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Sample records for prevents high glucose-induced

  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

    2007-07-01

    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. Serelaxin (recombinant human relaxin-2) prevents high glucose-induced endothelial dysfunction by ameliorating prostacyclin production in the mouse aorta.

    PubMed

    Ng, Hooi Hooi; Leo, Chen Huei; Parry, Laura J

    2016-05-01

    Diabetes-induced endothelial dysfunction is a critical initiating factor in the development of cardiovascular complications. Treatment with relaxin improves tumour necrosis factor α-induced endothelial dysfunction by enhancing endothelial nitric oxide synthase (eNOS) activity and restoring superoxide dismutase 1 protein in rat aortic rings ex vivo. It is, therefore, possible that relaxin treatment could alleviate endothelial dysfunction in diabetes. This study aimed to test the hypothesis that serelaxin (recombinant human relaxin-2) prevents high glucose-induced vascular dysfunction in the mouse aorta. Abdominal aortae were isolated from C57BL/6 male mice and incubated in M199 media for 3days with either normal glucose (5.5mM) or high glucose (30mM), and co-incubated with placebo (20mM sodium acetate) or 10nM serelaxin at 37°C in 5% CO2. Vascular function was analysed using wire-myography. High glucose significantly reduced the sensitivity to the endothelium-dependent agonist, acetylcholine (ACh) (pEC50; normal glucose=7.66±0.10 vs high glucose=7.29±0.10, n=11-12, P<0.05) and the contraction induced by NOS inhibitor, L-NAME (200μM) (normal glucose=59.9±8.3% vs high glucose=38.7±4.3%, n=6, P<0.05), but had no effect on the endothelium-independent agonist, sodium nitroprusside (SNP)-mediated relaxation. Treatment with serelaxin restored endothelial function (pEC50; 7.83±0.11, n=11) but not NO availability. The presence of the cyclooxygenase (COX) inhibitor, indomethacin (1μM) (pEC50; control=7.29±0.10 vs indo=7.74±0.18, n=6-12, P<0.05) and a superoxide dismutase mimetic, tempol (10μM) (pEC50; control=7.29±0.10 vs tempol=7.82±0.05, n=6-12, P<0.01) significantly improved sensitivity to ACh in high glucose treated aortae, but had no effect in serelaxin treated aortae. This suggests that high glucose incubation alters the superoxide and COX-sensitive pathway, which was normalized by co-incubation with serelaxin. Neither high glucose incubation nor serelaxin

  5. Delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells.

    PubMed

    Song, Seung Eun; Jo, Hye Jun; Kim, Yong-Woon; Cho, Young-Je; Kim, Jae-Ryong; Park, So-Young

    2016-04-01

    This study examined the effect of delphinidin on high glucose-induced cell proliferation and collagen synthesis in mesangial cells. Glucose dose-dependently (5.6-25 mM) increased cell proliferation and collagen I and IV mRNA levels, whereas pretreatment with delphinidin (50 μM) prevented cell proliferation and the increased collagen mRNA levels induced by high glucose (25 mM). High glucose increased reactive oxygen species (ROS) generation, and this was suppressed by pretreating delphinidin or the antioxidant N-acetyl cysteine. NADPH oxidase (NOX) 1 was upregulated by high glucose, but pretreatment with delphinidin abrogated this upregulation. Increased mitochondrial superoxide by 25 mM glucose was also suppressed by delphinidin. The NOX inhibitor apocynin and mitochondria-targeted antioxidant Mito TEMPO inhibited ROS generation and cell proliferation induced by high glucose. Phosphorylation of extracellular signal regulated kinase (ERK)1/2 was increased by high glucose, which was suppressed by delphinidin, apocynin or Mito TEMPO. Furthermore, PD98059 (an ERK1/2 inhibitor) prevented the high glucose-induced cell proliferation and increased collagen mRNA levels. Transforming growth factor (TGF)-β protein levels were elevated by high glucose, and pretreatment with delphinidin or PD98059 prevented this augmentation. These results suggest that delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells.

  6. Rutin Prevents High Glucose-Induced Renal Glomerular Endothelial Hyperpermeability by Inhibiting the ROS/Rhoa/ROCK Signaling Pathway.

    PubMed

    Wang, Xiaoming; Zhao, Xiaohong; Feng, Ting; Jin, Gang; Li, Zhenjiang

    2016-09-01

    Diabetic nephropathy is a progressive kidney disease caused by damage to the capillaries in the glomeruli. Endothelial dysfunction is an early sign of diabetic cardiovascular disease and may contribute to progressive diabetic nephropathy. Hyperglycemia-induced endothelial hyperpermeability is crucial to diabetic nephropathy. Rutin has beneficial effects on diabetic nephropathy, but the exact mechanisms of its protective effect remain elusive. The aim of this study was to assess the role of pretreatment with rutin in an in vitro model of hyperglycemia-induced barrier dysfunction in human renal glomerular endothelial cells. Human renal glomerular endothelial cells were exposed to rutin and/or hyperglycemia for 24 h. Hyperglycemia increased permeability and decreased the junction protein occludin in the cell-cell junction area and the total expression in human renal glomerular endothelial cells, whereas rutin treatment significantly corrected these abnormalities. Furthermore, hyperglycemia-induced activation of RhoA/ROCK was reversed by treatment with rutin or the knockdown of ROCK2. Interestingly, rutin prevented hyperglycemia-induced hyperpermeability, and dysfunction of the tight junction, a high level of reactive oxygen species, and activation of RhoA/ROCK were significantly abolished with the knockdown of Nrf2. In conclusion, rutin significantly prevented hyperglycemia-disrupted renal endothelial barrier function by inhibiting the RhoA/ROCK signaling pathway through decreasing reactive oxygen species, which was mediated by the activation of Nrf2. Our results may explain, at least in part, some beneficial effects of rutin that may be applicable to the treatment of vascular disorders in diabetic nephropathy. PMID:27552253

  7. 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.

  8. Resveratrol ameliorates high glucose-induced protein synthesis in glomerular epithelial cells.

    PubMed

    Lee, Myung-Ja; Feliers, Denis; Sataranatarajan, Kavithalakshmi; Mariappan, Meenalakshmi M; Li, Manli; Barnes, Jeffrey L; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S

    2010-01-01

    High glucose-induced protein synthesis in the glomerular epithelial cell (GEC) is partly dependent on reduction in phosphorylation of AMP-activated protein kinase (AMPK). We evaluated the effect of resveratrol, a phytophenol known to stimulate AMPK, on protein synthesis. Resveratrol completely inhibited high glucose stimulation of protein synthesis and synthesis of fibronectin, an important matrix protein, at 3 days. Resveratrol dose-dependently increased AMPK phosphorylation and abolished high glucose-induced reduction in its phosphorylation. We examined the effect of resveratrol on critical steps in mRNA translation, a critical event in protein synthesis. Resveratrol inhibited high glucose-induced changes in association of eIF4E with eIF4G, phosphorylation of eIF4E, eEF2, eEF2 kinase and, p70S6 kinase, indicating that it affects important events in both initiation and elongation phases of mRNA translation. Upstream regulators of AMPK in high glucose-treated GEC were explored. High glucose augmented acetylation of LKB1, the upstream kinase for AMPK, and inhibited its activity. Resveratrol prevented acetylation of LKB1 and restored its activity in high glucose-treated cells; this action did not appear to depend on SIRT1, a class III histone deacetylase. Our data show that resveratrol ameliorates protein synthesis by regulating the LKB1-AMPK axis.

  9. The antioxidant edaravone prevents cardiac dysfunction by suppressing oxidative stress in type 1 diabetic rats and in high-glucose-induced injured H9c2 cardiomyoblasts.

    PubMed

    Ji, Lei; Liu, Yingying; Zhang, Ying; Chang, Wenguang; Gong, Junli; Wei, Shengnan; Li, Xudong; Qin, Ling

    2016-09-01

    Edaravone, a radical scavenger, has been recognized as a potential protective agent for cardiovascular diseases. However, little is known about the effect of edaravone in cardiac complications associated with diabetes. Here, we have demonstrated that edaravone prevents cardiac dysfunction and apoptosis in the streptozotocin-induced type 1 diabetic rat heart. Mechanistic studies revealed that edaravone treatment improved cardiac function and restored superoxide dismutase levels. In addition, treatment of diabetic animals by edaravone increased protein expressions of sirtuin-1 (SIRT-1), peroxisome proliferator activated receptor γ coactivator α (PGC-1α), nuclear factor like-2 (NRF-2), and B cell lymphoma 2 (Bcl-2), and reduced protein expressions of Bax and Caspase-3 compared to the control group. High glucose incubation resulted in the production of reactive oxygen species (ROS) and cell death. Treatment of high-glucose-incubated H9c2 cells by edaravone reduced ROS production and cell death. In addition, the treatment of high-glucose-incubated H9c2 cells by edaravone increased the activity of antioxidative stress by increasing SIRT-1, PGC-1α, and NRF-2, and this treatment also reduced apoptosis by increasing Bcl-2 expression and reducing Bax and Caspase-3 expressions. Knockdown SIRT-1 with small interferer RNA abolished the effects of edaravone. Overall, our data demonstrated that edaravone may be an effective agent against the development of diabetic cardiomyopathy. PMID:27376621

  10. 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

  11. 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

  12. Blockade of chronic high glucose-induced endothelial apoptosis by Sasa borealis bamboo extract.

    PubMed

    Choi, Yean-Jung; Lim, Hyeon-Sook; Choi, Jung-Suk; Shin, Seung-Yong; Bae, Ji-Young; Kang, Sang-Wook; Kang, Il-Jun; Kang, Young-Hee

    2008-05-01

    Hyperglycemia is a causal factor in the development of diabetic vascular complications including impaired vascular smooth muscle contractility and increased cell proliferation. The present study was designed to investigate the effects of Sasa borealis water-extract (SBwE) on chronic hyperglycemia-induced oxidative stress and apoptosis in human umbilical endothelial cells (HUVEC). HUVEC were cultured in 5.5 mM low glucose, 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control, or 33 mM high glucose for 5 days in the absence and presence of 1-30 microg/ ml SBwE. Caspase-3 activation and Annexin V staining revealed chronic high glucose-induced endothelial apoptotic toxicity with a generation of oxidants detected by DCF-fluorescence, and these effects were reversed by SBwE at > or =1 microg/ml in a dose-dependent manner. Cytoprotective SBwE substantially reduced the sustained high glucose-induced expression of endothelial nitric oxide synthase and attenuated the formation of peroxynitrite radicals. The suppressive effects of SBwE were most likely mediated through blunting activation of PKC beta 2 and NADPH oxidase promoted by high glucose. In addition, this bamboo extract modulated the high glucose-triggered mitogen-activated protein kinase-dependent upregulation of heat-shock proteins. Our results suggest that SBwE suppressed these detrimental effects caused by PKC-dependent peroxynitrite formation via activation of NADPH oxidase and induction of nitric oxide synthase and heat-shock protein family that may be essential mechanisms responsible for increased apoptotic oxidative stress in diabetic vascular complications. Moreover, the blockade of high glucose-elicited heat-shock protein induction appeared to be responsible for SBwE-alleviated endothelial apoptosis. Therefore, SBwE may be a therapeutic agent for the prevention and treatment of diabetic endothelial dysfunction and related complications. PMID:18375828

  13. Protective effects of andrographolide derivative AL-1 on high glucose-induced oxidative stress in RIN-m cells.

    PubMed

    Yan, Hui; Li, Yongmei; Yang, Yali; Zhang, Zaijun; Zhang, Gaoxiao; Sun, Yewei; Yu, Pei; Wang, Yuqiang; Xu, Lipeng

    2016-01-01

    AL-1 is a novel andrographolide derivative synthesized by conjugating andrographolide and alpha lipoic acid. AL-1 has been found to increase insulin secretion, decrease blood glucose level and protect β-cell mass and function in alloxan-induced diabetic mouse model. However, the protective mechanism of AL-1 on high glucose-induced pancreatic β-cell injury is still not clear. In the present study, we found that AL-1 reduced reactive oxygen species (ROS) and nitric oxide (NO) generation induced by high glucose in RIN-m cells, and which elevated the activities of superoxide dismutase (SOD) and catalase (CAT). In addition, AL-1 increased the expression of NF-E2-related factor 2 (Nrf2), thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO- 1) proteins in RIN-m cells. These results suggest that AL-1 prevented RIN-m cells from high glucose-induced oxidative damage via upregulation of Nrf2 signaling pathway.

  14. Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells.

    PubMed

    Liu, Jingli; Yang, Jianhong

    2016-01-01

    Uncarboxylated osteocalcin, an osteoblast-derived protein, plays an important role in the regulation of glucose metabolism. It has previously been demonstrated that high glucose levels inhibit osteoblast proliferation and differentiation. However, the mechanisms through which uncarboxylated osteocalcin regulates osteoblast proliferation and differentiation under high glucose conditions remain unclear. Thus, in the present study, we aimed to examine the effects of uncarboxylated osteocalcin on the proliferation and differentiation of MC3T3-E1 cells under high glucose conditions. We demonstrated that high glucose levels induced the production of reactive oxygen species (ROS) in MC3T3-E1 cells, and this production was inhibited by treatment with uncarboxylated osteocalcin and N-acetyl-L-cysteine (NAC), a ROS scavenger. In addition, we found that uncarboxylated osteocalcin reduced high glucose‑induced oxidative stress and increased the mRNA expression of the osteogenic markers, runt-related transcription factor 2 (Runx2), osterix and osteocalcin, as well as the formation of mineralized nodules; it also inhibited adipogenic differentiation, as shown by a decrease in the mRNA expression of the adipogenic markers, peroxisome proliferator‑activated receptor γ (PPARγ), adipocyte fatty acid-binding protein (adipocyte protein 2; aP2) and fatty acid synthase (FAS), and reduced lipid drop accumulation. Furthermore, we found that uncarboxylated osteocalcin inhibited PI3K/Akt signaling which was induced by ROS and facilitated the osteogenic differentiation of MC3T3-E1 cells under high glucose conditions. Taken together and to the best of ou knowledge, our results demonstrate for the first time that uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by inhibiting the activation of PI3K/Akt in MC3T3-E1 cells. Therefore, we suggest that uncarboxylated osteocalcin may be a potential therapeutic agent for diabetes

  15. Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia.

    PubMed

    Aoshima, Naoya; Fujie, Yoshiko; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

    2014-01-01

    Inadequate calorie intake or starvation has been suggested as a cause of neonatal jaundice, which can further cause permanent brain damage, kernicterus. This study experimentally investigated whether additional glucose treatments induce the bilirubin-metabolizing enzyme--UDP-glucuronosyltransferase (UGT) 1A1--to prevent the onset of neonatal hyperbilirubinemia. Neonatal humanized UGT1 (hUGT1) mice physiologically develop jaundice. In this study, UGT1A1 expression levels were determined in the liver and small intestine of neonatal hUGT1 mice that were orally treated with glucose. In the hUGT1 mice, glucose induced UGT1A1 in the small intestine, while it did not affect the expression of UGT1A1 in the liver. UGT1A1 was also induced in the human intestinal Caco-2 cells when the cells were cultured in the presence of glucose. Luciferase assays demonstrated that not only the proximal region (-1300/-7) of the UGT1A1 promoter, but also distal region (-6500/-4050) were responsible for the induction of UGT1A1 in the intestinal cells. Adequate calorie intake would lead to the sufficient expression of UGT1A1 in the small intestine to reduce serum bilirubin levels. Supplemental treatment of newborns with glucose solution can be a convenient and efficient method to treat neonatal jaundice while allowing continuous breastfeeding. PMID:25209391

  16. Epigenetic regulation of high glucose-induced proinflammatory cytokine productionin monocytes by curcumin

    PubMed Central

    Yun, Jung-Mi; Jialal, Ishwarlal; Devaraj, Sridevi

    2010-01-01

    Diabetes is a pro-inflammatory state. We have previously shown increased monocyte pro-inflammatory cytokines in patients with Type 1 and Type 2 diabetes. High glucose induces pro-inflammatory cytokines via epigenetic changes. Curcumin, a polyphenol responsible for the yellow color of the spice turmeric, is known to exert potent anti-inflammatory activity in vitro. Recent studies indicate that it may regulate chromatin remodeling by inhibiting histone acetylation. In this study, we aimed to test the effect of curcumin on histone acetylation and pro-inflammatory cytokine secretion under high-glucose conditions in human monocytes. Human monocytic (THP-1) cells were cultured in presence of mannitol (osmolar control, mannitol) or normoglycemic (NG, 5.5 mmol/L glucose) or hyperglycemic (HG, 25 mmol/L glucose) conditions in absence or presence of curcumin (1.5-12.5μM) for 72 h. Cytokine level, nuclear factor κB (NF-κB) transactivation, histone deacetylases (HDACs) activity, histone acetylases (HATs) activity were measured by western blots, qRT-PCR, ELISA, Immunofluorescence (IF) staining. HG significantly induced histone acetylation, NF-κB activity and pro-inflammatory cytokine (IL-6, TNF-α and MCP-1) release from THP-1 cells. Curcumin suppressed NF-κB binding and cytokine release in THP-1 cells. Also, since p300 histone acetyltransferase is a coactivator of NF-κB, we examined its acetylation. Curcumin treatment also significantly reduced HAT activity, level of p300 and acetylated CBP/p300 gene expression, and induced histone deacetylase 2 (HDAC2) expression by curcumin. These results indicate that curcumin decreases HG-induced cytokine production in monocytes via epigenetic changes involving NF-κB. In conclusion, curcumin supplementation by reducing vascular inflammation may prevent diabetic complications. PMID:20655188

  17. 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.

  18. Epigallocatechin gallate, a constituent of green tea, regulates high glucose-induced apoptosis.

    PubMed

    Oh, Chang Joo; Yang, Eun Sun; Shin, Seoung Woo; Choi, Seong Hun; Park, Chan Ik; Yang, Chae Ha; Park, Jeen-Woo

    2008-01-01

    A high concentration of glucose has been implicated as a causal factor in initiation and progression of diabetic complications, and there is evidence to suggest that hyperglycemia increases the production of free radicals and oxidative stress. Therefore, compounds that scavenge reactive oxygen species may confer regulatory effects on high glucose-induced apoptosis. Epigallocatechin gallate (EGCG), the major polyphenolic of green tea, is reported to have an antioxidant activity. We investigated the effect of EGCG on high glucose-induced apoptosis in U937 cells. Upon exposure to 35 mM glucose for 2 days, there was a distinct difference between untreated cells and cells pre-treated with 1 microM EGCG for 2 h in regard to cellular redox status and oxidative DNA damage to cells. EGCG pre-treated cells showed significant suppression of apoptotic features such as DNA fragmentation, damage to mitochondrial function, and modulation of apoptotic marker proteins upon exposure to high glucose. This study indicates that EGCG may play an important role in regulating the apoptosis induced by high glucose presumably through scavenging of reactive oxygen species.

  19. Heme oxygenase-1-derived bilirubin protects endothelial cells against high glucose-induced damage.

    PubMed

    He, Meihua; Nitti, Mariapaola; Piras, Sabrina; Furfaro, Anna Lisa; Traverso, Nicola; Pronzato, Maria Adelaide; Mann, Giovanni E

    2015-12-01

    Hyperglycemia and diabetes are associated with endothelial cell dysfunction arising from enhanced oxidative injury, leading to the progression of diabetic vascular pathologies. The redox-sensitive transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a master regulator of antioxidant genes, such as heme oxygenase-1 (HO-1), involved in cellular defenses against oxidative stress. We have investigated the pathways involved in high glucose-induced activation of HO-1 in endothelial cells and examined the molecular mechanisms underlying cytoprotection. Elevated d-glucose increased intracellular generation of reactive oxygen species (ROS), leading to nuclear translocation of Nrf2 and HO-1 expression in bovine aortic endothelial cells, with no changes in cell viability. Superoxide scavenging and inhibition of endothelial nitric oxide synthase (eNOS) abrogated upregulation of HO-1 expression by elevated glucose. Inhibition of HO-1 increased the sensitivity of endothelial cells to high glucose-mediated damage, while addition of bilirubin restored cell viability. Our findings establish that exposure of endothelial cells to high glucose leads to activation of endogenous antioxidant defense genes via the Nrf2/ARE pathway. Upregulation of HO-1 provides cytoprotection against high glucose-induced oxidative stress through the antioxidant properties of bilirubin. Modulation of the Nrf2 pathway in the early stages of diabetes may thus protect against sustained damage by hyperglycemia during progression of the disease.

  20. High glucose induced nuclear factor kappa B mediated inhibition of endothelial cell migration.

    PubMed

    Hamuro, Masao; Polan, Jodie; Natarajan, Mohan; Mohan, Sumathy

    2002-06-01

    Delayed wound healing and accelerated atherosclerosis are common vascular complications of diabetes mellitus. Although elevated blood glucose level is the major contributing factor, mechanisms that mediate these complications are not clearly understood. In the present study, we have demonstrated that elevated glucose inhibits endothelial cell migration, thereby delaying wound healing. Our results clearly indicated that high glucose (10 or 30 mM) induced activation of nuclear factor kappa B (NF-kappaB) inhibited endothelial cell migration (P<0.05). High glucose induced NF-kappaB DNA binding activity may mediate this inhibition of migration by regulating intracellular nitric oxide. In vitro wound healing model in human aortic endothelial cells (HAEC) were used to evaluate cell migration under the influence of high glucose. The migration inhibited by high glucose was restored by NF-kappaB inhibitors (including E3-4-methylphenyl sulfonyl-2-propenenitrile, N-tosyl-Lys-chloromethylketone (TLCK), or over-expression of inhibitor subunit of kappaB) and endothelial nitric oxide synthase inhibitors (N-methyl-L-arginine (L-NMMA); and Nomega-nitro-L-arginine methyl ester (L-NAME)). Furthermore, NF-kappaB inhibitors attenuated high glucose induced eNOS expression and intracellular nitric oxide (NO) production. Cytoskeletal immunofluorescence staining confirmed differences in actin distribution in HAEC incubated in high glucose in the presence or absence of NF-kappaB and NO inhibitors, explaining the differences observed in migration. In summary, our results for the first time suggest therapeutic strategies involving inhibition of NF-kappaB activation induced by high glucose, which may improve wound healing and help avoid some of the vascular complications of diabetes.

  1. Autophagy is involved in high glucose-induced heart tube malformation

    PubMed Central

    Wang, Guang; Huang, Wen-qing; Cui, Shu-dan; Li, Shuai; Wang, Xiao-yu; Li, Yan; Chuai, Manli; Cao, Liu; Li, Jiang-chao; Lu, Da-xiang; Yang, Xuesong

    2015-01-01

    Both pre-gestational and gestational diabetes have an adverse impact on heart development, but little is known about the influence on the early stage of heart tube formation. Using early gastrulating chick embryos, we investigated the influence of high glucose on the process of heart tube formation, specifically during the primary heart field phase. We demonstrated that high-glucose exposure resulted in 3 types of heart tube malformation: 1) ventricular hypertrophy, 2) ventricular hypertrophy with dextrocardia and 3) ventricular hypertrophy and dextrocardia with the fusion anomaly of a bilateral primary heart tube. Next, we found that these malformation phenotypes of heart tubes might mainly originate from the migratory anomaly of gastrulating precardiac mesoderm cells rather than cell proliferation in the developmental process of bilateral primary heart field primordia. The treatment of rapamycin (RAPA), an autophagy inducer, led to a similar heart tube malformation phenotype as high glucose. Additionally, high-glucose exposure promoted the expression of the key autophagy protein LC3B in early chick tissue. Atg7 is strongly expressed in the fusion site of bilateral primary heart tubes. All of these data imply that autophagy could be involved in the process of high-glucose-induced malformation of the heart tube. PMID:25738919

  2. Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes.

    PubMed

    Zhang, Bin; Chen, Yaping; Shen, Qiang; Liu, Guiyan; Ye, Jingxue; Sun, Guibo; Sun, Xiaobo

    2016-01-01

    Hyperglycemia, as well as diabetes mellitus, has been shown to trigger cardiac cell apoptosis. We have previously demonstrated that myricitrin prevents endothelial cell apoptosis. However, whether myricitrin can attenuate H9c2 cell apoptosis remains unknown. In this study, we established an experiment model in H9c2 cells exposed to high glucose. We tested the hypothesis that myricitrin may inhibit high glucose (HG)-induced cardiac cell apoptosis as determined by TUNEL staining. Furthermore, myricitrin promoted antioxidative enzyme production, suppressed high glucose-induced reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) in H9c2 cells. This agent significantly inhibited apoptotic protein expression, activated Akt and facilitated the transcription of NF-E2-related factor 2 (Nrf2)-mediated protein (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1) expression as determined by Western blotting. Significantly, an Akt inhibitor (LY294002) or HO-1 inhibitor (ZnPP) not only inhibited myricitrin-induced HO-1/NQO-1 upregulation but also alleviated its anti-apoptotic effects. In summary, these observations demonstrate that myricitrin activates Nrf2-mediated anti-oxidant signaling and attenuates H9c2 cell apoptosis induced by high glucose via activation of Akt signaling. PMID:27399653

  3. Endoplasmic Reticulum Stress-Mediated Apoptosis Contributing to High Glucose-Induced Vascular Smooth Muscle Cell Calcification.

    PubMed

    Zhu, Qiang; Guo, Runmin; Liu, Chang; Fu, Duguan; Liu, Fuyuan; Hu, Jiefen; Jiang, Hong

    2015-01-01

    Vascular calcification (VC) is a common feature in patients with type 2 diabetes mellitus, a metabolic disorder that is characterized by hyperglycemia (high blood glucose) in the context of insulin resistance and a relative lack of insulin. Recently, a few studies have indicated that a high concentration of glucose amplifies the osteogenesis of vascular smooth muscle cells (VSMCs). Some previous reports state that endoplasmic reticulum (ER) stress-mediated apoptosis was activated in and contributed to VC. However, whether or not high glucose could induce ER stress-mediated apoptosis and then involve the pathogenesis of VC remains unclear. The purpose of the present study was to investigate whether high blood glucose-induced VC in diabetes mellitus is caused by the ER response and subsequent apoptosis. We examined the effects of high glucose on the ER stress response of VSMCs. High glucose treatment drastically increased the ER stress response in VSMCs. The high glucose-induced osteoblastic differentiation of VSMCs was significantly attenuated by pretreatment with 500 μM of 4-PBA (an ER stress inhibitor) prior to the exposure to high glucose, as evidenced by decreases in the expression of Runx2 and activity of alkaline phosphatase, as well as calcium nodules. These results suggest that high glucose induces the ER stress response and apoptosis, leading to high glucose-elicited VC.

  4. Endoplasmic Reticulum Stress-Mediated Apoptosis Contributing to High Glucose-Induced Vascular Smooth Muscle Cell Calcification.

    PubMed

    Zhu, Qiang; Guo, Runmin; Liu, Chang; Fu, Duguan; Liu, Fuyuan; Hu, Jiefen; Jiang, Hong

    2015-01-01

    Vascular calcification (VC) is a common feature in patients with type 2 diabetes mellitus, a metabolic disorder that is characterized by hyperglycemia (high blood glucose) in the context of insulin resistance and a relative lack of insulin. Recently, a few studies have indicated that a high concentration of glucose amplifies the osteogenesis of vascular smooth muscle cells (VSMCs). Some previous reports state that endoplasmic reticulum (ER) stress-mediated apoptosis was activated in and contributed to VC. However, whether or not high glucose could induce ER stress-mediated apoptosis and then involve the pathogenesis of VC remains unclear. The purpose of the present study was to investigate whether high blood glucose-induced VC in diabetes mellitus is caused by the ER response and subsequent apoptosis. We examined the effects of high glucose on the ER stress response of VSMCs. High glucose treatment drastically increased the ER stress response in VSMCs. The high glucose-induced osteoblastic differentiation of VSMCs was significantly attenuated by pretreatment with 500 μM of 4-PBA (an ER stress inhibitor) prior to the exposure to high glucose, as evidenced by decreases in the expression of Runx2 and activity of alkaline phosphatase, as well as calcium nodules. These results suggest that high glucose induces the ER stress response and apoptosis, leading to high glucose-elicited VC. PMID:26890314

  5. 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.

  6. 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

  7. 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.

  8. 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. PMID:25771124

  9. Gallic Acid Decreases Inflammatory Cytokine Secretion Through Histone Acetyltransferase/Histone Deacetylase Regulation in High Glucose-Induced Human Monocytes.

    PubMed

    Lee, Wooje; Lee, Sang Yeol; Son, Young-Jin; Yun, Jung-Mi

    2015-07-01

    Hyperglycemia contributes to diabetes and several diabetes-related complications. Gallic acid is a polyhydroxy phenolic compound found in various natural products. In this study, we investigated the effects and mechanism of gallic acid on proinflammatory cytokine secretion in high glucose-induced human monocytes (THP-1 cells). THP-1 cells were cultured under normoglycemic or hyperglycemic conditions, in the absence or presence of gallic acid. Hyperglycemic conditions significantly induced histone acetylation, nuclear factor-κB (NF-κB) activation, and proinflammatory cytokine release from THP-1 cells, whereas gallic acid suppressed NF-κB activity and cytokine release. It also significantly reduced CREB-binding protein/p300 (CBP/p300, a NF-κB coactivator) gene expression, acetylation levels, and CBP/p300 histone acetyltransferase (HAT) activity. In addition, histone deacetylase 2 (HDAC2) expression was significantly induced. These results suggest that gallic acid inhibits hyperglycemic-induced cytokine production in monocytes through epigenetic changes involving NF-κB. Therefore, gallic acid may have potential for the treatment and prevention of diabetes and its complications.

  10. Myt3 suppression sensitizes islet cells to high glucose-induced cell death via Bim induction.

    PubMed

    Tennant, B R; Vanderkruk, B; Dhillon, J; Dai, D; Verchere, C B; Hoffman, B G

    2016-01-01

    Diabetes is a chronic disease that results from the body's inability to properly control circulating blood glucose levels. The loss of glucose homoeostasis can arise from a loss of β-cell mass because of immune-cell-mediated attack, as in type 1 diabetes, and/or from dysfunction of individual β-cells (in conjunction with target organ insulin resistance), as in type 2 diabetes. A better understanding of the transcriptional pathways regulating islet-cell survival is of great importance for the development of therapeutic strategies that target β-cells for diabetes. To this end, we previously identified the transcription factor Myt3 as a pro-survival factor in islets following acute suppression of Myt3 in vitro. To determine the effects of Myt3 suppression on islet-cell survival in vivo, we used an adenovirus to express an shRNA targeting Myt3 in syngeneic optimal and marginal mass islet transplants, and demonstrate that suppression of Myt3 impairs the function of marginal mass grafts. Analysis of grafts 5 weeks post-transplant revealed that grafts transduced with the shMyt3 adenovirus contained ~20% the number of transduced cells as grafts transduced with a control adenovirus. In fact, increased apoptosis and significant cell loss in the shMyt3-transduced grafts was evident after only 5 days, suggesting that Myt3 suppression sensitizes islet cells to stresses present in the early post-transplant period. Specifically, we find that Myt3 suppression sensitizes islet cells to high glucose-induced cell death via upregulation of the pro-apoptotic Bcl2 family member Bim. Taken together these data suggest that Myt3 may be an important link between glucotoxic and immune signalling pathways. PMID:27195679

  11. 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

  12. 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.

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

    PubMed

    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) environment 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.

  14. Neuroprotective Effects of Ginsenoside Rb1 on High Glucose-Induced Neurotoxicity in Primary Cultured Rat Hippocampal Neurons

    PubMed Central

    Liu, Di; Zhang, Hong; Gu, Wenjuan; Liu, Yuqin; Zhang, Mengren

    2013-01-01

    Ginsenoside Rb1 is one of the main active principles in traditional herb ginseng and has been reported to have a wide variety of neuroprotective effects. Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, so the present study aimed to observe the effects of ginsenoside Rb1 on ER stress signaling pathways in high glucose-treated hippocampal neurons. The results from MTT, TUNEL labeling and Annexin V-FITC/PI/Hoechst assays showed that incubating neurons with 50 mM high glucose for 72h decreased cell viability and increased the number of apoptotic cells whereas treating neurons with 1 μM Rb1 for 72h protected the neurons against high glucose-induced cell damage. Further molecular mechanism study demonstrated that Rb1 suppressed the activation of ER stress-associated proteins including protein kinase RNA (PKR)-like ER kinase (PERK) and C/EBP homology protein (CHOP) and downregulation of Bcl-2 induced by high glucose. Moreover, Rb1 inhibited both the elevation of intracellular reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential induced by high glucose. In addition, the high glucose-induced cell apoptosis, activation of ER stress, ROS accumulation and mitochondrial dysfunction can also be attenuated by the inhibitor of ER stress 4-phenylbutyric acid (4-PBA) and anti-oxidant N-acetylcysteine(NAC). In conclusion, these results suggest that Rb1 may protect neurons against high glucose-induced cell injury through inhibiting CHOP signaling pathway as well as oxidative stress and mitochondrial dysfunction. PMID:24223941

  15. 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.

  16. ZLN005 protects cardiomyocytes against high glucose-induced cytotoxicity by promoting SIRT1 expression and autophagy.

    PubMed

    Li, Wenju; Li, Xiaoli; Wang, Bin; Chen, Yan; Xiao, Aiping; Zeng, Di; Ou, Dongbo; Yan, Song; Li, Wei; Zheng, Qiangsun

    2016-07-01

    Diabetic cardiomyopathy increases the risk for the development of heart failure independent of coronary artery disease and hypertension. Either type 1 or type 2 diabetes is often accompanied by varying degrees of hyperglycemia, which has been proven to induce myocardial apoptosis in animal models. Recently, a novel small molecule, ZLN005, has been reported to show antidiabetic efficacy in a mouse model, possibly by induction of PGC-1α expression. In this study, we investigated whether ZLN005 protects cardiomyocytes against high glucose-induced cytotoxicity and the mechanisms involved. Neonatal mouse cardiomyocytes were incubated with media containing 5.5 or 33mM glucose for 24h in the presence or absence of ZLN005. ZLN005 treatment led to ameliorated cardiomyocyte oxidative injury, enhanced cell viability, and reduced apoptosis in the high glucose environment. Western blot analysis revealed that high glucose suppressed cardiomyocyte autophagy, whereas ZLN005 increased the expression of autophagy marker proteins ATG5, beclin1, and LC3 II/LC3 I; this increase was accompanied by increased expression of SIRT1. Furthermore, EX527, a SIRT1-specific inhibitor, weakened the protective effects of ZLN005 on cardiomyocytes subjected to high glucose. Taken together, these results suggest that ZLN005 suppresses high glucose-induced cardiomyocyte injury by promoting SIRT1 expression and autophagy. PMID:27208585

  17. 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.

  18. Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro

    PubMed Central

    Lv, Zhimei; Hu, Mengsi; Ren, Xiaoxu; Fan, Minghua; Zhen, Junhui; Chen, Liqun; Lin, Jiangong; Ding, Nannan; Wang, Qun; Wang, Rong

    2016-01-01

    Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin) rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation. PMID:26881253

  19. Tadalafil Integrates Nitric Oxide-Hydrogen Sulfide Signaling to Inhibit High Glucose-induced Matrix Protein Synthesis in Podocytes*

    PubMed Central

    Lee, Hak Joo; Feliers, Denis; Mariappan, Meenalakshmi M.; Sataranatarajan, Kavithalakshmi; Choudhury, Goutam Ghosh; Gorin, Yves; Kasinath, Balakuntalam S.

    2015-01-01

    Diabetes-induced kidney cell injury involves an increase in matrix protein expression that is only partly alleviated by current treatment, prompting a search for new modalities. We have previously shown that hydrogen sulfide (H2S) inhibits high glucose-induced protein synthesis in kidney podocytes. We tested whether tadalafil, a phosphodiesterase 5 inhibitor used to treat erectile dysfunction, ameliorates high glucose stimulation of matrix proteins by generating H2S in podocytes. Tadalafil abrogated high glucose stimulation of global protein synthesis and matrix protein laminin γ1. Tadalafil inhibited high glucose-induced activation of mechanistic target of rapamycin complex 1 and laminin γ1 accumulation in an AMP-activated protein kinase (AMPK)-dependent manner. Tadalafil increased AMPK phosphorylation by stimulating calcium-calmodulin kinase kinase β. Tadalafil rapidly increased the expression and activity of the H2S-generating enzyme cystathionine γ-lyase (CSE) by promoting its translation. dl-Propargylglycine, a CSE inhibitor, and siRNA against CSE inhibited tadalafil-induced AMPK phosphorylation and abrogated the tadalafil effect on high glucose stimulation of laminin γ1. In tadalafil-treated podocytes, we examined the interaction between H2S and nitric oxide (NO). Nω-Nitro-l-arginine methyl ester and 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, inhibitors of NO synthase (NOS) and soluble guanylyl cyclase, respectively, abolished tadalafil induction of H2S and AMPK phosphorylation. Tadalafil rapidly augmented inducible NOS (iNOS) expression by increasing its mRNA, and siRNA for iNOS and 1400W, an iNOS blocker, inhibited tadalafil stimulation of CSE expression and AMPK phosphorylation. We conclude that tadalafil amelioration of high glucose stimulation of synthesis of proteins including matrix proteins in podocytes requires integration of the NO-H2S-AMPK axis leading to the inhibition of high glucose-induced mechanistic target of rapamycin complex 1

  20. MicroRNA-21 Orchestrates High Glucose-induced Signals to TOR Complex 1, Resulting in Renal Cell Pathology in Diabetes*

    PubMed Central

    Dey, Nirmalya; Das, Falguni; Mariappan, Meenalakshmi M.; Mandal, Chandi Charan; Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh

    2011-01-01

    Hyperglycemia induces a wide array of signaling pathways in the kidney that lead to hypertrophy and matrix expansion, eventually culminating in progressive kidney failure. High glucose-induced reduction of the tumor suppressor protein phosphatase and tensin homolog deleted in chromosome 10 (PTEN) contributes to renal cell hypertrophy and matrix expansion. We identified microRNA-21 (miR-21) as the molecular link between high glucose and PTEN suppression. Renal cortices from OVE26 type 1 diabetic mice showed significantly elevated levels of miR-21 associated with reduced PTEN and increased fibronectin content. In renal mesangial cells, high glucose increased the expression of miR-21, which targeted the 3′-UTR of PTEN mRNA to inhibit PTEN protein expression. Overexpression of miR-21 mimicked the action of high glucose, which included a reduction in PTEN expression and a concomitant increase in Akt phosphorylation. In contrast, expression of miR-21 Sponge, to inhibit endogenous miR-21, prevented down-regulation of PTEN and phosphorylation of Akt induced by high glucose. Interestingly, high glucose-stimulated miR-21 inactivated PRAS40, a negative regulator of TORC1. Finally, miR-21 enhanced high glucose-induced TORC1 activity, resulting in renal cell hypertrophy and fibronectin expression. Thus, our results identify a previously unrecognized function of miR-21 that is the reciprocal regulation of PTEN levels and Akt/TORC1 activity that mediate critical pathologic features of diabetic kidney disease. PMID:21613227

  1. 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.

