for 17 d and a purified high glucose diet for the last 4 d of the 21-d feeding period. Adrenalectomy equalized plasma insulin concentrations, pancreatic islet size, rates of insulin secretion in response to 20 mmol/L glucose and insulin mRNA relative abundance in ob/ob and lean mice fed the commercial diet, but the threshold for glucose-induced insulin secretion determined by a linear glucose gradient remained lower in islets from adrenalectomized ob/ob mice than in those from lean mice (3.8 +/- 0.1 vs. 4.9 +/- 0.2 mmol/L glucose), and addition of acetylcholine to the perifusate lowered the threshold to only 2.0 +/- 0.1 mmol/L glucose in islets from ob/ob mice vs. 3.3 +/- 0.1 mmol/L glucose in lean mice. Switching from the commercial diet to the glucose diet for 4 d increased plasma insulin concentrations -10-fold in islets from adrenalectomized ob/ob mice without affecting islet size, 20 mmol/L glucose-induced insulin secretion or insulin mRNA abundance. Consumption of the glucose diet did, however, markedly lower the threshold for glucose-induced insulin secretion in islets from adrenalectomized ob/ob mice to approximate the abnormally low glucose thresholds in intact ob/ob mice.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Statins suppress glucose-induced plasminogen activator inhibitor-1 expression by regulating RhoA and nuclear factor-κB activities in cardiac microvascular endothelial cells.

    PubMed

    Ni, Xiao-Qing; Zhu, Jian-Hua; Yao, Ning-Hua; Qian, Juan; Yang, Xiang-Jun

    2013-01-01

    The aim of this study was to investigate the possible proinflammatory signaling pathways involved in statin inhibition of glucose-induced plasminogen activator inhibitor-1 (PAI-1) expression in cardiac microvascular endothelial cells (CMECs). Primary rat CMECs were grown in the presence of 5.7 or 23 mmol/L glucose. PAI-1 mRNA and protein expression levels were measured by realtime polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay, respectively. A pull-down assay was performed to determine RhoA activity. IκBα protein expression was measured by Western blotting, nuclear factor (NF)-κB activation was detected by electrophoretic mobility shift assay and its transcription activity was determined by a dual luciferase reporter gene assay. PAI-1 mRNA and protein expression levels were both increased with high glucose concentrations, but they were significantly suppressed by simvastatin and atorvastatin treatment (P < 0.01) and the effects were reversed by mevalonate (100 μmol/L) and geranylgeranyl pyrophosphate (10 μmol/L) but not farnesyl pyrophosphate (10 μmol/L). Such effects were similar to those of a RhoA inhibitor, C3 exoenzyme (5 μg/mL), inhibitors of RhoA kinase (ROCK), Y-27632 (10 μmol/L) and hydroxyfasudil (10 μmol/L) and an NF-κB inhibitor, BAY 11-7082 (5 μmol/L). High glucose-induced RhoA and NF-κB activations in CMECs were both significantly inhibited by statins (P < 0.01). Simvastatin and atorvastatin equally suppress high glucose-induced PAI-1 expression. These effects of statins may occur partly by regulating the RhoA/ROCK-NF-κB pathway. The multifunctional roles of statins may be particularly beneficial for patients with metabolic syndrome.

  7. Adiponectin increases glucose-induced insulin secretion through the activation of lipid oxidation.

    PubMed

    Patané, G; Caporarello, N; Marchetti, P; Parrino, C; Sudano, D; Marselli, L; Vigneri, R; Frittitta, L

    2013-12-01

    The expression of adiponectin receptors has been demonstrated in human and rat pancreatic beta cells, where globular (g) adiponectin rescues rat beta cells from cytokine and fatty acid-induced apoptosis. The aim of our study was to evaluate whether adiponectin has a direct effect on insulin secretion and the metabolic pathways involved. Purified human pancreatic islets and rat beta cells (INS-1E) were exposed (1 h) to g-adiponectin, and glucose-induced insulin secretion was measured. A significant increase in glucose-induced insulin secretion was observed in the presence of g-adiponectin (1 nmol/l) with respect to control cells in both human pancreatic islets (n = 5, p < 0.05) and INS-1E cells (n = 5, p < 0.001). The effect of globular adiponectin on insulin secretion was independent of AMP-dependent protein kinase (AMPK) activation or glucose oxidation. In contrast, g-adiponectin significantly increased oleate oxidation (n = 5, p < 0.05), and the effect of g-adiponectin (p < 0.001) on insulin secretion by INS-1E was significantly reduced in the presence of etomoxir (1 μmol/l), an inhibitor of fatty acid beta oxidation. g-Adiponectin potentiates glucose-induced insulin secretion in both human pancreatic islets and rat beta cells via an AMPK independent pathway. Increased fatty acid oxidation rather than augmented glucose oxidation is the mechanism responsible. Overall, our data indicate that, in addition to its anti-apoptotic action, g-adiponectin has another direct effect on beta cells by potentiating insulin secretion. Adiponectin, therefore, in addition to its well-known effect on insulin sensitivity, has important effects at the pancreatic level.

  8. Uncoupling protein 2 negatively regulates glucose-induced glucagon-like peptide 1 secretion.

    PubMed

    Zhang, Hongjie; Li, Jing; Liang, Xiangying; Luo, Yun; Zen, Ke; Zhang, Chen-Yu

    2012-04-01

    It is known that endogenous levels of the incretin hormone glucagon-like peptide 1 (GLP1) can be enhanced by various secretagogues, but the mechanism underlying GLP1 secretion is still not fully understood. We assessed the possible effect of uncoupling protein 2 (UCP2) on GLP1 secretion in mouse intestinal tract and NCI-H716 cells, a well-characterized human enteroendocrine L cell model. Localization of UCP2 and GLP1 in the gastrointestinal tract was assessed by immunofluorescence staining. Ucp2 mRNA levels in gut were analyzed by quantitative RT-PCR. Human NCI-H716 cells were transiently transfected with siRNAs targeting UCP2. The plasma and ileum tissue levels of GLP1 (7-36) amide were measured using an ELISA kit. UCP2 was primarily expressed in the mucosal layer and colocalized with GLP1 in gastrointestinal mucosa. L cells secreting GLP1 also expressed UCP2. After glucose administration, UCP2-deficient mice showed increased glucose-induced GLP1 secretion compared with wild-type littermates. GLP1 secretion increased after NCI-H716 cells were transfected with siRNAs targeting UCP2. UCP2 was markedly upregulated in ileum tissue from ob/ob mice, and GLP1 secretion decreased compared with normal mice. Furthermore, GLP1 secretion increased after administration of genipin by oral gavage. Taken together, these results reveal an inhibitory role of UCP2 in glucose-induced GLP1 secretion.

  9. A Prevention Program for Middle-School High Risk Youth.

    ERIC Educational Resources Information Center

    Gittman, Elizabeth; Cassata, Marian

    A 5-year federally funded substance abuse prevention program targeted 426 high risk middle-school youth from 4 school districts in Nassau County, New York. Combining a child-centered model with a systemic approach, the program's goal was to prevent or delay the onset of alcohol and other drug use. High-risk youth were identified by school…

  10. Cancer Prevention Fellowship Program Aims for High Marks | Division of Cancer Prevention

    Cancer.gov

    For nearly 30 years, the NCI Cancer Prevention Fellowship Program (CPFP) has provided funding support for post-doctoral Fellows with a goal to train the future generation of researchers and leaders in the field. Infographic Highlight Cancer Prevention Fellowship Program Aims for High Marks |

  11. High School Teachers' Perceptions of Cyberbullying Prevention and Intervention Strategies

    ERIC Educational Resources Information Center

    Stauffer, Sterling; Heath, Melissa Allen; Coyne, Sarah Marie; Ferrin, Scott

    2012-01-01

    Recent meta-analyses indicate that bully prevention programs produce minimal change in student behavior. This study examined 66 high school teachers' perceptions regarding the effect of cyberbullying on students, which intervening strategies teachers would use when dealing with cyberbullying, and which prevention strategies would assist in…

  12. Evaluation of high myopia complications prevention program in university freshmen

    PubMed Central

    Tseng, Gow-Lieng; Chen, Cheng-Yu

    2016-01-01

    Abstract High myopia is a global eye health problem because of its high incidence of sight-threatening complications. Due to the role of awareness, self-examination, and preventive behavior in prevention of morbidity of high myopia complications, promoting knowledge, capabilities, and attitude of high myopic personnel are required in this regard. In this quasi-experiment study, 31 freshmen with high myopia in a national university were enrolled in 2014. The data were collected by validated and reliable questionnaire based on health belief model (HBM) and self-efficacy theory. The intervention program consisted of 1 educational session lasting 150 minutes by lecturing of high myopia complications, virtual reality experiencing, similarity modeling, and quibbling a film made on high myopia complications preventive concepts. Implementing the educational program showed immediate effect in knowledge, perceived susceptibility, perceived severity, self-efficacy, and preventive behavior intention. While 6 weeks after the educational program, significant increases were observed in cues to action, self-efficacy, and preventive behavior intention. This article provided that, after a single session, there was positive improvement in high myopia complication prevention behavior intention among participants. These positive effects confirmed the efficacy of the education program and will probably induce behavior change. PMID:27749586

  13. A Mixed Methods Study of High School Dropout Prevention Programs

    ERIC Educational Resources Information Center

    Hibler, Derrick, Sr.

    2013-01-01

    In the United States in 2011, 6,000 students between the ages of 16 and 24 dropped out of high school on a daily basis. Educators have developed numerous dropout prevention programs to address this problem. However, little research exists examining how high school principals and counselors engage students in these programs. The purpose of this…

  14. Nigella sativa seed extracts enhance glucose-induced insulin release from rat-isolated Langerhans islets.

    PubMed

    Rchid, Halima; Chevassus, Hugues; Nmila, Rachid; Guiral, Carine; Petit, Pierre; Chokaïri, Mustapha; Sauvaire, Yves

    2004-10-01

    Nigella sativa L. 'Black cumin' (Ranunculaceae) is one of the plants commonly used in Moroccan folk medicine for treatment of various ailments including diabetes mellitus. The present study was undertaken to investigate the effect of different N. sativa seed extracts on insulin secretion. Different fractions of the seed were prepared: the defatted fraction (HR II), which was divided into two subfractions: the first (HR III) containing acidic and neutral compounds and the second (HR IV) containing basic compounds. The insulin secretory effects of these extracts were evaluated individually at different concentrations (0.01, 0.1, 1 and 5 mg/mL), in vitro in isolated rat pancreatic islets in the presence of 8.3 mmol/L glucose. The results show that addition of the defatted whole extract or of the basic subfraction of the seed in the incubation medium significantly increased glucose-induced insulin release from the islets. In the case of the acidic and neutral subfraction, the stimulatory effect was observed only for the higher concentration (5 mg/mL). However, a clear concentration-dependent increase in insulin release from isolated pancreatic islets was observed for the basic subfraction. Our data show that the antidiabetic properties of N. sativa seeds may be, at least partly, mediated by stimulated insulin release, and that the basic subfraction largely contributes to this stimulatory effect. Further phytochemical studies are underway in order to isolate the pharmacological compound(s) responsible for the insulinotropic effect of N. sativa seeds.

  15. Triphenyltin impairs insulin secretion by decreasing glucose-induced NADP(H) and ATP production in hamster pancreatic β-cells.

    PubMed

    Miura, Yoshikazu; Hori, Yuichi; Kimura, Shinzo; Hachiya, Hiroyuki; Sakurai, Yuichirou; Inoue, Kenichi; Sawada, Tokihiko; Kubota, Keiichi

    2012-09-28

    Oral administration of triphenyltin chloride (TPT) (6 mg/100g body weight) inhibits insulin secretion by decreasing glucose-induced cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in pancreatic β-cells of the hamster. To test the possibility that the abnormal level of the [Ca(2+)](i) induced by TPT administration could be due to a defect in the metabolic signal of glucose in the β-cells, we tested the effects of TPT administration on the glucose-induced NAD(P)H and ATP production, and on the changes of membrane potential and [Ca(2+)](i) by glucose and high K(+) in the β-cells. The [Ca(2+)](i) was measured in islet cells loaded with fura-2. TPT administration significantly reduced the NAD(P)H and ATP production, the depolarization of plasma membrane, and insulin secretion by 15 mM glucose in islet cells. TPT administration also reduced the insulin secretion by 10mM dihydroxyacetone and glyceraldehyde. However, TPT administration did not affect the increase of [Ca(2+)](i) and the insulin secretion by 30 mMK(+) or 100 μM tolbutamide, and the membrane potential by 30 mMK(+), and the insulin secretion by 10mM α-ketoisocaproic acid and 0.5mM formycin A, an analog of ATP in the presence of 15 mM glucose. These results suggested that the pathogenesis of TPT-induced hyperglycemia in hamster involves the reduction of [Ca(2+)](i) and insulin secretion in response to K(ATP) channel-dependent depolarization, which is related to the decrease of NAD(P)H and ATP production in pancreatic islet cells after glucose metabolism.

  16. Effects of Comprehensive, Multiple High-Risk Behaviors Prevention Program on High School Students

    ERIC Educational Resources Information Center

    Collier, Crystal

    2013-01-01

    The purpose of this mixed methods study was to examine the effect of a multiple high-risk behaviors prevention program applied comprehensively throughout an entire school-system involving universal, selective, and indicated levels of students at a local private high school during a 4-year period. The prevention program was created based upon the…

  17. Preventing ash agglomeration during gasification of high-sodium lignite

    SciTech Connect

    Robert S. Dahlin; Johnny R. Dorminey; WanWang Peng; Roxann F. Leonard; Pannalal Vimalchand

    2009-01-15

    Various additives were evaluated to assess their ability to prevent ash agglomeration during the gasification of high-sodium lignite. Additives that showed promise in simple muffle furnace tests included meta-kaolin, vermiculite, two types of silica fume, and one type of bauxite. Additives that were tested and rejected included dolomite, calcite, sand flour, kaolinite, fine kaolin, and calcined bauxite. Based on the muffle furnace test results, the meta-kaolin was selected for a follow-on demonstration in a pilot-scale coal gasifier. Pilot-scale testing showed that the addition of coarse (minus 14-mesh, 920-{mu}m mean size) meta-kaolin at a feed rate roughly equivalent to the ash content of the lignite (10 wt %) successfully prevented agglomeration and deposition problems during gasification of high-sodium lignite at a maximum operating temperature of 927{sup o}C (1700{sup o}F). 13 refs., 24 figs., 1 tab.

  18. L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2.

    PubMed

    Nakatsu, Daiki; Horiuchi, Yuta; Kano, Fumi; Noguchi, Yoshiyuki; Sugawara, Taichi; Takamoto, Iseki; Kubota, Naoto; Kadowaki, Takashi; Murata, Masayuki

    2015-03-10

    Increase in the concentration of plasma L-cysteine is closely associated with defective insulin secretion from pancreatic β-cells, which results in type 2 diabetes (T2D). In this study, we investigated the effects of prolonged L-cysteine treatment on glucose-stimulated insulin secretion (GSIS) from mouse insulinoma 6 (MIN6) cells and from mouse pancreatic islets, and found that the treatment reversibly inhibited glucose-induced ATP production and resulting GSIS without affecting proinsulin and insulin synthesis. Comprehensive metabolic analyses using capillary electrophoresis time-of-flight mass spectrometry showed that prolonged L-cysteine treatment decreased the levels of pyruvate and its downstream metabolites. In addition, methyl pyruvate, a membrane-permeable form of pyruvate, rescued L-cysteine-induced inhibition of GSIS. Based on these results, we found that both in vitro and in MIN6 cells, L-cysteine specifically inhibited the activity of pyruvate kinase muscle isoform 2 (PKM2), an isoform of pyruvate kinases that catalyze the conversion of phosphoenolpyruvate to pyruvate. L-cysteine also induced PKM2 subunit dissociation (tetramers to dimers/monomers) in cells, which resulted in impaired glucose-induced ATP production for GSIS. DASA-10 (NCGC00181061, a substituted N,N'-diarylsulfonamide), a specific activator for PKM2, restored the tetramer formation and the activity of PKM2, glucose-induced ATP production, and biphasic insulin secretion in L-cysteine-treated cells. Collectively, our results demonstrate that impaired insulin secretion due to exposure to L-cysteine resulted from its direct binding and inactivation of PKM2 and suggest that PKM2 is a potential therapeutic target for T2D.

  19. Prevention

    MedlinePlus

    ... our e-newsletter! Aging & Health A to Z Prevention Basic Facts & Information Some factors that affect your ... control of the things that you can change. Preventive Recommendations for Adults Aged 65 and Older The ...

  20. Prevention

    MedlinePlus

    ... Is Strong Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... to avoid secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  1. Preventing and Managing Toxicities of High-Dose Methotrexate.

    PubMed

    Howard, Scott C; McCormick, John; Pui, Ching-Hon; Buddington, Randall K; Harvey, R Donald

    2016-12-01

    : High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m(2), is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%-12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated.

  2. Protective Effects of Liraglutide and Linagliptin in C. elegans as a New Model for Glucose-Induced Neurodegeneration.

    PubMed

    Wongchai, K; Schlotterer, A; Lin, J; Humpert, P M; Klein, T; Hammes, H-P; Morcos, M

    2016-01-01

    Liraglutide and linagliptin are novel drugs for the treatment of diabetes. Antioxidative and neuroprotective effects have been described for both compounds. However, it is not yet known, whether these mechanisms are also protective against diabetic retinal neurodegeneration. We assessed the antioxidative and neuroprotective capabilities of liraglutide and linagliptin as well as the signaling pathways involved, by using C. elegans as a model for glucose-induced neurodegeneration. C. elegans were cultivated under conditions, which mimic clinical hyperglycemia, and treated with 160 μmol/l liraglutide or 13 μmol/l linagliptin. Oxidative stress was reduced by 29 or 78% and methylglyoxal-derived advanced glycation endproducts (AGEs) by 33 or 22%, respectively. This resulted in an improved neuronal function by 42 or 60% and an extended mean lifespan by 9 or 11%, respectively. Antioxidative and AGE reducing effects of liraglutide and linagliptin were not dependent on v-akt murine thymoma viral oncogene homologue 1/forkhead box O1 (AKT1/FOXO). Neuroprotection by liraglutide was AKT1/FOXO dependent, yet AKT1/FOXO independent upon linagliptin treatment. Both liraglutide and linagliptin exert neuroprotective effects in an experimental model for glucose-induced neurodegeneration, however, the signaling pathways differ in the present study. Further pharmacological intervention with these pathways may help to delay the clinical onset of diabetic retinopathy by preserving neuronal integrity.

  3. High-altitude illnesses: physiology, risk factors, prevention, and treatment.

    PubMed

    Taylor, Andrew T

    2011-01-01

    High-altitude illnesses encompass the pulmonary and cerebral syndromes that occur in non-acclimatized individuals after rapid ascent to high altitude. The most common syndrome is acute mountain sickness (AMS) which usually begins within a few hours of ascent and typically consists of headache variably accompanied by loss of appetite, nausea, vomiting, disturbed sleep, fatigue, and dizziness. With millions of travelers journeying to high altitudes every year and sleeping above 2,500 m, acute mountain sickness is a wide-spread clinical condition. Risk factors include home elevation, maximum altitude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-acclimatization, genetic make-up, and pre-existing diseases. At higher altitudes, sleep disturbances may become more profound, mental performance is impaired, and weight loss may occur. If ascent is rapid, acetazolamide can reduce the risk of developing AMS, although a number of high-altitude travelers taking acetazolamide will still develop symptoms. Ibuprofen can be effective for headache. Symptoms can be rapidly relieved by descent, and descent is mandatory, if at all possible, for the management of the potentially fatal syndromes of high-altitude pulmonary and cerebral edema. The purpose of this review is to combine a discussion of specific risk factors, prevention, and treatment options with a summary of the basic physiologic responses to the hypoxia of altitude to provide a context for managing high-altitude illnesses and advising the non-acclimatized high-altitude traveler.

  4. Preventing Raman Lasing in High-Q WGM Resonators

    NASA Technical Reports Server (NTRS)

    Savchenkov, Anatoliy; Matsko, Andrey; Strekalov, Dmitry; Maleki, Lute

    2007-01-01

    A generic design has been conceived to suppress the Raman effect in whispering- gallery-mode (WGM) optical resonators that have high values of the resonance quality factor (Q). Although it is possible to exploit the Raman effect (even striving to maximize the Raman gain to obtain Raman lasing), the present innovation is intended to satisfy a need that arises in applications in which the Raman effect inhibits the realization of the full potential of WGM resonators as frequency-selection components. Heretofore, in such applications, it has been necessary to operate high-Q WGM resonators at unattractively low power levels to prevent Raman lasing. (The Raman-lasing thresholds of WGM optical resonators are very low and are approximately proportional to Q(sup -2)). Heretofore, two ways of preventing Raman lasting at high power levels have been known, but both entail significant disadvantages: A resonator can be designed so that the optical field is spread over a relatively large mode volume to bring the power density below the threshold. For any given combination of Q and power level, there is certain mode volume wherein Raman lasing does not start. Unfortunately, a resonator that has a large mode volume also has a high spectral density, which is undesirable in a typical photonic application. A resonator can be cooled to the temperature of liquid helium, where the Raman spectrum is narrower and, therefore, the Raman gain is lower. However, liquid-helium cooling is inconvenient. The present design overcomes these disadvantages, making it possible to operate a low-spectral-density (even a single-mode) WGM resonator at a relatively high power level at room temperature, without risk of Raman lasing.

  5. Monomethylated-adenines potentiate glucose-induced insulin production and secretion via inhibition of phosphodiesterase activity in rat pancreatic islets.

    PubMed

    Boland, Brandon B; Alarcón, Cristina; Ali, Almas; Rhodes, Christopher J

    2015-01-01

    Monomethyladenines have effects on DNA repair, G-protein-coupled receptor antagonism and autophagy. In islet ß-cells, 3-methyladenine (3-MA) has been implicated in DNA-repair and autophagy, but its mechanism of action is unclear. Here, the effect of monomethylated adenines was examined in rat islets. 3-MA, N6-methyladenine (N6-MA) and 9-methyladenine (9-MA), but not 1- or 7-monomethylated adenines, specifically potentiated glucose-induced insulin secretion (3-4 fold; p ≤ 0.05) and proinsulin biosynthesis (∼2-fold; p ≤ 0.05). Using 3-MA as a 'model' monomethyladenine, it was found that 3-MA augmented [cAMP]i accumulation (2-3 fold; p ≤ 0.05) in islets within 5 minutes. The 3-, N6- and 9-MA also enhanced glucose-induced phosphorylation of the cAMP/protein kinase-A (PKA) substrate cAMP-response element binding protein (CREB). Treatment of islets with pertussis or cholera toxin indicated 3-MA mediated elevation of [cAMP]i was not mediated via G-protein-coupled receptors. Also, 3-MA did not compete with 9-cyclopentyladenine (9-CPA) for adenylate cyclase inhibition, but did for the pan-inhibitor of phosphodiesterase (PDE), 3-isobutyl-1-methylxanthine (IBMX). Competitive inhibition experiments with PDE-isoform specific inhibitors suggested 3-MA to have a preference for PDE4 in islet ß-cells, but this was likely reflective of PDE4 being the most abundant PDE isoform in ß-cells. In vitro enzyme assays indicated that 3-, N6- and 9-MA were capable of inhibiting most PDE isoforms found in ß-cells. Thus, in addition to known inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3'K)/m Target of Rapamycin (mTOR) signaling, 3-MA also acts as a pan-phosphodiesterase inhibitor in pancreatic ß-cells to elevate [cAMP]i and then potentiate glucose-induced insulin secretion and production in parallel.

  6. Psychosis Prevention: A Modified Clinical High Risk Perspective From the Recognition and Prevention (RAP) Program

    PubMed Central

    Cornblatt, Barbara A.; Carrión, Ricardo E.; Auther, Andrea; McLaughlin, Danielle; Olsen, Ruth H.; John, Majnu; Correll, Christoph U.

    2016-01-01

    Objective Early intervention and prevention of psychosis remain a major challenge. Prediction would be greatly advanced with improved ability to identify individuals at true risk, which, at present, is moderate at best. The authors tested a modified strategy to improve prediction by selecting a more homogeneous high-risk sample (attenuated positive symptom criteria only, age range of mid-teens to early 20s) than is currently standard, combined with a systematic selection of neurodevelopmental deficits. Method A sample of 101 treatment-seeking adolescents (mean age, 15.9 years) at clinical high risk for psychosis were followed clinically for up to 5 years (mean follow-up time, 3.0 years, SD=1.6). Adolescents were included only if they exhibited one or more attenuated positive symptoms at moderate to severe, but not psychotic, severity levels. Cox regression was used to derive a risk index. Results The overall conversion rate to psychosis was 28.3%. The final predictor model, with a positive predictive validity of 81.8%, consisted of four variables: disorganized communication, suspiciousness, verbal memory deficits, and decline in social functioning during follow-up. Significant effects also suggest narrowing the risk age range to 15–22 years. Conclusions Clinical high risk criteria that emphasize disorganized communication and suspiciousness while also including compromised verbal memory and declining social functioning have the potential to improve predictive accuracy compared with attenuated positive symptoms used alone. On the resulting risk index (a weighted combination of the predictors), low scores were interpreted as signifying minimal risk, with little treatment necessary, high scores as suggesting aggressive intervention, and intermediate scores, although less informative, as supporting psychosocial treatment. PMID:26046336

  7. Do high concentrations of microcystin prevent Daphnia control of phytoplankton?

    PubMed

    Chislock, Michael F; Sarnelle, Orlando; Jernigan, Lauren M; Wilson, Alan E

    2013-04-15

    Toxin-producing cyanobacteria have frequently been hypothesized to limit the ability of herbivorous zooplankton (such as Daphnia) to control phytoplankton biomass by inhibiting feeding, and in extreme cases, causing zooplankton mortality. Using limnocorral experiments in hyper-eutrophic ponds located in Alabama and Michigan (U.S.A.), we tested the hypothesis that high levels of cyanobacteria and microcystin, a class of hepatotoxins produced by several cyanobacterial genera, prevent Daphnia from strongly reducing phytoplankton abundance. At the start of the first experiment (Michigan), phytoplankton communities were dominated by toxic Microcystis and Anabaena (∼96% of total phytoplankton biomass), and concentrations of microcystin were ∼3 μg L⁻¹. Two weeks after adding Daphnia pulicaria from a nearby eutrophic lake, microcystin levels increased to ∼6.5 μg L⁻¹, yet Daphnia populations increased exponentially (r = 0.24 day⁻¹). By the third week, Daphnia had suppressed phytoplankton biomass by ∼74% relative to the no Daphnia controls and maintained reduced phytoplankton biomass until the conclusion of the five-week experiment. In the second experiment (Alabama), microcystin concentrations were greater than 100 μg L⁻¹, yet a mixture of three D. pulicaria clones from eutrophic lakes in southern MI increased and again reduced phytoplankton biomass, in this case by over 80%. The ability of Daphnia to increase in abundance and suppress phytoplankton biomass, despite high initial levels of cyanobacteria and microcystin, indicates that the latter does not prevent strong control of phytoplankton biomass by Daphnia genotypes that are adapted to environments with abundant cyanobacteria and associated cyanotoxins.

  8. Prevention

    MedlinePlus

    ... Ban For Clinicians Clinical Recognition Specimen Collection Treatment Smallpox Vaccine Guidance Infection Control: Hospital Infection Control: Home ... Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections Poxvirus Prevention Recommend on ...

  9. PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells.

    PubMed

    Miele, Claudia; Raciti, Gregory Alexander; Cassese, Angela; Romano, Chiara; Giacco, Ferdinando; Oriente, Francesco; Paturzo, Flora; Andreozzi, Francesco; Zabatta, Assunta; Troncone, Giancarlo; Bosch, Fatima; Pujol, Anna; Chneiweiss, Hervé; Formisano, Pietro; Beguinot, Francesco

    2007-03-01

    The phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (ped/pea-15) gene is overexpressed in human diabetes and causes this abnormality in mice. Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. However, they showed impaired insulin response to hyperglycemia. Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells. Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. Overexpression of PED/PEA-15 dysregulates beta-cell function and is sufficient to impair glucose tolerance in mice.

  10. "Cancer--Educate to Prevent"--high-school teachers, the new promoters of cancer prevention education campaigns.

    PubMed

    Barros, Ana; Moreira, Luís; Santos, Helena; Ribeiro, Nuno; Carvalho, Luís; Santos-Silva, Filipe

    2014-01-01

    Cancer is one of the leading causes of death worldwide, and thus represents a priority for national public health programs. Prevention has been assumed as the best strategy to reduce cancer burden, however most cancer prevention programs are implemented by healthcare professionals, which constrain range and educational impacts. We developed an innovative approach for cancer prevention education focused on high-school biology teachers, considered privileged mediators in the socialization processes. A training program, "Cancer, Educate to Prevent" was applied, so that the teachers were able to independently develop and implement prevention campaigns focused on students and school-related communities. The program encompassed different educational modules, ranging from cancer biology to prevention campaigns design. Fifty-four teachers were empowered to develop and implement their own cancer prevention campaigns in a population up to five thousands students. The success of the training program was assessed through quantitative evaluation--questionnaires focused on teachers' cancer knowledge and perceptions, before the intervention (pre-test) and immediately after (post-test). The projects developed and implemented by teachers were also evaluated regarding the intervention design, educational contents and impact on the students' knowledge about cancer. This study presents and discusses the results concerning the training program "Cancer, Educate to Prevent" and clearly shows a significant increase in teacher's cancer literacy (knowledge and perceptions) and teachers' acquired proficiency to develop and deliver cancer prevention campaigns with direct impact on students' knowledge about cancer. This pilot study reinforces the potential of high-school teachers and schools as cancer prevention promoters and opens a new perspective for the development and validation of cancer prevention education strategies, based upon focused interventions in restricted targets (students

  11. Involvement of AMPK in regulating the degradation of MAD2B under high glucose in neuronal cells.

    PubMed

    Meng, Xianfang; Chu, Guangpin; Ye, Chen; Tang, Hui; Qiu, Ping; Hu, Yue; Li, Man; Zhang, Chun

    2016-12-13

    Although our recent study has demonstrated that mitotic spindle assembly checkpoint protein (MAD2B) mediates high glucose-induced neuronal apoptosis, the mechanisms for MAD2B degradation under hyperglycaemia have not yet been elucidated. In this study, we first found that the activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) was decreased in neurons, accompanied with the increased expression of MAD2B. Mechanistically, we demonstrated that activation of AMPK with its activators such as AICAR and metformin decreased the expression of MAD2B, indicating a role of AMPK in regulating the expression of MAD2B. Moreover, activation of AMPK prevented neuronal cells from high glucose-induced injury as demonstrated by the reduced expression of cyclin B1 and percentage of apoptosis as detected by TUNEL. We further found that when total protein synthesis was suppressed by chlorhexidine, the degradation of MAD2B was slower in high glucose-treated neurons and was mainly dependent on the ubiquitin-proteasome system. Finally, it was indicated that high glucose inhibited the ubiquitination of MAD2B, which could be reversed by activation of AMPK. Collectively, this study demonstrates that AMPK acts as a key regulator of MAD2B expression, suggesting that activation of AMPK signalling might be crucial for the treatment of high glucose-induced neuronal injury.

  12. Dynamin-related protein 1 mediates low glucose-induced endothelial dysfunction in human arterioles.

    PubMed

    Tanner, Michael J; Wang, Jingli; Ying, Rong; Suboc, Tisha B; Malik, Mobin; Couillard, Allison; Branum, Amberly; Puppala, Venkata; Widlansky, Michael E

    2017-03-01

    Intensive glycemic regulation has resulted in an increased incidence of hypoglycemia. Hypoglycemic burden correlates with adverse cardiovascular complications and contributes acutely and chronically to endothelial dysfunction. Prior data indicate that mitochondrial dysfunction contributes to hypoglycemia-induced endothelial dysfunction, but the mechanisms behind this linkage remain unknown. We attempt to determine whether clinically relevant low-glucose (LG) exposures acutely induce endothelial dysfunction through activation of the mitochondrial fission process. Characterization of mitochondrial morphology was carried out in cultured endothelial cells by using confocal microscopy. Isolated human arterioles were used to explore the effect LG-induced mitochondrial fission has on the formation of detrimental reactive oxygen species (ROS), bioavailability of nitric oxide (NO), and endothelial-dependent vascular relaxation. Fluorescence microscopy was employed to visualize changes in mitochondrial ROS and NO levels and videomicroscopy applied to measure vasodilation response. Pharmacological disruption of the profission protein Drp1 with Mdivi-1 during LG exposure reduced mitochondrial fragmentation among vascular endothelial cells (LG: 0.469; LG+Mdivi-1: 0.276; P = 0.003), prevented formation of vascular ROS (LG: 2.036; LG+Mdivi-1: 1.774; P = 0.005), increased the presence of NO (LG: 1.352; LG+Mdivi-1: 1.502; P = 0.048), and improved vascular dilation response to acetylcholine (LG: 31.6%; LG+Mdivi-1; 78.5% at maximum dose; P < 0.001). Additionally, decreased expression of Drp1 via siRNA knockdown during LG conditions also improved vascular relaxation. Exposure to LG imparts endothelial dysfunction coupled with altered mitochondrial phenotypes among isolated human arterioles. Disruption of Drp1 and subsequent mitochondrial fragmentation events prevents impaired vascular dilation, restores mitochondrial phenotype, and implicates mitochondrial fission as a primary

  13. Bioactive fraction of Saraca indica prevents diabetes induced cataractogenesis: An aldose reductase inhibitory activity

    PubMed Central

    Somani, Gauresh; Sathaye, Sadhana

    2015-01-01

    Background: The present study was designed to investigate the effect of Saraca indica (SI) flowers extract and different bioactive fraction on in vitro aldose reductase (AR) inhibitory activity, high glucose-induced cataract in goat lens and in vivo streptozotocin (STZ; 45 mg/kg, i.p) induced cataract in rats. Methods: Extract of flowers of SI tested for inhibition against rat lens AR. Furthermore, bioactive fraction was investigated against high glucose-induced opacification of the lens in vitro lens culture and STZ induced diabetic cataract in rats. Identification of the bioactive component was attempted through high-performance thin-layer chromatography, high-performance liquid chromatography and liquid chromatography-mass spectrometry analysis. Results: Ethyl acetate fraction of S. indica (EASI) produced maximum inhibition that may be due to high phenolic content. Goat lenses in media containing glucose developed a distinctly opaque ring in 72 h and treatment with EASI fraction lowered lens opacity in 72 h. Prolonged treatment with EASI to STZ-induced diabetic rats inhibited the AR activity and delayed cataract progression in a dose dependent manner. Conclusion: Ethyl acetate fraction of S. indica fraction has potential to inhibit rat lens AR enzyme and prevent cataractogenesis not only in goat lens model (in vitro), but also in STZ induced diabetic rats (in vivo). This study is suggestive of the anticataract activity of EASI fraction that could be attributed to the phytoconstituents present in the same. PMID:25709218

  14. Glucose-induced activation of the plasma membrane H(+)-ATPase in Fusarium oxysporum.

    PubMed

    Brandão, R L; Castro, I M; Passos, J B; Nicoli, J R; Thevelein, J M

    1992-08-01

    Addition of glucose and other sugars to derepressed cells of the fungus Fusarium oxysporum var. lini triggered activation of the plasma membrane H(+)-ATPase within 5 min. Glucose was the best activator while galactose and lactose had a lesser effect. The activation was not prevented by previous addition of cycloheximide and it was fully reversible when the glucose was removed. The activation process in vivo also caused changes in the kinetic properties of the enzyme. The non-activated enzyme had an apparent Km of about 3.2 mM for ATP whereas the activated enzyme showed an apparent Km of 0.26 mM. In addition, the pH optimum of the H(+)-ATPase changed from 6.0 to 7.5 upon activation. The activated enzyme was more sensitive to inhibition by vanadate. When F. oxysporum was cultivated in media containing glucose as the major carbon source, enhanced H(+)-ATPase activity was largely confined to the period corresponding to the lag phase, i.e. just before the start of acidification of the medium. This suggests that the activation process might play a role in the onset of extracellular acidification. Addition of glucose to F. oxysporum var. lini cells also caused an increase in the cAMP level. No reliable increase could be demonstrated for the other sugars. Addition of proton ionophores such as DNP and CCCP at pH 5.0 caused both a large increase in the intracellular level of cAMP and in the activity of the plasma membrane H(+)-ATPase. Inhibition of the DNP-induced increase in the cAMP level by acridine orange also resulted in inhibition of the activation of plasma membrane H(+)-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Effect of Betula pendula Leaf Extract on α-Glucosidase and Glutathione Level in Glucose-Induced Oxidative Stress

    PubMed Central

    Bljajić, Kristina; Šoštarić, Nina; Petlevski, Roberta; Vujić, Lovorka; Brajković, Andrea; Fumić, Barbara; de Carvalho, Isabel Saraiva

    2016-01-01

    B. pendula leaf is a common ingredient in traditional herbal combinations for treatment of diabetes in southeastern Europe. Present study investigated B. pendula ethanolic and aqueous extract as inhibitors of carbohydrate hydrolyzing enzymes, as well as their ability to restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress. Phytochemical analysis revealed presence of rutin and other quercetin derivatives, as well as chlorogenic acid. In general, ethanolic extract was richer in phenolic substances than the aqueous extract. Furthermore, a comprehensive analysis of antioxidant activity of two extracts (determined by DPPH and ABTS radical scavenging activity, total antioxidant activity, and chelating activity as well as ferric-reducing antioxidant power) has shown that ethanolic extract was better radical scavenger and metal ion reductant. In addition, ethanolic extract effectively increased cellular glutathione levels caused by hyperglycemia and inhibited α-glucosidase with the activity comparable to that of acarbose. Therefore, in vitro research using B. pendula plant extracts has confirmed their antidiabetic properties. PMID:27668005

  16. Role of Nodal-PITX2C signaling pathway in glucose-induced cardiomyocyte hypertrophy.

    PubMed

    Su, Dongmei; Jing, Sun; Guan, Lina; Li, Qian; Zhang, Huiling; Gao, Xiaobo; Ma, Xu

    2014-06-01

    Pathological cardiac hypertrophy is a major cause of morbidity and mortality in cardiovascular disease. Recent studies have shown that cardiomyocytes, in response to high glucose (HG) stimuli, undergo hypertrophic growth. While much work still needs to be done to elucidate this important mechanism of hypertrophy, previous works have showed that some pathways or genes play important roles in hypertrophy. In this study, we showed that sublethal concentrations of glucose (25 mmol/L) could induce cardiomyocyte hypertrophy with an increase in the cellular surface area and the upregulation of the atrial natriuretic peptide (ANP) gene, a hypertrophic marker. High glucose (HG) treatments resulted in the upregulation of the Nodal gene, which is under-expressed in cardiomyocytes. We also determined that the knockdown of the Nodal gene resisted HG-induced cardiomyocyte hypertrophy. The overexpression of Nodal was able to induce hypertrophy in cardiomyocytes, which was associated with the upregulation of the PITX2C gene. We also showed that increases in the PITX2C expression, in response to Nodal, were mediated by the Smad4 signaling pathway. This study is highly relevant to the understanding of the effects of the Nodal-PITX2C pathway on HG-induced cardiomyocyte hypertrophy, as well as the related molecular mechanisms.

  17. Bovine retinal pericytes are resistant to glucose-induced oxidative stress in vitro.

    PubMed

    Agardh, Carl-David; Hultberg, Björn; Nayak, Ramesh C; Farthing-Nayak, Pamela; Agardh, Elisabet

    2005-01-01

    Diabetic retinopathy is a sight-threatening complication of diabetes, and loss of pericytes represents early signs of its development. We tested the hypothesis that high glucose levels may induce signs of oxidative stress in cultured bovine retinal pericytes. Pericytes were exposed to either normal (5.5 mM) or high (22 mM) glucose levels for 1, 3, and 5 days. Signs of oxidative stress were measured by expression of copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase using real-time RTPCR. To elucidate the role of oxidative stress, we also measured glutathione (GSH) concentration in the cells and investigated the impact of thiol-reactive metal ions and hydrogen peroxide (H(2)O(2)) on intracellular GSH. Despite the stimulation with high glucose, thiol-reactive metal ions, or H(2)O(2), there was no clear increased expression of antioxidant enzymes or influence of GSH levels. Lipid peroxidation (malondialdehyde level) was increased in bovine aortic smooth muscle cells, but not in bovine retinal pericytes. The data indicate that pericytes do not develop oxidative stress in response to hyperglycemia. However, it is not definitively excluded that oxidative stress may occur after longer time periods of glucose stimulation.

  18. HB-EGF release mediates glucose-induced activation of the epidermal growth factor receptor in mesangial cells.

    PubMed

    Uttarwar, L; Peng, F; Wu, D; Kumar, S; Gao, B; Ingram, A J; Krepinsky, J C

    2011-04-01

    Glomerular matrix accumulation is a hallmark of diabetic nephropathy. We showed that transactivation of the epidermal growth factor receptor (EGFR) is an important mediator of matrix upregulation in mesangial cells (MC) in response to high glucose (HG). Here, we study the mechanism of EGFR transactivation. In primary MC, EGFR transactivation by 1 h of HG (30 mM) was unaffected by inhibitors of protein kinase C, reactive oxygen species, or the angiotensin II AT1 receptor. However, general metalloprotease inhibition, as well as specific inhibitors of heparin-binding EGF-like growth factor (HB-EGF), prevented both EGFR and downstream Akt activation. HB-EGF was released into the medium by 30 min of HG, and this depended on metalloprotease activity. One of the metalloproteases shown to cleave proHB-EGF is ADAM17 (TACE). HG, but not an osmotic control, activated ADAM17, and its inhibition prevented EGFR and Akt activation and HB-EGF release into the medium. siRNA to either ADAM17 or HB-EGF prevented HG-induced EGFR transactivation. We previously showed that EGFR/Akt signaling increases transforming growth factor (TGF)-β1 transcription through the transcription factor activator protein (AP)-1. HG-induced AP-1 activation, as assessed by EMSA, was abrogated by inhibitors of metalloproteases, HB-EGF and ADAM17. HB-EGF and ADAM17 siRNA also prevented AP-1 activation. Finally, these inhibitors and siRNA prevented TGF-β1 upregulation by HG. Thus, HG-induced EGFR transactivation in MC is mediated by the release of HB-EGF, which requires activity of the metalloprotease ADAM17. The mechanism of ADAM17 activation awaits identification. Targeting upstream mediators of EGFR transactivation including HB-EGF or ADAM17 provides novel therapeutic targets for the treatment of diabetic nephropathy.

  19. Ethylene acts as a negative regulator of glucose induced lateral root emergence in Arabidopsis.

    PubMed

    Singh, Manjul; Gupta, Aditi; Laxmi, Ashverya

    2015-01-01

    Plants, being sessile organisms, are more exposed to the hazards of constantly changing environmental conditions globally. During the lifetime of a plant, the root system encounters various challenges such as obstacles, pathogens, high salinity, water logging, nutrient scarcity etc. The developmental plasticity of the root system provides brilliant adaptability to plants to counter the changes exerted by both external as well as internal cues and achieve an optimized growth status. Phytohormones are one of the major intrinsic factors regulating all aspects of plant growth and development both independently as well as through complex signal integrations at multiple levels. We have previously shown that glucose (Glc) and brassinosteroid (BR) signalings interact extensively to regulate lateral root (LR) development in Arabidopsis. (1) Auxin efflux as well as influx and downstream signaling components are also involved in Glc-BR regulation of LR emergence. Here, we provide evidence for involvement of ethylene signaling machinery downstream to Glc and BR in regulation of LR emergence.

  20. Ethylene acts as a negative regulator of glucose induced lateral root emergence in Arabidopsis

    PubMed Central

    Singh, Manjul; Gupta, Aditi; Laxmi, Ashverya

    2015-01-01

    Plants, being sessile organisms, are more exposed to the hazards of constantly changing environmental conditions globally. During the lifetime of a plant, the root system encounters various challenges such as obstacles, pathogens, high salinity, water logging, nutrient scarcity etc. The developmental plasticity of the root system provides brilliant adaptability to plants to counter the changes exerted by both external as well as internal cues and achieve an optimized growth status. Phytohormones are one of the major intrinsic factors regulating all aspects of plant growth and development both independently as well as through complex signal integrations at multiple levels. We have previously shown that glucose (Glc) and brassinosteroid (BR) signalings interact extensively to regulate lateral root (LR) development in Arabidopsis.1 Auxin efflux as well as influx and downstream signaling components are also involved in Glc-BR regulation of LR emergence. Here, we provide evidence for involvement of ethylene signaling machinery downstream to Glc and BR in regulation of LR emergence. PMID:26236960

  1. Emerging technologies for the prevention of dental caries. Are current methods of prevention sufficient for the high risk patient?

    PubMed Central

    Bretz, Walter A; Rosa, Odila P S

    2011-01-01

    Fluorides and chlorhexidine are technologies that are 65 and 40 yeas old, respectively. This overview argues that current methods of caries prevention are not effective for the high caries risk patient. In this review examples, arguments and recommendations are provided to address the high caries risk patient that include: failure of comprehensive chemical modalities treatments to address the high caries risk patient; ecological alteration - would this be an effective approach?; and biomaterials and oral microbiome research to address the high caries risk patient. PMID:21726223

  2. Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats

    SciTech Connect

    Minor, Robin K.; Smith, Daniel L.; Sossong, Alex M.; Kaushik, Susmita; Poosala, Suresh; Spangler, Edward L.; Roth, George S.; Lane, Mark; Allison, David B.; Cabo, Rafael de; Ingram, Donald K.; Mattison, Julie A.

    2010-03-15

    Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolarization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.

  3. Initial Indicators of Effectiveness for a High School Drug Prevention Program

    ERIC Educational Resources Information Center

    Fearnow-Kenney, Melodie D.; Wyrick, David L.; Jackson-Newsom, Julia; Wyrick, Cheryl H.; Hansen, William B.

    2003-01-01

    All Stars, Sr. is a comprehensive high school health education supplement designed to prevent high-risk behaviors among adolescents. The program includes topics such as personal health, nutrition, interpersonal relationships, and stress, with a special emphasis on drug prevention. Effective research-based programs that target late onset prevention…

  4. Inhibition of SGLT2 alleviates diabetic nephropathy by suppressing high glucose-induced oxidative stress in type 1 diabetic mice.

    PubMed

    Hatanaka, Takashi; Ogawa, Daisuke; Tachibana, Hiromi; Eguchi, Jun; Inoue, Tatsuyuki; Yamada, Hiroshi; Takei, Kohji; Makino, Hirofumi; Wada, Jun

    2016-08-01

    It is unclear whether the improvement in diabetic nephropathy by sodium glucose cotransporter 2 (SGLT2) inhibitors is caused by a direct effect on SGLT2 or by the improvement in hyperglycemia. Here, we investigated the effect of dapagliflozin on early-stage diabetic nephropathy using a mouse model of type 1 diabetes and murine proximal tubular epithelial cells. Eight-week-old Akita mice were treated with dapagliflozin or insulin for 12 weeks. Body weight, urinary albumin excretion, blood pressure, as well as levels of blood glucose and hemoglobin A1c were measured. Expansion of the mesangial matrix, interstitial fibrosis, and macrophage infiltration in kidneys were evaluated by histology. Oxidative stress and apoptosis were evaluated in kidneys and cultured proximal tubular epithelial cells. Compared with nontreated mice, dapagliflozin and insulin decreased blood glucose and hemoglobin A1c levels equally. Urine volume and water intake increased significantly in the dapagliflozin-treated group compared with those in the insulin-treated group, but there were no differences in body weight or blood pressure between the two groups. Macrophage infiltration and fibrosis in renal interstitium improved significantly in the dapagliflozin group compared with the insulin group. Oxidative stress was attenuated by dapagliflozin, and suppression occurred in a dose-dependent manner. RNAi knockdown of SGLT2 resulted in reduced oxidative stress. Dapagliflozin ameliorates diabetic nephropathy by suppressing hyperglycemia-induced oxidative stress in a manner independent of hyperglycemia improvement in Akita mice. Our findings suggest that dapagliflozin may be a novel therapeutic approach for the treatment of diabetic nephropathy.

  5. A Preventive Dental Program for "High Risk" Children

    ERIC Educational Resources Information Center

    Meskin, Lawrence H.; And Others

    1977-01-01

    A dental health program in an elementary school succeeded in identifying children considered to be "high risk" in oral health and, through treatment and education, significantly improved their dental health. (JD)

  6. Sources of HIV-Prevention Information for Individuals at High Risk.

    ERIC Educational Resources Information Center

    Sagrestano, Lynda M.; Heiss-Wendt, Renate M.; Mizan, Ainon N.; Kittleson, Mark J.; Sarvela, Paul D.