  2. Cytoprotective mechanism of ferulic acid against high glucose-induced oxidative stress in cardiomyocytes and hepatocytes

    PubMed Central

    Song, Yuan; Wen, Luona; Sun, Jianxia; Bai, Weibin; Jiao, Rui; Hu, Yunfeng; Peng, Xichun; He, Yong; Ou, Shiyi

    2016-01-01

    Background Ferulic acid (FA), a phenolic acid, is a potential therapy for diabetes mellitus. FA has been shown to protect against hepatic and myocardial injury and oxidative stress in obese rats with late-stage diabetes, but the mechanism of the antioxidative activity of FA is still unclear. Objective The aim of this study was to elucidate whether FA can prevent damage to cardiomyocytes and hepatocytes caused by high glucose (HG)-induced oxidative stress and whether the protection effects of FA on these cells are related to the Keap1-Nrf2-ARE signaling pathways. Design Cells were divided into four groups: a control group (cultured with normal medium), an HG group (medium containing 80 mmol/L glucose), an FA+HG group (medium containing 80 mmol/L glucose and 1, 5, or 10 µg/mL FA), and a dimethylbiguanide (DMBG)+HG group (medium containing 80 mmol/L glucose and 50 µg/mL DMBG). Results FA treatment significantly increased cell viability and significantly decreased cell apoptosis compared with the HG-treated group. Moreover, FA down-regulated the expression of Keap1 protein and up-regulated the expression of Nrf2 protein and gene transcription of HO-1 and glutathione S-transferase (GST) in a dose-dependent manner. Conclusion FA alleviated the HG-induced oxidative stress and decreased cell apoptosis in hepatocytes and cardiomyocytes. These effects were associated with the Keap1-Nrf2-ARE signaling pathway. PMID:26869273

  3. 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

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

    PubMed

    Fan, Yue; Qiao, Yuan; Huang, Jianmei; Tang, Minke

    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

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25710929

  6. Effects of Danggui Buxue Tang, a traditional Chinese herbal decoction, on high glucose-induced proliferation and expression of extracellular matrix proteins in glomerular mesangial cells.

    PubMed

    Ke, Hao-Liang; Zhang, Ying-Wen; Zhou, Bi-Fa; Zhen, Rui-Tang

    2012-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage failure of the kidney, but the efficacy of currently available strategies for the prevention of DN remains unsatisfactory. In this study, we investigated the effects of Danggui Buxue Tang (DBT), a Chinese herbal decoction prepared from Radix Astragali (RA) and Radix Angelicae sinensis (RAS), on high glucose-induced proliferation and expression of laminin, type IV collagen (collagen IV) and fibronectin in glomerular mesangial cells (GMCs). The cell proliferation was determined by MTT assay, and the expression of collagen IV, laminin and fibronectin in GMCs was detected by ELISA assay. It was shown that high glucose clearly induced the proliferation of GMCs and increased the release of collagen IV, laminin and fibronectin. Treatment with RA, RAS and DBT inhibited cell proliferation and the expression of collagen IV, laminin and fibronectin induced by high glucose, with DBT, especially at the highest concentration (DBT20), exhibiting a stronger effect than RA and RAS alone. Thus, it is concluded that DBT inhibits increased cell proliferation and the expression of major extracellular matrix proteins that are induced by high glucose, indicating its value for prophylaxis and therapy of DN at the early stages.

  7. Effects of methanolic extracts of edible plants on RAGE in high-glucose-induced human endothelial cells.

    PubMed

    Okada, Mizue; Okada, Yoshinori

    2015-01-01

    Advanced glycation end products' (AGEs) engagement of a cell-surface receptor for AGEs (RAGE) has been causally implicated in the pathogenesis of vascular complications in diabetic patients. Methanolic extracts from edible plants (MEEP) are naturally occurring phenolic compounds. The phenolic compounds have been reported to possess potent radical-scavenging properties. We investigated whether MEEP could inhibit high glucose-induced RAGE production through interference with reactive oxygen species generation in endothelial cells (ECs). ECs were incubated with 4.5 g/l of glucose in culture medium treated with 21 MEEP. Determination of RAGE production in the culture supernatants was performed by colorimetric ELISA. DNA damage was determined by using the 8-hydroxydeoxyguanosine ELISA kit. Because peroxynitrite radicals with stronger toxicity were produced by nitric oxide radical (NO), the NO scavenging activity of MEEP was assessed as nitrite generation. Peroxynitrite radical-dependent oxidation inhibition by MEEP was estimated by the Crow method. The results showed that four extracts reduced RAGE production. The extract from onion peel showed the highest RAGE production inhibition activity, followed by that of onion rhizome, cow pea and burdock. The results showed that RAGE production is correlated with the above-mentioned indicators. This study supports the utilization of four extracts for improved treatment of diabetic complications. PMID:26407112

  8. 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.

  9. Protective Role of Glucagon-Like Peptide-1 Against High-Glucose-Induced Endothelial Oxidative Damage

    PubMed Central

    Guo, Lixin; Qiao, Yue; Zhang, Lina; Pan, Qi

    2015-01-01

    Abstract To investigate the protective effect of glucagon-like peptide-1 (GLP-1) against cell damage induced by high glucose. Human umbilical vein endothelial cells (HUVECs) were divided into control group (5.5 mmol/L) and high glucose groups (19, 33, or 47 mmol/L), which were cultured with different concentrations of glucose for 48 hours, respectively. Cell viability was measured with MTT assay. Levels of intracellular reactive oxygen species (ROS) were monitored by flow cytometry and apoptotic cell death was measured by staining with Annexin V-FITC and propidium iodide. Cultured cells were detected with intercellular adhesion molecule 1 (ICAM-1), VCAM-1, and JNK on protein. Compared with the control group, cell viability was decreased by 20% and 37%, respectively, when cultured under 33 and 47 mM, while increased in different GLP-1-treated groups (0.01 L, 0.1, 1, and 10 nmol/L). The GLP-1 treatment significantly reduced the ROS level of high glucose treatment group but not impact on the control group. Meanwhile, the level of apoptosis was elevated in the high glucose treatment group. Early apoptosis was significantly reversed in the GLP-1-treated group (0.1, 1, and 10 nmol/L). Late apoptosis was uniquely decreased in the GLP-1 concentrations of 10 nmol/L. Furthermore, GLP-1 could also reduce the protein levels of ICAM-1, VCAM-1, and phospho JNK in the endothelial cells with high glucose treatment. GLP-1 could inhibit cell apoptosis and reduce ROS generation and JNK-Bax signaling pathway activation, which were induced by high glucose treatment. PMID:26632709

  10. 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.

  11. 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.

  12. 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.

  13. Vicenin-2 and scolymoside inhibit high-glucose-induced vascular inflammation in vitro and in vivo.

    PubMed

    Ku, Sae-Kwang; Bae, Jong-Sup

    2016-03-01

    The vascular inflammatory process has been suggested to play a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether 2 structurally related flavonoids found in Cyclopia subternata, vicenin-2 and scolymoside, can suppress high-glucose (HG)-induced vascular inflammatory processes in human umbilical vein endothelial cells (HUVECs) and mice. The effects of vicenin-2 and scolymoside on HG-induced vascular inflammation were determined by measuring vascular permeability, leukocyte adhesion and migration, cell adhesion molecule (CAM) expression levels, and reactive oxygen species (ROS) formation. In addition, the anti-inflammation mechanism was investigated using immunofluorescence staining and Western blotting. The data showed that HG markedly increased vascular permeability, monocyte adhesion, expression of CAMs, formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-κB. Remarkably, pretreatment with vicenin-2 and scolymoside attenuated all of the above-mentioned vascular inflammatory effects of HG. HG-induced vascular inflammatory responses are critical events underlying the development of various diabetic complications; therefore, our results suggest that vicenin-2 and scolymoside have significant therapeutic benefits against diabetic complications and atherosclerosis.

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

    SciTech Connect

    Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.; Huang, J.-S.

    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.

  15. 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.

  16. Aralia taibaiensis Protects Cardiac Myocytes against High Glucose-Induced Oxidative Stress and Apoptosis.

    PubMed

    Duan, Jialin; Wei, Guo; Guo, Chao; Cui, Jia; Yan, Jiajia; Yin, Ying; Guan, Yue; Weng, Yan; Zhu, Yanrong; Wu, Xiaoxiao; Wang, Yanhua; Xi, Miaomiao; Wen, Aidong

    2015-01-01

    Patients with type 2 diabetes have increased cardiovascular disease risk compared with those without diabetes. Hyperglycemia can induce reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. Our previous study has demonstrated that the total saponins of Aralia taibaiensis (sAT), a frequently-used antidiabetic medicine in traditional Chinese medicine (TCM), can scavenge free radicals in vitro and have good anti-oxidant ability on lipid peroxidation of rat liver microsomes. This work was designed to investigate whether sAT could protect the heart while it was used in the treatment of diabetes. Oxidative stress was induced in H9c2 cells by high glucose (33 mM) and glucose oxidase (15 mU, G/GO) and the protective effects of sAT were evaluated. Treatment of H9c2 cells with G/GO resulted in an increase in cell death, intracellular ROS level and cell oxidative injury, which were markedly reduced by sAT treatment. Further study revealed that sAT induced the nuclear translocation of Nrf2 and expression of its downstream targets. Moreover, Nrf2 siRNA markedly abolished the cytoprotective effects of sAT. sAT exerted cytoprotective effects against oxidative stress induced by hyperglycemia and the cardioprotective effects of sAT might be through the Nrf2/ARE pathway. Thus, sAT might be a promising candidate for the treatment of diabetic cardiomyopathy. PMID:26446201

  17. Curcumin attenuates high glucose-induced podocyte apoptosis by regulating functional connections between caveolin-1 phosphorylation and ROS

    PubMed Central

    Sun, Li-na; Liu, Xiang-chun; Chen, Xiang-jun; Guan, Guang-ju; Liu, Gang

    2016-01-01

    Aim: Caveolin-1 (cav-1) is a major multifunctional scaffolding protein of caveolae. Cav-1 is primarily expressed in mesangial cells, renal proximal tubule cells and podocytes in kidneys. Recent evidence shows that the functional connections between cav-1 and ROS play a key role in many diseases. In this study we investigated whether regulating the functional connections between cav-1 and ROS in kidneys contributed to the beneficial effects of curcumin in treating diabetic nephropathy in vitro and in vivo. Methods: Cultured mouse podocytes (mpc5) were incubated in a high glucose (HG, 30 mmol/L) medium for 24, 48 or 72 h. Male rats were injected with STZ (60 mg/kg, ip) to induce diabetes. ROS generation, SOD activity, MDA content and caspase-3 activity in the cultured cells and kidney cortex homogenate were determined. Apoptotic proteins and cav-1 phosphorylation were analyzed using Western blot analyses. Results: Incubation in HG-containing medium time-dependently increased ROS production, oxidative stress, apoptosis, and cav-1 phosphorylation in podocytes. Pretreatment with curcumin (1, 5, and 10 μmol/L) dose-dependently attenuated these abnormalities in HG-treated podocytes. Furthermore, in HG-containing medium, the podocytes transfected with a recombinant plasmid GFP-cav-1 Y14F (mutation at a cav-1 phosphorylation site) exhibited significantly decreased ROS production and apoptosis compared with the cells transfected with empty vector. In diabetic rats, administration of curcumin (100 or 200 mg/kg body weight per day, ig, for 8 weeks) not only significantly improved the renal function, but also suppressed ROS levels, oxidative stress, apoptosis and cav-1 phosphorylation in the kidneys. Conclusion: Curcumin attenuates high glucose-induced podocyte apoptosis in vitro and diabetic nephropathy in vivo partly through regulating the functional connections between cav-1 phosphorylation and ROS. PMID:26838071

  18. 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

  19. High glucose induces apoptosis and suppresses proliferation of adult rat neural stem cells following in vitro ischemia

    PubMed Central

    2013-01-01

    Background Post-stroke hyperglycemia appears to be associated with poor outcome from stroke, greater mortality, and reduced functional recovery. Focal cerebral ischemia data support that neural stem cells (NSCs) play an important role in post-ischemic repair. Here we sought to evaluate the negative effects of hyperglycemia on the cellular biology of NSCs following anoxia, and to test whether high glucose affects NSC recovery from ischemic injury. Results In this study, we used immortalized adult neural stem cells lines and we induced in vitro ischemia by 6 h oxygen and glucose deprivation (OGD) in an anaerobic incubator. Reperfusion was performed by returning cells to normoxic conditions and the cells were then incubated in experimental medium with various concentrations of glucose (17.5, 27.75, 41.75, and 83.75 mM) for 24 h. We found that high glucose (≥27.75 mM) exposure induced apoptosis of NSCs in a dose-dependent manner after exposure to OGD, using an Annexin V/PI apoptosis detection kit. The cell viability and proliferative activity of NSCs following OGD in vitro, evaluated with both a Cell Counting kit-8 (CCK-8) assay and a 5-ethynyl-2’-deoxyuridine (EdU) incorporation assay, were inhibited by high glucose exposure. Cell cycle analysis showed that high glucose exposure increased the percentage of cells in G0/G1-phase, and reduced the percentage of cells in S-phase. Furthermore, high glucose exposure was found to significantly induce the activation of c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) and suppress extracellular signal-regulated kinase 1/2 (ERK1/2) activity. Conclusions Our results demonstrate that high glucose induces apoptosis and inhibits proliferation of NSCs following OGD in vitro, which may be associated with the activation of JNK/p38 MAPK pathways and the delay of G1-S transition in the cells. PMID:23452440

  20. 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

  1. 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

  2. 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. PMID:26114862

  3. High glucose induces suppression of insulin signalling and apoptosis via upregulation of endogenous IL-1beta and suppressor of cytokine signalling-1 in mouse pancreatic beta cells.

    PubMed

    Venieratos, Panagiotis D; Drossopoulou, Garyfalia I; Kapodistria, Katerina D; Tsilibary, Effie C; Kitsiou, Paraskevi V

    2010-05-01

    Chronic hyperglycemia and inflammatory cytokines disrupt and/or attenuate signal transduction pathways that promote normal beta-cell survival, leading to the destruction of endocrine pancreas in type 2 diabetes. There is convincing evidence that autocrine insulin signalling exerts protective anti-apoptotic effects on beta cells. Suppressors of cytokine signalling (SOCS) were induced by several cytokines and inhibit insulin-initiated signal transduction. The aim of this study was to investigate whether high glucose can influence endogenous interleukin-1beta (IL-1beta) and SOCS expression thus affecting insulin signalling and survival in insulin-producing mouse pancreatic beta cells (betaTC-6). Results showed that prolonged exposure of betaTC-6 cells to increased glucose concentrations resulted in significant inhibition of insulin-induced tyrosine phosphorylation of the insulin receptor (IR), and insulin receptor substrate-2 (IRS-2) as well as PI3-kinase activation. These changes were accompanied by impaired activation of the anti-apoptotic signalling protein Akt and annulment of Akt-mediated suppression of the Forkhead family of transcription factors (FoxO) activation. Glucose-induced attenuation of IRS-2/Akt-mediated signalling was associated with increased IL-1beta expression. Enhanced endogenous IL-1beta specifically induced mRNA and protein expression of SOCS-1 in betaTC-6 cells. Inhibition of SOCS-1 expression by SOCS-1-specific small interfering RNA restored IRS-2/PI3K-mediated Akt phosphorylation suppressed by high glucose. The upregulation of endogenous cytokine signalling and FoxO activation were accompanied by enhanced caspase-3 activation and increased susceptibility of cells to apoptosis. These results indicated that glucose-induced endogenous IL-1beta expression increased betaTC-6 cells apoptosis by inhibiting, at least in part, IRS-2/Akt-mediated signalling through SOCS-1 upregulation.

  4. 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

  5. High glucose induces Smad activation via the transcriptional coregulator p300 and contributes to cardiac fibrosis and hypertrophy

    PubMed Central

    2014-01-01

    Background Despite advances in the treatment of heart failure, mortality remains high, particularly in individuals with diabetes. Activated transforming growth factor beta (TGF-β) contributes to the pathogenesis of the fibrotic interstitium observed in diabetic cardiomyopathy. We hypothesized that high glucose enhances the activity of the transcriptional co-activator p300, leading to the activation of TGF-β via acetylation of Smad2; and that by inhibiting p300, TGF-β activity will be reduced and heart failure prevented in a clinically relevant animal model of diabetic cardiomyopathy. Methods p300 activity was assessed in H9c2 cardiomyoblasts under normal glucose (5.6 mmol/L—NG) and high glucose (25 mmol/L—HG) conditions. 3H-proline incorporation in cardiac fibroblasts was also assessed as a marker of collagen synthesis. The role of p300 activity in modifying TGF-β activity was investigated with a known p300 inhibitor, curcumin or p300 siRNA in vitro, and the functional effects of p300 inhibition were assessed using curcumin in a hemodynamically validated model of diabetic cardiomyopathy – the diabetic TG m(Ren-2)27 rat. Results In vitro, H9c2 cells exposed to HG demonstrated increased p300 activity, Smad2 acetylation and increased TGF-β activity as assessed by Smad7 induction (all p < 0.05 c/w NG). Furthermore, HG induced 3H-proline incorporation as a marker of collagen synthesis (p < 0.05 c/w NG). p300 inhibition, using either siRNA or curcumin reduced p300 activity, Smad acetylation and TGF-β activity (all p < 0.05 c/w vehicle or scrambled siRNA). Furthermore, curcumin therapy reduced 3H-proline incorporation in HG and TGF-β stimulated fibroblasts (p < 0.05 c/w NG). To determine the functional significance of p300 inhibition, diabetic Ren-2 rats were randomized to receive curcumin or vehicle for 6 weeks. Curcumin treatment reduced cardiac hypertrophy, improved diastolic function and reduced extracellular matrix production, without

  6. Glucose-induced serum- and glucocorticoid-regulated kinase activation in oncofetal fibronectin expression

    SciTech Connect

    Khan, Zia A.; Barbin, Yousef P.; Farhangkhoee, Hana; Beier, Norbert; Scholz, Wolfgang; Chakrabarti, Subrata . E-mail: subrata.chakrabarti@fmd.uwo.ca

    2005-04-01

    Preferential expression of oncofetal extra domain-B fibronectin (EDB{sup +} FN), a proposed angiogenic marker, has been shown in proliferative diabetic retinopathy. High levels of glucose also increase EDB{sup +} FN expression in endothelial cells (ECs) via transforming growth factor-{beta}1 (TGF-{beta}1) and endothelin-1 (ET-1). The present study was aimed at elucidating the role of serum- and glucocorticoid-regulated kinase (SGK-1) in glucose-induced EDB{sup +} FN expression. Using human macro- and microvascular ECs, we show that high levels of glucose, TGF-{beta}1, and ET-1 increase the EDB{sup +} FN expression via SGK-1 alteration at the mRNA, protein, and activity levels. Inhibition of TGF-{beta}1 and ET-1 prevented glucose-induced SGK-1 activation and the EDB{sup +} FN expression. Furthermore, using siRNA-mediated SGK-1 gene silencing, we show that glucose-induced EDB{sup +} FN expression can be completely prevented. These findings provide first evidence of glucose-induced SGK-1 activation in altered EDB{sup +} FN expression and provide novel avenues for therapeutic modalities.

  7. High Glucose-Induced Repression of RAR/RXR In Cardiomyocytes is Mediated Through Oxidative Stress/JNK Signaling

    PubMed Central

    Singh, Amar Bahadur; Guleria, Rakeshwar S.; Nizamutdinova, Irina T.; Baker, Kenneth M.; Pan, Jing

    2011-01-01

    The biological actions of retinoids are mediated by nuclear retinoic acid receptors (RARs) and retinoid × receptors (RXRs). We have recently reported that decreased expression of RARα and RXRα has an important role in high glucose (HG)-induced cardiomyocyte apoptosis. However, the regulatory mechanisms of HG effects on RARα and RXRα remain unclear. Using neonatal cardiomyocytes, we found that ligand-induced promoter activity of RAR and RXR was significantly suppressed by HG. HG promoted protein destabilization and serine-phosphorylation of RARα and RXRα. Proteasome inhibitor MG132 blocked the inhibitory effect of HG on RARα and RXRα. Inhibition of intracellular reactive oxidative species (ROS) abolished the HG effect. In contrast, H2O2 stimulation suppressed the expression and ligand-induced promoter activity of RARα and RXRα. HG promoted phosphorylation of ERK1/2, JNK and p38 MAP kinases, which was abrogated by an ROS inhibitor. Inhibition of JNK, but not ERK and p38 activity, reversed HG effects on RARα and RXRα. Activation of JNK by over expressing MKK7 and MEKK1, resulted in significant downregulation of RARα and RXRα. Ligand-induced promoter activity of RARα and RXRα was also suppressed by overexpression of MEKK1. HG-induced cardiomyocyte apoptosis was potentiated by activation of JNK, and prevented by ATRA and inhibition of JNK. Silencing the expression of RARα and RXRα activated the JNK pathway. In conclusion, HG-induced oxidative stress and activation of the JNK pathway negatively regulated expression/activation of RAR and RXR. The impaired RAR/RXR signaling and oxidative stress/JNK pathway forms a vicious circle, which significantly contributes to hyperglycemia induced cardiomyocyte apoptosis. PMID:21882190

  8. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells.

    PubMed

    Cheng, Xiaofei; Ni, Bin; Zhang, Feng; Hu, Ying; Zhao, Jie

    2016-01-01

    Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism. PMID:27635402

  9. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    PubMed Central

    Cheng, Xiaofei; Ni, Bin; Zhang, Feng; Hu, Ying

    2016-01-01

    Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  10. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    PubMed Central

    Cheng, Xiaofei; Ni, Bin; Zhang, Feng; Hu, Ying

    2016-01-01

    Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism. PMID:27635402

  11. CTRP9 induces mitochondrial biogenesis and protects high glucose-induced endothelial oxidative damage via AdipoR1 -SIRT1- PGC-1α activation.

    PubMed

    Cheng, Liang; Li, Bin; Chen, Xu; Su, Jie; Wang, Hongbing; Yu, Shiqiang; Zheng, Qijun

    2016-09-01

    Vascular lesions caused by endothelial dysfunction are the most common and serious complication of diabetes. The vasoactive potency of CTRP9 has been reported in our previous study via nitric oxide (NO) production. However, the effect of CTRP9 on vascular endothelial cells remains unknown. This study aimed to investigate the protection role of CTRP9 in the primary aortic vascular endothelial cells and HAECs under high-glucose condition. We found that the aortic vascular endothelial cells isolated from mice fed with a high fat diet generated more ROS production than normal cells, along with decreased mitochondrial biogenesis, which was also found in HAECs treated with high glucose. However, the treatment of CTPR9 significantly reduced ROS production and increased the activities of endogenous antioxidant enzymes, the expression of PGC-1α, NRF1, TFAM, ATP5A1 and SIRT1, and the activity of cytochrome c oxidase, indicating an induction of mitochondrial biogenesis. Furthermore, silencing the expression of SIRT1 in HAECs impeded the effect of CTRP9 on mitochondrial biogenesis, while silencing the expression of AdipoR1 in HAECs reversed the expression of SIRT1 and PGC-1α. Based on these findings, this study showed that CTRP9 might induce mitochondrial biogenesis and protect high glucose-induced endothelial oxidative damage via AdipoR1-SIRT1-PGC-1α signaling pathway. PMID:27349872

  12. Reactive oxygen species and nuclear factor-kappa B pathway mediate high glucose-induced Pax-2 gene expression in mouse embryonic mesenchymal epithelial cells and kidney explants.

    PubMed

    Chen, Y-W; Liu, F; Tran, S; Zhu, Y; Hébert, M-J; Ingelfinger, J R; Zhang, S-L

    2006-11-01

    Diabetic mellitus confers a major risk of congenital malformations, and is associated with diabetic embryopathy, affecting multiple organs including the kidney. The DNA paired box-2 (Pax-2) gene is essential in nephrogenesis. We investigated whether high glucose alters Pax-2 gene expression and aimed to delineate its underlying mechanism(s) of action using both in vitro (mouse embryonic mesenchymal epithelial cells (MK4) and ex vivo (kidney explant from Hoxb7-green florescent protein (GFP) mice) approaches. Pax-2 gene expression was determined by reverse transcriptase-polymerase chain reaction, Western blotting, and immunofluorescent staining. A fusion gene containing the full-length 5'-flanking region of the human Pax-2 promoter linked to a luciferase reporter gene, pGL-2/hPax-2, was transfected into MK4 cells with or without dominant negative IkappaBalpha (DN IkappaBalpha) cotransfection. Fusion gene expression level was quantified by cellular luciferase activity. Reactive oxygen species (ROS) generation was measured by lucigenin assay. Embryonic kidneys from Hoxb7-GFP mice were cultured ex vivo. High D(+) glucose (25 mM), compared to normal glucose (5 mM), specifically induced Pax-2 gene expression in MK4 cells and kidney explants. High glucose-induced Pax-2 gene expression is mediated, at least in part, via ROS generation and activation of the nuclear factor kappa B signaling pathway, but not via protein kinase C, p38 mitogen-activated protein kinase (MAPK), and p44/42 MAPK signaling.

  13. 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

  14. [Microdevice for the investigation of high-glucose induced lifespan and the protective effect of polydatin in C. elegans].

    PubMed

    Zhu, Guoli; Yin, Fangchao; Wang, Li; Zhang, Min; Jiang, Lei; Qin, Jianhua

    2016-02-01

    Caenorhabditis elegans (C. elegans) has been widely used as a model organism for biomedical research due to its sufficient homology with human at molecular or genomic level. In this work, we describe a microfluidic device not only to investigate the response of C. elegans including lifespan and oxidative stress, but also to evaluate the protective effect of polydatin induced by high-glucose condition. It was found that the mean lifespan of worms was significantly reduced and the oxidative stress protein GST-4 was increased in worms that are subjected to high glucose. However, a certain dose of polydatin could weaken the increased oxidative stress induced by high-glucose and extend the lifespan, indicating the protective effect of polydatin against the toxic of high-glucose. The established approach is simple to operate, easy for realtime imaging and multiparatemer evaluations in parallel, providing a potential platform for drug evaluation/screening in a high throughput format at single animal resolution. PMID:27382717

  15. 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

  16. Biphasic Response to Luteolin in MG-63 Osteoblast-Like Cells under High Glucose-Induced Oxidative Stress

    PubMed Central

    Abbasi, Naser; Khosravi, Afra; Aidy, Ali; Shafiei, Massoumeh

    2016-01-01

    Background: Clinical evidence indicates the diabetes-induced impairment of osteogenesis caused by a decrease in osteoblast activity. Flavonoids can increase the differentiation and mineralization of osteoblasts in a high-glucose state. However, some flavonoids such as luteolin may have the potential to induce cytotoxicity in osteoblast-like cells. This study was performed to investigate whether a cytoprotective concentration range of luteolin could be separated from a cytotoxic concentration range in human MG-63 osteoblast-like cells in high-glucose condition. Methods: Cells were cultured in a normal- or high-glucose medium. Cell viability was determined with the MTT assay. The formation of intracellular reactive oxygen species (ROS) was measured using probe 2’,7’ -dichlorofluorescein diacetate, and osteogenic differentiation was evaluated with an alkaline phosphatase bioassay. Results: ROS generation, reduction in alkaline phosphatase activity, and cell death induced by high glucose were inhibited by lower concentrations of luteolin (EC50, 1.29±0.23 µM). Oxidative stress mediated by high glucose was also overcome by N-acetyl-L-cysteine. At high concentrations, luteolin caused osteoblast cell death in normal- and high-glucose states (IC50, 34±2.33 and 27±2.42 µM, respectively), as represented by increased ROS and decreased alkaline phosphatase activity. Conclusion: Our results indicated that the cytoprotective action of luteolin in glucotoxic condition was manifested in much lower concentrations, by a factor of approximately 26 and 20, than was its cytotoxic activity, which occurred under normal or glucotoxic condition, respectively. PMID:26989282

  17. SIRT1 Is a Regulator in High Glucose-Induced Inflammatory Response in RAW264.7 Cells

    PubMed Central

    Cai, Weixia; Jia, Wenbin; Yang, Longlong; Dong, Maolong; Zhu, Xiongxiang; Su, Linlin; Hu, Dahai

    2015-01-01

    Sepsis is defined as a systemic inflammatory response syndrome that disorders the functions of host immune system, including the imbalance between pro- and anti-inflammatory responses mediated by immune macrophages. Sepsis could also induce acute hyperglycemia. Studies have shown that the silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+-dependent deacetylase, mediates NF-κb deacetylation and inhibits its function. Therefore, SIRT1 is likely to play an important role in high glucose-mediated inflammatory signalings. Here we demonstrate that high glucose significantly downregulates both the mRNA and protein levels of SIRT1 and upregulates the mRNA level and the release of two pro-inflammatory cytokines, IL-1β and TNF-α, in RAW264.7 macrophages. Interestingly, the reduced level of SIRT1 by high glucose is remarkably upregulated by SIRT1 activator SRT1720, while the level and the release of IL-1β and TNF-α significantly decrease with the use of SRT1720. However, when the function of SIRT1 is inhibited by EX527 or its expression is suppressed by RNAi, the upregulated level and release of IL-1β and TNF-α by high glucose are further increased. Taken together, these findings collectively suggest that SIRT1 is an important regulator in many high glucose-related inflammatory diseases such as sepsis. PMID:25793995

  18. Agmatine Ameliorates High Glucose-Induced Neuronal Cell Senescence by Regulating the p21 and p53 Signaling

    PubMed Central

    Song, Juhyun; Lee, Byeori; Kang, Somang; Oh, Yumi; Kim, Eosu; Kim, Chul-Hoon; Song, Ho-Taek

    2016-01-01

    Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes mellitus. Neuronal senescence leads to the secretion of pro-inflammatory cytokines, the production of reactive oxygen species, and the alteration of cellular homeostasis. Agmatine, which is biosynthesized by arginine decarboxylation, has been reported in previous in vitro to exert a protective effect against various stresses. In present study, agmatine attenuated the cell death and the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha and CCL2 in high glucose in vitro conditions. Moreover, the senescence associated-β-galatosidase's activity in high glucose exposed neuronal cells was reduced by agmatine. Increased p21 and reduced p53 in high glucose conditioned cells were changed by agmatine. Ultimately, agmatine inhibits the neuronal cell senescence through the activation of p53 and the inhibition of p21. Here, we propose that agmatine may ameliorate neuronal cell senescence in hyperglycemia. PMID:26924930

  19. Ghrelin inhibits high glucose-induced 16HBE cells apoptosis by regulating Wnt/β-catenin pathway.

    PubMed

    Liu, Xiaoyan; Chen, Dilong; Wu, Zhongjun; Li, Jing; Li, Jianqiang; Zhao, Hui; Liu, Tanzhen

    2016-09-01

    Ghrelin has a protective effect on diabetes and its complications. To expound its probable molecular mechanisms, we investigated the effects of ghrelin on high glucose (HG)-induced cell apoptosis and intracellular signaling pathways in cultured human bronchial epithelial cells (16HBE). In this study, we firstly came to conclusion that HG-induced 16HBE apoptosis was significantly inhibited by co-treatment of ghrelin. The molecular mechanism of ghrelin-induced protective effects for lungs is still not understood. We reported here for the first time that ghrelin can not only eliminate apoptosis of 16HBE, but also regulate the disordered cell cycle caused by HG. We speculated here that ghrelin inhibits the apoptosis of 16HBE by regulating the abnormal cell cycle to some extent. The mechanism may be that ghrelin up-regulates the expression of cyclin D1 via regulating Wnt/β-catenin pathway, which has an intimate relationship with lung diseases. These results suggested the possible role of ghrelin in treating diabetic lung diseases, especially in view of its low toxicity in humans. PMID:27378423

  20. 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.

  1. Role for high-glucose-induced protein O-GlcNAcylation in stimulating cardiac fibroblast collagen synthesis

    PubMed Central

    Aguilar, Hugo; Fricovsky, Eduardo; Ihm, Sang; Schimke, Magdalena; Maya-Ramos, Lisandro; Aroonsakool, Nakon; Ceballos, Guillermo; Dillmann, Wolfgang; Villarreal, Francisco

    2014-01-01

    Excess enzyme-mediated protein O-GlcNAcylation is known to occur with diabetes mellitus. A characteristic of diabetic cardiomyopathy is the development of myocardial fibrosis. The role that enhanced protein O-GlcNAcylation plays in modulating the phenotype of cardiac fibroblasts (CF) is unknown. To address this issue, rat CF were cultured in normal glucose (NG; 5 mM glucose) or high-glucose (HG; 25 mM) media for 48 h. Results demonstrate that CF cultured in HG have higher levels (∼50%) of overall protein O-GlcNAcylation vs. NG cells. Key regulators of collagen synthesis such as transforming-growth factor-β1 (TGF-β1), SMADs 2/3, and SMAD 7 protein levels, including those of arginase I and II, were altered, leading to increases in collagen levels. The nuclear transcription factor Sp1 and arginase II evidence excess O-GlcNAcylation in HG cells. Expression in CF of an adenovirus coding for the enzyme N-acetylglucosaminidase, which removes O-GlcNAc moieties from proteins, decreased Sp1 and arginase II O-GlcNAcylation and restored HG-induced perturbations in CF back to NG levels. These findings may have important pathophysiological implications for the development of diabetes-induced cardiac fibrosis. PMID:24553187

  2. MicroRNA-218 promotes high glucose-induced apoptosis in podocytes by targeting heme oxygenase-1.

    PubMed

    Yang, Haibo; Wang, Qingjun; Li, Sutong

    2016-03-18

    Emerging evidence has demonstrated that microRNAs (miRNAs) play a mediatory role in the pathogenesis of diabetic nephropathy. In this study, we found that miR-218 was upregulated in high glucose (HG) treated podocytes, which are essential components of the glomerular filtration barrier and a major prognostic determinant in diabetic nephropathy. Additionally, up-regulation of miR-218 was accompanied by an increased rate of podocyte death and down-regulation in the level of nephrin, a key marker of podocytes. However, inhibition of miR-218 exerted the opposite effect. In addition, the dual-luciferase reporter assay showed that miR-218 directly targeted the 3'-untranslated region of heme oxygenase-1 (HO-1), and further study confirmed an increase of HO-1 in HG-treated podocytes transfected with anti-miR-218. Knockdown of HO-1 blocked the anti-apoptotic effect of anti-miR-218. Furthermore, inhibition of miR-218 was associated with decreased expression of the known pro-apoptotic molecule p38-mitogen-activated protein kinase (p38-MAPK) activation. Following preconditioning with SB203580, an inhibitor of p38-MAPK, the stimulatory effect of HG on podocyte apoptosis was strikingly ameliorated. These findings suggested that miR-218 accelerated HG-induced podocyte apoptosis through directly down-regulating HO-1 and facilitating p38-MAPK activation. PMID:26876575

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

    PubMed Central

    Chen, Minjiang; Zheng, Hong; Wei, Tingting; Wang, Dan; Xia, Huanhuan; Zhao, Liangcai; Ji, Jiansong

    2016-01-01

    Objective. High glucose- (HG-) induced neuronal cell death is responsible for the development of diabetic neuropathy. However, the effect of HG on metabolism in neuronal cells is still unclear. Materials and Methods. The neural-crest derived PC12 cells were cultured for 72 h in the HG (75 mM) or control (25 mM) groups. We used NMR-based metabolomics to examine both intracellular and extracellular metabolic changes in HG-treated PC12 cells. Results. We found that the reduction in intracellular lactate may be due to excreting more lactate into the extracellular medium under HG condition. HG also induced the changes of other energy-related metabolites, such as an increased succinate and creatine phosphate. Our results also reveal that the synthesis of glutamate from the branched-chain amino acids (isoleucine and valine) may be enhanced under HG. Increased levels of intracellular alanine, phenylalanine, myoinositol, and choline were observed in HG-treated PC12 cells. In addition, HG-induced decreases in intracellular dimethylamine, dimethylglycine, and 3-methylhistidine may indicate a downregulation of methyl group metabolism. Conclusions. Our metabolomic results suggest that HG-induced neuronal cell death may be attributed to a series of metabolic changes, involving energy metabolism, amino acids metabolism, osmoregulation and membrane metabolism, and methyl group metabolism. PMID:27413747

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

    PubMed

    Chen, Minjiang; Zheng, Hong; Wei, Tingting; Wang, Dan; Xia, Huanhuan; Zhao, Liangcai; Ji, Jiansong; Gao, Hongchang

    2016-01-01

    Objective. High glucose- (HG-) induced neuronal cell death is responsible for the development of diabetic neuropathy. However, the effect of HG on metabolism in neuronal cells is still unclear. Materials and Methods. The neural-crest derived PC12 cells were cultured for 72 h in the HG (75 mM) or control (25 mM) groups. We used NMR-based metabolomics to examine both intracellular and extracellular metabolic changes in HG-treated PC12 cells. Results. We found that the reduction in intracellular lactate may be due to excreting more lactate into the extracellular medium under HG condition. HG also induced the changes of other energy-related metabolites, such as an increased succinate and creatine phosphate. Our results also reveal that the synthesis of glutamate from the branched-chain amino acids (isoleucine and valine) may be enhanced under HG. Increased levels of intracellular alanine, phenylalanine, myoinositol, and choline were observed in HG-treated PC12 cells. In addition, HG-induced decreases in intracellular dimethylamine, dimethylglycine, and 3-methylhistidine may indicate a downregulation of methyl group metabolism. Conclusions. Our metabolomic results suggest that HG-induced neuronal cell death may be attributed to a series of metabolic changes, involving energy metabolism, amino acids metabolism, osmoregulation and membrane metabolism, and methyl group metabolism. PMID:27413747

  5. Oxidative Stress-Activated NHE1 Is Involved in High Glucose-Induced Apoptosis in Renal Tubular Epithelial Cells

    PubMed Central

    Wu, Yiqing; Zhang, Min; Liu, Rui

    2016-01-01

    Purpose Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes mellitus involving disturbances in electrolytes and the acid-base balance caused by a disorder of glucose metabolism. NHE1 is a Na+/H+ exchanger responsible for keeping intracellular pH (pHi) balance and cell growth. Our study aimed to investigate roles of NHE1 in high glucose (HG)-induced apoptosis in renal tubular epithelial cells. Materials and Methods Renal epithelial tubular cell line HK-2 was cultured in medium containing 5 mM or 30 mM glucose. Then, cell apoptosis, oxidative stress, NHE1 expression, and pHi were evaluated. NHE1 siRNA and inhibitor were used to evaluate its role in cell apoptosis. Results HG significantly increased cell apoptosis and the production of reactive oxygen species (ROS) and 8-OHdG (p<0.05). Meanwhile, we found that HG induced the expression of NHE1 and increased the pHi from 7.0 to 7.6 after 48 h of incubation. However, inhibiting NHE1 using its specific siRNA or antagonist DMA markedly reduced cell apoptosis stimulated by HG. In addition, suppressing cellular oxidative stress using antioxidants, such as glutathione and N-acetyl cysteine, significantly reduced the production of ROS, accompanied by a decrease in NHE1. We also found that activated cyclic GMP-Dependent Protein Kinase Type I (PKG) signaling promoted the production of ROS, which contributed to the regulation of NHE1 functions. Conclusion Our study indicated that HG activates PKG signaling and elevates the production of ROS, which was responsible for the induction of NHE1 expression and dysfunction, as well as subsequent cell apoptosis, in renal tubular epithelial cells. PMID:27401659

  6. 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

  7. The Inhibitory Effect of Rhein on Proliferation of High Glucose-induced Mesangial Cell Through Cell Cycle Regulation and Induction of Cell Apoptosis

    PubMed Central

    Xu, Shouzhu; Lv, Yanying; Zhao, Jing; Wang, Junping; Wang, Guangjian; Wang, Siwang

    2016-01-01

    Objectives: Increased mesangial cell proliferation and accumulation of extracellular matrix (ECM) are the major pathological features of early-stage diabetic nephropathy. This study was sought to investigate the inhibitory effects of rhein (RH) on high glucose (HG)-cultured mesangial cells. Specially, we focus on the analysis of proliferation rate, cell cycle regulation, apoptosis, and the expression of collagen IV and laminin. Materials and Methods: The established rat renal mesangial cell (RMC) line was cultured in medium with different concentrations of glucose (5.6 mM or 25 mM) and RH (40 μM, 20 μM, and 10 μM). Pro-treated cells were collected at 12 h, 24 h, and 48 h for cell proliferation analysis and after 24 h for the experiments of flow cytometry, transmission electron microscope, real-time polymerase chain reaction, and Western blotting. Results: Our data shows HG can promote the proliferation of RMCs and RH has an inhibitory effect on HG-induced RMC proliferation and expression of ECM. Based on our data, we hypothesize this inhibitory effect might be a result of cell cycle regulation and the induction of cellular apoptosis. Conclusion: RH can inhibit cellular proliferation and downregulate the expression of ECM under the circumstance of HG. The mechanism of growth suppression may be due to cell cycle arrest at G1 phase, induction of cell apoptosis, and upregulation of apoptotic mediators bax and caspase-3. SUMMARY Rhein (RH) has an inhibitory effect on high glucose.induced rat mesangial cells proliferationRH has an inhibitory effect on the expression of extracellular matrixRH has a growth.suppression effectRH can upregulate the expression of apoptotic mediators bax and caspase-3All above shows RH is one of the main active ingredient in Shenkang injection. Abbreviations used: RH: Rhein, ECM: Extracellular matrix, DN: Diabetic nephropathy, RMC: Renal mesangial cell, SKI: Shenkang injection, MTT: 3-(4,5-dimethylthiazol–2-yl)-2,5-diphenyltetrazolium

  8. 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 Central

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

    2013-01-01

    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. PMID:24076121

  9. 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.