    2001-01-01

    Identified the best methods of reaching people at high risk with HIV-prevention messages. Data from men who had sex with men, injection drug users, sex workers, HIV-positive people, heterosexuals, migrant workers, and perinatal women indicated that over 70 percent were exposed to HIV-prevention messages, though sources of exposure varied by risk…

  7. Participation in Counseling Programs: High-Risk Participants are Reluctant to Accept HIV-Prevention Counseling

    ERIC Educational Resources Information Center

    Earl, Allison; Albarracin, Dolores; Durantini, Marta R.; Gunnoe, Joann B.; Leeper, Josh; Levitt, Justin H.

    2009-01-01

    HIV-prevention intervention effectiveness depends on understanding whether clients with highest need for HIV-prevention counseling accept it. With this objective, a field study with a high-risk community sample from the southeastern United States (N = 350) investigated whether initial knowledge about HIV, motivation to use condoms,…

  8. Excess glucose induces hypoxia-inducible factor-1α in pancreatic cancer cells and stimulates glucose metabolism and cell migration

    PubMed Central

    Liu, Zhiwen; Jia, Xiaohui; Duan, Yijie; Xiao, Huijie; Sundqvist, Karl-Gösta; Permert, Johan; Wang, Feng

    2013-01-01

    Pancreatic cancer patients frequently show hyperglycemia, but it is uncertain whether hyperglycemia stimulates pancreatic cancer cells. We have investigated whether excess glucose induces hypoxia-inducible factor-1α (HIF-1α) and stimulates glucose metabolism and cell migration in pancreatic cancer cells. We studied wild-type (wt) MiaPaCa2 pancreatic cancer cells and a MiaPaCa2 subline (namely si-MiaPaCa2) that had HIF-1α-specific small interfering RNA. Wt-MiaPaCa2 cells are known to be HIF-1α-positive in hypoxia and HIF-1α-negative in normoxia, whereas si-MiaPaCa2 cells are devoid of HIF-1α in both normoxia and hypoxia. We incubated these cells with different amounts of glucose and determined HIF-1α mRNA and protein by real-time polymerase chain reaction and western blotting. We determined glucose consumption, lactate production and intracellular hexokinase-II and ATP to assess glucose metabolisms and determined pyruvate dehydrogenase kinase-1, reactive oxygen species and fumarate to assess mitochondrial activities. Further, we studied cell migration using a Boyden chamber. Excess glucose (16.7−22.2mM) increased HIF-1α in hypoxic wt-MiaPaCa2 cells. HIF-1α expression increased ATP contents and inhibited mitochondrial activities. Extracellular glucose and hypoxia stimulated glucose metabolisms independent of HIF-1α. Excess glucose stimulated the migration of wt- and si-MiaPaCa2 cells in both normoxia and hypoxia. Thus, glucose stimulated cell migration independent of HIF-1α. Nevertheless, hypoxic wt-MiaPaCa2 cells showed greater migrating ability than their si-MiaPaCa2 counterparts. We conclude that (1) excess glucose increases HIF-1α and ATP in hypoxic wt-MiaPaCa2 cells, (2) extracellular glucose and hypoxia regulate glucose metabolisms independent of HIF-1α and (3) glucose stimulates cell migration by mechanisms that are both dependent on HIF-1α and independent of it. PMID:23377827

  9. Sustaining the utilization and high quality implementation of tested and effective prevention programs using the communities that care prevention system.

    PubMed

    Fagan, Abigail A; Hanson, Koren; Briney, John S; David Hawkins, J

    2012-06-01

    This paper describes the extent to which communities implementing the Communities That Care (CTC) prevention system adopt, replicate with fidelity, and sustain programs shown to be effective in reducing adolescent drug use, delinquency, and other problem behaviors. Data were collected from directors of community-based agencies and coalitions, school principals, service providers, and teachers, all of whom participated in a randomized, controlled evaluation of CTC in 24 communities. The results indicated significantly increased use and sustainability of tested, effective prevention programs in the 12 CTC intervention communities compared to the 12 control communities, during the active phase of the research project when training, technical assistance, and funding were provided to intervention sites, and 2 years following provision of such resources. At both time points, intervention communities also delivered prevention services to a significantly greater number of children and parents. The quality of implementation was high in both conditions, with only one significant difference: CTC sites were significantly more likely than control sites to monitor the quality of implementation during the sustainability phase of the project.

  10. Participation in Counseling Programs: High-Risk Participants Are Reluctant to Accept HIV-Prevention Counseling

    PubMed Central

    Earl, Allison; Albarracín, Dolores; Durantini, Marta R.; Gunnoe, Joann B.; Leeper, Josh; Levitt, Justin H.

    2013-01-01

    HIV-prevention intervention effectiveness depends on understanding whether clients with highest need for HIV-prevention counseling accept it. With this objective, a field study with a high-risk community sample from the southeastern United States (N = 350) investigated whether initial knowledge about HIV, motivation to use condoms, condom-use-relevant behavioral skills, and prior condom use correlate with subsequent acceptance of an HIV-prevention counseling session. Ironically, participants with high (vs. low) motivation to use condoms, high (vs. low) condom-use-relevant behavioral skills, and high (vs. low) prior condom use were more likely to accept the HIV-prevention counseling. Moreover, the influence of motivation to use condoms, condom-use-relevant behavioral skills, and prior condom use on acceptance of the counseling was mediated by expectations that the counseling session would be useful. Methods to reduce barriers to recruitment of clients for counseling programs are discussed. PMID:19634960

  11. Effectiveness of Additives in Improving Fuel Lubricity and Preventing Pump Failure at High Temperature

    DTIC Science & Technology

    2013-01-01

    the specified 1,700 rpm, the housing pressure on pump No. 1 dropped significantly. Fuel began spewing out of test stand gear box and the pump seized...UNCLASSIFIED EFFECTIVENESS OF ADDITIVES IN IMPROVING FUEL LUBRICITY AND PREVENTING PUMP FAILURE AT HIGH TEMPERATURE INTERIM REPORT TFLRF...UNCLASSIFIED EFFECTIVENESS OF ADDITIVES IN IMPROVING FUEL LUBRICITY AND PREVENTING PUMP FAILURE AT HIGH TEMPERATURE INTERIM REPORT TFLRF No. 437

  12. High school coaches' assessments, intentions to use, and use of a concussion prevention toolkit: Centers for Disease Control and Prevention's heads up: concussion in high school sports.

    PubMed

    Sawyer, Richard J; Hamdallah, Myriam; White, Debbie; Pruzan, Marcia; Mitchko, Jane; Huitric, Michele

    2010-01-01

    This study evaluated school coaches' perceptions, assessments, and use of a toolkit to prevent and manage concussions among school athletes. A computer-assisted telephone survey was conducted with a stratified, random sample of high school coaches (n = 497; response rate = 39.3%; cooperation rate = 81.5%) from five states. Most reported that they had used or planned to use kit materials. Most (81%) in schools with a written plan for preventing and managing concussions indicated that the toolkit could be used to improve it and 96% of coaches in schools without a plan indicated that the kit could be used to develop one. Most assessed the kit as visually appealing, easy to use, and containing appropriate content. There were no significant differences among coaches with differing professional experience or for sports with different injury rates. Among those with other concussion-prevention materials, most indicated greater satisfaction with the toolkit.

  13. Relative Effectiveness of Continued, Lapsed, and Delayed Smoking Prevention Intervention in Senior High School Students.

    ERIC Educational Resources Information Center

    Eckhardt, Laura; And Others

    1997-01-01

    Reports findings from the final year of a tobacco use prevention project for junior and senior high school students. After three years of intervention with junior high students, researchers assessed the relative effectiveness of continued, lapsed, and delayed interventions in high school. In grade 11, continued intervention students had the lowest…

  14. [Dementia prevention: potential treatments and how to target high risk patients].

    PubMed

    Samaras, Nikolaos; Samaras, Dimitrios; Frangos, Emilia; Forster, Alexandre

    2013-05-22

    The burden related to the ever-increasing dementia prevalence in older individuals, imposes the implementation of prevention strategies. It is now known that brain lesions related to Alzheimer's disease precede the onset of the first symptoms. Consequently, prevention strategies should be implemented early, before clinically overt dementia. Blood and spine fluid tests, electroencephalogram, brain magnetic resonance and brain nuclear imaging should help physicians to better target "high-risk" patients prone to benefit from such strategies, already in a preclinical disease stage. Since no efficient pharmacological treatments exist for the time being, lifestyle factors such as nutritionand physical exercise are the cornerstones for dementia prevention.

  15. Shell-Less Chick Embryo Culture as an Alternative in vitro Model to Investigate Glucose-Induced Malformations in Mammalian Embryos

    PubMed Central

    Datar, Savita; Bhonde, Ramesh R.

    2005-01-01

    We have developed a simple shell-less chick embryo culture system to study glucose-induced malformations. This system involves the culturing of chick embryos from the second day to the fifth day of incubation, with associated yolk and thick and thin albumen outside the egg shell. The system allows the observation of embryonic development of chicks in a glass bowl. Developing embryos at 24 h, 48 h and 72 h incubation, corresponding to the Hamberger Hamilton (HH) stages from 7 to 21, were treated with two concentrations of glucose (50 mM and 100 mM) for 24 h. Glucose treatment resulted in a mortality rate of over 70% in younger embryos. Furthermore, a variety of malformations such as retarded growth, abnormal heart development, macrosomia, exencephaly, etc. were observed in older embryos, which were similar to those reported in mammalian embryos as a consequence of diabetic pregnancy. The glucose-induced malformations were found to be concentration- and stage-dependent, thus emphasizing the roles of the degree of hyperglycemia and the stage of embryonic development in diabetic growth anomalies. Here we demonstrate for the first time that the present system can be used (i) for experiments at early stages of chick embryo development and (ii) for assessing the effects of acute glucose toxicity similar to those reported for mammalian embryos in a hyperglycemic environment. PMID:17491698

  16. Increased Glucose-induced Secretion of Glucagon-like Peptide-1 in Mice Lacking the Carcinoembryonic Antigen-related Cell Adhesion Molecule 2 (CEACAM2)*

    PubMed Central

    Ghanem, Simona S.; Heinrich, Garrett; Lester, Sumona G.; Pfeiffer, Verena; Bhattacharya, Sumit; Patel, Payal R.; DeAngelis, Anthony M.; Dai, Tong; Ramakrishnan, Sadeesh K.; Smiley, Zachary N.; Jung, Dae Y.; Lee, Yongjin; Kitamura, Tadahiro; Ergun, Suleyman; Kulkarni, Rohit N.; Kim, Jason K.; Giovannucci, David R.; Najjar, Sonia M.

    2016-01-01

    Carcinoembryonic antigen-related cell adhesion molecule 2 (CEACAM2) regulates food intake as demonstrated by hyperphagia in mice with the Ceacam2 null mutation (Cc2−/−). This study investigated whether CEACAM2 also regulates insulin secretion. Ceacam2 deletion caused an increase in β-cell secretory function, as assessed by hyperglycemic clamp analysis, without affecting insulin response. Although CEACAM2 is expressed in pancreatic islets predominantly in non-β-cells, basal plasma levels of insulin, glucagon and somatostatin, islet areas, and glucose-induced insulin secretion in pooled Cc2−/− islets were all normal. Consistent with immunofluorescence analysis showing CEACAM2 expression in distal intestinal villi, Cc2−/− mice exhibited a higher release of oral glucose-mediated GLP-1, an incretin that potentiates insulin secretion in response to glucose. Compared with wild type, Cc2−/− mice also showed a higher insulin excursion during the oral glucose tolerance test. Pretreating with exendin(9–39), a GLP-1 receptor antagonist, suppressed the effect of Ceacam2 deletion on glucose-induced insulin secretion. Moreover, GLP-1 release into the medium of GLUTag enteroendocrine cells was increased with siRNA-mediated Ceacam2 down-regulation in parallel to an increase in Ca2+ entry through L-type voltage-dependent Ca2+ channels. Thus, CEACAM2 regulates insulin secretion, at least in part, by a GLP-1-mediated mechanism, independent of confounding metabolic factors. PMID:26586918

  17. School-Based Drug Abuse Prevention Programs in High School Students

    ERIC Educational Resources Information Center

    Sharma, Manoj; Branscum, Paul

    2013-01-01

    Drug abuse, or substance abuse, is a substantial public health problem in the United States, particularly among high school students. The purpose of this article was to review school-based programs implemented in high schools for substance abuse prevention and to suggest recommendations for future interventions. Included were English language…

  18. Transdermal deferoxamine prevents pressure-induced diabetic ulcers.

    PubMed

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W; Maan, Zeshaan N; Rennert, Robert C; Inayathullah, Mohammed; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V; Whitmore, Arnetha J; Walmsley, Graham G; Galvez, Michael G; Whittam, Alexander J; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C

    2015-01-06

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.

  19. Transdermal deferoxamine prevents pressure-induced diabetic ulcers

    PubMed Central

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

    2015-01-01

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

  20. Notoginsenoside R1 attenuates glucose-induced podocyte injury via the inhibition of apoptosis and the activation of autophagy through the PI3K/Akt/mTOR signaling pathway

    PubMed Central

    Huang, Guodong; Zou, Bingyu; Lv, Jianzhen; Li, Tongyu; Huai, Guoli; Xiang, Shaowei; Lu, Shilong; Luo, Huan; Zhang, Yaping; Jin, Yi; Wang, Yi

    2017-01-01

    Injury to terminally differentiated podocytes contributes ignificantly to proteinuria and glomerulosclerosis. The aim of this study was to examine the protective effects of notoginsenoside R1 (NR1) on the maintenance of podocyte number and foot process architecture via the inhibition of apoptosis, the induction of autophagy and the maintenance pf podocyte biology in target cells. The effects of NR1 on conditionally immortalized human podocytes under high glucose conditions were evaluated by determining the percentage apoptosis, the percentage autophagy and the expression levels of slit diaphragm proteins. Our results revealed that NR1 protected the podocytes against high glucose-induced injury by decreasing apoptosis, increasing autophagy and by promoting cytoskeletal recovery. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was further investigated in order to elucidate the mechanisms responsible for the protective effects of NR1 on podocytes. Our data indicated that treatment with NR increased the phosphorylation levels of PI3K, Akt and mTOR, leading to the activation of the PI3K/Akt/mTOR signaling pathway in podocytes. To the best of our knowledge, this is the first in vitro study to demonstrate that NR1 protects podocytes by activating the PI3K/Akt/mTOR pathway. PMID:28112381

  1. Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy | Division of Cancer Prevention

    Cancer.gov

    This randomized phase III trial studies antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. |

  2. Harm Reduction for the Prevention of Youth Gambling Problems: Lessons Learned From Adolescent High-Risk Behavior Prevention Programs

    ERIC Educational Resources Information Center

    Dickson, Laurie M.; Derevensky, Jeffrey L.; Gupta, Rina

    2004-01-01

    Despite the growing popularity of the harm reduction approach in the field of adolescent alcohol and substance abuse, a harm reduction approach to prevention and treatment of youth problem gambling remains largely unexplored. This article poses the question of whether the harm reduction paradigm is a promising approach to the prevention of…

  3. Meta-Analysis on Dating Violence Prevention among Middle and High Schools

    ERIC Educational Resources Information Center

    Ting, Siu-Man Raymond

    2009-01-01

    Meta-analysis was applied to study the empirical research from 1990-2007 regarding the effectiveness of the dating violence prevention programs in middle and high schools on students' knowledge and attitudes. The results show that overall the program participants improved their knowledge and attitudes towards dating violence. Implications for…

  4. Acupressure in Controlling Nausea in Young Patients Receiving Highly Emetogenic Chemotherapy | Division of Cancer Prevention

    Cancer.gov

    RATIONALE: Acupressure wristbands may prevent or reduce nausea and caused by chemotherapy. It is not yet known whether standard care is more effective with or without acupressure wristbands in controlling acute and delayed nausea. PURPOSE: This randomized phase III trial is studying how well acupressure wristbands work with or without standard care in controlling nausea in young patients receiving highly emetogenic chemotherapy. |

  5. Project Peace: The Evaluation of a Skill-Based Violence Prevention Program for High School Adolescents.

    ERIC Educational Resources Information Center

    de Anda, Diane

    1999-01-01

    Describes a study of high school students who participated in a cognitive-behavioral violence prevention program. The basic premise was that changing behavior involves learning new behaviors, and thought processes mediate behaviors. Results indicated a significant improvement in students' sense of safety in the school environment, attitudes toward…

  6. High School Health-Education Teachers' Perceptions and Practices Related to Teaching HIV Prevention

    ERIC Educational Resources Information Center

    Herr, Scott W.; Telljohann, Susan K.; Price, James H.; Dake, Joseph A.; Stone, Gregory E.

    2012-01-01

    Background: HIV/AIDS is one of the leading causes of illness and death in the United States with individuals between the ages of 13 and 19 years being especially vulnerable for infection. The purpose of this study was to examine the attitudes, perceptions, and instructional practices of high school health teachers toward teaching HIV prevention.…

  7. Randomized Controlled Trial of a Preventive Intervention for Perinatal Depression in High-Risk Latinas

    ERIC Educational Resources Information Center

    Le, Huynh-Nhu; Perry, Deborah F.; Stuart, Elizabeth A.

    2011-01-01

    Objective: A randomized controlled trial was conducted to evaluate the efficacy of a cognitive-behavioral (CBT) intervention to prevent perinatal depression in high-risk Latinas. Method: A sample of 217 participants, predominantly low-income Central American immigrants who met demographic and depression risk criteria, were randomized into usual…

  8. Going the Distance: Delivery of High School Drug Prevention via Distance Education

    ERIC Educational Resources Information Center

    Wyrick, David L.; Fearnow-Kenney, Melodie; Wyrick, Cheryl Haworth; Orsini, Muhsin Michael; Strack, Robert W.; Milroy, Jeffrey J.

    2010-01-01

    The purpose of this project was to develop a technology that can be used in schools where there are insufficient resources to implement a quality drug prevention program. The specific technology--distance education via teleconferencing--allows a highly qualified teacher to deliver programs in such settings with increased quality. A promising high…

  9. The Effectiveness of an Alcohol Abuse Prevention Program among High School Students in Rural Missouri.

    ERIC Educational Resources Information Center

    Dixon, David J.; McLearen, Alix M.

    2002-01-01

    A three-pronged program to prevent underage drinking delivered alcohol education and anti-drinking messages to high school students and their parents and distributed pertinent information to local alcohol retailers in a rural community. Compared to a control community, students in the intervention community were less likely to develop risky…

  10. The Effectiveness of Peer-Led FAS/FAE Prevention Presentations in Middle and High Schools

    ERIC Educational Resources Information Center

    Boulter, Lyn

    2007-01-01

    Pregnant women and women who might become pregnant, including middle school- and high school-age adolescents, continue to consume alcohol, placing themselves at risk of having a child with the effects of prenatal alcohol exposure. However, most prevention programs that attempt to increase public awareness and knowledge of FAS and related disorders…

  11. Dropout Prevention in Middle and High Schools: From Research to Practice

    ERIC Educational Resources Information Center

    Wilkins, Julia; Bost, Loujeania Williams

    2016-01-01

    Based on work with state and local education agencies in dropout prevention for students with disabilities, successful research-based interventions are described along with details of how these interventions have been implemented in middle and high schools across the country. The interventions that have helped students with disabilities graduate…

  12. Violence Prevention at Thurgood Marshall Academy Public Charter High School. Summary Brief

    ERIC Educational Resources Information Center

    Fontaine, Jocelyn; Debus-Sherrill, Sara; Downey, P. Mitchell; Lowry, Samantha S.

    2010-01-01

    This summary brief is based on research conducted by the Urban Institute's Justice Policy Center on the violence prevention activities taking place at the Thurgood Marshall Academy Public Charter High School during the 2008-2009 school year. Researchers from the Justice Policy Center conducted an assessment of the school's violence prevention…

  13. A Curriculum Framework for Junior and Senior High Child Abuse Prevention Programs.

    ERIC Educational Resources Information Center

    Miller, Pamela R.

    This curriculum guide for junior and senior high child abuse prevention programs is designed for flexibility. Part 1, the introduction, discusses the goals and objectives for using the material, including designing presentations and assessing the needs of students. Part 2 provides a framework for presentations including examples of a 1-day and…

  14. Core Competencies and the Prevention of High-Risk Sexual Behavior

    ERIC Educational Resources Information Center

    Charles, Vignetta Eugenia; Blum, Robert Wm.

    2008-01-01

    Adolescent sexual risk-taking behavior has numerous individual, family, community, and societal consequences. In an effort to contribute to the research and propose new directions, this chapter applies the core competencies framework to the prevention of high-risk sexual behavior. It describes the magnitude of the problem, summarizes explanatory…

  15. Field trial on glucose-induced insulin and metabolite responses in Estonian Holstein and Estonian Red dairy cows in two herds

    PubMed Central

    2010-01-01

    Background Insulin secretion and tissue sensitivity to insulin is considered to be one of the factors controlling lipid metabolism post partum. The objective of this study was to compare glucose-induced blood insulin and metabolite responses in Estonian Holstein (EH, n = 14) and Estonian Red (ER, n = 14) cows. Methods The study was carried out using the glucose tolerance test (GTT) performed at 31 ± 1.9 days post partum during negative energy balance. Blood samples were obtained at -15, -5, 5, 10, 20, 30, 40, 50 and 60 min relative to infusion of 0.15 g/kg BW glucose and analysed for glucose, insulin, triglycerides (TG), non-esterified fatty acids (NEFA), cholesterol and β-hydroxybutyrate (BHB). Applying the MIXED Procedure with the SAS System the basal concentration of cholesterol, and basal concentration and concentrations at post-infusion time points for other metabolites, area under the curve (AUC) for glucose and insulin, clearance rate (CR) for glucose, and maximum increase from basal concentration for glucose and insulin were compared between breeds. Results There was a breed effect on blood NEFA (P < 0.05) and a time effect on all metabolites concentration (P < 0.01). The following differences were observed in EH compared to ER: lower blood insulin concentration 5 min after glucose infusion (P < 0.05), higher glucose concentration 20 (P < 0.01) and 30 min (P < 0.05) after infusion, and higher NEFA concentration before (P < 0.01) and 5 min after infusion (P < 0.05). Blood TG concentration in ER remained stable, while in EH there was a decrease from the basal level to the 40th min nadir (P < 0.01), followed by an increase to the 60th min postinfusion (P < 0.01). Conclusion Our results imply that glucose-induced changes in insulin concentration and metabolite responses to insulin differ between EH and ER dairy cows. PMID:20089161

  16. Serum amyloid P component prevents high-density lipoprotein-mediated neutralization of lipopolysaccharide.

    PubMed

    de Haas, C J; Poppelier, M J; van Kessel, K P; van Strijp, J A

    2000-09-01

    Lipopolysaccharide (LPS) is an amphipathic macromolecule that is highly aggregated in aqueous preparations. LPS-binding protein (LBP) catalyzes the transfer of single LPS molecules, segregated from an LPS aggregate, to high-density lipoproteins (HDL), which results in the neutralization of LPS. When fluorescein isothiocyanate-labeled LPS (FITC-LPS) is used, this transfer of LPS monomers to HDL can be measured as an increase in fluorescence due to dequenching of FITC-LPS. Recently, serum amyloid P component (SAP) was shown to neutralize LPS in vitro, although only in the presence of low concentrations of LBP. In this study, we show that SAP prevented HDL-mediated dequenching of FITC-LPS, even in the presence of high concentrations of LBP. Human bactericidal/permeability-increasing protein (BPI), a very potent LPS-binding and -neutralizing protein, also prevented HDL-mediated dequenching of FITC-LPS. Furthermore, SAP inhibited HDL-mediated neutralization of both rough and smooth LPS in a chemiluminescence assay quantifying the LPS-induced priming of neutrophils in human blood. SAP bound both isolated HDL and HDL in serum. Using HDL-coated magnetic beads prebound with SAP, we demonstrated that HDL-bound SAP prevented the binding of LPS to HDL. We suggest that SAP, by preventing LPS binding to HDL, plays a regulatory role, balancing the amount of LPS that, via HDL, is directed to the adrenal glands.

  17. Evaluation of a Public Awareness Campaign to Prevent High School Dropout.

    PubMed

    Babinski, Leslie M; Corra, Ashley J; Gifford, Elizabeth J

    2016-08-01

    Many advocacy organizations devote time and resources to increasing community awareness and educating the public in an effort to gain support for their issue. One such effort, the Dropout Prevention Campaign by America's Promise Alliance, aimed to increase the visibility of the high school dropout problem and mobilize the community to take action. The objective of this paper is to evaluate the framing of the Dropout Prevention Campaign in television news media. To evaluate this campaign, television news coverage about high school dropout in 12 U.S. communities (N = 982) was examined. A content analysis of news transcripts was conducted and coded to determine the definition of the problem, the reasons for dropout and the possible solutions. Findings indicated that the high school dropout problem was most often framed (30 % of news segments) in terms of the economic and societal implications for the community. Individual student factors as well as broader societal influences were frequently discussed as possible reasons for dropout. The most commonly mentioned solutions were school-based interventions. News segments that mentioned America's Promise Alliance were more likely to frame the issue as a crisis and to use statistics to illustrate that point. Solutions that were more likely to appear in America's Promise segments promoted community and cross-sector involvement, consistent with the messages promoted by the Dropout Prevention Campaign. The findings suggest that a media content analysis can be an effective framework for analyzing a prevention campaign.

  18. Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice

    PubMed Central

    Dinh, Chi H. L.; Yu, Yinghua; Szabo, Alexander; Zhang, Qingsheng; Zhang, Peng; Huang, Xu-Feng

    2016-01-01

    Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora. PMID:26920068

  19. Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice.

    PubMed

    Dinh, Chi H L; Yu, Yinghua; Szabo, Alexander; Zhang, Qingsheng; Zhang, Peng; Huang, Xu-Feng

    2016-04-01

    Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora.

  20. “The Internet is a Mask”: High School Students' Suggestions for Preventing Cyberbullying

    PubMed Central

    Parris, Leandra N.; Varjas, Kris; Meyers, Joel

    2014-01-01

    Introduction: Interactions through technology have an important impact on today's youth. While some of these interactions are positive, there are concerns regarding students engaging in negative interactions like cyberbullying behaviors and the negative impact these behaviors have on others. The purpose of the current study was to explore participant suggestions for both students and adults for preventing cyberbullying incidents. Methods: Forty high school students participated in individual, semi-structured interviews. Participant experiences and perceptions were coded using constant comparative methods to illustrate ways in which students and adults may prevent cyberbullying from occurring within their school and community. Results: Students reported that peers would benefit from increasing online security, as well as becoming more aware of their cyber-surroundings. Regarding adult-provided prevention services, participants often discussed that there is little adults can do to reduce cyberbullying. Reasons included the difficulties in restricting online behaviors or providing effective consequences. However, some students did discuss the use of in-school curricula while suggesting that adults blame people rather than technology as potential ways to prevent cyberbullying. Conclusion: Findings from the current study indicate some potential ways to improve adult efforts to prevent cyberbullying. These strategies include parent/teacher training in technology and cyberbullying, interventions focused more on student behavior than technology restriction, and helping students increase their online safety and awareness. PMID:25157306

  1. Alcohol, Tobacco, and Other Drug Misuse Prevention and Cessation Programming for Alternative High School Youth: A Review

    ERIC Educational Resources Information Center

    Sussman, Steve; Arriaza, Bridget; Grigsby, Timothy J.

    2014-01-01

    Background: Relative to youth in regular high schools, alternative high school (AHS) youth are at high risk for alcohol, tobacco, and other drug (ATOD) misuse. Prevention and cessation efforts are needed for this population. Methods: A systematic, exhaustive literature search was completed to identify ATOD misuse prevention and cessation research…

  2. Lanthanum prevents high phosphate-induced vascular calcification by preserving vascular smooth muscle lineage markers.

    PubMed

    Ciceri, Paola; Elli, Francesca; Brenna, Irene; Volpi, Elisa; Romagnoli, Solange; Tosi, Delfina; Braidotti, Paola; Brancaccio, Diego; Cozzolino, Mario

    2013-06-01

    Vascular calcification (VC) represents a major cardiovascular risk factor in chronic kidney disease patients. High phosphate (Pi) levels are strongly associated with VC in this population. Therefore, Pi binders are commonly used to control high Pi levels. The aim of this work was to study the mechanism of action of lanthanum chloride (LaCl3) on the progression of Pi-induced VC through its direct effect on vascular smooth muscle cells (VSMCs) in vitro. High Pi induced VSCM Ca deposition. We evaluated the action of LaCl3, compared to gadolinium chloride (GdCl3), and found different effects on the modulation of VSMC lineage markers, such as α-actin and SM22α. In fact, only LaCl3 preserved the expression of both VSMC lineage markers compared to high Pi-treated cells. Interestingly, both LaCl3 and GdCl3 reduced the high Pi-induced elevations of bone morphogenic protein 2 mRNA expression, with no reduction of the high core binding factor-alpha 1 mRNA levels observed in calcified VSMCs. Furthermore, we also found that only LaCl3 completely prevented the matrix GLA protein mRNA levels and osteonectin protein expression elevations induced by high Pi compared to GdCl3. Finally, LaCl3, in contrast to GdCl3, prevented the high Pi-induced downregulation of Axl, a membrane tyrosine kinase receptor involved in apoptosis. Thus, our results suggest that LaCl3 prevents VC by preserving VSMC lineage markers and by decreasing high Pi-induced osteoblastic differentiation.

  3. The National Cross-Site Evaluation of High-Risk Youth Programs: Findings on Designing and Implementing Effective Prevention Programs for Youth at High Risk. Monograph Series.

    ERIC Educational Resources Information Center

    Hermann, Jack; Sambrano, Soledad; Springer, J. Fred; Nister, Mary; Sale, Elizabeth; Brounstein, Paul J.; Cordray, David; Shadish, Will; Kasim, Rafa; Pan, Wei

    This document summarizes findings from the Center for Substance Abuse Prevention's National Cross-Site Evaluation of High-Risk Youth Programs, which identified characteristics associated with strong substance abuse prevention outcomes in 48 prevention programs. It provides concrete guidance regarding what elements of design and implementation are…

  4. Des-acyl ghrelin prevents heatstroke-like symptoms in rats exposed to high temperature and high humidity.

    PubMed

    Inoue, Yoshiyuki; Hayashi, Yujiro; Kangawa, Kenji; Suzuki, Yoshihiro; Murakami, Noboru; Nakahara, Keiko

    2016-02-26

    We have shown previously that des-acyl ghrelin decreases body temperature in rats through activation of the parasympathetic nervous system. Here we investigated whether des-acyl ghrelin ameliorates heatstroke in rats exposed to high temperature. Peripheral administration of des-acyl ghrelin significantly attenuated hyperthermia induced by exposure to high-temperature (35°C) together with high humidity (70-80%). Although biochemical analysis revealed that exposure to high temperature significantly increased hematocrit and the serum levels of aspartate amino transferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), creatinine and electrolytes (Na(+), K(+), Cl(-)), most of these heatstroke-associated reactions were significantly reduced by treatment with des-acyl ghrelin. The level of des-acyl ghrelin in plasma was also found to be significantly increased under high-temperature conditions. These results suggest that des-acyl ghrelin could be useful for preventing heatstroke under high temperature condition.

  5. Adapting an HIV prevention intervention for high-risk, incarcerated adolescents.

    PubMed

    Hurd, Noelle M; Valerio, Melissa A; Garcia, Nicole M; Scott, Anthony A

    2010-02-01

    This study examined the effectiveness of an adapted 4-session HIV prevention program. Participants included 490 adolescents who participated in either the 8- or the adapted 4-session HIVEd program. Analyses to identify mean changes in HIV-related knowledge, attitudes, self-efficacy, and behavioral intentions between participants in either the 4- (n = 274) or 8-session (n = 216) programs were completed. Findings indicate participants in both programs had positive changes at post interview across all study outcomes. No significant differences in changes between participants in the 4- and 8-session programs were found except that male adolescents in the 4-session program had significantly higher mean changes in condom knowledge (p < .01). The adaptation of the 8-session HIVEd program was undertaken to better reach and accommodate the needs of a high risk incarcerated adolescent population. Findings demonstrate that HIV prevention interventions for high risk populations may be successfully adapted and condensed when based on rigorously evaluated and theoretically driven programs.

  6. Bystander Sexual Violence Prevention Program: Outcomes for High- and Low-Risk University Men.

    PubMed

    Elias-Lambert, Nada; Black, Beverly M

    2015-05-05

    This research reports the findings of an evaluation of a peer-facilitated, bystander sexual violence prevention program to determine its effectiveness at changing attitudes and behaviors related to sexual violence with university males who are at low- and high-risk of using sexually coercive behavior. Bystander interventions focus on men and women as bystanders to change social norms in a peer culture that supports abusive behaviors. Few studies have examined the effectiveness of these interventions with high-risk populations, which is the focus of this study. A bystander sexual violence prevention program was presented to 142 fraternity members. A quasi-experimental design utilizing pre-, post-, and follow-up surveys was used to compare the effectiveness of this prevention program with university males who are at low- and high-risk of using sexually coercive behavior in intervention and comparison groups. Participants' risk status was measured prior to the intervention using the Modified-Sexual Experiences Survey. The measures evaluated changes in attitudes (rape myth acceptance and bystander attitudes) and behaviors (sexually coercive behaviors, sexually coercive behavioral intentions, and bystander behaviors). Data analyses included Repeated-Measures Analysis of Covariances. The findings suggest that a bystander sexual violence prevention program has a positive impact on attitudes and behaviors related to sexual violence among fraternity members, however, the program had less impact on high-risk males. The results of this study will expand our ability to design programs that can have an impact on reducing sexual violence on campus by ensuring the programs are having the desired impact on the target audience.

  7. Resveratrol potentiates rapamycin to prevent hyperinsulinemia and obesity in male mice on high fat diet

    PubMed Central

    Leontieva, O V; Paszkiewicz, G; Demidenko, Z N; Blagosklonny, M V

    2013-01-01

    High doses of rapamycin, an antiaging agent, can prevent obesity in mice on high fat diet (HFD). Obesity is usually associated with hyperinsulinemia. Here, we showed that rapamycin given orally, at doses that did not affect weight gain in male mice on HFD, tended to decrease fasting insulin levels. Addition of resveratrol, which alone did not affect insulin levels, potentiated the effect of rapamycin, so that the combination decreased obesity and prevented hyperinsulinemia. Neither rapamycin nor resveratrol, and their combination affected fasting levels of glucose (despite lowering insulin levels), implying that the combination might prevent insulin resistance. We and others previously reported that resveratrol at high doses inhibited the mTOR (Target of Rapamycin) pathway in cell culture. Yet, as we confirmed here, this effect was observed only at super-pharmacological concentrations. At pharmacological concentrations, resveratrol did not exert ‘rapamycin-like effects' on cellular senescence and did not inhibit the mTOR pathway in vitro, indicating nonoverlapping therapeutic mechanisms of actions of rapamycin and resveratrol in vivo. Although, like rapamycin, resveratrol decreased insulin-induced HIF-1-dependent transcription in cell culture, resveratrol did not inhibit mTOR at the same concentrations. Given distinct mechanisms of action of rapamycin and resveratrol at clinically relevant doses, their combination warrants further investigation as a potential antiaging, antiobesity and antidiabetic modality. PMID:23348586

  8. Reduced fatalism and increased prevention behavior after two high-profile lung cancer events.

    PubMed

    Portnoy, David B; Leach, Corinne R; Kaufman, Annette R; Moser, Richard P; Alfano, Catherine M

    2014-01-01

    The positive impact of media coverage of high-profile cancer events on cancer prevention behaviors is well-established. However, less work has focused on potential adverse psychological reactions to such events, such as fatalism. Conducting 3 studies, the authors explored how the lung cancer death of Peter Jennings and diagnosis of Dana Reeve in 2005 related to fatalism. Analysis of a national media sample in Study 1 found that media coverage of these events often focused on reiterating the typical profile of those diagnosed with lung cancer; 38% of the media mentioned at least 1 known risk factor for lung cancer, most often smoking. Data from a nationally representative survey in Study 2 found that respondents reported lower lung cancer fatalism, after, compared with before, the events (OR = 0.16, 95% CI [0.03, 0.93]). A sustained increase in call volume to the national tobacco Quitline after these events was found in Study 3. These results suggest that there is a temporal association between high-profile cancer events, the subsequent media coverage, psychological outcomes, and cancer prevention behaviors. These results suggest that high-profile cancer events could be leveraged as an opportunity for large-scale public heath communication campaigns through the dissemination of cancer prevention messages and services.

  9. Effects of a Comprehensive, Multiple Risky Behavior Prevention Program on High School Students

    PubMed Central

    Onwuegbuzie, Anthony J.; LaChapelle, Alicia

    2016-01-01

    The purpose of this research study was to examine the effect of a multiple risky behaviors prevention program applied comprehensively throughout an entire school system involving universal, selective, and indicated levels of students at a local private high school during a 4-year period. The noncurriculum prevention program was created based upon the key elements of effective prevention programming and the need to address the growing variety of risky behaviors that the youth face today. Results (n = 469 to 614) indicated that 7 out of 15 risky behaviors statistically significantly decreased throughout the 4-year study, with 6 behaviors involving alcohol and drugs. However, many of the targeted non-substance-use risky behaviors displayed inconsistent prevalence rate patterns without statistically significant changes. These findings indicate that the frequency and intensity of programming for non-substance-use behaviors should be increased to a value at least equal to that of the substance-use behaviors. Implications for schools, prevention specialists, and future program development and research are discussed. PMID:27672475

  10. TRPV1 activation prevents high-salt diet-induced nocturnal hypertension in mice.

    PubMed

    Hao, Xinzhong; Chen, Jing; Luo, Zhidan; He, Hongbo; Yu, Hao; Ma, Liqun; Ma, Shuangtao; Zhu, Tianqi; Liu, Daoyan; Zhu, Zhiming

    2011-03-01

    High dietary salt-caused hypertension is associated with increasing reactive oxygen species generation and reduced nitric oxide (NO) bioavailability. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, is proposed to be involved in Dahl salt-sensitive hypertension, as determined in acute or short-term experiments. However, it remains unknown whether activation of TRPV1 by dietary capsaicin could prevent the vascular oxidative stress and hypertension induced by a high-salt diet. Here, we report that consumption of a high-salt diet blunted endothelium-dependent relaxation in mesenteric resistance arteries and elevated nocturnal blood pressure in mice. These effects were associated with increased superoxide anion generation and reduced NO levels in mesenteric vessels in mice on a high-salt diet. However, chronic administration of capsaicin reduced the high-salt diet-induced endothelial dysfunction and nocturnal hypertension in part by preventing the generation of superoxide anions and NO reduction of mesenteric arteries through vascular TRPV1 activation. Our findings provide new insights into the role of TRPV1 channels in the long-term regulation of blood pressure in response to high-salt intake. TRPV1 activation through chronic dietary capsaicin may represent a promising lifestyle intervention in populations with salt-sensitive hypertension.

  11. Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet.

    PubMed

    Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

    2013-01-15

    Caffeine alleviates cognitive impairment associated with a variety of health conditions. In this study, we examined the effect of caffeine treatment on chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced impairment of learning and memory in rats. Chronic psychosocial stress, WD and caffeine (0.3 g/L in drinking water) were simultaneously administered for 3 months to adult male Wistar rats. At the conclusion of the 3 months, and while the previous treatments continued, rats were tested in the radial arm water maze (RAWM) for learning, short-term and long-term memory. This procedure was applied on a daily basis to all animals for 5 consecutive days or until the animal reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Chronic stress and/or WD groups caused impaired learning, which was prevented by chronic caffeine administration. In the memory tests, chronic caffeine administration also prevented memory impairment during chronic stress conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and stress/WD groups indicated that caffeine normalizes memory impairment in these groups. These results showed that chronic caffeine administration prevented stress and/or WD-induced impairment of spatial learning and memory.

  12. [Tobacco: knowledge, reasoning and opinion of high school students in Doubs. Reflections on prevention].

    PubMed

    Michaud, C; Saraiva, I; Henry, Y; Dodane, M

    2003-03-01

    The prevalence of smoking has increased among young people aged 14 to 18 between 1993 and 1999, and most notably among girls within the same period. These observations illustrate the necessity for significant changes in mass media campaigns and education programmes related to the prevention of smoking among youth. The objective of this survey, initiated by the city of Besançon and the French National Mutual Insurance of Doubs, was to describe and analyse the knowledge and rationale of high school students on tobacco and their opinions in terms of prevention. Twelve public and private high schools in Besançon and Morteau (Doubs-France) participated in the survey; the group also represented a mix of general and professional schools. The questionnaire was filled out by 970 students selected at random. 96% of the students indicated cancer as being the main illness linked to tobacco and 94% stated that second-hand smoke constitutes a health risk. 61% admitted to seeking out the psychoactive effects of smoking. The students responses confirm that the types of messages relayed in a smoking prevention campaign which have an impact on them are: evoking fear of death (74%) and the use of humor (16%). One-third of high school students find that it is unacceptable to forbid smoking on school premises. The knowledge of the dangers related to smoking is not sufficient to keep young people from smoking and confirms that an educational approach based solely on knowledge and facts will not be sufficient to decrease their tobacco consumption. It is important to take into account the image that young people have of tobacco as a means to combat stress in future prevention strategies and campaigns.

  13. Bardoxolone Methyl Prevents Mesenteric Fat Deposition and Inflammation in High-Fat Diet Mice

    PubMed Central

    Dinh, Chi H. L.; Szabo, Alexander; Yu, Yinghua; Camer, Danielle; Wang, Hongqin; Huang, Xu-Feng

    2015-01-01

    Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue. PMID:26618193

  14. High-school smoking prevention: results of a three-year longitudinal study.

    PubMed

    Johnson, C A; Hansen, W B; Collins, L M; Graham, J W

    1986-10-01

    This study compared two strategies for preventing cigarette smoking among high-school students. One strategy emphasized social-pressure resistance skills, while the other focused on education about health concerns which are relevant to high-school students. Additionally, the use of same-age peer leaders and the use of familiar models in media presentations were investigated. The results suggest that social-influences resistance training was efficacious in reducing transitions to higher use by those who had previously experimented with cigarettes. Health education was most effective in preventing initial experimentation among those who had not smoked prior to the beginning of the study. Neither program was effective in limiting transitions among those who had gone beyond the experimental stage of smoking, and neither had any effect on encouraging cessation. There were no differences which could be attributed to peer leaders or to familiar media models. During later adolescence, a combined health education and social skills training approach is advocated. It is suggested that while there are some gains by implementing programs during late adolescence, prevention programs targeted at younger students may be more effective generally.

  15. The NARCONON™ drug education curriculum for high school students: A non-randomized, controlled prevention trial

    PubMed Central

    Lennox, Richard D; Cecchini, Marie A

    2008-01-01

    Background An estimated 13 million youths aged 12 to 17 become involved with alcohol, tobacco and other drugs annually. The number of 12- to 17-year olds abusing controlled prescription drugs increased an alarming 212 percent between 1992 and 2003. For many youths, substance abuse precedes academic and health problems including lower grades, higher truancy, drop out decisions, delayed or damaged physical, cognitive, and emotional development, or a variety of other costly consequences. For thirty years the Narconon program has worked with schools and community groups providing single educational modules aimed at supplementing existing classroom-based prevention activities. In 2004, Narconon International developed a multi-module, universal prevention curriculum for high school ages based on drug abuse etiology, program quality management data, prevention theory and best practices. We review the curriculum and its rationale and test its ability to change drug use behavior, perceptions of risk/benefits, and general knowledge. Methods After informed parental consent, approximately 1000 Oklahoma and Hawai'i high school students completed a modified Center for Substance Abuse Prevention (CSAP) Participant Outcome Measures for Discretionary Programs survey at three testing points: baseline, one month later, and six month follow-up. Schools assigned to experimental conditions scheduled the Narconon curriculum between the baseline and one-month follow-up test; schools in control conditions received drug education after the six-month follow-up. Student responses were analyzed controlling for baseline differences using analysis of covariance. Results At six month follow-up, youths who received the Narconon drug education curriculum showed reduced drug use compared with controls across all drug categories tested. The strongest effects were seen in all tobacco products and cigarette frequency followed by marijuana. There were also significant reductions measured for alcohol and

  16. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.

    PubMed

    Bowen, T Scott; Eisenkolb, Sophia; Drobner, Juliane; Fischer, Tina; Werner, Sarah; Linke, Axel; Mangner, Norman; Schuler, Gerhard; Adams, Volker

    2017-01-01

    Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P < 0.05). Diaphragm forces were impaired by ∼15-20% in DOCA-salt vs. sham-treated mice (P < 0.05), but this effect was prevented after HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P < 0.05). Enzyme activity of NADPH oxidase was higher, but superoxide dismutase was lower, with MyHC oxidation elevated by ∼50%. HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P < 0.05) after a 30 min exposure to H2O-2 (1 mM). Our data suggest that hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.

  17. Treating High-grade Lesions to Prevent Anal Cancer in HIV-infected People

    Cancer.gov

    This study, called the ANCHOR trial, will investigate whether screening and prevention methods similar to those used to prevent cervical cancer can help prevent anal cancer in HIV-infected men and women.

  18. Sexual abuse prevention with high-risk males: the roles of victim empathy and rape myths.

    PubMed

    Schewe, P A; O'Donohue, W

    1993-01-01

    The outcome of two sexual abuse prevention programs, one emphasizing victim empathy and the other stressing modifying rape myths, was evaluated with high-risk males. Sixty-eight high-risk males, as determined by self-reported likelihood of committing sexual abuse, were randomly assigned to an empathy-treatment, a facts-treatment, or a no-treatment control group. Treatment effects were assessed using subjects' pre- and post-treatment scores on the Likelihood of Sexually Abusing scale, the Rape Empathy Scale, the Acceptance of Interpersonal Violence scale, the Adversarial Sexual Beliefs Scale, and a test of self-reported sexual arousal to forced versus consenting sex. In addition, posttest scores on an Asch-type conformity measure were obtained. Results of validity checks indicated that high-risk subjects differed from low-risk subjects on a number of rape-related variables, that the victim-empathy condition increased subjects' empathy, and that subjects found both treatments to be credible and helpful. Comparisons between the empathy-, facts-, and no-treatment group contraindicated the practice of dispelling rape myths as a method of preventing rape among high-risk males.

  19. The National Cross-Site Evaluation of High-Risk Youth Programs: Making Prevention Effective for Adolescent Boys and Girls: Gender Differences in Substance Use and Prevention. Monograph Series.

    ERIC Educational Resources Information Center

    Springer, J. Fred; Sambrano, Soledad; Sale, Elizabeth; Kasim, Rafa; Hermann, Jack

    This document summarizes findings from the Center for Substance Abuse Prevention's National Cross-Site Evaluation of High-Risk Youth Programs, which identified characteristics associated with strong substance abuse prevention outcomes in 48 prevention programs. Results indicate that overall, boys and girls respond to prevention differently. Boys…

  20. An evaluation of a Canadian peer-driven injury prevention programme for high-risk adolescents.

    PubMed

    Tenn, L; Dewis, M E

    1996-02-01

    The mortality and morbidity resulting from serious trauma in adolescence, particularly head and spinal cord injury, constitutes a health problem of major proportions. Although many community-based prevention programmes have been reported in this last decade, few of these describe an evaluation component. In this study, a school-based prevention programme was developed by a peer group and presented by them to high-risk adolescents. The study aimed to test the efficacy of this intervention compared to the delivery of a prevention presentation to a similar group by a health care professional and compared to a control group. Measures of health locus of control, self-efficacy and behavioural intent were supplemented by open-ended items related to risk-taking behaviour change. At post-test and at 4-month follow-up, there was little evidence in the quantitative measures to support the effectiveness of the intervention for reducing injury risk factors. More encouraging findings were seen in the qualitative data. Explanations for why the intervention did not result in the expected outcomes are offered.