  10. Resveratrol protects DAergic PC12 cells from high glucose-induced oxidative stress and apoptosis: effect on p53 and GRP75 localization.

    PubMed

    Renaud, Justine; Bournival, Julie; Zottig, Ximena; Martinoli, Maria-Grazia

    2014-01-01

    Resveratrol (RESV), a polyphenolic natural compound, has long been acknowledged to have cardioprotective and antiinflammatory actions. Evidence suggests that RESV has antioxidant properties that reduce the formation of reactive oxygen species leading to oxidative stress and apoptotic death of dopaminergic (DAergic) neurons in Parkinson's disease (PD). Recent literature has recognized hyperglycemia as a cause of oxidative stress reported to be harmful for the nervous system. In this context, our study aimed (a) to evaluate the effect of RESV against high glucose (HG)-induced oxidative stress in DAergic neurons, (b) to study the antiapoptotic properties of RESV in HG condition, and c) to analyze RESV's ability to modulate p53 and GRP75, a p53 inactivator found to be under expressed in postmortem PD brains. Our results suggest that RESV protects DAergic neurons against HG-induced oxidative stress by diminishing cellular levels of superoxide anion. Moreover, RESV significantly reduces HG-induced apoptosis in DAergic cells by modulating DNA fragmentation and the expression of several genes implicated in the apoptotic cascade, such as Bax, Bcl-2, cleaved caspase-3, and cleaved PARP-1. RESV also prevents the pro-apoptotic increase of p53 in the nucleus induced by HG. Such data strengthens the correlation between hyperglycemia and neurodegeneration, while providing new insight on the high occurrence of PD in patients with diabetes. This study enlightens potent neuroprotective roles for RESV that should be considered as a nutritional recommendation for preventive and/or complementary therapies in controlling neurodegenerative complications in diabetes. PMID:24218232

  11. Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

    PubMed

    Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

    2016-09-01

    As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders.

  12. Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

    PubMed

    Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

    2016-09-01

    As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders. PMID:27378427

  13. 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

  14. 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.

  15. 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…

  16. Exogenous spermine ameliorates high glucose-induced cardiomyocytic apoptosis via decreasing reactive oxygen species accumulation through inhibiting p38/JNK and JAK2 pathways.

    PubMed

    He, Yuqin; Yang, Jinxia; Li, Hongzhu; Shao, Hongjiang; Wei, Can; Wang, Yuehong; Li, Meixiu; Xu, Changqing

    2015-01-01

    Reactive oxygen species (ROS) generation has been suggested to play a vital role in the initiation and progression of diabetic cardiomyopathy, a major complication of diabetes mellitus. Recent studies reveal that spermine possesses proliferative, antiaging and antioxidative properties. Thus, we hypothesized that spermine could decrease apoptosis via suppressing ROS accumulation induced by high glucose (HG) in cardiomyocytes. Cultured neonatal rat ventricle cardiomyocytes were treated with normal glucose (NG) (5 mM) or HG (25 mM) in the presence or absence of spermine for 48 h. The cell activity, apoptosis, ROS production, T-SOD and GSH activities, MDA content and GSSG level were assessed. The results showed that HG induced lipid peroxidation and the increase of intracellular ROS formation and apoptosis in primary cardiomyocytes. Spermine could obviously improve the above-mentioned changes. Western blot analysis revealed that spermine markedly inhibited HG-induced the phosphorylation of p38/JNK MAPKs and JAK2. Moreover, spermine had better antioxidative and anti-apoptotic effects than N-acetyl-L-cysteine (NAC). Taken together, the present data suggested that spermine could suppress ROS accumulation to decrease cardiomyocytes apoptosis in HG condition, which may be attributed to the inhibition of p38/JNK and JAK2 activation and its natural antioxidative property. Our findings may highlight a new therapeutic intervention for the prevention of diabetic cardiomyopathy. PMID:26884823

  17. Exogenous spermine ameliorates high glucose-induced cardiomyocytic apoptosis via decreasing reactive oxygen species accumulation through inhibiting p38/JNK and JAK2 pathways

    PubMed Central

    He, Yuqin; Yang, Jinxia; Li, Hongzhu; Shao, Hongjiang; Wei, Can; Wang, Yuehong; Li, Meixiu; Xu, Changqing

    2015-01-01

    Reactive oxygen species (ROS) generation has been suggested to play a vital role in the initiation and progression of diabetic cardiomyopathy, a major complication of diabetes mellitus. Recent studies reveal that spermine possesses proliferative, antiaging and antioxidative properties. Thus, we hypothesized that spermine could decrease apoptosis via suppressing ROS accumulation induced by high glucose (HG) in cardiomyocytes. Cultured neonatal rat ventricle cardiomyocytes were treated with normal glucose (NG) (5 mM) or HG (25 mM) in the presence or absence of spermine for 48 h. The cell activity, apoptosis, ROS production, T-SOD and GSH activities, MDA content and GSSG level were assessed. The results showed that HG induced lipid peroxidation and the increase of intracellular ROS formation and apoptosis in primary cardiomyocytes. Spermine could obviously improve the above-mentioned changes. Western blot analysis revealed that spermine markedly inhibited HG-induced the phosphorylation of p38/JNK MAPKs and JAK2. Moreover, spermine had better antioxidative and anti-apoptotic effects than N-acetyl-L-cysteine (NAC). Taken together, the present data suggested that spermine could suppress ROS accumulation to decrease cardiomyocytes apoptosis in HG condition, which may be attributed to the inhibition of p38/JNK and JAK2 activation and its natural antioxidative property. Our findings may highlight a new therapeutic intervention for the prevention of diabetic cardiomyopathy. PMID:26884823

  18. Investigating the protective effect of lithium against high glucose-induced neurotoxicity in PC12 cells: involvements of ROS, JNK and P38 MAPKs, and apoptotic mitochondria pathway.

    PubMed

    Aminzadeh, A; Dehpour, A R; Safa, M; Mirzamohammadi, S; Sharifi, A M

    2014-11-01

    Hyperglycemia that occurs under the diabetic condition is a major cause of diabetic complications such as diabetic neuropathy, one of the most common diabetes-related complications. It is well known that hyperglycemia could result in generation of reactive oxygen species (ROS). Over production of ROS recommended as an important mediator for apoptotic signaling pathway as well as a key early event in the development of diabetic neuropathy. Recently, many studies have indicated that lithium has robust neuroprotective effect in relation to several neurodegenerative diseases. The present study aimed to examine effects of lithium on high glucose (HG)-induced neurotoxicity and to determine some of the underlying molecular mechanisms involved in this response in PC12 cells as a neuronal culture model for diabetic neuropathy. PC12 cells were pretreated with different concentrations of lithium for 7 days, exposed to HG for 24 h. Cell viability was measured by MTT assay. ROS and lipid peroxidation levels as well as superoxide dismutase activity were measured. In order to examine the underlying molecular mechanisms, the expressions of Bax, Bcl-2, Caspase-3, total and phosphorylated JNK and P38 MAPK were also analyzed by Western blotting. The present results indicated that pretreatment with 1 mM lithium has protected PC12 cells against HG-induced apoptotic cell death. It could reduce ROS generation, Bax/Bcl-2 ratio, Caspase-3 activation, and JNK and P38 MAPK phosphorylation. It may be concluded that in HG condition, lithium pretreatment could prevent mitochondrial apoptosis as well as JNK and P38 MAPK pathway in PC12 cells.

  19. Prevention of High Blood Pressure

    MedlinePlus

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

  20. The protective effects of endogenous hydrogen sulfide modulator, S-propargyl-cysteine, on high glucose-induced apoptosis in cardiomyocytes: A novel mechanism mediated by the activation of Nrf2.

    PubMed

    Yang, Hebei; Mao, Yicheng; Tan, Bo; Luo, Shanshan; Zhu, Yizhun

    2015-08-15

    S-propargyl-cysteine (SPRC) is a novel synthetic molecule exerting antioxidant effects via elevating generation of endogenous H2S. Our study aimed to elucidate possible antioxidant mechanisms of SPRC in hyperglycemia-induced oxidative stress. H9C2 cells were treated with SPRC or NaHS at the indicated concentration before being treated with high glucose for 48h. Follow-up experiments were based on detailed description given in Section 2. SD rats were injected with Streptozocin (STZ) to induce diabetes as previously reported. Diabetic rats were administrated with SPRC, NaHS or solution respectively for one week before the rats were killed for follow-up experiments. Our work found that SPRC remarkably attenuated high glucose induced generation of reactive oxygen species and apoptosis in H9C2 cells. SPRC increased stability and nuclear translocation of Nuclear factor erythroid 2-related factor 2 (Nrf2), up-regulated expression of antioxidant enzyme superoxide dismutase (SOD) and interfered with the interaction between Kelch-like ECH-associated protein 1 (KEAP1) and Nrf2. SPRC activated Nrf2 via Cystathionase-γ-lyase (CSE) and Akt pathway. CSE inhibitor PAG and Akt inhibitor LY294002 could reverse the protective effects of SPRC. Knockdown of Nrf2 by shRNA also blocked SPRC up-regulated expression of CSE. Similar results of protein expression and hypoglycemic activity of SPRC were observed in STZ induced diabetic rats.

  1. Berberine attenuates high glucose-induced fibrosis by activating the G protein-coupled bile acid receptor TGR5 and repressing the S1P2/MAPK signaling pathway in glomerular mesangial cells.

    PubMed

    Yang, Zhiying; Li, Jie; Xiong, Fengxiao; Huang, Junying; Chen, Cheng; Liu, Peiqing; Huang, Heqing

    2016-08-15

    Berberine (BBR) exerts powerful renoprotective effects on diabetic nephropathy (DN), but the underlying mechanisms remain unclear. We previously demonstrated that activation of the G protein-coupled bile acid receptor TGR5 ameliorates diabetic nephropathy by inhibiting the activation of the sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 2 (S1P2) signaling pathway. In this study, we explored the role of TGR5 in the BBR-induced downregulation of sphingosine 1-phosphate receptor 2 (S1P2)/mitogen-activated protein kinase (MAPK)-mediated fibrosis in glomerular mesangial cells (GMCs). Results showed that, BBR suppressed the expression of FN, ICAM-1, and TGF-β1 in high-glucose cultures of GMCs, and the phosphorylation level of c-Jun/c-Fos was downregulated. The high glucose lowered TGR5 expression in a time-dependent manner; this effect was reversed by BBR in a dose-dependent manner. The TGR5 agonist INT-777 decreased the high glucose-induced FN, ICAM-1, and TGF-β1 protein contents. In addition, TGR5 siRNA blocked S1P2 degradation by BBR. And MAPK signaling, which plays important regulatory roles in the pathological progression of DN, was activated by TGR5 siRNA. Apart from this, MAPK signaling as well as FN, ICAM-1, and TGF-β1 suppressed by BBR under high glucose conditions were limited by TGR5 depletion. Thus, BBR decreases FN, ICAM-1, and TGF-β1 levels under high glucose conditions in GMCs possibly by activating TGR5 and inhibiting S1P2/MAPK signaling. PMID:27292312

  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

    2016-02-01

    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. 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

  4. Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in Peromyscus leucopus.

    PubMed

    Labinskyy, Nazar; Mukhopadhyay, Partha; Toth, Janos; Szalai, Gabor; Veres, Monika; Losonczy, Gyorgy; Pinto, John T; Pacher, Pal; Ballabh, Praveen; Podlutsky, Andrej; Austad, Steven N; Csiszar, Anna; Ungvari, Zoltan

    2009-04-01

    Vascular aging is characterized by increased oxidative stress and proinflammatory phenotypic alterations. Metabolic stress, such as hyperglycemia in diabetes, is known to increase the production of ROS and promote inflammatory gene expression, accelerating vascular aging. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower steady-state production of ROS and/or superior resistance to the prooxidant effects of metabolic stress. We tested this hypothesis using two taxonomically related rodents, the white-footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), which show a more than twofold difference in maximum lifespan potential (8.2 and 3.5 yr, respectively). We compared interspecies differences in steady-state and high glucose (HG; 30 mmol/l)-induced production of O(2)(*-) and H(2)O(2), endothelial function, mitochondrial ROS generation, and inflammatory gene expression in cultured aortic segments. In P. leucopus aortas, steady-state endothelial O(2)(*-) and H(2)O(2) production and ROS generation by mitochondria were less than in M. musculus vessels. Furthermore, vessels of P. leucopus were more resistant to the prooxidant effects of HG. Primary fibroblasts from P. leucopus also exhibited less steady-state and HG-induced ROS production than M. musculus cells. In M. musculus arteries, HG elicited significant upregulation of inflammatory markers (TNF-alpha, IL-6, ICAM-1, VCAM, and monocyte chemoattractant protein-1). In contrast, the proinflammatory effects of HG were blunted in P. leucopus vessels. Thus, increased life span potential in P. leucopus is associated with decreased cellular ROS generation and increased resistance to prooxidant and proinflammatory effects of metabolic stress, which accord with predictions of the oxidative stress hypothesis of aging.

  5. CKIP-1 ameliorates high glucose-induced expression of fibronectin and intercellular cell adhesion molecule-1 by activating the Nrf2/ARE pathway in glomerular mesangial cells.

    PubMed

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

    2016-09-15

    Glucose and lipid metabolism disorders as well as oxidative stress (OSS) play important roles in diabetic nephropathy (DN). Glucose and lipid metabolic dysfunctions are the basic pathological changes of chronic microvascular complications of diabetes mellitus, such as DN. OSS can lead to the accumulation of extracellular matrix and inflammatory factors which will accelerate the progress of DN. Casein kinase 2 interacting protein-1 (CKIP-1) mediates adipogenesis, cell proliferation and inflammation under many circumstances. However, whether CKIP-1 is involved in the development of DN remains unknown. Here, we show that CKIP-1 is a novel regulator of resisting the development of DN and the underlying molecular mechanism is related to activating the nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) antioxidative stress pathway. The following findings were obtained: (1) The treatment of glomerular mesangial cells (GMCs) with high glucose (HG) decreased CKIP-1 levels in a time-dependent manner; (2) CKIP-1 overexpression dramatically reduced fibronectin (FN) and intercellular adhesionmolecule-1 (ICAM-1) expression. Depletion of CKIP-1 further induced the production of FN and ICAM-1; (3) CKIP-1 promoted the nuclear accumulation, DNA binding, and transcriptional activity of Nrf2. Moreover, CKIP-1 upregulated the expression of Nrf2 downstream genes, heme oxygenase (HO-1) and superoxide dismutase 1 (SOD1); and ultimately decreased the levels of reactive oxygen species (ROS). The molecular mechanisms clarify that the advantageous effect of CKIP-1 on DN are well connected with the activation of the Nrf2/ARE antioxidative stress pathway. PMID:27481061

  6. High Glucose-induced O-GlcNAcylated Carbohydrate Response Element-binding Protein (ChREBP) Mediates Mesangial Cell Lipogenesis and Fibrosis

    PubMed Central

    Park, Min-Jung; Kim, Dong-Il; Lim, Seul-Ki; Choi, Joo-Hee; Han, Ho-Jae; Yoon, Kyung-Chul; Park, Soo-Hyun

    2014-01-01

    Carbohydrate response element-binding protein (ChREBP) is a transcription factor responsible for carbohydrate metabolism in the liver. However, the role of ChREBP in diabetic nephropathy has not been elucidated. Thus, we investigated the role of ChREBP in mesangial cells in diabetic nephropathy. Treatment with 25 mm glucose (high glucose; HG) increased cellular O-GlcNAc and O-GlcNAcylated ChREBP in mesangial cells compared with normal 5.5 mm glucose. O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino N-phenylcarbamate (PUGNAc), a drug that increases O-GlcNAc, augmented the expression of ChREBP targets, whereas DON, a drug that decreases O-GlcNAc and O-GlcNAcase overexpression, mitigated the increase with HG. O-GlcNAc augmented the protein stability, transcriptional activity, and nuclear translocation of ChREBP. HG treatment also stimulated lipid accumulation and the contents of triglyceride and cholesterol in mesangial cells. In addition, HG triggered expression of hypoxia-inducible factor 1-α, vascular endothelial growth factor, and extracellular matrix components related to nephrosclerosis. The ChREBP mutant, W130A, did not exhibit HG-induced lipid accumulation and fibrotic proteins, suggesting that the Trp-130 residue in the MCR3 domain is important in the development of glomerulosclerosis. O-GlcNAcylated ChREBP was elevated in mesangium cells of streptozotocin-induced diabetic rats. In conclusion, HG increased the O-GlcNAcylated ChREBP level, which resulted in lipid accumulation and up-regulation of fibrotic proteins in mesangial cells. These effects may lead mesangial cells to an ultimately pathological state. PMID:24616092

  7. 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

  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. High Blood Cholesterol Prevention

    MedlinePlus

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  10. Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells.

    PubMed

    Chen, Shali; Feng, Biao; George, Biju; Chakrabarti, Rana; Chen, Megan; Chakrabarti, Subrata

    2010-01-01

    Sustained hyperglycemia in diabetes causes alteration of a large number of transcription factors and mRNA transcripts, leading to tissue damage. We investigated whether p300, a transcriptional coactivator with histone acetyl transferase activity, regulates glucose-induced activation of transcription factors and subsequent upregulation of vasoactive factors and extracellular matrix (ECM) proteins in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated in varied glucose concentrations and were studied after p300 small interfering RNA (siRNA) transfection, p300 overexpression, or incubation with the p300 inhibitor curcumin. Histone H2AX phosphorylation and lysine acetylation were examined for oxidative DNA damage and p300 activation. Screening for transcription factors was performed with the Luminex system. Alterations of selected transcription factors were validated. mRNA expression of p300, endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and fibronectin (FN) and its splice variant EDB(+)FN and FN protein production were analyzed. HUVECs in 25 mmol/l glucose showed increased p300 production accompanied by increased binding of p300 to ET-1 and FN promoters, augmented histone acetylation, H2AX phosphorylation, activation of multiple transcription factors, and increased mRNA expression of vasoactive factors and ECM proteins. p300 overexpression showed a glucose-like effect on the mRNA expression of ET-1, VEGF, and FN. Furthermore, siRNA-mediated p300 blockade or chemical inhibitor of p300 prevented such glucose-induced changes. Similar mRNA upregulation was also seen in the organ culture of vascular tissues, which was prevented by p300 siRNA transfection. Data from these studies suggest that glucose-induced p300 upregulation is an important upstream epigenetic mechanism regulating gene expression of vasoactive factors and ECM proteins in endothelial cells and is a potential therapeutic target for diabetic complications.

  11. GLUCOSE-INDUCED INTESTINAL VASODILATION VIA ADENOSINE A1 RECEPTORS REQUIRES NITRIC OXIDE BUT NOT K+ATP CHANNELS

    PubMed Central

    Matheson, Paul J.; Li, Na; Harris, Patrick D.; Zakaria, El Rasheid; Garrison, R. Neal

    2010-01-01

    INTRODUCTION Both nitric oxide (NO) and adenosine A1 receptor activation mediate microvascular vasodilation during intestinal glucose absorption. Our overall hypothesis is that ATP utilization during glucose absorption would increase adenosine metabolite release, which acts on adenosine A1 receptors to alter endothelial production of NO and/or activate ATP-dependent potassium channels (K+ATP) to dilate intestinal microvessels. METHODS Intravital videomicroscopy of the rat jejunum was used to record the vascular responses of inflow (termed 1A) arterioles and proximal (p3A) and distal (d3A) premucosal arterioles during exposure to isotonic glucose or mannitol solutions alone or in the presence of the selective nitric oxide synthase (NOS) inhibitor (L-NMMA), an adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX)), or a K+ATP channel inhibitor (glibenclamide). RESULTS As expected, glucose exposure caused rapid dilation of both p3A and d3A arterioles, while mannitol exposure had no effect on microvascular diameters. Adenosine A1 receptor blockade completely prevented glucose-induced dilation of the premucosal arterioles. NOS inhibition significantly blunted the glucose-induced vasodilation of the premucosal arterioles, but had little effect in the mannitol group. Simultaneous application of both the NOS inhibitor and the adenosine A1 receptor antagonist gave the same reduction in glucose-induced dilation of the premucosal arterioles as the adenosine A1 receptor antagonist alone. Blockade of K+ATP channels with glibenclamide did not attenuate glucose-induced vasodilation of the premucosal arterioles. CONCLUSIONS These data suggest that glucose-induced vasodilation of premucosal jejunal arterioles is mediated through adenosine A1 receptors, and NO at least partially mediates the adenosine A1 receptor-induced vasodilation. In addition, K+ATP channels are not involved in premucosal arteriolar vasodilation during intestinal glucose exposure. PMID

  12. 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. PMID:23512199

  13. Bradykinin receptors and EphB2/EphrinB2 pathway in response to high glucose-induced osteoblast dysfunction and hyperglycemia-induced bone deterioration in mice.

    PubMed

    Wu, Min; Ai, Wenting; Chen, Lin; Zhao, Sihai; Liu, Enqi

    2016-03-01

    This study was carried out in order to investigate bone dysfunction and the involvement of bradykinin receptors and the Eph/Ephrin signaling pathway in osteoblasts and in mice with diabetes-related osteoporosis in response to exposure to high glucose. Osteogenic transdifferentiation was inhibited when the osteoblasts were exposed to high glucose, and the expression levels of bone formation-related genes [Runx2 and alkaline phosphatase (ALP)] were decreased, while those of bone resorption-related genes [matrix metalloproteinase (MMP)9 and carbonic anhydrase II (CAII)] were increased. Moreover, the mRNA and protein expression levels of bradykinin receptor B1 (BK1R)/bradykinin receptor B2 (BK2R) and EphB2/EphrinB2 were significantly decreased in the osteoblasts following exposure to high glucose. Intriguingly, the interaction between BK2R and EphB2/EphrinB2 was confirmed, and BK2R loss-of-function significantly decreased the mRNA and protein expression levels of EphB2/EphrinB4. In vivo, hyperglycemia induced the disequilibrium of calcium homeostasis through the inhibition of bone formation and the acceleration of bone resorption, which was manifested by the reduction of trabecular bone mass of the primary and secondary spongiosa, as well as by the increase in the number of mature osteoclasts throughout the proximal tibial metaphysis in mice with diabetes-related osteoporosis. Furthermore, the mRNA and protein expression levels of BK1R/BK2R and EphB2/EphrinB2 in the tibias of the mice with diabetes-related osteoporosis were significantly decreased. These results demonstrate that bradykinin receptors and the EphB4/EphrinB2 pathway mediate the development of complications in mice with diabetes-related osteoporosis and suggest that the inactivation of bradykinin receptors and the EphB4/EphrinB2 pathway enhance the severity of complications in mice with diabetes-related osteoporosis. PMID:26782642

  14. Bradykinin receptors and EphB2/EphrinB2 pathway in response to high glucose-induced osteoblast dysfunction and hyperglycemia-induced bone deterioration in mice

    PubMed Central

    WU, MIN; AI, WENTING; CHEN, LIN; ZHAO, SIHAI; LIU, ENQI

    2016-01-01

    This study was carried out in order to investigate bone dysfunction and the involvement of bradykinin receptors and the Eph/Ephrin signaling pathway in osteoblasts and in mice with diabetes-related osteoporosis in response to exposure to high glucose. Osteogenic transdifferentiation was inhibited when the osteoblasts were exposed to high glucose, and the expression levels of bone formation-related genes [Runx2 and alkaline phosphatase (ALP)] were decreased, while those of bone resorption-related genes [matrix metalloproteinase (MMP)9 and carbonic anhydrase II (CAII)] were increased. Moreover, the mRNA and protein expression levels of bradykinin receptor B1 (BK1R)/bradykinin receptor B2 (BK2R) and EphB2/EphrinB2 were significantly decreased in the osteoblasts following exposure to high glucose. Intriguingly, the interaction between BK2R and EphB2/EphrinB2 was confirmed, and BK2R loss-of-function significantly decreased the mRNA and protein expression levels of EphB2/EphrinB4. In vivo, hyperglycemia induced the disequilibrium of calcium homeostasis through the inhibition of bone formation and the acceleration of bone resorption, which was manifested by the reduction of trabecular bone mass of the primary and secondary spongiosa, as well as by the increase in the number of mature osteoclasts throughout the proximal tibial metaphysis in mice with diabetes-related osteoporosis. Furthermore, the mRNA and protein expression levels of BK1R/BK2R and EphB2/EphrinB2 in the tibias of the mice with diabetes-related osteoporosis were significantly decreased. These results demonstrate that bradykinin receptors and the EphB4/EphrinB2 pathway mediate the development of complications in mice with diabetes-related osteoporosis and suggest that the inactivation of bradykinin receptors and the EphB4/EphrinB2 pathway enhance the severity of complications in mice with diabetes-related osteoporosis. PMID:26782642

  15. Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism.

    PubMed

    Mason, R Preston; Jacob, Robert F

    2015-02-01

    Lipid oxidation leads to endothelial dysfunction, inflammation, and foam cell formation during atherogenesis. Glucose also contributes to lipid oxidation and promotes pathologic changes in membrane structural organization, including the development of cholesterol crystalline domains. In this study, we tested the comparative effects of eicosapentaenoic acid (EPA), an omega-3 fatty acid indicated for the treatment of very high triglyceride (TG) levels, and other TG-lowering agents (fenofibrate, niacin, and gemfibrozil) on lipid oxidation in human low-density lipoprotein (LDL) as well as membrane lipid vesicles prepared in the presence of glucose (200 mg/dL). We also examined the antioxidant effects of EPA in combination with atorvastatin o-hydroxy (active) metabolite (ATM). Glucose-induced changes in membrane structural organization were measured using small angle x-ray scattering approaches and correlated with changes in lipid hydroperoxide (LOOH) levels. EPA was found to inhibit LDL oxidation in a dose-dependent manner (1.0-10.0 µM) and was distinguished from the other TG-lowering agents, which had no significant effect as compared to vehicle treatment alone. Similar effects were observed in membrane lipid vesicles exposed to hyperglycemic conditions. The antioxidant activity of EPA, as observed in glucose-treated vesicles, was significantly enhanced in combination with ATM. Glucose treatment produced highly-ordered, membrane-restricted, cholesterol crystalline domains, which correlated with increased LOOH levels. Of the agents tested in this study, only EPA inhibited glucose-induced cholesterol domain formation. These data demonstrate that EPA, at pharmacologic levels, inhibits hyperglycemia-induced changes in membrane lipid structural organization through a potent antioxidant mechanism associated with its distinct, physicochemical interactions with the membrane bilayer. PMID:25449996

  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. Effects of plant extracts on the reversal of glucose-induced impairment of stress-resistance in Caenorhabditis elegans.

    PubMed

    Fitzenberger, Elena; Deusing, Dorothé Jenni; Wittkop, Anette; Kler, Adolf; Kriesl, Erwin; Bonnländer, Bernd; Wenzel, Uwe

    2014-03-01

    Enhanced blood glucose levels are a hallmark of diabetes and are associated with diabetic complications and a reduction of lifespan. In order to search for plant extracts that display preventive activities in such a scenario, we tested 16 extracts used in human nutrition for their survival enhancing activities in the nematode Caenorhabditis elegans. Nematodes were exposed for 48 h to 10 mM glucose in the absence or presence of 0.1% extract. Thereafter, survival was measured at 37 °C. Extracts made from coffee, kola, rooibos and cinnamon, did not influence the glucose-induced reduction of survival. Those made from ginseng, camomile, lime blossom, paraguay tea, balm, rhodiola, black tea, or knotgrass all extended the lifespan of the glucose-treated nematodes significantly but did not rescue survival completely. Extracts from the leaves of blackberries, from hibiscus, elderberries, or jiaogulan completely countered the glucose-induced survival reduction. A potent activation of the proteasome was shown for the most preventive extracts suggesting a more efficient degradation of proteins impaired by glucose. In conclusion, we present a simple animal model to screen for plant extracts with potency to reverse glucose toxicity. Extracts from blackberry leaves, hibiscus, elderberries, and jiaogulan were identified as very potent in this regard whose exact mechanisms of action appear worthwile to investigate at the molecular level. PMID:24390728

  18. The protective effects of beta-casomorphin-7 against glucose -induced renal oxidative stress in vivo and vitro.

    PubMed

    Zhang, Wei; Miao, Jinfeng; Wang, Shanshan; Zhang, Yuanshu

    2013-01-01

    Oxidative stress is implicated in the pathogenesis of diabetic nephropathy. The present study aimed to investigate the effect of β-casomorphin-7 (BCM7) on the oxidative stress occurring in kidney tissue in streptozotocin (STZ)-induced diabetic rats and proximal tubular epithelial cells (NRK-52E) exposure to high glucose (HG) by using biochemical methods. There is a significant decrease in plasma insulin and a significant increase in plasma glucagon in the rats of diabetic group. Oral administration of BCM7 for 30 days to rats with STZ-induced diabetes resulted in a significant increase in serum level of insulin, and a decrease in the level of glucagon. Moreover, rats with STZ-induced diabetes had lower levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidative capacity (T-AOC), higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the kidney than that in the control rats. The administration of BCM7 altered the changes of SOD, GPx, T-AOC, MDA and H2O2 in the kidney of diabetic rats. Furthermore, BCM7 alleviated high glucose-induced decreasement in SOD and GPx activity, increasement in MDA contents in the NRK-52E cells. BCM7 ameliorated the changes of angiotensin converting enzyme (ACE) and ACE2 levels in the kidney of diabetic rats and BCM7 lowered the levels of angiotensin (Ang)II in the kidney of diabetic rats and culture medium for cells. Moreover losartan (antagonist of angiotensin II type I receptor) lowered the high glucose-induced oxidative stress in the NRK-52E cells. Our results suggest that administration of BCM7 would alleviate high glucose-induced renal oxidative stress in vivo and in vitro, which may be associated with down regulation of the concentration of Ang II partly. PMID:23658831

  19. 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.

  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. Effect of chemical chaperones on glucose-induced lysozyme modifications.

    PubMed

    Bathaie, S Zahra; Nobakht, B B Fateme; Mirmiranpour, Hossein; Jafarnejad, Akbar; Moosavi-Nejad, S Zahra

    2011-10-01

    Nonenzymatic glycation of biomacromolecules occurs due to the diabetes mellitus and ageing. A number of small molecules, known as chemical chaperones, stabilize protein conformation against thermal and chemically induced denaturation. These compounds are including: polyamines (e.g. spermine and spermidine), amino acids (e.g. lysine) and polyols (e.g. glycerol). In this study the effect of spermidine (Spd), spermine (Spm), and glycerol on glycation, structure and function of lysozyme (LZ), as an extra-cellular protein, by different techniques is investigated. LZ is incubated with or without glucose (50 or 100 mM) in the absence or presence of Spd/Spm/glycerol at 37 °C up to 16 weeks. All the observed changes of glycated-LZ in comparison with the native protein, including: increased fluorescence emission, alteration in the secondary and tertiary structure, and reduced electrophoretic mobility- indicate its structural changes that are accompanied with its reduced activity. Glucose in the presence or absence of Spd induces the protein dimerization, but glucose plus Spm induces its trimmerization. In contrast, glycerol inhibits the LZ glycation and prevents the large changes on its structure and function. Glucose binds lysine residues, decreases the protein positive charges and induces some alterations in its structure and activity. Polyamines also directly bind to LZ, increase its positive charges and hence induce more glycation; more conformational changes, oligomerization and its inactivation in the presence of glucose, but glycerol affect the protein environment and preserve protein from these harmful effects.

  3. In vivo and in vitro glucose-induced biphasic insulin secretion in the mouse: pattern and role of cytoplasmic Ca2+ and amplification signals in beta-cells.

    PubMed

    Henquin, Jean-Claude; Nenquin, Myriam; Stiernet, Patrick; Ahren, Bo

    2006-02-01

    The mechanisms underlying biphasic insulin secretion have not been completely elucidated. We compared the pattern of plasma insulin changes during hyperglycemic clamps in mice to that of glucose-induced insulin secretion and cytosolic calcium concentration ([Ca(2+)](c)) changes in perifused mouse islets. Anesthetized mice were infused with glucose to clamp blood glucose at 8.5 (baseline), 11.1, 16.7, or 30 mmol/l. A first-phase insulin response consistently peaked at 1 min, and a slowly ascending second phase occurred at 16.7 and 30 mmol/l glucose. Glucose-induced insulin secretion in vivo is thus biphasic, with a similarly increasing second phase in the mouse as in humans. In vitro, square-wave stimulation from a baseline of 3 mmol/l glucose induced similar biphasic insulin secretion and [Ca(2+)](c) increases, with sustained and flat second phases. The glucose dependency (3-30 mmol/l) of both changes was sigmoidal with, however, a shift to the right of the relation for insulin secretion compared with that for [Ca(2+)](c). The maximum [Ca(2+)](c) increase was achieved by glucose concentrations, causing half-maximum insulin secretion. Because this was true for both phases, we propose that contrary to current concepts, amplifying signals are also implicated in first-phase glucose-induced insulin secretion. To mimic in vivo conditions, islets were stimulated with high glucose after being initially perifused with 8.5 instead of 3.0 mmol/l glucose. First-phase insulin secretion induced by glucose at 11.1, 16.7, and 30 mmol/l was decreased by approximately 50%, an inhibition that could not be explained by commensurate decreases in [Ca(2+)](c) or in the pool of readily releasable granules. Also unexpected was the gradually ascending pattern of the second phase, now similar to that in vivo. These observations indicated that variations in prestimulatory glucose can secondarily affect the magnitude and pattern of subsequent glucose-induced insulin secretion.

  4. Ascorbate Reverses High Glucose- and RAGE-induced Leak of the Endothelial Permeability Barrier

    PubMed Central

    Meredith, M. Elizabeth; Qu, Zhi-chao; May, James M.

    2014-01-01

    High glucose concentrations due to diabetes increase leakage of plasma constituents across the endothelial permeability barrier. We sought to determine whether vitamin C, or ascorbic acid (ascorbate), could reverse such high glucose-induced increases in endothelial barrier permeability. Human umbilical vein endothelial cells and two brain endothelial cell lines cultured at 25 mM glucose showed increases in endothelial barrier permeability to radiolabeled inulin compared to cells cultured at 5 mM glucose. Acute loading of the cells for 30–60 min with ascorbate before the permeability assay prevented the high glucose-induced increase in permeability and decreased basal permeability at 5 mM glucose. High glucose-induced barrier leakage was mediated largely by activation of the receptor for advanced glycation end products (RAGE), since it was prevented by RAGE blockade and mimicked by RAGE ligands. Intracellular ascorbate completely prevented RAGE ligand-induced increases in barrier permeability. The high glucose-induced increase in endothelial barrier permeability was also acutely decreased by several cell-penetrant antioxidants, suggesting that at least part of the ascorbate effect could be due to its ability to act as an antioxidant. PMID:24472555

  5. 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…

  6. Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel.

    PubMed

    Oya, Manami; Kitaguchi, Tetsuya; Harada, Kazuki; Numano, Rika; Sato, Takahiro; Kojima, Masayasu; Tsuboi, Takashi

    2015-07-01

    Ghrelin is synthesized in X/A-like cells of the gastric mucosa, which plays an important role in the regulation of energy homeostasis. Although ghrelin secretion is known to be induced by neurotransmitters or hormones or by nutrient sensing in the ghrelin-secreting cells themselves, the mechanism of ghrelin secretion is not clearly understood. In the present study, we found that changing the extracellular glucose concentration from elevated (25  mM) to optimal (10 mM) caused an increase in the intracellular Ca2+ concentration ([Ca2+]i) in ghrelin-secreting mouse ghrelinoma 3-1 (MGN3-1) cells (n=32, P<0.01), whereas changing the glucose concentration from elevated to lowered (5 or 1 mM) had little effect on [Ca2+]i increase. Overexpression of a closed form of an ATP-sensitive K+ (KATP) channel mutant suppressed the 10  mM glucose-induced [Ca2+]i increase (n=8, P<0.01) and exocytotic events (n=6, P<0.01). We also found that a low concentration of a KATP channel opener, diazoxide, with 25  mM glucose induced [Ca2+]i increase (n=23, P<0.01) and ghrelin secretion (n≥3, P<0.05). In contrast, the application of a low concentration of a KATP channel blocker, tolbutamide, significantly induced [Ca2+]i increase (n=15, P<0.01) and ghrelin secretion (n≥3, P<0.05) under 5 mM glucose. Furthermore, the application of voltage-dependent Ca2+ channel inhibitors suppressed the 10 mM glucose-induced [Ca2+]i increase (n≥26, P<0.01) and ghrelin secretion (n≥5, P<0.05). These findings suggest that KATP and voltage-dependent Ca2+ channels are involved in glucose-dependent ghrelin secretion in MGN3-1 cells.

  7. Glucose-induced toxicity in insulin-producing pituitary cells that coexpress GLUT2 and glucokinase. Implications for metabolic engineering.

    PubMed

    Faradji, R N; Havari, E; Chen, Q; Gray, J; Tornheim, K; Corkey, B E; Mulligan, R C; Lipes, M A

    2001-09-28

    We have shown that intermediate lobe (IL) pituitary cells can be engineered to produce sufficient amounts of insulin (ins) to cure diabetes in nonobese diabetic mice but, unlike transplanted islets, ILins cells evade immune attack. To confer glucose-sensing capabilities into these cells, they were further modified with recombinant adenoviruses to express high levels of GLUT2 and the beta-cell isoform of glucokinase (GK). Although expression of GLUT2 alone had negligible effects on glucose usage and lactate production, expression of GK alone resulted in approximately 2-fold increase in glycolytic flux within the physiological (3-20 mm) glucose range. GLUT2/GK coexpression further increased glycolytic flux at 20 mm glucose but disproportionately increased flux at 3 mm glucose. Despite enhanced glycolytic fluxes, GLUT2/GK-coexpressing cells showed glucose dose-dependent accumulation of hexose phosphates, depletion of intracellular ATP, and severe apoptotic cell death. These studies demonstrate that glucose-sensing properties can be introduced into non-islet cells by the single expression of GK and that glucose responsiveness can be augmented by the coexpression of GLUT2. However, in the metabolic engineering of surrogate beta cells, it is critical that the levels of the components be closely optimized to ensure their physiological function and to avoid the deleterious consequences of glucose-induced toxicity.

  8. Dropout Prevention: A Study of Prevention Programs Used by High Schools to Increase Graduation Rate

    ERIC Educational Resources Information Center

    Simmons, Christopher L.

    2013-01-01

    This mixed methods study focused on the relationship between dropout prevention programs and graduation rates in one school district in Florida during the 2010-2011 school year. The dropout prevention program data analyzed included high school principals' perceptions in regard to perceived effectiveness, fidelity of implementation, cost efficacy,…

  9. 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…

  10. 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

  11. Effects of calcium buffering on glucose-induced insulin release in mouse pancreatic islets: an approximation to the calcium sensor

    PubMed Central

    Pertusa, José A G; Sanchez-Andrés, Juan V; Martín, Franz; Soria, Bernat

    1999-01-01

    The properties of the calcium sensor for glucose-induced insulin secretion have been studied using cell-permeant Ca2+ buffers with distinct kinetics and affinities. In addition, submembrane cytosolic Ca2+ distribution has been modelled after trains of glucose-induced action potential-like depolarizations. Slow Ca2+ buffers (around 1 mmol l−1 intracellular concentration) with different affinities (EGTA and Calcium Orange-5N) did not significantly affect glucose-induced insulin release. Modelling showed no effect on cytosolic Ca2+ concentrations at the outermost shell (0.05 μm), their effects being observed in the innermost shells dependent on Ca2+ affinity. In contrast, fast Ca2+ buffers (around 1 mmol l−1 intracellular concentration) with different affinities (BAPTA and Calcium Green-5N) caused a 50% inhibition of early insulin response and completely blocked the late phase of glucose-induced insulin response, their simulations showing a decrease of [Ca2+]i at both the inner and outermost shells. These data are consistent with the existence in pancreatic β-cells of a higher affinity Ca2+ sensor than that proposed for neurons. Moreover, these data are consistent with the proposed existence of two distinct pools of granules: (i) ‘primed’ vesicles, colocalized with Ca2+ channels and responsible of the first phase of insulin release; and (ii) ‘reserved pool’ vesicles, not colocalized and responsible for the second phase. PMID:10523416

  12. Long-term exposure of proximal tubular epithelial cells to glucose induces transforming growth factor-beta 1 synthesis via an autocrine PDGF loop.

    PubMed

    Fraser, Donald; Brunskill, Nigel; Ito, Takafumi; Phillips, Aled

    2003-12-01

    We have recently reported increased transforming growth factor (TGF)-beta1 gene transcription in proximal tubular cells within 12 hours of exposure to 25 mmol/L D-glucose, with a requirement for a second stimulus such as platelet-derived growth factor (PDGF) to increase its translation in short-term experiments. In the current study we investigated the effect on TGF-beta 1 production of prolonged exposure of proximal tubular cells to high glucose concentrations. Enzyme-linked immunosorbent assay of cell culture supernatant showed significant increase in latent TGF-beta 1 only after 7 days exposure to high glucose. Radiolabeling of glucose-stimulated cells with (3)H amino acids and subsequent immunoprecipitation of TGF-beta 1 demonstrated de novo synthesis from day 5 of high glucose exposure onwards. Similarly, polysome analysis showed enhanced translation of TGF-beta mRNA after 4 or more days of high glucose exposure. TGF-beta 1 synthesis, following addition of glucose, was inhibited by blockade of the PDGF-alpha receptor subunit. Glucose did not alter PDGF expression, nor expression of PDGF alpha-receptors. Activation of the receptor following addition of 25 mm D-glucose could be demonstrated suggesting increased sensitivity to endogenous PDGF. Exposure to glucose activated p38MAP kinase, and inhibition of this activation abrogated both glucose induced TGF-beta 1 transcriptional activation and TGF-beta 1 synthesis. Inhibition of p38MAP kinase did not influence the effect of exogenous PDGF when cells were stimulated sequentially by glucose and PDGF. We postulate that glucose induces an early increase in TGF-beta 1 transcription via activation of p38MAP kinase. In addition, glucose causes a late increase in PDGF-dependent TGF-beta 1 translation by enhancing cellular sensitivity to PDGF. This provides a potential explanation for the clinical observation that prolonged poor glycemic control may contribute to progression of diabetic nephropathy. PMID:14633628

  13. MicroRNAs involved in the mitogen-activated protein kinase cascades pathway during glucose-induced cardiomyocyte hypertrophy.

    PubMed

    Shen, E; Diao, Xuehong; Wang, Xiaoxia; Chen, Ruizhen; Hu, Bing

    2011-08-01

    Cardiac hypertrophy is a key structural feature of diabetic cardiomyopathy in the late stage of diabetes. Recent studies show that microRNAs (miRNAs) are involved in the pathogenesis of cardiac hypertrophy in diabetic mice, but more novel miRNAs remain to be investigated. In this study, diabetic cardiomyopathy, characterized by hypertrophy, was induced in mice by streptozotocin injection. Using microarray analysis of myocardial tissue, we were able to identify changes in expression in 19 miRNA, of which 16 miRNAs were further validated by real-time PCR and a total of 3212 targets mRNA were predicted. Further analysis showed that 31 GO functions and 16 KEGG pathways were enriched in the diabetic heart. Of these, MAPK signaling pathway was prominent. In vivo and in vitro studies have confirmed that three major subgroups of MAPK including ERK1/2, JNK, and p38, are specifically upregulated in cardiomyocyte hypertrophy during hyperglycemia. To further explore the potential involvement of miRNAs in the regulation of glucose-induced cardiomyocyte hypertrophy, neonatal rat cardiomyocytes were exposed to high glucose and transfected with miR-373 mimic. Overexpression of miR-373 decreased the cell size, and also reduced the level of its target gene MEF2C, and miR-373 expression was regulated by p38. Our data highlight an important role of miRNAs in diabetic cardiomyopathy, and implicate the reliability of bioinformatics analysis in shedding light on the mechanisms underlying diabetic cardiomyopathy.

  14. 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…

  15. HIGH GLUCOSE INDUCES TOLL-LIKE RECEPTOR EXPRESSION IN HUMAN MONOCYTES: MECHANISM OF ACTIVATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Hyperglycemia induced inflammation is central in diabetes complications and monocytes are important in orchestrating these effects. Toll-like receptors (TLRs) play a key role in innate immune responses as well as inflammation. However, there is a paucity of data examining the expression a...

  16. High School Students' Perceptions of Alcohol Prevention Programs

    ERIC Educational Resources Information Center

    Ogenchuk, Marcella

    2012-01-01

    The purpose of this study was to explore Grade 11 students' perceptions of programs related to the prevention of alcohol use in high school settings through an analysis of quantitative and qualitative data elicited from student questionnaires (n=452) and focus groups. It was found that students felt a need for increased information on alcohol…

  17. 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…

  18. 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.

  19. Highly active antiretroviral treatment for the prevention of HIV transmission

    PubMed Central

    2010-01-01

    In 2007 an estimated 33 million people were living with HIV; 67% resided in sub-Saharan Africa, with 35% in eight countries alone. In 2007, there were about 1.4 million HIV-positive tuberculosis cases. Globally, approximately 4 million people had been given highly active antiretroviral therapy (HAART) by the end of 2008, but in 2007, an estimated 6.7 million were still in need of HAART and 2.7 million more became infected with HIV. Although there has been unprecedented investment in confronting HIV/AIDS - the Joint United Nations Programme on HIV/AIDS estimates $13.8 billion was spent in 2008 - a key challenge is how to address the HIV/AIDS epidemic given limited and potentially shrinking resources. Economic disparities may further exacerbate human rights issues and widen the increasingly divergent approaches to HIV prevention, care and treatment. HIV transmission only occurs from people with HIV, and viral load is the single greatest risk factor for all modes of transmission. HAART can lower viral load to nearly undetectable levels. Prevention of mother to child transmission offers proof of the concept of HAART interrupting transmission, and observational studies and previous modelling work support using HAART for prevention. Although knowing one's HIV status is key for prevention efforts, it is not known with certainty when to start HAART. Building on previous modelling work, we used an HIV/AIDS epidemic of South African intensity to explore the impact of testing all adults annually and starting persons on HAART immediately after they are diagnosed as HIV positive. This theoretical strategy would reduce annual HIV incidence and mortality to less than one case per 1000 people within 10 years and it would reduce the prevalence of HIV to less than 1% within 50 years. To explore HAART as a prevention strategy, we recommend further discussions to explore human rights and ethical considerations, clarify research priorities and review feasibility and acceptability

  20. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25713368

  2. 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 ...

  3. Rosuvastatin Treatment Affects Both Basal and Glucose-Induced Insulin Secretion in INS-1 832/13 Cells

    PubMed Central

    Salunkhe, Vishal A.; Elvstam, Olof; Eliasson, Lena; Wendt, Anna

    2016-01-01

    Rosuvastatin is a member of the statin family. Like the other statins it is prescribed to lower cholesterol levels and thereby reduce the risk of cardiovascular events. Rosuvastatin lowers the cholesterol levels by inhibiting the key enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) in the cholesterol producing mevalonate pathway. It has been recognized that apart from their beneficial lipid lowering effects, statins also exhibit diabetogenic properties. The molecular mechanisms behind these remain unresolved. To investigate the effects of rosuvastatin on insulin secretion, we treated INS-1 832/13 cells with varying doses (20 nM to 20 μM) of rosuvastatin for 48 h. At concentrations of 2 μM and above basal insulin secretion was significantly increased. Using diazoxide we could determine that rosuvastatin did not increase basal insulin secretion by corrupting the KATP channels. Glucose-induced insulin secretion on the other hand seemed to be affected differently at different rosuvastatin concentrations. Rosuvastatin treatment (20 μM) for 24–48 h inhibited voltage-gated Ca2+ channels, which lead to reduced depolarization-induced exocytosis of insulin-containing granules. At lower concentrations of rosuvastatin (≤ 2 μM) the stimulus-secretion coupling pathway was intact downstream of the KATP channels as assessed by the patch clamp technique. However, a reduction in glucose-induced insulin secretion could be observed with rosuvastatin concentrations as low as 200 nM. The inhibitory effects of rosuvastatin on glucose-induced insulin secretion could be reversed with mevalonate, but not squalene, indicating that rosuvastatin affects insulin secretion through its effects on the mevalonate pathway, but not through the reduction of cholesterol biosynthesis. Taken together, these data suggest that rosuvastatin has the potential to increase basal insulin secretion and reduce glucose-induced insulin secretion. The latter is possibly an unavoidable

  4. Rosuvastatin Treatment Affects Both Basal and Glucose-Induced Insulin Secretion in INS-1 832/13 Cells.

    PubMed

    Salunkhe, Vishal A; Elvstam, Olof; Eliasson, Lena; Wendt, Anna

    2016-01-01

    Rosuvastatin is a member of the statin family. Like the other statins it is prescribed to lower cholesterol levels and thereby reduce the risk of cardiovascular events. Rosuvastatin lowers the cholesterol levels by inhibiting the key enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) in the cholesterol producing mevalonate pathway. It has been recognized that apart from their beneficial lipid lowering effects, statins also exhibit diabetogenic properties. The molecular mechanisms behind these remain unresolved. To investigate the effects of rosuvastatin on insulin secretion, we treated INS-1 832/13 cells with varying doses (20 nM to 20 μM) of rosuvastatin for 48 h. At concentrations of 2 μM and above basal insulin secretion was significantly increased. Using diazoxide we could determine that rosuvastatin did not increase basal insulin secretion by corrupting the KATP channels. Glucose-induced insulin secretion on the other hand seemed to be affected differently at different rosuvastatin concentrations. Rosuvastatin treatment (20 μM) for 24-48 h inhibited voltage-gated Ca(2+) channels, which lead to reduced depolarization-induced exocytosis of insulin-containing granules. At lower concentrations of rosuvastatin (≤ 2 μM) the stimulus-secretion coupling pathway was intact downstream of the KATP channels as assessed by the patch clamp technique. However, a reduction in glucose-induced insulin secretion could be observed with rosuvastatin concentrations as low as 200 nM. The inhibitory effects of rosuvastatin on glucose-induced insulin secretion could be reversed with mevalonate, but not squalene, indicating that rosuvastatin affects insulin secretion through its effects on the mevalonate pathway, but not through the reduction of cholesterol biosynthesis. Taken together, these data suggest that rosuvastatin has the potential to increase basal insulin secretion and reduce glucose-induced insulin secretion. The latter is possibly an unavoidable

  5. Optimization of extraction and purification of arctiin from Fructus arctii and its protection against glucose-induced rat aortic endothelial cell injury.

    PubMed

    Lu, Lai-chun; Zhang, Rong; Song, Ming-bao; Zhou, Shi-wen; Qian, Gui-sheng

    2014-05-01

    To develop an efficient method for extracting and purifying the active ingredient, arctiin, from Fructus arctii and to investigate the protective effect of arctiin against glucose-induced rat aortic endothelial cell (RAEC) injury was investigated. Using a L9 (34) orthogonal array and two-step column chromatography (with AB-8 macroporous resin) arctiin extraction was optimized using a reflux method with 70% ethanol. The RAECs were then treated with different concentrations of arctiin (1, 10, or 100 μg/ml). The effects of arctiin on cell viability in a high glucose medium, malondialdehyde (MDA) levels, and lactate dehydrogenase were measured using commercially available assays. After extraction, the purity of arctiin reached 95.7%. In rats, arctiin was shown to stimulate the proliferation of RAECs in a high glucose medium in a dose-dependent manner. Exposure of RAECs to high glucose resulted in a significant increase in MDA and release of lactate dehydrogenase. This was accompanied by significant increase in nitric oxide release and expression of antiendothelial nitric oxide synthase. This technique resulted in relatively pure arctiin extraction. Furthermore, the results from this study suggest that arctiin could potentially function as a protector against vascular endothelial cell injury and further investigation is warranted. PMID:24163109

  6. Evidence for inositol triphosphate as a second messenger for glucose-induced calcium signalling in budding yeast.

    PubMed

    Tisi, Renata; Belotti, Fiorella; Wera, Stefaan; Winderickx, Joris; Thevelein, Johan M; Martegani, Enzo

    2004-02-01

    The Saccharomyces cerevisiae phospholipase C Plc1 is involved in cytosolic transient glucose-induced calcium increase, which also requires the Gpr1/Gpa2 receptor/G protein complex and glucose hexokinases. Differing from mammalian cells, this increase in cytosolic calcium concentration is mainly due to an influx from the external medium. No inositol triphosphate receptor homologue has been identified in the S. cerevisiae genome; and, therefore, the transduction mechanism from Plc1 activation to calcium flux generation still has to be identified. Inositol triphosphate (IP(3)) in yeast is rapidly transformed into IP(4) and IP(5) by a dual kinase, Arg82. Then another kinase, Ipk1, phosphorylates the IP(5) into IP(6). In mutant cells that do not express either of these kinases, the glucose-induced calcium signal was not only detectable but was even wider than in the wild-type strain. IP(3) accumulation upon glucose addition was completely absent in the plc1Delta strain and was amplified both by deletion of either ARG82 or IPK1 genes and by overexpression of PLC1. These results taken together suggest that Plc1p activation by glucose, leading to cleavage of PIP(2) and generation of IP(3), seems to be sufficient for raising the calcium level in the cytosol. This is the first indication for a physiological role of IP(3) signalling in S. cerevisiae. Many aspects about the signal transduction mechanism and the final effectors require further study.

  7. High-Altitude Illnesses: Physiology, Risk Factors, Prevention, and Treatment

    PubMed Central

    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. PMID:23908794

  8. 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.

  9. Prevention

    MedlinePlus

    ... Prevention Treatment 2003 U.S. Outbreak African Rodent Importation Ban For Clinicians Clinical Recognition Specimen Collection Treatment Smallpox ... Examining Animals with Suspected Monkeypox African Rodent Importation Ban Resources Related Links Poxvirus Molluscum Contagiosum Orf Virus ( ...

  10. The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP increases in pancreatic β-cells.

    PubMed

    Tarasov, Andrei I; Semplici, Francesca; Ravier, Magalie A; Bellomo, Elisa A; Pullen, Timothy J; Gilon, Patrick; Sekler, Israel; Rizzuto, Rosario; Rutter, Guy A

    2012-01-01

    Glucose induces insulin release from pancreatic β-cells by stimulating ATP synthesis, membrane depolarisation and Ca(2+) influx. As well as activating ATP-consuming processes, cytosolic Ca(2+) increases may also potentiate mitochondrial ATP synthesis. Until recently, the ability to study the role of mitochondrial Ca(2+) transport in glucose-stimulated insulin secretion has been hindered by the absence of suitable approaches either to suppress Ca(2+) uptake into these organelles, or to examine the impact on β-cell excitability. Here, we have combined patch-clamp electrophysiology with simultaneous real-time imaging of compartmentalised changes in Ca(2+) and ATP/ADP ratio in single primary mouse β-cells, using recombinant targeted (Pericam or Perceval, respectively) as well as entrapped intracellular (Fura-Red), probes. Through shRNA-mediated silencing we show that the recently-identified mitochondrial Ca(2+) uniporter, MCU, is required for depolarisation-induced mitochondrial Ca(2+) increases, and for a sustained increase in cytosolic ATP/ADP ratio. By contrast, silencing of the mitochondrial Na(+)-Ca(2+) exchanger NCLX affected the kinetics of glucose-induced changes in, but not steady state values of, cytosolic ATP/ADP. Exposure to gluco-lipotoxic conditions delayed both mitochondrial Ca(2+) uptake and cytosolic ATP/ADP ratio increases without affecting the expression of either gene. Mitochondrial Ca(2+) accumulation, mediated by MCU and modulated by NCLX, is thus required for normal glucose sensing by pancreatic β-cells, and becomes defective in conditions mimicking the diabetic milieu.

  11. "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

  12. High dynamic range image display with halo and clipping prevention.

    PubMed

    Guarnieri, Gabriele; Marsi, Stefano; Ramponi, Giovanni

    2011-05-01

    The dynamic range of an image is defined as the ratio between the highest and the lowest luminance level. In a high dynamic range (HDR) image, this value exceeds the capabilities of conventional display devices; as a consequence, dedicated visualization techniques are required. In particular, it is possible to process an HDR image in order to reduce its dynamic range without producing a significant change in the visual sensation experienced by the observer. In this paper, we propose a dynamic range reduction algorithm that produces high-quality results with a low computational cost and a limited number of parameters. The algorithm belongs to the category of methods based upon the Retinex theory of vision and was specifically designed in order to prevent the formation of common artifacts, such as halos around the sharp edges and clipping of the highlights, that often affect methods of this kind. After a detailed analysis of the state of the art, we shall describe the method and compare the results and performance with those of two techniques recently proposed in the literature and one commercial software. PMID:21078576

  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.

  16. 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

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

    PubMed

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

    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

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

    PubMed

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

    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.

  19. Drug Prevention with High Risk Families and Young Children.

    ERIC Educational Resources Information Center

    Hahn, Ellen J.; Hall, Lynne A.; Simpson, Mary Rado

    1998-01-01

    Examines the effects of a school and home-based drug-abuse prevention program on risk factors for subsequent alcohol, tobacco, and other drug (ATOD) use among children. The parent-child intervention had no effect on parent or child risk factors, but the program was favorably received by parents and children. (Author/MKA)

  20. AIDS and us: are we failing to prevent a highly preventable disease?

    PubMed

    Quah, S R

    1992-10-01

    The Singapore Ministry of Health (MOH) developed an Advisory Committee on AIDS in 1985, to be joined by an AIDS Task Force and a National Advisory Committee on AIDS in 1987. MOH figures for 1985-91 indicate that 95 people were infected with HIV in Singapore, of whom 33 developed AIDS. These rate are far lower than those observed in other countries throughout the world. Nonetheless, individuals, the government, and international donor agencies must remain vigilant in the country to stem the spread of HIV. Medical and research communities worldwide struggle to develop effective treatments and vaccines for HIV, but other problems related to individual behavior and social policy also thwart the success of efforts against HIV and AIDS. Specifically, private choices made regarding sexual behavior and drug consumption; the lack of a sense of personal risk; and the justified fear of being socially stigmatized if diagnosed with HIV infection or AIDS impede prevention. These latter factors are closely related to social policy and may include the government's role in the screening of blood for transfusion; mandatory HIV testing; reaching sexual contacts of HIV infected persons and AIDS patients; and educational campaigns. These issues are presented with consideration of how they relate to developed countries and the US. While the lack of a sense of being at personal risk and the fear of social stigma related to AIDS may exist in Singapore, the individual right to privacy has been overlooked in Singapore. AIDS is a notifiable disease under the Infectious Disease Act and includes mandatory reporting and contact tracing as routinely applied to venereal disease. While overall HIV prevalence appears low in Singapore and social policy remains supportive of HIV preventive interventions, preventive efforts must be maintained and intensified in the years ahead. Newly pubescent and adolescent youths must be informed about infection risks and preventive strategy; the entire population

  1. Glucose induced activation of canonical Wnt signaling pathway in hepatocellular carcinoma is regulated by DKK4

    PubMed Central

    Chouhan, Surbhi; Singh, Snahlata; Athavale, Dipti; Ramteke, Pranay; Pandey, Vimal; Joseph, Jomon; Mohan, Rajashekar; Shetty, Praveen Kumar; Bhat, Manoj Kumar

    2016-01-01

    Elevated glycemic index, an important feature of diabetes is implicated in an increased risk of hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of this association are relatively less explored. Present study investigates the effect of hyperglycemia over HCC proliferation. We observed that high glucose culture condition (HG) specifically activates canonical Wnt signaling in HCC cells, which is mediated by suppression of DKK4 (a Wnt antagonist) expression and enhanced β-catenin level. Functional assays demonstrated that a normoglycemic culture condition (NG) maintains constitutive expression of DKK4, which controls HCC proliferation rate by suppressing canonical Wnt signaling pathway. HG diminishes DKK4 expression leading to loss of check at G0/G1/S phases of the cell cycle thereby enhancing HCC proliferation, in a β-catenin dependent manner. Interestingly, in NOD/SCID mice supplemented with high glucose, HepG2 xenografted tumors grew rapidly in which elevated levels of β-catenin, c-Myc and decreased levels of DKK4 were detected. Knockdown of DKK4 by shRNA promotes proliferation of HCC cells in NG, which is suppressed by treating cells exogenously with recombinant DKK4 protein. Our in vitro and in vivo results indicate an important functional role of DKK4 in glucose facilitated HCC proliferation. PMID:27272409

  2. Glucose induced activation of canonical Wnt signaling pathway in hepatocellular carcinoma is regulated by DKK4.

    PubMed

    Chouhan, Surbhi; Singh, Snahlata; Athavale, Dipti; Ramteke, Pranay; Pandey, Vimal; Joseph, Jomon; Mohan, Rajashekar; Shetty, Praveen Kumar; Bhat, Manoj Kumar

    2016-06-08

    Elevated glycemic index, an important feature of diabetes is implicated in an increased risk of hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of this association are relatively less explored. Present study investigates the effect of hyperglycemia over HCC proliferation. We observed that high glucose culture condition (HG) specifically activates canonical Wnt signaling in HCC cells, which is mediated by suppression of DKK4 (a Wnt antagonist) expression and enhanced β-catenin level. Functional assays demonstrated that a normoglycemic culture condition (NG) maintains constitutive expression of DKK4, which controls HCC proliferation rate by suppressing canonical Wnt signaling pathway. HG diminishes DKK4 expression leading to loss of check at G0/G1/S phases of the cell cycle thereby enhancing HCC proliferation, in a β-catenin dependent manner. Interestingly, in NOD/SCID mice supplemented with high glucose, HepG2 xenografted tumors grew rapidly in which elevated levels of β-catenin, c-Myc and decreased levels of DKK4 were detected. Knockdown of DKK4 by shRNA promotes proliferation of HCC cells in NG, which is suppressed by treating cells exogenously with recombinant DKK4 protein. Our in vitro and in vivo results indicate an important functional role of DKK4 in glucose facilitated HCC proliferation.

  3. Glucose-induced β-catenin acetylation enhances Wnt signaling in cancer.

    PubMed

    Chocarro-Calvo, Ana; García-Martínez, Jose Manuel; Ardila-González, Soraya; De la Vieja, Antonio; García-Jiménez, Custodia

    2013-02-01

    Nuclear accumulation of β-catenin, a widely recognized marker of poor cancer prognosis, drives cancer cell proliferation and senescence bypass and regulates incretins, critical regulators of fat and glucose metabolism. Diabetes, characterized by elevated blood glucose levels, is associated with increased cancer risk, partly because of increased insulin growth factor 1 signaling, but whether elevated glucose directly impacts cancer-associated signal-transduction pathways is unknown. Here, we show that high glucose is essential for nuclear localization of β-catenin in response to Wnt signaling. Glucose-dependent β-catenin nuclear retention requires lysine 354 and is mediated by alteration of the balance between p300 and sirtuins that trigger β-catenin acetylation. Consequently β-catenin accumulates in the nucleus and activates target promoters under combined glucose and Wnt stimulation, but not with either stimulus alone. Our results reveal a mechanism by which high glucose enhances signaling through the cancer-associated Wnt/β-catenin pathway and may explain the increased frequency of cancer associated with obesity and diabetes.

  4. High Glucose Up-regulates ADAM17 through HIF-1α in Mesangial Cells.

    PubMed

    Li, Renzhong; Uttarwar, Lalita; Gao, Bo; Charbonneau, Martine; Shi, Yixuan; Chan, John S D; Dubois, Claire M; Krepinsky, Joan C

    2015-08-28

    We previously showed that ADAM17 mediates high glucose-induced matrix production by kidney mesangial cells. ADAM17 expression is increased in diabetic kidneys, suggesting that its up-regulation may augment high glucose profibrotic responses. We thus studied the effects of high glucose on ADAM17 gene regulation. Primary rat mesangial cells were treated with high glucose (30 mm) or mannitol as osmotic control. High glucose dose-dependently increased ADAM17 promoter activity, transcript, and protein levels. This correlated with augmented ADAM17 activity after 24 h versus 1 h of high glucose. We tested involvement of transcription factors shown in other settings to regulate ADAM17 transcription. Promoter activation was not affected by NF-κB or Sp1 inhibitors, but was blocked by hypoxia-inducible factor-1α (HIF-1α) inhibition or down-regulation. This also prevented ADAM17 transcript and protein increases. HIF-1α activation by high glucose was shown by its increased nuclear translocation and activation of the HIF-responsive hypoxia-response element (HRE)-luciferase reporter construct. Assessment of ADAM17 promoter deletion constructs coupled with mutation analysis and ChIP studies identified HIF-1α binding to its consensus element at -607 as critical for the high glucose response. Finally, inhibitors of epidermal growth factor receptor (EGFR) and downstream PI3K/Akt, or ADAM17 itself, prevented high glucose-induced HIF-1α activation and ADAM17 up-regulation. Thus, high glucose induces ADAM17 transcriptional up-regulation in mesangial cells, which is associated with augmentation of its activity. This is mediated by HIF-1α and requires EGFR/ADAM17 signaling, demonstrating the potentiation by ADAM17 of its own up-regulation. ADAM17 inhibition thus provides a potential novel therapeutic strategy for the treatment of diabetic nephropathy.

  5. 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. PMID:26236960

  6. Insulin granule trafficking in beta-cells: mathematical model of glucose-induced insulin secretion.

    PubMed

    Bertuzzi, Alessandro; Salinari, Serenella; Mingrone, Geltrude

    2007-07-01

    A mathematical model that represents the dynamics of intracellular insulin granules in beta-cells is proposed. Granule translocation and exocytosis are controlled by signals assumed to be essentially related to ATP-to-ADP ratio and cytosolic Ca(2+) concentration. The model provides an interpretation of the roles of the triggering and amplifying pathways of glucose-stimulated insulin secretion. Values of most of the model parameters were inferred from available experimental data. The numerical simulations represent a variety of experimental conditions, such as the stimulation by high K(+) and by different time courses of extracellular glucose, and the predicted responses agree with published experimental data. Model capacity to represent data measured in a hyperglycemic clamp was also tested. Model parameter changes that may reflect alterations of beta-cell function present in type 2 diabetes are investigated, and the action of pharmacological agents that bind to sulfonylurea receptors is simulated.

  7. Effect of (-)-epigallocatechin-3-gallate on glucose-induced human serum albumin glycation.

    PubMed

    Li, M; Hagerman, A E

    2015-01-01

    (-)-Epigallocatechin-3-gallate (EGCg) is a naturally occurring polyphenol found in plant-based foods and beverages such as green tea. Although EGCg can eliminate carbonyl species produced by glucose autoxidation and thus can inhibit protein glycation, it is also reported to be a pro-oxidant that stimulates protein glycation in vitro. To better understand the balance between antioxidant and pro-oxidant features of EGCg, we evaluated EGCg-mediated bioactivities in a human serum albumin (HSA)/glucose model by varying three different parameters (glucose level, EGCg concentration, and time of exposure to EGCg). Measurements of glycation-induced fluorescence, protein carbonyls, and electrophoretic mobility showed that the level of HSA glycation was positively related to the glucose level over the range 10-100 mM during a 21-day incubation at 37°C and pH: 7.4. Under mild glycemic pressure (10 mM), long exposure to EGCg enhanced HSA glycation, while brief exposure to low concentrations of EGCg did not. Under high glycemic pressure (100 mM glucose), long exposure to EGCg inhibited glycation. For the first time we showed that brief exposure to EGCg reversed glycation-induced fluorescence, indicating a restorative effect. In conclusion, our research identified glucose level, EGCg concentration, and time of exposure as critical factors dictating EGCg bioactivities in HSA glycation. EGCg did not affect HSA glycation under normal physiological conditions but had a potential therapeutic effect on HSA severely damaged by glycation.

  8. 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.

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

    PubMed Central

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

    2009-01-01

    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. PMID:20026095

  10. 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…

  11. High School Senior Athletes As Peer Educators and Role Models: An Innovative Approach to Drug Prevention.

    ERIC Educational Resources Information Center

    Palmer, James; And Others

    1989-01-01

    Describes four-day drug prevention institute designed to prepare high school senior athletes to present prevention activities to junior high and elementary students and to provide early intervention for those athletes who were already experimenting with drugs themselves. Positive response from local school, civic, and community leaders and…

  12. Glucose-induced insulin secretion in uremia: role of 1 alpha,25(HO)2-vitamin D3.

    PubMed

    Allegra, V; Luisetto, G; Mengozzi, G; Martimbianco, L; Vasile, A

    1994-01-01

    To evaluate the role and mechanism of action of calcitriol on glucose-induced insulin secretion in uremia, 17 patients with severe chronic renal failure were studied. Glucose metabolism was investigated by the intravenous glucose tolerance test (IVGTT) before and after treatment for 21 days with 0.5 microgram/day of calcitriol and 500 mg/day of calcium (C+Ca) (6 cases) or 0.5 microgram/day of calcitriol alone (C) (11 cases). After these evaluations the patients on C+Ca were shifted to C and 6 patients on C were shifted to C+Ca, and IVGTT was repeated 21 days after the shift. For each test plasma glucose (G), immunoreactive insulin (IRI) and C-peptide (C-p) were measured at -30, 0, 2, 5, 15, 30, 45, 60 min, and baseline plasma values of 1 alpha,25(HO)2-vitamin D3, C-terminal parathyroid hormone (PTH-C), intact parathyroid hormone (PTH-I), calcitonin, and serum values of total and ionized calcium were dosed. Also, glucose constant decay (K-G), insulin response (IRI area), C-p production (C-p area), insulinogenic index (IGI) and insulin resistance index (RI) were calculated. A historical group of 21 healthy volunteers formed the normal controls. 1 alpha,25(HO)2-vitamin D3 plasma levels in uremic patients before treatment were significantly lower than normal range. As compared to controls, uremic patients showed significantly lower K-G, IRI area and IGI values and significantly higher RI values. After treatment with C or C+Ca, the insulin response improved significantly at 2 and 5 min and G decrement was more marked at 30, 45 and 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Reduced AMPKα2 protein expression restores glucose-induced insulin secretion in islets from calorie-restricted rats.

    PubMed

    Amaral, Maria Esméria C; Ribeiro, Rosane A; Vanzela, Emerielle C; Barbosa-Sampaio, Helena C

    2016-02-01

    In a state of caloric restriction (CR), improved insulin action was associated with the activation of AMP-activated kinase (AMPK). Here, we verified whether AMPK was involved in impaired β-cell function in islets from rats subjected to CR for 21 days. Eight-week-old male rats were distributed into a control (CTL) group that was fed an isocaloric diet ad libitum or a CR group that received 60% of the food consumed by the CTL group. From days 18-21, CTL and CR rats were treated with sense (CTLS and CRS) or antisense (CTLAS and CRAS) AMPKα2 oligonucleotides. Caloric restriction was associated with decreased body weight, perigonadal fat pads and insulinaemia, while higher glucose tolerance was observed in CRS rats. Antisense treatment normalized insulinaemia and glucose tolerance in CRAS rats and increased cholesterolaemia in CRAS and CTLAS groups. These effects were associated with reduced pAMPK/AMPK protein expression in the liver of rats treated with antisense oligonucleotides. Additionally, CRS islets showed higher pAMPK/AMPK content and lower glucose-induced insulin release. As expected, antisense oligonucleotides against AMPKα2 efficiently reduced pAMPK/AMPK protein in CRAS and CTLAS islets. The lower AMPK content in CRAS islets normalized the insulin secretion in islets exposed to 16.7 mM glucose. In addition, CTLAS islets presented higher insulin secretion at 2.8 and 16.7 mM glucose. These findings support the hypothesis that higher AMPK protein expression is involved in impaired β-cell function in islets from rats subjected to CR for 21 days. PMID:27102713

  14. Ginseng extracts restore high-glucose induced vascular dysfunctions by altering triglyceride metabolism and downregulation of atherosclerosis-related genes.

    PubMed

    Chan, Gabriel Hoi-Huen; Law, Betty Yuen-Kwan; Chu, John Man-Tak; Yue, Kevin Kin-Man; Jiang, Zhi-Hong; Lau, Chi-Wai; Huang, Yu; Chan, Shun-Wan; Ying-Kit Yue, Patrick; Wong, Ricky Ngok-Shun

    2013-01-01

    The king of herbs, Panax ginseng, has been used widely as a therapeutic agent vis-à-vis its active pharmacological and physiological effects. Based on Chinese pharmacopeia Ben Cao Gang Mu and various pieces of literature, Panax ginseng was believed to exert active vascular protective effects through its antiobesity and anti-inflammation properties. We investigated the vascular protective effects of ginseng by administrating ginseng extracts to rats after the induction of diabetes. We found that Panax ginseng can restore diabetes-induced impaired vasorelaxation and can reduce serum triglyceride but not cholesterol level in the diabetic rats. The ginseng extracts also suppressed the expression of atherosclerosis-related genes and altered the expression of lipid-related genes. The results provide evidence that Panax ginseng improves vascular dysfunction induced by diabetes and the protective effects may possibly be due to the downregulation of atherosclerosis-related genes and altered lipid metabolism, which help to restore normal endothelium functions.