  1. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    Neuregulin 4 (NRG4), an epidermal growth factor-like signaling molecule, plays an important role in cell-to-cell communication during tissue development. Its function to regulate energy metabolism has recently been reported. This current study was designed to assess the preventive and therapeutic effects of NRG4 overexpression on high fat diet (HFD)-induced obesity. Using the hydrodynamic gene transfer method, we demonstrate that Nrg4 gene transfer in mice suppressed the development of diet-induced obesity, but did not affect pre-existing adiposity and body weight in obese mice. Nrg4 gene transfer curbed HFD-induced hepatic steatosis by inhibiting lipogenesis and PPARγ-mediated lipid storage. Concurrently, overexpression of NRG4 reduced chronic inflammation in both preventive and treatment studies, evidenced by lower mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and macrophage chemokine Mcp1, resulting in improved insulin sensitivity. Collectively, these results demonstrate that overexpression of the Nrg4 gene by hydrodynamic gene delivery prevents HFD-induced weight gain and fatty liver, alleviates obesity-induced chronic inflammation and insulin resistance, and supports the health benefits of NRG4 in managing obesity and obesity-associated metabolic disorders. PMID:27184920

  2. Biphasic effect of alpha-linolenic acid on glucose-induced dysmorphogenesis and lipoperoxidation in whole rat embryo in culture.

    PubMed

    Chirino-Galindo, Gladys; Barrera-Argüelles, Jorge-Israel; Trejo-González, Ninna-Leslie; Mejía-Zepeda, Ricardo; Palomar-Morales, Martín

    2017-03-18

    Type 1 diabetes mellitus complicated with pregnancy, know as diabetic embryopathy, is the cause of neonatal malformations and low for gestational age neonates. With the use of the whole-embryo culture system, it has been demonstrated that high glucose causes embryo dysmorphogenesis, and that oxidative stress appears to be the main mechanism. In recent years, beneficial effect of omega-3 fatty acids has been demonstrated in various diabetic models, and in diabetic complications. Since diabetic embryopathy is mediated probably through membrane lipoperoxidation, This study was designed to find if omega-3 fatty acids could ameliorate the effect of high glucose over the dysmorphogenesis of whole rat embryo in culture. Postimplantational rat embryos were cultured in hyperglycemic media, with addition of alpha-linolenic acid, and morphologic and morphometric parameters were registered. Also, lipoperoxidation and fatty acids composition were measured in cultured embryos. Growth of embryos cultured in presence of glucose was very affected, whereas lipoperoxidation was increased, and it was found that Triton X-100 causes similar results than glucose. Addition of low micromolar doses of alpha-linolenic acid overcome the effect of high glucose or Triton X-100, but higher doses does not ameliorates the effects of the carbohydrate or the detergent. Paradoxically, there are not significant changes in fatty acids composition, although the U/S fatty acids ratio shows an increasing tendency by high glucose and a normalizing tendency by omega-3 fatty acids. In conclusion, glucose and Triton X-100 induces in vitro dysmorphogenesis in post-implantational rat embryos associated with increased lipoperoxidation; and this nocive effect could be ameliorated by low micromolar doses of ALA.

  3. Neonatal air leak syndrome and the role of high-frequency ventilation in its prevention.

    PubMed

    Jeng, Mei-Jy; Lee, Yu-Sheng; Tsao, Pei-Chen; Soong, Wen-Jue

    2012-11-01

    Air leak syndrome includes pulmonary interstitial emphysema, pneumothorax, pneumomediastinum, pneumopericardium, pneumoperitoneum, subcutaneous emphysema, and systemic air embolism. The most common cause of air leak syndrome in neonates is inadequate mechanical ventilation of the fragile and immature lungs. The incidence of air leaks in newborns is inversely related to the birth weight of the infants, especially in very-low-birth-weight and meconium-aspirated infants. When the air leak is asymptomatic and the infant is not mechanically ventilated, there is usually no specific treatment. Emergent needle aspiration and/or tube drainage are necessary in managing tension pneumothorax or pneumopericardium with cardiac tamponade. To prevent air leak syndrome, gentle ventilation with low pressure, low tidal volume, low inspiratory time, high rate, and judicious use of positive end expiratory pressure are the keys to caring for mechanically ventilated infants. Both high-frequency oscillatory ventilation (HFOV) and high-frequency jet ventilation (HFJV) can provide adequate gas exchange using extremely low tidal volume and supraphysiologic rate in neonates with acute pulmonary dysfunction, and they are considered to have the potential to reduce the risks of air leak syndrome in neonates. However, there is still no conclusive evidence that HFOV or HFJV can help to reduce new air leaks in published neonatal clinical trials. In conclusion, neonatal air leaks may present as a thoracic emergency requiring emergent intervention. To prevent air leak syndrome, gentle ventilations are key to caring for ventilated infants. There is insufficient evidence showing the role of HFOV and HFJV in the prevention or reduction of new air leaks in newborn infants, so further investigation will be necessary for future applications.

  4. High elastic modulus polymer electrolytes suitable for preventing thermal runaway in lithium batteries

    DOEpatents

    Mullin, Scott; Panday, Ashoutosh; Balsara, Nitash Pervez; Singh, Mohit; Eitouni, Hany Basam; Gomez, Enrique Daniel

    2014-04-22

    A polymer that combines high ionic conductivity with the structural properties required for Li electrode stability is useful as a solid phase electrolyte for high energy density, high cycle life batteries that do not suffer from failures due to side reactions and dendrite growth on the Li electrodes, and other potential applications. The polymer electrolyte includes a linear block copolymer having a conductive linear polymer block with a molecular weight of at least 5000 Daltons, a structural linear polymer block with an elastic modulus in excess of 1.times.10.sup.7 Pa and an ionic conductivity of at least 1.times.10.sup.-5 Scm.sup.-1. The electrolyte is made under dry conditions to achieve the noted characteristics. In another aspect, the electrolyte exhibits a conductivity drop when the temperature of electrolyte increases over a threshold temperature, thereby providing a shutoff mechanism for preventing thermal runaway in lithium battery cells.

  5. Vitamin E prevents high-fat high-carbohydrates diet-induced memory impairment: the role of oxidative stress.

    PubMed

    Alzoubi, Karem H; Khabour, Omar F; Salah, Heba A; Hasan, Zuheir

    2013-07-02

    Memory and learning are impaired by imbalanced diet consumption. High-fat high-carbohydrate diet (HFCD) induces oxidative stress, which results in neuronal damage and interference with synaptic transmission; hence, a decline in cognitive function. Vitamin E is a fat soluble antioxidant that is believed to have positive effects on learning and memory. In this study, we tested the hypothesis that chronic administration of vitamin E prevents learning and memory impairment induced by HFCD. In addition, possible molecular targets for HFCD, and vitamin E that lead to cognitive effects were examined. Vitamin E and/or HFCD were concurrently administered to animals for 6 weeks. Thereafter, behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM). Additionally, brain derived neurotrophic factor (BDNF) level and antioxidant markers were assessed in the hippocampus. The results of this project revealed that HFCD impairs both short-term and long-term memories (p<0.05). The administration of vitamin E prevented the memory impairment induced by HFCD consumption (p<0.05). The consumption of HFCD reduced activities of hippocampal superoxide dismutase (SOD) and catalase (p<0.05); whereas the levels of thiobarbituric acid reactive substances (TBARS) and oxidized glutathione (GSSG) were elevated (p<0.05). The administration of vitamin E normalized the effect of HFCD on the oxidative stress markers. None of the treatments induced changes in the levels of BDNF or glutathione peroxidase (GPx). In conclusion, HFCD induces memory impairment, and the administration of vitamin E prevented this impairment probably through normalizing antioxidant mechanisms in the hippocampus.

  6. Resveratrol increases glucose induced GLP-1 secretion in mice: a mechanism which contributes to the glycemic control.

    PubMed

    Dao, Thi-Mai Anh; Waget, Aurélie; Klopp, Pascale; Serino, Matteo; Vachoux, Christelle; Pechere, Laurent; Drucker, Daniel J; Champion, Serge; Barthélemy, Sylvain; Barra, Yves; Burcelin, Rémy; Sérée, Eric

    2011-01-01

    Resveratrol (RSV) is a potent anti-diabetic agent when used at high doses. However, the direct targets primarily responsible for the beneficial actions of RSV remain unclear. We used a formulation that increases oral bioavailability to assess the mechanisms involved in the glucoregulatory action of RSV in high-fat diet (HFD)-fed diabetic wild type mice. Administration of RSV for 5 weeks reduced the development of glucose intolerance, and increased portal vein concentrations of both Glucagon-like peptid-1 (GLP-1) and insulin, and intestinal content of active GLP-1. This was associated with increased levels of colonic proglucagon mRNA transcripts. RSV-mediated glucoregulation required a functional GLP-1 receptor (Glp1r) as neither glucose nor insulin levels were modulated in Glp1r-/- mice. Conversely, levels of active GLP-1 and control of glycemia were further improved when the Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin was co-administered with RSV. In addition, RSV treatment modified gut microbiota and decreased the inflammatory status of mice. Our data suggest that RSV exerts its actions in part through modulation of the enteroendocrine axis in vivo.

  7. Resveratrol Increases Glucose Induced GLP-1 Secretion in Mice: A Mechanism which Contributes to the Glycemic Control

    PubMed Central

    Dao, Thi-Mai Anh; Waget, Aurélie; Klopp, Pascale; Serino, Matteo; Vachoux, Christelle; Pechere, Laurent; Drucker, Daniel J.; Champion, Serge; Barthélemy, Sylvain; Barra, Yves; Burcelin, Rémy; Sérée, Eric

    2011-01-01

    Resveratrol (RSV) is a potent anti-diabetic agent when used at high doses. However, the direct targets primarily responsible for the beneficial actions of RSV remain unclear. We used a formulation that increases oral bioavailability to assess the mechanisms involved in the glucoregulatory action of RSV in high-fat diet (HFD)-fed diabetic wild type mice. Administration of RSV for 5 weeks reduced the development of glucose intolerance, and increased portal vein concentrations of both Glucagon-like peptid-1 (GLP-1) and insulin, and intestinal content of active GLP-1. This was associated with increased levels of colonic proglucagon mRNA transcripts. RSV-mediated glucoregulation required a functional GLP-1 receptor (Glp1r) as neither glucose nor insulin levels were modulated in Glp1r-/- mice. Conversely, levels of active GLP-1 and control of glycemia were further improved when the Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin was co-administered with RSV. In addition, RSV treatment modified gut microbiota and decreased the inflammatory status of mice. Our data suggest that RSV exerts its actions in part through modulation of the enteroendocrine axis in vivo. PMID:21673955

  8. The Effectiveness of School-Based Smoking Prevention Interventions among Low- and High-SES European Teenagers

    ERIC Educational Resources Information Center

    Mercken, L.; Moore, L.; Crone, M. R.; De Vries, H.; De Bourdeaudhuij, I.; Lien, N.; Fagiano, F.; Vitoria, P. D.; Van Lenthe, F. J.

    2012-01-01

    Preventing smoking initiation among adolescents of lower socio-economic groups is crucial for the reduction of socio-economic inequalities in health. The aim of the present study was to examine whether effective smoking prevention interventions in Europe are equally effective among adolescents of low- and high-socio-economic status (SES). As part…

  9. High-Performance Workforce. National Dropout Prevention Center/Network Newsletter. Volume 19, Number 1, Winter 2007

    ERIC Educational Resources Information Center

    Duckenfield, Marty, Ed.

    2007-01-01

    The "National Dropout Prevention Newsletter" is published quarterly by the National Dropout Prevention Center/Network. This issue contains the following articles: (1) Preparing for the Demands of the New World Economy (Patrick J. O'Connor); (2) Connecting At-Risk Youth to the High-Performance Workforce (Patrick J. O'Connor); (3) Butler…

  10. Violence Prevention in Schools: A Case Study of the Thurgood Marshall Academy Public Charter High School. Final Report

    ERIC Educational Resources Information Center

    Fontaine, Jocelyn; Debus-Sherrill, Sara; Downey, P. Mitchell; Lowry, Samantha S.

    2010-01-01

    This report is based on research conducted by the Urban Institute's Justice Policy Center on the violence prevention activities taking place at the Thurgood Marshall Academy Public Charter High School during the 2008-2009 school year. Based on an assessment of the school's violence prevention approach using qualitative and quantitative data from…

  11. Implementing an Alcohol and Other Drug Use Prevention Program Using University-High School Partnerships: Challenges and Lessons Learned

    ERIC Educational Resources Information Center

    Milroy, Jeffrey J.; Orsini, Muhsin Michael; Wyrick, David L.; Fearnow-Kenney, Melodie; Wagoner, Kimberly G.; Caldwell, Rebecca

    2015-01-01

    Background: School-based alcohol and other drug use prevention remains an important national strategy. Collaborative partnerships between universities and high schools have the potential to enhance prevention programming; however, there are challenges to sustaining such partnerships. Purpose: The purpose of this commentary is to underscore…

  12. Integrating Life Skills Into a Theory-Based Drug-Use Prevention Program: Effectiveness among Junior High Students in Taiwan

    ERIC Educational Resources Information Center

    Huang, Chiu-Mieh; Chien, Li-Yin; Cheng, Chin-Feng; Guo, Jong-Long

    2012-01-01

    Background: Drug use has been noted among students in Taiwan during the past decade and schools have a role in preventing or delaying students' drug use. We developed and evaluated a school-based, drug-use prevention program integrating the theory of planned behavior (TPB) and life skills for junior high school students. Methods: We recruited 441…

  13. The first Iranian recommendations on prevention, evaluation and management of high blood pressure.

    PubMed

    Noohi, Feridoun; Sarrafzadegan, Nizal; Khosravi, Alireza; Andalib, Elham

    2012-01-01

    This paper presents the complete report of the first Iranian Recommendations on Prevention, Evaluation and Management of High Blood Pressure. The purpose is to provide an evidence-based approach to the prevention, management and control of hypertension (HTN) by adapting the most internationally known and used guidelines to the local health care status with consideration of the currently available data and based on the locally conducted researches on HTN as well as social and health care requirements. A working group of national and international experts participated in discussions and collaborated in decision-making, writing and reviewing the whole report. Multiple subcommittees worked together to review the recent national and international literature on HTN in different areas. We used the evaluation tool that is called "AGREE" and considered a score of > 60% as a high score. We adapted the Canadian Hypertension Education Program (CHEP), the United Kingdom's National Institute for Health and Clinical Excellence (NICE) and the US-based joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7). The key topics that are highlighted in this report include: The importance of ambulatory and self-measurement of blood pressure, evaluation of cardiovascular risk in HTN patients, the role of lifestyle modification in the prevention of HTN and its control with more emphasis on salt intake reduction and weight control, introducing pharmacotherapy suitable for uncomplicated HTN or specific situations and the available drugs in Iran, highlighting the importance of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers and calcium channel blockers as the first line therapy in many situations, the non-use of beta blockers as the first time treatment except in specific conditions, treating HTN in women, children, obese and elderly patients, the patient compliance to improve HTN control, practical guidelines to improve

  14. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12.

    PubMed

    Deusing, Dorothé Jenni; Beyrer, Melanie; Fitzenberger, Elena; Wenzel, Uwe

    2015-05-08

    Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors.

  15. Glucose Induces Sensitivity to Oxygen Deprivation and Modulates Insulin/IGF-1 Signaling and Lipid Biosynthesis in Caenorhabditis elegans

    PubMed Central

    Garcia, Anastacia M.; Ladage, Mary L.; Dumesnil, Dennis R.; Zaman, Khadiza; Shulaev, Vladimir; Azad, Rajeev K.; Padilla, Pamela A.

    2015-01-01

    Diet is a central environmental factor that contributes to the phenotype and physiology of individuals. At the root of many human health issues is the excess of calorie intake relative to calorie expenditure. For example, the increasing amount of dietary sugars in the human diet is contributing to the rise of obesity and type 2 diabetes. Individuals with obesity and type 2 diabetes have compromised oxygen delivery, and thus it is of interest to investigate the impact a high-sugar diet has on oxygen deprivation responses. By utilizing the Caenorhabditis elegans genetic model system, which is anoxia tolerant, we determined that a glucose-supplemented diet negatively impacts responses to anoxia and that the insulin-like signaling pathway, through fatty acid and ceramide synthesis, modulates anoxia survival. Additionally, a glucose-supplemented diet alters lipid localization and initiates a positive chemotaxis response. Use of RNA-sequencing analysis to compare gene expression responses in animals fed either a standard or glucose-supplemented diet revealed that glucose impacts the expression of genes involved with multiple cellular processes including lipid and carbohydrate metabolism, stress responses, cell division, and extracellular functions. Several of the genes we identified show homology to human genes that are differentially regulated in response to obesity or type 2 diabetes, suggesting that there may be conserved gene expression responses between C. elegans fed a glucose-supplemented diet and a diabetic and/or obesity state observed in humans. These findings support the utility of the C. elegans model for understanding the molecular mechanisms regulating dietary-induced metabolic diseases. PMID:25762526

  16. Scale prevention at high LSI, high cycles, and high pH without the need for acid feed

    SciTech Connect

    Perez, L.A.; Freese, D.T.

    1997-08-01

    Open recirculating cooling water systems are widely used in different industries, such as refineries, petrochemical, fertilizer, air conditioning, manufacturing operations, utility power stations, etc. Scale control at high LSI and high pH without acid feed is difficult to achieve. The problem dramatically increases in cooling towers when PVC tower film fill is used. Compounds that are able to enhance the performance of typical scale inhibitors have been developed. When topped off with these enhancing compounds, typical scale inhibitors are able to control calcium carbonate and silicate-related scale formation on metal heat exchanger and cooling water tower film fill surfaces in cycled waters having high LSI ({approximately} 3.0), high alkalinity (500--700 mg/L as CaCO{sub 3}), and high pH (8.5 or higher). The enhancing compounds have excellent chlorine and soluble iron tolerance and are compatible with traditional biocides.

  17. Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes.

    PubMed

    Irles, Esperanza; Ñeco, Patricia; Lluesma, Mónica; Villar-Pazos, Sabrina; Santos-Silva, Junia Carolina; Vettorazzi, Jean F; Alonso-Magdalena, Paloma; Carneiro, Everardo M; Boschero, Antonio C; Nadal, Ángel; Quesada, Ivan

    2015-03-15

    Obesity is associated with insulin resistance and is known to be a risk factor for type-2 diabetes. In obese individuals, pancreatic beta-cells try to compensate for the increased insulin demand in order to maintain euglycemia. Most studies have reported that this adaptation is due to morphological changes. However, the involvement of beta-cell functional adaptations in this process needs to be clarified. For this purpose, we evaluated different key steps in the glucose-stimulated insulin secretion (GSIS) in intact islets from female ob/ob obese mice and lean controls. Obese mice showed increased body weight, insulin resistance, hyperinsulinemia, glucose intolerance and fed hyperglycemia. Islets from ob/ob mice exhibited increased glucose-induced mitochondrial activity, reflected by enhanced NAD(P)H production and mitochondrial membrane potential hyperpolarization. Perforated patch-clamp examination of beta-cells within intact islets revealed several alterations in the electrical activity such as increased firing frequency and higher sensitivity to low glucose concentrations. A higher intracellular Ca(2+) mobilization in response to glucose was also found in ob/ob islets. Additionally, they displayed a change in the oscillatory pattern and Ca(2+) signals at low glucose levels. Capacitance experiments in intact islets revealed increased exocytosis in individual ob/ob beta-cells. All these up-regulated processes led to increased GSIS. In contrast, we found a lack of beta-cell Ca(2+) signal coupling, which could be a manifestation of early defects that lead to beta-cell malfunction in the progression to diabetes. These findings indicate that beta-cell functional adaptations are an important process in the compensatory response to obesity.

  18. Systematic Review of Abstinence-Plus HIV Prevention Programs in High-Income Countries

    PubMed Central

    Underhill, Kristen; Operario, Don; Montgomery, Paul

    2007-01-01

    Background Abstinence-plus (comprehensive) interventions promote sexual abstinence as the best means of preventing HIV, but also encourage condom use and other safer-sex practices. Some critics of abstinence-plus programs have suggested that promoting safer sex along with abstinence may undermine abstinence messages or confuse program participants; conversely, others have suggested that promoting abstinence might undermine safer-sex messages. We conducted a systematic review to investigate the effectiveness of abstinence-plus interventions for HIV prevention among any participants in high-income countries as defined by the World Bank. Methods and Findings Cochrane Collaboration systematic review methods were used. We included randomized and quasi-randomized controlled trials of abstinence-plus programs for HIV prevention among any participants in any high-income country; trials were included if they reported behavioural or biological outcomes. We searched 30 electronic databases without linguistic or geographical restrictions to February 2007, in addition to contacting experts, hand-searching conference abstracts, and cross-referencing papers. After screening 20,070 abstracts and 325 full published and unpublished papers, we included 39 trials that included approximately 37,724 North American youth. Programs were based in schools (10), community facilities (24), both schools and community facilities (2), health care facilities (2), and family homes (1). Control groups varied. All outcomes were self-reported. Quantitative synthesis was not possible because of heterogeneity across trials in programs and evaluation designs. Results suggested that many abstinence-plus programs can reduce HIV risk as indicated by self-reported sexual behaviours. Of 39 trials, 23 found a protective program effect on at least one sexual behaviour, including abstinence, condom use, and unprotected sex (baseline n = 19,819). No trial found adverse program effects on any behavioural outcome

  19. Preventing Violence Among High-Risk Youth and Communities with Economic, Policy, and Structural Strategies.

    PubMed

    Massetti, Greta M; David-Ferdon, Corinne

    2016-02-12

    Youth violence is preventable, and the reduction of health disparities is possible with evidence-based approaches. Achieving community-wide reductions in youth violence and health disparities has been limited in part because of the lack of prevention strategies to address community risk factors. CDC-supported research has resulted in three promising community-level approaches: Business Improvement Districts (BIDs) in Los Angeles, California; alcohol policy to reduce youth access in Richmond, Virginia; and the Safe Streets program in Baltimore, Maryland. Evaluation findings indicated that BIDs in Los Angeles were associated with a 12% reduction in robberies (one type of violent crime) and an 8% reduction in violent crime overall. In Richmond's alcohol policy program, investigators found that the monthly average of ambulance pickups for violent injuries among youth aged 15-24 years had a significantly greater decrease in the intervention (19.6 to 0 per 1,000) than comparison communities (7.4 to 3.3 per 1,000). Investigators of Safe Streets found that some intervention communities experienced reductions in homicide and/or nonfatal shootings, but results were not consistent across communities. Communitywide rates of violence can be changed in communities with disproportionately high rates of youth violence associated with entrenched health disparities and socioeconomic disadvantage. Community-level strategies are a critical part of comprehensive approaches necessary to achieve broad reductions in violence and health disparities.

  20. Dietary Rosa mosqueta (Rosa rubiginosa) oil prevents high diet-induced hepatic steatosis in mice.

    PubMed

    D'Espessailles, Amanda; Dossi, Camila G; Espinosa, Alejandra; González-Mañán, Daniel; Tapia, Gladys S

    2015-09-01

    The effects of dietary Rosa mosqueta (RM, Rosa rubiginosa) oil, rich in α-linolenic acid, in the prevention of liver steatosis were studied in mice fed a high fat diet (HFD). C57BL/6j mice were fed either a control diet or HFD with or without RM oil for 12 weeks. The results indicate that RM oil supplementation decreases fat infiltration of the liver from 43.8% to 6.2%, improving the hepatic oxidative state, insulin levels, HOMA index, and both body weight and adipose tissue weight of HFD plus RM treated animals compared to HFD without supplementation. In addition, the DHA concentration in the liver was significantly increased in HFD fed mice with RM oil compared to HFD (3 vs. 1.6 g per 100 g FAME). The n-6/n-3 ratio was not significantly modified by treatment with RM. Our findings suggest that RM oil supplementation prevents the development of hepatic steatosis and the obese phenotype observed in HFD fed mice.

  1. Postural muscle atrophy prevention and recovery and bone remodelling through high frequency proprioception for astronauts

    NASA Astrophysics Data System (ADS)

    Riva, Dario; Rossitto, Franco; Battocchio, Luciano

    2009-09-01

    The difficulty in applying active exercises during space flights increases the importance of passive countermeasures, but coupling load and instability remains indispensable for generating high frequency (HF) proprioceptive flows and preventing muscle atrophy and osteoporosis. The present study, in microgravity conditions during a parabolic flight, verified whether an electronic system, composed of a rocking board, a postural reader and a bungee-cord loading apparatus creates HF postural instability comparable to that reachable on the Earth. Tracking the subject, in single stance, to real-time visual signals is necessary to obtain HF instability situations. The bungee-cord loading apparatus allowed the subject to manage the 81.5% body weight load (100% could easily be exceeded). A preliminary training programme schedule on the Earth and in space is suggested. Comparison with a pathological muscle atrophy is presented. The possibility of generating HF proprioceptive flows could complement current countermeasures for the prevention and recovery of muscle atrophy and osteoporosis in terrestrial and space environments. These exercises combine massive activation of spindles and joint receptors, applying simultaneously HF variations of pressure to different areas of the sole of the foot. This class of exercises could improve the effectiveness of current countermeasures, reducing working time and fatigue.

  2. Evaluation of indicated suicide risk prevention approaches for potential high school dropouts.

    PubMed Central

    Thompson, E A; Eggert, L L; Randell, B P; Pike, K C

    2001-01-01

    OBJECTIVES: This study evaluated the efficacy of 2 indicated preventive interventions, postintervention and at 9-month follow-up. METHODS: Drawn from a pool of potential high school dropouts, 460 youths were identified as being at risk for suicide and participated in 1 of 3 conditions randomly assigned by school: (1) Counselors CARE (C-CARE) (n = 150), a brief one-to-one assessment and crisis intervention; (2) Coping and Support Training (CAST) (n = 155), a small-group skills-building and social support intervention delivered with C-CARE; and (3) usual-care control (n = 155). Survey instruments were administered pre-intervention, following C-CARE (4 weeks), following CAST (10 weeks), and at a 9-month follow-up. RESULTS: Growth curve analyses showed significant rates of decline in attitude toward suicide and suicidal ideation associated with the experimental interventions. C-CARE and CAST, compared with usual care, also were effective in reducing depression and hopelessness. Among females, reductions in anxiety and anger were greater in response to the experimental programs. CAST was most effective in enhancing and sustaining personal control and problem-solving coping for males and females. CONCLUSIONS: School-based, indicated prevention approaches are feasible and effective for reducing suicidal behaviors and related emotional distress and for enhancing protective factors. PMID:11344882

  3. Longitudinal Impact of Two Universal Preventive Interventions in First Grade on Educational Outcomes in High School

    PubMed Central

    Bradshaw, Catherine P.; Zmuda, Jessika H.; Kellam, Sheppard G.; Ialongo, Nicholas S.

    2013-01-01

    This study examined the longitudinal effects of 2 first-grade universal preventive interventions on academic outcomes (e.g., achievement, special education service use, graduation, postsecondary education) through age 19 in a sample of 678 urban, primarily African American children. The classroom-centered intervention combined the Good Behavior Game (H. H. Barrish, Saunders, & Wolfe, 1969) with an enhanced academic curriculum, whereas a second intervention, the Family–School Partnership, focused on promoting parental involvement in educational activities and bolstering parents’ behavior management strategies. Both programs aimed to address the proximal targets of aggressive behavior and poor academic achievement. Although the effects varied by gender, the classroom-centered intervention was associated with higher scores on standardized achievement tests, greater odds of high school graduation and college attendance, and reduced odds of special education service use. The intervention effects of the Family–School Partnership were in the expected direction; however, only 1 effect reached statistical significance. The findings of this randomized controlled trial illustrate the long-term educational impact of preventive interventions in early elementary school. PMID:23766545

  4. Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It was investigated the preventive effects of the flavanones hesperidin, eriocitrin and eriodictyol on the oxidative stress and systemic inflammation induced by high-fat diet in C57BL/6J mice. The mice received a standard diet (9.5% kcal from fat), high-fat diet (45% kcal from fat) or high fat diet ...

  5. Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy.

    PubMed

    Pai, Chen-Hsueh; Yen, Ching-Tzu; Chen, Chie-Pein; Yu, I-Shing; Lin, Shu-Wha; Lin, Shu-Rung

    2016-01-01

    Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2) and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg), and decreased pup weight (~50%) and size (~24%), but these adverse effects were ameliorated in TXAS knockout (KO) mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway.

  6. High-sodium intake prevents pregnancy-induced decrease of blood pressure in the rat.

    PubMed

    Beauséjour, Annie; Auger, Karine; St-Louis, Jean; Brochu, Michéle

    2003-07-01

    Despite an increase of circulatory volume and of renin-angiotensin-aldosterone system (RAAS) activity, pregnancy is paradoxically accompanied by a decrease in blood pressure. We have reported that the decrease in blood pressure was maintained in pregnant rats despite overactivation of RAAS following reduction in sodium intake. The purpose of this study was to evaluate the impact of the opposite condition, e.g., decreased activation of RAAS during pregnancy in the rat. To do so, 0.9% or 1.8% NaCl in drinking water was given to nonpregnant and pregnant Sprague-Dawley rats for 7 days (last week of gestation). Increased sodium intakes (between 10- and 20-fold) produced reduction of plasma renin activity and aldosterone in both nonpregnant and pregnant rats. Systolic blood pressure was not affected in nonpregnant rats. However, in pregnant rats, 0.9% sodium supplement prevented the decreased blood pressure. Moreover, an increase of systolic blood pressure was obtained in pregnant rats receiving 1.8% NaCl. The 0.9% sodium supplement did not affect plasma and fetal parameters. However, 1.8% NaCl supplement has larger effects during gestation as shown by increased plasma sodium concentration, hematocrit level, negative water balance, proteinuria, and intrauterine growth restriction. With both sodium supplements, decreased AT1 mRNA levels in the kidney and in the placenta were observed. Our results showed that a high-sodium intake prevents the pregnancy-induced decrease of blood pressure in rats. Nonpregnant rats were able to maintain homeostasis but not the pregnant ones in response to sodium load. Furthermore, pregnant rats on a high-sodium intake (1.8% NaCl) showed some physiological responses that resemble manifestations observed in preeclampsia.

  7. Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective.

    PubMed

    Homaira, Nusrat; Rawlinson, William; Snelling, Thomas L; Jaffe, Adam

    2014-01-01

    Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups.

  8. Bardoxolone methyl prevents the development and progression of cardiac and renal pathophysiologies in mice fed a high-fat diet.

    PubMed

    Camer, Danielle; Yu, Yinghua; Szabo, Alexander; Wang, Hongqin; Dinh, Chi H L; Huang, Xu-Feng

    2016-01-05

    Obesity caused by the consumption of a high-fat (HF) diet is a major risk factor for the development of associated complications, such as heart and kidney failure. A semi-synthetic triterpenoid, bardoxolone methyl (BM) was administrated to mice fed a HF diet for 21 weeks to determine if it would prevent the development of obesity-associated cardiac and renal pathophysiologies. Twelve week old male C57BL/6J mice were fed a lab chow (LC), HF (40% fat), or a HF diet supplemented with 10 mg/kg/day BM in drinking water. After 21 weeks, the left ventricles of hearts and cortex of kidneys of mice were collected for analysis. Histological analysis revealed that BM prevented HF diet-induced development of structural changes in the heart and kidneys. BM prevented HF diet-induced decreases in myocyte number in cardiac tissue, although this treatment also elevated cardiac endothelin signalling molecules. In the kidneys, BM administration prevented HF diet-induced renal corpuscle hypertrophy and attenuated endothelin signalling. Furthermore, in both the hearts and kidneys of mice fed a HF diet, BM administration prevented HF diet-induced increases in fat accumulation, macrophage infiltration and tumour necrosis factor alpha (TNFα) gene expression. These findings suggest that BM prevents HF diet-induced developments of cardiac and renal pathophysiologies in mice fed a chronic HF diet by preventing inflammation. Moreover, these results suggest that BM has the potential as a therapeutic for preventing obesity-induced cardiac and renal pathophysiologies.

  9. Practicing provider-initiated HIV testing in high prevalence settings: consent concerns and missed preventive opportunities

    PubMed Central

    2011-01-01

    measures. Informants expressed frustration related to their experienced inability to 'opt-out' or decline from the provider-initiated HIV testing services. Conclusion Counselling emerged as a highly valued process during HIV testing. However, counselling efforts were limited in the implementation of the provider-initiated opt-out HIV testing model. The approach was moreover not perceived as voluntary. This raises serious ethical concerns and implies missed preventive opportunities inherent in the counselling concept. Moreover, implementation of the new testing approach seem to add a burden to pregnant women as disproportionate numbers of women get to know their HIV status, reveal their HIV status to their spouse and recruit their spouses to go for a test. We argue that there is an urgent need to reconsider the manner in which the provider initiated HIV testing model is implemented in order to protect the client's autonomy and to maximise access to HIV prevention. PMID:21507273

  10. High intracellular pH reversibly prevents gating-charge immobilization in squid axons.

    PubMed Central

    Wanke, E; Testa, P L; Prestipino, G; Carbone, E

    1983-01-01

    Squid giant axons were used to study the reversible effects of high intracellular pH (pHi) on gating currents. Under depolarization, when Na channels are activated, internal solutions buffered at high pHi (10.2) affect considerably the time course of gating charge associated with channel closing, QOFF, with almost no alteration of QON records. In particular, at pHi 10.2 the charge corresponding to the fast phase of IgOFF, measured after long depolarizing pulses (7.7 ms), was consistently larger than that recorded at physiological pHi (7.2). This suggests that high pH prevents immobilization of gating charges induced by Na inactivation. In this respect, the present data agree reasonably well with previous observations, which show that pHi greater than 7.2 reversibly removes the fast Na inactivation with little effects on activation kinetics (Carbone, E., P. L. Testa, and E. Wanke, 1981, Biophys. J., 35:393-413; Brodwick, M.S., and D. C. Eaton, 1978, Science [Wash. DC], 200:1494-1496). Unexpectedly, high pH increases the amount of charge associated with the slow phase of IgOFF. In our opinion, this might be the result of either an increment of the net charge produced by the exposure to high pHi or that gating charges that return to the closed state might experience a larger fraction of the potential drop across the membrane (Neumcke, B., W. Schwarz, and R. Stampfli, 1980, Biophys. J., 31:325-332). PMID:6652218

  11. High Intensity Exercise Countermeasures does not Prevent Orthostatic Intolerance Following Prolonged Bed Rest

    NASA Technical Reports Server (NTRS)

    Platts, Steven H.; Stenger, Michael B.; Ploutz-Snyder, Lori L.; Lee, Stuart M. C.

    2014-01-01

    Approximately 20% of Space Shuttle astronauts became presyncopal during operational stand and 80deg head-up tilt tests, and the prevalence of orthostatic intolerance increases after longer missions. Greater than 60% of the US astronauts participating in Mir and early International Space Station missions experienced presyncope during post-flight tilt tests, perhaps related to limitations of the exercise hardware that prevented high intensity exercise training until later ISS missions. The objective of this study was to determine whether an intense resistive and aerobic exercise countermeasure program designed to prevent cardiovascular and musculoskeletal deconditioning during 70 d of bed rest (BR), a space flight analog, would protect against post-BR orthostatic intolerance. METHODS Twenty-six subjects were randomly assigned to one of three groups: non-exercise controls (n=11) or one of two exercise groups (ExA, n=8; ExB, n=7). Both ExA and ExB groups performed the same resistive and aerobic exercise countermeasures during BR, but one exercise group received testosterone supplementation while the other received a placebo during BR in a double-blinded fashion. On 3 d/wk, subjects performed lower body resistive exercise and 30 min of continuous aerobic exercise (=75% max heart rate). On the other 3 d/wk, subjects performed only highintensity, interval-style aerobic exercise. Orthostatic intolerance was assessed using a 15-min 80? head-up tilt test performed 2 d (BR-2) before and on the last day of BR (BR70). Plasma volume was measured using carbon monoxide rebreathing on BR-3 and before rising on the first recovery day (BR+0). The code for the exercise groups has not been broken, and results are reported here without group identification. RESULTS Only one subject became presyncopal during tilt testing on BR-2, but 7 of 11 (63%) controls, 3 of 8 (38%) ExA, and 4 of 7 (57%) ExB subjects were presyncopal on BR70. Survival analysis of post-BR tilt tests revealed no

  12. High-Density Lipoprotein Prevents Endoplasmic Reticulum Stress-Induced Downregulation of Liver LOX-1 Expression.

    PubMed

    Hong, Dan; Li, Ling-Fang; Gao, Hai-Chao; Wang, Xiang; Li, Chuan-Chang; Luo, Ying; Bai, Yong-Ping; Zhang, Guo-Gang

    2015-01-01

    Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a specific cell-surface receptor for oxidized-low-density lipoprotein (ox-LDL). The impact of high-density lipoprotein (HDL) on endoplasmic reticulum (ER) stress-mediated alteration of the LOX-1 level in hepatocytes remains unclear. We aimed to investigate the impact on LOX-1 expression by tunicamycin (TM)-induced ER stress and to determine the effect of HDL on TM-affected LOX-1 expression in hepatic L02 cells. Overexpression or silencing of related cellular genes was conducted in TM-treated cells. mRNA expression was evaluated using real-time polymerase chain reaction (PCR). Protein expression was analyzed by western blot and immunocytochemistry. Lipid uptake was examined by DiI-ox-LDL, followed by flow cytometric analysis. The results showed that TM induced the upregulation of ER chaperone GRP78, downregulation of LOX-1 expression, and lipid uptake. Knock down of IRE1 or XBP-1 effectively restored LOX-1 expression and improved lipid uptake in TM-treated cells. HDL treatment prevented the negative impact on LOX-1 expression and lipid uptake induced by TM. Additionally, 1-10 μg/mL HDL significantly reduced the GRP78, IRE1, and XBP-1 expression levels in TM-treated cells. Our findings reveal that HDL could prevent the TM-induced reduction of LOX-1 expression via inhibiting the IRE1/XBP-1 pathway, suggesting a new mechanism for beneficial roles of HDL in improving lipid metabolism.

  13. Preventing diverticular disease. Review of recent evidence on high-fibre diets.

    PubMed Central

    Aldoori, Walid; Ryan-Harshman, Milly

    2002-01-01

    OBJECTIVE: To review recent evidence on dietary factors associated with diverticular disease (DD) with special emphasis on dietary fibre. QUALITY OF EVIDENCE: MEDLINE was searched from January 1966 to December 2001 for articles on the relationship between dietary and other lifestyle factors and DD. Most articles either focused on dietary intervention in treating symptomatic DD or were case-control studies with inherent limitations for studying diet-disease associations. Only one large prospective study of male health professionals in the United States assessed diet at baseline and before initial diagnosis of DD. MAIN MESSAGE: A diet high in fibre mainly from fruits and vegetables and low in total fat and red meat decreases risk of DD. Evidence indicates that the insoluble component of fibre is strongly associated with lower risk of DD; this association was particularly strong for cellulose. Caffeine and alcohol do not substantially increase risk of DD, nor does obesity, but higher levels of physical activity seem to reduce risk of DD. CONCLUSION: A diet high in fibre and low in total fat and red meat and a lifestyle with more physical activity might help prevent DD. PMID:12449547

  14. High-impact exercise in rats prior to and during suspension can prevent bone loss

    PubMed Central

    Yanagihara, G.R.; Paiva, A.G.; Gasparini, G.A.; Macedo, A.P.; Frighetto, P.D.; Volpon, J.B.; Shimano, A.C.

    2016-01-01

    High-impact exercise has been considered an important method for treating bone loss in osteopenic experimental models. In this study, we investigated the effects of osteopenia caused by inactivity in femora and tibiae of rats subjected to jump training using the rat tail suspension model. Eight-week-old female Wistar rats were divided into five groups (n=10 each group): jump training for 2 weeks before suspension and training during 3 weeks of suspension; jump training for 2 weeks before suspension; jump training only during suspension; suspension without any training; and a control group. The exercise protocol consisted of 20 jumps/day, 5 days/week, with a jump height of 40 cm. The bone mineral density of the femora and tibiae was measured by double energy X-ray absorptiometry and the same bones were evaluated by mechanical tests. Bone microarchitecture was evaluated by scanning electron microscopy. One-way ANOVA was used to compare groups. Significance was determined as P<0.05. Regarding bone mineral density, mechanical properties and bone microarchitecture, the beneficial effects were greater in the bones of animals subjected to pre-suspension training and subsequently to training during suspension, compared with the bones of animals subjected to pre-suspension training or to training during suspension. Our results indicate that a period of high impact exercise prior to tail suspension in rats can prevent the installation of osteopenia if there is also training during the tail suspension. PMID:26840705

  15. Preventing Pregnancy in High School Students: Observations From a 3-Year Longitudinal, Quasi-Experimental Study

    PubMed Central

    Dierschke, Nicole; Lowe, Diana; Plastino, Kristen

    2016-01-01

    Objectives. To assess whether a sexual health education intervention reduces pregnancy rates in high school students. Methods. We performed a secondary analysis of a 3-year quasi-experimental study performed in South Texas from 2011 to 2015 in which 1437 students without a history of pregnancy at baseline were surveyed each fall and spring. Potentially confounding risk factors considered included sexual behaviors, intentions, and demographics. The outcome measure was self-reported pregnancy status for male and female students. We performed analyses for male and female students using separate discrete time-to-event models. Results. We found no difference in pregnancy rates between intervention and comparison students within the first 3 years of high school. Female and male students in the intervention groups had pregnancy hazard ratios of, respectively, 1.62 (95% CI = 0.9, 2.61; P = .1) and 0.78 (95% CI = 0.44, 1.48; P = .4) relative to the comparison groups. Conclusions. The educational intervention had no impact on the pregnancy rate. Social media tools in pregnancy prevention programs should be adaptive to new technologies and rapidly changing adolescent preferences for these services. PMID:27689503

  16. Odontella aurita-enriched diet prevents high fat diet-induced liver insulin resistance.

    PubMed

    Amine, Hamza; Benomar, Yacir; Haimeur, Adil; Messaouri, Hafida; Meskini, Nadia; Taouis, Mohammed

    2016-01-01

    The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways.

  17. High-impact exercise in rats prior to and during suspension can prevent bone loss.

    PubMed

    Yanagihara, G R; Paiva, A G; Gasparini, G A; Macedo, A P; Frighetto, P D; Volpon, J B; Shimano, A C

    2016-03-01

    High-impact exercise has been considered an important method for treating bone loss in osteopenic experimental models. In this study, we investigated the effects of osteopenia caused by inactivity in femora and tibiae of rats subjected to jump training using the rat tail suspension model. Eight-week-old female Wistar rats were divided into five groups (n=10 each group): jump training for 2 weeks before suspension and training during 3 weeks of suspension; jump training for 2 weeks before suspension; jump training only during suspension; suspension without any training; and a control group. The exercise protocol consisted of 20 jumps/day, 5 days/week, with a jump height of 40 cm. The bone mineral density of the femora and tibiae was measured by double energy X-ray absorptiometry and the same bones were evaluated by mechanical tests. Bone microarchitecture was evaluated by scanning electron microscopy. One-way ANOVA was used to compare groups. Significance was determined as P<0.05. Regarding bone mineral density, mechanical properties and bone microarchitecture, the beneficial effects were greater in the bones of animals subjected to pre-suspension training and subsequently to training during suspension, compared with the bones of animals subjected to pre-suspension training or to training during suspension. Our results indicate that a period of high impact exercise prior to tail suspension in rats can prevent the installation of osteopenia if there is also training during the tail suspension.

  18. Detection of High-Risk Human Papillomaviruses in the Prevention of Cervical Cancer in India.

    PubMed

    Baskaran, Krishnan; Kumar, P Kranthi; Karunanithi, Santha; Sethupathy, Subramanian; Thamaraiselvi, B; Swaruparani, S

    2015-01-01

    Human papillomaviruses (HPVs) are small, non-enveloped, double-stranded DNA viruses that infect epithelial tissues. Specific genotypes of human papillomavirus are the single most common etiological agents of cervical intraepithelial lesions and cervical cancer. Cervical cancer usually arises at squamous metaplastic epithelium of transformation zone (TZ) of the cervix featuring infection with one or more oncogenic or high-risk HPV (HR- HPV) types. A hospital- based study in a rural set up was carried out to understand the association of HR-HPV with squamous intraepithelial lesions (SILs) and cervical cancer. In the present study, HR-HPV was detected in 65.7% of low-grade squamous intraepithelial lesions (LSILs), 84.6% of high-grade squamous intraepithelial lesions (HSILs) and 94% of cervical cancer as compared to 10.7% of controls. The association of HPV infection with SIL and cervical cancer was analyzed with Chi square test (p<0.001). The significant association found confirmed that detection of HR-HPV is a suitable candidate for early identification of cervical precancerous lesions and in the prevention of cervical cancer in India.

  19. High-intensity exercise training for the prevention of type 2 diabetes mellitus.

    PubMed

    Rynders, Corey A; Weltman, Arthur

    2014-02-01

    Aerobic exercise training and diet are recommended for the primary prevention of type 2 diabetes mellitus and cardiovascular disease. The American Diabetes Association (ADA) recommends that adults with prediabetes engage in ≥ 150 minutes per week of moderate activity and target a 7% weight loss. However, traditional moderate-intensity (MI) exercise training programs are often difficult to sustain for prediabetic adults; a commonly cited barrier to physical activity in this population is the "lack of time" to exercise. When matched for total energy expenditure, high-intensity (HI) exercise training has a lower overall time commitment compared with traditional low-intensity (LI) or MI exercise training. Several recent studies comparing HI exercise training with LI and MI exercise training reported that HI exercise training improves skeletal muscle metabolic control and cardiovascular function in a comparable and/or superior way relative to LI and MI exercise training. Although patients can accrue all exercise benefits by performing LI or MI activities such as walking, HI activities represent a time-efficient alternative to meeting physical activity guidelines. High-intensity exercise training is a potent tool for improving cardiometabolic risk for prediabetic patients with limited time and may be prescribed when appropriate.

  20. Opportunities for technology-based HIV prevention programming among high school students in Cape Town, South Africa.

    PubMed

    Ybarra, Michele L; Mwaba, Kelvin; Prescott, Tonya L; Roman, Nicolette V; Rooi, Bronwyn; Bull, Sheana

    2014-01-01

    One in three new cases of HIV in South Africa is among adolescents. Given that adolescents are particularly affected, scalable, and cost-effective prevention programs are urgently needed. This study aims to identify opportunities to integrate technology into youth HIV prevention efforts. In 2012, 1107 8th-11th graders completed a paper-and-pencil survey. Respondents were enrolled in one of three public high schools in Langa, a lower income community in Cape Town, South Africa. Eighty-nine percent of respondents have used text messaging (SMS) and 86% have gone online. If an HIV prevention program was offered online, 66% of youth would be somewhat or extremely likely to access it; slightly fewer (55%) felt the same about SMS-based programming. In comparison, 85% said they would be somewhat or extremely likely to access a school-based HIV prevention program. Interest in Internet- (60%) and SMS-based (54%) HIV prevention programming was similar for youth who had a self-appraised risk of HIV compared to youth who appraised their risk to be lower, as it was for youth who were tired of hearing messages about HIV prevention. Technology use is common - even among high school students who live in lower income communities. At the same time, these data reveal that it is not uncommon for youth to be tired of hearing messages about HIV prevention, and many of the typical topics key to HIV prevention have low interest levels among youth. HIV prevention researchers need to be mindful of the extent of existing programming that youth are exposed to. Technology-based programming may be especially amenable to meeting these requirements because of its novelty especially in developing countries, and because interactive functionality can be easily integrated into the program design. Given the preference for school- and Internet-based programming, it seems that a hybrid approach is likely feasible and acceptable.

  1. “Cancer – Educate to Prevent” – High-School Teachers, the New Promoters of Cancer Prevention Education Campaigns

    PubMed Central

    Barros, Ana; Moreira, Luís; Santos, Helena; Ribeiro, Nuno; Carvalho, Luís; Santos-Silva, Filipe

    2014-01-01

    Cancer is one of the leading causes of death worldwide, and thus represents a priority for national public health programs. Prevention has been assumed as the best strategy to reduce cancer burden, however most cancer prevention programs are implemented by healthcare professionals, which constrain range and educational impacts. We developed an innovative approach for cancer prevention education focused on high-school biology teachers, considered privileged mediators in the socialization processes. A training program, “Cancer, Educate to Prevent” was applied, so that the teachers were able to independently develop and implement prevention campaigns focused on students and school-related communities. The program encompassed different educational modules, ranging from cancer biology to prevention campaigns design. Fifty-four teachers were empowered to develop and implement their own cancer prevention campaigns in a population up to five thousands students. The success of the training program was assessed through quantitative evaluation – questionnaires focused on teachers' cancer knowledge and perceptions, before the intervention (pre-test) and immediately after (post-test). The projects developed and implemented by teachers were also evaluated regarding the intervention design, educational contents and impact on the students' knowledge about cancer. This study presents and discusses the results concerning the training program “Cancer, Educate to Prevent” and clearly shows a significant increase in teacher's cancer literacy (knowledge and perceptions) and teachers' acquired proficiency to develop and deliver cancer prevention campaigns with direct impact on students' knowledge about cancer. This pilot study reinforces the potential of high-school teachers and schools as cancer prevention promoters and opens a new perspective for the development and validation of cancer prevention education strategies, based upon focused interventions in restricted targets

  2. Every Student Succeeds Act Primer: High School Dropout Prevention and Reengagement of Out-of-School Youth

    ERIC Educational Resources Information Center

    Alliance for Excellent Education, 2016

    2016-01-01

    The Every Student Succeeds Act (ESSA) of 2015 includes several provisions that support state and district efforts to prevent students from dropping out of high school and reengage out-of-school youth. Under ESSA, state plans must describe how the state will work with school districts to transition students from middle school to high school and…

  3. Survey of Parents of Middle/High School Students. Beliefs and Attitudes Regarding HIV/AIDS Prevention Education.

    ERIC Educational Resources Information Center

    Rutt, Dan

    This study, commissioned by the Lucas County (Ohio) Health Department, was designed to assess parental beliefs and attitudes related to HIV/AIDS prevention for youth, particularly in middle and high schools. In November 1996, 400 telephone interviews were completed with parents of middle/high school students in Lucas County. Names were randomly…

  4. Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis.

    PubMed

    Alsanea, Sary; Gao, Mingming; Liu, Dexi

    2017-02-14

    Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-γ 2 (Pparγ2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.

  5. Low TGFβ1 expression prevents and high expression exacerbates diabetic nephropathy in mice

    PubMed Central

    Hathaway, Catherine K.; Gasim, Adil M. H.; Grant, Ruriko; Chang, Albert S.; Kim, Hyung-Suk; Madden, Victoria J.; Bagnell, C. Robert; Jennette, J. Charles; Smithies, Oliver; Kakoki, Masao

    2015-01-01

    Nephropathy develops in many but not all patients with long-standing type 1 diabetes. Substantial efforts to identify genotypic differences explaining this differential susceptibility have been made, with limited success. Here, we show that the expression of the transforming growth factor β1 gene (Tgfb1) affects the development of diabetic nephropathy in mice. To do this we genetically varied Tgfb1 expression in five steps, 10%, 60%, 100%, 150%, and 300% of normal, in mice with type 1 diabetes caused by the Akita mutation in the insulin gene (Ins2Akita). Although plasma glucose levels were not affected by Tgfb1 genotype, many features of diabetic nephropathy (mesangial expansion, elevated plasma creatinine and urea, decreased creatinine clearance and albuminuria) were progressively ameliorated as Tgfb1 expression decreased and were progressively exacerbated when expression was increased. The diabetic 10% hypomorphs had comparable creatinine clearance and albumin excretion to wild-type mice and no harmful changes in renal morphology. The diabetic 300% hypermorphs had ∼1/3 the creatinine clearance of wild-type mice, >20× their albumin excretion, ∼3× thicker glomerular basement membranes and severe podocyte effacement, matching human diabetic nephropathy. Switching Tgfb1 expression from low to high in the tubules of the hypomorphs increased their albumin excretion more than 10-fold but creatinine clearance remained high. Switching Tgfb1 expression from low to high in the podocytes markedly decreased creatinine clearance, but minimally increased albumin excretion. Decreasing expression of Tgfb1 could be a promising option for preventing loss of renal function in diabetes. PMID:25902541

  6. Optimizing Violence Prevention Programs: An Examination of Program Effectiveness among Urban High School Students

    ERIC Educational Resources Information Center

    Thompkins, Amanda C.; Chauveron, Lisa M.; Harel, Ofer; Perkins, Daniel F.

    2014-01-01

    Background: While demand for youth violence prevention programs increases, the ability of the school-day schedule to accommodate their time requirements has diminished. Viable school-based prevention programs must strike a balance between brevity and effectiveness. This article reports results from an effectiveness trial of a 12-session…

  7. Caffeine prevents changes in muscle caused by high-intensity interval training.

    PubMed

    Vieira, Juliano M; Gutierres, Jessié M; Carvalho, Fabiano B; Pereira, Luciane B; Oliveira, Liziele S; Morsch, Vera Maria; Schetinger, Maria Rosa C; Rodrigues, Marília V; Leitemperger, Jossiele; Loro, Vânia; Krewer, Cristina C; Vencato, Marina S; Spanevello, Roselia M

    2017-02-17

    The use of ergogenic substances such as caffeine has become a strategy to enhance sports performance. In the present study we evaluated the effects of high-intensity interval training (HIIT) associated with caffeine intake on acetylcholinesterase (AChE) and Ca(2+)ATPase activity and glycogen levels in the muscles of rats were evaluated. The animals were divided in groups: control, caffeine 4 or 8mg/kg, HIIT, HIIT plus caffeine 4 or caffeine 8mg/kg. Our results showed a decrease in glycogen levels in muscle in all trained groups after acute session exercise, while that an increase in glycogen levels was observed in all groups in relation to control in chronic exercise protocol. HIIT increases the thickness of the left ventricle and the Ca(2+)-ATPase activity and decrease the AChE activity in gastrocnemius muscle. Caffeine treatment prevents changes in enzymes activities as well as left ventricular hypertrophy adaptation induced by HIIT. Our findings suggest that caffeine modulates crucial pathways for muscle contraction in HIIT.

  8. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction

    PubMed Central

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T.; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R.; Rattan, Ramandeep

    2015-01-01

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent. PMID:25895126

  9. High-Throughput Luciferase-Based Assay for the Discovery of Therapeutics That Prevent Malaria

    PubMed Central

    2016-01-01

    In order to identify the most attractive starting points for drugs that can be used to prevent malaria, a diverse chemical space comprising tens of thousands to millions of small molecules may need to be examined. Achieving this throughput necessitates the development of efficient ultra-high-throughput screening methods. Here, we report the development and evaluation of a luciferase-based phenotypic screen of malaria exoerythrocytic-stage parasites optimized for a 1536-well format. This assay uses the exoerythrocytic stage of the rodent malaria parasite, Plasmodium berghei, and a human hepatoma cell line. We use this assay to evaluate several biased and unbiased compound libraries, including two small sets of molecules (400 and 89 compounds, respectively) with known activity against malaria erythrocytic-stage parasites and a set of 9886 diversity-oriented synthesis (DOS)-derived compounds. Of the compounds screened, we obtain hit rates of 12–13 and 0.6% in preselected and naïve libraries, respectively, and identify 52 compounds with exoerythrocytic-stage activity less than 1 μM and having minimal host cell toxicity. Our data demonstrate the ability of this method to identify compounds known to have causal prophylactic activity in both human and animal models of malaria, as well as novel compounds, including some exclusively active against parasite exoerythrocytic stages. PMID:27275010

  10. Small-area analysis: targeting high-risk areas for adolescent pregnancy prevention programs.

    PubMed

    Gould, J B; Herrchen, B; Pham, T; Bera, S; Brindis, C

    1998-01-01

    Traditional methods of identifying areas in need of adolescent pregnancy prevention programs may overlook small localities with high levels of adolescent childbearing in communities and counties where this is not a universal problem. The present study assessed the potential of a "geomapping" approach based on measurement of the number of births occurring to teens 15-17 years old in each California (US) zip code in 1992-94. A total of 415 zip codes with teen birth rates in excess of the state's 75th percentile cut-off point (62.8 births/1000) were identified. 210 of these zip codes, accounting for 96% of all births to 15-17 year olds in the 75th-percentile zip codes, differed significantly (p 0.01) from the state average of 44.5 births/1000 15-17 year olds. 178 (85%) of these 210 "hot spots" also included birth rates exceeding the third quartile among teens 10-14 and/or 18-19 years old. Panels of local experts reviewed these "hot spots" for accuracy and grouped them into 82 potential project areas on the basis of demographics, geography, and political infrastructure. Although there was substantial variation, localities with the highest teen birth rates tended to be characterized by minority overrepresentation, poverty, and poor prenatal care coverage. In addition to identifying areas with unmet need, this approach encourages community participation in program development.

  11. Maternal high-fat diet prevents developmental programming by early-life stress

    PubMed Central

    Rincel, M; Lépinay, A L; Delage, P; Fioramonti, J; Théodorou, V S; Layé, S; Darnaudéry, M

    2016-01-01

    Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development. PMID:27898075

  12. Prevention of cardiovascular diseases and highly concentrated n-3 polyunsaturated fatty acids (PUFAs).

    PubMed

    Weber, Heinz S; Selimi, Dzevair; Huber, Gustav

    2006-12-01

    30 years ago the observation of a lower incidence of cardiovascular diseases in Inuits (Eskimos) was related to the higher fish consumption when compared to the residual Danish population. Clinical studies confirmed this finding. It was explained by the higher content of polyunsaturated fatty acids (PUFA) in fish, especially of omega-3 PUFAs. Experimental studies in cell cultures and also in animals with and without infarction models verified the anti-arrhythmic effect of omega-3 PUFAs among other possible contributing factors when compared to other fatty acids. In clinical studies a significant reduction (ca. 40%) of sudden cardiac deaths (SCD) could be found in patients after an acute myocardial infarction, if they were treated with at least 1 g omega-3 PUFAs daily, either by consumption of fish twice weekly or of a highly purified preparation omega-3 PUFAs in capsules. These findings led to recommendations of the American Heart Association and the European Society of Cardiology to a higher fish consumption and/or the daily intake of 1 g omega-3 PUFAs for primary and especially for secondary prevention of cardiovascular diseases. The much fewer side-effects, and the standardised dosage on one hand and the negative effect of the sometimes higher mercury content of fish make the intake of omega-3 PUFAs as capsules the better choice.

  13. Alternating Diet as a Preventive and Therapeutic Intervention for High Fat Diet-induced Metabolic Disorder

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    This study presents the alternating diet as a new strategy in combating obesity and metabolic diseases. Lean or obese mice were fed a high-fat diet (HFD) for five days and switched to a regular diet for one (5 + 1), two (5 + 2), or five (5 + 5) days before switching back to HFD to start the second cycle, for a total of eight weeks (for prevention) or five weeks (for treatment) without limiting animals’ access to food. Our results showed that animals with 5 + 2 and 5 + 5 diet alternations significantly inhibited body weight and fat mass gain compared to animals fed an HFD continuously. The dietary switch changed the pattern of daily caloric intake and suppressed HFD-induced adipose macrophage infiltration and chronic inflammation, resulting in improved insulin sensitivity and alleviated fatty liver. Alternating diet inhibited HFD-induced hepatic Pparγ-mediated lipid accumulation and activated the expression of Pparα and its target genes. Alternating diet in the 5 + 5 schedule induced weight loss in obese mice and reversed the progression of metabolic disorders, including hepatic steatosis, glucose intolerance, and inflammation. The results provide direct evidence to support that alternating diet represents a new intervention in dealing with the prevalence of diet-induced obesity. PMID:27189661

  14. Gomisin N inhibits adipogenesis and prevents high-fat diet-induced obesity

    PubMed Central

    Jang, Min-Kyung; Yun, Ye-Rang; Kim, Ji-Hyun; Park, Mi-Hee; Jung, Myeong Ho

    2017-01-01

    Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition. GN inhibited the extracellular signal-regulated kinase and phosphoinositide 3-kinase/protein kinase B signaling in the MCE process and activated AMP-activated protein kinase. Furthermore, GN downregulated CCAT/enhancer-binding protein β (C/EBPβ) and histone H3K9 demethylase JMJD2B during early stages of adipogenesis, and therefore repressed the expression of C/EBPβ-targeted cell cycle genes. In addition, GN also repressed the expression of histone H3K4 methyltransferase MLL4 and reduced PPARγ expression. Moreover, GN effectively lowered the final body weight, adipose tissue mass, and reduced the serum levels of glucose, total triglyceride, and cholesterol in the HFD-induced obese mice. GN also markedly reduced hepatic triglyceride level induced by HFD. Collectively, these findings suggest that GN has potential as a novel agent for the prevention and treatment of obesity. PMID:28067305

  15. Crack prevention of highly bent metal thin films in woven electronic textiles

    NASA Astrophysics Data System (ADS)

    Kinkeldei, T.; Cherenack, K.; Zysset, C.; Woo, N. C.; Tröster, G.

    2011-08-01

    Recent smart textile fabrication methods that are aimed at increasing the integration of electronics with textiles have involved fabricating micro-electronic components directly at the yarn level. Our approach to creating smart textiles is to fabricate thin-film devices and interconnects on plastic strips to create `e-fibers' and weave them into a textile using a commercial weaving machine. e-Fibers are exposed to bending radii as small as 165 μm during weaving. If patterned interconnect lines and device layers on the surface of the e-fiber are not designed correctly, they will crack due to the high strain and lose their electronic functionality. Brittle sensor and transistor device layers may be protected locally using rigid encapsulation materials, but cracking remains an issue for long metal interconnect lines which require flexibility. We investigated two strain-control methods to prevent the thin-film interconnect lines from cracking during weaving: (1) patterning the metal interconnect lines with a geometric design to slow propagation and merging of cracks and (2) encapsulation of interconnect lines to shift the deposited films to the neutral plain of the substrate. The mechanical behavior of interconnect lines exposed to tensile bending was studied by measuring the change in interconnect resistance versus bending radii ranging from 5 mm to 50 μm. The critical bending radius, XC, defined as the radius at which the normalized interconnect resistance changes to 1.1 (indicating the onset of film rupturing) was 150 μm for standard interconnect lines. Patterned interconnect lines had a radius XC of 115 μm while encapsulated interconnect lines never reached this critical bending radius and showed a maximum resistance change of 1.02 at 100 μm. These results show that it is possible to design interconnect lines with reduced cracking behavior when exposed to high strain during commercial weaving.

  16. Interleukin-6 as a Potential Indicator for Prevention of High Risk Adenoma Recurrence by Dietary Flavonols in the Polyp Prevention Trial

    PubMed Central

    Bobe, Gerd; Albert, Paul S.; Sansbury, Leah B.; Lanza, Elaine; Schatzkin, Arthur; Colburn, Nancy H.; Cross, Amanda J.

    2010-01-01

    Serum interleukin (IL)-6, a pro-inflammatory cytokine, is considered an indicator of inflammation and may be an indicator of colorectal carcinogenesis given that inflammation can promote carcinogenesis. Flavonols, which can be found in fruits and vegetables, may inhibit colorectal carcinogenesis partly by inhibiting inflammation. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) to determine whether serum IL-6 was associated with colorectal adenoma recurrence and flavonol intake and, thus may serve as a risk indicator and as a response indicator to dietary flavonols. Serum IL-6 concentrations at baseline, year 1 and 3 were measured in 872 participants from the intervention arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Intake of flavonols, especially of isorhamnetin, kaempferol, and quercetin, was inversely associated with serum IL-6 concentrations (highest vs. lowest flavonol intake quartile, 1.80 vs. 2.20 pg/mL) and high risk (OR = 0.51, 95% CI: 0.26–0.98) and advanced adenoma recurrence (OR = 0.17, 95% CI: 0.06–0.50). A decrease in IL-6 concentration during the trial was inversely associated with high risk (OR = 0.44, 95% CI: 0.23–0.84) and advanced adenoma recurrence (OR = 0.47, 95% CI: 0.19–1.18). Individuals with above median flavonol intake and equal or below median IL-6 change after baseline had the lowest risk of recurrence of high risk and advanced adenoma. Our results suggest that serum IL-6 may serve as a risk indicator and as a response indicator to dietary flavonols for colorectal cancer prevention. PMID:20484173

  17. Social norms marketing: a prevention strategy to decrease high-risk drinking among college students.

    PubMed

    Ott, Carol H; Haertlein, Carol

    2002-06-01

    We describe a social-norms marketing approach to moderating college student drinking behaviors and correcting student misperceptions about campus drinking. The intervention has the potential to be applied to other health behaviors where misperceptions abound, such as those related to cigarette smoking, eating disorders, sexual health, and sexual assault. Even though nurses are actively working on alcohol and other drug (AOD) prevention efforts on college campuses, little data based research have been published. Collaborative efforts between faculty from different disciplines, including nursing and nurse health educators, can be an effective combination for preventing alcohol abuse and for initiating sound research-based campus prevention programs.

  18. Microbicide Acceptability Among High-Risk Urban U.S. Women: Experiences and Perceptions of Sexually Transmitted HIV Prevention

    PubMed Central

    Weeks, Margaret R.; Mosack, Katie E.; Abbott, Maryann; Sylla, Laurie Novick; Valdes, Barbara; Prince, Mary

    2005-01-01

    SUMMARY A study of microbicide acceptability among high-risk African American, Puerto Rican, non-Hispanic White, and other women in Hartford, Connecticut indicated limited experience with vaginal contraceptives but significant interest in and willingness to adopt vaginal microbicides for HIV/STI prevention. Objectives To measure microbicide acceptability among high-risk women in Hartford, Connecticut and contextual factors likely to affect acceptability and use. Goal To assess usefulness of microbicides for HIV/STI prevention for high-risk women. Study Design Ethnographic interviews (n=75) and a survey (n=471) explored women’s perspectives on HIV/STI prevention, vaginal contraceptives similar to microbicides, and microbicide acceptability. Participants (n=94) in a two-week behavioral trial used an over-the-counter vaginal moisturizer to simulate microbicide use during sex with primary, casual, and/or paying partners. Results Findings showed limited experience with vaginal contraceptives, but high interest in microbicides as an alternative to condoms, indicated by an acceptability index score of 2.73 (SD .49, scale 1–4) in the overall sample. General microbicide acceptability varied by ethnicity, prior contraceptive and violence/abuse experiences, relationship power, and other attitudinal factors. The simulation trial indicated significant willingness to use the product in various locations and with all types of partners. Conclusions Vaginal microbicides may improve prevention outcomes for high-risk inner-city women. PMID:15502677

  19. Media literacy as a prevention intervention for college women at low- or high-risk for eating disorders.

    PubMed

    Coughlin, Janelle W; Kalodner, Cynthia

    2006-03-01

    This study examined whether the media literacy program, ARMED, is an effective prevention intervention for college women at low- or high-risk for an eating disorder. Changes in eating disorder risk factors were assessed in low- (n=26) and high-risk (n=19) women participating in a two-session media literacy intervention as compared to low- (n=31) and high-risk (n=16) controls. Women at high-risk for an eating disorder reported significant decreases in body dissatisfaction, drive for thinness, feelings of ineffectiveness, and internalization of societal standards of beauty after participating in ARMED, whereas control participants did not. No significant decreases in perfectionism, physical appearance comparisons, or awareness of societal standards of beauty were reported among high-risk participants. Changes in eating disorder risk factors were not found among low-risk participants, regardless of treatment condition. Findings suggest that media literacy may be an effective secondary prevention intervention for eating disorders.

  20. Thermophilic nitrate-reducing microorganisms prevent sulfate reduction in cold marine sediments incubated at high temperature

    NASA Astrophysics Data System (ADS)

    Nepomnyashchaya, Yana; Rezende, Julia; Hubert, Casey

    2014-05-01

    Hydrogen sulphide produced during metabolism of sulphate-reducing microorganisms (SRM) is toxic, corrosive and causes detrimental oil reservoir souring. During secondary oil recovery, injecting oil reservoirs with seawater that is rich in sulphate and that also cools high temperature formations provides favourable growth conditions for SRM. Nitrate addition can prevent metabolism of SRM by stimulating nitrate-reducing microorganisms (NRM). The investigations of thermophilic NRM are needed to develop mechanisms to control the metabolism of SRM in high temperature oil field ecosystems. We therefore established a model system consisting of enrichment cultures of cold surface marine sediments from the Baltic Sea (Aarhus Bay) that were incubated at 60°C. Enrichments contained 25 mM nitrate and 40 mM sulphate as potential electron acceptors, and a mixture of the organic substrates acetate, lactate, propionate, butyrate (5 mM each) and yeast extract (0.01%) as potential carbon sources and electron donors. Slurries were incubated at 60°C both with and without initial pasteurization at 80°C for 2 hours. In the enrichments containing both nitrate and sulphate, the concentration of nitrate decreased indicating metabolic activity of NRM. After a four-hour lag phase the rate of nitrate reduction increased and the concentration of nitrate dropped to zero after 10 hours of incubation. The concentration of nitrite increased as the reduction of nitrate progressed and reached 16.3 mM after 12 hours, before being consumed and falling to 4.4 mM after 19-day of incubation. No evidence for sulphate reduction was observed in these cultures during the 19-day incubation period. In contrast, the concentration of sulphate decreased up to 50% after one week incubation in controls containing only sulphate but no nitrate. Similar sulfate reduction rates were seen in the pasteurized controls suggesting the presence of heat resistant SRM, whereas nitrate reduction rates were lower in the

  1. Estradiol prevents fat accumulation and overcomes leptin resistance in female high-fat diet mice.

    PubMed

    Litwak, Sara A; Wilson, Jenny L; Chen, Weiyi; Garcia-Rudaz, Cecilia; Khaksari, Mohammad; Cowley, Michael A; Enriori, Pablo J

    2014-11-01

    In premenopausal and menopausal women in particular, suboptimal estrogens have been linked to the development of the metabolic syndrome as major contributors to fat accumulation. At the same time, estrogens have been described to have a role in regulating body metabolic status. We evaluated how endogenous or administered estrogens impact on the changes associated with high-fat diet (HFD) consumption in 2 different paradigms; ovarian-intact and in ovariectomized mice. When estradiol (E2) was cyclically administered to ovarian-intact HFD-fed mice for 12 weeks, animals gained significantly less weight than ovarian-intact vehicle controls (P < .01). This difference was mainly due to a reduced caloric intake but not to an increase in energy expenditure or locomotor activity. This E2 treatment regime to mice exposed to HFD was overall able to avoid the increase of visceral fat content to levels of those found in mice fed a regular chow diet. In the ovariectomized model, the main body weight and fat content reducing action of E2 was not only through decreasing food intake but also by increasing the whole-body energy expenditure, locomotor activity, and by inducing fat oxidation. Importantly, these animals became responsive to the anorexigenic effects of leptin in contrast to the vehicle-treated and the pair-fed control groups (P < .01). Further, in vitro hypothalamic secretion experiments revealed that treatment of obese mice with E2 is able to modulate the secretion of appetite-regulating neuropeptides; namely, E2 increased the secretion of the anorectic neuropeptide α-melanocyte-stimulating hormone and decreased the secretion of the orexigenic neuropetides neuropeptide Y and Agouti-related peptide. In conclusion, differences in response to E2 treatment of HFD-fed animals depend on their endogenous estrogenic status. Overall, E2 administration overcomes arcuate leptin resistance and partially prevents fat accumulation on these mice.

  2. High-fish consumption and risk prevention: assessment of exposure to methylmercury in Portugal.

    PubMed

    Carvalho, C M L; Matos, A I N M; Mateus, M L; Santos, A P M; Batoreu, M C C

    2008-01-01

    The aim of this study was to evaluate the exposure to methylmercury (MeHg) of potential populations at risk living in Portugal. To ascertain youth exposure, a questionnaire was distributed to 300 students of a middle secondary school in Sesimbra and to 429 students studying in Canecas, selected as the control population. The average number of fish meals consumed by person was 4.1 and 3 per week in Sesimbra and Canecas, respectively. The subpopulations of high intake (PHI) corresponding to those ingesting 7 or more fish meals per week were also analyzed separately, with 17% of the students belonging to the PHI of Sesimbra versus 6.1% in Canecas. Socioeconomic aspects such as relative's professional involvement with fisheries correlated with the higher intakes in Sesimbra. Fish samples were collected in the dock of Sesimbra and total mercury (Hg) was determined by flow injection cold vapor atomic fluorescence spectroscopy (FI-CV-AFS). The mean value found for nonpredators was 0.035 microg/g. Dogfish specimens surpassed the legislated limit for predator species and increased the predators mean to 1 microg/g. The cross-sectional data were integrated with the fish analysis results to estimate the population exposure to MeHg. The indices of risk calculated for youth reached values of 4.5, demonstrating the existence of risk to a part of the population exceeding the provisional tolerable weekly intake (PTWI) level mandated by WHO (1.6 microg/kg bw). The results indicate that monitoring of Hg levels in fish is mandatory and counseling should be provided to populations at risk, encouraging them to prevent the risk.

  3. Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice.

    PubMed

    Kaczmarczyk, Melissa M; Machaj, Agnieszka S; Chiu, Gabriel S; Lawson, Marcus A; Gainey, Stephen J; York, Jason M; Meling, Daryl D; Martin, Stephen A; Kwakwa, Kristin A; Newman, Andrew F; Woods, Jeffrey A; Kelley, Keith W; Wang, Yanyan; Miller, Michael J; Freund, Gregory G

    2013-09-01

    The prevalence of childhood obesity has risen dramatically and coincident with this upsurge is a growth in adverse childhood psychological conditions including impulsivity, depression, anxiety and attention deficit/hyperactive disorder (ADHD). Due to confounds that exist when determining causality of childhood behavioral perturbations, controversy remains as to whether overnutrition and/or childhood obesity is important. Therefore, we examined juvenile mice to determine if biobehaviors were impacted by a short-term feeding (1-3wks) of a high-fat diet (HFD). After 1wk of a HFD feeding, mouse burrowing and spontaneous wheel running were increased while mouse exploration of the open quadrants of a zero maze, perfect alternations in a Y-maze and recognition of a novel object were impaired. Examination of mouse cortex, hippocampus and hypothalamus for dopamine and its metabolites demonstrated increased homovanillic acid (HVA) concentrations in the hippocampus and cortex that were associated with decreased cortical BDNF gene expression. In contrast, pro-inflammatory cytokine gene transcripts and serum IL-1α, IL-1β, TNF-α and IL-6 were unaffected by the short-term HFD feeding. Administration to mice of the psychostimulant methylphenidate prevented HFD-dependent impairment of learning/memory. HFD learning/memory impairment was not inhibited by the anti-depressants desipramine or reboxetine nor was it blocked in IDO or IL-1R1 knockout mice. In sum, a HFD rapidly impacts dopamine metabolism in the brain appearing to trigger anxiety-like behaviors and learning/memory impairments prior to the onset of weight gain and/or pre-diabetes. Thus, overnutrition due to fats may be central to childhood psychological perturbations such as anxiety and ADHD.

  4. America's Promise Alliance Dropout Prevention Summits: Mobilizing Action to Address the High School Dropout Crisis Across the Nation

    ERIC Educational Resources Information Center

    Gifford, Beth; Evans, Kelly

    2011-01-01

    In this final evaluation of the America's Promise Dropout Prevention Summits, the evaluation reveals that the Summits not only served as the catalyst for the creation of new programs and collaborative efforts around ending the high school dropout crisis, but strengthened existing work, political and public awareness, and funding at the state,…

  5. Effect of Social Cognitive Theory-Based HIV Education Prevention Program among High School Students in Nanjing, China

    ERIC Educational Resources Information Center

    Li, Xiaoming; Zhang, Liying; Mao, Rong; Zhao, Qun; Stanton, Bonita

    2011-01-01

    This study was designed to evaluate potential preventive effects of a cultural adaption of the Focus on Kids (FOK) program among Chinese adolescents through a quasi-experimental intervention trial in Nanjing, China. High school students were assigned to either experimental groups (n = 140) or control groups (n = 164) by schools (with three schools…

  6. Brief Cognitive-Behavioral Depression Prevention Program for High-Risk Adolescents Outperforms Two Alternative Interventions: A Randomized Efficacy Trial

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Seeley, John R.; Gau, Jeff M.

    2008-01-01

    In this depression prevention trial, 341 high-risk adolescents (mean age = 15.6 years, SD = 1.2) with elevated depressive symptoms were randomized to a brief group cognitive-behavioral (CB) intervention, group supportive-expressive intervention, bibliotherapy, or assessment-only control condition. CB participants showed significantly greater…

  7. Suicide Prevention among High School Students: Evaluation of a Nonrandomized Trial of a Multi-Stage Suicide Screening Program

    ERIC Educational Resources Information Center

    Torcasso, Gina; Hilt, Lori M.

    2017-01-01

    Background: Suicide is a leading cause of death among youth. Suicide screening programs aim to identify mental health issues and prevent death by suicide. Objective: The present study evaluated outcomes of a multi-stage screening program implemented over 3 school years in a moderately-sized Midwestern high school. Methods: One hundred ninety-three…

  8. Acetylsalicylic Acid and Eflornithine in Treating Patients at High Risk for Colorectal Cancer | Division of Cancer Prevention

    Cancer.gov

    This phase II trial is studying how well giving acetylsalicylic acid together with eflornithine works in treating patients at high risk for colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acetylsalicylic acid and eflornithine may prevent colorectal cancer. |

  9. Prevention for Preschoolers at High Risk for Conduct Problems: Immediate Outcomes on Parenting Practices and Child Social Competence

    ERIC Educational Resources Information Center

    Brotman, Laurie Miller; Gouley, Kathleen Kiely; Chesir-Teran, Daniel; Dennis, Tracy; Klein, Rachel G.; Shrout, Patrick

    2005-01-01

    This study investigated the immediate impact of an 8-month center- and home-based prevention program for preschoolers at high risk for conduct problems. We report immediate program effects on observed and self-rated parenting practices and observed child behavior with peers. Ninety-nine preschool-age siblings of adjudicated youths and their…

  10. Eicosapentaenoic acid prevents high fat diet-induced metabolic disorders: Genomic and metabolomic analyses of underlying mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously our lab demonstrated eicosapenaenoic acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity by decreasing insulin resistance, glucose intolerance and inflammation. In the current study, we used genomic and metabolomic approaches to further investigate the molecular basis for t...

  11. Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation.

    PubMed

    Bai, Yang; Cui, Wenpeng; Xin, Ying; Miao, Xiao; Barati, Michelle T; Zhang, Chi; Chen, Qiang; Tan, Yi; Cui, Taixing; Zheng, Yang; Cai, Lu

    2013-04-01

    This study was to investigate whether sulforaphane (SFN) can prevent diabetic cardiomyopathy. Type 1 diabetes was induced in FVB mice by multiple intraperitoneal injections with low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without SFN at 0.5mg/kg daily in five days of each week for 3 months and then kept until 6 months. At 3 and 6 months of diabetes, blood pressure and cardiac function were assessed. Cardiac fibrosis, inflammation, and oxidative damage were assessed by Western blot, real-time qPCR, and histopathological examination. SFN significantly prevented diabetes-induced high blood pressure and cardiac dysfunction at both 3 and 6 months, and also prevented diabetes-induced cardiac hypertrophy (increased the ratio of heart weight to tibia length and the expression of atrial natriuretic peptide mRNA and protein) and fibrosis (increased the accumulation of collagen and expression of connective tissue growth factor and tissue growth factor-β). SFN also almost completely prevented diabetes-induced cardiac oxidative damage (increased accumulation of 3-nitrotyrosine and 4-hydroxynonenal) and inflammation (increased tumor necrotic factor-α and plasminogen activator inhibitor 1 expression). SFN up-regulated NFE2-related factor 2 (Nrf2) expression and transcription activity that was reflected by increased Nrf2 nuclear accumulation and phosphorylation as well as the mRNA and protein expression of Nrf2 downstream antioxidants. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the SFN's prevention of high glucose-induced fibrotic response. These results suggest that diabetes-induced cardiomyopathy can be prevented by SFN, which was associated with the up-regulated Nrf2 expression and transcription function.

  12. Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF.

    PubMed

    Moy, Gregory A; McNay, Ewan C

    2013-01-17

    Obesity, high-fat diets, and subsequent type 2 diabetes (T2DM) are associated with cognitive impairment. Moreover, T2DM increases the risk of Alzheimer's disease (AD) and leads to abnormal elevation of brain beta-amyloid levels, one of the hallmarks of AD. The psychoactive alkaloid caffeine has been shown to have therapeutic potential in AD but the central impact of caffeine has not been well-studied in the context of a high-fat diet. Here we investigated the impact of caffeine administration on metabolism and cognitive performance, both in control rats and in rats placed on a high-fat diet. The effects of caffeine were significant: caffeine both (i) prevented the weight-gain associated with the high-fat diet and (ii) prevented cognitive impairment. Caffeine did not alter hippocampal metabolism or insulin signaling, likely because the high-fat-fed animals did not develop full-blown diabetes; however, caffeine did prevent or reverse a decrease in hippocampal brain-derived neurotrophic factor (BDNF) seen in high-fat-fed animals. These data confirm that caffeine may serve as a neuroprotective agent against cognitive impairment caused by obesity and/or a high-fat diet. Increased hippocampal BDNF following caffeine administration could explain, at least in part, the effects of caffeine on cognition and metabolism.

  13. The Costs of Scaling Up HIV Prevention for High Risk Groups: Lessons Learned from the Avahan Programme in India

    PubMed Central

    Chandrashekar, Sudhashree; Guinness, Lorna; Pickles, Michael; Shetty, Govindraj Y.; Alary, Michel; Vickerman, Peter; Vassall, Anna

    2014-01-01

    Objective The study objective is to measure, analyse costs of scaling up HIV prevention for high-risk groups in India, in order to assist the design of future HIV prevention programmes in South Asia and beyond. Design Prospective costing study. Methods This study is one of the most comprehensive studies of the costs of HIV prevention for high-risk groups to date in both its scope and size. HIV prevention included outreach, sexually transmitted infections (STI) services, condom provision, expertise enhancement, community mobilisation and enabling environment activities. Economic costs were collected from 138 non-government organisations (NGOs) in 64 districts, four state level lead implementing partners (SLPs), and the national programme level (Bill and Melinda Gates Foundation (BMGF)) office over four years using a top down costing approach, presented in US$ 2011. Results Mean total unit costs (2004–08) per person reached at least once a year and per monthly contact were US$ 235(56–1864) and US$ 82(12–969) respectively. 35% of the cost was incurred by NGOs, 30% at the state level SLP and 35% at the national programme level. The proportion of total costs by activity were 34% for expertise enhancement, 37% for programme management (including support and supervision), 22% for core HIV prevention activities (outreach and STI services) and 7% for community mobilisation and enabling environment activities. Total unit cost per person reached fell sharply as the programme expanded due to declining unit costs above the service level (from US$ 477 per person reached in 2004 to US$ 145 per person reached in 2008). At the service level also unit costs decreased slightly over time from US$ 68 to US$ 64 per person reached. Conclusions Scaling up HIV prevention for high risk groups requires significant investment in expertise enhancement and programme administration. However, unit costs decreased with programme expansion in spite of an increase in the scope of activities

  14. Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions

    SciTech Connect

    Gupta, Chanchal; Kaur, Jasmine; Tikoo, Kulbhushan

    2014-05-15

    Hyperglycemia is a critical risk factor for development and progression of breast cancer. We have recently reported that high glucose induces phosphorylation of histone H3 at Ser 10 as well as de-phosphorylation of GSK-3β at Ser 9 in MDA-MB-231 cells. Here, we elucidate the mechanism underlying hyperglycemia-induced proliferation in MDA-MB-231 breast cancer cells. We provide evidence that hyperglycemia led to increased DNA methylation and DNMT1 expression in MDA-MB-231 cells. High glucose condition led to significant increase in the expression of PCNA, cyclin D1 and decrease in the expression of PTPN 12, p21 and PTEN. It also induced hypermethylation of DNA at the promoter region of PTPN 12, whereas hypomethylation at Vimentin and Snail. Silencing of GSK-3β by siRNA prevented histone H3 phosphorylation and reduced DNMT1 expression. We show that chromatin obtained after immunoprecipitation with phospho-histone H3 was hypermethylated under high glucose condition, which indicates a cross-talk between DNA methylation and histone H3 phosphorylation. ChIP-qPCR analysis revealed up-regulation of DNMT1 and metastatic genes viz. Vimentin, Snail and MMP-7 by phospho-histone H3, which were down-regulated upon GSK-3β silencing. To the best of our knowledge, this is the first report which shows that interplay between GSK-3β activation, histone H3 phosphorylation and DNA methylation directs proliferation of breast cancer cells. - Highlights: • High glucose induces phosphorylation of histone H3 and dephosphorylation of GSK-3β. • Moreover, hyperglycemia also leads to increased DNA methylation in MDA-MB-231 cells. • Inhibition of GSK-3β prevented histone H3 phosphorylation and reduced DNMT1 levels. • Interplay exists between GSK-3β, histone H3 phosphorylation and DNA methylation.

  15. Opportunities for technology-based HIV prevention programming among high school students in Cape Town, South Africa

    PubMed Central

    Mwaba, Kelvin; Prescott, Tonya L.; Roman, Nicolette V.; Rooi, Bronwyn; Bull, Sheana

    2014-01-01

    One in three new cases of HIV in South Africa is among adolescents. Given that adolescents are particularly affected, scalable and cost-effective prevention programs are urgently needed. This study aims to identify opportunities to integrate technology into youth HIV prevention efforts. In 2012, 1,107 8th – 11th graders completed a paper-and-pencil survey. Respondents were enrolled in one of three public high schools in Langa. Because it is the closest black township to Cape Town, Langa has the highest density of people in the region. Eighty-nine percent of respondents have used text messaging (SMS) and 86% have gone online. If an HIV prevention program was offered online, 66% of youth would be somewhat or extremely likely to access it; slightly fewer (55%) felt the same about SMS-based programming. In comparison, 85% said they would be somewhat or extremely likely to access a school-based HIV prevention program. Interest in Internet-(60%) and SMS-based (54%) HIV prevention programming was similar for youth who had a self-appraised risk for HIV compared to youth who appraised their risk to be lower, as it was for youth who were tired of hearing messages about HIV prevention. Technology use is common – even among high school students who live in lower income communities. At the same time, these data reveal that it is not uncommon for youth to be tired of hearing messages about HIV prevention, and many of the typical topics key to HIV prevention have low interest levels among youth. HIV prevention researchers need to be mindful of the extent of existing programming that youth are exposed to. Technology-based programming may be especially amenable to meeting these requirements because of its novelty especially in developing countries, and because interactive functionality can be easily integrated into the program design. Given the preference for school- and Internet-based programming, it seems that a hybrid approach is likely feasible and acceptable. PMID:25022287

  16. miR-146a regulates glucose induced upregulation of inflammatory cytokines extracellular matrix proteins in the retina and kidney in diabetes

    PubMed Central

    Chen, Shali; Feng, Biao; Thomas, Anu Alice

    2017-01-01

    Hyperglycemic damage to the endothelial cells (ECs) leads to increased synthesis of inflammatory cytokines. We have previously shown miR-146a downregulation in ECs and in the tissues of diabetic mice. Here we investigated the role of miR-146a, in the production of specific inflammatory cytokines and extracellular matrix (ECM) proteins in retina and kidneys in diabetes. We generated an endothelial specific miR-146a overexpressing transgenic mice (TG). We investigated these mice and wild type (WT) controls with or without streptozotocin (STZ) induced diabetes. Retinal and renal cortical tissues from the mice were examined for mRNAs for specific inflammatory markers, (ECM) proteins and inflammation inducible transcription factor by real time RT-PCR. Corresponding proteins, where possible, were examined using immunofluorescence or ELISA. In parallel, we examined ECs following incubation with various levels of glucose with or without miR-146a mimic transfection. In the retina and kidneys of WT mice with diabetes, increased expression of inflammatory markers (IL-6, TNFα, IL1β) in association augmented expression of ECM proteins (collagen 1αIV, fibronectin) and NF κB-P65 were observed, compared to WT non-diabetic controls. These changes were prevented in diabetic miR-146a TG mice along with retinal and renal functional and structural changes. In vitro studies showed similar changes in the ECs exposed to high glucose. Such changes were corrected in the cells following miR-146a mimic transfection. Further analyses of renal cortical tissues showed diabetes induced significant upregulation of two regulators of NFκB, namely Interleukin-1 associated Kinase 1 and tumour necrosis factor receptor associated factor. Such changes were prevented in diabetic TG animals. These data indicate that augmented production of inflammatory cytokines and ECM proteins in the retina and kidneys in diabetes are regulated through endothelium derived miR-146a. Identification of such novel

  17. Development of an intervention model for the prevention of aspiration pneumonia in high-risk patients on a medical-surgical unit.

    PubMed

    Echevarria, Ilia M; Schwoebel, Ann

    2012-01-01

    Aspiration pneumonia is associated with significantly high morbidity and mortality rates, accompanied by high health care costs. As a result, aspiration pneumonia preventive efforts are a national priority. The development of an intervention model for the prevention of aspiration pneumonia in high-risk medical-surgical inpatients at an urban teaching hospital is described. The intervention model consists of the implementation and evaluation of a risk assessment tool and development of an aspiration pneumonia prevention protocol.

  18. Fruit juice drinks prevent endogenous antioxidant response to high-fat meal ingestion.

    PubMed

    Miglio, Cristiana; Peluso, Ilaria; Raguzzini, Anna; Villaño, Deborah V; Cesqui, Eleonora; Catasta, Giovina; Toti, Elisabetta; Serafini, Mauro

    2014-01-28

    High-fat meals (HFM) induce metabolic stress, leading to the activation of protective mechanisms, including inflammation and endogenous antioxidant defences. In the present study, we investigated the effects of antioxidant-rich fruit juice drinks on the endogenous antioxidant response induced by HFM. In a double-blind, cross-over design (10 d washout), fourteen overweight volunteers were randomly assigned to one of the following interventions: HFM+500 ml placebo beverage (HFM-PB, free from fruit); HFM+500 ml antioxidant beverage 1 (HFM-AB1; apple, grape, blueberry and pomegranate juices and grape skin, grape seed and green tea extracts); HFM+500 ml antioxidant beverage 2 (HFM-AB2; pineapple, black currant and plum juices). HFM-PB consumption increased the plasma levels of thiols (SH) (4 h, P< 0·001) and uric acid (UA) (2 h, P< 0·01) and total radical-trapping antioxidant parameter (TRAP) (4 h, P< 0·01). Following the consumption of drinks, UA production was significantly reduced with respect to placebo beverage consumption 8 h after HFM-AB2 consumption (P< 0·05). SH levels were reduced 0·5 (P< 0·05), 1 (P< 0·05) and 2 h (P< 0·01) after HFM-AB1 consumption and 2, 4 and 8 h (P< 0·05) after HFM-AB2 consumption. Plasma TRAP (2 h, P< 0·001) and urinary ferric reducing antioxidant power (0-8 h, P< 0·01) were increased by HFM-AB1 consumption, the drink with the highest in vitro antioxidant capacity, but not by HFM-AB2 consumption. In urine, UA levels were significantly increased from basal levels after the consumption of HFM-PB and HFM-AB2. However, neither of the beverages increased the urinary excretion of UA with respect to the placebo beverage. In conclusion, the increase in UA and SH levels induced by HFM as part of an endogenous antioxidant response to postprandial stress can be prevented by the concomitant ingestion of antioxidant-rich fruit juice drinks.

  19. Evaluation of the Centers for Disease Control and Prevention's Concussion Initiative for High School Coaches: "Heads up: Concussion in High School Sports"

    ERIC Educational Resources Information Center

    Sarmiento, Kelly; Mitchko, Jane; Klein, Cynthia; Wong, Sharon

    2010-01-01

    Background: To reduce the number of sports-related concussions, the Centers for Disease Control and Prevention (CDC), with the support of partners and experts in the field, has developed a tool kit for high school coaches with practical, easy-to-use concussion-related information. This study explores the success of the tool kit in changing…

  20. Gentamicin-Impregnated Collagen Sponge: Effectiveness in Preventing Sternal Wound Infection in High-Risk Cardiac Surgery

    PubMed Central

    Rapetto, Filippo; Bruno, Vito D.; Guida, Gustavo; Marsico, Roberto; Chivasso, Pierpaolo; Zebele, Carlo

    2016-01-01

    Sternal wound infections represent one of the most frequent complications after cardiac surgery and are associated with high postoperative mortality. Several preventive methods have been introduced, and recently, gentamicin-impregnated collagen sponges (GICSs) have shown a promising effect in reducing the incidence of this type of complications. Gentamicin is an aminoglycoside antibiotic that has been widely used to treat infections caused by multiresistant bacteria; despite its effectiveness, its systemic use carries a risk of toxicity. GICSs appear to overcome this side effect, topically delivering high antibiotic concentrations to the wound and thus reducing the toxic-related events. Although several retrospective analyses and randomized controlled trials have studied the use of GICSs in cardiac surgery, conclusions regarding their efficacy in preventing sternal wound infection are inconsistent. We have reviewed the current literature focusing on high-risk patients. PMID:27279734

  1. Dropout Prevention and the Model-Minority Stereotype: Reflections from an Asian American High School Dropout

    ERIC Educational Resources Information Center

    Wexler, Jade; Pyle, Nicole

    2012-01-01

    A recent review of the research by the U.S. Department of Education Institute of Education Sciences has resulted in the recommendation of six promising practices to ensure that all students are actively engaged in school and on a path to post-secondary success (Dynarski et al. in Dropout prevention: A practice guide (NCEE 2008-4025)). The purpose…

  2. Supporting Families in a High-Risk Setting: Proximal Effects of the SAFEChildren Preventive Intervention

    ERIC Educational Resources Information Center

    Tolan, Patrick; Gorman-Smith, Deborah; Henry,David

    2004-01-01

    Four hundred twenty-four families who resided in inner-city neighborhoods and had a child entering 1st grade were randomly assigned to a control condition or to a family-focused preventive intervention combined with academic tutoring. SAFEChildren, which was developed from a developmental-ecological perspective, emphasizes developmental tasks and…

  3. Preventing Child Abuse: An Evaluation of Services to High-Risk Families.

    ERIC Educational Resources Information Center

    Daro, Deborah; And Others

    In 1988 the William Penn Foundation awarded nearly $6 million to agencies in the Philadelphia (Pennsylvania) area for a variety of programs aimed at preventing child abuse. The 4 programs selected targeted parents who most needed but were least likely to have access to parent education and support services. The Foundation appointed the National…

  4. An Evaluation of the Olweus Bullying Prevention Program's Effectiveness in a High School Setting

    ERIC Educational Resources Information Center

    Losey, Raymond Alan

    2009-01-01

    An ecological approach to bullying prevention is critical for the reduction of bullying and victimization. Any intervention implemented in a school to reduce bullying should include a variety of targets on all levels of the ecology and these interventions need to be sustainable by the school following introduction of the intervention. Schools are…

  5. Using Anti-Tobacco Industry Messages to Prevent Smoking among High-Risk Adolescents

    ERIC Educational Resources Information Center

    Thrasher, James F.; Niederdeppe, Jeffrey D.; Jackson, Christine; Farrelly, Matthew C.

    2006-01-01

    Media campaigns to prevent adolescent tobacco use in the United States increasingly focus on the deceitful practices of the tobacco industry; however, little is known about how adolescents at elevated smoking risk respond to this strategy. This study used data from a nationally representative survey of 10,035 adolescents, ages 12-17 years, in…

  6. eHealth Interventions for HIV Prevention in High-Risk Men Who Have Sex With Men: A Systematic Review

    PubMed Central

    Travers, Jasmine; Rojas, Marlene; Carballo-Diéguez, Alex

    2014-01-01

    Background While the human immunodeficiency virus (HIV) incidence rate has remained steady in most groups, the overall incidence of HIV among men who have sex with men (MSM) has been steadily increasing in the United States. eHealth is a platform for health behavior change interventions and provides new opportunities for the delivery of HIV prevention messages. Objective The purpose of this systematic review was to examine the use of eHealth interventions for HIV prevention in high-risk MSM. Methods We systematically searched PubMed, OVID, ISI Web of Knowledge, Google Scholar, and Google for articles and grey literature reporting the original results of any studies related to HIV prevention in MSM and developed a standard data collection form to extract information on study characteristics and outcome data. Results In total, 13 articles met the inclusion criteria, of which five articles targeted HIV testing behaviors and eight focused on decreasing HIV risk behaviors. Interventions included Web-based education modules, text messaging (SMS, short message service), chat rooms, and social networking. The methodological quality of articles ranged from 49.4-94.6%. Wide variation in the interventions meant synthesis of the results using meta-analysis would not be appropriate. Conclusions This review shows evidence that eHealth for HIV prevention in high-risk MSM has the potential to be effective in the short term for reducing HIV risk behaviors and increasing testing rates. Given that many of these studies were short term and had other limitations, but showed strong preliminary evidence of improving outcomes, additional work needs to rigorously assess the use of eHealth strategies for HIV prevention in high-risk MSM. PMID:24862459

  7. Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Change

    DTIC Science & Technology

    2013-10-01

    for ovarian cancer. In addition, Project 5 will determine if these biomarkers and associated precursor lesions are modifiable by oral contraceptives ...3. Determine whether oral contraceptives (OCPs) and NSAIDs reduce the morphologic and molecular changes that are associated with early “ovarian... contraceptives (OCPs) or anti- inflammatory agents, as OCPs in particular are known to prevent ovarian cancer and impact survival. Research site: Johns

  8. Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration

    PubMed Central

    Mamalis, Andrew; Koo, Eugene; Isseroff, R. Rivkah; Murphy, William; Jagdeo, Jared

    2015-01-01

    Background Skin fibrosis is a significant medical problem that leads to a functional, aesthetic, and psychosocial impact on quality-of-life. Light-emitting diode-generated 633-nm red light (LED-RL) is part of the visible light spectrum that is not known to cause DNA damage and is considered a safe, non-invasive, inexpensive, and portable potential alternative to ultraviolet phototherapy that may change the treatment paradigm of fibrotic skin disease. Objective The goal of our study was to investigate the how reactive oxygen species (ROS) free radicals generated by high fluence LED-RL inhibit the migration of skin fibroblasts, the main cell type involved in skin fibrosis. Fibroblast migration speed is increased in skin fibrosis, and we studied cellular migration speed of cultured human skin fibroblasts as a surrogate measure of high fluence LED-RL effect on fibroblast function. To ascertain the inhibitory role of LED-RL generated ROS on migration speed, we hypothesized that resveratrol, a potent antioxidant, could prevent the photoinhibitory effects of high fluence LED-RL on fibroblast migration speed. Methods High fluence LED-RL generated ROS were measured by flow cytometry analysis using dihydrorhodamine (DHR). For purposes of comparison, we assessed the effects of ROS generated by hydrogen peroxide (H2O2) on fibroblast migration speed and the ability of resveratrol, a well known antioxidant, to prevent LED-RL and H2O2 generated ROS-associated changes in fibroblast migration speed. To determine whether resveratrol could prevent the high fluence LED-RL ROS-mediated photoinhibition of human skin fibroblast migration, treated cells were incubated with resveratrol at concentrations of 0.0001% and 0.001% for 24 hours, irradiated with high fluences LED-RL of 480, 640, and 800 J/cm2. Results High fluence LED-RL increases intracellular fibroblast ROS and decreases fibroblast migration speed. LED-RL at 480, 640 and 800 J/cm2 increased ROS levels to 132.8%, 151.0%, and 158

  9. The social justice roots of the Mentors in Violence Prevention model and its application in a high school setting.

    PubMed

    Katz, Jackson; Heisterkamp, H Alan; Fleming, Wm Michael

    2011-06-01

    The social justice roots and theory of the Mentors in Violence Prevention (MVP) model is presented, followed by an empirical study examining the influence of MVP in high school settings. Findings reveal students exposed to the MVP model are more likely to see forms of violence as being wrong and are more likely to take actions to intervene than students not exposed to the program. Findings support the premises on which MVP is founded.