  15. Phlorotannins from Brown Algae: inhibition of advanced glycation end products formation in high glucose induced Caenorhabditis elegans.

    PubMed

    Shakambari, Ganeshan; Ashokkumar, Balasubramaniem; Varalakshmi, Perumal

    2015-06-01

    Advanced Glycation End products (AGE) generated in a non enzymatic protein glycation process are frequently associated with diabetes, aging and other chronic diseases. Here, we explored the protective effect of phlorotannins from brown algae Padina pavonica, Sargassum polycystum and Turbinaria ornata against AGEs formation. Phlorotannins were extracted from brown algae with methanol and its purity was analyzed by TLC and RP-HPLC-DAD. Twenty five grams of P. pavonica, S. polycystum, T. ornata yielded 27.6 ± 0.8 μg/ml, 37.7 μg/ml and 37.1 ± 0.74 μg/ml of phloroglucinol equivalent of phlorotannins, respectively. Antioxidant potentials were examined through DPPH assay and their IC50 values were P. pavonica (30.12 ± 0.99 μg), S. polycystum (40.9 ± 1.2 μg) and T. ornata (22.9 ± 1.3 μg), which was comparatively lesser than the control ascorbic acid (46 ± 0.2 μg). Further, anti-AGE activity was examined in vitro by BSA-glucose assay with the extracted phlorotannins of brown algae (P. pavonica, 15.16 ± 0.26 μg/ml; S. polycystum, 35.245 ± 2.3 μg/ml; T. ornata, 22.7 ± 0.3 μg/ml), which revealed the required concentration to inhibit 50% of albumin glycation (IC50) were lower for extracts than controls (phloroglucinol, 222.33 ± 4.9 μg/ml; thiamine, 263 μg/ml). Furthermore, brown algal extracts containing phlorotannins (100 μl) exhibited protective effects against AGE formation in vivo in C. elegans with induced hyperglycemia. PMID:26155677

  16. Surgery to prevent stroke. High hopes and deep disappointment.

    PubMed

    Jennett, B

    1989-01-01

    Carotid endarterectomy and EC/IC bypass grafting have been widely adopted for patients considered at risk from stroke, without good evidence of efficacy. Unjustified claims for surgery usually derive from overestimating the dangers of the disease without surgery, while perioperative risks are underestimated. Inadequate follow-up and choosing irrelevant outcome measures often add to the confusion. All these factors apply to surgery for stroke. A trial of EC/IC bypass in 1,377 patients from three continents took 8 years to complete and showed no benefit in patients randomized to surgery. Reluctance to accept this result led to detailed critiques of this trial in several journals, largely based on the discovery that many patients had been operated on in some centers without having been randomized. In reply, the investigators showed that these cases did not affect the "resounding negativity of the results." Lack of good data about the prognosis of patients with TIAs or minor strokes was the fundamental reason for so much misplaced surgical effort. This applies equally to carotid endarterectomy, for which large trials are currently being completed. Had there been a reliable data base of patients at risk of stroke, prospectively collected and followed, the efficacy of these two operations could have been determined much sooner, and inappropriate diffusion might have been prevented.

  17. 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…

  18. A Birth Defects Prevention Curriculum for Inner-City Junior High School Students.

    ERIC Educational Resources Information Center

    Cohen, Ellen J.; Cohen, Carl I.

    1981-01-01

    Educators have begun to recognize that the public school system is an ideal setting in which to introduce the topic of birth defects prevention. A highly structured two week curriculum was developed using March of Dimes materials to teach inner-city school children about birth defects prevention. (JN)

  19. An African-Centered Model of Prevention for African-American Youth at High Risk.

    ERIC Educational Resources Information Center

    Goddard, Lawford L., Ed.

    The chapters of this report provide a starting point for the development of authentic prevention strategies for use in the African-American community, specifically for high risk youth. It is neither a "how to" manual nor a mandate for specific program details, but it does highlight the key components of alcohol and other drug abuse prevention. The…

  20. 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,…

  1. 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

  2. Oriented perforation to prevent casing collapse for highly inclined wells

    SciTech Connect

    Morita, Nobuo; McLeod, H.

    1995-09-01

    This paper shows that the oriented-perforation technique is an effective method to control casing collapse problems for highly inclined wells. Three wells were perforated with 180{degree} phasing in the maximum in-situ stress direction. These three wells did not experience casing collapse, while surrounding wells with the standard perforation technique did. Two of the three wells with oriented perforations experienced significantly reduced sand problems. Numerical analysis was conducted to compare how effective orient perforations were in minimizing casing failure when a sheared zone was created around a well during drilling and production.

  3. Mitigation of starch and glucose-induced postprandial glycemic excursion in rats by antioxidant-rich green-leafy vegetables’ juice

    PubMed Central

    Tiwari, Ashok Kumar; Jyothi, Atmakuri Lakshmana; Tejeswini, Vasantharao Brahma; Madhusudana, Kuncha; Kumar, Domati Anand; Zehra, Amtul; Agawane, Sachin Bharat

    2013-01-01

    Objective: Consumption of green-leafy vegetables is being advocated beneficial for type 2 diabetes mellitus individuals possibly because they are cost effective source of potent biological antioxidants. This research analyzed various phytochemicals, free radicals scavenging antioxidant potentials and starch digesting enzymes inhibitory activities in fresh juice of nine green-leafy vegetables. Furthermore, this study also investigated influence of these vegetables juice on starch and glucose induced postprandial glycemic load. Materials and Methods: Phytochemical constituents, in vitro free radicals scavenging antioxidant and enzymes inhibitory activities were evaluated applying various reported methods. Post-prandial glycemic excursion was induced in rats pretreated with vegetables juice by oral administration of starch and glucose. Results: All the leafy vegetables juice displayed potent free radicals scavenging activities. Juice of amaranthus, rumex, palak and raphanus displayed potential anti-oxidative property by reducing H2O2 induced hemolysis in rats red blood cells RBCs. Ajwain and rumex juice showed pancreatic α-amylase inhibitory activity. Alternanthera, ajwain, methi, amaranthus and sowa leaves juice displayed intestinal α-glucosidase inhibitory activity. Juice of raphanus, ajwain and sowa significantly mitigated starch-induced postprandial glycemic load. Amaranthus leaves juice potently mitigated glucose-induced postprandial glycemic load and also reduced hemoglobin glycation induced by glucose in vitro. Conclusions: This investigation finds that juice of leafy vegetables is potent source of biological antioxidants. In addition, juice of raphanus, ajwain and sowa leaves possess capacity to mitigate starch induced postprandial glycemic burden and amaranthus leaves’ juice can reduce glucose induced postprandial glycemic excursion. PMID:24143048

  4. Glucose-induced hyperaccumulation of cyclic AMP and defective glucose repression in yeast strains with reduced activity of cyclic AMP-dependent protein kinase.

    PubMed

    Mbonyi, K; van Aelst, L; Argüelles, J C; Jans, A W; Thevelein, J M

    1990-09-01

    Addition of glucose or related fermentable sugars to derepressed cells of the yeast Saccharomyces cerevisiae triggers a RAS-mediated cyclic AMP (cAMP) signal that induces a protein phosphorylation cascade. In yeast mutants (tpk1w1, tpk2w1, and tpk3w1) containing reduced activity of cAMP-dependent protein kinase, fermentable sugars, as opposed to nonfermentable carbon sources, induced a permanent hyperaccumulation of cAMP. This finding confirms previous conclusions that fermentable sugars are specific stimulators of cAMP synthesis in yeast cells. Despite the huge cAMP levels present in these mutants, deletion of the gene (BCY1) coding for the regulatory subunit of cAMP-dependent protein kinase severely reduced hyperaccumulation of cAMP. Glucose-induced hyperaccumulation of cAMP was also observed in exponential-phase glucose-grown cells of the tpklw1 and tpk2w1 strains but not the tpk3w1 strain even though addition of glucose to glucose-repressed wild-type cells did not induce a cAMP signal. Investigation of mitochondrial respiration by in vivo 31P nuclear magnetic resonance spectroscopy showed the tpk1w1 and tpk2w1 strains, to be defective in glucose repression. These results are consistent with the idea that the signal transmission pathway from glucose to adenyl cyclase contains a glucose-repressible protein. They also show that a certain level of cAMP-dependent protein phosphorylation is required for glucose repression. Investigation of the glucose-induced cAMP signal and glucose-induced activation of trehalase in derepressed cells of strains containing only one of the wild-type TPK genes indicates that the transient nature of the cAMP signal is due to feedback inhibition by cAMP-dependent protein kinase.

  5. Violence Prevention after Columbine: A Survey of High School Mental Health Professionals

    ERIC Educational Resources Information Center

    Crepeau-Hobson, M. Franci; Filaccio, Marylynne; Gottfried, Linda

    2005-01-01

    The authors examined changes in mental health services and violence prevention strategies in public high schools since the shootings at Columbine High School. Surveys were mailed to school mental health professionals at public high schools in Colorado. Respondents included school counselors, school psychologists, school social workers, principals,…

  6. 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

    2015-01-01

    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.

  7. 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

  8. 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…

  9. Dynamics of glucose-induced membrane recruitment of protein kinase C beta II in living pancreatic islet beta-cells.

    PubMed

    Pinton, Paolo; Tsuboi, Takashi; Ainscow, Edward K; Pozzan, Tullio; Rizzuto, Rosario; Rutter, Guy A

    2002-10-01

    The mechanisms by which glucose may affect protein kinase C (PKC) activity in the pancreatic islet beta-cell are presently unclear. By developing adenovirally expressed chimeras encoding fusion proteins between green fluorescent protein and conventional (betaII), novel (delta), or atypical (zeta) PKCs, we show that glucose selectively alters the subcellular localization of these enzymes dynamically in primary islet and MIN6 beta-cells. Examined by laser scanning confocal or total internal reflection fluorescence microscopy, elevated glucose concentrations induced oscillatory translocations of PKCbetaII to spatially confined regions of the plasma membrane. Suggesting that increases in free cytosolic Ca(2+) concentrations ([Ca(2+)](c)) were primarily responsible, prevention of [Ca(2+)](c) increases with EGTA or diazoxide completely eliminated membrane recruitment, whereas elevation of cytosolic [Ca(2+)](c) with KCl or tolbutamide was highly effective in redistributing PKCbetaII both to the plasma membrane and to the surface of dense core secretory vesicles. By contrast, the distribution of PKCdelta.EGFP, which binds diacylglycerol but not Ca(2+), was unaffected by glucose. Measurement of [Ca(2+)](c) immediately beneath the plasma membrane with a ratiometric "pericam," fused to synaptic vesicle-associated protein-25, revealed that depolarization induced significantly larger increases in [Ca(2+)](c) in this domain. These data demonstrate that nutrient stimulation of beta-cells causes spatially and temporally complex changes in the subcellular localization of PKCbetaII, possibly resulting from the generation of Ca(2+) microdomains. Localized changes in PKCbetaII activity may thus have a role in the spatial control of insulin exocytosis.

  10. 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. |

  11. Project ASPIRE: an Interactive, Multimedia Smoking Prevention and Cessation curriculum for culturally diverse high school students.

    PubMed

    Prokhorov, Alexander V; Kelder, Steven H; Shegog, Ross; Conroy, Jennifer L; Murray, Nancy; Peters, Ronald; Cinciripini, Paul M; De Moor, Carl; Hudmon, Karen S; Ford, Kentya H

    2010-05-01

    A Smoking Prevention Interactive Experience (ASPIRE) is an innovative, computer-based smoking prevention and cessation intervention delivered to a culturally diverse population of high school students. Founded in the Transtheoretical Model of Change, five main and two "booster" sessions comprise the interactive intervention. Here we describe the intervention and the baseline characteristics from our study sample of 1,574 10th graders from 16 high schools in Houston, Texas. Environmental and behavioral smoking risk factors were assessed, and the two intervention groups were comparable with respect to most measured variables. The intervention program holds considerable promise in its ability to reduce smoking among teens.

  12. 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…

  13. 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…

  14. 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. |

  15. 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…

  16. High School Success: An Effective Intervention for Achievement and Dropout Prevention

    ERIC Educational Resources Information Center

    Lowder, Christopher Michael

    2012-01-01

    The purpose of this mixed-design study was to use quantitative and qualitative research to explore the effects of High School Success (a course for at-risk ninth graders) and its effectiveness on student achievement, attendance, and dropout prevention. The research questions address whether there is a significant difference between at-risk ninth…

  17. 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…

  18. 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…

  19. 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…

  20. High School Smoking Prevention: The Relative Efficacy of Varied Treatments and Instructors.

    ERIC Educational Resources Information Center

    Perry, Cheryl L.; And Others

    1983-01-01

    Compared the effectiveness of a social consequence curriculum to health effects curriculums in a high school smoking prevention program. Results showed none of the programs was significantly more successful in reducing smoking onset or encouraging cessation. Teacher-taught programs were as effective as those taught by college students. (JAC)

  1. A High School Depression and Suicide Prevention Program: A Collaboration between Health Education and Psychological Services.

    ERIC Educational Resources Information Center

    Moilanen, Donna L.; Bradbury, Susan

    2002-01-01

    Examined a collaboration between health education and psychological services in generating a high school depression and suicide prevention program. The five-component program raised awareness of teen depression and suicide, increased communication about these issues within the school and community, and provided information about available…

  2. 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…

  3. 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.…

  4. 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…

  5. 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

  6. 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. PMID:27357504

  7. Comparative study of preventive protocols in children at high cariogenic risk.

    PubMed

    Martínez, María C; Tolcachir, Betina; Lescano de Ferrer, Alfonsina; Bojanich, María A; Barembaum, Silvina R; Calamari, Silvia E; Azcurra, Ana I

    2012-01-01

    The aim of this study was to compare the efficacy of two preventive protocols -fluoride gel (F) alone or combined with chlorhexidine varnishes (CHX) - on sialochemical, clinical and microbiological parameters in a group of children at high cariogenic risk Two therapeutic-preventive protocols were applied in 73 children at high cariogenic risk (average age 6.2 +/- 1.4 years old) and clinical parameters (simplified oral hygiene index: OHI-S; decayed, missing and filled teeth: dmf index; sugar intake and exposure to fluoride), as well as sialochemical parameters (salivary pH and flow, buffer capacity) and microbiological parameters (CFU/mg of dental biofilm of Streptococcus mutans group) were recorded and correlated before and after the protocols. Association was found between parameters that cause deficient control of dental biofilm: high values of OHIS index, CFU/mg dental biofilm, sugar intake and the d component of dmft index, and lower values of salivary flow rate and buffer capacity. After the protocols, a significant decrease was found in OHI-S and CFU/mg dental biofilm. No significant difference was found with children's gender and age. The association observed between OHI-S and cariogenic bacteria emphasizes the importance of prevention, especially regarding the oral health of the most vulnerable children. The early inclusion of F associated with CHX in the initial step of preventive and therapeutic protocols would provide benefits regarding oral microbe control while children acquire new habits of oral hygiene.

  8. Activation of corticotropin-releasing factor receptors in the rostral ventrolateral medulla is required for glucose-induced sympathoexcitation.

    PubMed

    Bardgett, Megan E; Sharpe, Amanda L; Toney, Glenn M

    2014-11-15

    Energy expenditure is determined by metabolic rate and diet-induced thermogenesis. Normally, energy expenditure increases due to neural mechanisms that sense plasma levels of ingested nutrients/hormones and reflexively increase sympathetic nerve activity (SNA). Here, we investigated neural mechanisms of glucose-driven sympathetic activation by determining contributions of neuronal activity in the hypothalamic paraventricular nucleus (PVN) and activation of corticotropin-releasing factor (CRF) receptors in the rostral ventrolateral medulla (RVLM). Glucose was infused intravenously (150 mg/kg, 10 min) in male rats to raise plasma glucose concentration to a physiological postprandial level. In conscious rats, glucose infusion activated CRF-containing PVN neurons and TH-containing RVLM neurons, as indexed by c-Fos immunofluorescence. In α-chloralose/urethane-anesthetized rats, glucose infusion increased lumbar and splanchnic SNA, which was nearly prevented by prior RVLM injection of the CRF receptor antagonist astressin (10 pmol/50 nl). This cannot be attributed to a nonspecific effect, as sciatic afferent stimulation increased SNA and ABP equivalently in astressin- and aCSF-injected rats. Glucose-stimulated sympathoexcitation was largely reversed during inhibition of PVN neuronal activity with the GABA-A receptor agonist muscimol (100 pmol/50 nl). The effects of astressin to prevent glucose-stimulated sympathetic activation appear to be specific to interruption of PVN drive to RVLM because RVLM injection of astressin prior to glucose infusion effectively prevented SNA from rising and prevented any fall of SNA in response to acute PVN inhibition with muscimol. These findings suggest that activation of SNA, and thus energy expenditure, by glucose is initiated by activation of CRF receptors in RVLM by descending inputs from PVN. PMID:25269482

  9. The efficacy of a high school rape prevention program in Israel.

    PubMed

    Moor, Avigail

    2011-01-01

    Sexual violence against women and girls in Israel is rather prevalent. To address this problem, the Association of Rape Crisis Centers in Israel (ARCCI) provides rape prevention programs for middle to high school teens. These programs have been in place for several decades, but their effectiveness has not been evaluated empirically to date. This study seeks to fill this gap by performing an evaluation of one such preventive program. Three hundred and ninety-four 11th graders completed a preintervention and postintervention questionnaire, assessing their rape-related attitudes and behaviors. Results indicate a significant improvement following the workshop in the understanding of what distinguishes rape from mutually consensual relations, along with a substantial shift in many rape-supportive attitudes. At the same time, some victim blaming still remained. Likewise, self-reported behavioral changes were minimal, possibly because of a ceiling effect. Implications for future rape prevention programs in Israel are discussed. PMID:21846018

  10. The efficacy of a high school rape prevention program in Israel.

    PubMed

    Moor, Avigail

    2011-01-01

    Sexual violence against women and girls in Israel is rather prevalent. To address this problem, the Association of Rape Crisis Centers in Israel (ARCCI) provides rape prevention programs for middle to high school teens. These programs have been in place for several decades, but their effectiveness has not been evaluated empirically to date. This study seeks to fill this gap by performing an evaluation of one such preventive program. Three hundred and ninety-four 11th graders completed a preintervention and postintervention questionnaire, assessing their rape-related attitudes and behaviors. Results indicate a significant improvement following the workshop in the understanding of what distinguishes rape from mutually consensual relations, along with a substantial shift in many rape-supportive attitudes. At the same time, some victim blaming still remained. Likewise, self-reported behavioral changes were minimal, possibly because of a ceiling effect. Implications for future rape prevention programs in Israel are discussed.

  11. 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.

  12. “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

  13. Preventing dyslipidemia by Chlorella pyrenoidosa in rats and hamsters after chronic high fat diet treatment.

    PubMed

    Cherng, Jong-Yuh; Shih, Mei-Fen

    2005-05-13

    The effects of Chlorella pyrenoidosa on serum lipid profiles, after concomitant long-term treatment of high-fat diet (HFD) in rats and hamsters was studied. Wistar rats and Syrian hamsters were fed with or without various concentrations of Chlorella pyrenoidosa contained high-fat diet (CHFD) for 2, 4 and 8 weeks prior to assay of serum lipids. Fasting triglycerides, total cholesterol, and LDL cholesterol as well as HDL cholesterol levels in high-fat diet treated rats and hamster were determined. Results showed that triglycerides, total cholesterol and LDL cholesterol levels in HFD treated rats and hamsters were increased from the normal rodent diet (NRD) treated controls after 2, 4, and 8-week treatments. However, the presence of Chlorella pyrenoidosa in high-fat diets significantly decreased the levels of triglycerides, total cholesterol and LDL cholesterol with comparison to HFD group in rats and hamsters. The total cholesterol/HDL ratios, an indication of occurrence of coronary heart disease, were decreased in all CHFD treated grouped rats and hamsters which suggests administration of Chlorella pyrenoidosa could lower the occurring risk of heart diseases. In conclusion, Chlorella pyrenoidosa has the ability to prevent dyslipidemia in chronic high-fat fed animals and could be potential in use to prevent intestinal absorption of redundant lipid from our daily intake and subsequently to prevent hyperlipidemia as well as atherosclerosis. PMID:15850594

  14. 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…

  15. 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…

  16. An intravenous medication safety system: preventing high-risk medication errors at the point of care.

    PubMed

    Hatcher, Irene; Sullivan, Mark; Hutchinson, James; Thurman, Susan; Gaffney, F Andrew

    2004-10-01

    Improving medication safety at the point of care--particularly for high-risk drugs--is a major concern of nursing administrators. The medication errors most likely to cause harm are administration errors related to infusion of high-risk medications. An intravenous medication safety system is designed to prevent high-risk infusion medication errors and to capture continuous quality improvement data for best practice improvement. Initial testing with 50 systems in 2 units at Vanderbilt University Medical Center revealed that, even in the presence of a fully mature computerized prescriber order-entry system, the new safety system averted 99 potential infusion errors in 8 months.

  17. 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. PMID:26773867

  18. 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.

  19. 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

  20. Edible Bird's Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats

    PubMed Central

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ooi, Der-Jiun; Sarega, Nadarajan; Azmi, Nur Hanisah; Ismail, Norsharina; Chan, Kim Wei; Hou, Zhiping; Yusuf, Norhayati Binti

    2015-01-01

    Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance. PMID:26273674

  1. Edible Bird's Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats.

    PubMed

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ooi, Der-Jiun; Sarega, Nadarajan; Azmi, Nur Hanisah; Ismail, Norsharina; Chan, Kim Wei; Hou, Zhiping; Yusuf, Norhayati Binti

    2015-01-01

    Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance. PMID:26273674

  2. 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.

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

    PubMed

    Collier, Crystal; Onwuegbuzie, Anthony J; LaChapelle, Alicia; Davison, Jessica

    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

  4. 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

  5. Cyclocarya paliurus prevents high fat diet induced hyperlipidemia and obesity in Sprague-Dawley rats.

    PubMed

    Yao, Xiaoming; Lin, Zi; Jiang, Cuihua; Gao, Meng; Wang, Qingqing; Yao, Nan; Ma, Yonglan; Li, Yue; Fang, Shengzuo; Shang, Xulan; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2015-08-01

    Cyclocarya paliurus (CP; qing qian liu), which is used as an herbal tea in China, has been confirmed to have therapeutic effects on hyperlipidemia and obesity, and therefore it is widely consumed to prevent metabolic diseases such as hyperlipidemia and diabetes. In this study, we investigated the preventive effects of CP on obesity and hyperlipidemia, as well as the underlying mechanisms involved in intestinal secretion of apolipoprotein (apo) B48. Sprague-Dawley rats were fed a high-fat diet (HFD) and with or without various concentrations of an ethanol extract of CP (CPE; 2, 4, or 8 g·(kg body mass)(-1)) administered by gavage for 8 weeks. From the results we see that CPE dose-dependently blocked increases in body mass, and decreased food utilization as well as visceral fat mass. Decreased serum levels of total cholesterol, triglycerides, and low density lipoprotein cholesterol, and elevated levels of high density lipoprotein cholesterol, as well as lowered levels of total cholesterol and triglycerides in the liver were also noticed in CPE-treated rats. Magnetic resonance images indicated that the abnormal fat storage induced by the HFD was obviously suppressed by CPE. In addition, ELISA analysis showed reduced fasting serum apoB48 in the CPE treatment groups. Based on the above results, CPE shows a promising preventive effect on obesity and hyperlipidemia, partially through suppressing intestinal apoB48 overproduction.

  6. Cyclocarya paliurus prevents high fat diet induced hyperlipidemia and obesity in Sprague-Dawley rats.

    PubMed

    Yao, Xiaoming; Lin, Zi; Jiang, Cuihua; Gao, Meng; Wang, Qingqing; Yao, Nan; Ma, Yonglan; Li, Yue; Fang, Shengzuo; Shang, Xulan; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2015-08-01

    Cyclocarya paliurus (CP; qing qian liu), which is used as an herbal tea in China, has been confirmed to have therapeutic effects on hyperlipidemia and obesity, and therefore it is widely consumed to prevent metabolic diseases such as hyperlipidemia and diabetes. In this study, we investigated the preventive effects of CP on obesity and hyperlipidemia, as well as the underlying mechanisms involved in intestinal secretion of apolipoprotein (apo) B48. Sprague-Dawley rats were fed a high-fat diet (HFD) and with or without various concentrations of an ethanol extract of CP (CPE; 2, 4, or 8 g·(kg body mass)(-1)) administered by gavage for 8 weeks. From the results we see that CPE dose-dependently blocked increases in body mass, and decreased food utilization as well as visceral fat mass. Decreased serum levels of total cholesterol, triglycerides, and low density lipoprotein cholesterol, and elevated levels of high density lipoprotein cholesterol, as well as lowered levels of total cholesterol and triglycerides in the liver were also noticed in CPE-treated rats. Magnetic resonance images indicated that the abnormal fat storage induced by the HFD was obviously suppressed by CPE. In addition, ELISA analysis showed reduced fasting serum apoB48 in the CPE treatment groups. Based on the above results, CPE shows a promising preventive effect on obesity and hyperlipidemia, partially through suppressing intestinal apoB48 overproduction. PMID:26203820

  7. 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.

  8. 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

  9. Involvement of the CDC25 gene product in the signal transmission pathway of the glucose-induced RAS-mediated cAMP signal in the yeast Saccharomyces cerevisiae.

    PubMed

    van Aelst, L; Jans, A W; Thevelein, J M

    1991-02-01

    Addition of glucose or related fermentable sugars to derepressed cells of the yeast Saccharomyces cerevisiae triggers a RAS-protein-mediated cAMP signal, which induces a protein phosphorylation cascade. Yeast strains without a functional CDC25 gene were deficient in basal cAMP synthesis and in the glucose-induced cAMP signal. Addition of dinitrophenol, which in wild-type strains strongly stimulates in vivo cAMP synthesis by lowering intracellular pH, did not enhance the cAMP level. cdc25 disruption mutants, in which the basal cAMP level was restored by the RAS2val19 oncogene or by disruption of the gene (PDE2) coding for the high-affinity phosphodiesterase, were still deficient in the glucose- and acidification-induced cAMP responses. These results indicate that the CDC25 gene product is required not only for basal cAMP synthesis in yeast but also for specific activation of cAMP synthesis by the signal transmission pathway leading from glucose to adenyl cyclase. They also show that intracellular acidification stimulates the pathway at or upstream of the CDC25 protein. When shifted to the restrictive temperature, cells with the temperature sensitive cdc25-5 mutation lost their cAMP content within a few minutes. After prolonged incubation at the restrictive temperature, cells with this mutation, and also those with the temperature sensitive cdc25-1 mutation, arrested at the 'start' point (in G1) of the cell cycle, and subsequently accumulated in the resting state G0. In contrast with cdc25-5 cells, however, the cAMP level did not decrease and normal glucose- and acidification-induced cAMP responses were observed when cdc25-1 cells were shifted to the restrictive temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. 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.

  11. MPGD for breast cancer prevention: a high resolution and low dose radiation medical imaging

    NASA Astrophysics Data System (ADS)

    Gutierrez, R. M.; Cerquera, E. A.; Mañana, G.

    2012-07-01

    Early detection of small calcifications in mammograms is considered the best preventive tool of breast cancer. However, existing digital mammography with relatively low radiation skin exposure has limited accessibility and insufficient spatial resolution for small calcification detection. Micro Pattern Gaseous Detectors (MPGD) and associated technologies, increasingly provide new information useful to generate images of microscopic structures and make more accessible cutting edge technology for medical imaging and many other applications. In this work we foresee and develop an application for the new information provided by a MPGD camera in the form of highly controlled images with high dynamical resolution. We present a new Super Detail Image (S-DI) that efficiently profits of this new information provided by the MPGD camera to obtain very high spatial resolution images. Therefore, the method presented in this work shows that the MPGD camera with SD-I, can produce mammograms with the necessary spatial resolution to detect microcalcifications. It would substantially increase efficiency and accessibility of screening mammography to highly improve breast cancer prevention.

  12. 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. PMID:8060907

  13. 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.

  14. 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…

  15. Repression of the glucose-inducible outer-membrane protein OprB during utilization of aromatic compounds and organic acids in Pseudomonas putida CSV86.

    PubMed

    Shrivastava, Rahul; Basu, Bhakti; Godbole, Ashwini; Mathew, M K; Apte, Shree K; Phale, Prashant S

    2011-05-01

    Pseudomonas putida CSV86 shows preferential utilization of aromatic compounds over glucose. Protein analysis and [¹⁴C]glucose-binding studies of the outer membrane fraction of cells grown on different carbon sources revealed a 40 kDa protein that was transcriptionally induced by glucose and repressed by aromatics and succinate. Based on 2D gel electrophoresis and liquid chromatography-tandem mass spectrometry analysis, the 40 kDa protein closely resembled the porin B of P. putida KT2440 and carbohydrate-selective porin OprB of various Pseudomonas strains. The purified native protein (i) was estimated to be a homotrimer of 125 kDa with a subunit molecular mass of 40 kDa, (ii) displayed heat modifiability of electrophoretic mobility, (iii) showed channel conductance of 166 pS in 1 M KCl, (iv) permeated various sugars (mono-, di- and tri-saccharides), organic acids, amino acids and aromatic compounds, and (v) harboured a glucose-specific and saturable binding site with a dissociation constant of 1.3 µM. These results identify the glucose-inducible outer-membrane protein of P. putida CSV86 as a carbohydrate-selective protein OprB. Besides modulation of intracellular glucose-metabolizing enzymes and specific glucose-binding periplasmic space protein, the repression of OprB by aromatics and organic acids, even in the presence of glucose, also contributes significantly to the strain's ability to utilize aromatics and organic acids over glucose.

  16. Redox Signal-mediated Enhancement of the Temperature Sensitivity of Transient Receptor Potential Melastatin 2 (TRPM2) Elevates Glucose-induced Insulin Secretion from Pancreatic Islets.

    PubMed

    Kashio, Makiko; Tominaga, Makoto

    2015-05-01

    Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive Ca(2+)-permeable cation channel expressed by pancreatic β cells where channel function is constantly affected by body temperature. We focused on the physiological functions of redox signal-mediated TRPM2 activity at body temperature. H2O2, an important molecule in redox signaling, reduced the temperature threshold for TRPM2 activation in pancreatic β cells of WT mice but not in TRPM2KO cells. TRPM2-mediated [Ca(2+)]i increases were likely caused by Ca(2+) influx through the plasma membrane because the responses were abolished in the absence of extracellular Ca(2+). In addition, TRPM2 activation downstream from the redox signal plus glucose stimulation enhanced glucose-induced insulin secretion. H2O2 application at 37 °C induced [Ca(2+)]i increases not only in WT but also in TRPM2KO β cells. This was likely due to the effect of H2O2 on KATP channel activity. However, the N-acetylcysteine-sensitive fraction of insulin secretion by WT islets was increased by temperature elevation, and this temperature-dependent enhancement was diminished significantly in TRPM2KO islets. These data suggest that endogenous redox signals in pancreatic β cells elevate insulin secretion via TRPM2 sensitization and activity at body temperature. The results in this study could provide new therapeutic approaches for the regulation of diabetic conditions by focusing on the physiological function of TRPM2 and redox signals.

  17. 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.

  18. An approach to primary preventive treatment for children with high blood pressure in a total community.

    PubMed

    Frank, G C; Farris, R P; Ditmarsen, P; Voors, A W; Berenson, G S

    1982-01-01

    A model designed as primary hypertension prevention for children ranking high in blood pressure, selected from a total population, was applied to a semirural, biracial community. A Dietary/Exercise Alteration Program Trial (ADAPT), in combination with low-dose medication, was tested on 48 children aged 8-18 years who were randomly selected from 100 children consistently in the upper blood pressure decile. The interactive model a) focuses on a major public health problem that is measurable and modifiable, b) outlines a preventive approach to involve children and parents in establishing healthy life styles, and c) converts community limitations into resources. The comprehensive program was developed to support eating and exercise modifications accepted for hypertension treatment without placing children in a sick role. Sodium reduction, weight control, and regular exercise are the life-style changes promoted. Indicators for evaluating development and implementation of ADAPT are presented. The commitment to written pledges, ie, making simple behavioral changes, had a significant inverse association with post-treatment sodium and energy intakes in regression models that included the child's curriculum and physical activity class attendance. ADAPT represents an initial approach for developing primary preventive treatment of early essential hypertension in a pediatric population.

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

    PubMed

    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

  20. 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

  1. Bone Loss from High Repetitive High Force Loading is Prevented by Ibuprofen Treatment

    PubMed Central

    Jain, Nisha X.; Barr-Gillespie, Ann E.; Clark, Brian D.; Kietrys, David M.; Wade, Christine K.; Litvin, Judith; Popoff, Steven N.; Barbe, Mary F.

    2014-01-01

    We examined roles of loading and inflammation on forearm bones in a rat model of upper extremity overuse. Trabecular structure in distal radius and ulna was examined in three groups of young adult rats: 1) 5% food-restricted that underwent an initial training period of 10 min/day for 5 weeks to learn the repetitive task (TRHF); 2) rats that underwent the same training before performing a high repetition high force task, 2 hours/day for 12 weeks (HRHF); and 3) food-restricted only (FRC). Subsets were treated with oral ibuprofen (IBU). TRHF rats had increased trabecular bone volume and numbers, osteoblasts, and serum osteocalcin, indicative of bone adaptation. HRHF rats had constant muscle pulling forces, showed limited signs of bone adaptation, but many signs of bone resorption, including decreased trabecular bone volume and bone mineral density, increased osteoclasts and bone inflammatory cytokines, and reduced median nerve conduction velocity (15%). HRHF+IBU rats showed no trabecular resorptive changes, no increased osteoclasts or bone inflammatory cytokines, no nerve inflammation, preserved nerve conduction, and increased muscle voluntary pulling forces. Ibuprofen treatment preserved trabecular bone quality by reducing osteoclasts and bone inflammatory cytokines, and improving muscle pulling forces on bones as a result of reduced nerve inflammation. PMID:24583543

  2. Physiology in Medicine: A physiologic approach to prevention and treatment of acute high-altitude illnesses.

    PubMed

    Luks, Andrew M

    2015-03-01

    With the growing interest in adventure travel and the increasing ease and affordability of air, rail, and road-based transportation, increasing numbers of individuals are traveling to high altitude. The decline in barometric pressure and ambient oxygen tensions in this environment trigger a series of physiologic responses across organ systems and over a varying time frame that help the individual acclimatize to the low oxygen conditions but occasionally lead to maladaptive responses and one or several forms of acute altitude illness. The goal of this Physiology in Medicine article is to provide information that providers can use when counseling patients who present to primary care or travel medicine clinics seeking advice about how to prevent these problems. After discussing the primary physiologic responses to acute hypoxia from the organ to the molecular level in normal individuals, the review describes the main forms of acute altitude illness--acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema--and the basic approaches to their prevention and treatment of these problems, with an emphasis throughout on the physiologic basis for the development of these illnesses and their management.

  3. Physiology in Medicine: A physiologic approach to prevention and treatment of acute high-altitude illnesses.

    PubMed

    Luks, Andrew M

    2015-03-01

    With the growing interest in adventure travel and the increasing ease and affordability of air, rail, and road-based transportation, increasing numbers of individuals are traveling to high altitude. The decline in barometric pressure and ambient oxygen tensions in this environment trigger a series of physiologic responses across organ systems and over a varying time frame that help the individual acclimatize to the low oxygen conditions but occasionally lead to maladaptive responses and one or several forms of acute altitude illness. The goal of this Physiology in Medicine article is to provide information that providers can use when counseling patients who present to primary care or travel medicine clinics seeking advice about how to prevent these problems. After discussing the primary physiologic responses to acute hypoxia from the organ to the molecular level in normal individuals, the review describes the main forms of acute altitude illness--acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema--and the basic approaches to their prevention and treatment of these problems, with an emphasis throughout on the physiologic basis for the development of these illnesses and their management. PMID:25539941

  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. High energy diets prevent the enhancing effects of emotional arousal on memory.

    PubMed

    Ross, Amy P; Darling, Jenna N; Parent, Marise B

    2013-10-01

    Over the past five decades, per capita caloric intake has increased by approximately 28% in the United States. Excessive intake of calories from fats and sugars (high energy diets; HEDs) negatively impacts hippocampal-dependent memory. These deleterious effects of HEDs on hippocampal function involve HED-induced decreases in neuronal growth factors, neurogenesis, and synaptic plasticity. Given that HEDs also alter responses to emotional arousal, the present experiment determined whether the effects of HEDs on memory depend on the emotional arousal produced by the memory task during encoding. Rats were fed a high fat/sugar cafeteria-style diet for 4 weeks and then tested in a low or high emotional arousal version of a spatial object place recognition task. The results demonstrated that the HED prevented the memory-enhancing effects of emotional arousal. Thus, altered responses to emotional arousal likely contribute to HED-induced memory impairments, particularly in stressful memory tasks such as the spatial water maze.

  6. 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 Tech…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. Impact of a School-Based Sexual Abuse Prevention Education Program on the Knowledge and Attitude of High School Girls

    ERIC Educational Resources Information Center

    Ogunfowokan, Adesola A.; Fajemilehin, Reuben B.

    2012-01-01

    Sexual abuse has been considered a public health issue because of the various health implications resulting from it. The school nurse has a responsibility in assisting the high school girl to prevent victimization. This study adopted a quasi-experimental design in which a sexual abuse prevention education package was developed and used to educate…

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

    PubMed Central

    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

  13. Myeloperoxidase deletion prevents high-fat diet-induced obesity and insulin resistance.

    PubMed

    Wang, Qilong; Xie, Zhonglin; Zhang, Wencheng; Zhou, Jun; Wu, Yue; Zhang, Miao; Zhu, Huaiping; Zou, Ming-Hui

    2014-12-01

    Activation of myeloperoxidase (MPO), a heme protein primarily expressed in granules of neutrophils, is associated with the development of obesity. However, whether MPO mediates high-fat diet (HFD)-induced obesity and obesity-associated insulin resistance remains to be determined. Here, we found that consumption of an HFD resulted in neutrophil infiltration and enhanced MPO expression and activity in epididymal white adipose tissue, with an increase in body weight gain and impaired insulin signaling. MPO knockout (MPO(-/-)) mice were protected from HFD-enhanced body weight gain and insulin resistance. The MPO inhibitor 4-aminobenzoic acid hydrazide reduced peroxidase activity of neutrophils and prevented HFD-enhanced insulin resistance. MPO deficiency caused high body temperature via upregulation of uncoupling protein-1 and mitochondrial oxygen consumption in brown adipose tissue. Lack of MPO also attenuated HFD-induced macrophage infiltration and expression of proinflammatory cytokines. We conclude that activation of MPO in adipose tissue contributes to the development of obesity and obesity-associated insulin resistance. Inhibition of MPO may be a potential strategy for prevention and treatment of obesity and insulin resistance.