  10. Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism.

    PubMed

    Deminice, Rafael; da Silva, Robin P; Lamarre, Simon G; Kelly, Karen B; Jacobs, René L; Brosnan, Margaret E; Brosnan, John T

    2015-04-01

    The purpose of this study was to examine the effects of betaine supplementation on the regulation of one-carbon metabolism and liver lipid accumulation induced by a high-fat diet in rats. Rats were fed one of three different liquid diets: control diet, high-fat diet and high-fat diet supplemented with betaine. The control and high-fat liquid diets contained, respectively, 35 and 71 % of energy derived from fat. Betaine supplementation involved the addition of 1 % (g/L) to the diet. After three weeks on the high-fat diet the rats had increased total liver fat concentration, liver triglycerides, liver TBARS and plasma TNF-α. The high-fat diet decreased the hepatic S-adenosylmethionine concentration and the S-adenosylmethionine/S-adenosylhomocysteine ratio compared to the control as well as altering the expression of genes involved in one-carbon metabolism. Betaine supplementation substantially increased the hepatic S-adenosylmethionine concentration (~fourfold) and prevented fatty liver and hepatic injury induced by the high-fat diet. It was accompanied by the normalization of the gene expression of BHMT, GNMT and MGAT, which code for key enzymes of one-carbon metabolism related to liver fat accumulation. In conclusion, the regulation of the expression of MGAT by betaine supplementation provides an additional and novel mechanism by which betaine supplementation regulates lipid metabolism and prevents accumulation of fat in the liver.

  11. Preventing Perinatal Depression in High Risk Women: Moving the Mothers and Babies Course from Clinical Trials to Community Implementation.

    PubMed

    Le, Huynh-Nhu; Perry, Deborah F; Mendelson, Tamar; Tandon, S Darius; Muñoz, Ricardo F

    2015-10-01

    A growing research literature highlights the public health need for preventive interventions to reduce symptoms and incidence of perinatal depression among vulnerable populations. The Mothers and Babies (MB) course is a cognitive-behavioral intervention designed to teach mood regulation skills to English- and Spanish-speaking low-income women at high risk for perinatal depression. We describe the development of the MB course and evaluate the extent to which research findings support efficacy, effectiveness, and dissemination based on the Society for Prevention Research Standards Committee's standards of evidence. Our review of research and implementation activities suggests that the MB intervention demonstrates promising evidence for efficacy in reducing depressive symptoms; empirical support for prevention of major depressive episodes is still preliminary. Work is in progress to evaluate program effectiveness and prepare for broad dissemination and implementation. The MB course shows promise as an intervention for low-income women at risk for perinatal mood issues. Spanish and English intervention materials have been developed that can be delivered in different settings (hospitals, home visiting), in different dosages (6, 8, or 12 sessions), and via different modalities (group, individual). Evaluating the MB course against current standards is intended to inform other prevention intervention development research.

  12. Maternal methyl donors supplementation during lactation prevents the hyperhomocysteinemia induced by a high-fat-sucrose intake by dams.

    PubMed

    Cordero, Paul; Milagro, Fermin I; Campion, Javier; Martinez, J Alfredo

    2013-12-16

    Maternal perinatal nutrition may program offspring metabolic features. Epigenetic regulation is one of the candidate mechanisms that may be affected by maternal dietary methyl donors intake as potential controllers of plasma homocysteine levels. Thirty-two Wistar pregnant rats were randomly assigned into four dietary groups during lactation: control, control supplemented with methyl donors, high-fat-sucrose and high-fat-sucrose supplemented with methyl donors. Physiological outcomes in the offspring were measured, including hepatic mRNA expression and global DNA methylation after weaning. The newborns whose mothers were fed the obesogenic diet were heavier longer and with a higher adiposity and intrahepatic fat content. Interestingly, increased levels of plasma homocysteine induced by the maternal high-fat-sucrose dietary intake were prevented in both sexes by maternal methyl donors supplementation. Total hepatic DNA methylation decreased in females due to maternal methyl donors administration, while Dnmt3a hepatic mRNA levels decreased accompanying the high-fat-sucrose consumption. Furthermore, a negative association between Dnmt3a liver mRNA levels and plasma homocysteine concentrations was found. Maternal high-fat-sucrose diet during lactation could program offspring obesity features, while methyl donors supplementation prevented the onset of high hyperhomocysteinemia. Maternal dietary intake also affected hepatic DNA methylation metabolism, which could be linked with the regulation of the methionine-homocysteine cycle.

  13. Maternal Methyl Donors Supplementation during Lactation Prevents the Hyperhomocysteinemia Induced by a High-Fat-Sucrose Intake by Dams

    PubMed Central

    Cordero, Paul; Milagro, Fermin I.; Campion, Javier; Martinez, J. Alfredo

    2013-01-01

    Maternal perinatal nutrition may program offspring metabolic features. Epigenetic regulation is one of the candidate mechanisms that may be affected by maternal dietary methyl donors intake as potential controllers of plasma homocysteine levels. Thirty-two Wistar pregnant rats were randomly assigned into four dietary groups during lactation: control, control supplemented with methyl donors, high-fat-sucrose and high-fat-sucrose supplemented with methyl donors. Physiological outcomes in the offspring were measured, including hepatic mRNA expression and global DNA methylation after weaning. The newborns whose mothers were fed the obesogenic diet were heavier longer and with a higher adiposity and intrahepatic fat content. Interestingly, increased levels of plasma homocysteine induced by the maternal high-fat-sucrose dietary intake were prevented in both sexes by maternal methyl donors supplementation. Total hepatic DNA methylation decreased in females due to maternal methyl donors administration, while Dnmt3a hepatic mRNA levels decreased accompanying the high-fat-sucrose consumption. Furthermore, a negative association between Dnmt3a liver mRNA levels and plasma homocysteine concentrations was found. Maternal high-fat-sucrose diet during lactation could program offspring obesity features, while methyl donors supplementation prevented the onset of high hyperhomocysteinemia. Maternal dietary intake also affected hepatic DNA methylation metabolism, which could be linked with the regulation of the methionine-homocysteine cycle. PMID:24351826

  14. Psychosocial Implications of Homophobia and HIV Stigma in Social Support Networks: Insights for High-Impact HIV Prevention among Black Men Who Have Sex with Men

    ERIC Educational Resources Information Center

    Garcia, Jonathan; Parker, Caroline; Parker, Richard G.; Wilson, Patrick A.; Philbin, Morgan; Hirsch, Jennifer S.

    2016-01-01

    Black men who have sex with men (BMSM) bear an increasingly disproportionate burden of HIV in the United States. The Centers for Disease Control and Prevention recommends high-impact combination prevention for populations at high risk for HIV infection, such as BMSM. However, few scholars have considered the types of behavioral interventions that…

  15. Arsenic ambient conditions preventing surface degradation of GaAs during capless annealing at high temperatures

    NASA Technical Reports Server (NTRS)

    Kang, C. H.; Kondo, K.; Lagowski, J.; Gatos, H. C.

    1987-01-01

    Changes in surface morphology and composition caused by capless annealing of GaAs were studied as a function of annealing temperature, T(GaAs), and the ambient arsenic pressure controlled by the temperature, T(As), of an arsenic source in the annealing ampul. It was established that any degradation of the GaAs surface morphology could be completely prevented, providing that T(As) was more than about 0.315T(GaAs) + 227 C. This empirical relationship is valid up to the melting point temperature of GaAs (1238 C), and it may be useful in some device-processing steps.

  16. Bardoxolone methyl prevents insulin resistance and the development of hepatic steatosis in mice fed a high-fat diet.

    PubMed

    Camer, Danielle; Yu, Yinghua; Szabo, Alexander; Dinh, Chi H L; Wang, Hongqin; Cheng, Licai; Huang, Xu-Feng

    2015-09-05

    High-fat (HF) diet-induced obesity is a major risk factor for the development of insulin resistance and hepatic steatosis. We examined the hypothesis that bardoxolone methyl (BM) would prevent the development of insulin resistance and hepatic steatosis in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC), HF (40% fat), or HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. Glucose metabolism was assessed using a glucose tolerance test (GTT) and insulin sensitivity test (IST). Signalling molecules involved in insulin resistance, inflammation, and lipid metabolism were examined in liver tissue via western blotting and RT-PCR. BM prevented HF diet-induced insulin resistance and alterations in the protein levels of protein tyrosine phosphatase 1B (PTP1B), forkhead box protein O1 (FOXO1) and BDNF, and expression of the insulin receptor (IR), IRS-1 and glucose-6-phosphatase (G6Pase) genes. Furthermore, BM prevented fat accumulation in the liver and decreases in the β-oxidation gene, peroxisomal acyl-coenzyme A oxidase 1 (ACOX) in mice fed a HF diet. In the livers of HF fed mice, BM administration prevented HF diet-induced macrophage infiltration, inflammation as indicated by reduced IL-6 and signal transducer and activator of transcription 3 (STAT3) protein levels and TNFα mRNA expression, and increased nuclear factor-like 2 (Nrf2) mRNA expression and nuclear protein levels. These findings suggest that BM prevents HF diet induced insulin resistance and the development of hepatic steatosis in mice fed a chronic HF diet through modulation of molecules involved in insulin signalling, lipid metabolism and inflammation in the liver.

  17. Reducing High Risk Behaviors among Street Living Youth: Outcomes of an Integrated Prevention Intervention.

    PubMed

    Carmona, Jasmin; Slesnick, Natasha; Guo, Xiamei; Letcher, Amber

    2014-08-01

    Research efforts to reduce Human Immunodeficiency Virus (HIV) risk behavior among street living youth have shown disappointing outcomes, with few studies reporting reduced risk behaviors. The current study tested the impact of an integrated HIV prevention intervention, and predictors of change, for youth (N=270) between the ages of 14 to 20 years receiving substance use treatment through a drop-in center. Condom use, HIV knowledge, number of sexual partners and behaviors associated with an overall HIV risk index were assessed at baseline, 3, 6 and 12 months post-baseline. Findings suggest that HIV prevention integrated with substance use treatment is associated with increased condom use and reduced sex partners. However, the effects on condom use were short lived and dissipated by 12 months post-baseline. Higher treatment attendance and baseline substance use predicted increased condom use. Although no significant change was observed in the overall HIV risk index, increases in depressive symptoms were associated with increases in the index score, as well as more sexual partners. Future research should determine whether successful intervention requires reinforcement of risk reduction behaviors while youth remain homeless.

  18. Waste minimization/pollution prevention study of high-priority waste streams

    SciTech Connect

    Ogle, R.B.

    1994-03-01

    Although waste minimization has been practiced by the Metals and Ceramics (M&C) Division in the past, the effort has not been uniform or formalized. To establish the groundwork for continuous improvement, the Division Director initiated a more formalized waste minimization and pollution prevention program. Formalization of the division`s pollution prevention efforts in fiscal year (FY) 1993 was initiated by a more concerted effort to determine the status of waste generation from division activities. The goal for this effort was to reduce or minimize the wastes identified as having the greatest impact on human health, the environment, and costs. Two broad categories of division wastes were identified as solid/liquid wastes and those relating to energy use (primarily electricity and steam). This report presents information on the nonradioactive solid and liquid wastes generated by division activities. More specifically, the information presented was generated by teams of M&C staff members empowered by the Division Director to study specific waste streams.

  19. Are High Proanthocyanidins Key to Cranberry Efficacy in the Prevention of Recurrent Urinary Tract Infection?

    PubMed

    Vostalova, Jitka; Vidlar, Ales; Simanek, Vilim; Galandakova, Adela; Kosina, Pavel; Vacek, Jan; Vrbkova, Jana; Zimmermann, Benno F; Ulrichova, Jitka; Student, Vladimir

    2015-10-01

    Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n = 89) or a placebo group (n = 93) and received daily 500 mg of cranberry for 6 months. The number of UTI diagnoses was counted. The intent-to-treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p = 0.04, with an age-standardized 12-month UTI history (p = 0.01)]. The Kaplan-Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p = 0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs.

  20. Prevention approaches to enhance resilience among high-risk youth: comments on the papers of Dishion & Connell and Greenberg.

    PubMed

    Kumpfer, Karol L; Summerhays, Julia Franklin

    2006-12-01

    This article synthesizes research on resilience theory and its implications for prevention interventions to increase resilience in high-risk children and adolescents. In addition, this response to both the articles by Drs. Greenberg and Dishion summarizes their key points. Their papers discuss the neuroscience substrate behind two major mediators of antisocial behaviors, namely lack of self-regulation and executive function problems. In addition, we present an overall Resilience Framework that will help the reader organize the aspects of resilience discussed by these two researchers into a transactional process model. This article extends prior researchers' suggestion that resilience is the product of the interaction of genetic, biological, and environmental precursors to a further consideration of higher-level cognitive precursors, such as purpose in life and existential meaning. The relevance of resilience to the prevention of negative outcomes in high-risk children of alcoholics (COAs) and substance abusers is covered. Within this third wave of resilience research on prevention interventions, we present data suggesting that family strengthening approaches have the greatest impact on increasing resilience.

  1. Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeated treatment with high-dose levetiracetam.

    PubMed

    Itoh, Kouichi; Inamine, Moriyoshi; Oshima, Wataru; Kotani, Masaharu; Chiba, Yoichi; Ueno, Masaki; Ishihara, Yasuhiro

    2015-05-22

    The management of status epilepticus (SE) is important to prevent mortality and the development of post-SE symptomatic epilepsy. Acquired epilepsy after an initial brain insult by SE can be experimentally reproduced in the murine model of SE induced by pilocarpine. In the present study, we evaluated the possibility of treatment with a high-dose of levetiracetam in this model. Repeated treatment with high-dose levetiracetam after termination of SE by diazepam significantly prevented the incidence of spontaneous recurrent seizures and mortality for at least 28 days. To determine the brain alterations after SE, magnetic resonance imaging was performed. Both T2-weighted imaging and diffusion-weighted imaging showed changes in the limbic regions. These changes in the limbic regions demonstrated the development of cytotoxic edema three hours after SE, followed by the development of vasogenic edema two days after SE. In the pilocarpine-SE model, the incidence of spontaneous recurrent seizures after SE was strongly associated with neuronal damage within a few hours to days after SE by the development of vasogenic edema via the breakdown of the blood-brain barrier in the limbic regions. High-dose levetiracetam significantly suppressed the parameters in the limbic areas. These data indicate that repeated treatment with high-dose levetiracetam for at least two days after SE termination by diazepam is important for controlling the neuronal damage by preventing brain edema. Therefore, these findings suggest that early treatment with high-dose levetiracetam after SE termination by diazepam may protect against adverse sequelae via the inhibition of neurotoxicity induced by brain edema events.

  2. The National Cross-Site Evaluation of High-Risk Youth Programs. Preventing Substance Abuse: Major Findings from the National Cross-Site Evaluation of High-Risk Youth Programs. Monograph Series.

    ERIC Educational Resources Information Center

    Springer, J. Fred; Sambrano, Soledad; Sale, Elizabeth; Kasim, Rafa; Herman, Jack

    This multiple-site study assessed 48 prevention programs for high-risk youth funded by the Center for Substance Abuse Prevention, identifying program characteristics associated with strong substance abuse prevention outcomes. Data analysis indicated that substance abuse programs reduced rates of substance use, and the positive effects of program…

  3. A Case Study in Communication Strategies used for Pressure Ulcer Prevention in a Nursing Home with High IT Sophistication

    PubMed Central

    Alexander, Gregory L.; Madsen, Richard

    2012-01-01

    Current strategies for improving the care of millions of elderly people living in nursing homes (NH) include the implementation of information technology (IT). Few studies exist about the implementation of NH IT although there is evidence of increasing NH IT sophistication globally. NH IT sophistication includes a measure of the maturity and diversity of IT used to support resident care, clinical support, and administration. The current paper includes a case study of 1 NH known to have high IT sophistication in the Midwestern USA. The NH was purposively selected from 185 NHs taking part in a statewide evaluation of NH IT sophistication in Missouri. This NH reported the highest IT sophistication among 185 NHs. The research aim was to explore communication strategies for evidence based pressure ulcer preventions in NH IT. Focus group and observational data were collected to assess facilitators and barriers to communicating pressure ulcer preventions. PMID:24199033

  4. High Structural Stability of Textile Implants Prevents Pore Collapse and Preserves Effective Porosity at Strain

    PubMed Central

    Klinge, Uwe; Otto, Jens; Mühl, Thomas

    2015-01-01

    Reinforcement of tissues by use of textiles is encouraged by the reduced rate of recurrent tissue dehiscence but for the price of an inflammatory and fibrotic tissue reaction to the implant. The latter mainly is affected by the size of the pores, whereas only sufficiently large pores are effective in preventing a complete scar entrapment. Comparing two different sling implants (TVT and SIS), which are used for the treatment of urinary incontinence, we can demonstrate that the measurement of the effective porosity reveals considerable differences in the textile construction. Furthermore the changes of porosity after application of a tensile load can indicate a structural instability, favouring pore collapse at stress and questioning the use for purposes that are not “tension-free.” PMID:25973427

  5. Reducing Internalizing Symptoms among High-Risk, Hispanic Adolescents: Mediators of a Preventive Family Intervention

    PubMed Central

    Perrino, Tatiana; Brincks, Ahnalee; Howe, George; Brown, C. Hendricks; Prado, Guillermo; Pantin, Hilda

    2016-01-01

    Familias Unidas is a family-focused preventive intervention that has been found to reduce drug use and sexual risk behaviors among Hispanic adolescents. In some trials, Familias Unidas has also been found to be efficacious in reducing adolescent internalizing symptoms (i.e., depressive and anxiety symptoms), even though the intervention did not specifically target internalizing symptoms. This study examines potential mediators or mechanisms by which Familias Unidas influences internalizing symptoms, specifically the role of intervention-targeted improvements in parent-adolescent communication and reductions in youth externalizing behaviors. A total of 213 Hispanic eighth grade students with a history of externalizing behavior problems and their primary caregivers were recruited from the public school system. Participants, with a mean age of 13.8 years, were randomized into the Familias Unidas intervention or community practice control condition, and assessed at baseline, 6-months, 18-months, and 30-months post-baseline. A cascading mediation model was tested in which the Familias Unidas intervention was hypothesized to decrease adolescent internalizing symptoms through two mediators: improvements in parent-adolescent communication leading to decreases in externalizing behaviors. Findings show that the intervention had significant direct effects on youth internalizing symptoms at 30-months post-baseline. In addition, the cascading mediation model was supported in which the Familias Unidas intervention predicted significant improvements in parent-adolescent communication at 6-months, subsequently decreasing externalizing behaviors at 18-months, and ultimately reducing youth internalizing symptoms at 30-months post-baseline. Implications for prevention interventions are discussed. PMID:27154768

  6. Effect of Precede-Proceed Model on Preventive Behaviors for Type 2 Diabetes Mellitus in High-Risk Individuals.

    PubMed

    Moshki, Mahdi; Dehnoalian, Atefeh; Alami, Ali

    2017-04-01

    This study sought to assess the effect of precede-proceed model on preventive behaviors for type 2 diabetes mellitus (DM) in high-risk individuals. In this semi-experimental study, 164 high-risk individuals for type 2 DM were selected and were randomly divided into two groups of intervention and control ( n = 85). Educational intervention was performed as a single session face-to-face instruction for 1.5 hr for the intervention group participants. Data were collected before (baseline) and immediately and 1 month after the intervention in the two groups. The mean score of predisposing (knowledge) factors ( p = .001), reinforcing factors ( p = .001), and enabling factors ( p = .02) were significantly different at baseline and 1 month after the intervention in the intervention group compared with the control group ( p < .05). A significant improvement occurred in the nutritional habits of high-risk participants in the intervention group at 1 month after the intervention compared with controls ( p = .001). The precede-proceed model can be effective for promoting the preventive behaviors for type 2 DM in high-risk individuals.

  7. Cinnamaldehyde supplementation prevents fasting-induced hyperphagia, lipid accumulation, and inflammation in high-fat diet-fed mice.

    PubMed

    Khare, Pragyanshu; Jagtap, Sneha; Jain, Yachna; Baboota, Ritesh K; Mangal, Priyanka; Boparai, Ravneet K; Bhutani, Kamlesh K; Sharma, Shyam S; Premkumar, Louis S; Kondepudi, Kanthi K; Chopra, Kanwaljit; Bishnoi, Mahendra

    2016-01-01

    Cinnamaldehyde, a bioactive component of cinnamon, is increasingly gaining interest for its preventive and therapeutic effects against metabolic complications like type-2 diabetes. This study is an attempt to understand the effect of cinnamaldehyde in high-fat diet (HFD)-associated increase in fasting-induced hyperphagia and related hormone levels, adipose tissue lipolysis and inflammation, and selected cecal microbial count in mice. Cinnamaldehyde, at 40 µM dose, prevented lipid accumulation and altered gene expression toward lipolytic phenotype in 3T3-L1 preadipocyte cell lines. In vivo, cinnamaldehyde coadministration prevented HFD-induced body weight gain, decreased fasting-induced hyperphagia, as well as circulating leptin and leptin/ghrelin ratio. In addition to that, cinnamaldehyde altered serum biochemical parameters related to lipolysis, that is, glycerol and free fatty acid levels. At transcriptional level, cinnamaldehyde increased anorectic gene expression in hypothalamus and lipolytic gene expression in visceral white adipose tissue. Furthermore, cinnamaldehyde also decreased serum IL-1β and inflammatory gene expression in visceral white adipose tissue. However, cinnamaldehyde did not modulate the population of selected gut microbial (Lactobacillus, Bifidibaceria, and Roseburia) count in cecal content. In conclusion, cinnamaldehyde increased adipose tissue lipolysis, decreased fasting-induced hyperphagia, normalized circulating levels of leptin/ghrelin ratio, and reduced inflammation in HFD-fed mice, which augurs well for its antiobesity role.

  8. Child sexual abuse, links to later sexual exploitation/high-risk sexual behavior, and prevention/treatment programs.

    PubMed

    Lalor, Kevin; McElvaney, Rosaleen

    2010-10-01

    This paper reviews the literature on the nature and incidence of child sexual abuse, explores the link between child sexual abuse and later sexual exploitation, and reviews the literature on prevention strategies and effective interventions in child sexual abuse services. Our understanding of the international epidemiology of child sexual abuse is considerably greater than it was just 10 years ago, and studies from around the world are examined. Childhood sexual abuse can involve a wide number of psychological sequelae, including low self-esteem, anxiety, and depression. Numerous studies have noted that child sexual abuse victims are vulnerable to later sexual revictimization, as well as the link between child sexual abuse and later engagement in high-risk sexual behaviour. Survivors of child sexual abuse are more likely to have multiple sex partners, become pregnant as teenagers, and experience sexual assault as adults. Various models which attempt to account for this inter-relationship are presented; most invoke mediating variables such as low self-esteem, drug/alcohol use, PTSD and distorted sexual development. Prevention strategies for child sexual abuse are examined including media campaigns, school-based prevention programmes, and therapy with abusers. The results of a number of meta-analyses are examined. However, researchers have identified significant methodological limitations in the extant research literature that impede the making of recommendations for implementing existing therapeutic programmes unreservedly.

  9. Does High Alveolar Fluid Reabsorption Prevent HAPE in Individuals with Exaggerated Pulmonary Hypertension in Hypoxia?

    PubMed

    Betz, Theresa; Dehnert, Christoph; Bärtsch, Peter; Schommer, Kai; Mairbäurl, Heimo

    2015-12-01

    An exaggerated increase in pulmonary arterial systolic pressure (PAsP) is a highlight of high altitude pulmonary edema (HAPE). However, the incidence of HAPE at 4559 m was much lower in altitude-naïve individuals with exaggerated pulmonary vasoconstriction (HPV) in normobaric hypoxia than in known HAPE-susceptibles, indicating that elevated PAsP alone is insufficient to induce HAPE. A decreased nasal potential difference (NPD) has been found in HAPE-susceptibles, where, based on animal models, NPD serves as surrogate of alveolar epithelial ion transport. We hypothesize that those HAPE-resistant individuals with high HPV may be protected by elevated alveolar Na and fluid reabsorption, which might be detected as increased NPD. To test this hypothesis, we measured NPD in normoxia of subjects who were phenotyped in previous studies as high altitude tolerant (controls), known HAPE-susceptibles with high HPV (HP+HAPE), as well as individuals with high HPV but without HAPE (HP-no-HAPE) at 4559 m. NPD and amiloride-sensitive NPD were lower in HP+HAPE than in controls, whereas HP-no-HAPE were not different from either group. There were no differences in Cl-transport between groups. Our results show low nasal ion transport in HAPE but higher transport in those individuals with the highest HPV but without HAPE. This indicates that in some individuals with high PAsP at high altitude high alveolar fluid reabsorption might protect them from HAPE.

  10. A Study of Prevention and Retention Strategies for Successful Urban Secondary High School Hispanic Students

    ERIC Educational Resources Information Center

    Lopez, Roberto Ibarra

    2013-01-01

    Hispanic high school students have a dropout rate that ranges from 35 percent to 55 percent depending on what type of report you may be referencing. Add rates for all high school students. Hispanic youth endure the challenges of language barriers, single parent households, working to help their family, or fighting off gang involvement in their…

  11. Intestinal CX3C chemokine receptor 1high (CX3CR1high) myeloid cells prevent T-cell-dependent colitis

    PubMed Central

    Kayama, Hisako; Ueda, Yoshiyasu; Sawa, Yukihisa; Jeon, Seong Gyu; Ma, Ji Su; Okumura, Ryu; Kubo, Atsuko; Ishii, Masaru; Okazaki, Taku; Murakami, Masaaki; Yamamoto, Masahiro; Yagita, Hideo; Takeda, Kiyoshi

    2012-01-01

    Adequate activation of CD4+ T lymphocytes is essential for host defense against invading pathogens; however, exaggerated activity of effector CD4+ T cells induces tissue damage, leading to inflammatory disorders such as inflammatory bowel diseases. Several unique subsets of intestinal innate immune cells have been identified. However, the direct involvement of innate immune cell subsets in the suppression of T-cell-dependent intestinal inflammation is poorly understood. Here, we report that intestinal CX3C chemokine receptor 1high (CX3CR1high) CD11b+ CD11c+ cells are responsible for prevention of intestinal inflammation through inhibition of T-cell responses. These cells inhibit CD4+ T-cell proliferation in a cell contact-dependent manner and prevent T-cell-dependent colitis. The suppressive activity is abrogated in the absence of the IL-10/Stat3 pathway. These cells inhibit T-cell proliferation by two steps. Initially, CX3CR1high CD11b+ CD11c+ cells preferentially interact with T cells through highly expressed intercellular adhesion molecule-1/vascular cell adhesion molecule-1; then, they fail to activate T cells because of defective expression of CD80/CD86. The IL-10/Stat3 pathway mediates the reduction of CD80/CD86 expression. Transfer of wild-type CX3CR1high CD11b+ CD11c+ cells prevents development of colitis in myeloid-specific Stat3-deficient mice. Thus, these cells are regulatory myeloid cells that are responsible for maintaining intestinal homeostasis. PMID:22403066

  12. Intestinal CX3C chemokine receptor 1(high) (CX3CR1(high)) myeloid cells prevent T-cell-dependent colitis.

    PubMed

    Kayama, Hisako; Ueda, Yoshiyasu; Sawa, Yukihisa; Jeon, Seong Gyu; Ma, Ji Su; Okumura, Ryu; Kubo, Atsuko; Ishii, Masaru; Okazaki, Taku; Murakami, Masaaki; Yamamoto, Masahiro; Yagita, Hideo; Takeda, Kiyoshi

    2012-03-27

    Adequate activation of CD4(+) T lymphocytes is essential for host defense against invading pathogens; however, exaggerated activity of effector CD4(+) T cells induces tissue damage, leading to inflammatory disorders such as inflammatory bowel diseases. Several unique subsets of intestinal innate immune cells have been identified. However, the direct involvement of innate immune cell subsets in the suppression of T-cell-dependent intestinal inflammation is poorly understood. Here, we report that intestinal CX(3)C chemokine receptor 1(high) (CX(3)CR1(high)) CD11b(+) CD11c(+) cells are responsible for prevention of intestinal inflammation through inhibition of T-cell responses. These cells inhibit CD4(+) T-cell proliferation in a cell contact-dependent manner and prevent T-cell-dependent colitis. The suppressive activity is abrogated in the absence of the IL-10/Stat3 pathway. These cells inhibit T-cell proliferation by two steps. Initially, CX(3)CR1(high) CD11b(+) CD11c(+) cells preferentially interact with T cells through highly expressed intercellular adhesion molecule-1/vascular cell adhesion molecule-1; then, they fail to activate T cells because of defective expression of CD80/CD86. The IL-10/Stat3 pathway mediates the reduction of CD80/CD86 expression. Transfer of wild-type CX(3)CR1(high) CD11b(+) CD11c(+) cells prevents development of colitis in myeloid-specific Stat3-deficient mice. Thus, these cells are regulatory myeloid cells that are responsible for maintaining intestinal homeostasis.

  13. Preventive effects of taurine on development of hepatic steatosis induced by a high-fat/cholesterol dietary habit.

    PubMed

    Chang, Yuan-Yen; Chou, Chung-Hsi; Chiu, Chih-Hsien; Yang, Kuo-Tai; Lin, Yi-Ling; Weng, Wei-Lien; Chen, Yi-Chen

    2011-01-12

    Nonalcoholic fatty liver (NAFL) is also called hepatic steatosis and has become an emergent liver disease in developed and developing nations. This study was to exam the preventive effects of taurine (Tau) on the development of hepatic steatosis via a hamster model. Although hepatic steatosis of hamsters was induced by feeding a high-fat/cholesterol diet, drinking water containing 0.35 and 0.7% Tau improved (p < 0.05) the serum lipid profile. Meanwhile, the smaller (p < 0.05) liver sizes and lower (p < 0.05) hepatic lipids in high-fat/cholesterol dietary hamsters drinking Tau may be partially due to higher (p < 0.05) fecal cholesterol, triacylglycerol, and bile acid outputs. In the regulation of lipid homeostasis, drinking a Tau solution upregulated (p < 0.05) low-density lipoprotein receptor and CYP7A1 gene expressions in high-fat/cholesterol dietary hamsters, which result in increased fecal cholesterol and bile acid outputs. Drinking a Tau solution also upregulated (p < 0.05) peroxisome proliferator-activated receptor-α (PPAR-α) and uncoupling protein 2 (UPC2) gene expressions in high-fat/cholesterol dietary hamsters, thus increasing energy expenditure. Besides, Tau also enhanced (p < 0.05) liver antioxidant capacities (GSH, TEAC, SOD, and CAT) and decreased (p < 0.05) lipid peroxidation (MDA), which alleviated liver damage in the high-fat/cholesterol dietary hamsters. Therefore, Tau shows preventive effects on the development of hepatic steatosis induced by a high-fat/cholesterol dietary habit.

  14. High-Dose Viscum album Extract Treatment in the Prevention of Recurrent Bladder Cancer: A Retrospective Case Series

    PubMed Central

    von Schoen-Angerer, Tido; Wilkens, Johannes; Kienle, Gunver S; Kiene, Helmut; Vagedes, Jan

    2015-01-01

    Introduction: Viscum album extract (European mistletoe), containing immuno-active compounds with dose-dependent cytotoxic activity, is being used as an adjuvant cancer treatment in Europe. Few studies have yet been done with high-dose, fever-inducing Viscum album treatment. Objective: To explore whether subcutaneous injections of high-dose Viscum album have a preventive effect on risk of recurrence of bladder cancer. Methods: We retrospectively analyzed the case records of patients with resectable bladder cancer who underwent initiation of high-dose Viscum album treatment at our clinic between January 2006 and December 2012. Main Outcome Measures: We calculated tumor recurrence and progression risk and explored case records to assess whether treatment had a likely, possible, or unlikely beneficial effect. Results: Eight patients were identified, 7 of whom had nonmuscle-invasive bladder cancer and 1 with muscle-invasive cancer. Four patients had frequently recurring tumors before treatment. Among the 8 patients, 28 episodes of recurrence were observed. Median tumor-free follow-up duration was 48.5 months. High-dose Viscum album showed a possible beneficial effect in 5 of 8 patients, could not be assessed in 2 patients, and had an uncertain effect in 1 patient. No tumor progression was observed. Treatment was generally well tolerated and no patient stopped treatment because of side effects. Conclusion: High-dose Viscum album treatment may have interrupted frequently recurring tumors in individual patients with recurrent bladder cancer. Prospective studies are needed to assess whether this treatment offers an additional, bladder-sparing preventive option for patients with intermediate- to high-risk nonmuscleinvasive bladder cancer. PMID:26517439

  15. Efficacy Trial of a Brief Cognitive-Behavioral Depression Prevention Program for High-Risk Adolescents: Effects at 1- and 2-Year Follow-Up

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Gau, Jeff M.; Wade, Emily

    2010-01-01

    Objective: To evaluate the effects of a brief group cognitive-behavioral (CB) depression prevention program for high-risk adolescents with elevated depressive symptoms at 1- and 2-year follow-up. Method: In this indicated prevention trial, 341 at-risk youths were randomized to a group CB intervention, group supportive expressive intervention, CB…

  16. Pediatric burn injuries from day-old campfires: a highly morbid and preventable problem.

    PubMed

    Antonoff, Mara B; Abbott, Andrea M; Rood, Jody; Mohr, Wm J

    2011-01-01

    The purpose of this study was to review the authors' experience with pediatric burns from day-old campfires. The authors sought to characterize the operative courses, hospitalizations, and complications arising from burn injuries in this patient population. After Institutional Review Board approval, charts were retrospectively reviewed of pediatric patients seeking care for burn injuries at a regional burn center over 6 years. From June 2002 to September 2008, 30 pediatric patients sought care for burn injuries sustained in campfires; 25 (83.3%) of these occurred in fire pits with previously extinguished fires; 68% were male, with median age of 2.0 years (range, 14 months to 17 years). The median TBSA burned was 2% (range, 1-40%). The most common burn locations were hand (68%), forearm (28%), and foot (24%). Additional locations included back, arm, abdomen, and thigh. Eighteen patients (72%) required hospital admission; among these patients, mean number of hospitalizations was 1.3 (range, 1-2) and mean length of stay was 5 days (range, 1-22 days). This group accounted for 23 admissions, 96 hospital days, 3 intensive care unit days, 16 operations under general anesthesia, and 30 procedural sedations/dressing changes under anesthesia. Operative procedures included 9 full-thickness skin grafts, 13 split-thickness skin grafts, 2 escharotomies, and 1 amputation. Complications included one death (4%), one graft loss (4%), two cellulitis (8%), and four scar hypertrophies (16%). Day-old campfires may cause significant burns in the pediatric population, resulting in considerable short- and long-term morbidities and utilization of health care resources. Our experience with this patient population lends justification for campaigns aimed to prevent such injuries.

  17. High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

    PubMed Central

    Hathaway, Catherine K.; Chang, Albert S.; Grant, Ruriko; Kim, Hyung-Suk; Madden, Victoria J.; Bagnell, C. Robert; Jennette, J. Charles; Smithies, Oliver; Kakoki, Masao

    2016-01-01

    Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2Akita gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease. PMID:26858454

  18. Remote ischemic preconditioning for prevention of high-altitude diseases: fact or fiction?

    PubMed

    Berger, Marc Moritz; Macholz, Franziska; Mairbäurl, Heimo; Bärtsch, Peter

    2015-11-15

    Preconditioning refers to exposure to brief episodes of potentially adverse stimuli and protects against injury during subsequent exposures. This was first described in the heart, where episodes of ischemia/reperfusion render the myocardium resistant to subsequent ischemic injury, which is likely caused by reactive oxygen species (ROS) and proinflammatory processes. Protection of the heart was also found when preconditioning was performed in an organ different from the target, which is called remote ischemic preconditioning (RIPC). The mechanisms causing protection seem to include stimulation of nitric oxide (NO) synthase, increase in antioxidant enzymes, and downregulation of proinflammatory cytokines. These pathways are also thought to play a role in high-altitude diseases: high-altitude pulmonary edema (HAPE) is associated with decreased bioavailability of NO and increased generation of ROS, whereas mechanisms causing acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) seem to involve cytotoxic effects by ROS and inflammation. Based on these apparent similarities between ischemic damage and AMS, HACE, and HAPE, it is reasonable to assume that RIPC might be protective and improve altitude tolerance. In studies addressing high-altitude/hypoxia tolerance, RIPC has been shown to decrease pulmonary arterial systolic pressure in normobaric hypoxia (13% O2) and at high altitude (4,342 m). Our own results indicate that RIPC transiently decreases the severity of AMS at 12% O2. Thus preliminary studies show some benefit, but clearly, further experiments to establish the efficacy and potential mechanism of RIPC are needed.

  19. Second generation tyrosine kinase inhibitors prevent disease progression in high-risk (high CIP2A) chronic myeloid leukaemia patients.

    PubMed

    Lucas, C M; Harris, R J; Holcroft, A K; Scott, L J; Carmell, N; McDonald, E; Polydoros, F; Clark, R E

    2015-07-01

    High cancerous inhibitor of PP2A (CIP2A) protein levels at diagnosis of chronic myeloid leukaemia (CML) are predictive of disease progression in imatinib-treated patients. It is not known whether this is true in patients treated with second generation tyrosine kinase inhibitors (2G TKI) from diagnosis, and whether 2G TKIs modulate the CIP2A pathway. Here, we show that patients with high diagnostic CIP2A levels who receive a 2G TKI do not progress, unlike those treated with imatinib (P=<0.0001). 2G TKIs induce more potent suppression of CIP2A and c-Myc than imatinib. The transcription factor E2F1 is elevated in high CIP2A patients and following 1 month of in vivo treatment 2G TKIs suppress E2F1 and reduce CIP2A; these effects are not seen with imatinib. Silencing of CIP2A, c-Myc or E2F1 in K562 cells or CML CD34+ cells reactivates PP2A leading to BCR-ABL suppression. CIP2A increases proliferation and this is only reduced by 2G TKIs. Patients with high CIP2A levels should be offered 2G TKI treatment in preference to imatinib. 2G TKIs disrupt the CIP2A/c-Myc/E2F1 positive feedback loop, leading to lower disease progression risk. The data supports the view that CIP2A inhibits PP2Ac, stabilising E2F1, creating a CIP2A/c-Myc/E2F1 positive feedback loop, which imatinib cannot overcome.

  20. A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia

    PubMed Central

    Zabul, Piotr; Wozniak, Michal; Slominski, Andrzej T.; Preis, Krzysztof; Gorska, Magdalena; Korozan, Marek; Wieruszewski, Jan; Zmijewski, Michal A.; Zabul, Ewa; Tuckey, Robert; Kuban-Jankowska, Alicja; Mickiewicz, Wieslawa; Knap, Narcyz

    2015-01-01

    A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F2t-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia. PMID:26068234

  1. Men as Allies: The Efficacy of a High School Rape Prevention Intervention

    ERIC Educational Resources Information Center

    Hillenbrand-Gunn, Theresa L.; Heppner, Mary J.; Mauch, Pamela A.; Park, Hyun-joo

    2010-01-01

    This study investigated the effects of a Men as Allies--based intervention on high school students' rape-supportive attitudes and behaviors. As hypothesized at posttest, the male and female experimental groups demonstrated a significant decrease in rape-supportive attitudes, which was maintained at follow-up. Male participants viewed peers'…

  2. Preventing Substance Use among High School Athletes: The ATLAS and ATHENA Programs

    ERIC Educational Resources Information Center

    Goldberg, Linn; Eliot, Diane

    2005-01-01

    This article will provide information about two worthwhile programs that deal with education of high school athletes about use and abuse of steroids and other areas. Based on rationale and expressed need, program descriptions will be provided including summaries of relevant program results. Guidelines for what practitioners need to consider when…

  3. Afterschool: A High School Dropout Prevention Tool. Afterschool Alert Issue Brief No.38

    ERIC Educational Resources Information Center

    Afterschool Alliance, 2009

    2009-01-01

    Over one million students who enter ninth grade each year fail to graduate with their peers four years later because they drop out of school. Seven thousand students drop out of school every day, and each year roughly 1.2 million students fail to graduate from high school. More than half of these students are from minority groups. Afterschool …

  4. High saturated fat feeding prevents left ventricular dysfunction and enhances mitochondrial function in heart failure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulation of lipids in the heart is associated with contractile dysfunction, and has been proposed to be a causative factor in mitochondrial dysfunction. We have previously shown that administration of a high saturated fat diet in heart failure (HF) increased mitochondrial respiration and ETC com...

  5. Web-Based Media Literacy to Prevent Tobacco Use among High School Students

    ERIC Educational Resources Information Center

    Phelps-Tschang, Jane S.; Miller, Elizabeth; Rice, Kristen; Primack, Brian A.

    2015-01-01

    Facilitator-led smoking media literacy (SML) programs have improved media literacy and reduced intention to smoke. However, these programs face limitations including high costs and barriers to standardization. We examined the efficacy of a Web-based media literacy program in improving smoking media literacy skills among adolescents. Sixty-six 9th…

  6. Global expansion of high pathogenicity avian influenza: implications on prevention and control programs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The H5N1 high pathogenicity avian influenza (HPAI) virus emerged in China during 1996 and has spread to infect poultry and/or wild birds in 63 countries during the past 18 years. The majority of the recent outbreaks of H5N1 HPAI have occurred in Indonesia, Egypt, Vietnam, and Bangladesh, in decreas...

  7. Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

  8. Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Changes

    DTIC Science & Technology

    2014-10-01

    that i) reproductive hormone signaling is altered in HGSC, that ii) reproductive hormone receptor status (ERα/PR) may be an important indicator of...microenvironment ovulatory stresses, which may include altered reproductive hormone levels and the ovulatory inflammatory response. The...inflammatory response and altered reproductive hormone physiology. Keywords: BRCA, fallopian tube epithelium, high-grade serous carcinoma INTRODUCTION In 2013

  9. Acquaintance Rape Prevention with High-Risk Women: Identification and Inoculation.

    ERIC Educational Resources Information Center

    Himelein, Melissa J.

    1999-01-01

    Reasons are presented why rape education programming for women who have been sexually victimized may need to be different and separate from general programming. A process for identifying high-risk women is described. "Inoculation," a counseling group process, is described. Evaluation, feedback, and recommendations are reported. (EMK)

  10. Global expansion of high pathogenicity avian influenza: implications on prevention and control programs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The H5N1 high pathogenicity avian influenza (HPAI) virus emerged in China during 1996 and has spread to infect poultry and/or wild birds in 63 countries during the past 18 years. The majority of the recent outbreaks of H5N1 HPAI have occurred in Indonesia, Egypt, Vietnam, and Bangladesh, in decreasi...

  11. Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity.

    PubMed

    Kooptiwut, Suwattanee; Hanchang, Wanthanee; Semprasert, Namoiy; Junking, Mutita; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

    2015-03-01

    Hypogonadism in men is associated with an increased incidence of type 2 diabetes. Supplementation with testosterone has been shown to protect pancreatic β-cell against apoptosis due to toxic substances including streptozotocin and high glucose. One of the pathological mechanisms of glucose-induced pancreatic β-cell apoptosis is the induction of the local rennin-angiotensin-aldosterone system (RAAS). The role of testosterone in regulation of the pancreatic RAAS is still unknown. This study aims to investigate the protective action of testosterone against glucotoxicity-induced pancreatic β-cell apoptosis via alteration of the pancreatic RAAS pathway. Rat insulinoma cell line (INS-1) cells or isolated male mouse islets were cultured in basal and high-glucose media in the presence or absence of testosterone, losartan, and angiotensin II (Ang II), then cell apoptosis, cleaved caspase 3 expression, oxidative stress, and expression of angiotensin II type 1 receptor (AGTR1) and p47(phox) mRNA and protein were measured. Testosterone and losartan showed similar effects in reducing pancreatic β-cell apoptosis. Testosterone significantly reduced expression of AGTR1 protein in INS-1 cells cultured in high-glucose medium or high-glucose medium with Ang II. Testosterone decreased the expression of AGTR1 and p47(phox) mRNA and protein in comparison with levels in cells cultured in high-glucose medium alone. Furthermore, testosterone attenuated superoxide production when co-cultured with high-glucose medium. In contrast, when cultured in basal glucose, supplementation of testosterone did not have any effect on cell apoptosis, oxidative stress, and expression of AGT1R and p47(phox). In addition, high-glucose medium did not increase cleaved caspase 3 in AGTR1 knockdown experiments. Thus, our results indicated that testosterone prevents pancreatic β-cell apoptosis due to glucotoxicity through reduction of the expression of ATGR1 and its signaling pathway.

  12. Effect of fluoride varnish on caries prevention of partially erupted of permanent molar in high caries risk.

    PubMed

    Suwansingha, Orawan; Rirattanapong, Praphasri

    2012-05-01

    The objective of this study was to measure the effectiveness of fluoride varnish as a public health intervention to prevent caries on partially erupted first and second permanent molars among 6-11 year old children at high risk for caries. In a six-month clinical trial, 105 children were randomly divided into a fluoride varnish (Duraphat) group (117 molars) or a control group (117 molars). The chi-square test used to compare caries occurrence in each group with a 95% level of confidence (p<0.05) at the intervals of 3 months. Compared to control, fluoride varnish resulted in 79% and 77.5% caries reduction in partially erupted permanent molars at 3 and 6 months, respectively. There were statistically significant differences in caries progression between the groups at 3 and 6 months. Fluoride varnish significantly reduced carious lesions in partially erupted molars at six months among high caries risk children.

  13. High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.

    PubMed

    Akiyama, Hiroki; Takase, Hiroshi; Kubo, Fumito; Miki, Tohru; Yamamoto, Masahide; Tomita, Makoto; Mochizuki, Manabu; Miura, Osamu; Arai, Ayako

    2016-10-01

    In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m(2) ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).