  14. Using anti-tobacco industry messages to prevent smoking among high-risk adolescents.

    PubMed

    Thrasher, James F; Niederdeppe, Jeffrey D; Jackson, Christine; Farrelly, Matthew C

    2006-06-01

    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 order to test whether reactions to anti-industry advertisements (ads), the attitudes these ads target, and the relationship between these attitudes and smoking differed by social bonding and sensation-seeking risk factors. Results indicated that anti-industry ad reactions and the strength of anti-industry attitudes were comparable between high- and low-sensation seeking adolescents, whereas weakly bonded adolescents had less favorable ad reactions and weaker anti-industry attitudes than strongly bonded adolescents. Social bonding also moderated the influence of sensation seeking on anti-industry ad reactions, such that sensation seeking had a positive influence among more strongly bonded adolescents and no influence among weakly bonded adolescents. Finally, the relationship between anti-industry attitudes and smoking appeared consistent across risk groups, whether risk was defined using social bonding, sensation seeking or the interaction between them. Overall, these results suggest that anti-industry messages are a promising strategy for preventing smoking among high- and low-risk adolescents alike. PMID:16492681

  15. High altitude pulmonary edema-clinical features, pathophysiology, prevention and treatment.

    PubMed

    Paralikar, Swapnil J

    2012-05-01

    High altitude pulmonary edema (HAPE) is a noncardiogenic pulmonary edema which typically occurs in lowlanders who ascend rapidly to altitudes greater than 2500-3000 m. Early symptoms of HAPE include a nonproductive cough, dyspnoea on exertion and reduced exercise performance. Later, dyspnoea occurs at rest. Clinical features are cyanosis, tachycardia, tachypnoea and elevated body temperature generally not exceeding 38.5°C. Rales are discrete initially and located over the middle lung fields. HAPE mainly occurs due to exaggerated hypoxic pulmonary vasoconstriction and elevated pulmonary artery pressure. It has been observed that HAPE is a high permeability type of edema occurring also due to leaks in the capillary wall ('stress failure'). Slow descent is the most effective method for prevention; in addition, graded ascent and time for acclimatization, low sleeping altitudes, avoidance of alcohol and sleeping pills, and avoidance of exercise are the key to preventing HAPE. Treatment of HAPE consists of immediate improvement of oxygenation either by supplemental oxygen, hyperbaric treatment, or by rapid descent. PMID:23580834

  16. Glucose-induced inhibition of the appetitive brain response to visual food cues in polycystic ovary syndrome patients.

    PubMed

    Van Vugt, Dean A; Krzemien, Alicja; Alsaadi, Hanin; Frank, Tamar C; Reid, Robert L

    2014-04-16

    We postulate that insulin regulation of food intake is compromised when insulin resistance is present. In order to investigate the effect of insulin sensitivity on appetitive brain responses, we conducted functional magnetic resonance imaging studies in a group of women diagnosed with polycystic ovary syndrome (PCOS) in which insulin sensitivity ranged from normal to resistant. Subjects (n=19) were imaged while viewing pictures of high calorie (HC) foods and low calorie (LC) foods after ingesting either 75 g glucose or an equivalent volume of water. The insulin sensitive group showed reduced blood oxygen level dependent (BOLD) signal in response to food pictures following glucose ingestion in numerous corticolimbic brain regions, whereas the insulin resistant group did not. There was a significant interaction between insulin sensitivity (sensitive vs resistant) and condition (water vs glucose). The largest clusters identified included the left insula, bilateral limbic/parahippocampal gyrus/culmen/midbrain, bilateral limbic lobe/precuneus, and left superior/mid temporal gyrus/parietal for HC and LC stimuli combined, the left parahippocampal gyrus/fusiform/pulvinar/midbrain for HC pictures, and the left superior/mid temporal gyrus/parietal and middle/inferior frontal gyrus/orbitofrontal cortex for LC pictures. Furthermore, BOLD signal in the anterior cingulate, medial frontal gyrus, posterior cingulate/precuneus, and parietal cortex during a glucose challenge correlated negatively with insulin sensitivity. We conclude the PCOS women with insulin resistance have an impaired brain response to a glucose challenge. The inability of postprandial hyperinsulinemia to inhibit brain responsiveness to food cues in insulin resistant subjects may lead to greater non-homeostatic eating. PMID:24583185

  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. Alaska pollack protein prevents the accumulation of visceral fat in rats fed a high fat diet.

    PubMed

    Oishi, Yoshie; Dohmoto, Nobuhiko

    2009-04-01

    In the first study (Study 1), 4-wk-old Sprague-Dawley (SD) rats were fed high fat diets containing casein, Alaska pollack, yellowfin tuna, or chicken as the protein source for 28 d. The purpose of this study was to compare the effect of Alaska pollack protein with other animal proteins (casein, yellowfin tuna, and chicken) on the prevention of visceral fat accumulation. We found that Alaska pollack protein was a more potent inhibitor of visceral fat accumulation than the other proteins (p<0.05). In the second study (Study 2), we determined the quantity of Alaska pollack protein needed to have an effect. To test this, 4-wk-old SD rats were fed diets containing different percentages of Alaska pollack proteins (0, 3, 10, 30 or 100%) to replace casein as the protein source for 28 d. The diets with 30 or 100% Alaska pollack protein as the protein source prevented visceral fat accumulation and elevated plasma adiponectin levels. Based on these findings, an inhibitory effect on the accumulation of visceral fats can be achieved by consuming a diet in which 30% or more of the total protein content comes from Alaska pollack. PMID:19436142

  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

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

    2009-11-01

    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. 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.

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

    PubMed Central

    Pai, Chen-Hsueh; Yen, Ching-Tzu; Chen, Chie-Pein; Yu, I-Shing

    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. PMID:26974824

  6. 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. PMID:26974824

  7. 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.

  8. Electrolyte-carbohydrate beverage prevents water loss in the early stage of high altitude training.

    PubMed

    Yanagisawa, Kae; Ito, Osamu; Nagai, Satsuki; Onishi, Shohei

    2012-01-01

    To prevent water loss in the early stage of high altitude training, we focused on the effect of electrolyte-carbohydrate beverage (EC). Subjects were 16 male university students who belonged to a ski club. They had ski training at an altitude of 1,800 m. The water (WT) group drank only water, and the EC group drank only an electrolyte-carbohydrate beverage. They arrived at the training site in the late afternoon. The study started at 7 pm on the day of arrival and continued until noon of the 4(th) day. In the first 12 hours, 1 L of beverages were given. On the second and third days, 2.5 L of beverages were given. All subjects ate the same meals. Each morning while in fasting condition, subjects were weighed and blood was withdrawn for various parameters (hemoglobin, hematocrit, sodium, potassium and aldosterone). Urine was collected at 12 hour intervals for a total 60 hours (5 times). The urine volume, gravity, sodium and potassium concentrations were measured. Peripheral oxygen saturation and heart rate were measured during sleep with a pulse oximeter. Liquid intakes in both groups were similar, hence the electrolytes intake was higher in the EC group than in the WT group. The total urine volume was lower in the EC group than in the WT group, respectively (p<0.05). Plasma volume decreased in the WT group and increased in the EC group but a significant difference was not observed in the final value. Aldosterone concentration tended to be less in the EC group than in the WT group. Electrolyte-carbohydrate beverage in the early stage of high altitude training may be effective in decreasing urinary output and preventing loss of blood plasma volume.

  9. Probiotic supplementation prevents high-fat, overfeeding-induced, insulin resistance in humans

    PubMed Central

    Hulston, Carl J.; Churnside, Amelia A.; Venables, Michelle C.

    2015-01-01

    The purpose of this study was to determine whether probiotic supplementation (Lactobacillus casei Shirota [LcS]) prevents diet-induced insulin resistance in humans. Seventeen healthy individuals were randomised to probiotic (n = 8) or control (n = 9) groups. The probiotic group consumed an LcS-fermented milk drink twice daily for 4 weeks whereas the control group received no supplementation. Subjects maintained their normal diet for the first 3 weeks of the study, after which they consumed a high-fat (65% energy) high-energy (+50% kcal) diet for 7 days. Whole body insulin sensitivity was assessed via an oral glucose tolerance test conducted before and after overfeeding. Body mass increased by 0.6 ± 0.2 kg in the control group (p < 0.05) and 0.3 ± 0.2 kg in the probiotic group (p > 0.05). Fasting plasma glucose concentrations increased following 7 days of overeating (control group only; 5.3 ± 0.1 vs. 5.6 ± 0.2 mmol/L, p < 0.05) whereas fasting serum insulin concentrations were maintained in both groups. Glucose AUC increased by 10% (from 817 ± 45 to 899 ± 39 mmol/L/120 min, p < 0.05) and whole body insulin sensitivity decreased by 27% (from 5.3 ± 1.4 to 3.9 ± 0.9, p < 0.05) in the control group, whereas normal insulin sensitivity was maintained in the probiotic group (4.4 ± 0.8 and 4.5 ± 0.9 before and after overeating, respectively, p > 0.05). These results suggest that probiotic supplementation may be useful in the prevention of diet-induced metabolic diseases such as type II diabetes. PMID:25630516

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

    PubMed Central

    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. PMID:25548575

  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 Central

    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. PMID:25923692

  13. 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. PMID:25923692

  14. 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. PMID:26840705

  15. Spirulina prevents atherosclerosis by reducing hypercholesterolemia in rabbits fed a high-cholesterol diet.

    PubMed

    Cheong, Sun Hee; Kim, Mi Yeon; Sok, Dai-Eun; Hwang, Seock-Yeon; Kim, Jin Hee; Kim, Hye Ran; Lee, Jeung Hee; Kim, Yun-Bae; Kim, Mee Ree

    2010-01-01

    The anti-atherogenic effects of spirulina (Spirulina platensis) were investigated in the New Zealand White (NZW) rabbit model. The animal had hypercholesterolemia induced by being fed a high cholesterol diet (HCD) containing 0.5% cholesterol for 4 wk, and then fed a HCD supplemented with 1 or 5% spirulina (SP1 or SP5) for an additional 8 wk. Spirulina supplementation lowered intimal surface of the aorta by 32.2 to 48.3%, compared to HCD. Serum triglyceride (TG) and total cholesterol (TC) significantly were reduced in SP groups. After 8 wk, serum low density lipoprotein cholesterol (LDL-C) remarkably decreased by 26.4% in SP1 and 41.2% in SP5, compared to HCD. On the other hand, high density lipoprotein cholesterol (HDL-C) was markedly increased in SP1 and SP5 compared with that in the HCD group from 2 to 8 wk. These results suggest that spirulina intake can cause the reduction of hypercholesterolemic atherosclerosis, associated with a decrease in levels of serum TC, TG and LDL-C, and an elevation of HDL-C level. Spirulina may, therefore, be beneficial in preventing atherosclerosis and reducing risk factors for cardiovascular diseases. PMID:20354344

  16. 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

  17. 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

  18. 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.

  19. 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. PMID:26459640

  20. 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.

  1. Origin and prevention of high contact resistance in multilevel metal-polyimide structures

    NASA Astrophysics Data System (ADS)

    Day, David R.; Senturia, Stephen D.

    1982-05-01

    When polyimide is used as the insulating dielectric in multilevel-metal structures, a high contact resistance can result within the interconnecting vias. This paper examines the particular case of oxygen plasma patterning of the polyimide using a photoresist mask. Auger analysis in combination with compositional depth profiling was employed on a series of samples to measure surface composition of etched vias in polyimide. Results show two effects which, together, can account for high contact resistance: first, there is a thicker than normal aluminum oxide layer on the first level metal surface (due to exposure to the oxygen plasma); second, there is a thin, etch-resistant carbonaceous film (due to redeposition of organic material during plasma etching) that prevents oxide thinning through chemical means. It was found that by lowering the plasma pressure to 50 mTorr near the end of the etch, the organic film can be removed. In the absence of the carbonaceous layer, the oxide can then be chemically thinned to produce clean aluminum surfaces within the vias.

  2. 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

  3. 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.

  4. 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.

  5. “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

  6. 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.

  7. 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…

  8. The Challenge of Improving Urban High School Graduation Outcomes: Findings from a Randomized Study of Dropout Prevention Efforts

    ERIC Educational Resources Information Center

    Mac Iver, Martha Abele

    2011-01-01

    This 5-year longitudinal randomized study focused on the effects of a dropout prevention program implemented at two urban high schools. The program incorporated the characteristics of personalization found in previous research to have some positive effects, and typical of the type of programs implemented in many high schools nationwide. The…

  9. Whole School Improvement and Restructuring as Prevention and Promotion: Lessons from STEP and the Project on High Performance Learning Communities.

    ERIC Educational Resources Information Center

    Felner, Robert D.; Favazza, Antoinette; Shim, Minsuk; Brand, Stephen; Gu, Kenneth; Noonan, Nancy

    2001-01-01

    Describes the School Transitional Environment Project and its successor, the Project on High Performance Learning Communities, that have contributed to building a model for school improvement called the High Performance Learning Communities. The model seeks to build the principles of prevention into whole school change. Presents findings from…

  10. 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…

  11. Preventing Poor Mental Health and School Dropout of Mexican American Adolescents Following the Transition to Junior High School

    ERIC Educational Resources Information Center

    Gonzales, Nancy A.; Dumka, Larry E.; Deardorff, Julianna; Carter, Sara Jacobs; McCray, Adam

    2004-01-01

    This study provided an initial test of the Bridges to High School Program, an intervention designed to prevent school disengagement and negative mental health trajectories during the transition to junior high school. The intervention included an adolescent coping skills intervention, a parenting skills intervention, and a family strengthening…

  12. High parental monitoring prevents adolescents from engaging in risky sexual practices in Harar, Ethiopia

    PubMed Central

    Dessie, Yadeta; Berhane, Yemane; Worku, Alemayehu

    2014-01-01

    Background Emerging findings have shown that high parental monitoring of adolescents’ sexual and reproductive health (SRH) communications between parents and adolescents and good parenting styles prevent adolescents from engaging in risky sexual practices. Objective The aim of this study was to examine the associations of parental monitoring, parent–adolescent SRH communications, and parenting styles with risky sexual practices among adolescents in Harar, Ethiopia. Designs This was a cross-sectional study conducted on adolescents aged 13–18 who had sexual initiations. Adolescents who failed to use any contraceptive method and/or condom during last sexual intercourse and who experienced multiple sexual partners in the 12 months prior to the study were taken as ‘at risk’. In view of these, the adolescents risk count ranged from zero to three – greater number indicates higher count of risky sexual practices. Poisson regression model was used to examine the associations and p<0.05 indicated a statistical significance. Results It was found out that 301 of 633 (47.55%; 95% CI=43.62%, 51.45%) adolescents experienced one or more risky sexual practices. High parental monitoring compared to low decreases the Incidence Rate of engaging in risky sexual practices by 28% (adjusted incidence rate ratio, or IRR=0.72; 95% CI=0.520, 0.986). Those who had a satisfactory level of SRH communications with their parents compared to poor communicators experianced less incidence rate of risky sexual practices which was marginal (adjusted IRR=0.82; 95% CI=0.637, 1.051). Conclusions A significant proportion of the adolescents engaged in one or more risky sexual practices. Importantly, high parental monitoring decreases the likelihood of these risky practices. Therefore, parents need to be encouraged to keep an eye on their young children. PMID:25398086

  13. 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

  14. 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…

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

    PubMed

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

    2015-05-10

    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.

  16. 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

  17. Cinchonine Prevents High-Fat-Diet-Induced Obesity through Downregulation of Adipogenesis and Adipose Inflammation

    PubMed Central

    Jung, Sung A.; Choi, Miseon; Kim, Sohee; Yu, Rina; Park, Taesun

    2012-01-01

    Cinchonine (C19H22N2O) is a natural compound of Cinchona bark. Although cinchonine's antiplatelet effect has been reported in the previous study, antiobesity effect of cinchonine has never been studied. The main objective of this study was to investigate whether cinchonine reduces high-fat-diet- (HFD-) induced adipogenesis and inflammation in the epididymal fat tissues of mice and to explore the underlying mechanisms involved in these reductions. HFD-fed mice treated with 0.05% dietary cinchonine for 10 weeks had reduced body weight gain (−38%), visceral fat-pad weights (−26%), and plasma levels of triglyceride, free fatty acids, total cholesterol, and glucose compared with mice fed with the HFD. Moreover, cinchonine significantly reversed HFD-induced downregulations of WNT10b and galanin-mediated signaling molecules and key adipogenic genes in the epididymal adipose tissues of mice. Cinchonine also attenuated the HFD-induced upregulation of proinflammatory cytokines by inhibiting toll-like-receptor-2- (TLR2-) and TLR4-mediated signaling cascades in the adipose tissue of mice. Our findings suggest that dietary cinchonine with its effects on adipogenesis and inflammation may have a potential benefit in preventing obesity. PMID:22675336

  18. Postoperative High-Dose-Rate Brachytherapy in the Prevention of Keloids

    SciTech Connect

    Veen, Ronald E. Kal, Henk B.

    2007-11-15

    Background: The aim of this study is to show the efficiency of keloidectomy and postoperative interstitial high-dose-rate (HDR) brachytherapy in the prevention of keloids. Methods and Materials: Between 1998 and 2004, 35 patients with 54 keloids were treated postoperatively with HDR brachytherapy. The first HDR dose was applied within 6 hours after surgery, and two additional HDR doses were administered on the next day with a six-hour interval. The majority of patients received 6 Gy as the first dose postsurgery and two fractions of 4 Gy (38 keloids) on the next day. Seven keloids were treated postoperatively with three fractions of 6 Gy. The biologically effective dose (BED), derived from the linear quadratic concept, was applied to calculate the BED for the various radiation regimens. The keloid recurrence rates at specific BED values were compared with those derived for other fractionation schemes in the literature. Results: Four recurrences/nonsatisfactory results out of nine treated keloids were observed after treatments with 1 x 4 Gy + 2 x 3 Gy. Only one recurrence out of 38 was found after 1 x 6 Gy + 2 x 4 Gy and none after 3 x 6 Gy. Better cosmetic results were found at the higher-dose schemes. Conclusion: The results of this study prove the effectiveness of HDR brachytherapy after keloidectomy provided that the total HDR dose is sufficient. Currently our scheme is 3 x 6 Gy.

  19. 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

  20. 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.

  1. Initial impact of the Fast Track prevention trial for conduct problems: I. The high-risk sample. Conduct Problems Prevention Research Group.

    PubMed

    1999-10-01

    Fast Track is a multisite, multicomponent preventive intervention for young children at high risk for long-term antisocial behavior. Based on a comprehensive developmental model, intervention included a universal-level classroom program plus social skills training, academic tutoring, parent training, and home visiting to improve competencies and reduce problems in a high-risk group of children selected in kindergarten. At the end of Grade 1, there were moderate positive effects on children's social, emotional, and academic skills; peer interactions and social status; and conduct problems and special-education use. Parents reported less physical discipline and greater parenting satisfaction/ease of parenting and engaged in more appropriate/consistent discipline, warmth/positive involvement, and involvement with the school. Evidence of differential intervention effects across child gender, race, site, and cohort was minimal. PMID:10535230

  2. Initial impact of the Fast Track prevention trial for conduct problems: I. The high-risk sample. Conduct Problems Prevention Research Group.

    PubMed

    1999-10-01

    Fast Track is a multisite, multicomponent preventive intervention for young children at high risk for long-term antisocial behavior. Based on a comprehensive developmental model, intervention included a universal-level classroom program plus social skills training, academic tutoring, parent training, and home visiting to improve competencies and reduce problems in a high-risk group of children selected in kindergarten. At the end of Grade 1, there were moderate positive effects on children's social, emotional, and academic skills; peer interactions and social status; and conduct problems and special-education use. Parents reported less physical discipline and greater parenting satisfaction/ease of parenting and engaged in more appropriate/consistent discipline, warmth/positive involvement, and involvement with the school. Evidence of differential intervention effects across child gender, race, site, and cohort was minimal.

  3. 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

  4. 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.

  5. 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. PMID:23411461

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

    PubMed Central

    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, Kristen A.; Newman, Andrew F.; Woods, Jeffrey A.; Kelley, Keith W.; Wang, Yanyan; Miller, Michael J.; Freund, Gregory G.

    2013-01-01

    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 (1–3 wks) of a high-fat diet (HFD). After 1 wk 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. PMID:23411461

  7. 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.

  8. The Prevention of Depression and Anxiety in a Sample of High-Risk Adolescents: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Dobson, Keith S.; Hopkins, Jamie Ahnberg; Fata, Ladan; Scherrer, Martin; Allan, Lauren C.

    2010-01-01

    This study investigated the efficacy of cognitive behavioural therapy (CBT) techniques in preventing depression and anxiety in a group of adolescent high school students with elevated risk for developing emotional disorders. Students were screened using a measure of depression severity and clinical interview. Following screening procedures,…

  9. 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...

  10. 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. |

  11. 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,…

  12. 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…

  13. Fire Safety for Consumers. Economics (High School). Fire Safety for Texans: Fire and Burn Prevention Curriculum Guide.

    ERIC Educational Resources Information Center

    Texas State Commission on Fire Protection, Austin.

    This booklet comprises the high school economics component of a series of curriculum guides on fire and burn prevention. It is designed to meet the age-specific needs of eleventh and twelfth grade students. Objectives include: (1) developing an awareness of adult responsibilities to preserve family, property, and economy; (2) preparing for…

  14. Preventive measures to prevent loss to follow-up in highly active antiretroviral therapy (HAART): implementing a strategy in Ziguinchor (Casamance, Senegal) in 2014.

    PubMed

    Randé, H; Rouffy, D

    2016-05-01

    Since 2010, the Pharmacie et Aide Humanitaire (PAH) in Casamance (Senegal) has been maintaining a software package (Tacojo) that allows monthly monitoring of the distribution of treatment to every patient with HIV infection receiving highly active antiretroviral therapy (HAART). We used this program to set up measures to prevent the loss to follow-up of patients receiving HAART. Our involvement focused on two main areas. First, each patient is routinely contacted after inclusion, to help us to understand the patient's experience of the disease and the treatment. This process aims to improve adherence to the treatment. Then, all patients who miss an appointment are routinely contacted by telephone within seven days of that appointment. The goal is to understand the reasons for the absence and to encourage patients to continue their treatment. Despite the lack of distance due to the relative newness of this program, these preventive measures have shown hopeful results (80% of the patients came back after a call). It would be interesting to apply it in a sustainable manner and in more medical facilities. PMID:27412981

  15. Determinants of Knowledge and Biosecurity Preventive Behaviors for Highly Pathogenic Avian Influenza Risk Among Chinese Poultry Farmers.

    PubMed

    Cui, Bin; Liu, Zong Ping

    2016-06-01

    Biosecurity measures are the first line of defense against highly pathogenic avian influenza (HPAI) on farms. It is generally recognized that an individual's behavior can be influenced by the knowledge they possess. However, empirical study has not reported an association between poultry producers' awareness of HPAI symptoms and their actual biosecurity actions. The aim of this study is to classify knowledge items of HPAI by exploratory factor analysis (EFA) and to examine the determinants of different types of knowledge and the effect of different types of knowledge on biosecurity preventive behaviors (BPBs). The survey (n = 297) was conducted using a questionnaire to measure the level of awareness of items related to HPAI and the actual adoption of BPBs among poultry farmers in the Chinese province of Jiangsu. The EFA revealed three main types of knowledge, which were categorized as avian influenza (AI) epidemic characteristics, primary biosecurity preventive knowledge (basic biosecurity preventive knowledge against AI), and essential biosecurity preventive knowledge (crucial biosecurity preventive knowledge against infection of AI). Multivariate regression showed that only poultry farmers' awareness of essential biosecurity preventive knowledge was positively associated with their actual BPBs. Additionally, educational attainment, number of years of experience raising poultry, farming operation size, and training were associated both with BPB and most of the knowledge factors or knowledge items. Training of existing poultry farmers is probably a feasible scheme; furthermore, the training should focus on the essential biosecurity preventive knowledge. On the other hand, policy initiatives to encourage large-scale poultry farming while discouraging small-scale backyard poultry husbandry would be an effective method of improving the management standards of rural poultry farming. PMID:27309291

  16. Determinants of Knowledge and Biosecurity Preventive Behaviors for Highly Pathogenic Avian Influenza Risk Among Chinese Poultry Farmers.

    PubMed

    Cui, Bin; Liu, Zong Ping

    2016-06-01

    Biosecurity measures are the first line of defense against highly pathogenic avian influenza (HPAI) on farms. It is generally recognized that an individual's behavior can be influenced by the knowledge they possess. However, empirical study has not reported an association between poultry producers' awareness of HPAI symptoms and their actual biosecurity actions. The aim of this study is to classify knowledge items of HPAI by exploratory factor analysis (EFA) and to examine the determinants of different types of knowledge and the effect of different types of knowledge on biosecurity preventive behaviors (BPBs). The survey (n = 297) was conducted using a questionnaire to measure the level of awareness of items related to HPAI and the actual adoption of BPBs among poultry farmers in the Chinese province of Jiangsu. The EFA revealed three main types of knowledge, which were categorized as avian influenza (AI) epidemic characteristics, primary biosecurity preventive knowledge (basic biosecurity preventive knowledge against AI), and essential biosecurity preventive knowledge (crucial biosecurity preventive knowledge against infection of AI). Multivariate regression showed that only poultry farmers' awareness of essential biosecurity preventive knowledge was positively associated with their actual BPBs. Additionally, educational attainment, number of years of experience raising poultry, farming operation size, and training were associated both with BPB and most of the knowledge factors or knowledge items. Training of existing poultry farmers is probably a feasible scheme; furthermore, the training should focus on the essential biosecurity preventive knowledge. On the other hand, policy initiatives to encourage large-scale poultry farming while discouraging small-scale backyard poultry husbandry would be an effective method of improving the management standards of rural poultry farming.

  17. [Neural tube defects and folic acid: a historical overview of a highly successful preventive intervention].

    PubMed

    Vásquez, Adriana Ordoñez; Suarez-Obando, Fernando

    2015-12-01

    This article gives a broad overview of part of the historical evolution of medical knowledge about neural tube defects (NTD) and the discovery of vitamin B9 or folic acid, as well as some relevant research events that, over the course of several centuries, defined the relationships between the understanding of central nervous system embryology, the discovery of the vitamin, the correlation between folic acid and cell proliferation and lastly the development of preventive measures for this type of defects. This narrative allows us to examine historically relevant concepts underlying clinical actions with a populational impact that prevent NTDs via folic acid consumption prior to conception.

  18. 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

  19. Recruiting and Retaining High-Risk Adolescents into Family-Based HIV Prevention Intervention Research

    ERIC Educational Resources Information Center

    Kapungu, Chisina T.; Nappi, Carla N.; Thakral, Charu; Miller, Steven A.; Devlin, Catharine; McBride, Cami; Hasselquist, Emily; Coleman, Gloria; Drozd, Derek; Barve, Chinmayee; Donenberg, Geri; DiClemente, Ralph; Brown, Larry

    2012-01-01

    The purpose of this study was to examine the effectiveness of evidence-based recruitment and retention strategies for a longitudinal, family-based HIV prevention intervention study targeting adolescents in psychiatric care by (1) determining consent rate (recruitment), rate of participation at the first intervention session (retention), and…

  20. 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…

  1. 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…

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

    ERIC Educational Resources Information Center

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

    2009-01-01

    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…

  3. Adapting an HIV Prevention Intervention for High-Risk, Incarcerated Adolescents

    ERIC Educational Resources Information Center

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

    2010-01-01

    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-…

  4. The Effects of a Violence Prevention Program on Alternative High School Students

    ERIC Educational Resources Information Center

    Triplett, Carla A.

    2013-01-01

    This study addressed the effectiveness of a violence prevention program in an inner-city alternative school setting. The researcher, an administrator at the school, used a prepackaged curriculum targeting lessons on violence in an eight-week study with the entire school population. Students met bi-weekly with a team of two teachers to review and…

  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. Suicide Prevention in the Schools: Guidelines for Middle and High School Settings. Second Edition

    ERIC Educational Resources Information Center

    Capuzzi, David

    2009-01-01

    In this book, David Capuzzi, a renowned expert on suicide, encourages suicide prevention in schools through the use of a clear and effective crisis management plan designed to identify and serve at-risk youth. His concise, step-by-step framework provides essential information for school counselors, administrators, and faculty on suicide…

  7. The Preventive Approach to Children at High Risk for Psychopathology and Psychosis.

    ERIC Educational Resources Information Center

    Anthony, E. James

    1982-01-01

    Primary prevention, as applied to the children of psychotics, should be directed against the transmission of psychosis to the next generation of adults and toward the relief of psychopathology in the children. It should be remembered that genetic and environmental factors interact in the etiology of mental illness. (Author/CMG)

  8. 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…

  9. Today's "High Stakes" Employment Discrimination Suits: Using Training to Prevent Financial Disaster.

    ERIC Educational Resources Information Center

    Kelleher, Christopher G.

    1994-01-01

    Either losing or winning an employment discrimination case can be financially devastating to a college or university. A prevention plan includes: changing the attitudes of individuals throughout the institution; reviewing policies and practices; fostering better communication; encouraging cooperation between administrators and human resource…

  10. 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…

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. Copper addition prevents the inhibitory effects of interleukin 1-beta on rat pancreatic islets.

    PubMed

    Vinci, C; Caltabiano, V; Santoro, A M; Rabuazzo, A M; Buscema, M; Purrello, R; Rizzarelli, E; Vigneri, R; Purrello, F

    1995-01-01

    Since copper [Cu(II)] is a necessary cofactor for both intra-mitochondrial enzymes involved in energy production and hydroxyl scavenger enzymes, two hypothesised mechanisms for action of interleukin-I beta (IL-1 beta), we studied whether Cu(II) addition could prevent the inhibitory effect of IL-1 beta on insulin release and glucose oxidation in rat pancreatic islets. Islets were incubated with or without 50 U/ml IL-1 beta, in the presence or absence of various concentrations of Cu(II)-GHL (Cu(II) complexed with glycyl-L-histidyl-L-lysine, a tripeptide known to enhance copper uptake into cultured cells). CuSO4 (1-1000 ng/ml) was used as a control for Cu(II) effect when present as an inorganic salt. At the end of the incubation period, insulin secretion was evaluated in the presence of either 2.8 mmol/l (basal insulin secretion) or 16.7 mmol/l glucose (glucose-induced release). In control islets basal insulin secretion was 92.0 +/- 11.4 pg.islet-1 h-1 (mean +/- SEM, n = 7) and glucose-induced release was 2824.0 +/- 249.0 pg.islet-1 h-1. In islets pre-exposed to 50 U/ml IL-1 beta, basal insulin release was not significantly affected but glucose-induced insulin release was greatly reduced (841.2 +/- 76.9, n = 7, p < 0.005). In islets incubated with IL-1 beta and Cu-GHL (0.4 mumol/l, maximal effect) basal secretion was 119.0 +/- 13.1 pg.islet-1 h-1 and glucose-induced release was 2797.2 +/- 242.2, (n = 7, p < 0.01 in respect to islets exposed to IL-1 beta alone).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7744228

  16. 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

  17. 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…

  18. 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.

  19. Influenza in the elderly. Prevention is the best strategy in high-risk populations.

    PubMed

    Bradley, S F

    1996-02-01

    Diagnosis of influenza can be difficult in the elderly because of coexisting disease or communication difficulties. However, since the infection often results in complications and may be lethal in these patients, early identification is imperative. Influenza virus vaccine (Fluogen, Fluzone, FluShield) may prevent infection or reduce the severity of complications, even though response may be attenuated in elderly patients. Newer vaccines under investigation may prove to be more efficacious. Education is necessary to improve rates of vaccination, particularly among residents and staff of nursing homes. Antiviral agents are important adjuncts in the fight against influenza, but they are not a substitute for vaccination.

  20. 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.

  1. 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. PMID:26268913

  2. 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.

  3. A novel 3D high-content assay identifies compounds that prevent fibroblast invasion into tissue surrogates.

    PubMed

    Wenzel, Carsten; Otto, Saskia; Prechtl, Stefan; Parczyk, Karsten; Steigemann, Patrick

    2015-11-15

    Invasion processes underlie or accompany several pathological processes but only a limited number of high-throughput capable phenotypic models exist to test anti-invasive compounds in vitro. We here evaluated 3D co-cultures as a high-content phenotypic screening system for fibrotic invasive processes. 3D multicellular spheroids were used as living tissue surrogates in co-culture with fluorescently labeled lung fibroblasts to monitor invasion processes by automated microscopy. This setup was used to screen a compound library containing 480 known bioactive substances. Identified hits prevented fibroblast invasion and could be subdivided into two hit classes. First, Prostaglandins were shown to prevent fibroblast invasion, most likely mediated by the prostaglandin EP2 receptor and generation of cAMP. Additionally, Rho-associated protein kinase (ROCK) inhibitors prevented fibroblast invasion, possibly by inactivation of myosin II. Importantly, both Prostaglandins and ROCK inhibitors are potential treatment options shown to be effective in in vitro and in vivo models of fibrotic diseases. This validates the presented novel phenotypic screening approach for the evaluation of potential inhibitors and the identification of novel compounds with activity in diseases that are associated with fibroblast invasion.

  4. 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.

  5. High-fat petrolatum-based moisturizers and prevention of work-related skin problems in wet-work occupations.

    PubMed

    Mygind, Karen; Sell, Lea; Flyvholm, Mari-Ann; Jepsen, Karen Frydendall

    2006-01-01

    The study presented is a randomized, controlled intervention study with the purpose of implementing an evidence-based skin disease prevention programme. The hypothesis explored in this article is whether a high-fat petrolatum-based moisturizer can be an alternative to protective gloves in wet-work occupations. The study population was all gut cleaners in Danish swine slaughterhouses, and data were collected by telephone interviews using a standardized questionnaire - The Nordic Occupational Skin Questionnaire (NOSQ-2002). At baseline, 644 (88%) gut cleaners responded and at 1-year follow-up 622 (72%). 135 gut cleaners in the intervention and 277 in the comparison group responded at both telephone interviews. In the intervention group, the eczema frequency was reduced significantly. Detailed analyses revealed that protective gloves are the overall most effective protective means and did not indicate that a high-fat moisturizer could be an alternative. Furthermore, the most extensive improvements could not be explained by combinations of protective behaviour but was found among those who had received information on, and was having discussions on prevention of skin problems. This only applied to the intervention group. A continuous focus on prevention of skin problems with information and discussions on the shop floor therefore seemed to be most important for reducing skin problems.

  6. Diets containing Sophora japonica L. prevent weight gain in high-fat diet-induced obese mice.

    PubMed

    Park, Kye Won; Lee, Ji-Eun; Park, Ki-Moon

    2009-11-01

    Obesity, a worldwide epidemic, is associated with metabolic diseases such as insulin resistance, dyslipidemia, hypertension, and heart disease. Many strategies, including natural alternative antiobesity agents, have been widely used to prevent obesity. Polyphenolic compounds and flavonoids from natural products are shown to inhibit adipogenesis. Because mature fruits of Sophora japonica L. were previously shown to contain antiadipogenic compounds, we hypothesized that diets with mature fruits of S japonica L. would prevent body weight gain in high-fat diet-induced obesity. Four-week-old mice were fed either a control high-fat diet, or high-fat diet containing 1% or 5% of S japonica L. for 4 weeks. The administration of S japonica L. fed in combination with a 30% high-fat diet significantly decreased body weight gain. S japonica L. also reduced serum and hepatic triglyceride, serum total, and high-density lipoprotein cholesterol. Consistent with the effects of lowering glucose level and fat mass, S japonica L. caused a decrease in the number of large adipocytes and a concomitant increase in the number of small adipocytes, which may explain at least in part the antiobesity effects of S japonica L. Together, these data provide evidence for roles of S japonica L. in the control of body weight and obesity-related metabolic diseases. PMID:19932871

  7. 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…

  8. A preventive intervention for enhancing resilience among highly stressed urban children.

    PubMed

    Cowen, E L; Wyman, P A; Work, W C; Iker, M R

    1995-03-01

    Describes the development and evaluation of a pilot 12-session, school-based preventive intervention designed to enhance resilience among inner-city children who have experienced major life stress. Thirty-six 4th-6th grade children participated in the intervention in groups of 5-8 co-led by school personnel. The curriculum focussed on understanding feelings in oneself and others, perspective-taking, social problem-solving, dealing with solvable and unsolvable problems, and building self-efficacy and esteem. Pre-post evaluation showed significant improvement among participants on teacher-rated indices of learning problems and task orientation and on child ratings of perceived self-efficacy, realistic control attributions and anxiety. Program limitations and factors that restrict generalization are considered and new directions for program development and research are proposed. PMID:24254528

  9. 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

  10. 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

  11. Fibroblast growth factor 21 prevents glycemic deterioration in insulin deficient mouse models of diabetes.

    PubMed

    Andersen, Birgitte; Omar, Bilal A; Rakipovski, Günaj; Raun, Kirsten; Ahrén, Bo

    2015-10-01

    In type 1 diabetes, there is a rapid loss of glycemic control immediately after onset of the disease. We aimed to determine if the deterioration of glycemic control that occurs early after the onset of insulin-deficient diabetes could be blunted by treatment with recombinant fibroblast growth factor 21 (FGF21). Normal C57BL/6J mice made diabetic by a single high dose injection of streptozotocin (STZ) were randomized to receive twice daily subcutaneous injection of vehicle or recombinant human FGF21 at doses of 0.3 and 1.0 mg/kg for 10 days. Body weight was recorded daily and 5 h fasted glucose, insulin, glucagon, free fatty acids and ketones were determined at 6 and 10 days post-randomization. The increase in fasting plasma glucose induced by STZ in untreated mice was prevented with FGF21 at 0.3 mg/kg BID. In contrast, at 1.0 mg/kg BID, FGF21 did not prevent the rise in plasma glucose after STZ. At the end of the study, plasma glucagon was significantly higher in the diabetic group treated with FGF21 1.0 mg/kg BID than in the untreated group. This was not seen for the group treated with FGF21 0.3 mg/kg BID. There were significant dose dependent reductions in plasma free fatty acids with FGF21 treatment but no significant change in plasma ketones (β-hydroxybutyrate). FGF21 treatment did not have significant effects on body weight in lean insulin deficient mice. In conclusion, FGF21 prevents increases in glycaemia and has lipid lowering properties in mouse models of insulin deficient diabetes, although by increasing the dose increased glucagon levels are seen and hyperglycemia persists.

  12. 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. PMID:26893251

  13. 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. PMID:20679329

  14. 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.

  15. 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…

  16. Preemptive therapy in the prevention of cytomegalovirus disease in high- and low-risk heart transplant recipients.

    PubMed

    Casquero, S; Rangel, D; Lage, E; Sobrino, M; Cristobo, P; Cordero, E; Cisneros, J M

    2012-09-01

    Cytomegalovirus (CMV) infection remains a major complication in recipients of solid organ transplantation. Based on available evidence, most centers are committed to an aggressive strategy, especially in high-risk patients, consisting of the use of universal prophylaxis in the posttransplantation period of maximum risk (3 months). In seropositive recipients there is no ideal model for prevention, although there is more acceptance in the international community for preemptive therapy. This paper shows the results obtained after analysis of a cohort of 86 patients undergoing heart transplantation in 2005-2011 at the Virgen del Rocío University Hospital, Seville. The 86 patients followed a strategy of preemptive therapy for both high- and low-risk recipients based on the use of antivirals for a variable period of ∼3 weeks when rising antigenemia was detected, determined by polymerase chain reaction above a set threshold. The incidence of CMV disease in our cohort was 4.6%. There are no data available from randomized clinical trials to establish which of the 2 strategies is more effective and safer in these patients, although there is a little experience with preemptive therapy in high-risk patients. Given our positive results and considering the adverse effects of antiviral prophylaxis derivatives, together with the development of resistance and the economic cost, we suggest an individualized prevention strategy at each center.

  17. The long-term prevention of tobacco use among junior high school students: classroom and telephone interventions.

    PubMed Central

    Elder, J P; Wildey, M; de Moor, C; Sallis, J F; Eckhardt, L; Edwards, C; Erickson, A; Golbeck, A; Hovell, M; Johnston, D

    1993-01-01

    OBJECTIVES. The purpose of this study was to implement and evaluate the effectiveness of a long-term tobacco use prevention program for junior high school students that used college undergraduate change agents and telephone boosters. METHODS. A psychosocial intervention combining refusal skills training, contingency management, and other tobacco use prevention methodologies such as telephone and mail boosters was implemented in 11 junior high schools in San Diego County, California. Eleven other junior high schools served as controls. Of the 2668 participants, 57% were White/non-Hispanic, 24% were Hispanic, and 19% were of other racial/ethnic groups. College undergraduates served as change agents for both the classroom and booster interventions, the latter of which was delivered in the third (ninth-grade) year of the program. RESULTS. At the end of the third year, the prevalence of tobacco use within the past month was 14.2% among the intervention students and 22.5% among the controls, yielding an odds ratio of 0.71 for analysis at the school level. CONCLUSIONS. Both college undergraduate change agents and direct one-to-one telephone interventions appear to provide cost-effective tobacco-related behavior modification. PMID:8362998

  18. 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

  19. Modified filter prevents conduction of microwave signals along high-voltage power supply leads

    NASA Technical Reports Server (NTRS)

    Mathison, R. P.

    1964-01-01

    Very lossy powdered iron material, in the lining of a polyester resin, replaces the dielectric material in the short coaxial transmission line of a simple filter. The lossy material absorbs microwave signals along high voltage power supply leads.

  20. 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

  1. 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.

  2. Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory.

    PubMed

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

    2015-06-01

    High fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood-brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), a HF (40% of energy as fat), or a HF diet supplemented with 10mg/kg/day BM orally for 21weeks. Recognition memory was assessed by performing a novel object recognition test on the treated mice. Downstream brain-derived neurotrophic factor (BDNF) signalling molecules were examined in the prefrontal cortex (PFC) and hippocampus of mice via Western blotting and N-methyl-d-aspartate (NMDA) receptor binding. BM treatment prevented HF diet-induced impairment in recognition memory (p<0.001). In HF diet fed mice, BM administration attenuated alterations in the NMDA receptor binding density in the PFC (p<0.05), however, no changes were seen in the hippocampus (p>0.05). In the PFC and hippocampus of the HF diet fed mice, BM administration improved downstream BDNF signalling as indicated by increased protein levels of BDNF, phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p<0.05). BM administration also prevented the HF diet-induced increase in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet-induced impairments in recognition memory by improving downstream BDNF signal transduction, increasing pAMPK, and reducing inflammation in the PFC and hippocampus.

  3. A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia.

    PubMed

    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-F(2t)-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

  4. 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

  5. Effect of social cognitive theory-based HIV education prevention program among high school students in Nanjing, China.

    PubMed

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

    2011-06-01

    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 in each condition). The participants completed a confidential questionnaire at baseline and 6-month post-intervention with a follow-up rate of 94.4% (287 of 304). The outcome measures included HIV knowledge, HIV-related perceptions based on the protection motivation theory, stigmatizing attitude toward people living with HIV/AIDS (PLWHA), intentions of health-related risk behaviors and sexual intercourse in the previous 6 months. Results showed a significant intervention effect at 6-month post-intervention in increasing HIV knowledge, decreasing perceptions of response cost associated with abstinence and reducing stigmatizing attitudes toward PLWHA, after controlling for key demographic characteristics and relevant baseline measures. Further mediation analysis suggested that HIV knowledge mediated the effect of intervention on stigma reduction. Findings from this study support the feasibility and initial efficacy of the cultural adaptation of FOK HIV prevention program among high school students in China.

  6. A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia.

    PubMed

    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

    2015-06-09

    A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F(2t)-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.

  7. 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.

  8. Suicide Prevention in the Schools: Guidelines for Middle and High School Settings.

    ERIC Educational Resources Information Center

    Capuzzi, David

    Suicide is the second leading cause of death among adolescents. Between 1981 and 1989, 7% of all those who suicide were children and adolescents aged five to 19 and during that time 16,585 adolescents between the ages of 15 and 19 committed suicide. Written for counselors and middle and high school personnel, this book examines the dynamics of…

  9. 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'…

  10. 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…

  11. Predicting Success, Preventing Failure: An Investigation of the California High School Exit Exam

    ERIC Educational Resources Information Center

    Zau, Andrew C.; Betts, Julian R.

    2008-01-01

    Many educators, parents, and policymakers continue to call for reforms to the California High School Exit Exam (CAHSEE), citing concern about the 10 percent of California students who do not graduate because of their failure to pass the test. By law, current funding for tutoring those at risk of failing the CAHSEE is targeted at those in grade 12…

  12. 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...

  13. 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,...

  14. The Tutoring and Dropout Prevention Program at Boys and Girls High School.

    ERIC Educational Resources Information Center

    Bedford-Stuyvesant Restoration Corp., Brooklyn, NY.

    In this project report problems with the tutoring program, objectives of the program and strategies employed by the program to deal with the problems are outlined. The school, Boys and Girls High School, its environment, and the program's sponsor, the Bedford Stuyvesant Restoration Corporation, Brooklyn, are described briefly. Results of the…

  15. 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...

  16. 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...

  17. 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 …

  18. Classroom Goal Structures and HIV and Pregnancy Prevention Education in Rural High School Health Classrooms

    ERIC Educational Resources Information Center

    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 and pregnancy instruction, 3 months after instruction, and 1 year after instruction). Results indicated…

  19. 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…

  20. Preventing Sudden Cardiac Death: Automated External Defibrillators in Ohio High Schools

    PubMed Central

    Lear, Aaron; Hoang, Minh-Ha; Zyzanski, Stephen J.

    2015-01-01

    Context Ohio passed legislation in 2004 for optional public funding of automated external defibrillators (AEDs) in all Ohio high schools. Objective To report occurrences of sudden cardiac arrest in which AEDs were used in Ohio high schools and to evaluate the adherence of Ohio high schools with AEDs to state law and published guidelines on AEDs and emergency action plans (EAPs) in schools. Design Cross-sectional survey. Setting Web-based survey. Patients or Other Participants A total of 264 of 827 schools that were members of the Ohio High School Athletic Association. Main Outcome Measure(s) We surveyed schools on AED use, AED maintenance, and EAPs. Results Twenty-five episodes of AED deployment at 22 schools over an 11-year period were reported; 8 (32%) involved students and 17 (68%) involved adults. The reported survival rate was 60% (n = 15). Most events (n = 20, 80%) in both students and adults occurred at or near athletic facilities. The annual use rate of AEDs was 0.7%. Fifty-three percent (n = 140) of schools reported having an EAP in place for episodes of cardiac arrest. Of the schools with EAPs, 57% (n = 80) reported having rehearsed them. Conclusions Our data supported the placement of AEDs in high schools given the frequency of use for sudden cardiac arrest and the survival rate reported. They also suggested the need for increased awareness of recommendations for EAPs and the need to formulate and practice EAPs. School EAPs should emphasize planning for events in the vicinity of athletic facilities. PMID:26381367

  1. The fallacy of enrolling only high-risk subjects in cancer prevention trials: Is there a "free lunch"?

    PubMed Central

    Baker, Stuart G; Kramer, Barnett S; Corle, Donald

    2004-01-01

    Background There is a common belief that most cancer prevention trials should be restricted to high-risk subjects in order to increase statistical power. This strategy is appropriate if the ultimate target population is subjects at the same high-risk. However if the target population is the general population, three assumptions may underlie the decision to enroll high-risk subject instead of average-risk subjects from the general population: higher statistical power for the same sample size, lower costs for the same power and type I error, and a correct ratio of benefits to harms. We critically investigate the plausibility of these assumptions. Methods We considered each assumption in the context of a simple example. We investigated statistical power for fixed sample size when the investigators assume that relative risk is invariant over risk group, but when, in reality, risk difference is invariant over risk groups. We investigated possible costs when a trial of high-risk subjects has the same power and type I error as a larger trial of average-risk subjects from the general population. We investigated the ratios of benefit to harms when extrapolating from high-risk to average-risk subjects. Results Appearances here are misleading. First, the increase in statistical power with a trial of high-risk subjects rather than the same number of average-risk subjects from the general population assumes that the relative risk is the same for high-risk and average-risk subjects. However, if the absolute risk difference rather than the relative risk were the same, the power can be less with the high-risk subjects. In the analysis of data from a cancer prevention trial, we found that invariance of absolute risk difference over risk groups was nearly as plausible as invariance of relative risk over risk groups. Therefore a priori assumptions of constant relative risk across risk groups are not robust, limiting extrapolation of estimates of benefit to the general population

  2. Analysis of baseline by treatment interactions in a drug prevention and health promotion program for high school male athletes.

    PubMed

    Fritz, Matthew S; MacKinnon, David P; Williams, Jason; Goldberg, Linn; Moe, Esther L; Elliot, Diane L

    2005-06-01

    This paper investigates baseline by treatment interactions (BTI) of a randomized anabolic steroid prevention program delivered to high school football players. Baseline by treatment interactions occur when a participant's score on an outcome variable is associated with both their pretreatment standing on the outcome variable and the treatment itself. The program was delivered to 31 high school football teams (Control=16, Treatment=15) in Oregon and Washington over the course of 3 years (Total N=3207). Although most interactions were nonsignificant, consistent baseline by treatment interactions were obtained for knowledge of the effects of steroid use and intentions to use steroids. Both of these interactions were beneficial in that they increased the effectiveness of the program for participants lower in knowledge and higher in intentions at baseline.

  3. Resveratrol Prevents β-Cell Dedifferentiation in Nonhuman Primates Given a High-Fat/High-Sugar Diet

    PubMed Central

    Fiori, Jennifer L.; Shin, Yu-Kyong; Kim, Wook; Krzysik-Walker, Susan M.; González-Mariscal, Isabel; Carlson, Olga D.; Sanghvi, Mitesh; Moaddel, Ruin; Farhang, Kathleen; Gadkaree, Shekhar K.; Doyle, Maire E.; Pearson, Kevin J.; Mattison, Julie A.; de Cabo, Rafael; Egan, Josephine M.

    2013-01-01

    Eating a “Westernized” diet high in fat and sugar leads to weight gain and numerous health problems, including the development of type 2 diabetes mellitus (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerhans, and improves insulin action. Although rodent models are helpful for understanding β-cell biology and certain aspects of T2DM pathology, they fail to reproduce the complexity of the human disease as well as that of nonhuman primates. Rhesus monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months, and pancreata were examined before overt dysglycemia occurred. Increased glucose-stimulated insulin secretion and insulin resistance occurred in both HFS and HFS+Resv diets compared with SD. Although islet size was unaffected, there was a significant decrease in β-cells and an increase in α-cells containing glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys were morphologically similar to SD. HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6–1, NKX2–2, and PDX1, which did not occur with resveratrol supplementation. Similar changes were observed in human islets where the effects of resveratrol were mediated through Sirtuin 1. These findings have implications for the management of humans with insulin resistance, prediabetes, and diabetes. PMID:23884882

  4. High post-annealing stability for perpendicular [Co/Ni] n multilayers by preventing interfacial diffusion

    NASA Astrophysics Data System (ADS)

    Li, Xu-Jing; Jiang, Shao-Long; Zhang, Jing-Yan; Han, Gang; Liu, Qian-Qian; Liu, Yi-Wei; Wang, Dong-Wei; Feng, Chun; Li, Ming-Hua; Yu, Guang-Hua

    2016-05-01

    This paper reports that by introducing an appropriate thickness of Cu spacer at a Co/Ni interface, the perpendicular magnetic anisotropy of [Co/Cu/Ni] n multilayers can be maintained at the annealing temperature as high as 400 °C, implying high post-annealing stability. X-ray reflectivity results demonstrate that the multilayers with Cu spacer exhibit good multilayer structure, indicating the weak intermixing of Co and Ni, which is one important reason for the enhanced post-annealing stability of perpendicular magnetic anisotropy. The result is of great importance for out-of-plane magnetized spintronic devices which need to be combined with complementary metal-oxide semiconductors.

  5. High-risk behaviors among adult men and women in Botswana: Implications for HIV/AIDS prevention efforts

    PubMed Central

    Keetile, Mpho

    2014-01-01

    Abstract 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. PMID:25293869

  6. 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

  7. 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.

  8. Early Identification and Prevention of the Spread of Ebola in High-Risk African Countries.

    PubMed

    Breakwell, Lucy; Gerber, A Russell; Greiner, Ashley L; Hastings, Deborah L; Mirkovic, Kelsey; Paczkowski, Magdalena M; Sidibe, Sekou; Banaski, James; Walker, Chastity L; Brooks, Jennifer C; Caceres, Victor M; Arthur, Ray R; Angulo, Frederick J

    2016-07-08

    In the late summer of 2014, it became apparent that improved preparedness was needed for Ebola virus disease (Ebola) in at-risk countries surrounding the three highly affected West African countries (Guinea, Sierra Leone, and Liberia). The World Health Organization (WHO) identified 14 nearby African countries as high priority to receive technical assistance for Ebola preparedness; two additional African countries were identified at high risk for Ebola introduction because of travel and trade connections. To enhance the capacity of these countries to rapidly detect and contain Ebola, CDC established the High-Risk Countries Team (HRCT) to work with ministries of health, CDC country offices, WHO, and other international organizations. From August 2014 until the team was deactivated in May 2015, a total of 128 team members supported 15 countries in Ebola response and preparedness. In four instances during 2014, Ebola was introduced from a heavily affected country to a previously unaffected country, and CDC rapidly deployed personnel to help contain Ebola. The first introduction, in Nigeria, resulted in 20 cases and was contained within three generations of transmission; the second and third introductions, in Senegal and Mali, respectively, resulted in no further transmission; the fourth, also in Mali, resulted in seven cases and was contained within two generations of transmission. Preparedness activities included training, developing guidelines, assessing Ebola preparedness, facilitating Emergency Operations Center establishment in seven countries, and developing a standardized protocol for contact tracing. CDC's Field Epidemiology Training Program Branch also partnered with the HRCT to provide surveillance training to 188 field epidemiologists in Côte d'Ivoire, Guinea-Bissau, Mali, and Senegal to support Ebola preparedness. Imported cases of Ebola were successfully contained, and all 15 priority countries now have a stronger capacity to rapidly detect and contain

  9. Early Identification and Prevention of the Spread of Ebola in High-Risk African Countries.

    PubMed

    Breakwell, Lucy; Gerber, A Russell; Greiner, Ashley L; Hastings, Deborah L; Mirkovic, Kelsey; Paczkowski, Magdalena M; Sidibe, Sekou; Banaski, James; Walker, Chastity L; Brooks, Jennifer C; Caceres, Victor M; Arthur, Ray R; Angulo, Frederick J

    2016-01-01

    In the late summer of 2014, it became apparent that improved preparedness was needed for Ebola virus disease (Ebola) in at-risk countries surrounding the three highly affected West African countries (Guinea, Sierra Leone, and Liberia). The World Health Organization (WHO) identified 14 nearby African countries as high priority to receive technical assistance for Ebola preparedness; two additional African countries were identified at high risk for Ebola introduction because of travel and trade connections. To enhance the capacity of these countries to rapidly detect and contain Ebola, CDC established the High-Risk Countries Team (HRCT) to work with ministries of health, CDC country offices, WHO, and other international organizations. From August 2014 until the team was deactivated in May 2015, a total of 128 team members supported 15 countries in Ebola response and preparedness. In four instances during 2014, Ebola was introduced from a heavily affected country to a previously unaffected country, and CDC rapidly deployed personnel to help contain Ebola. The first introduction, in Nigeria, resulted in 20 cases and was contained within three generations of transmission; the second and third introductions, in Senegal and Mali, respectively, resulted in no further transmission; the fourth, also in Mali, resulted in seven cases and was contained within two generations of transmission. Preparedness activities included training, developing guidelines, assessing Ebola preparedness, facilitating Emergency Operations Center establishment in seven countries, and developing a standardized protocol for contact tracing. CDC's Field Epidemiology Training Program Branch also partnered with the HRCT to provide surveillance training to 188 field epidemiologists in Côte d'Ivoire, Guinea-Bissau, Mali, and Senegal to support Ebola preparedness. Imported cases of Ebola were successfully contained, and all 15 priority countries now have a stronger capacity to rapidly detect and contain

  10. 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

  11. 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

  12. Low Magnitude and High Frequency Mechanical Loading Prevents Decreased Bone Formation Responses of 2T3 Preosteoblasts

    PubMed Central

    Patel, Mamta J.; Chang, Kyungh Hwa; Sykes, Michelle C.; Talish, Roger; Rubin, Clinton; Jo, Hanjoong

    2009-01-01

    Bone loss due to osteoporosis or disuse such as in paraplegia or microgravity is a significant health problem. As a treatment for osteoporosis, brief exposure of intact animals or humans to low magnitude and high frequency (LMHF) mechanical loading has been shown to normalize and prevent bone loss. However, the underlying molecular changes and the target cells by which LMHF mechanical loading alleviate bone loss are not known. Here, we hypothesized that direct application of LMHF mechanical loading to osteoblasts alters their cell responses, preventing decreased bone formation induced by disuse or microgravity conditions. To test our hypothesis, preosteoblast 2T3 cells were exposed to a disuse condition using the Random Positioning Machine (RPM) and intervened with an LMHF mechanical load (0.1-0.4g at 30Hz for 10-60 min/day). Exposure of 2T3 cells to the RPM decreased bone formation responses as determined by alkaline phosphatase (ALP) activity and mineralization even in the presence of a submaximal dose of BMP4 (20ng/ml). However, LMHF mechanical loading prevented the RPM-induced decrease in ALP activity and mineralization. Mineralization induced by LMHF mechanical loading was enhanced by treatment with bone morphogenic protein 4 (BMP4) and blocked by the BMP antagonist noggin, suggesting a role for BMPs in this response. In addition, LMHF mechanical loading rescued the RPM-induced decrease in gene expression of ALP, runx2, osteomodulin, parathyroid hormone receptor 1, and osteoglycin. These findings suggest that preosteoblasts may directly respond to LMHF mechanical loading to induce differentiation responses. The mechanosensitive genes identified here provide potential targets for pharmaceutical treatments that may be used in combination with low level mechanical loading to better treat osteoporosis or disuse-induced bone loss. PMID:19125415

  13. 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

  14. Experience-oriented tobacco-use prevention lecture using a COPD-simulation mask for junior high school students.

    PubMed

    Iizuka, Makito; Tomita, Kazuhide; Takeshima, Reiko

    2015-04-01

    We recently developed a mask that simulates the experience of having one of the major diseases caused by tobacco smoking: chronic obstructive pulmonary disease (COPD). Here we examined the effects of a tobacco-use prevention lecture accompanied by a pseudo-COPD experience created with this mask on adolescents' attitude toward smoking. Junior high school students (12-13 years old, n=165) in Japan were the subjects. The students attended a 30-min tobacco-use prevention lecture with slides and movie clips and engaged in a light exercise session wearing the COPD-simulation mask for 15min. Before and after the lecture, the students' attitudes toward smoking were evaluated by the Kano test for social nicotine dependence (KTSND). The total KTSND scores decreased significantly from 9.9±4.4 (mean±SD, n=149) to 7.5±5.3 (n=144). Ninety-eight students wore the COPD mask, and their modified Borg scale scores increased significantly from 0.7±1.0 to 3.2±2.1 after exercise (P<0.0001). To the questionnaire item "Do you think you understand the suffering of individuals with COPD?", 24 and 51 students answered "definitely yes" and "yes", whereas 16, 4 and 1 answered "Cannot say," "no" and "definitely no", respectively. The KTSND scores were significantly smaller in the former affirmative group compared to the latter negative group (P<0.05). Of the 98 students who wore the simulation mask, 83 reported being satisfied with this pseudo-COPD experience. The tobacco-use prevention lecture with the pseudo-COPD experience created by the simulation mask was effective and safe.

  15. 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

  16. 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.

  17. 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.

  18. Economic value of atopic dermatitis prevention via infant formula use in high-risk Malaysian infants

    PubMed Central

    Bhanegaonkar, Abhijeet J; Horodniceanu, Erica G; Abdul Latiff, Amir Hamzah; Woodhull, Sanjay; Khoo, Phaik Choo; Detzel, Patrick; Ji, Xiang

    2015-01-01

    Background Breastfeeding is best for infants and the World Health Organization recommends exclusive breastfeeding for at least the first 6 months of life. For those who are unable to be breastfed, previous studies demonstrate that feeding high-risk infants with hydrolyzed formulas instead of cow's milk formula (CMF) may decrease the risk of atopic dermatitis (AD). Objective To estimate the economic impact of feeding high-risk, not exclusively breastfed, urban Malaysian infants with partiallyhydrolyzed whey-based formula (PHF-W) instead of CMF for the first 17 weeks of life as an AD risk reduction strategy. Methods A cohort Markov model simulated the AD incidence and burden from birth to age 6 years in the target population fed with PHF-W vs. CMF. The model integrated published clinical and epidemiologic data, local cost data, and expert opinion. Modeled outcomes included AD-risk reduction, time spent post AD diagnosis, days without AD flare, quality-adjusted life years (QALYs), and costs (direct and indirect). Outcomes were discounted at 3% per year. Costs are expressed in Malaysian Ringgit (MYR; MYR 1,000 = United States dollar [US $]316.50). Results Feeding a high-risk infant PHF-W vs. CMF resulted in a 14% point reduction in AD risk (95% confidence interval [CI], 3%-23%), a 0.69-year (95% CI, 0.25-1.10) reduction in time spent post-AD diagnosis, additional 38 (95% CI, 2-94) days without AD flare, and an undiscounted gain of 0.041 (95% CI, 0.007-0.103) QALYs. The discounted AD-related 6-year cost estimates when feeding a high-risk infant with PHF-W were MYR 1,758 (US $556) (95% CI, MYR 917-3,033) and with CMF MYR 2,871 (US $909) (95% CI, MYR 1,697-4,278), resulting in a per-child net saving of MYR 1,113 (US $352) (95% CI, MYR 317-1,884) favoring PHF-W. Conclusion Using PHF-W instead of CMF in this population is expected to result in AD-related costs savings. PMID:25938073

  19. 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.

  20. High β-cell mass prevents streptozotocin-induced diabetes in thioredoxin-interacting protein-deficient mice

    PubMed Central

    Masson, Elodie; Koren, Shlomit; Razik, Fathima; Goldberg, Howard; Kwan, Edwin P.; Sheu, Laura; Gaisano, Herbert Y.; Fantus, I. George

    2010-01-01

    Thioredoxin-interacting protein (TxNIP) is an endogenous inhibitor of thioredoxin, a ubiquitous thiol oxidoreductase, that regulates cellular redox status. Diabetic mice exhibit increased expression of TxNIP in pancreatic islets, and recent studies suggest that TxNIP is a proapoptotic factor in β-cells that may contribute to the development of diabetes. Here, we examined the role of TxNIP deficiency in vivo in the development of insulin-deficient diabetes and whether it impacted on pancreatic β-cell mass and/or insulin secretion. TxNIP-deficient (Hcb-19/TxNIP−/−) mice had lower baseline glycemia, higher circulating insulin concentrations, and higher total pancreatic insulin content and β-cell mass than control mice (C3H). Hcb-19/TxNIP−/− did not develop hyperglycemia when injected with standard multiple low doses of streptozotocin (STZ), in contrast to C3H controls. Surprisingly, although β-cell mass remained higher in Hcb-19/TxNIP−/− mice compared with C3H after STZ exposure, the relative decrease induced by STZ was as great or even greater in the TxNIP-deficient animals. Consistently, cultured pancreatic INS-1 cells transfected with small-interfering RNA against TxNIP were more sensitive to cell death induced by direct exposure to STZ or to the combination of inflammatory cytokines interleukin-1β, interferon-γ, and tumor necrosis factor-α. Furthermore, when corrected for insulin content, isolated pancreatic islets from TxNIP−/− mice exhibited reduced glucose-induced insulin secretion. These data indicate that TxNIP functions as a regulator of β-cell mass and influences insulin secretion. In conclusion, the relative resistance of TxNIP-deficient mice to STZ-induced diabetes appears to be because of an increase in β-cell mass. However, TxNIP deficiency is associated with sensitization to STZ- and cytokine-induced β-cell death, indicating complex regulatory roles of TxNIP under different physiological and pathological conditions. PMID

  1. Oral Resveratrol Prevents Osteoarthritis Progression in C57BL/6J Mice Fed a High-Fat Diet

    PubMed Central

    Gu, Hailun; Li, Keyu; Li, Xingyao; Yu, Xiaolu; Wang, Wei; Ding, Lifeng; Liu, Li

    2016-01-01

    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. PMID:27104565

  2. Preventing overtraining in athletes in high-intensity sports and stress/recovery monitoring.

    PubMed

    Kellmann, M

    2010-10-01

    In sports, the importance of optimizing the recovery-stress state is critical. Effective recovery from intense training loads often faced by elite athletes can often determine sporting success or failure. In recent decades, athletes, coaches, and sport scientists have been keen to find creative, new methods for improving the quality and quantity of training for athletes. These efforts have consistently faced barriers, including overtraining, fatigue, injury, illness, and burnout. Physiological and psychological limits dictate a need for research that addresses the avoidance of overtraining, maximizes recovery, and successfully negotiates the fine line between high and excessive training loads. Monitoring instruments like the Recovery-Stress Questionnaire for Athletes can assist with this research by providing a tool to assess their perceived state of recovery. This article will highlight the importance of recovery for elite athletes and provide an overview of monitoring instruments.

  3. 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.

  4. High density lipoproteins and prevention of experimental atherosclerosis with special reference to tree shrews.

    PubMed

    She, M P; Xia, R Y; Ran, B F; Wong, Z L

    1990-01-01

    According to data obtained from epidemiological and experimental survey, serum HDL level is known to be correlated conversely with the incidence of atherosclerosis. Experimental data collected in this article explained part of its mechanism, which is described in four parts as follows: 1. The result of 3 successive experiments on experimental atherosclerosis in tree shrews (total of 96 animals available including 40 as the controls) showed that the serum HDL level had been kept persistantly to 69-88% of the total serum lipoproteins even after a high cholesterol intake for 32 weeks. The incidence of atheromatous lesions developed was only 0-9%, but the incidence of gall stone was very high, 48-84% by gross examination by the end of these experiments. 2. HDL are also capable of (1) promotion of monocyte migration activity; (2) enhancement of cholesterol clearance rate of aortic smooth muscle cells originally isolated from either rabbits or tree shrews; (3) inhibition of 20% of LDL degradation but with no inhibitory effect obtained on Ac-LDL degradation in the endothelial cells; (4) presence of specific binding sites for apo E free HDL on the surface of aortic smooth muscle cells from either rabbits or tree shrews which recognizes apo A1 as a ligand. 3. Data from 2 successive experiments in rabbits showed that HDL lipoproteins (mainly apo A1) possess an inhibitory effect on the development of atheromatous plaques, but not a very strong one. 4. The colesterol clearance effect of smooth muscle cells was markedly enhanced by apo A1/phospholipid liposomes (the apo A1 used was isolated from either rabbit's or tree shrew's serum) in vitro. PMID:2123379

  5. High density lipoproteins and prevention of experimental atherosclerosis with special reference to tree shrews.

    PubMed

    She, M P; Xia, R Y; Ran, B F; Wong, Z L

    1990-01-01

    According to data obtained from epidemiological and experimental survey, serum HDL level is known to be correlated conversely with the incidence of atherosclerosis. Experimental data collected in this article explained part of its mechanism, which is described in four parts as follows: 1. The result of 3 successive experiments on experimental atherosclerosis in tree shrews (total of 96 animals available including 40 as the controls) showed that the serum HDL level had been kept persistantly to 69-88% of the total serum lipoproteins even after a high cholesterol intake for 32 weeks. The incidence of atheromatous lesions developed was only 0-9%, but the incidence of gall stone was very high, 48-84% by gross examination by the end of these experiments. 2. HDL are also capable of (1) promotion of monocyte migration activity; (2) enhancement of cholesterol clearance rate of aortic smooth muscle cells originally isolated from either rabbits or tree shrews; (3) inhibition of 20% of LDL degradation but with no inhibitory effect obtained on Ac-LDL degradation in the endothelial cells; (4) presence of specific binding sites for apo E free HDL on the surface of aortic smooth muscle cells from either rabbits or tree shrews which recognizes apo A1 as a ligand. 3. Data from 2 successive experiments in rabbits showed that HDL lipoproteins (mainly apo A1) possess an inhibitory effect on the development of atheromatous plaques, but not a very strong one. 4. The colesterol clearance effect of smooth muscle cells was markedly enhanced by apo A1/phospholipid liposomes (the apo A1 used was isolated from either rabbit's or tree shrew's serum) in vitro.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Acute Thermotherapy Prevents Impairments in Cutaneous Microvascular Function Induced by a High Fat Meal.

    PubMed

    Harvey, Jennifer C; Roseguini, Bruno T; Goerger, Benjamin M; Fallon, Elizabeth A; Wong, Brett J

    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

  11. 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.

  12. Nuciferine Prevents Hepatic Steatosis and Injury Induced by a High-Fat Diet in Hamsters

    PubMed Central

    Li, Xiaoxia; Feng, Rennan; Guan, Chunmei; Wang, Yanwen; Li, Ying; Sun, Changhao

    2013-01-01

    Background Nuciferine is a major active aporphine alkaloid from the leaves of N. nucifera Gaertn that possesses anti-hyperlipidemia, anti-hypotensive, anti-arrhythmic, and insulin secretagogue activities. However, it is currently unknown whether nuciferine can benefit hepatic lipid metabolism. Methodology/Principal Findings In the current study, male golden hamsters were randomly divided into four groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with nuciferine (10 and 15 mg/kg·BW/day). After 8 weeks of intervention, HFD-induced increases in liver and visceral adipose tissue weight, dyslipidemia, liver steatosis, and mild necroinflammation in hamsters were analyzed. Nuciferine supplementation protected against HFD-induced changes, alleviated necroinflammation, and reversed serum markers of metabolic syndrome in hamsters fed a HFD. RT-PCR and western blot analyses revealed that hamsters fed a HFD had up-regulated levels of genes related to lipogenesis, increased free fatty acid infiltration, and down-regulated genes involved in lipolysis and very low density lipoprotein secretion. In addition, gene expression of cytochrome P4502E1 and tumor necrosis factor-α were also increased in the HFD group. Nuciferine supplementation clearly suppressed HFD-induced alterations in the expression of genes involved in lipid metabolism. Conclusions/Significance Nuciferine supplementation ameliorated HFD-induced dyslipidemia as well as liver steatosis and injury. The beneficial effects of nuciferine were associated with altered expression of hepatic genes involved in lipid metabolism. PMID:23691094

  13. Erchen Decoction Prevents High-Fat Diet Induced Metabolic Disorders in C57BL/6 Mice

    PubMed Central

    Gao, Bi-Zhen; Chen, Ji-Cheng; Liao, Ling-Hong; Xu, Jia-Qi; Lin, Xiao-Feng; Ding, Shan-Shan

    2015-01-01

    Erchen decoction (ECD) is a traditional Chinese medicine prescription, which is used in the treatment of obesity, hyperlipidemia, fatty liver, diabetes, hypertension, and other diseases caused by retention of phlegm dampness. In this study we investigated the potential mechanism of ECD, using metabolism-disabled mice induced by high-fat diet. Body weight and abdominal circumference were detected. OGTT was measured by means of collecting blood samples from the tail vein. Blood lipid levels and insulin were measured using biochemical assay kit. Real-time PCR was used to measure the CDKAL1 gene expression and western blot was used to measure the protein expression. Through the research, it was found that ECD showed markedly lower body weight and abdominal circumference than those in the HFD group. Consistently, we observed that ECD significantly improved glucose tolerance, promoted the secretion of insulin and decreased the level of TG, TC level. Meanwhile, we observed significantly increased CDKAL1 mRNA and protein level in the ECD group. Therefore, we speculate that the potential molecular mechanism of ECD is to promote the CDKAL1 expression, ameliorate islet cell function, and raise insulin levels to regulate the metabolic disorder. PMID:26504476

  14. N-Acetylneuraminic Acid Supplementation Prevents High Fat Diet-Induced Insulin Resistance in Rats through Transcriptional and Nontranscriptional Mechanisms

    PubMed Central

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ismail, Norsharina; Azmi, Nur Hanisah; Wong, Waiteng; Altine Adamu, Hadiza; Md Zamri, Nur Diyana; Ideris, Aini; Abdullah, Maizaton Atmadini

    2015-01-01

    N-Acetylneuraminic acid (Neu5Ac) is a biomarker of cardiometabolic diseases. In the present study, we tested the hypothesis that dietary Neu5Ac may improve cardiometabolic indices. A high fat diet (HFD) + Neu5Ac (50 or 400 mg/kg BW/day) was fed to rats and compared with HFD + simvastatin (10 mg/kg BW/day) or HFD alone for 12 weeks. Weights and serum biochemicals (lipid profile, oral glucose tolerance test, leptin, adiponectin, and insulin) were measured, and mRNA levels of insulin signaling genes were determined. The results indicated that low and high doses of sialic acid (SA) improved metabolic indices, although only the oral glucose tolerance test, serum triglycerides, leptin, and adiponectin were significantly better than those in the HFD and HFD + simvastatin groups (P < 0.05). Furthermore, the results showed that only high-dose SA significantly affected the transcription of hepatic and adipose tissue insulin signaling genes. The data suggested that SA prevented HFD-induced insulin resistance in rats after 12 weeks of administration through nontranscriptionally mediated biochemical changes that may have differentially sialylated glycoprotein structures at a low dose. At higher doses, SA induced transcriptional regulation of insulin signaling genes. These effects suggest that low and high doses of SA may produce similar metabolic outcomes in relation to insulin sensitivity through multiple mechanisms. These findings are worth studying further. PMID:26688813

  15. Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance and dysfunction in rats.

    PubMed

    Babacanoglu, C; Yildirim, N; Sadi, G; Pektas, M B; Akar, F

    2013-10-01

    Dietary intake of fructose and sucrose can cause development of metabolic and cardiovascular disorders. The consequences of high-fructose corn syrup (HFCS), a commonly consumed form of fructose and glucose, have poorly been examined. Therefore, in this study, we investigated whether HFCS intake (10% and 20% beverages for 12 weeks) impacts vascular reactivity to insulin and endothelin-1 in conjunction with insulin receptor substrate-1(IRS-1), endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) mRNA/proteins levels in aorta of rats. At challenge, we tested the effectiveness of resveratrol (28-30 mg/kg body weight/day) on outcomes of HFCS feeding. HFCS (20%) diet feeding increased plasma triglyceride, VLDL, cholesterol, insulin and glucose levels, but not body weights of rats. Impaired nitric oxide-mediated relaxation to insulin (10⁻⁹ to 3×10⁻⁶ M), and enhanced contraction to endothelin-1 (10⁻¹¹ to 10⁻⁸ M) were associated with decreased expression of IRS-1 and eNOS mRNA and protein, but increased expression of iNOS, in aortas of rats fed with HFCS. Resveratrol supplementation restored many features of HFCS-induced disturbances, probably by regulating eNOS and iNOS production. In conclusion, dietary HFCS causes vascular insulin resistance and endothelial dysfunction through attenuating IRS-1 and eNOS expressions as well as increasing iNOS in rats. Resveratrol has capability to recover HFCS-induced disturbances. PMID:23872130

  16. Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance and dysfunction in rats.