  14. High-risk behaviors among adult men and women in Botswana: implications for HIV/AIDS prevention efforts.

    PubMed

    Keetile, Mpho

    2014-01-01

    The government of Botswana has been spending a lot of money in the prevention, treatment, care and support for HIV/AIDS patient for decades. This paper uses data from the third Botswana AIDS Impact Survey (BAIS III) to explore high-risk behaviors of adults and how they affect government efforts to stop the spread of HIV/AIDS. The objective of this paper is to fill in the gap on the assessment of high-risk behaviors associated with HIV/AIDS and their implications on HIV/AIDS prevention efforts. A nationally representative sample of 10,159 men and women aged 20-64 years who had successfully completed the BAIS III individual questionnaire were used in the study. Both descriptive and binary logistic regression analyses were used for analysis. Crude odds ratios were obtained from gross effects model while adjusted odds ratios (AOR) were obtained from the net effects model. Statistically significant association was observed between multiple current partners and alcohol consumption (AOR = 1.5), drug abuse (AOR = 1.7), transactional sex (AOR = 2.6) and intergenerational sex (AOR = 1.07). Furthermore, statistically significant association was seen for inconsistent condom use and having tested for HIV (AOR = 1.5). These results show a worrying tendency that despite government's efforts to stop the spread of HIV/AIDS, adults in Botswana continue to indulge in high-risk behaviors. Therefore, any programs and policies on HIV/AIDS should first target these high-risk behaviors.

  15. Source segregation and food waste prevention activities in high-density households in a deprived urban area

    SciTech Connect

    Rispo, A.; Williams, I.D. Shaw, P.J.

    2015-10-15

    Highlights: • Study of waste management in economically and socially deprived high-density housing. • Food waste segregation, prevention and recycling activities investigated. • Study involved a waste audit and household survey of 1034 households. • Populations in such areas are “hard-to-reach”. • Exceptional efforts and additional resources are required to improve performance. - Abstract: A waste audit and a household questionnaire survey were conducted in high-density housing estates in one of the most economically and socially deprived areas of England (Haringey, London). Such areas are under-represented in published research. The study examined source segregation, potential participation in a food waste segregation scheme, and food waste prevention activities in five estates (1034 households). The results showed that: contamination of recyclables containers was low; ca. 28% of the mixed residual waste’s weight was recyclable; food waste comprised a small proportion of the waste from these residents, probably because of their relatively disadvantaged economic circumstances; and the recycling profile reflected an intermittent pattern of behaviour. Although the majority of respondents reported that they would participate in a food waste separation scheme, the response rate was low and many responses of “don’t know” were recorded. Municipalities committed to foster improved diversion from landfill need to recognise that there is no “quick and easy fix”, regardless of local or national aspirations. Lasting and sustained behaviour change requires time and the quality of service provision and associated infrastructure play a fundamental role in facilitating residents to participate effectively in waste management activities that maximise capture of source-segregated materials. Populations in deprived areas that reside in high-rise, high-density dwellings are “hard-to-reach” in terms of participation in recycling schemes and exceptional

  16. Heat Stress and Injury Prevention Practices During Summer High School Football Training in South Texas.

    PubMed

    Hearon, Christopher M; Ruiz, Alberto; Taylor, Zachary J

    The purpose was to describe practice conditions influencing the risk of heat stress to athletes in summer football training in South Texas high schools, and to compare these conditions to ACSM recommendations for heat stress/injury risk reduction in this population. Thirty (N=30) high school summer football practices were observed. Wet bulb globe temperature (WBGT) was measured before/after practices and practices were observed for: duration/structure; athlete clothing; and rest break frequency/duration/content. Practices averaged 125±31 min and WBGT (pre- to post-practice) was 29.7±2.1°C to 31.2±2.2°C for morning, and 31.2±1.6°C to 28.9±1.2°C for evening practices. Most practices included contact (93%), and a majority were full-contact (53%). Most athletes wore full pads (83%) and medium/dark colored clothing (73%). Outside of scheduled breaks athletes removed helmets (63%), sat/knelt (63%), and had access to fluid (90%). Athletic trainers were present at 93% of the practices. A typical practice had 3 rest breaks, each lasting approximately 5 min. During breaks, athletes were provided fluid (93%), removed helmets (89%), and sat/knelt (76%), but were rarely provided shade (2%). While none of the practice sessions were conducted in conditions warranting the cancellation of outside activity (WBGT>33.1°C), the environmental data confirms that this region presents athletes with a very high risk of heat stress/injury. While a majority of the schools were taking many of the precautionary measures recommended by ACSM, many of the guidelines were not being followed. Governing bodies of high school athletics need to encourage compliance with recommendations for the reduction of heat stress/injury in this population.

  17. A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation.

    PubMed

    Ho, Victor W; Leung, Kelvin; Hsu, Anderson; Luk, Beryl; Lai, June; Shen, Sung Yuan; Minchinton, Andrew I; Waterhouse, Dawn; Bally, Marcel B; Lin, Wendy; Nelson, Brad H; Sly, Laura M; Krystal, Gerald

    2011-07-01

    Since cancer cells depend on glucose more than normal cells, we compared the effects of low carbohydrate (CHO) diets to a Western diet on the growth rate of tumors in mice. To avoid caloric restriction-induced effects, we designed the low CHO diets isocaloric with the Western diet by increasing protein rather than fat levels because of the reported tumor-promoting effects of high fat and the immune-stimulating effects of high protein. We found that both murine and human carcinomas grew slower in mice on diets containing low amylose CHO and high protein compared with a Western diet characterized by relatively high CHO and low protein. There was no weight difference between the tumor-bearing mice on the low CHO or Western diets. Additionally, the low CHO-fed mice exhibited lower blood glucose, insulin, and lactate levels. Additive antitumor effects with the low CHO diets were observed with the mTOR inhibitor CCI-779 and especially with the COX-2 inhibitor Celebrex, a potent anti-inflammatory drug. Strikingly, in a genetically engineered mouse model of HER-2/neu-induced mammary cancer, tumor penetrance in mice on a Western diet was nearly 50% by the age of 1 year whereas no tumors were detected in mice on the low CHO diet. This difference was associated with weight gains in mice on the Western diet not observed in mice on the low CHO diet. Moreover, whereas only 1 mouse on the Western diet achieved a normal life span, due to cancer-associated deaths, more than 50% of the mice on the low CHO diet reached or exceeded the normal life span. Taken together, our findings offer a compelling preclinical illustration of the ability of a low CHO diet in not only restricting weight gain but also cancer development and progression.

  18. Prevention and control of highly pathogenic avian influenza with particular reference to H5N1.

    PubMed

    Capua, Ilaria; Cattoli, Giovanni

    2013-12-05

    Highly pathogenic avian influenza viruses of the H5N1 subtype emerged in Far East Asia in 1996 and spread in three continents in a period of 10 or less years. Before this event, avian influenza infections caused by highly pathogenic viruses had occurred in many different countries, causing minor or major outbreaks, and had always been eradicated. The unique features of these H5N1 viruses combined to the geographic characteristics of the area of emergence, including animal husbandry practices, has caused this subtype to become endemic in several Asian countries, as well as in Egypt. Our aim is to review the direct and indirect control strategies with the rationale for use, advantages and shortcomings - particularly resulting from practicalities linked to field application and economic constraints. Certainly, in low income countries which have applied vaccination, this has resulted in a failure to eradicate the infection. Although the number of infected countries has dropped from over 40 (2006) to under 10 (2012), the extensive circulation of H5N1 in areas with high poultry density still represents a risk for public and animal health.

  19. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    PubMed Central

    Day, Troy; Read, Andrew F.

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

  20. An educational programme on dengue fever prevention and control for females in Jeddah high schools.

    PubMed

    Ibrahim, N K; Abalkhail, B; Rady, M; Al-Bar, H

    2009-01-01

    A mass communication campaign was conducted at 20 randomly selected female high schools and 2 school supervision centres in Jeddah to improve knowledge, attitudes and practices of students, teachers and supervisors about dengue fever. A total of 5977 pre- and post-intervention questionnaires were completed and the intervention was conducted using lectures and audiovisual aids. A marked improvement in all areas of knowledge, attitudes and practices was observed after the programme in all groups. Students obtained the highest improvement in mean knowledge scores after the programme compared to the other 2 groups. There is a need to expand such programmes to all Jeddah schools.

  1. Health benefits of high-density lipoproteins in preventing cardiovascular diseases.

    PubMed

    Berrougui, Hicham; Momo, Claudia N; Khalil, Abdelouahed

    2012-01-01

    Plasma levels of high-density lipoprotein (HDL) are strongly and inversely correlated with atherosclerotic cardiovascular diseases. However, it is becoming clear that a functional HDL is a more desirable target than simply increasing HDL-cholesterol levels. The best known antiatherogenic function of HDL particles relates to their ability to promote reverse cholesterol transport from peripheral cells. However, HDL also possesses antioxidant, anti-inflammatory, and antithrombotic effects. This review focuses on the state of knowledge regarding assays of HDL heterogeneity and function and their relationship to cardiovascular diseases.

  2. Classroom Goal Structures and HIV/Pregnancy Prevention Education in Rural High School Health Classrooms

    PubMed Central

    Anderman, Eric M.; Cupp, Pamela K.; Lane, Derek R.; Zimmerman, Rick; Gray, DeLeon L.; O'Connell, Ann

    2011-01-01

    Over 5,000 adolescents enrolled in required rural high school health courses reported their perceptions of mastery and extrinsic goal structures in their health classrooms. Data were collected from all students at three time points (prior to HIV/pregnancy instruction, three months after instruction, and one year after instruction). Results indicated that classroom goal structures were related to both proximal and distal knowledge, attitudes, intentions, and efficacy beliefs. Results in particular indicate that the perception of a mastery goal structure in health education classrooms fosters knowledge, improved attitudes, enhanced efficacy beliefs, and lower intentions to have sexual intercourse. PMID:24876759

  3. Prevention of Ovarian High Grade Serous Carcinoma by Elucidating Its Early Changes

    DTIC Science & Technology

    2015-10-01

    in the female reproductive tract (Fig. 1A). The tumor weight was measured in 6 to 12 weeks of age which shows statistical difference in 12 weeks of...compared to FTE from normal control specimens and use an in vitro system and a mouse model to generate a molecularly defined carcinoma resembling HGSC from...normal FTE from high-risk women compared to FTE from normal control specimens and use an in vitro system and a mouse model to generate a molecularly

  4. Periparturient stress and immune suppression as a potential cause of retained placenta in highly productive dairy cows: examples of prevention.

    PubMed

    Mordak, Ryszard; Stewart, Peter Anthony; Anthony, Stewart Peter

    2015-12-02

    The immune system during the periparturient period is impaired. At this time the most important factor causing immune-suppression in highly productive cows is metabolic stress resulting from hormonal and metabolic fluctuations, a negative energy balance, shortage of proteins, minerals and vitamins which are required to meet the demands of the fetus as well as the onset of lactation. This stress can activate the hypothalamic-pituitary-adrenocortical axis (HPA), which results in increase plasma corticosteroids. As a result, the cortisol concentration during the periparturient period increases by several folds particularly on the day of calving. Cortisol is a powerful immune-suppressive agent. During stress, this hormone causes depression of the leukocyte proliferation and their functions. Decreased phagocytosis of neutrophils, decreased cytotoxic ability of lymphocytes, as well as depressed activity of their cytokines, make it impossible for the normal, efficient maternal immune recognition and rejection of fetal membranes (as a foreign, allogeneic tissue expressed fetal antigens-MHC class I proteins by trophoblast cells) and finally results in their retention in cows. The metabolic periparturient stress also activates production of catecholamines, especially adrenalin. Adrenalin activates adrenoreceptors of the myometrium and then causes hypotony or atony of the uterus. Thus, cortisol and adrenalin inhibit rejection and expulsion of fetal membranes and cause their retention. These mechanisms of retained placenta (RP) often have a metabolic etiology and occur in herds, where important infectious diseases causing placentitis are absent or prevented. The aim of this article is to show the fundamental mechanisms occurring during periparturient stress and the accompanied immune-suppression in cows, as well as their consequences in relation to RP. The paper also gives examples of the symptomatic prevention of RP in cows caused by metabolic and immune suppressive factors

  5. Lingonberries alter the gut microbiota and prevent low-grade inflammation in high-fat diet fed mice

    PubMed Central

    Heyman-Lindén, Lovisa; Kotowska, Dorota; Sand, Elin; Bjursell, Mikael; Plaza, Merichel; Turner, Charlotta; Holm, Cecilia; Fåk, Frida; Berger, Karin

    2016-01-01

    Background The gut microbiota plays an important role in the development of obesity and obesity-associated impairments such as low-grade inflammation. Lingonberries have been shown to prevent diet-induced obesity and low-grade inflammation. However, it is not known whether the effect of lingonberry supplementation is related to modifications of the gut microbiota. The aim of the present study was to describe whether consumption of different batches of lingonberries alters the composition of the gut microbiota, which could be relevant for the protective effect against high fat (HF)-induced metabolic alterations. Methods Three groups of C57BL/6J mice were fed HF diet with or without a supplement of 20% lingonberries from two different batches (Lingon1 and Lingon2) during 11 weeks. The composition and functionality of the cecal microbiota were assessed by 16S rRNA sequencing and PICRUSt. In addition, parameters related to obesity, insulin sensitivity, hepatic steatosis, inflammation and gut barrier function were examined. Results HF-induced obesity was only prevented by the Lingon1 diet, whereas both batches of lingonberries reduced plasma levels of markers of inflammation and endotoxemia (SAA and LBP) as well as modified the composition and functionality of the gut microbiota, compared to the HF control group. The relative abundance of Akkermansia and Faecalibacterium, genera associated with healthy gut mucosa and anti-inflammation, was found to increase in response to lingonberry intake. Conclusions Our results show that supplementation with lingonberries to an HF diet prevents low-grade inflammation and is associated with significant changes of the microbiota composition. Notably, the anti-inflammatory properties of lingonberries seem to be independent of effects on body weight gain. PMID:27125264

  6. A High School-Based Evaluation of TakeCARE, a Video Bystander Program to Prevent Adolescent Relationship Violence.

    PubMed

    Sargent, Kelli S; Jouriles, Ernest N; Rosenfield, David; McDonald, Renee

    2017-03-01

    Although bystander programs to prevent relationship and sexual violence have been evaluated with college students, few evaluations have been conducted with high school students. This study evaluated the effectiveness of TakeCARE, a brief video bystander program designed to promote helpful bystander behavior in situations involving relationship violence among high school students. Students (N = 1295; 52.5% female; 72.3% Hispanic) reported their bystander behavior at a baseline assessment. Classrooms (N = 66) were randomized to view TakeCARE or to a control condition, and high school counselors administered the video in the classrooms assigned to view TakeCARE. Students again reported their bystander behavior at a follow-up assessment approximately 3 months afterward. Results indicate that students who viewed TakeCARE reported more helpful bystander behavior at the follow-up assessment than students in the control condition. Results of exploratory analyses of the likelihood of encountering and intervening upon specific situations calling for bystander behavior are also reported. TakeCARE is efficacious when implemented in an urban high school by high school counselors.

  7. Green tea extract containing a highly absorbent catechin prevents diet-induced lipid metabolism disorder.

    PubMed

    Suzuki, Takashi; Kumazoe, Motofumi; Kim, Yoonhee; Yamashita, Shuya; Nakahara, Kanami; Tsukamoto, Shuntaro; Sasaki, Masako; Hagihara, Takatoki; Tsurudome, Yukari; Huang, Yuhui; Maeda-Yamamoto, Mari; Shinoda, Yuki; Yamaguchi, Wataru; Yamada, Koji; Tachibana, Hirofumi

    2013-09-25

    We investigated the effects of extracts of Benifuuki (a tea cultivar that contains methylated catechins such as epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me)) in mice fed a high-fat/high-sucrose (HF/HS) diet. This tea cultivar was then compared with an extract of Yabukita (a popular tea cultivar that lacks methylated catechins). For 6 weeks, C57BL/6J mice were fed either HF/HS diet with or without tea extracts from tea cultivars, which contained almost identical ingredients except for methylated catechins (i.e., Yabukita (0.2% and 1%) or Benifuuki (0.2% and 1%) extract powders). Supplementation with Benifuuki 0.2% markedly lowered plasma levels of TG and NEFAs compared with mice supplemented with Yabukita 0.2%. The diet containing Benifuuki 1% decreased adipose tissue weights, liver TG, and expression of lipogenic genes in the liver. These results suggested that Benifuuki had much greater lipid-lowering effects than Yabukita. Taken together, these data suggest that methylated catechins direct the strong lipid-lowering activity of Benifuuki.

  8. Oral Resveratrol Prevents Osteoarthritis Progression in C57BL/6J Mice Fed a High-Fat Diet.

    PubMed

    Gu, Hailun; Li, Keyu; Li, Xingyao; Yu, Xiaolu; Wang, Wei; Ding, Lifeng; Liu, Li

    2016-04-20

    The effects of resveratrol on osteoarthritis (OA) pathogenesis have been demonstrated in vitro and in animal models employing intra-articular injections. However, the potential for oral resveratrol supplements to mediate protective effects on OA have not been examined. Therefore, the aim of the present study was to investigate the potential anti-OA effects of oral resveratrol on mice fed a high-fat diet (HFD). C57BL/6J male mice were fed either a standard diet or a HFD, and a subset of the latter also received varying doses of resveratrol. Twelve weeks later, all of the animals were sacrificed and knee joints were evaluated with histological, immunohistochemical, and TUNEL analyses. Mice that received a HFD had significantly greater body weights than the control mice and also exhibited features consistent with knee OA. The mice that received a HFD in combination with low, intermediate, or high doses of resveratrol were only slightly heavier than the control mice at the end of 12 weeks. Quantitative histological assessments indicated that resveratrol treatment partly recovered joint structure in the mice that received a HFD, while high doses of resveratrol prevented the degradation of type II collagen into C-telopeptide of type II collagen (CTX-II) and retained type II collagen expression in cartilage. Furthermore, TUNEL analyses revealed a reduction in chondrocyte apoptosis in the resveratrol-treated mice compared with the HFD mice. Thus, oral resveratrol appears to exert anti-OA effects in a mouse model of HFD-induced OA, thereby highlighting the potential preventive and therapeutic value of administering resveratrol for obesity-associated OA.

  9. Glutamate dehydrogenase activator BCH stimulating reductive amination prevents high fat/high fructose diet-induced steatohepatitis and hyperglycemia in C57BL/6J mice

    PubMed Central

    Han, Seung Jin; Choi, Sung-E; Yi, Sang-A; Jung, Jong Gab; Jung, Ik-Rak; Shin, Maureen; Kang, Seok; Oh, Hyunhee; Kim, Hae Jin; Kim, Dae Jung; Kwon, Ji Eun; Choi, Cheol Soo; Lee, Kwan Woo; Kang, Yup

    2016-01-01

    Individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) induced by high calorie western diet are characterized by enhanced lipogenesis and gluconeogenesis in the liver. Stimulation of reductive amination may shift tricarboxylic acid cycle metabolism for lipogenesis and gluconeogenesis toward glutamate synthesis with increase of NAD+/NADH ratio and thus, ameliorate high calorie diet-induced fatty liver and hyperglycemia. Stimulation of reductive amination through glutamate dehydrogenase (GDH) activator 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) reduced both de novo lipogenesis and gluconeogenesis but increased the activities of sirtuins and AMP-activated kinase in primary hepatocytes. Long-term BCH treatment improved most metabolic alterations induced by high fat/high fructose (HF/HFr) diet in C57BL/6J mice. BCH prevented HF/HFr-induced fat accumulation and activation of stress/inflammation signals such as phospho-JNK, phospho-PERK, phospho-p38, and phospho-NFκB in liver tissues. Furthermore, BCH treatment reduced the expression levels of inflammatory cytokines such as TNF-α and IL-1β in HF/HFr-fed mouse liver. BCH also reduced liver collagen and plasma levels of alanine transaminase and aspartate transaminase. On the other hand, BCH significantly improved fasting hyperglycemia and glucose tolerance in HF/HFr-fed mice. In conclusion, stimulation of reductive amination through GDH activation can be used as a strategy to prevent high calorie western diet-induced NAFLD and T2D. PMID:27874078

  10. Getting Personal: Preventing Leadership Failure in a High Tech Air Force

    DTIC Science & Technology

    2010-02-01

    12 Effective Communication ……………………………………………………….…………. 13 Leadership Development……………………………………………………….……….…. 13 Management Skills...BIBLIOGRAPHY……………………………………..……………………………………….. 30 iv Preface I first became interested in the influence of high technology communication on...each other due to a general over-reliance on electronic communication . Around the same time I heard a story about a young lieutenant who did not know

  11. First-order chiral phase transition in high-energy collisions: Can nucleation prevent spinodal decomposition?

    SciTech Connect

    Scavenius, O.; Dumitru, A.; Fraga, E. S.; Lenaghan, J. T.; Jackson, A. D.

    2001-06-01

    We discuss homogeneous nucleation in a first-order chiral phase transition within an effective field theory approach to low-energy QCD. Exact decay rates and bubble profiles are obtained numerically and compared to analytic results obtained with the thin-wall approximation. The thin-wall approximation overestimates the nucleation rate for any degree of supercooling. The time scale for critical thermal fluctuations is calculated and compared to typical expansion times for high-energy hadronic or heavy-ion collisions. We find that significant supercooling is possible, and the relevant mechanism for phase conversion might be that of spinodal decomposition. Some potential experimental signatures of supercooling, such as an increase in the correlation length of the scalar condensate, are also discussed.

  12. Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

    SciTech Connect

    Yasuda-Yamahara, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi; Koya, Daisuke; Haneda, Masakzu; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

    2015-09-18

    Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.

  13. Microfluidic 3D bone tissue model for high-throughput evaluation of wound-healing and infection-preventing biomaterials.

    PubMed

    Lee, Joung-Hyun; Gu, Yexin; Wang, Hongjun; Lee, Woo Y

    2012-02-01

    We report the use of a microfluidic 3D bone tissue model, as a high-throughput means of evaluating the efficacy of biomaterials aimed at accelerating orthopaedic implant-related wound-healing while preventing bacterial infection. As an example of such biomaterials, inkjet-printed micropatterns were prepared to contain antibiotic and biphasic calcium phosphate (BCP) nanoparticles dispersed in a poly(D,L-lactic-co-glycolic) acid matrix. The micropatterns were integrated with a microfluidic device consisting of eight culture chambers. The micropatterns immediately and completely killed Staphylococcus epidermidis upon inoculation, and enhanced the calcified extracellular matrix production of osteoblasts. Without antibiotic elution, bacteria rapidly proliferated to result in an acidic microenvironment which was detrimental to osteoblasts. These results were used to demonstrate the tissue model's potential in: (i) significantly reducing the number of biomaterial samples and culture experiments required to assess in vitro efficacy for wound-healing and infection prevention and (ii) in situ monitoring of dynamic interactions of biomaterials with bacteria as wells as with tissue cells simultaneously.

  14. AAV8-mediated Sirt1 gene transfer to the liver prevents high carbohydrate diet-induced nonalcoholic fatty liver disease

    PubMed Central

    Vilà, Laia; Elias, Ivet; Roca, Carles; Ribera, Albert; Ferré, Tura; Casellas, Alba; Lage, Ricardo; Franckhauser, Sylvie; Bosch, Fatima

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease worldwide, and evidence suggests that it promotes insulin resistance and type 2 diabetes. Caloric restriction (CR) is the only available strategy for NAFLD treatment. The protein deacetylase Sirtuin1 (SIRT1), which is activated by CR, increases catabolic metabolism and decreases lipogenesis and inflammation, both involved in the development of NAFLD. Here we show that adeno-associated viral vectors of serotype 8 (AAV8)-mediated liver-specific Sirt1 gene transfer prevents the development of NAFLD induced by a high carbohydrate (HC) diet. Long-term hepatic SIRT1 overexpression led to upregulation of key hepatic genes involved in β-oxidation, prevented HC diet-induced lipid accumulation and reduced liver inflammation. AAV8-Sirt1–treated mice showed improved insulin sensitivity, increased oxidative capacity in skeletal muscle and reduced white adipose tissue inflammation. Moreover, HC feeding induced leptin resistance, which was also attenuated in AAV8-Sirt1–treated mice. Therefore, AAV-mediated gene transfer to overexpress SIRT1 specifically in the liver may represent a new gene therapy strategy to counteract NAFLD and related diseases such as type 2 diabetes. PMID:26015978

  15. Abstinence and Teenagers: Prevention Counseling Practices of Health Care Providers Serving High-Risk Patients in the United States

    PubMed Central

    Harper, Cynthia C.; Henderson, Jillian T.; Schalet, Amy; Becker, Davida; Stratton, Laura; Raine, Tina R.

    2010-01-01

    CONTEXT Abstinence-only education has had little demonstrable impact on teenagers’ sexual behaviors, despite significant policy and funding efforts. Given the struggle over resources to improve teenagers’ reproductive health outcomes, the views of clinicians serving teenagers at high risk for unintended pregnancy and STDs merit particular attention. METHODS In 2005, a qualitative study with 31 clinicians serving low-income, at-risk patients was conducted. A semistructured interview guide was used to ask clinicians about adolescent pregnancy, HIV and STD prevention counseling, and when they include abstinence. Thematic content analysis was used to examine the content of the counseling and the techniques used in different situations. RESULTS Providers reported offering comprehensive counseling, presenting abstinence as a choice for teenagers, along with information about contraceptives and condoms. Several providers mentioned that with young, sexually inexperienced teenagers, they discuss delaying sexual activity and suggest other ways to be affectionate, while giving information on condoms. Providers explained how they assess whether teenagers feel ready to be sexually active and try to impart skills for healthy relationships. Some described abstinence as giving teenagers a way to opt out of unwanted sexual activity. Many support abstinence if that is the patient’s desire, but routinely dispense condoms and contraceptives. CONCLUSIONS Overall, providers did not give abstinence counseling as a rigid categorical concept in their preventive practices, but as a health tool to give agency to teenagers within a harm reduction framework. Their approach may be informative for adolescent policies and programs in the future. PMID:20618752

  16. High-Intensity Interval Training Versus Moderate-Intensity Continuous Training in the Prevention/Management of Cardiovascular Disease.

    PubMed

    Hussain, Syed R; Macaluso, Andrea; Pearson, Stephen J

    Moderate-intensity continuous training (MICT) has long been considered the most effective exercise treatment modality for the prevention and management of cardiovascular disease (CVD), but more recently high-intensity interval training (HIIT) has been viewed as a potential alternative to MICT in accruing such benefits. HIIT was initially found to induce significant improvements in numerous physiological and health-related indices, to a similar if not superior extent to MICT. Since then, many studies have attempted to explore the potential clinical utility of HIIT, relative to MICT, with respect to treating numerous cardiovascular conditions, such as coronary artery disease, heart failure, stroke, and hypertension. Despite this, however, the efficacy of HIIT in reversing the specific symptoms and risk factors of these cardiovascular pathologies is not well understood. HIIT is often perceived as very strenuous, which could render it unsafe for those at risk of or afflicted with CVD, but these issues are also yet to be reviewed. Furthermore, the optimal HIIT protocol for each of the CVD cohorts has not been established. Thus, the purpose of this review article is to (1) evaluate the efficacy of HIIT relative to MICT in the prevention and management of cardiovascular conditions, and (2) explore any potential safety issues surrounding the suitability and/or tolerability of HIIT for patients with CVD, and the potential optimal prescriptive variables of HIIT for application in the clinical environment.

  17. Preventive maintenance basis: Volume 10 -- High voltage electric motors (5 kV and greater). Final report

    SciTech Connect

    Worledge, D.; Hinchcliffe, G.

    1997-07-01

    US nuclear plants are implementing preventive maintenance (PM) tasks with little documented basis beyond fundamental vendor information to support the tasks or their intervals. The Preventive Maintenance Basis project provides utilities with the technical basis for PM tasks and task intervals associated with 40 specific components such as valves, electric motors, pumps, and HVAC equipment. This report provides an overview of the PM Basis project and describes use of the PM Basis database. Volume 10 of the report provides a program of PM tasks suitable for application to high voltage (5kV and greater) electric motors in nuclear power plants. The PM tasks that are recommended provide a cost-effective way to intercept the causes and mechanisms that lead to degradation and failure. They can be used, in conjunction with material from other sources, to develop a complete PM program or to improve an existing program. Users of this information will be utility managers, supervisors, craft technicians, and training instructors responsible for developing, optimizing, or fine-tuning PM programs. Reactor Coolant Pumps motors (RCP`s) are not excluded from this report in so far as good PM practices for motors of the appropriate class are concerned. However, the special auxiliary equipment normally associated with RCP`s has not been included. Consequently, this report does not provide a complete PM program for RCP`s. Industry and vendor programs for RCP`s should be consulted for complete definition of RCP motor PM programs.

  18. Physical activity prevents alterations in mitochondrial ultrastructure and glucometabolic parameters in a high-sugar diet model.

    PubMed

    Barbosa de Queiroz, Karina; Honorato-Sampaio, Kinulpe; Rossoni Júnior, Joamyr Victor; Andrade Leal, Diego; Pinto, Angélica Barbosa G; Kappes-Becker, Lenice; Evangelista, Elisio Alberto; Guerra-Sá, Renata

    2017-01-01

    Endurance exercise is a remarkable intervention for the treatment of many diseases. Mitochondrial changes on skeletal muscle are likely important for many of the benefits provided by exercise. In this study, we aimed to evaluate the effects that a regular physical activity (swimming without workload) has on mitochondrial morphological alterations and glucometabolic parameters induced by a high-sugar diet (HSD). Weaned male Wistar rats fed with a standard diet or a HSD (68% carbohydrate) were subjected to 60 minutes of regular physical activity by swimming (without workload) for four- (20 sessions) or eight-week (40 sessions) periods. After training, animals were euthanized and the sera, adipose tissues, and skeletal muscles were collected for further analysis. The HSD increased body weight after an 8-week period; it also increased the fat pads and the adipose index, resulting in glucose intolerance and insulin resistance (IR). Transmission electron microscopy showed an increase in alterations of mitochondrial ultrastructure in the gastrocnemius muscle, as well as a decrease in superoxide dismutase (SOD) activity, and an increase in protein carbonylation. Regular physical activity partially reverted these alterations in rats fed a HSD, preventing mitochondrial morphological alterations and IR. Moreover, we observed a decrease in Pgc1α expression (qPCR analysis) in STD-EXE group and a less pronounced reduction in HSD-EXE group after an 8-week period. Thus, regular physical activity (swimming without workload) in rats fed a HSD can prevent mitochondrial dysfunction and IR, highlighting the crucial role for physical activity on metabolic homeostasis.

  19. High Intensity Resistive and Rowing Exercise Countermeasures Do Not Prevent Orthostatic Intolerance Following 70 Days of Bed Rest

    NASA Technical Reports Server (NTRS)

    Lee, Stuart M. C.; Stenger, Michael B.; Laurie, Steven S.; Ploutz-Snyder, Lori L.; Platts, Steven H.

    2015-01-01

    More than 60% of US astronauts participating in Mir and early International Space Station missions (greater than 5 months) were unable to complete a 10-min 80 deg head-up tilt test on landing day. This high incidence of post-spaceflight orthostatic intolerance may be related to limitations of the inflight exercise hardware that prevented high intensity training. PURPOSE: This study sought to determine if a countermeasure program that included intense lower-body resistive and rowing exercises designed to prevent cardiovascular and musculoskeletal deconditioning during 70 days of 6 deg head-down tilt bed rest (BR), a spaceflight analog, also would protect against post- BR orthostatic intolerance. METHODS: Sixteen males participated in this study and performed no exercise (Control, n=10) or performed an intense supine exercise protocol with resistive and aerobic components (Exercise, n=6). On 3 days/week, exercise subjects performed lower body resistive exercise and a 30-min continuous bout of rowing (greater than or equal to 75% max heart rate). On 3 other days/week, subjects performed only high-intensity, interval-style rowing. Orthostatic intolerance was assessed using a 15-min 80 deg head-up tilt test performed 2 days (BR-2) before and on the last day of BR (BR70). Plasma volume was measured using a carbon monoxide rebreathing technique on BR-3 and before rising on the first recovery day (BR+0). RESULTS: Following 70 days of BR, tilt tolerance time decreased significantly in both the Control (BR-2: 15.0 +/- 0.0, BR70: 9.9 +/- 4.6 min, mean +/- SD) and Exercise (BR-2: 12.2 +/- 4.7, BR70: 4.9 +/- 1.9 min) subjects, but the decreased tilt tolerance time was not different between groups (Control: -34 +/- 31, Exercise: -56 +/- 16%). Plasma volume also decreased (Control: -0.56 +/- 0.40, Exercise: -0.48 +/- 0.33 L) from pre to post-BR, with no differences between groups (Control: -18 +/- 11%, Exerciser: -15 +/-1 0%). CONCLUSIONS: These findings confirm previous reports

  20. Oxidative stress in rats fed a high-fat high-sucrose diet and preventive effect of polyphenols: Involvement of mitochondrial and NAD(P)H oxidase systems.

    PubMed

    Feillet-Coudray, C; Sutra, T; Fouret, G; Ramos, J; Wrutniak-Cabello, C; Cabello, G; Cristol, J P; Coudray, C

    2009-03-01

    Mitochondrial and NADPH oxidase systems and oxidative stress were investigated in 12 week high-fat high-sucrose (HFHS) diet-fed rats. A protective effect of wine polyphenol (PP) extract was also examined. In liver, maximal activities of CII and CII+III mitochondrial complexes were decreased but NADPH oxidase expression (p22(phox) and p47(phox)) and NADPH oxidase-dependent superoxide anion production were not modified, whereas oxidative stress (lipid and protein oxidation products and antioxidant systems) was increased with HFHS diet. In muscle, anion superoxide production was slightly increased while mitochondrial complex activities and lipid and protein oxidation products were not modified with HFHS diet. In heart, NADPH oxidase expression and superoxide anion production were increased, and maximal activity of mitochondrial respiratory chain complexes or oxidative stress parameters were not modified. Wine polyphenol extract had an inhibiting effect on liver oxidative stress and on heart NADPH oxidase expression and superoxide anion production, and on induction of hepatic steatosis with HFHS diet. Induction of mitochondrial dysfunction could be a primary event in the development of oxidative stress in liver, while in skeletal muscle and in heart the NADPH oxidase system seems to be mainly involved in oxidative stress. Wine polyphenol extract was shown to partially prevent oxidative stress in liver and heart tissues and to nearly completely prevent steatosis development in liver.

  1. Simultaneous EEG-fMRI at ultra-high field: artifact prevention and safety assessment.

    PubMed

    Jorge, João; Grouiller, Frédéric; Ipek, Özlem; Stoermer, Robert; Michel, Christoph M; Figueiredo, Patrícia; van der Zwaag, Wietske; Gruetter, Rolf

    2015-01-15

    The simultaneous recording of scalp electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can provide unique insights into the dynamics of human brain function, and the increased functional sensitivity offered by ultra-high field fMRI opens exciting perspectives for the future of this multimodal approach. However, simultaneous recordings are susceptible to various types of artifacts, many of which scale with magnetic field strength and can seriously compromise both EEG and fMRI data quality in recordings above 3T. The aim of the present study was to implement and characterize an optimized setup for simultaneous EEG-fMRI in humans at 7 T. The effects of EEG cable length and geometry for signal transmission between the cap and amplifiers were assessed in a phantom model, with specific attention to noise contributions from the MR scanner coldheads. Cable shortening (down to 12 cm from cap to amplifiers) and bundling effectively reduced environment noise by up to 84% in average power and 91% in inter-channel power variability. Subject safety was assessed and confirmed via numerical simulations of RF power distribution and temperature measurements on a phantom model, building on the limited existing literature at ultra-high field. MRI data degradation effects due to the EEG system were characterized via B0 and B1(+) field mapping on a human volunteer, demonstrating important, although not prohibitive, B1 disruption effects. With the optimized setup, simultaneous EEG-fMRI acquisitions were performed on 5 healthy volunteers undergoing two visual paradigms: an eyes-open/eyes-closed task, and a visual evoked potential (VEP) paradigm using reversing-checkerboard stimulation. EEG data exhibited clear occipital alpha modulation and average VEPs, respectively, with concomitant BOLD signal changes. On a single-trial level, alpha power variations could be observed with relative confidence on all trials; VEP detection was more limited, although

  2. Clinical significance of home blood pressure measurements for the prevention and management of high blood pressure.

    PubMed

    Imai, Yutaka; Hosaka, Miki; Elnagar, Noha; Satoh, Michihiro

    2014-01-01

    1. Ambulatory blood pressure (ABP) monitoring (M) provides BP information at many points on any particular day during unrestricted routine daily activities, whereas home blood pressure (HBP) monitoring provides a lot of BP information obtained under fixed times and conditions over a long period of time, thus mean values of HBP provide high reproducibility, and thus an overall superiority compared with ABP.  2. HBP is at least equally or better able than ABP to predict hypertensive target organ damage and prognosis of cardiovascular disease.  3. HBPM allows for ongoing disease monitoring by patients, improves adherence to antihypertensive treatment, and can provide health-care providers with timely clinical data and direct and immediate feedback regarding diagnosis and treatment of hypertension.  4. HBPM provides BP information in relation to time; that is, BP in the morning, in the evening and at night during sleep, and it is an essential tool for the diagnosis of white-coat and masked hypertension.  5. HBPM yields minimal alerting affects and no or minimal placebo effect, and can therefore distinguish small, but significant, serial changes in BP. It is thus the most practical method for monitoring BP in the day-to-day management of hypertension. 6. The superiority of HBPM over ABPM and clinic BPM is apparent from almost all practical and clinical research perspectives.

  3. Acute Thermotherapy Prevents Impairments in Cutaneous Microvascular Function Induced by a High Fat Meal

    PubMed Central

    Harvey, Jennifer C.; Roseguini, Bruno T.; Goerger, Benjamin M.; Fallon, Elizabeth A.

    2016-01-01

    We tested the hypothesis that a high fat meal (HFM) would impair cutaneous vasodilation, while thermotherapy (TT) would reverse the detrimental effects. Eight participants were instrumented with skin heaters and laser-Doppler (LD) probes and tested in three trials: control, HFM, and HFM + TT. Participants wore a water-perfused suit perfused with 33°C (control and HFM) or 50°C (HFM + TT) water. Participants consumed 1 g fat/kg body weight. Blood samples were taken at baseline and two hours post-HFM. Blood pressure was measured every 5–10 minutes. Microvascular function was assessed via skin local heating from 33°C to 39°C two hours after HFM. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVCmax). HFM had no effect on initial peak (48 ± 4 %CVCmax) compared to control (49 ± 4 %CVCmax) but attenuated the plateau (51 ± 4 %CVCmax) compared to control (63 ± 4 %CVCmax, P < 0.001). Initial peak was augmented in HFM + TT (66 ± 4 %CVCmax) compared to control and HFM (P < 0.05), while plateau (73 ± 3 % CVCmax) was augmented only compared to the HFM trial (P < 0.001). These data suggest that HFM negatively affects cutaneous vasodilation but can be minimized by TT. PMID:27595112

  4. High wind speeds prevent formation of a distinct bacterioneuston community in the sea-surface microlayer.

    PubMed

    Rahlff, Janina; Stolle, Christian; Giebel, Helge-Ansgar; Brinkhoff, Thorsten; Ribas-Ribas, Mariana; Hodapp, Dorothee; Wurl, Oliver

    2017-03-22

    The sea-surface microlayer (SML) at the boundary between atmosphere and hydrosphere represents a demanding habitat for bacteria. Wind speed is a crucial but poorly studied factor for its physical integrity. Increasing atmospheric burden of CO2, as suggested for future climate scenarios, may particularly act on this habitat at the air-sea interface. We investigated the effect of increasing wind speeds and different pCO2 levels on SML microbial communities in a wind-wave tunnel, which offered the advantage of low spatial and temporal variability. We found that enrichment of bacteria in the SML occurred solely at a U10 wind speed of ≤5.6 m s-1 in the tunnel and ≤4.1 m s-1 in the Baltic Sea. High pCO2 levels further intensified the bacterial enrichment in the SML during low wind speed. In addition, low wind speed and pCO2 induced the formation of a distinctive bacterial community as revealed by 16S rRNA gene fingerprints and influenced the presence or absence of individual taxonomic units within the SML. We conclude that physical stability of the SML below a system-specific wind speed threshold induces specific bacterial communities in the SML entailing strong implications for ecosystem functioning by wind-driven impacts on habitat properties, gas-exchange and matter cycling processes.

  5. Fucoidan prevents high-fat diet-induced obesity in animals by suppression of fat accumulation.

    PubMed

    Kim, Mi-Ja; Jeon, Joseph; Lee, Jin-Sil

    2014-01-01

    This study examines the antiobesity effects of fucoidan in an animal model of diet-induced obesity. Mice were fed a standard diet or high-fat diet (HFD) for 5 weeks. After that, the mice were divided into four experimental groups, with 10 mice per group, including a standard diet group, HFD group, HFD containing 1% fucoidan (HFD + FUCO 1%) group and HFD containing 2% fucoidan (HFD + FUCO 2%) group. The fucoidan supplementation group had significantly decreased body-weight gain, food efficiency ratio and relative liver and epididymal fat mass compared with the HFD group. The mice supplemented with fucoidan showed significantly reduced triglyceride, total cholesterol and low-density lipoprotein levels in the plasma. Liver steatosis induced by the HFD improved in the fucoidan-supplemented group. Furthermore, fucoidan affected the down-regulation expression patterns of epididymal adipose tissue genes such as peroxisome proliferator-activated receptor γ, adipose-specific fatty acid binding protein and acetyl CoA carboxylase. Therefore, fucoidan may be considered for use in improving obesity.

  6. The high-risk plaque initiative: primary prevention of atherothrombotic events in the asymptomatic population.

    PubMed

    Falk, Erling; Sillesen, Henrik; Muntendam, Pieter; Fuster, Valentin

    2011-10-01

    The High-Risk Plaque (HRP) Initiative is a research and development effort to advance the understanding, recognition, and management of asymptomatic individuals at risk for a near-term atherothrombotic event such as myocardial infarction or stroke. Clinical studies using the newest technologies have been initiated, including the BioImage Study in which novel approaches are tested in a typical health plan population. Asymptomatic at-risk individuals were enrolled, including a survey-only group (n = 865), a group undergoing traditional risk factor scoring (n = 718), and a group in which all were assessed for both risk factors and subclinical atherosclerosis (n = 6104). The latter two groups underwent baseline examination in a dedicated mobile facility equipped with advanced imaging tools suitable for noninvasive screening for subclinical atherosclerosis (coronary artery calcium by computed tomography [CT], carotid and aortic disease by ultrasound, and ankle-brachial index). Selected participants were offered advanced imaging (contrast-enhanced CT, magnetic resonance imaging, and positron emission tomography/CT). Plasma, PAXgene RNA, and DNA samples were obtained for biomarker discovery studies. All individuals will be followed until 600 major atherothrombotic events have occurred in those undergoing imaging.

  7. Primary prevention of stroke by a healthy lifestyle in a high-risk group

    PubMed Central

    Åkesson, Agneta; Wolk, Alicja

    2015-01-01

    Objective: To examine the impact of a healthy lifestyle on stroke risk in men at higher risk of stroke because of other cardiovascular diseases or conditions. Methods: Our study population comprised 11,450 men in the Cohort of Swedish Men who had a history of hypertension, high cholesterol levels, diabetes, heart failure, or atrial fibrillation. Participants had completed a questionnaire about diet and lifestyle and were free from stroke and ischemic heart disease at baseline (January 1, 1998). We defined a healthy lifestyle as a low-risk diet (≥5 servings/d of fruits and vegetables and <30 g/d of processed meat), not smoking, ≥150 min/wk of physical activity, body mass index of 18.5 to 25 kg/m2, and low to moderate alcohol consumption (>0 to ≤30 g/d). Ascertainment of stroke cases was accomplished through linkage with the National Inpatient Register and the Swedish Cause of Death Register. Results: During a mean follow-up of 9.8 years, we ascertained 1,062 incident stroke cases. The risk of total stroke and stroke types decreased with increasing number of healthy lifestyle factors. The multivariable relative risk of total stroke for men who achieved all 5 healthy lifestyle factors compared with men who achieved 0 or 1 factor was 0.28 (95% confidence interval 0.14–0.55). The corresponding relative risks (95% confidence interval) were 0.31 (0.15–0.66) for ischemic stroke and 0.32 (0.04–2.51) for hemorrhagic stroke. Conclusions: A healthy lifestyle is associated with a substantially reduced risk of stroke in men at higher risk of stroke. PMID:25934859

  8. Involvement of autophagy induction in penta-1,2,3,4,6-O-galloyl-β-D-glucose-induced senescence-like growth arrest in human cancer cells.

    PubMed

    Dong, Yinhui; Yin, Shutao; Jiang, Cheng; Luo, Xiaohe; Guo, Xiao; Zhao, Chong; Fan, Lihong; Meng, Yubing; Lu, Junxuan; Song, Xinhua; Zhang, Xudong; Chen, Ni; Hu, Hongbo

    2014-02-01

    Growing evidence has demonstrated that autophagy plays important and paradoxical roles in carcinogenesis, while senescence is considered to be a crucial tumor-suppressor mechanism in cancer prevention and treatment. In the present study we demonstrated that both autophagy and senescence were induced in response to penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG), a chemopreventive polyphonolic compound, in multiple types of cancer cells. Analysis of these 2 events over the experimental time course indicated that autophagy and senescence occurred in parallel early in the process and dissociated later. The long-term culture study suggested that a subpopulation of senescent cells may have the capacity to reenter the cell cycle. Inhibition of autophagy by either a chemical inhibitor or RNA interference led to a significant reduction of PGG-induced senescence, followed by induction of apoptosis. These results suggested that autophagy promoted senescence induction by PGG and that PGG might exert its anticancer activity through autophagy-mediated senescence. For the first time, these findings uncovered the relationships among autophagy, senescence, and apoptosis induced by PGG. In addition, we identified that unfolded protein response signaling played a pivotal role in the autophagy-mediated senescence phenotype. Furthermore, our data showed that activation of MAPK8/9/10 (mitogen-activated protein kinase 8/9/10/c-Jun N-terminal kinases) was an essential upstream signal for PGG-induced autophagy. Finally, the key in vitro results were validated in vivo in a xenograft mouse model of human HepG2 liver cancer. Our findings provided novel insights into understanding the mechanisms and functions of PGG-induced autophagy and senescence in human cancer cells.

  9. Metformin Ameliorates Dysfunctional Traits of Glibenclamide- and Glucose-Induced Insulin Secretion by Suppression of Imposed Overactivity of the Islet Nitric Oxide Synthase-NO System.

    PubMed

    Lundquist, Ingmar; Mohammed Al-Amily, Israa; Meidute Abaraviciene, Sandra; Salehi, Albert

    2016-01-01

    Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS)-NO system, a negative modulator of glucose-stimulated insulin release. In short-time incubations with isolated murine islets either glibenclamide or high glucose augmented insulin release associated with increased NO production from both neural and inducible NOS. Metformin addition suppressed the augmented NO generation coinciding with amplified insulin release. Islet culturing with glibenclamide or high glucose revealed pronounced fluorescence of inducible NOS in the beta-cells being abolished by metformin co-culturing. These findings were reflected in medium nitrite-nitrate levels. A glucose challenge following islet culturing with glibenclamide or high glucose revealed markedly impaired insulin response. Metformin co-culturing restored this response. Culturing murine islets and human islets from controls and type 2 diabetics with high glucose or high glucose + glibenclamide induced a pronounced decrease of cell viability being remarkably restored by metformin co-culturing. We show here, that imposed overactivity of the beta-cell NOS-NO system by glibenclamide or high glucose leads to insulin secretory dysfunction and reduced cell viability and also, importantly, that these effects are relieved by metformin inhibiting beta-cell NO overproduction from both neural and inducible NOS thus ameliorating a concealed negative influence by NO induced by sulfonylurea treatment and/or high glucose levels. This double-edged effect of glibenclamide on the beta-cellsuggests sulfonylurea monotherapy in type 2 diabetes being avoided.

  10. Metformin Ameliorates Dysfunctional Traits of Glibenclamide- and Glucose-Induced Insulin Secretion by Suppression of Imposed Overactivity of the Islet Nitric Oxide Synthase-NO System

    PubMed Central

    Lundquist, Ingmar; Mohammed Al-Amily, Israa; Meidute Abaraviciene, Sandra

    2016-01-01

    Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS)-NO system, a negative modulator of glucose-stimulated insulin release. In short-time incubations with isolated murine islets either glibenclamide or high glucose augmented insulin release associated with increased NO production from both neural and inducible NOS. Metformin addition suppressed the augmented NO generation coinciding with amplified insulin release. Islet culturing with glibenclamide or high glucose revealed pronounced fluorescence of inducible NOS in the beta-cells being abolished by metformin co-culturing. These findings were reflected in medium nitrite-nitrate levels. A glucose challenge following islet culturing with glibenclamide or high glucose revealed markedly impaired insulin response. Metformin co-culturing restored this response. Culturing murine islets and human islets from controls and type 2 diabetics with high glucose or high glucose + glibenclamide induced a pronounced decrease of cell viability being remarkably restored by metformin co-culturing. We show here, that imposed overactivity of the beta-cell NOS-NO system by glibenclamide or high glucose leads to insulin secretory dysfunction and reduced cell viability and also, importantly, that these effects are relieved by metformin inhibiting beta-cell NO overproduction from both neural and inducible NOS thus ameliorating a concealed negative influence by NO induced by sulfonylurea treatment and/or high glucose levels. This double-edged effect of glibenclamide on the beta-cellsuggests sulfonylurea monotherapy in type 2 diabetes being avoided. PMID:27820841

  11. HIV Testing and Engagement in Care among Highly Vulnerable Female Sex Workers: Implications for Treatment as Prevention Models

    PubMed Central

    Surratt, Hilary L.; O’Grady, Catherine; Kurtz, Steven P.; Buttram, Mance E.; Levi-Minzi, Maria A.

    2014-01-01

    Background Although emerging Treatment as Prevention models can be effective in reducing HIV incidence among high-risk populations, many HIV infected individuals remain undiagnosed or fail to engage in HIV care. Methods This study examined the factors associated with HIV testing and care among a population of substance using female sex workers. Results Recent HIV testing was associated with higher education level, having a regular health care provider or clinic, recent crack use, and higher sexual risk behaviors; HIV treatment utilization was associated with higher levels of social support, having a regular health care provider or clinic, housing stability and insurance coverage. Qualitative data revealed HIV-related stigma, denial, social isolation, and substance use as barriers to HIV testing and treatment; social support and accessibility of services were key enablers. Conclusions Improving HIV testing and linkage to treatment among female sex workers will require structural initiatives to reduce stigma and increase service seeking support. PMID:25130245

  12. The United Nations High Level Meeting on the Prevention and Control of Noncommunicable Diseases: a missed opportunity?

    PubMed

    Sivaramakrishnan, Kavita; Parker, Richard G

    2012-11-01

    The United Nations High Level Meeting on the Prevention and Control of Noncommunicable Diseases (September 19-20, 2011) provided an opportunity to recast the current global health agenda and offered a formidable platform to mobilize political will for concerted action. We argue that the opportunity was missed because the World Health Organization (WHO) neglected the politics of process that are key to mobilizing political support for global noncommunicable disease policies. Instead, it focused on the implementation process. The lessons to be drawn from the summit are critical because the WHO is the key agency that will be expected in the near future to steer further discussions and debate on the noncommunicable disease agenda.

  13. Resveratrol prevents high fat/sucrose diet-induced central arterial wall inflammation and stiffening in nonhuman primates.

    PubMed

    Mattison, Julie A; Wang, Mingyi; Bernier, Michel; Zhang, Jing; Park, Sung-Soo; Maudsley, Stuart; An, Steven S; Santhanam, Lakshmi; Martin, Bronwen; Faulkner, Shakeela; Morrell, Christopher; Baur, Joseph A; Peshkin, Leonid; Sosnowska, Danuta; Csiszar, Anna; Herbert, Richard L; Tilmont, Edward M; Ungvari, Zoltan; Pearson, Kevin J; Lakatta, Edward G; de Cabo, Rafael

    2014-07-01

    Central arterial wall stiffening, driven by a chronic inflammatory milieu, accompanies arterial diseases, the leading cause of cardiovascular (CV) morbidity and mortality in Western society. An increase in central arterial wall stiffening, measured as an increase in aortic pulse wave velocity (PWV), is a major risk factor for clinical CV disease events. However, no specific therapies to reduce PWV are presently available. In rhesus monkeys, a 2 year diet high in fat and sucrose (HFS) increases not only body weight and cholesterol, but also induces prominent central arterial wall stiffening and increases PWV and inflammation. The observed loss of endothelial cell integrity, lipid and macrophage infiltration, and calcification of the arterial wall were driven by genomic and proteomic signatures of oxidative stress and inflammation. Resveratrol prevented the HFS-induced arterial wall inflammation and the accompanying increase in PWV. Dietary resveratrol may hold promise as a therapy to ameliorate increases in PWV.

  14. CHOICES: an integrated behavioral intervention to prevent alcohol-exposed pregnancies among high-risk women in community settings.

    PubMed

    Velasquez, Mary M; von Sternberg, Kirk; Parrish, Danielle E

    2013-01-01

    CHOICES is an integrated behavioral intervention for prevention of prenatal alcohol exposure in women at high risk for alcohol-exposed pregnancies. The intervention uses motivational interviewing and cognitive-behavioral strategies, and targets adoption of effective contraception and reduction of alcohol use. The CHOICES intervention includes four manual-guided counseling sessions delivered by behavioral health counselors and one contraceptive session with a family planning clinician. CHOICES's efficacy has been established through a series of randomized controlled trials in settings including primary care, university hospital-based obstetrical/gynecology practices, urban jails, substance abuse treatment settings, and a media-recruited sample in three large cities. This article describes the CHOICES line of research including the epidemiology, feasibility, and efficacy studies. It also details the CHOICES intervention and the components of each session. In addition, the authors describe current studies testing modifications of the CHOICES intervention, the dissemination efforts to date, and implications for social work practice.

  15. Analysis of torque transmitting behavior and wheel slip prevention control during regenerative braking for high speed EMU trains

    NASA Astrophysics Data System (ADS)

    Xu, Kun; Xu, Guo-Qing; Zheng, Chun-Hua

    2016-04-01

    The wheel-rail adhesion control for regenerative braking systems of high speed electric multiple unit trains is crucial to maintaining the stability, improving the adhesion utilization, and achieving deep energy recovery. There remain technical challenges mainly because of the nonlinear, uncertain, and varying features of wheel-rail contact conditions. This research analyzes the torque transmitting behavior during regenerative braking, and proposes a novel methodology to detect the wheel-rail adhesion stability. Then, applications to the wheel slip prevention during braking are investigated, and the optimal slip ratio control scheme is proposed, which is based on a novel optimal reference generation of the slip ratio and a robust sliding mode control. The proposed methodology achieves the optimal braking performance without the wheel-rail contact information. Numerical simulation results for uncertain slippery rails verify the effectiveness of the proposed methodology.

  16. High levels of anti-Nef antibodies may prevent AIDS disease progression in vertically HIV-1-infected infants

    PubMed Central

    Corró, Guillermo; Crudeli, Cintia Milena; Rocco, Carlos Alberto; Marino, Silvia Alejandra; Sen, Luisa

    2014-01-01

    Introduction HIV-1-associated CD4+ T-cell depletion is a consequence of uninfected cell death. Nef is one of the viral factors that trigger apoptosis on bystander cells, though the plasma Nef levels do not correlate with Th lymphocytes counts. The aim of our study was to evaluate whether anti-Nef antibodies were involved in paediatric AIDS development and whether they can prevent the CD4+ T-cell depletion in vertically infected children. Methods Two hundred and seventy three HIV-1 vertically infected children seen at Garrahan Paediatric Hospital were randomly included in the study, adding 13 selected cases: seven LTNP (long-term non-progressors) and six RP (rapid progressors) children (n total=286). Specific anti-HIV-1-Nef antibodies were titrated by indirect ELISA and compared between groups. The plasma blocking effect on Nef-dependent cytotoxicity was evaluated in Jurkat cells using recombinant Nef as apoptotic stimulus and patient plasmas as blockers, measuring the apoptotic levels using Annexin-V stain and flow cytometry. Results Only 63.4% of the patients had specific anti-Nef antibodies, and the levels of anti-Nef antibodies found in the selected LTNPs plasmas were always significantly higher (p=1.55×10−4) than those in RPs or general HIV-1+ paediatric populations. The LTNPs’ plasma had a strong inhibitory effect on Nef-dependent cytotoxicity even at high dilutions, while RP plasmas had little or no effect on Nef-induced apoptosis. Discussion and conclusions High anti-Nef antibody levels are associated and predict slow or non-progression to AIDS in vertically HIV-1-infected children. They could be an efficient tool in preventing Nef-associated bystander effect, preserving CD4+ T-cells and the immune function in the context of paediatric HIV-1 infection. PMID:24560340

  17. Source segregation and food waste prevention activities in high-density households in a deprived urban area.

    PubMed

    Rispo, A; Williams, I D; Shaw, P J

    2015-10-01

    A waste audit and a household questionnaire survey were conducted in high-density housing estates in one of the most economically and socially deprived areas of England (Haringey, London). Such areas are under-represented in published research. The study examined source segregation, potential participation in a food waste segregation scheme, and food waste prevention activities in five estates (1034 households). The results showed that: contamination of recyclables containers was low; ca. 28% of the mixed residual waste's weight was recyclable; food waste comprised a small proportion of the waste from these residents, probably because of their relatively disadvantaged economic circumstances; and the recycling profile reflected an intermittent pattern of behaviour. Although the majority of respondents reported that they would participate in a food waste separation scheme, the response rate was low and many responses of "don't know" were recorded. Municipalities committed to foster improved diversion from landfill need to recognise that there is no "quick and easy fix", regardless of local or national aspirations. Lasting and sustained behaviour change requires time and the quality of service provision and associated infrastructure play a fundamental role in facilitating residents to participate effectively in waste management activities that maximise capture of source-segregated materials. Populations in deprived areas that reside in high-rise, high-density dwellings are "hard-to-reach" in terms of participation in recycling schemes and exceptional efforts and additional resources are usually required to improve performance.

  18. Impact of high cholesterol in a Parkinson's disease model: Prevention of lysosomal leakage versus stimulation of α-synuclein aggregation.

    PubMed

    Eriksson, Ida; Nath, Sangeeta; Bornefall, Per; Giraldo, Ana Maria Villamil; Öllinger, Karin

    2017-01-16

    Parkinson's disease is characterized by accumulation of intraneuronal cytoplasmic inclusions, Lewy bodies, which mainly consist of aggregated α-synuclein. Controversies exist as to whether high blood cholesterol is a risk factor for the development of the disease and whether statin treatment could have a protective effect. Using a model system of BE(2)-M17 neuroblastoma cells treated with the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)), we found that MPP(+)-induced cell death was accompanied by cholesterol accumulation in a lysosomal-like pattern in pre-apoptotic cells. To study the effects of lysosomal cholesterol accumulation, we increased lysosomal cholesterol through pre-treatment with U18666A and found delayed leakage of lysosomal contents into the cytosol, which reduced cell death. This suggests that increased lysosomal cholesterol is a stress response mechanism to protect lysosomal membrane integrity in response to early apoptotic stress. However, high cholesterol also stimulated the accumulation of α-synuclein. Treatment with the cholesterol-lowering drug lovastatin reduced MPP(+)-induced cell death by inhibiting the production of reactive oxygen species, but did not prevent lysosomal cholesterol increase nor affect α-synuclein accumulation. Our study indicates a dual role of high cholesterol in Parkinson's disease, in which it acts both as a protector against lysosomal membrane permeabilization and as a stimulator of α-synuclein accumulation.

  19. European Stroke Prevention Study 2: A study of low-dose acetylsalicylic acid and of high dose dipyridamole in secondary prevention of cerebro-vascular accidents.

    PubMed

    1995-11-01

    In spite of some data being added to our knowledge of the effect of antiplatelets in secondary prevention of brain ischemic lesion in recent years, the main reasons to perform a second European Stroke Prevention Study (ESPS 2), which started in 1987-1988, were: (a) clarify the relative roles of aspirin (ASA) and dipyridamole (DP) alone or in combination; (b) confirm the efficacy of small doses of ASA and, so doing, decrease the number of drop-outs due to ASA side effects; (c) join information to the effect of antiplatelets in complete stroke. General characteristics of the sample of 6602 patients are presented and compared with other major trials and series. The patients in the four treatment arms (aspirin, dipyridamole, aspirin + dipyridamole and placebo) are compared. The more relevant features and risk factors known to influence long term prognosis are described and discussed. The small proportion of patients included with TIA (23.7%) and the comparability among treatment groups are stressed. No relevant differences have been found, among groups, on the sex or age distribution, prevalence of hypertension, diabetes, previous vascular events or atrial fibrillation, nor in the characteristics of the accident leading to the inclusion in trial.

  20. Effects of Green Tea Gargling on the Prevention of Influenza Infection in High School Students: A Randomized Controlled Study

    PubMed Central

    Ide, Kazuki; Yamada, Hiroshi; Matsushita, Kumi; Ito, Miki; Nojiri, Kei; Toyoizumi, Kiichiro; Matsumoto, Keiji; Sameshima, Yoichi

    2014-01-01

    Background The anti-influenza virus activity of green tea catechins has been demonstrated in experimental studies, but clinical evidence has been inconclusive. School-aged children play an important role in the infection and spread of influenza in the form of school-based outbreaks. Preventing influenza infection among students is essential for reducing the frequency of epidemics and pandemics. As a non-pharmaceutical intervention against infection, gargling is also commonly performed in Asian countries but has not yet been extensively studied. Methods and Findings A randomized, open label, 2-group parallel study of 757 high school students (15 to 17 years of age) was conducted for 90 days during the influenza epidemic season from December 1st, 2011 to February 28th, 2012, in 6 high schools in Shizuoka Prefecture, Japan. The green tea gargling group gargled 3 times a day with bottled green tea, and the water gargling group did the same with tap water. The water group was restricted from gargling with green tea. The primary outcome measure was the incidence of laboratory-confirmed influenza using immunochromatographic assay for antigen detection. 757 participants were enrolled and 747 participants completed the study (384 in the green tea group and 363 in the water group). Multivariate logistic regression indicated no significant difference in the incidence of laboratory-confirmed influenza between the green tea group (19 participants; 4.9%) and the water group (25 participants; 6.9%) (adjusted OR, 0.69; 95%CI, 0.37 to 1.28; P = 0.24). The main limitation of the study is the adherence rate among high school students was lower than expected. Conclusions Among high school students, gargling with green tea three times a day was not significantly more efficacious than gargling with water for the prevention of influenza infection. In order to adequately assess the effectiveness of such gargling, additional large-scale randomized studies are needed. Trial Registration

  1. High homocysteine levels prevent via H2 S the CoCl2 -induced alteration of lymphocyte viability.

    PubMed

    Bruzzese, Laurie; Fenouillet, Emmanuel; Fromonot, Julien; Durand-Gorde, Josée-Martine; Condo, Jocelyne; Kipson, Nathalie; Mottola, Giovanna; Deharo, Pierre; Guieu, Régis; Ruf, Jean

    2016-08-01

    High homocysteine (HCy) levels are associated with lymphocyte-mediated inflammatory responses that are sometimes in turn related to hypoxia. Because adenosine is a potent lymphocyte suppressor produced in hypoxic conditions and shares metabolic pathways with HCy, we addressed the influence of high HCy levels on the hypoxia-induced, adenosine-mediated, alteration of lymphocyte viability. We treated mitogen-stimulated human lymphocytes isolated from healthy individuals and the human lymphoma T-cell line CEM with cobalt chloride (CoCl2 )to reproduce hypoxia. We found that CoCl2 -altered cell viability was dose-dependently reversed using HCy. In turn, the HCy effect was inhibited using DL-propargylglycine, a specific inhibitor of the hydrogen sulphide (H2 S)-synthesizing enzyme cystathionine-γ-lyase involved in HCy catabolism. We then addressed the intracellular metabolic pathway of adenosine and HCy, and the role of the adenosine A2A receptor (A2 A R). We observed that: (i) hypoxic conditions lowered the intracellular concentration of HCy by increasing adenosine production, which resulted in high A2 A R expression and 3', 5'-cyclic adenosine monophosphate production; (ii) increasing intracellular HCy concentration reversed the hypoxia-induced adenosinergic signalling despite high adenosine concentration by promoting both S-adenosylhomocysteine and H2 S production; (iii) DL-propargylglycine that inhibits H2 S production abolished the HCy effect. Together, these data suggest that high HCy levels prevent, via H2 S production and the resulting down-regulation of A2 A R expression, the hypoxia-induced adenosinergic alteration of lymphocyte viability. We point out the relevance of these mechanisms in the pathophysiology of cardiovascular diseases.

  2. Prostate cancer screening characteristics in men with BRCA1/2 mutations attending a high-risk prevention clinic

    PubMed Central

    Walker, Richard; Louis, Alyssa; Berlin, Alejandro; Horsburgh, Sheri; Bristow, Robert G.; Trachtenberg, John

    2014-01-01

    Introduction: The prostate-specific antigen (PSA) era and resultant early detection of prostate cancer has presented clinicians with the challenge of distinguishing indolent from aggressive tumours. Mutations in the BRCA1/2 genes have been associated with prostate cancer risk and prognosis. We describe the prostate cancer screening characteristics of BRCA1/2 mutation carriers, who may be classified as genetically-defined high risk, as compared to another high-risk cohort of men with a family history of prostate cancer to evaluate the utility of a targeted screening approach for these men. Methods: We reviewed patient demographics, clinical screening characteristics, pathological features, and treatment outcomes between a group of BRCA1 or BRCA2 mutation carriers and age-matched men with a family history of prostate cancer followed at our institutional Prostate Cancer Prevention Clinic from 1995 to 2012. Results: Screening characteristics were similar between the mutation carriers (n = 53) and the family history group (n = 53). Some cancers would be missed in both groups by using a PSA cut-off of >4 ug/L. While cancer detection was higher in the family history group (21% vs. 15%), the mutation carrier group was more likely to have intermediate- or high-risk disease (88% vs. 36%). BRCA2 mutation carriers were more likely to have aggressive disease, biological recurrence, and distant metastasis. Conclusions: In our cohort, regular screening appears justified for detecting prostate cancer in BRCA1 and BRCA2 carriers and other high-risk populations. Lowering PSA cut-offs and defining monitoring of PSA velocity as part of the screening protocol may be useful. BRCA2 is associated with more aggressive disease, while the outcome for BRCA1 mutation carriers requires further study. Large multinational studies will be important to define screening techniques for this unique high-risk population. PMID:25485004

  3. Oxidative stress and dysregulation of the taurine transporter in high-glucose-exposed human Schwann cells: implications for pathogenesis of diabetic neuropathy

    PubMed Central

    Askwith, Trevor; Zeng, Wei; Eggo, Margaret C.; Stevens, Martin J.

    2009-01-01

    In human Schwann cells, the role of taurine in regulating glucose-induced changes in antioxidant defense systems has been examined. Treatment with high glucose for 7 days induced reactive oxygen species, increased 4-hydroxynoneal adducts (20 ± 5%, P < 0.05) and poly(ADP-ribosyl)ated proteins (40 ± 13%, P < 0.05). Increases in these markers of oxidative stress were reversed by simultaneous incubation in 0.25 mM taurine. Both high glucose and taurine independently increased superoxide dismutase and catalase activity and decreased glutathione levels, but their effects were not additive. Glucose reduced taurine transporter (TauT) mRNA and protein in a dose-dependent manner with maximal decreases of 66 ± 6 and 63 ± 12%, respectively (P < 0.05 both). The Vmax for taurine uptake was decreased in 30 mM glucose from 61 ± 5 to 42 ± 3 pmol·min−1·mg protein−1 (P < 0.001). Glucose-induced TauT downregulation could be reversed by inhibition of aldose reductase, a pathway that depletes NADPH and increases osmotic stress and protein glycation. TauT protein was increased more than threefold, and the Vmax for taurine uptake doubled (P < 0.05 both) by prooxidants. TauT downregulation was reversed both by treatment with the antioxidant α-lipoic acid, which increased TauT mRNA by 60% and Vmax by 50% (P < 0.05 both), and by the aldose reductase inhibitor sorbinil, which increased TauT mRNA 380% and Vmax by 98% (P < 0.01 both). These data highlight the potential therapeutic benefits of taurine supplementation in diabetic complications and provide mechanisms whereby taurine restoration could be achieved in order to prevent or reverse diabetic complications. PMID:19602579

  4. Physical activity prevents alterations in mitochondrial ultrastructure and glucometabolic parameters in a high-sugar diet model

    PubMed Central

    Honorato-Sampaio, Kinulpe; Rossoni Júnior, Joamyr Victor; Andrade Leal, Diego; Pinto, Angélica Barbosa G.; Kappes-Becker, Lenice; Evangelista, Elisio Alberto; Guerra-Sá, Renata

    2017-01-01

    Endurance exercise is a remarkable intervention for the treatment of many diseases. Mitochondrial changes on skeletal muscle are likely important for many of the benefits provided by exercise. In this study, we aimed to evaluate the effects that a regular physical activity (swimming without workload) has on mitochondrial morphological alterations and glucometabolic parameters induced by a high-sugar diet (HSD). Weaned male Wistar rats fed with a standard diet or a HSD (68% carbohydrate) were subjected to 60 minutes of regular physical activity by swimming (without workload) for four- (20 sessions) or eight-week (40 sessions) periods. After training, animals were euthanized and the sera, adipose tissues, and skeletal muscles were collected for further analysis. The HSD increased body weight after an 8-week period; it also increased the fat pads and the adipose index, resulting in glucose intolerance and insulin resistance (IR). Transmission electron microscopy showed an increase in alterations of mitochondrial ultrastructure in the gastrocnemius muscle, as well as a decrease in superoxide dismutase (SOD) activity, and an increase in protein carbonylation. Regular physical activity partially reverted these alterations in rats fed a HSD, preventing mitochondrial morphological alterations and IR. Moreover, we observed a decrease in Pgc1α expression (qPCR analysis) in STD-EXE group and a less pronounced reduction in HSD-EXE group after an 8-week period. Thus, regular physical activity (swimming without workload) in rats fed a HSD can prevent mitochondrial dysfunction and IR, highlighting the crucial role for physical activity on metabolic homeostasis. PMID:28199417

  5. High-Intensity Interval Training with Vibration as Rest Intervals Attenuates Fiber Atrophy and Prevents Decreases in Anaerobic Performance

    PubMed Central

    Mueller, Sandro Manuel; Aguayo, David; Zuercher, Matthias; Fleischmann, Oliver; Boutellier, Urs; Auer, Maria; Jung, Hans H.; Toigo, Marco

    2015-01-01

    Aerobic high-intensity interval training (HIT) improves cardiovascular capacity but may reduce the finite work capacity above critical power (W′) and lead to atrophy of myosin heavy chain (MyHC)-2 fibers. Since whole-body vibration may enhance indices of anaerobic performance, we examined whether side-alternating whole-body vibration as a replacement for the active rest intervals during a 4x4 min HIT prevents decreases in anaerobic performance and capacity without compromising gains in aerobic function. Thirty-three young recreationally active men were randomly assigned to conduct either conventional 4x4 min HIT, HIT with 3 min of WBV at 18 Hz (HIT+VIB18) or 30 Hz (HIT+VIB30) in lieu of conventional rest intervals, or WBV at 30 Hz (VIB30). Pre and post training, critical power (CP), W′, cellular muscle characteristics, as well as cardiovascular and neuromuscular variables were determined. W′ (−14.3%, P = 0.013), maximal voluntary torque (−8.6%, P = 0.001), rate of force development (−10.5%, P = 0.018), maximal jumping power (−6.3%, P = 0.007) and cross-sectional areas of MyHC-2A fibers (−6.4%, P = 0.044) were reduced only after conventional HIT. CP, V̇O2peak, peak cardiac output, and overall capillary-to-fiber ratio were increased after HIT, HIT+VIB18, and HIT+VIB30 without differences between groups. HIT-specific reductions in anaerobic performance and capacity were prevented by replacing active rest intervals with side-alternating whole-body vibration, notably without compromising aerobic adaptations. Therefore, competitive cyclists (and potentially other endurance-oriented athletes) may benefit from replacing the active rest intervals during aerobic HIT with side-alternating whole-body vibration. Trial Registration ClinicalTrials.gov Identifier: NCT01875146 PMID:25679998

  6. High Adherence to CPAP Treatment Does Not Prevent the Continuation of Weight Gain among Severely Obese OSAS Patients

    PubMed Central

    Myllylä, Minna; Kurki, Samu; Anttalainen, Ulla; Saaresranta, Tarja; Laitinen, Tarja

    2016-01-01

    Study Objectives: Obstructive sleep apnea syndrome (OSAS) patients benefit from continuous positive airway pressure (CPAP) treatment in a dose-response manner. We determined adherence and weight control, as well as their predictors, among long-term CPAP users. Methods: Cohort of 1,023 OSAS patients had used CPAP on average of 6.6 ± 1.2 years. BMI was determined at baseline and at follow-up visits. There were 7.4 ± 1.7 BMI and 6.5 ± 1.8 CPAP usage measurements per patient on average. Using the Bayesian hierarchical model, we determined the patients' individual trends of BMI and adherence development. Patients with significantly increasing or decreasing trends were identified at the posterior probability level of > 90%. Results: The mean age in the cohort was 55.6 ± 9.8 years, BMI 33.5 ± 6.4 kg/m2, apnea-hypopnea index 33.7 ± 23.1, and CPAP usage 6.0 ± 1.8 h/day. The majority of patients had no significant change in BMI (mean annual weight gain 0.04 ± 0.29 kg/m2) or CPAP adherence (mean annual increase 11.4 ± 7.0 min/day). However, at the individual level, 10% of the patients showed significant annual weight gain (0.63 ± 0.35 kg/m2) during the 5-year follow-up period. At baseline these patients were already more severely obese (mean BMI 40.0 ± 5.9 kg/m2) despite being younger (mean 50.9 ± 9.5 years) than the rest of the cohort. Conclusions: In the majority of CPAP-treated OSAS patients, weight did not significantly change but gained slightly slower than in age-matched population in general. However, in 10% of patients, high adherence to CPAP treatment did not prevent the continuation of weight gain. These patients present a high-risk group for OSAS-related multimorbidity later in life. Citation: Myllylä M, Kurki S, Anttalainen U, Saaresranta T, Laitinen T. High adherence to CPAP treatment does not prevent the continuation of weight gain among severely obese OSAS patients. J Clin Sleep Med 2016;12(4):519–528. PMID:26888588

  7. Risk Factors and Prevention

    MedlinePlus

    ... atherosclerosis (“clogged” arteries) and High Blood Pressure . Preventing Arrhythmias and Heart Disease Prevent heart disease by lowering ... cholesterol, diabetes, and thyroid disease. Risk Factors For Arrhythmias and Heart Disease The following conditions can increase ...

  8. High dry bean intake and reduced risk of advanced colorectal adenoma recurrence among participants in the polyp prevention trial.

    PubMed

    Lanza, Elaine; Hartman, Terryl J; Albert, Paul S; Shields, Rusty; Slattery, Martha; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Lance, Peter; Daston, Cassandra; Schatzkin, Arthur

    2006-07-01

    Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial-based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18-0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial-based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.

  9. High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study.

    PubMed

    Zheng, Jin-Ping; Wen, Fu-Qiang; Bai, Chun-Xue; Wan, Huan-Ying; Kang, Jian; Chen, Ping; Yao, Wan-Zhen; Ma, Li-Jun; Xia, Qi-Kui; Gao, Yi; Zhong, Nan-Shan

    2013-04-01

    Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.

  10. A 'polypill' aimed at preventing cardiovascular disease could prove highly cost-effective for use in Latin America.

    PubMed

    Bautista, Leonelo E; Vera-Cala, Lina M; Ferrante, Daniel; Herrera, Víctor M; Miranda, J Jaime; Pichardo, Rafael; Sánchez Abanto, José R; Ferreccio, Catterina; Silva, Eglé; Oróstegui Arenas, Myriam; Chirinos, Julio A; Medina-Lezama, Josefina; Pérez, Cynthia M; Schapochnik, Norberto; Casas, Juan P

    2013-01-01

    We evaluated the cost-effectiveness of administering a daily "polypill" consisting of three antihypertensive drugs, a statin, and aspirin to prevent cardiovascular disease among high-risk patients in Latin America. We found that the lifetime risk of cardiovascular disease could be reduced by 15 percent in women and by 21 percent in men if the polypill were used by people with a risk of cardiovascular disease equal to or greater than 15 percent over ten years. Attaining this goal would require treating 26 percent of the population at a cost of $34-$36 per quality-adjusted life-year. Offering the polypill to women at high risk and to men age fifty-five or older would be the best approach and would yield acceptable incremental cost-effectiveness ratios. The polypill would be very cost-effective even in the country with the lowest gross national income in our study. However, policy makers must weigh the value of intervention with the polypill against other interventions, as well as their country's willingness and ability to pay for the intervention.

  11. German high school students' attitudes and interest in cancer and factors influencing proactive behaviour for cancer prevention.

    PubMed

    Heuckmann, Benedikt; Asshoff, Roman

    2014-09-01

    Cancer diseases are pertinent topics to young people, who are confronted with the issue through media or family members that suffer from these diseases. Based on a paper-and-pencil questionnaire, we investigated German high school students' (N = 369, 16-18 years old) interest in and their attitudes towards cancer. Attitude was assessed measuring multiple dimensions that included scales to measure several components: the cognitive (beliefs about the controllability of cancer), the affective (emotional responses towards cancer) and the behavioural (intention for proactive behaviour towards cancer) components. A student assessment of carcinogenic risk factor was executed. Our results suggest that students' willingness to deal with the topic cancer (e.g. to communicate about cancer or to reconsider their lifestyle) is highly dependent on their interest, their emotional responses and their beliefs about the controllability of cancer. Their assessment of carcinogenic risk factors does not have a direct influence on their intentions to behave proactively against cancer but might have an indirect influence on their beliefs about the controllability of cancer. Based on these results, we have drawn teaching implications and discussed which factors should be included in teaching processes in order to stimulate proactive behaviour related to cancer prevention.

  12. MicroRNA-134 Contributes to Glucose-Induced Endothelial Cell Dysfunction and This Effect Can Be Reversed by Far-Infrared Irradiation

    PubMed Central

    Wang, Yen-Li; Chang, Shih-Ting; Liao, Ko-Hsun; Lo, Hung-Hao; Chiu, Ya-Lin; Hsieh, Tsung-Han; Huang, Tse-Shun; Lin, Chin-Sheng; Cheng, Shu-Meng; Cheng, Cheng-Chung

    2016-01-01

    Diabetes mellitus (DM) is a metabolic disease that is increasing worldwide. Furthermore, it is associated with the deregulation of vascular-related functions, which can develop into major complications among DM patients. Endothelial colony forming cells (ECFCs) have the potential to bring about medical repairs because of their post-natal angiogenic activities; however, such activities are impaired by high glucose- (HG) and the DM-associated conditions. Far-infrared radiation (FIR) transfers energy as heat that is perceived by the thermoreceptors in human skin. Several studies have revealed that FIR improves vascular endothelial functioning and boost angiogenesis. FIR has been used as anti-inflammatory therapy and as a clinical treatment for peripheral circulation improvement. In addition to vascular repair, there is increasing evidence to show that FIR can be applied to a variety of diseases, including cardiovascular disorders, hypertension and arthritis. Yet mechanism of action of FIR and the biomarkers that indicate FIR effects remain unclear. MicroRNA-134 (miR-134-5p) was identified by small RNA sequencing as being increased in high glucose (HG) treated dfECFCs (HG-dfECFCs). Highly expressed miR-134 was also validated in dmECFCs by RT-qPCR and it is associated with impaired angiogenic activities of ECFCs. The functioning of ECFCs is improved by FIR treatment and this occurs via a reduction in the level of miR-134 and an increase in the NRIP1 transcript, a direct target of miR-134. Using a mouse ischemic hindlimb model, the recovery of impaired blood flow in the presence of HG-dfECFCs was improved by FIR pretreatment and this enhanced functionality was decreased when there was miR-134 overexpression in the FIR pretreated HG-dfECFCs. In conclusion, our results reveal that the deregulation of miR-134 is involved in angiogenic defects found in DM patients. FIR treatment improves the angiogenic activity of HG-dfECFCs and dmECFCs and FIR has potential as a treatment

  13. Cooperation between HMGA1, PDX-1, and MafA is Essential for Glucose-Induced Insulin Transcription in Pancreatic Beta Cells

    PubMed Central

    Arcidiacono, Biagio; Iiritano, Stefania; Chiefari, Eusebio; Brunetti, Francesco S.; Gu, Guoqiang; Foti, Daniela Patrizia; Brunetti, Antonio

    2014-01-01

    The high-mobility group AT-hook 1 (HMGA1) protein is a nuclear architectural factor that can organize chromatin structures. It regulates gene expression by controlling the formation of stereospecific multiprotein complexes called “enhanceosomes” on the AT-rich regions of target gene promoters. Previously, we reported that defects in HMGA1 caused decreased insulin receptor expression and increased susceptibility to type 2 diabetes mellitus in humans and mice. Interestingly, mice with disrupted HMGA1 gene had significantly smaller islets and decreased insulin content in their pancreata, suggesting that HMGA1 may have a direct role in insulin transcription and secretion. Herein, we investigate the regulatory roles of HMGA1 in insulin transcription. We provide evidence that HMGA1 physically interacts with PDX-1 and MafA, two critical transcription factors for insulin gene expression and beta-cell function, both in vitro and in vivo. We then show that the overexpression of HMGA1 significantly improves the transactivating activity of PDX-1 and MafA on human and mouse insulin promoters, while HMGA1 knockdown considerably decreased this transactivating activity. Lastly, we demonstrate that high glucose stimulus significantly increases the binding of HMGA1 to the insulin (INS) gene promoter, suggesting that HMGA1 may act as a glucose-sensitive element controlling the transcription of the INS gene. Together, our findings provide evidence that HMGA1, by regulating PDX-1- and MafA-induced transactivation of the INS gene promoter, plays a critical role in pancreatic beta-cell function and insulin production. PMID:25628604

  14. Collaborative Evaluation of a High School Prevention Curriculum: How Methods of Collaborative Evaluation Enhanced a Randomized Control Trial to Inform Program Improvement

    ERIC Educational Resources Information Center

    Orsini, Muhsin Michael; Wyrick, David L.; Milroy, Jeffrey J.

    2012-01-01

    Blending high-quality and rigorous research with pure evaluation practice can often be best accomplished through thoughtful collaboration. The evaluation of a high school drug prevention program (All Stars Senior) is an example of how perceived competing purposes and methodologies can coexist to investigate formative and summative outcome…

  15. An Evaluation of a Social Norms Marketing Project for Tobacco Prevention with Middle, High, and College Students; Use of Funds from the Tobacco Master Settlement (Virginia)

    ERIC Educational Resources Information Center

    Martino-Mcallister, Jeanne; Wessel, Maria Theresa

    2005-01-01

    The "Anti-Tobacco Media Blitz" (ATMB), a social-norms marketing program, was utilized for tobacco prevention with middle and high school students. University students assisted middle and high school students with the implementation of this campaign, which included a variety of media. Students worked in teams to design, develop, and…

  16. Prevention and reversal of diet-induced leptin resistance with a sugar-free diet despite high fat content.

    PubMed

    Shapiro, Alexandra; Tümer, Nihal; Gao, Yongxin; Cheng, Kit-Yan; Scarpace, Philip J

    2011-08-01

    Chronic consumption of a Western-type diet, containing both elevated sugar and fat, results in leptin resistance. We hypothesised that fructose, as part of the sugar component of Western-type diets, is one causative ingredient in the development of leptin resistance and that removal of this component will prevent leptin resistance despite high fat (HF) content. We fed rats a sugar-free (SF), 30 % HF (SF/HF) diet or a 40 % high-fructose (HFr), 30 % HF (HFr/HF) diet for 134 d. The HFr/HF diet resulted in impaired anorexic and body-weight responses to both peripherally (0·6 mg/kg, assessed on day 65 of the diet) and centrally (1·5 μg/d, assessed on days 129-134) administered leptin, whereas SF/HF-fed rats were fully leptin responsive. At day 70, half the HFr/HF-fed animals were switched to the SF/HF diet, reversing the leptin resistance (assessed 18 d after the diet switch). The HFr/HF diet elevated serum leptin and reduced adiponectin, and levels were restored abruptly at day 3 after switching to the SF/HF diet. These data demonstrate that a diet containing both HFr and fat leads to leptin resistance, while an isoenergetic SF/HF diet does not. Moreover, removal of fructose from this diet reverses the leptin resistance and the elevated leptin, suggesting a cause-and-effect relationship. These data suggest that fructose is the bioactive component of a HF/high-sugar diet that is essential for the induction of leptin resistance.

  17. Impact of a Randomized Campus/Community Trial to Prevent High-Risk Drinking among College Students

    PubMed Central

    Wolfson, Mark; Champion, Heather; McCoy, Thomas P.; Rhodes, Scott D.; Ip, Edward H.; Blocker, Jill N.; Martin, Barbara Alvarez; Wagoner, Kimberly G.; O’Brien, Mary Claire; Sutfin, Erin L.; Mitra, Ananda; DuRant, Robert H.

    2013-01-01

    Background High-risk drinking by college students continues to pose a significant threat to public health. Despite increasing evidence of the contribution of community-level and campus-level environmental factors to high risk drinking, there have been few rigorous tests of interventions that focus on changing these interlinked environments. The Study to Prevent Alcohol Related Consequences (SPARC) assessed the efficacy of a comprehensive intervention using a community organizing approach to implement environmental strategies in and around college campuses. The goal of SPARC was to reduce high-risk drinking and alcohol-related consequences among college students. Methods Ten universities in North Carolina were randomized to an Intervention or Comparison condition. Each Intervention school was assigned a campus/community organizer. The organizer worked to form a campus-community coalition, which developed and implemented a strategic plan to use environmental strategies to reduce high-risk drinking and its consequences. The intervention was implemented over a period of 3 years. Primary outcome measures were assessed using a web-based survey of students. Measures of high-risk drinking included number of days alcohol was consumed, number of days of binge drinking, and greatest number of drinks consumed (all in the past 30 days); and number of days one gets drunk in a typical week. Measures of alcohol-related consequences included indices of moderate consequences due to one’s own drinking, severe consequences due to one’s own drinking, interpersonal consequences due to others’ drinking, and community consequences due to others’ drinking (all using a past 30-day timeframe). Measure of alcohol-related injuries included (1) experiencing alcohol-related injuries and (2) alcohol-related injuries caused to others. Results We found significant decreases in the Intervention group compared to the Comparison group in severe consequences due to students’ own drinking and

  18. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    SciTech Connect

    Kover, Karen; Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu; Tasch, James; Hager, Melissa; Clements, Mark; Moore, Wayne V.

    2015-06-19

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose-induced

  19. Working with High-Risk Youth in Prevention and Early Intervention Programs: Toward a Comprehensive Wellness Model.

    ERIC Educational Resources Information Center

    Mills, Roger C.; And Others

    1988-01-01

    Addresses issues such as dropouts, teenage pregnancy, drug abuse, suicide, and other health-damaging behaviors. Presents a theory of youth development and learning, and an integrated, interactive and reciprocal model for the prevention of health-damaging behavior. Addresses the role of the schools in prevention. (Author/BH)

  20. High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

    PubMed Central

    Gordon, Elizabeth M.; Figueroa, Debbie M.; Barochia, Amisha V.; Yao, Xianglan; Levine, Stewart J.

    2016-01-01

    Apolipoprotein A-I (apoA-I) and high-density lipoproteins (HDL) mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury (ALI), asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of ALI, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach. PMID:27708582

  1. Enhanced oral bioavailability of a cancer preventive agent (SR13668) by employing polymeric nanoparticles with high drug loading.

    PubMed

    Shen, Hao; Banerjee, Aryamitra A; Mlynarska, Paulina; Hautman, Mathew; Hong, Seungpyo; Kapetanovic, Izet M; Lyubimov, Alexander V; Liu, Ying

    2012-10-01

    SR13668 [2,10-Dicarbethoxy-6-methoxy-5,7-dihydro-indolo-(2,3-b)carbazole] has been proven effective in cancer prevention, but the limited bioavailability has hindered its clinical translation. In this study, we have developed a continuous, scalable process to form stable poly(lactic-co-glycolic acid) nanoparticles encapsulating SR13668, based on understanding of the competitive kinetics of nanoprecipitation and spray drying. The optimized formulation achieved high drug loading (33.3 wt %) and small particles (150 nm) with narrow size distribution. The prepared nanoparticle suspensions through flash nanoprecipitation were spray dried to achieve long-term stability and to conveniently adjust the nanoparticle concentration before use. In vitro release of SR13668 from the nanosuspensions was measured in a solution with separated organic and aqueous phases to overcome the limit of SR13668 low water solubility. Higher oral bioavailability of SR13668 by employing polymeric nanoparticles compared with the Labrasol® formulation was demonstrated in a mouse model.

  2. Brief cognitive-behavioral depression prevention program for high-risk adolescents outperforms two alternative interventions: a randomized efficacy trial.

    PubMed

    Stice, Eric; Rohde, Paul; Seeley, John R; Gau, Jeff M

    2008-08-01

    In this depression prevention trial, 341 high-risk adolescents (mean age = 15.6 years, SD = 1.2) with elevated depressive symptoms were randomized to a brief group cognitive-behavioral (CB) intervention, group supportive-expressive intervention, bibliotherapy, or assessment-only control condition. CB participants showed significantly greater reductions in depressive symptoms than did supportive-expressive, bibliotherapy, and assessment-only participants at posttest, though only the difference compared with assessment controls was significant at 6-month follow-up. CB participants showed significantly greater improvements in social adjustment and reductions in substance use at posttest and 6-month follow-up than did participants in all 3 other conditions. Supportive-expressive and bibliotherapy participants showed greater reductions in depressive symptoms than did assessment-only controls at certain follow-up assessments but produced no effects for social adjustment and substance use. CB, supportive-expressive, and bibliotherapy participants showed a significantly lower risk for major depression onset over the 6-month follow-up than did assessment-only controls. The evidence that this brief CB intervention reduced risk for future depression onset and outperformed alternative interventions for certain ecologically important outcomes suggests that this intervention may have clinical utility.

  3. Preventing high-risk drinking in youth in the workplace: a web-based normative feedback program.

    PubMed

    Doumas, Diana M; Hannah, Elizabeth

    2008-04-01

    This study evaluated the efficacy of an alcohol web-based personalized feedback program delivered in the workplace to young adults. Participants (N = 124) were randomly assigned to one of three conditions: web-based feedback (WI), web-based feedback plus a 15-minute motivational interviewing session (MI), or a control group. Results indicated that participants in the intervention group (WI and MI conditions combined) reported significantly lower levels of drinking than those in the control group at a 30-day follow-up. This was particularly true for participants classified as high-risk drinkers at the baseline assessment. Similar results were found when comparing the WI condition to the control group. No differences were found between the WI and MI conditions, indicating that the addition of a 15-minute motivational interviewing session did not increase the efficacy of the web-based feedback program. Findings support the use of web-based feedback as a stand-alone alcohol prevention program for young adults in the workplace.

  4. High-Throughput Screening Platform Identifies Small Molecules That Prevent Sequestration of Plasmodium falciparum–Infected Erythrocytes

    PubMed Central

    Gullingsrud, Justin; Milman, Neta; Saveria, Tracy; Chesnokov, Olga; Williamson, Kathryn; Srivastava, Anand; Gamain, Benoit; Duffy, Patrick E.; Oleinikov, Andrew V.

    2015-01-01

    Background. We developed a 2-step approach to screen molecules that prevent and/or reverse Plasmodium falciparum–infected erythrocyte (IE) binding to host receptors. IE adhesion and sequestration in vasculature causes severe malaria, and therefore antiadhesion therapy might be useful as adjunctive treatment. IE adhesion is mediated by the polymorphic family (approximately 60 members) of P. falciparum EMP1 (PfEMP1) multidomain proteins. Methods. We constructed sets of PfEMP1 domains that bind ICAM-1, CSA, or CD36, receptors that commonly support IE binding. Combinations of domain-coated beads were assayed by Bio-Plex technology as a high-throughput molecular platform to screen antiadhesion molecules (antibodies and small molecules). Molecules identified as so-called hits in the screen (first step) then could be assayed individually for inhibition of binding of live IE to receptors (second step). Results. In proof-of-principle studies, the antiadhesion activity of several antibodies was concordant in Bio-Plex and live IE assays. Using this 2-step approach, we identified several molecules in a small molecule library of 10 000 compounds that could inhibit and reverse binding of IEs to ICAM-1 and CSA receptors. Conclusion. This 2-step screening approach should be efficient for identification of antiadhesion drug candidates for falciparum malaria. PMID:25355939

  5. Acetylshikonin from Zicao Prevents Obesity in Rats on a High-Fat Diet by Inhibiting Lipid Accumulation and Inducing Lipolysis

    PubMed Central

    Zhu, Banghao

    2016-01-01

    Various drugs have been developed to treat obesity, but these have undesirable secondary effects, and an efficient but non-toxic anti-obesity drug from natural sources is desired. This study investigated the anti-obesity effects and mechanisms of action of acetylshikonin (AS)—which is used in traditional Chinese medicine—in rats on a high-fat diet (HFD). Rats were fed a normal diet or an HFD; the latter group was received no treatment or were treated with 100, 300, or 900 mg/kg AS extract by intragastric administration for 6 weeks. In addition, 3T3-L1 adipocytes were treated with AS and the effects on adipogenesis and lipolysis were evaluated by western blot analysis of adipogenic transcription factors and lipid-metabolizing enzyme levels and the phosphorylation status of protein kinase (PK) A and hormone-sensitive lipase (HSL). AS prevented HFD-induced obesity including reduction in body weight, white adipose tissue content, liver mass, and serum triglyceride and free fatty acid levels in rats. It also suppressed the expression of adipogenic differentiation transcription factors and decreased the expression of the adipocyte-specific proteins HSL and adipose triglyceride lipase (ATGL). Furthermore, AS treatment induced lipolysis, leading to the release of glycerol and increased in PKA and HSL phosphorylation. These findings demonstrate that AS has anti-obesity effects in a rat model and may be a safe treatment for obesity in humans. PMID:26771185

  6. Preventive effect of Monascus-fermented products enriched with ubiquinones on type 2 diabetic rats induced by a high-fructose plus high-fat diet.

    PubMed

    Pyo, Young-Hee; Lee, Kyung-Won

    2014-07-01

    The aim of the present study was to investigate whether the aqueous extract of Monascus-fermented grains (MFGEs) enriched with ubiquinones (Coenzyme Qs, CoQ9+CoQ10) alleviates high-fructose (60%) plus high-fat (20%) diet (HFD)-induced hyperglycemia and hepatic oxidative stress in male Sprague-Dawley rats. Animals were fed HFD for 16 weeks and orally administered with MFGEs (300 mg/kg/day) or atorvastatin (20 mg/kg/day) for the last 4 weeks of the study. HFD-fed rats exhibited hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and impaired insulin sensitivity. MFGE treatment prevented the increase in glucose levels and index of insulin resistance in the HFD-induced diabetic rats. A significant decrease in hepatic lipid peroxidation and significant increases in hepatic superoxide dismutase, catalase, and glutathione peroxidase were observed in the MFGE supplemented group. The results suggest that dietary supplementation with MFGEs enriched with CoQs exerts an antidiabetic effect in type 2 diabetic rats by improving insulin resistance and hepatic antioxidant enzymes.

  7. Strategies for disease prevention and health promotion in maternal and child health: the "ecologic" versus the "high risk" approach.

    PubMed

    Chamberlin, R W

    1984-06-01

    This article advocates an ecological approach to prevention of maternal and child health problems such as adolescent pregnancy, low birthweight, developmental disabilities, and child abuse. Over the past decade, the most widely used strategy for addressing these problems has been based on the concept of high risk. This approach assumes that retrospective data can identify a relatively small number of families that will produce the majority of child health and developmental problems in a community and concentrates resources on this group. However, this approach tends to produce either a large at risk group, most of whom will not develop the outcome under question, or a small group with a higher incidence of problems but representative of only a tiny fraction of the total number of children in the community who develop problems. The difficulties inherent in attempting to predict who is at risk of developing what conditions has led to the search for more effective preventive strategies. The ecological approach assumes that child health and development outcomes are related to parent functioning, which is influenced by both formal (health and human service providers) and informal (family and friends) community support systems, in turn influenced by cultural values and government policies. Interventions based on this model aim to improve community resources that can strengthen family functioning. In addition to primary health care services, such a program should include 5 components at the local community level: 1) a representative community council; 2) a community-wide health education program; 3) basic parent support services (parent-child centers, birthing centers, home visitors, homemaker services, transportation); 4) a consumer advocacy organization; and 5) a reliable assessment system. Forming a coordinating council and advocacy group involves little or no extra governmental expense, and existing data sources can be used for needs assessment and program monitoring

  8. Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development.

    PubMed

    Moraes-Silva, Ivana Cinthya; Mostarda, Cristiano; Moreira, Edson Dias; Silva, Kleiton Augusto Santos; dos Santos, Fernando; de Angelis, Kátia; Farah, Vera de Moura Azevedo; Irigoyen, Maria Claudia

    2013-03-15

    High fructose consumption contributes to metabolic syndrome incidence, whereas exercise training promotes several beneficial adaptations. In this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 wk. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index and glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured, whereas heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations compared with all the other groups in insulin resistance (in mg · dl(-1) · min(-1): F: 3.4 ± 0.2; C: 4.7 ± 0.2; CT: 5.0 ± 0.5 FT: 4.6 ± 0.4), mean BP (in mmHG: F: 117 ± 2; C: 100 ± 2; CT: 98 ± 2; FT: 105 ± 2), and Lee index (in g/mm: F = 0.31 ± 0.001; C = 0.29 ± 0.001; CT = 0.27 ± 0.002; FT = 0.28 ± 0.002), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an ≈ 50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well as in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption.

  9. High risk for RSV bronchiolitis in late preterms and selected infants affected by rare disorders: a dilemma of specific prevention.

    PubMed

    Manzoni, P; Paes, B; Resch, B; Mejias, A; Ramilo, O; Carbonell-Estrany, X; Bont, L

    2012-05-01

    Respiratory syncytial virus (RSV) is the most frequent aetiologic agent that causes bronchiolitis and lower respiratory tract infection in infants. These infections may be severe and even life-threatening in selected high-risk populations. Traditional, well-established, high-risk populations are preterm infants with or without chronic lung disease and children with congenital heart disease. For these children, RSV prophylaxis using palivizumab, a monoclonal anti-RSV humanised antibody against the F-protein of RSV, has proven safe and efficacious in preventing RSV-related hospitalisation. Recently, a number of rare medical conditions have been associated with the risk of severe RSV infections. Evidence of safety and efficacy of RSV prophylaxis in these populations is lacking. Given the low incidence of these conditions, randomised trials are not feasible. A practical, opinion-based approach to this dilemma is offered in this paper. It is proposed that these rare disorders may qualify for RSV prophylaxis if the association between a specific condition and the risk of severe RSV infection is confirmed in at least 3 independent publications, of which at least 1 includes a prospective cohort study. To facilitate pharmaco-economic analyses, at least one of the three studies must also report on the absolute risk of severe RSV infection in the specified illness. The authors believe that qualification criteria will enable caregivers to target RSV prophylaxis more effectively in children with rare conditions and the proposed approach provides direction for future epidemiological studies on the risk of severe RSV infection in children with these uncommon, medical illnesses.

  10. HIV among immigrants living in high-income countries: a realist review of evidence to guide targeted approaches to behavioural HIV prevention

    PubMed Central

    2012-01-01

    Background Immigrants from developing and middle-income countries are an emerging priority in HIV prevention in high-income countries. This may be explained in part by accelerating international migration and population mobility. However, it may also be due to the vulnerabilities of immigrants including social exclusion along with socioeconomic, cultural and language barriers to HIV prevention. Contemporary thinking on effective HIV prevention stresses the need for targeted approaches that adapt HIV prevention interventions according to the cultural context and population being addressed. This review of evidence sought to generate insights into targeted approaches in this emerging area of HIV prevention. Methods We undertook a realist review to answer the research question: ‘How are HIV prevention interventions in high-income countries adapted to suit immigrants’ needs?’ A key goal was to uncover underlying theories or mechanisms operating in behavioural HIV prevention interventions with immigrants, to uncover explanations as how and why they work (or not) for particular groups in particular contexts, and thus to refine the underlying theories. The realist review mapped seven initial mechanisms underlying culturally appropriate HIV prevention with immigrants. Evidence from intervention studies and qualitative studies found in systematic searches was then used to test and refine these seven mechanisms. Results Thirty-four intervention studies and 40 qualitative studies contributed to the analysis and synthesis of evidence. The strongest evidence supported the role of ‘consonance’ mechanisms, indicating the pivotal need to incorporate cultural values into the intervention content. Moderate evidence was found to support the role of three other mechanisms – ‘understanding’, ‘specificity’ and ‘embeddedness’ – which indicated that using the language of immigrants, usually the ‘mother tongue’, targeting (in terms of ethnicity) and the use of

  11. Preventing preterm births: trends and potential reductions with current interventionsin 39 very high human development index countries

    PubMed Central

    Chang, Hannah H.; Larson, Jim; Blencowe, Hannah; Spong, Catherine Y.; Howson, Christopher P.; Cairns-Smith, Sarah; Lackritz, Eve M.; Lee, Shoo K.; Mason, Elizabeth; Serazin, Andrew C.; Walani, Salimah; Simpson, Joe Leigh; Lawn, Joy E.

    2013-01-01

    Summary Background Each year,1.1 million babies die from prematurity, andmany survivors are disabled. Worldwide, 15 million babies are preterm(<37 weeks’ gestation),withtwo decades of increasing ratesinalmost all countries with reliable data. Improved care of babies has reduced mortality in high-income countries, although effective interventions have yet to be scaled-up in most low-income countries. A 50% reduction goal for preterm-specific mortality by 2025 has been set in the “Born Too Soon” report. However, for preterm birth prevention,understanding of drivers and potential impact of preventive interventions is limited. We examine trends and estimate the potential reduction in preterm birthsforvery high human development index (VHHDI) countries if current evidence-based interventions were widely implemented. This analysis is to inform a “Born Too Soon” rate reduction target. Methods Countries were assessed for inclusion based on availability and quality ofpreterm prevalence data (2000-2010), and trend analyses with projections undertaken. We analysed drivers of rate increases in the USA, 1998-2004. For 39 VHHDI countrieswith >10,000 births, country-by-country analyses were performed based on target population, incremental coverage increase,and intervention efficacy. Cost savings were estimated based on reported costs for preterm care in the USAadjusted usingWorld Bank purchasing power parity. Findings From 2010, even if all VHHDI countries achieved annual preterm birth rate reductions of the best performers, (Sweden and Netherlands), 2000-2010 or 2005-2010(Lithuania, Estonia)), rates would experience a relative reduction of<5% by 2015 on average across the 39 countries.Our analysis of preterm birth rise 1998-2004 in USA suggests half the change is unexplained, but important drivers includeinductions/cesareandelivery and ART.For all 39 VHHDI countries, five interventionsmodeling at high coveragepredicted 5%preterm birth rate relative reduction from 9

  12. Resveratrol Prevention of Diabetic Nephropathy Is Associated with the Suppression of Renal Inflammation and Mesangial Cell Proliferation: Possible Roles of Akt/NF-κB Pathway.

    PubMed

    Xu, Feng; Wang, Yuehui; Cui, Wenpeng; Yuan, Hang; Sun, Jing; Wu, Man; Guo, Qiaoyan; Kong, Lili; Wu, Hao; Miao, Lining

    2014-01-01

    The present study was to investigate the protection of resveratrol (RSV) in diabetes associated with kidney inflammation and cell proliferation. Rat mesangial cell and streptozotocin-induced type 1 diabetes mouse model were used. In vitro, RSV attenuated high glucose-induced plasminogen activator inhibitor (PAI-1) expression and mesangial cell proliferation, as well as Akt and nuclear factor-kappa B (NF- κ B) activation. The similar results were recaptured in the experiment with Akt inhibitors. In vivo, mice were divided into three groups: control group, diabetes mellitus (DM) group, and RSV-treated DM group. Compared with control group, the kidney weight to body weight ratio and albumin to creatinine ratio were increased in DM group, but not in RSV-treated DM group. Furthermore, the increased expression of PAI-1 and intercellular adhesion molecule-1 in diabetic renal cortex were also reduced by RSV administration. Besides, the kidney p-Akt/Akt ratio and NF- κ B were significantly increased in DM group; however, these changes were reversed in RSV-treated DM group. Additionally, immunohistochemistry results indicated that RSV treatment reduced the density of proliferating cell nuclear antigen-positive cells significantly in glomeruli of diabetic mice. These results suggest that RSV prevents diabetes-induced renal inflammation and mesangial cell proliferation possibly through Akt/NF- κ B pathway inhibition.

  13. Prevention--a cost-effective way to fight the non-communicable disease epidemic: an academic perspective of the United Nations High-level NCD Meeting.

    PubMed

    Probst-Hensch, Nicole; Tanner, Marcel; Kessler, Claudia; Burri, Christian; Künzli, Nino

    2011-09-07

    The United Nations General Assembly has convened a Summit on non-communicable diseases (NCDs), an historic moment in the global combat of these disorders. Lifestyles in increasingly urban and globalised environments have led to a steep surge in NCD incidence in low and middle income countries, where two thirds of all NCD deaths occur (most importantly from cancer, cardiovascular and respiratory disease as well as diabetes). Treatment of NCDs is usually long term and expensive, thus threatening patients' and nations' budgets and putting them at high risk for poverty. The NCD Summit offers an opportunity for strengthening and shaping primary prevention, the most cost-effective instrument to fight major risk factors such as tobacco smoking, alcohol abuse, physical inactivity and unhealthy diet. From a Swiss perspective, we also emphasised the efforts for new laws on prevention and diagnosis registration, in accordance with the recommendations of the NCD summit in order to strengthen primary prevention and disease monitoring. In addition, the need for structural prevention across all policy sectors with leadership in environmental policy making to prevent NCDs as well as the need to adapt and strengthen primary health care are equally relevant for Switzerland. To compliment efforts in primary prevention, the field of NCDs requires special R&D platforms for affordable NCD drugs and diagnostics for neglected population segments in both Switzerland and low and middle income countries. Switzerland has a track record in research and development against diseases of poverty on a global scale that now needs to be applied to NCDs.

  14. Rape prevention

    MedlinePlus

    Date rape - prevention; Sexual assault - prevention ... Centers for Disease Control and Prevention. Sexual assault and abuse and STDs. In: 2015 sexually transmitted diseases treatment guidelines 2015. Updated June 4, 2015. www.cdc.gov/ ...

  15. A Mitochondrial-Targeted Coenzyme Q Analog Prevents Weight Gain and Ameliorates Hepatic Dysfunction in High-Fat–Fed Mice

    PubMed Central

    Fink, Brian D.; Herlein, Judith A.; Guo, Deng Fu; Kulkarni, Chaitanya; Weidemann, Benjamin J.; Yu, Liping; Grobe, Justin L.; Rahmouni, Kamal; Kerns, Robert J.

    2014-01-01

    We hypothesized that the mitochondrial-targeted antioxidant, mitoquinone (mitoQ), known to have mitochondrial uncoupling properties, might prevent the development of obesity and mitigate liver dysfunction by increasing energy expenditure, as opposed to reducing energy intake. We administered mitoQ or vehicle (ethanol) to obesity-prone C57BL/6 mice fed high-fat (HF) or normal-fat (NF) diets. MitoQ (500 µM) or vehicle (ethanol) was added to the drinking water for 28 weeks. MitoQ significantly reduced total body mass and fat mass in the HF-fed mice but had no effect on these parameters in NF mice. Food intake was reduced by mitoQ in the HF-fed but not in the NF-fed mice. Average daily water intake was reduced by mitoQ in both the NF- and HF-fed mice. Hypothalamic expression of neuropeptide Y, agouti-related peptide, and the long form of the leptin receptor were reduced in the HF but not in the NF mice. Hepatic total fat and triglyceride content did not differ between the mitoQ-treated and control HF-fed mice. However, mitoQ markedly reduced hepatic lipid hydroperoxides and reduced circulating alanine aminotransferase, a marker of liver function. MitoQ did not alter whole-body oxygen consumption or liver mitochondrial oxygen utilization, membrane potential, ATP production, or production of reactive oxygen species. In summary, mitoQ added to drinking water mitigated the development of obesity. Contrary to our hypothesis, the mechanism involved decreased energy intake likely mediated at the hypothalamic level. MitoQ also ameliorated HF-induced liver dysfunction by virtue of its antioxidant properties without altering liver fat or mitochondrial bioenergetics. PMID:25301169

  16. The effectiveness of preventative mass vaccination regimes against the incidence of highly pathogenic avian influenza on Java Island, Indonesia.

    PubMed

    Bett, B; McLaws, M; Jost, C; Schoonman, L; Unger, F; Poole, J; Lapar, M L; Siregar, E S; Azhar, M; Hidayat, M M; Dunkle, S E; Mariner, J

    2015-04-01

    We conducted an operational research study involving backyard and semicommercial farms on Java Island, Indonesia, between April 2008 and September 2009 to evaluate the effectiveness of two preventive mass vaccination strategies against highly pathogenic avian influenza (HPAI). One regimen used Legok 2003 H5N1 vaccine, while the other used both Legok 2003 H5N1 and HB1 Newcastle disease (ND) vaccine. A total of 16 districts were involved in the study. The sample size was estimated using a formal power calculation technique that assumed a detectable effect of treatment as a 50% reduction in the baseline number of HPAI-compatible outbreaks. Within each district, candidate treatment blocks with village poultry populations ranging from 80 000 to 120 000 were created along subdistrict boundary lines. Subsequently, four of these blocks were randomly selected and assigned one treatment from a list that comprised control, vaccination against HPAI, vaccination against HPAI + ND. Four rounds of vaccination were administered at quarterly intervals beginning in July 2008. A vaccination campaign involved vaccinating 100 000 birds in a treatment block, followed by another 100 000 vaccinations 3 weeks later as a booster dose. Data on disease incidence and vaccination coverage were also collected at quarterly intervals using participatory epidemiological techniques. Compared with the unvaccinated (control) group, the incidence of HPAI-compatible events declined by 32% (P = 0.24) in the HPAI-vaccinated group and by 73% (P = 0.00) in the HPAI- and ND-vaccinated group. The effect of treatment did not vary with time or district. Similarly, an analysis of secondary data from the participatory disease and response (PDSR) database revealed that the incidence of HPAI declined by 12% in the HPAI-vaccinated group and by 24% in the HPAI + ND-vaccinated group. The results suggest that the HPAI + ND vaccination significantly reduced the incidence of HPAI-compatible events in mixed populations of

  17. A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain.

    PubMed

    Jornayvaz, François R; Jurczak, Michael J; Lee, Hui-Young; Birkenfeld, Andreas L; Frederick, David W; Zhang, Dongyang; Zhang, Xian-Man; Samuel, Varman T; Shulman, Gerald I

    2010-11-01

    Low-carbohydrate, high-fat ketogenic diets (KD) have been suggested to be more effective in promoting weight loss than conventional caloric restriction, whereas their effect on hepatic glucose and lipid metabolism and the mechanisms by which they may promote weight loss remain controversial. The aim of this study was to explore the role of KD on liver and muscle insulin sensitivity, hepatic lipid metabolism, energy expenditure, and food intake. Using hyperinsulinemic-euglycemic clamps, we studied insulin action in mice fed a KD or regular chow (RC). Body composition was assessed by ¹H magnetic resonance spectroscopy. Despite being 15% lighter (P < 0.001) than RC-fed mice because of a 17% increase in energy expenditure (P < 0.001), KD-fed mice manifested severe hepatic insulin resistance, as reflected by decreased suppression (0% vs. 100% in RC-fed mice, P < 0.01) of endogenous glucose production during the clamp. Hepatic insulin resistance could be attributed to a 350% increase in hepatic diacylglycerol content (P < 0.001), resulting in increased activation of PKCε (P < 0.05) and decreased insulin receptor substrate-2 tyrosine phosphorylation (P < 0.01). Food intake was 56% (P < 0.001) lower in KD-fed mice, despite similar caloric intake, and could partly be attributed to a more than threefold increase (P < 0.05) in plasma N-acylphosphatidylethanolamine concentrations. In conclusion, despite preventing weight gain in mice, KD induces hepatic insulin resistance secondary to increased hepatic diacylglycerol content. Given the key role of nonalcoholic fatty liver disease in the development of type 2 diabetes and the widespread use of KD for the treatment of obesity, these results may have potentially important clinical implications.

  18. Preventing effects of joint contracture by high molecular weight hyaluronan injections in a rat immobilized knee model

    PubMed Central

    Kanazawa, Kenji; Hagiwara, Yoshihiro; Tsuchiya, Masahiro; Yabe, Yutaka; Sonofuchi, Kazuaki; Koide, Masashi; Sekiguchi, Takuya; Itaya, Nobuyuki; Ando, Akira; Saijo, Yoshifumi; Itoi, Eiji

    2015-01-01

    Purpose: To elucidate preventive effects of high molecular weight hyaluronan (HMWHA) on the joint capsule of immobilized knees in rats. Materials and Methods: Unilateral knee joints of rats were immobilized with an internal fixator. Either 50 μl of HMWHA (Im-HA group) or 50 μl of saline (control group) was administered intra-articularly once a week after surgery. Sagittal sections were prepared from the medial midcondylar region of the knee joints and assessed by histological, histomorphometric, and immunohistochemical methods. Gene expressions related to inflammation, fibrotic conditions, and hypoxia were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Tissue elasticity of the capsule from both groups was examined using a scanning acoustic microscope (SAM). Results: CD68 positive cells decreased in adhesion areas of the synovial membrane after 1 week in both groups. The length of the superficial layer in the synovial membrane of the Im-HA group was significantly longer than those in the control group over a period of 4 to 8 weeks with significantly small numbers of CD68 positive cells. The gene expressions of IL-6, IL-1β, TGF-β, CTGF, COL1a1, COL3a1, SPARC, and HIF1-α were significantly lower in the Im-HA group compared to those in the control group. The sound speed of the anterior and posterior synovial membrane increased significantly (a reduction in elasticity) in the control group compared to those in the Im-HA group during weeks 1 to 4. Conclusions: This study demonstrated that HMWHA injections suppressed inflammatory, fibrotic, and hypoxic conditions observed in the immobilized joint capsule. PMID:26097527

  19. Comparison of the Effects of Four Suicide Prevention Programs for Family and Friends of High-Risk Suicidal Men Who Do Not Seek Help Themselves

    ERIC Educational Resources Information Center

    Mishara, Brian L.; Houle, Janie; Lavoie, Brigitte

    2005-01-01

    Callers to a suicide prevention center concerned about high risk men were randomly invited to participate in one of four programs: Information Session, Information Session with Telephone Follow-up, Rapid Referral to mental health and abuse programs, or Telephone Support. Comparison of pre-test, 2 month post-test and 6 months follow-up with 131…

  20. Preventive Intervention for Preschoolers at High Risk for Antisocial Behavior: Long-Term Effects on Child Physical Aggression and Parenting Practices

    ERIC Educational Resources Information Center

    Brotman, Laurie Miller; Gouley, Kathleen Kiely; Huang, Keng-Yen; Rosenfelt, Amanda; O'Neal, Colleen; Klein, Rachel G.; Shrout, Patrick

    2008-01-01

    This article presents long-term effects of a preventive intervention for young children at high risk for antisocial behavior. Ninety-two children (M age = 4 years) were randomly assigned to an 8-month family intervention or no-intervention control condition and assessed 4 times over a 24-month period. Intent-to-treat analyses revealed significant…

  1. An Effectiveness Trial of a Selected Dissonance-Based Eating Disorder Prevention Program for Female High School Students: Long-Term Effects

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Shaw, Heather; Gau, Jeff

    2011-01-01

    Objective: Efficacy trials found that a dissonance-based eating disorder prevention program in which female high school and college students with body image concerns critique the thin ideal reduced eating disorder risk factors, eating disorder symptoms, and future eating disorder onset. The present effectiveness trial tested whether this program…

  2. High- and Low-Level Dissonance-Based Eating Disorder Prevention Programs with Young Women with Body Image Concerns: An Experimental Trial

    ERIC Educational Resources Information Center

    McMillan, Whitney; Stice, Eric; Rohde, Paul

    2011-01-01

    Objective: As cognitive dissonance is theorized to contribute to the effects of dissonance-based eating disorder prevention programs, we evaluated a high-dissonance version of this program against a low-dissonance version and a wait-list control condition to provide an experimental test of the mechanism of intervention effects. Method: Female…

  3. Evaluation of the New York City Dropout Prevention Initiative. Final Report on the High Schools for Year Three, 1987-88. Part One: Program Description, Findings, and Recommendations.

    ERIC Educational Resources Information Center

    Grannis, Joseph; And Others

    This document comprises part 1 of a two-part evaluation of the third-year implementation of the New York City Board of Education's 3-year high school Dropout Prevention Initiative (DPI). It describes the DPI and presents the evaluation findings and recommendations. (Part 2 comprises reports on 8 special substudies of the program in year 3.) The…

  4. Evaluation of the New York City Dropout Prevention Initiative. Final Report on the High Schools for Year Two, 1986-87.

    ERIC Educational Resources Information Center

    Grannis, Joseph; And Others

    This evaluation of the second-year (1986-87) implementation of the New York City (New York) Dropout Prevention Initiative (DPI) in 13 high schools focuses on student characteristics and outcomes, with a discussion of a set of statistical data on program services, findings on school-level indicators of program effectiveness, and an analysis of…

  5. An Evaluation of Immediate Outcomes and Fidelity of a Drug Abuse Prevention Program in Continuation High Schools: Project towards No Drug Abuse (TND)

    ERIC Educational Resources Information Center

    Lisha, Nadra E.; Sun, Ping; Rohrbach, Louise A.; Spruijt-Metz, Donna; Unger, Jennifer B.; Sussman, Steve

    2012-01-01

    The present study provides an implementation fidelity, process, and immediate outcomes evaluation of Project Towards No Drug Abuse (TND), a drug prevention program targeting continuation high school youth (n = 1426) at risk for drug abuse. A total of 24 schools participated in three randomized conditions: TND Only, TND and motivational…

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

    PubMed

    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.

  7. Recruiting, Linking, and Retaining High-risk Transgender Women into HIV Prevention and Care Services: An Overview of Barriers, Strategies, and Lessons Learned

    PubMed Central

    Reback, Cathy J.; Ferlito, Dahlia; Kisler, Kimberly A.; Fletcher, Jesse B.

    2016-01-01

    Despite disproportionately high HIV prevalence rates and high risk for HIV acquisition and transmission, trans women in the United States are less likely than other high-risk populations to be aware of their HIV status or to perceive HIV infection as a serious health threat. Furthermore, concurrently high rates of unstable housing, few legal employment opportunities, lack of social support, and distrust of social service providers limit trans women's interest or ability to be recruited by, retained within, or linked into HIV prevention and care services. This article provides an overview of the barriers that prevent many high-risk trans women from being recruited, linked, and retained within HIV prevention and care services as well as accessing HIV testing services, and discusses several strategies for overcoming these barriers. Best practices in working with high-risk trans women include hiring trans women indigenous to the local trans communities, designing culturally specific recruitment and retention strategies including the creation of living “community maps” to ensure successful community outreach, the construction of a trans women-specific CAB to create dialogue with community stakeholders including consumers, and extensive cultural sensitivity training for staff and community collaborators to sensitize them to the specific needs of high-risk trans women participants. PMID:27110227

  8. Preeclampsia prevention

    PubMed Central

    Herrera-Medina, Rodolfo; Pineda, Lucia M

    2015-01-01

    Background: Preeclampsia is the main complication of pregnancy in developing countries. Calcium starting at 14 weeks of pregnancy is indicated to prevent the disease. Recent advances in prevention of preeclampsia endorse the addition of conjugated linoleic acid. Objective: To estimate the protective effect from calcium alone, compared to calcium plus conjugated linoleic acid in nulliparous women at risk of preeclampsia. Methods: A case-control design nested in the cohort of nulliparous women attending antenatal care from 2010 to 2014. The clinical histories of 387 cases of preeclampsia were compared with 1,054 normotensive controls. The exposure was prescriptions for calcium alone, the first period, or calcium plus conjugated linoleic acid, the second period, from 12 to 16 weeks of gestational age to labor. Confounding variables were controlled, allowing only nulliparous women into the study and stratifying by age, education and ethnic group. Results: The average age was 26.4 yrs old (range= 13-45), 85% from mixed ethnic backgrounds and with high school education. There were no differences between women who received calcium carbonate and those who did not (OR= 0.96; 95% CI= 0.73-1.27). The group of adolescents (13 to 18 years old) in the calcium plus conjugated linoleic acid was protected for preeclampsia (OR= 0.00; 95% CI= 0.00-0.44) independent of the confounder variables. Conclusions: 1. Calcium supplementation during pregnancy did not have preventive effects on preeclampsia. 2. Calcium plus Conjugated Linoleic acid provided to adolescents was observed to have preventive effect on Preeclampsia. PMID:26848195

  9. Exposure and preventive measure to reduce high and daily exposure to Bacillus thuringiensis in potted plant production.

    PubMed

    Madsen, Anne Mette; Zervas, Athanasios; Tendal, Kira; Matthiesen, Christoffer B; Koponen, Ismo Kalevi; Hansen, Erik Wind

    2014-07-01

    The bacterium Bacillus thuringiensis (Bt) is the active organism in a variety of commercially available products used worldwide as biopesticides. Bt products are applied in large outdoor areas as well as in indoor environments. Even though it has been sold for decades, not much is known about the occupational exposure to Bt. The aim of this study was to obtain knowledge about the exposure to Bt subspecies israelensis (Bti) in a propagation section in a greenhouse, where Bti is applied hourly by a spray boom, and to test a preventive measure to reduce the exposure to airborne Bti. Furthermore, we wanted to study the exposure during work with potted plants treated earlier with Bti. Exposure to aerosols with Bti was measured repeatedly by personal and stationary samplers before and after the intervention. Bti was identified by polymerase chain reaction in air and soil samples. Personal exposure to inhalable Bti in the propagation section was 3×10(5) cfu m(-3) (median level, n = 22); the personal exposure of people working with plants treated earlier with Bti was 3200 cfu m(-3) (median level, n = 17). The highest single measure was found for the person working with the spray boom (7×10(5) cfu m(-3)) but airborne Bti was present at all sampling stations in the propagation section. Bti constituted a high share of the airborne cultivable bacteria and a smaller share of the soilborne bacteria in the propagation section. In a human cell assay, spiking an aerosol sample with a product with Bti increased the inflammatory potential of an aerosol sample from the greenhouse significantly. Based on the inflammatory potential and the high personal exposure, a cover around the spray boom was built as an attempt to reduce the daily exposure to Bti. The cover reduced the personal exposure to Bti from 3.0×10(5) cfu m(-3) to 1.8×10(4) cfu m(-3). The exposure was thus reduced by a factor 17, which is a considerable reduction. Bti was present in different particle size fractions with

  10. Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices

    PubMed Central

    Sezdi, Mana

    2016-01-01

    A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older technology devices and predictive maintenance for newer high-tech devices. For preventive maintenance development, 589 older technology devices were subjected to performance verification and safety testing (PVST). For predictive maintenance development, the manufacturers' recommendations were used for 134 high-tech devices. These strategies were evaluated in terms of device reliability. This study recommends the use of two different maintenance strategies for old and new devices at hospitals in developing countries. Thus, older technology devices that applied only corrective maintenance will be included in maintenance like high-tech devices. PMID:27195666

  11. Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices.

    PubMed

    Sezdi, Mana

    2016-01-01

    A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older technology devices and predictive maintenance for newer high-tech devices. For preventive maintenance development, 589 older technology devices were subjected to performance verification and safety testing (PVST). For predictive maintenance development, the manufacturers' recommendations were used for 134 high-tech devices. These strategies were evaluated in terms of device reliability. This study recommends the use of two different maintenance strategies for old and new devices at hospitals in developing countries. Thus, older technology devices that applied only corrective maintenance will be included in maintenance like high-tech devices.

  12. Preventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress in male Wistar rats.

    PubMed

    Reddy, Singareddy Sreenivasa; Ramatholisamma, Pasurla; Karuna, Rasineni; Saralakumari, Desireddy

    2009-09-01

    High intake of dietary fructose exerts a number of adverse metabolic effects. The aim of the present study was to investigate whether aqueous extract of Tinospora cordifolia stem (TCAE) alleviates high-fructose diet-induced insulin resistance and oxidative stress in rats. High-fructose diet (66% of fructose) and TCAE (400 mg/kg/day) were given simultaneously for a period of 60 days. Fructose fed rats showed hyperglycemia, hyperinsulinemia, hypertriglyceridemia, impaired glucose tolerance and impaired insulin sensitivity (P<0.05). TCAE treatment prevented the rise in glucose levels by 21.3%, insulin by 51.5%, triglycerides by 54.12% and glucose-insulin index by 59.8% of the fructose fed rats. Regarding liver antioxidant status, fructose fed rats showed higher values of lipid peroxidation (91.3%), protein carbonyl groups (44%) and lowered GSH levels (42.1%) and, lowered activities of enzymatic antioxidants, while TCAE treatment prevented all these observed abnormalities. In conclusion, our data indicate the preventive role of T. cordifolia against fructose-induced insulin resistance and oxidative stress; hence this plant could be used as an adjuvant therapy for the prevention and/or management of chronic diseases characterized by hyperinsulinemia, hypertriglyceridemia, insulin resistance and aggravated antioxidant status.

  13. Dietary β-conglycinin prevents fatty liver induced by a high-fat diet by a decrease in peroxisome proliferator-activated receptor γ2 protein.

    PubMed

    Yamazaki, Tomomi; Kishimoto, Kyoko; Miura, Shinji; Ezaki, Osamu

    2012-02-01

    Diets high in sucrose/fructose or fat can result in hepatic steatosis (fatty liver). Mice fed a high-fat diet, especially that of saturated-fat-rich oil, develop fatty liver with an increase in peroxisome proliferator-activated receptor (PPAR) γ2 protein in liver. The fatty liver induced by a high-fat diet is improved by knockdown of liver PPARγ2. In this study, we investigated whether β-conglycinin (a major protein of soy protein) could reduce PPARγ2 protein and prevent high-fat-diet-induced fatty liver in ddY mice. Mice were fed a high-starch diet (70 energy% [en%] starch) plus 20% (wt/wt) sucrose in their drinking water or a high-safflower-oil diet (60 en%) or a high-butter diet (60 en%) for 11 weeks, by which fatty liver is developed. As a control, mice were fed a high-starch diet with drinking water. Either β-conglycinin or casein (control) was given as dietary protein. β-Conglycinin supplementation completely prevented fatty liver induced by each type of diet, along with a reduction in adipose tissue weight. β-Conglycinin decreased sterol regulatory element-binding protein (SREBP)-1c and carbohydrate response element-binding protein (ChREBP) messenger RNAs (mRNAs) in sucrose-supplemented mice, whereas it decreased PPARγ2 mRNA (and its target genes CD36 and FSP27), but did not decrease SREBP-1c and ChREBP mRNAs, in mice fed a high-fat diet. β-Conglycinin decreased PPARγ2 protein and liver triglyceride (TG) concentration in a dose-dependent manner in mice fed a high-butter diet; a significant decrease in liver TG concentration was observed at a concentration of 15 en%. In conclusion, β-conglycinin effectively prevents fatty liver induced by a high-fat diet through a decrease in liver PPARγ2 protein.

  14. High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodeling.

    PubMed

    Santiago, Jon-Jon; McNaughton, Leslie J; Koleini, Navid; Ma, Xin; Bestvater, Brian; Nickel, Barbara E; Fandrich, Robert R; Wigle, Jeffrey T; Freed, Darren H; Arora, Rakesh C; Kardami, Elissavet

    2014-01-01

    Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD) and 68% (±25 SD) of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs) expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II) up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2) reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial) tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes deleterious

  15. Evaluating the potential impact of mass praziquantel administration for HIV prevention in Schistosoma haematobium high-risk communities.

    PubMed

    Ndeffo Mbah, Martial L; Gilbert, Jennifer A; Galvani, Alison P

    2014-06-01

    Genital infection with Schistosoma haematobium is prevalent in sub-Saharan Africa. Epidemiological studies have observed that genital schistosomiasis is associated with an increased odd of HIV infection among women. We used mathematical modeling to explore the potential impact of mass preventive chemotherapy against schistosomiasis on HIV transmission in three sub-Saharan Africa countries: Angola, Kenya, and Zambia. We developed a model of female genital schistosomiasis (FGS) and HIV transmission dynamics, fitting it to data of HIV and S. haematobium prevalences as well as co-infection. We simulated targeted mass drug administration (MDA) with praziquantel to school-age children and mass treatment of the entire community. We estimated that, in S. haematobium high-risk communities, targeted annual treatment of school-age children could reduce HIV prevalence by 20% (95% CI: 12-31%) in Angola, 16% (95% CI: 10-32%) in Kenya, and 6% (95% CI: 3-18%) in Zambia after the first 20 years of intervention; and would reduce HIV incidence by 15% (95% CI: 13-32%) in Angola, 22% (95% CI: 18-42%) in Kenya, and 9% (95% CI: 3-22%) in Zambia. Extending the intervention to adults could reduce HIV prevalence by an additional 2.2% (95% CI: 0.2-12.0%) in Angola, 1.8% (95% CI: 0.1-5.2%) in Kenya, and 0.3% (95% CI: 0.1-2.1%) in Zambia; and would reduce HIV incidence by an additional 1.8% (95% CI: 0.0-14.4%) in Angola, 6.1% (95% CI: 0.5-12.6%) in Kenya, and 0.8% (95% CI: 0.0-2.7%) in Zambia. We showed that the exacerbation of HIV transmission due to FGS and the probability of developing FGS as a result of childhood infection with S. haematobium, were the most important factors in determining the effectiveness of praziquantel MDA for reducing HIV transmission. Praziquantel MDA may be an innovative measure for reducing schistosomiasis and HIV transmission in sub-Saharan Africa, the effectiveness of which varies with HIV prevalence.

  16. Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth.

    PubMed

    Patkee, Wishwanath R A; Carr, Georgina; Baker, Emma H; Baines, Deborah L; Garnett, James P

    2016-04-01

    Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P. aeruginosa infections across airway epithelial (Calu-3) cultures by limiting glucose permeability. We also explored the effect of P. aeruginosa and metformin on airway epithelial barrier function by investigating changes in tight junction protein abundance. Apical P. aeruginosa growth increased with basolateral glucose concentration, reduced transepithelial electrical resistance (TEER) and increased paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose flux. Similar effects on bacterial growth and TEER were observed with the AMP activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide. Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction in the abundance of tight junction proteins, claudin-1 and occludin. Our study highlights the potential of metformin to reduce hyperglycaemia-induced P. aeruginosa growth through airway epithelial tight junction modulation, and that claudin-1 and occludin could be important targets to regulate glucose permeability across airway epithelia and supress bacterial growth. Further investigation into the mechanisms regulating metformin and P. aeruginosa action on airway epithelial tight junctions could yield new therapeutic targets to prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use of antibiotics.

  17. Preliminary Testing of a Program to Prevent Type 2 Diabetes among High-Risk Youth.(research Papers)

    ERIC Educational Resources Information Center

    Grey, Margaret; Berry, Diane; Davidson, Maryanne; Galasso, Pam; Gustafson, Elaine; Melkus, Gail

    2004-01-01

    Type 2 diabetes is increasing among youth, with minority youth at highest risk. This preliminary study tested the feasibility of a school-based program to prevent type 2 diabetes in youth at risk. Forty-one participants (age 12.6 [+ or -] 1.1 years; 63% female, 51% African American, 44% Hispanic, and 5% Caucasian) were randomly assigned to one of…

  18. Suicide Risk Protocols: Addressing the Needs of High Risk Youths Identified through Suicide Prevention Efforts and in Clinical Settings

    ERIC Educational Resources Information Center

    Heilbron, Nicole; Goldston, David; Walrath, Christine; Rodi, Michael; McKeon, Richard

    2013-01-01

    Several agencies have emphasized the importance of establishing clear protocols or procedures to address the needs of youths who are identified as suicidal through suicide prevention programs or in emergency department settings. What constitutes optimal guidelines for developing and implementing such protocols, however, is unclear. At the request…

  19. Examining the Feasibility and Acceptability of a Motivational Interviewing Early Intervention Program to Prevent High School Dropout

    ERIC Educational Resources Information Center

    Iachini, Aidyn L.; Rogelberg, Sandra; Terry, John David; Lutz, Amy

    2016-01-01

    This article describes Aspire, a new motivational interviewing (MI) early intervention program designed to prevent dropout among students repeating the ninth grade, and then examines the feasibility and acceptability of this program through a mixed-methods approach. The Aspire program is a nine-lesson curriculum grounded in MI with an emphasis on…

  20. An Effectiveness Trial of a Dissonance-Based Eating Disorder Prevention Program for High-Risk Adolescent Girls

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Gau, Jeff; Shaw, Heather

    2009-01-01

    Efficacy trials indicate that an eating disorder prevention program involving dissonance-inducing activities that decrease thin-ideal internalization reduces risk for current and future eating pathology, yet it is unclear whether this program produces effects under real-world conditions. The present effectiveness trial tested whether this program…

  1. Predictors of Colorectal Screening in Rural Colorado: Testing to Prevent Colon Cancer in the High Plains Research Network

    ERIC Educational Resources Information Center

    Young, Walter F.; McGloin, Joe; Zittleman, Linda; West, David R.; Westfall, John M.

    2007-01-01

    Context: Colorectal cancer is the second leading cause of cancer death in the United States, yet screening rates are well below target levels. Rural communities may face common and unique barriers to health care, particularly preventive health care. Purpose: To establish baseline attitudinal, knowledge, belief, and behavior measures on colorectal…

  2. Fall Prevention: Simple Tips to Prevent Falls

    MedlinePlus

    ... fall-prevention plan. High heels, floppy slippers and shoes with slick soles can make you slip, stumble ... your stocking feet. Instead, wear properly fitting, sturdy shoes with nonskid soles. Sensible shoes may also reduce ...

  3. Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity.

    PubMed

    Maamoun, Hatem; Zachariah, Matshediso; McVey, John H; Green, Fiona R; Agouni, Abdelali

    2017-03-01

    Most of diabetic cardiovascular complications are attributed to endothelial dysfunction and impaired angiogenesis. Endoplasmic Reticulum (ER) and oxidative stresses were shown to play a pivotal role in the development of endothelial dysfunction in diabetes. Hemeoxygenase-1 (HO-1) was shown to protect against oxidative stress in diabetes; however, its role in alleviating ER stress-induced endothelial dysfunction remains not fully elucidated. We aim here to test the protective role of HO-1 against high glucose-mediated ER stress and endothelial dysfunction and understand the underlying mechanisms with special emphasis on oxidative stress, inflammation and cell death. Human Umbilical Vein Endothelial Cells (HUVECs) were grown in either physiological or intermittent high concentrations of glucose for 5days in the presence or absence of Cobalt (III) Protoporphyrin IX chloride (CoPP, HO-1 inducer) or 4-Phenyl Butyric Acid (PBA, ER stress inhibitor). Using an integrated cellular and molecular approach, we then assessed ER stress and inflammatory responses, in addition to apoptosis and angiogenic capacity in these cells. Our results show that HO-1 induction prevented high glucose-mediated increase of mRNA and protein expression of key ER stress markers. Cells incubated with high glucose exhibited high levels of oxidative stress, activation of major inflammatory and apoptotic responses [nuclear factor (NF)-κB and c-Jun N-terminal kinase (JNK)] and increased rate of apoptosis; however, cells pre-treated with CoPP or PBA were fully protected. In addition, high glucose enhanced caspases 3 and 7 cleavage and activity and augmented cleaved poly ADP ribose polymerase (PARP) expression whereas HO-1 induction prevented these effects. Finally, HO-1 induction and ER stress inhibition prevented high glucose-induced reduction in NO release and impaired the angiogenic capacity of HUVECs, and enhanced vascular endothelial growth factor (VEGF)-A expression. Altogether, we show here the

  4. An Evaluation of Intravaginal Rings as a Potential HIV Prevention Device in Urban Kenya: Behaviors and Attitudes That Might Influence Uptake within a High-Risk Population

    PubMed Central

    Wakasiaka, Sabina; Hoang, Tina Dan My; Bwayo, Job Joab; del Rio, Carlos; Priddy, Frances H.

    2008-01-01

    Abstract Purpose We sought to assess the potential acceptability of intravaginal rings (IVRs) as an HIV prevention method among at-risk women and men. Methods We conducted a qualitative assessment of initial attitudes toward IVRs, current HIV prevention methods, and common behavioral practices among female sex workers (FSWs) and men who frequent FSWs in Mukuru, an urban slum community in Nairobi, Kenya. Nineteen women and 21 men took part in six focus group discussions. Results Most participants, both male and female, responded positively to the concept of an IVR as a device for delivering microbicides. Women particularly liked the convenience offered by its slow-release capacity. Some female respondents raised concerns about whether male customers would discover the ring and respond negatively, whereas others thought it unlikely that their clients would feel the ring. Focus groups conducted with male clients of FSWs suggested that many would be enthusiastic about women, and particularly sex workers, using a microbicide ring, but that women's fears about negative responses to covert use were well founded. Overall, this high-risk population of FSWs and male clients in Nairobi was very open to the IVR as a potential HIV prevention device. Conclusion Themes that emerged from the focus groups highlight the importance of understanding attitudes toward IVRs as well as cultural practices that may impact IVR use in high-risk populations when pursuing clinical development of this potential HIV prevention device. PMID:18681822

  5. Using the Information-Motivation-Behavioral Skills Model to Guide the Development of an HIV Prevention Smartphone Application for High-Risk MSM.

    PubMed

    Aliabadi, Negar; Carballo-Dieguez, Alex; Bakken, Suzanne; Rojas, Marlene; Brown, William; Carry, Monique; Mosley, Jocelyn Patterson; Gelaude, Deborah; Schnall, Rebecca

    2015-12-01

    HIV remains a significant public health problem among men who have sex with men (MSM). MSM comprise 2% of the U.S. population, but constitute 56% of persons living with HIV. Mobile health technology is a promising tool for HIV prevention. The purpose of this study was to identify the desired content, features and functions of a mobile application (app) for HIV prevention in high-risk MSM. We conducted five focus group sessions with 33 MSM. Focus group recordings were transcribed and coded using themes informed by the information-motivation-behavioral (IMB) skills model. Participants identified information needs related to HIV prevention: HIV testing and prophylaxis distribution centers, support groups/peers, and HIV/STI disease/treatment information. Areas of motivation to target for the app included: attitudes and intentions. Participants identified behavioral skills to address with an app: using condoms correctly, negotiating safer sex, recognizing signs of HIV/STI. Findings from this work provide insight into the desired content of a mobile app for HIV prevention in high-risk MSM.

  6. Psychosocial Implications of Homophobia and HIV Stigma in Social Support Networks: Insights for High-Impact HIV Prevention Among Black Men Who Have Sex With Men.

    PubMed

    Garcia, Jonathan; Parker, Caroline; Parker, Richard G; Wilson, Patrick A; Philbin, Morgan; Hirsch, Jennifer S

    2016-04-01

    Black men who have sex with men (BMSM) bear an increasingly disproportionate burden of HIV in the United States. The Centers for Disease Control and Prevention recommends high-impact combination prevention for populations at high risk for HIV infection, such as BMSM. However, few scholars have considered the types of behavioral interventions that combined with biomedical prevention could prove effective for mitigating the epidemic among BMSM. Between June 2013 and May 2014, we conducted three in-depth interviews each with 31 BMSM, interviews with 17 community stakeholders, and participant observation in New York City to understand the sociocultural and structural factors that may affect the acceptance of and adherence to oral preexposure prophylaxis among BMSM and to inform an adherence clinical trial. BMSM and community leaders frequently described condomless sex as a consequence of psychosocial factors and economic circumstances stemming from internalized homophobia resulting from rejection by families and religious groups. BMSM revealed that internalized homophobia and HIV stigma resulted in perceived lack of self- and community efficacy in accepting and adhering to preexposure prophylaxis. Our results indicate that addressing internalized homophobia and fostering emotional social support in peer networks are key elements to improve the effectiveness of combination prevention among BMSM.

  7. Using the Information-Motivation-Behavioral Skills Model to Guide the Development of an HIV Prevention Smartphone Application for High-Risk MSM

    PubMed Central

    Aliabadi, Negar; Carballo-Dieguez, Alex; Bakken, Suzanne; Rojas, Marlene; Brown, William; Carry, Monique; Mosley, Jocelyn Patterson; Gelaude, Deborah; Schnall, Rebecca

    2016-01-01

    HIV remains a significant public health problem among men who have sex with men (MSM). MSM comprise 2% of the U.S. population, but constitute 56% of persons living with HIV. Mobile health technology is a promising tool for HIV prevention. The purpose of this study was to identify the desired content, features and functions of a mobile application (app) for HIV prevention in high-risk MSM. We conducted five focus group sessions with 33 MSM. Focus group recordings were transcribed and coded using themes informed by the information-motivation-behavioral (IMB) skills model. Participants identified information needs related to HIV prevention: HIV testing and prophylaxis distribution centers, support groups/peers, and HIV/STI disease/treatment information. Areas of motivation to target for the app included: attitudes and intentions. Participants identified behavioral skills to address with an app: using condoms correctly, negotiating safer sex, recognizing signs of HIV/STI. Findings from this work provide insight into the desired content of a mobile app for HIV prevention in high-risk MSM. PMID:26595265

  8. Allergy prevention.

    PubMed

    Muche-Borowski, Cathleen; Kopp, Matthias; Reese, Imke; Sitter, Helmut; Werfel, Thomas; Schäfer, Torsten

    2010-09-01

    The further increase of allergies in industrialized countries demands evidence-based measures of primary prevention. The recommendations as published in the guideline of 2004 were updated and consented on the basis of a systematic literature search. Evidence from the period February 2003-May 2008 was searched in the electronic databases Cochrane and MEDLINE as well as in reference lists of recent reviews and by contacting experts. The retrieved citations were screened for relevance first by title and abstract and in a second step as full paper. Levels of evidence were assigned to each included study and the methodological quality of the studies was assessed as high or low. Finally the revised recommendations were formally consented (nominal group process) by representatives of relevant societies and organizations including a self-help group. Of originally 4556 hits, 217 studies (4 Cochrane Reviews, 14 meta-analyses, 19 randomized controlled trials, 135 cohort and 45 case-control studies) were included and critically appraised. Grossly unchanged remained the recommendations on avoiding environmental tobacco smoke, breast-feeding over 4 months (alternatively hypoallergenic formulas for children at risk), avoiding a mold-promoting indoor climate, vaccination according to current recommendations, and avoidance of furry pets (especially cats) in children at risk. The recommendation on reducing the house dust mite allergen exposure as a measure of primary prevention was omitted and the impact of a delayed introduction of supplementary food was reduced. New recommendations were adopted concerning fish consumption (during pregnancy / breast-feeding and as supplementary food in the first year), avoidance of overweight, and reducing the exposure to indoor and outdoor air pollutants. The revision of this guideline on a profound evidence basis led to (1) a confirmation of existing recommendations, (2) substantial revisions, and (3) new recommendations. Thereby it is possible

  9. Polyp Prevention Trial

    Cancer.gov

    The primary objective of the Polyp Prevention Trial (PPT) is to determine whether a low fat, high fiber, high vegetable and fruit eating plan will decrease the recurrence of adenomatous polyps of the large bowel.

  10. High uptake of naloxone-based overdose prevention training among previously incarcerated syringe-exchange program participants

    PubMed Central

    Barocas, Joshua A.; Baker, Lisa; Hull, Shawnika J.; Stokes, Scott; Westergaard, Ryan P.

    2016-01-01

    Background Incarceration is common among people who inject drugs. Prior research has shown that incarceration is a marker of elevated risk for opioid overdose, suggesting that the criminal justice system may be an important, under-utilized venue for implementing overdose prevention strategies. To better understand the feasibility and acceptability of such strategies, we evaluated the utilization of naloxone-based overdose prevention training among people who inject drugs with and without a history of incarceration. Methods We surveyed clients who utilize a multi-site syringe exchange program (SEP) in 2 cities in the Midwestern United States. Participants completed an 88-item, computerized survey assessing history of incarceration, consequences associated with injection, injecting practices, and uptake of harm reduction strategies. Results Among 543 respondents who injected drugs in the prior 30 days, 243 (43%) reported prior incarceration. Comparing those with and without a history of incarceration, there were no significant differences with respect to age, gender, or race. Those who observed an overdose, experienced overdose, and received training to administer or have administered naloxone were more likely to report incarceration. Overall, 69% of previously incarcerated clients had been trained to administer naloxone. Conclusion People who inject drugs with a history of incarceration appear to have a higher risk of opioid overdose than those never incarcerated, and are more willing to utilize naloxone as an overdose prevention strategy. Naloxone training and distribution is an important component of comprehensive prevention services for persons with opioid use disorders. Expansion of services for persons leaving correctional facilities should be considered. PMID:26143300

  11. Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

    PubMed Central

    Yano, Shuya; Takehara, Kiyoto; Miwa, Shinji; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2016-01-01

    We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model. PMID:27689331

  12. Poison Prevention

    MedlinePlus

    ... the Word Shop AAP Find a Pediatrician Safety & Prevention Immunizations All Around At Home At Play On ... Listen Español Text Size Email Print Share Poison Prevention Page Content Article B