    PubMed

    Babacanoglu, C; Yildirim, N; Sadi, G; Pektas, M B; Akar, F

    2013-10-01

    Dietary intake of fructose and sucrose can cause development of metabolic and cardiovascular disorders. The consequences of high-fructose corn syrup (HFCS), a commonly consumed form of fructose and glucose, have poorly been examined. Therefore, in this study, we investigated whether HFCS intake (10% and 20% beverages for 12 weeks) impacts vascular reactivity to insulin and endothelin-1 in conjunction with insulin receptor substrate-1(IRS-1), endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) mRNA/proteins levels in aorta of rats. At challenge, we tested the effectiveness of resveratrol (28-30 mg/kg body weight/day) on outcomes of HFCS feeding. HFCS (20%) diet feeding increased plasma triglyceride, VLDL, cholesterol, insulin and glucose levels, but not body weights of rats. Impaired nitric oxide-mediated relaxation to insulin (10⁻⁹ to 3×10⁻⁶ M), and enhanced contraction to endothelin-1 (10⁻¹¹ to 10⁻⁸ M) were associated with decreased expression of IRS-1 and eNOS mRNA and protein, but increased expression of iNOS, in aortas of rats fed with HFCS. Resveratrol supplementation restored many features of HFCS-induced disturbances, probably by regulating eNOS and iNOS production. In conclusion, dietary HFCS causes vascular insulin resistance and endothelial dysfunction through attenuating IRS-1 and eNOS expressions as well as increasing iNOS in rats. Resveratrol has capability to recover HFCS-induced disturbances.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. The Prevention of Diabetic Cardiomyopathy by Non-Mitogenic Acidic Fibroblast Growth Factor Is Probably Mediated by the Suppression of Oxidative Stress and Damage

    PubMed Central

    Zhang, Chi; Zhang, Linbo; Chen, Shali; Feng, Biao; Lu, Xuemian; Bai, Yang; Liang, Guang; Tan, Yi; Shao, Minglong; Skibba, Melissa; Jin, Litai; Li, Xiaokun; Chakrabarti, Subrata; Cai, Lu

    2013-01-01

    Background Emerging evidence showed the beneficial effect of acidic fibroblast growth factor (aFGF) on heart diseases. The present study investigated whether non-mitogenic aFGF (nm-aFGF) can prevent diabetic cardiomyopathy and the underlying mechanisms, if any. Methodology/Principal Findings Type 1 diabetes was induced in mice by multiple intraperitoneal injections of low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without nm-aFGF at 10 µg/kg daily for 1 and 6 months. Blood pressure and cardiac function were assessed. Cardiac H9c2 cell, human microvascular endothelial cells, and rat cardiomyocytes were exposed to high glucose (25 mM) for mimicking an in vitro diabetic condition for mechanistic studies. Oxidative stress, DNA damage, cardiac hypertrophy and fibrosis were assessed by real-time qPCR, immunofluorescent staining, Western blotting, and pathological examination. Nm-aFGF significantly prevented diabetes-induced hypertension and cardiac dysfunction at 6 months. Mechanistic studies demonstrated that nm-aFGF showed the similar preventive effect as the native aFGF on high glucose-induced oxidative stress (increase generation of reactive oxygen species) and damage (cellular DNA oxidation), cell hypertrophy, and fibrotic response (increased mRNA expression of fibronectin) in three kinds of cells. These in vitro findings were recaptured by examining the heart of the diabetic mice with and without nm-aFGF. Conclusions These results suggest that nm-aFGF can prevent diabetic cardiomyopathy, probably through attenuation of cardiac oxidative stress, hypertrophy, and fibrosis. PMID:24349248

  2. Caveolin-1 prevents sustained angiotensin II-induced resistance artery constriction and obesity-induced high blood pressure

    PubMed Central

    Czikora, Istvan; Feher, Attila; Lucas, Rudolf; Fulton, David J. R.

    2014-01-01

    The type 1 angiotensin II (ANG II) receptor (AT1R) undergoes internalization following stimulation by ANG II. Internalization reduces cell surface AT1Rs, and it is required for AT1R resensitization. In this process AT1R may interact with caveolin-1 (Cav1), the main scaffolding protein of caveolae. We hypothesized that the interaction between Cav1 and AT1R delays AT1R resensitization and thereby prevents sustained ANG II-induced resistance artery (RA) constriction under normal conditions and in experimental obesity. In rat and mouse skeletal muscle RA (diameter: ∼90–120 μm) ANG II-induced constrictions were reduced upon repeated (30-min apart) administrations. Upon disruption of caveolae with methyl-β-cyclodextrin or in RA of Cav1 knockout mice, repeated ANG II applications resulted in essentially maintained constrictions. In vascular smooth muscle cells, AT1R interacted with Cav1, and the degree of cell surface interactions was reduced by long-term (15-min), but not short-term (2-min), exposure to ANG II. When Cav1 was silenced, the amount of membrane-associated AT1R was significantly reduced by a short-term ANG II exposure. Moreover, Cav1 knockout mice fed a high-fat diet exhibited augmented and sustained RA constriction to ANG II and had elevated systemic blood pressure, when compared with normal or high-fat fed wild-type mice. Thus, Cav1, through a direct interaction, delays internalization and subsequent resensitization of AT1R. We suggest that this mechanism prevents sustained ANG II-induced RA constriction and elevated systemic blood pressure in diet-induced obesity. PMID:25527780

  3. Prevention of high fructose-induced metabolic syndrome in male wistar rats by aqueous extract of Tamarindus indica seed.

    PubMed

    Shahraki, Mohammd Reza; Harati, Mehdi; Shahraki, Ahamd Reza

    2011-01-01

    Tamarindus indica is used as a traditional treatment for diabetes. To elucidate whether Tamarindus indica seed aqueous extract (TSE) ameliorates metabolic syndrome in hyperinsulinemic rats, we evaluated serum insulin, dehydroepiandrosterone sulfate (DHEAS), triglyceride (TG), total cholesterol (TC), very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), and glucose levels in fructose-fed rats. Animals were divided into three groups; control (C) receiving tap water, fructose-fed (F) and TSE-treated fructose-fed rats (F-T) both receiving tap water supplemented with 10% (w/v) fructose. Water was prepared every day for a period of 8 weeks for all three groups. F-T rats were fed with TSE via gavage feeding at the dose of 20 mg/0.5 ml distilled water/100 g body weight per day. Fasting serum glucose levels of three groups were comparable. TSE treatment prevented the increase in fasting serum insulin, TG, TC, VLDL, and LDL in the F-T group (P<0.01) when comparing with the F group. Fructose feeding led to a decrease in fasting serum DHEAS, and HDL levels in the F group (P<0.01) compared with the control. TSE treatment prevented the decrease in fasting serum DHEAS, and HDL levels in the F-T group (P<0.01) while these results were not seen in control rats. It is indicated that the hyperinsulinemia in fructose-fed insulin resistant rats are associated with low levels of DHEAS, and HDL; and high levels of TC, VLDL, LDL, and TG. TSE supplementation probably ameliorates metabolic syndrome due to the improved insulin action.

  4. Prevention of high fructose-induced metabolic syndrome in male wistar rats by aqueous extract of Tamarindus indica seed.

    PubMed

    Shahraki, Mohammd Reza; Harati, Mehdi; Shahraki, Ahamd Reza

    2011-01-01

    Tamarindus indica is used as a traditional treatment for diabetes. To elucidate whether Tamarindus indica seed aqueous extract (TSE) ameliorates metabolic syndrome in hyperinsulinemic rats, we evaluated serum insulin, dehydroepiandrosterone sulfate (DHEAS), triglyceride (TG), total cholesterol (TC), very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), and glucose levels in fructose-fed rats. Animals were divided into three groups; control (C) receiving tap water, fructose-fed (F) and TSE-treated fructose-fed rats (F-T) both receiving tap water supplemented with 10% (w/v) fructose. Water was prepared every day for a period of 8 weeks for all three groups. F-T rats were fed with TSE via gavage feeding at the dose of 20 mg/0.5 ml distilled water/100 g body weight per day. Fasting serum glucose levels of three groups were comparable. TSE treatment prevented the increase in fasting serum insulin, TG, TC, VLDL, and LDL in the F-T group (P<0.01) when comparing with the F group. Fructose feeding led to a decrease in fasting serum DHEAS, and HDL levels in the F group (P<0.01) compared with the control. TSE treatment prevented the decrease in fasting serum DHEAS, and HDL levels in the F-T group (P<0.01) while these results were not seen in control rats. It is indicated that the hyperinsulinemia in fructose-fed insulin resistant rats are associated with low levels of DHEAS, and HDL; and high levels of TC, VLDL, LDL, and TG. TSE supplementation probably ameliorates metabolic syndrome due to the improved insulin action. PMID:21713743

  5. Analysis of Arabidopsis glucose insensitive growth Mutants Reveals the Involvement of the Plastidial Copper Transporter PAA1 in Glucose-Induced Intracellular Signaling1[W][OA

    PubMed Central

    Lee, Shin Ae; Yoon, Eun Kyung; Heo, Jung-Ok; Lee, Mi-Hyun; Hwang, Indeok; Cheong, Hyeonsook; Lee, Woo Sung; Hwang, Yong-sic; Lim, Jun

    2012-01-01

    Sugars play important roles in many aspects of plant growth and development, acting as both energy sources and signaling molecules. With the successful use of genetic approaches, the molecular components involved in sugar signaling have been identified and their regulatory roles in the pathways have been elucidated. Here, we describe novel mutants of Arabidopsis (Arabidopsis thaliana), named glucose insensitive growth (gig), identified by their insensitivity to high-glucose (Glc)-induced growth inhibition. The gig mutant displayed retarded growth under normal growth conditions and also showed alterations in the expression of Glc-responsive genes under high-Glc conditions. Our molecular identification reveals that GIG encodes the plastidial copper (Cu) transporter PAA1 (for P1B-type ATPase 1). Interestingly, double mutant analysis indicated that in high Glc, gig is epistatic to both hexokinase1 (hxk1) and aba insensitive4 (abi4), major regulators in sugar and retrograde signaling. Under high-Glc conditions, the addition of Cu had no effect on the recovery of gig/paa1 to the wild type, whereas exogenous Cu feeding could suppress its phenotype under normal growth conditions. The expression of GIG/PAA1 was also altered by mutations in the nuclear factors HXK1, ABI3, and ABI4 in high Glc. Furthermore, a transient expression assay revealed the interaction between ABI4 and the GIG/PAA1 promoter, suggesting that ABI4 actively regulates the transcription of GIG/PAA1, likely binding to the CCAC/ACGT core element of the GIG/PAA1 promoter. Our findings indicate that the plastidial Cu transporter PAA1, which is essential for plastid function and/or activity, plays an important role in bidirectional communication between the plastid and the nucleus in high Glc. PMID:22582133

  6. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

    PubMed

    Jaber, Lutfi; Karim, Igbaria A; Jawdat, Abu Moch; Fausi, Mawasi; Merlob, Paul

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P < 0.001). Age and religion had no significant effect. An urgent need exists to improve the awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity).

  7. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

    PubMed

    Jaber, Lutfi; Karim, Igbaria A; Jawdat, Abu Moch; Fausi, Mawasi; Merlob, Paul

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P < 0.001). Age and religion had no significant effect. An urgent need exists to improve the awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity). PMID:15050876

  8. 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. PMID:26233881

  9. 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.

  10. 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

  11. MicroRNA-27a Induces Mesangial Cell Injury by Targeting of PPARγ, and its In Vivo Knockdown Prevents Progression of Diabetic Nephropathy

    PubMed Central

    Wu, Lina; Wang, Qingzhu; Guo, Feng; Ma, Xiaojun; Ji, Hongfei; Liu, Fei; Zhao, Yanyan; Qin, Guijun

    2016-01-01

    MicroRNAs play important roles in the pathogenesis of diabetic nephropathy (DN). In this study, we found that high glucose upregulated miR-27a expression in cultured glomerular mesangial cells and in the kidney glomeruli of streptozotocin (STZ)-induced diabetic rats. miR-27a knockdown prevented high glucose-induced mesangial cell proliferation and also blocked the upregulation of extracellular matrix (ECM)-associated profibrotic genes. Reduction of cell proliferation and profibrotic gene expression by a miR-27a inhibitor depended upon the expression of peroxisome proliferator-activated receptor γ (PPARγ). Further studies showed that miR-27a negatively regulated PPARγ expression by binding to the 3′-untranslated region of rat PPARγ. An antisense oligonucleotide specific to miR-27a (antagomir-27a) significantly reduced renal miR-27a expression in STZ-induced diabetic rats and significantly increased PPARγ levels. Antagomir-27a also reduced kidney ECM accumulation and proteinuria in STZ-induced diabetic rats. These findings suggest that specific reduction of renal miR-27a decreases renal fibrosis, which may be explained in part by its regulation of PPARγ, and that targeting miR-27a may represent a novel therapeutic approach for DN. PMID:27184517

  12. Grape powder supplementation prevents oxidative stress-induced anxiety-like behavior, memory impairment, and high blood pressure in rats.

    PubMed

    Allam, Farida; Dao, An T; Chugh, Gaurav; Bohat, Ritu; Jafri, Faizan; Patki, Gaurav; Mowrey, Christopher; Asghar, Mohammad; Alkadhi, Karim A; Salim, Samina

    2013-06-01

    We examined whether or not grape powder treatment ameliorates oxidative stress-induced anxiety-like behavior, memory impairment, and hypertension in rats. Oxidative stress in Sprague-Dawley rats was produced by using L-buthionine-(S,R)-sulfoximine (BSO). Four groups of rats were used: 1) control (C; injected with vehicle and provided with tap water), 2) grape powder-treated (GP; injected with vehicle and provided for 3 wk with 15 g/L grape powder dissolved in tap water), 3) BSO-treated [injected with BSO (300 mg/kg body weight), i.p. for 7 d and provided with tap water], and 4) BSO plus grape powder-treated (GP+BSO; injected with BSO and provided with grape powder-treated tap water). Anxiety-like behavior was significantly greater in BSO rats compared with C or GP rats (P < 0.05). Grape powder attenuated BSO-induced anxiety-like behavior in GP+BSO rats. BSO rats made significantly more errors in both short- and long-term memory tests compared with C or GP rats (P < 0.05), which was prevented in GP+BSO rats. Systolic and diastolic blood pressure was significantly greater in BSO rats compared with C or GP rats (P < 0.05), whereas grape powder prevented high blood pressure in GP+BSO rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK-1/2) was activated (P < 0.05), whereas levels of glyoxalase-1 (GLO-1), glutathione reductase-1 (GSR-1), calcium/calmodulin-dependent protein kinase type IV (CAMK-IV), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were significantly less (P < 0.05) in BSO but not in GP+BSO rats compared with C or GP rats. We suggest that by regulating brain ERK-1/2, GLO-1, GSR-1, CAMK-IV, CREB, and BDNF levels, grape powder prevents oxidative stress-induced anxiety, memory impairment, and hypertension in rats. PMID:23596160

  13. 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

  14. 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

  15. MicroRNA-134 Contributes to Glucose-Induced Endothelial Cell Dysfunction and This Effect Can Be Reversed by Far-Infrared Irradiation.

    PubMed

    Wang, Hsei-Wei; Su, Shu-Han; 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

  16. 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. PMID:23061828

  17. 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.

  18. 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.

  19. Venous thrombosis in multiple sclerosis patients after high-dose intravenous methylprednisolone: the preventive effect of enoxaparin.

    PubMed

    Kalanie, Hossein; Harandi, Ali Amini; Alidaei, Shapoor; Heidari, Daryoosh; Shahbeigi, Saeed; Ghorbani, Mehdi

    2011-01-01

    Aim. This study was designed to examine the possible role of high-dose intravenous methylprednisolone (IVMP) in the development of venous thrombosis (VT). The cerebral one anecdotally had been reported in patients with relapsing remitting multiple sclerosis (RRMS) in acute attacks and the possible preventive role of enoxaparin. Material and Methods. From a pool of 520 patients, 388 patients with definite RRMS who fulfilled entry characteristics were selected and randomly received either a 5-day course of daily 1 gr IVMP or the aforementioned plus 5 days of daily subcutaneous 40 units of enoxaparin according to a predefined protocol. Results. Mean age, gender ratio, mean relapse rate, and EDSS were similar in both groups of patients (P > 0.05). Finally, 366 patients remained in the study. Of 188 patients treated with IVMP with 855 relapses, 5 developed VT (0.37% per patient per year and 0.58% per each course of IVMP) within 3 to 15 days of starting therapy. None of the 178 patients who experienced 809 relapses who received IVMP plus enoxaparin developed such complications. Conclusion. The study implies that high-dose IVMP in MS exacerbation may increase the risk of VT and prophylactic anticoagulant treatment in this setting is warranted. PMID:22242201

  20. Venous Thrombosis in Multiple Sclerosis Patients after High-Dose Intravenous Methylprednisolone: The Preventive Effect of Enoxaparin

    PubMed Central

    Kalanie, Hossein; Harandi, Ali Amini; Alidaei, Shapoor; Heidari, Daryoosh; Shahbeigi, Saeed; Ghorbani, Mehdi

    2011-01-01

    Aim. This study was designed to examine the possible role of high-dose intravenous methylprednisolone (IVMP) in the development of venous thrombosis (VT). The cerebral one anecdotally had been reported in patients with relapsing remitting multiple sclerosis (RRMS) in acute attacks and the possible preventive role of enoxaparin. Material and Methods. From a pool of 520 patients, 388 patients with definite RRMS who fulfilled entry characteristics were selected and randomly received either a 5-day course of daily 1 gr IVMP or the aforementioned plus 5 days of daily subcutaneous 40 units of enoxaparin according to a predefined protocol. Results. Mean age, gender ratio, mean relapse rate, and EDSS were similar in both groups of patients (P > 0.05). Finally, 366 patients remained in the study. Of 188 patients treated with IVMP with 855 relapses, 5 developed VT (0.37% per patient per year and 0.58% per each course of IVMP) within 3 to 15 days of starting therapy. None of the 178 patients who experienced 809 relapses who received IVMP plus enoxaparin developed such complications. Conclusion. The study implies that high-dose IVMP in MS exacerbation may increase the risk of VT and prophylactic anticoagulant treatment in this setting is warranted. PMID:22242201

  1. Cooperation between HMGA1, PDX-1, and MafA is Essential for Glucose-Induced Insulin Transcription in Pancreatic Beta Cells.

    PubMed

    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.

  2. 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 evaluate…

  3. 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…

  4. 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

  5. Mechanistic evaluation of the glucose-induced reduction in initial burst release of octreotide acetate from poly(D,L-lactide-co-glycolide) microspheres.

    PubMed

    Wang, Juan; Wang, Barbara M; Schwendeman, Steven P

    2004-05-01

    One major obstacle for development of injectable biodegradable microspheres for controlled peptide and protein delivery is the high initial burst of drug release occurring over the first day of incubation. We describe here the significant reduction in initial burst release of a highly water-soluble model peptide, octreotide acetate, from poly(D,L-lactide-co-glycolide) microspheres by the co-encapsulation of a small amount of glucose (e.g., 0.2%w/w), i.e., from 30+/-20% burst - glucose to 8+/-3% + glucose (mean+/-SD, n=4). This reduction is unexpected since hydrophilic additives are known to increase porosity of microspheres, causing an increase in permeability to mass transport and a higher burst. Using the double emulsion-solvent evaporation method of encapsulation, the effect of glucose on initial burst in an acetate buffer pH 4 was found to depend on polymer concentration, discontinuous phase/continuous phase ratio, and glucose content. Extensive characterization studies were performed on two microsphere batches, +/-0.2% glucose, to elucidate the mechanism of this effect. However, no significant difference was observed with respect to specific surface area, porosity, internal and external morphology and drug distribution. Continuous monitoring of the first 24-h release of octreotide acetate from these two batches disclosed that even though their starting release rates were close, the microspheres + glucose exhibited a much lower release rate between 0.2 and 24h compared to those - glucose. The microspheres + glucose showed a denser periphery and a reduced water uptake at the end of 24-h release, indicating decreased permeability. However, this effect at times was offset as glucose content was further increased to 1%, causing an increase in surface area and porosity. In summary, we conclude that the effect of glucose on initial burst are determined by two factors: (1) increased initial burst due to increased osmotic pressure during encapsulation and drug release

  6. Glucose-Induced Oxidative Stress Reduces Proliferation in Embryonic Stem Cells via FOXO3A/β-Catenin-Dependent Transcription of p21(cip1).

    PubMed

    McClelland Descalzo, Darcie L; Satoorian, Tiffany S; Walker, Lauren M; Sparks, Nicole R L; Pulyanina, Polina Y; Zur Nieden, Nicole I

    2016-07-12

    Embryonic stem cells (ESCs), which are derived from a peri-implantation embryo, are routinely cultured in medium containing diabetic glucose (Glc) concentrations. While pregnancy in women with pre-existing diabetes may result in small embryos, whether such high Glc levels affect ESC growth remains uncovered. We show here that long-term exposure of ESCs to diabetic Glc inhibits their proliferation, thereby mimicking in vivo findings. Molecularly, Glc exposure increased oxidative stress and activated Forkhead box O3a (FOXO3a), promoting increased expression and activity of the ROS-removal enzymes superoxide dismutase and catalase and the cell-cycle inhibitors p21(cip1) and p27(kip1). Diabetic Glc also promoted β-catenin nuclear localization and the formation of a complex with FOXO3a that localized to the promoters of Sod2, p21(cip1), and potentially p27(kip1). Our results demonstrate an adaptive response to increases in oxidative stress induced by diabetic Glc conditions that promote ROS removal, but also result in a decrease in proliferation.

  7. Glucose-Induced Oxidative Stress Reduces Proliferation in Embryonic Stem Cells via FOXO3A/β-Catenin-Dependent Transcription of p21(cip1).

    PubMed

    McClelland Descalzo, Darcie L; Satoorian, Tiffany S; Walker, Lauren M; Sparks, Nicole R L; Pulyanina, Polina Y; Zur Nieden, Nicole I

    2016-07-12

    Embryonic stem cells (ESCs), which are derived from a peri-implantation embryo, are routinely cultured in medium containing diabetic glucose (Glc) concentrations. While pregnancy in women with pre-existing diabetes may result in small embryos, whether such high Glc levels affect ESC growth remains uncovered. We show here that long-term exposure of ESCs to diabetic Glc inhibits their proliferation, thereby mimicking in vivo findings. Molecularly, Glc exposure increased oxidative stress and activated Forkhead box O3a (FOXO3a), promoting increased expression and activity of the ROS-removal enzymes superoxide dismutase and catalase and the cell-cycle inhibitors p21(cip1) and p27(kip1). Diabetic Glc also promoted β-catenin nuclear localization and the formation of a complex with FOXO3a that localized to the promoters of Sod2, p21(cip1), and potentially p27(kip1). Our results demonstrate an adaptive response to increases in oxidative stress induced by diabetic Glc conditions that promote ROS removal, but also result in a decrease in proliferation. PMID:27411103

  8. 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

  9. Reduced hepatic mitochondrial respiration following acute high-fat diet is prevented by PGC-1α overexpression.

    PubMed

    Morris, E Matthew; Jackman, Matthew R; Meers, Grace M E; Johnson, Ginger C; Lopez, Jordan L; MacLean, Paul S; Thyfault, John P

    2013-12-01

    Changes in substrate utilization and reduced mitochondrial respiratory capacity following exposure to energy-dense, high-fat diets (HFD) are putatively key components in the development of obesity-related metabolic disease. We examined the effect of a 3-day HFD on isolated liver mitochondrial respiration and whole body energy utilization in obesity-prone (OP) rats. We also examined if hepatic overexpression of peroxisomal proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial respiratory capacity and biogenesis, would modify liver and whole body responses to the HFD. Acute, 3-day HFD (45% kcal) in OP rats resulted in increased daily energy intake, energy balance, weight gain, and adiposity, without an increase in liver triglyceride (triacylglycerol) accumulation. HFD-fed OP rats also displayed decreased whole body substrate switching from the dark to the light cycle, which was paired with reductions in hepatic mitochondrial respiration of multiple substrates in multiple respiratory states. Hepatic PGC-1α overexpression was observed to protect whole body substrate switching, as well as maintain mitochondrial respiration, following the acute HFD. Additionally, liver PGC-1α overexpression did not alter whole body dietary fatty acid oxidation but resulted in greater storage of dietary free fatty acids in liver lipid, primarily as triacylglycerol. Together, these data demonstrate that a short-term HFD can result in a decrease in metabolic flexibility and hepatic mitochondrial respiratory capacity in OP rats that is completely prevented by hepatic overexpression of PGC-1α.

  10. High Mobility and Low Use of Malaria Preventive Measures Among the Jarai Male Youth Along the Cambodia-Vietnam Border.

    PubMed

    Gryseels, Charlotte; Peeters Grietens, Koen; Dierickx, Susan; Xuan, Xa Nguyen; Uk, Sambunny; Bannister-Tyrrell, Melanie; Trienekens, Suzan; Ribera, Joan Muela; Hausmann-Muela, Susanna; Gerrets, René; D'Alessandro, Umberto; Sochantha, Tho; Coosemans, Marc; Erhart, Annette

    2015-10-01

    Malaria control along the Vietnam-Cambodia border presents a challenge for both countries' malaria elimination targets as the region is forested, inhabited by ethnic minority populations, and potentially characterized by early and outdoor malaria transmission. A mixed methods study assessed the vulnerability to malaria among the Jarai population living on both sides of the border in the provinces of Ratanakiri (Cambodia) and Gia Lai (Vietnam). A qualitative study generated preliminary hypotheses that were quantified in two surveys, one targeting youth (N = 498) and the other household leaders (N = 449). Jarai male youth, especially in Cambodia, had lower uptake of preventive measures (57.4%) and more often stayed overnight in the deep forest (35.8%) compared with the female youth and the adult population. Among male youth, a high-risk subgroup was identified that regularly slept at friends' homes or outdoors, who had fewer bed nets (32.5%) that were torn more often (77.8%). The vulnerability of Jarai youth to malaria could be attributed to the transitional character of youth itself, implying less fixed sleeping arrangements in nonpermanent spaces or non-bed sites. Additional tools such as long-lasting hammock nets could be suitable as they are in line with current practices.

  11. 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

  12. High Mobility and Low Use of Malaria Preventive Measures among the Jarai Male Youth along the Cambodia–Vietnam Border

    PubMed Central

    Gryseels, Charlotte; Peeters Grietens, Koen; Dierickx, Susan; Xuan, Xa Nguyen; Uk, Sambunny; Bannister-Tyrrell, Melanie; Trienekens, Suzan; Ribera, Joan Muela; Hausmann-Muela, Susanna; Gerrets, René; D'Alessandro, Umberto; Sochantha, Tho; Coosemans, Marc; Erhart, Annette

    2015-01-01

    Malaria control along the Vietnam–Cambodia border presents a challenge for both countries' malaria elimination targets as the region is forested, inhabited by ethnic minority populations, and potentially characterized by early and outdoor malaria transmission. A mixed methods study assessed the vulnerability to malaria among the Jarai population living on both sides of the border in the provinces of Ratanakiri (Cambodia) and Gia Lai (Vietnam). A qualitative study generated preliminary hypotheses that were quantified in two surveys, one targeting youth (N = 498) and the other household leaders (N = 449). Jarai male youth, especially in Cambodia, had lower uptake of preventive measures (57.4%) and more often stayed overnight in the deep forest (35.8%) compared with the female youth and the adult population. Among male youth, a high-risk subgroup was identified that regularly slept at friends' homes or outdoors, who had fewer bed nets (32.5%) that were torn more often (77.8%). The vulnerability of Jarai youth to malaria could be attributed to the transitional character of youth itself, implying less fixed sleeping arrangements in nonpermanent spaces or non-bed sites. Additional tools such as long-lasting hammock nets could be suitable as they are in line with current practices. PMID:26283747

  13. 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.

  14. Reduced hepatic mitochondrial respiration following acute high-fat diet is prevented by PGC-1α overexpression

    PubMed Central

    Morris, E. Matthew; Jackman, Matthew R.; Meers, Grace M. E.; Johnson, Ginger C.; Lopez, Jordan L.; MacLean, Paul S.

    2013-01-01

    Changes in substrate utilization and reduced mitochondrial respiratory capacity following exposure to energy-dense, high-fat diets (HFD) are putatively key components in the development of obesity-related metabolic disease. We examined the effect of a 3-day HFD on isolated liver mitochondrial respiration and whole body energy utilization in obesity-prone (OP) rats. We also examined if hepatic overexpression of peroxisomal proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial respiratory capacity and biogenesis, would modify liver and whole body responses to the HFD. Acute, 3-day HFD (45% kcal) in OP rats resulted in increased daily energy intake, energy balance, weight gain, and adiposity, without an increase in liver triglyceride (triacylglycerol) accumulation. HFD-fed OP rats also displayed decreased whole body substrate switching from the dark to the light cycle, which was paired with reductions in hepatic mitochondrial respiration of multiple substrates in multiple respiratory states. Hepatic PGC-1α overexpression was observed to protect whole body substrate switching, as well as maintain mitochondrial respiration, following the acute HFD. Additionally, liver PGC-1α overexpression did not alter whole body dietary fatty acid oxidation but resulted in greater storage of dietary free fatty acids in liver lipid, primarily as triacylglycerol. Together, these data demonstrate that a short-term HFD can result in a decrease in metabolic flexibility and hepatic mitochondrial respiratory capacity in OP rats that is completely prevented by hepatic overexpression of PGC-1α. PMID:24091599

  15. 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

  16. High Mobility and Low Use of Malaria Preventive Measures Among the Jarai Male Youth Along the Cambodia-Vietnam Border.

    PubMed

    Gryseels, Charlotte; Peeters Grietens, Koen; Dierickx, Susan; Xuan, Xa Nguyen; Uk, Sambunny; Bannister-Tyrrell, Melanie; Trienekens, Suzan; Ribera, Joan Muela; Hausmann-Muela, Susanna; Gerrets, René; D'Alessandro, Umberto; Sochantha, Tho; Coosemans, Marc; Erhart, Annette

    2015-10-01

    Malaria control along the Vietnam-Cambodia border presents a challenge for both countries' malaria elimination targets as the region is forested, inhabited by ethnic minority populations, and potentially characterized by early and outdoor malaria transmission. A mixed methods study assessed the vulnerability to malaria among the Jarai population living on both sides of the border in the provinces of Ratanakiri (Cambodia) and Gia Lai (Vietnam). A qualitative study generated preliminary hypotheses that were quantified in two surveys, one targeting youth (N = 498) and the other household leaders (N = 449). Jarai male youth, especially in Cambodia, had lower uptake of preventive measures (57.4%) and more often stayed overnight in the deep forest (35.8%) compared with the female youth and the adult population. Among male youth, a high-risk subgroup was identified that regularly slept at friends' homes or outdoors, who had fewer bed nets (32.5%) that were torn more often (77.8%). The vulnerability of Jarai youth to malaria could be attributed to the transitional character of youth itself, implying less fixed sleeping arrangements in nonpermanent spaces or non-bed sites. Additional tools such as long-lasting hammock nets could be suitable as they are in line with current practices. PMID:26283747

  17. Actin dynamics regulated by the balance of neuronal Wiskott-Aldrich syndrome protein (N-WASP) and cofilin activities determines the biphasic response of glucose-induced insulin secretion.

    PubMed

    Uenishi, Eita; Shibasaki, Tadao; Takahashi, Harumi; Seki, Chihiro; Hamaguchi, Hitomi; Yasuda, Takao; Tatebe, Masao; Oiso, Yutaka; Takenawa, Tadaomi; Seino, Susumu

    2013-09-01

    Actin dynamics in pancreatic β-cells is involved in insulin secretion. However, the molecular mechanisms of the regulation of actin dynamics by intracellular signals in pancreatic β-cells and its role in phasic insulin secretion are largely unknown. In this study, we elucidate the regulation of actin dynamics by neuronal Wiskott-Aldrich syndrome protein (N-WASP) and cofilin in pancreatic β-cells and demonstrate its role in glucose-induced insulin secretion (GIIS). N-WASP, which promotes actin polymerization through activation of the actin nucleation factor Arp2/3 complex, was found to be activated by glucose stimulation in insulin-secreting clonal pancreatic β-cells (MIN6-K8 β-cells). Introduction of a dominant-negative mutant of N-WASP, which lacks G-actin and Arp2/3 complex-binding region VCA, into MIN6-K8 β-cells or knockdown of N-WASP suppressed GIIS, especially the second phase. We also found that cofilin, which severs F-actin in its dephosphorylated (active) form, is converted to the phosphorylated (inactive) form by glucose stimulation in MIN6-K8 β-cells, thereby promoting F-actin remodeling. In addition, the dominant-negative mutant of cofilin, which inhibits activation of endogenous cofilin, or knockdown of cofilin reduced the second phase of GIIS. However, the first phase of GIIS occurs in the G-actin predominant state, in which cofilin activity predominates over N-WASP activity. Thus, actin dynamics regulated by the balance of N-WASP and cofilin activities determines the biphasic response of GIIS.

  18. 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.

  19. Preventative effect of Zingiber officinale on insulin resistance in a high-fat high-carbohydrate diet-fed rat model and its mechanism of action.

    PubMed

    Li, Yiming; Tran, Van H; Kota, Bhavani P; Nammi, Srinivas; Duke, Colin C; Roufogalis, Basil D

    2014-08-01

    Insulin resistance is a core component of metabolic syndrome and usually precedes the development of type 2 diabetes mellitus. We have examined the preventative effect of an ethanol extract of ginger (Zingiber officinale, Zingiberaceae) on insulin resistance in a high-fat high-carbohydrate (HFHC) diet-fed rat model of metabolic syndrome. The HFHC control rats displayed severe insulin resistance, whilst rats treated with ginger extract (200 mg/kg) during HFHC diet feeding showed a significant improvement of insulin sensitivity using the homeostatic model assessment of insulin resistance (HOMA-IR) after 10 weeks (p < 0.01). An in vitro mechanistic study showed that (S)-[6]-gingerol, the major pungent phenolic principle in ginger, dose-dependently (from 50 to 150 μM) increased AMPK α-subunit phosphorylation in L6 skeletal muscle cells. This was accompanied by a time-dependent marked increment of PGC-1α mRNA expression and mitochondrial content in L6 skeletal muscle cells. These results suggest that the protection from HFHC diet-induced insulin resistance by ginger is likely associated with the increased capacity of energy metabolism by its major active component (S)-[6]-gingerol.

  20. 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

  1. Vitamin C prevents the effects of high rearing temperatures on the quality of broiler thigh meat1.

    PubMed

    Ferreira, I B; Matos Junior, J B; Sgavioli, S; Vicentini, T I; Morita, V S; Boleli, I C

    2015-05-01

    We investigated the effects of incubation temperatures and vitamin C injections into eggs (treatments: 37.5ºC, 39ºC, 39ºC+vitamin C) on resultant chick pectoralis major and sartorius muscle fiber hypertrophy, as well as their effects on the quality of breast and over-thigh meat of broilers reared under cold, control, or hot temperatures. Incubation at 39ºC increased the shear force and reduced meat redness in breast meat (P < 0.05). Vitamin C prevented these high temperature incubation effects [shear force (kgf cm(-2)): 37.5ºC = 2.34, 39ºC = 2.79, 39ºC+vitamin C = 2.44; redness: 37.5ºC = 2.64, 39ºC = 1.90, 39ºC+vitamin C = 2.30], but reduced water content (37.5ºC = 74.81%, 39ºC = 74.53%, 39ºC+vitamin C = 69.39%) (P < 0.05). Cold rearing temperatures increased breast meat redness (a*: cold = 2.78, control = 2.12, hot = 1.98), while hot rearing temperatures reduced the muscle fiber area (cold = 5.413 μm(2), control = 5.612 μm(2), hot = 4.448 μm(2)) (P < 0.05) without altering meat quality (P > 0.05). Hot rearing temperatures increased the cooking loss (cold = 30.10%, control = 33.66%, hot = 37.01%), shear force (cold = 3.05 kgf cm(-2), control = 3.43 kgf cm(-2), hot = 4.29 kgf cm(-2)) and redness (a*: cold = 4.63, control = 3.55, hot = 3.20) in the over-thigh meat of broilers from eggs incubated at 37.5ºC, increasing the area of muscle fibers, while cold rearing temperatures diminished cooking loss and shear force, reducing the muscle fiber area (P < 0.05). Incubation at 39ºC and 39ºC+vitamin C prevented the effects of hot and cold rearing temperatures, by diminishing and increasing the muscle fiber area, respectively.

  2. Vitamin C prevents the effects of high rearing temperatures on the quality of broiler thigh meat1.

    PubMed

    Ferreira, I B; Matos Junior, J B; Sgavioli, S; Vicentini, T I; Morita, V S; Boleli, I C

    2015-05-01

    We investigated the effects of incubation temperatures and vitamin C injections into eggs (treatments: 37.5ºC, 39ºC, 39ºC+vitamin C) on resultant chick pectoralis major and sartorius muscle fiber hypertrophy, as well as their effects on the quality of breast and over-thigh meat of broilers reared under cold, control, or hot temperatures. Incubation at 39ºC increased the shear force and reduced meat redness in breast meat (P < 0.05). Vitamin C prevented these high temperature incubation effects [shear force (kgf cm(-2)): 37.5ºC = 2.34, 39ºC = 2.79, 39ºC+vitamin C = 2.44; redness: 37.5ºC = 2.64, 39ºC = 1.90, 39ºC+vitamin C = 2.30], but reduced water content (37.5ºC = 74.81%, 39ºC = 74.53%, 39ºC+vitamin C = 69.39%) (P < 0.05). Cold rearing temperatures increased breast meat redness (a*: cold = 2.78, control = 2.12, hot = 1.98), while hot rearing temperatures reduced the muscle fiber area (cold = 5.413 μm(2), control = 5.612 μm(2), hot = 4.448 μm(2)) (P < 0.05) without altering meat quality (P > 0.05). Hot rearing temperatures increased the cooking loss (cold = 30.10%, control = 33.66%, hot = 37.01%), shear force (cold = 3.05 kgf cm(-2), control = 3.43 kgf cm(-2), hot = 4.29 kgf cm(-2)) and redness (a*: cold = 4.63, control = 3.55, hot = 3.20) in the over-thigh meat of broilers from eggs incubated at 37.5ºC, increasing the area of muscle fibers, while cold rearing temperatures diminished cooking loss and shear force, reducing the muscle fiber area (P < 0.05). Incubation at 39ºC and 39ºC+vitamin C prevented the effects of hot and cold rearing temperatures, by diminishing and increasing the muscle fiber area, respectively. PMID:25810411

  3. On the mechanism of polypropylene fibres in preventing fire spalling in self-compacting and high-performance cement paste

    SciTech Connect

    Liu, X. Ye, G.; De Schutter, G.; Yuan, Y.; Taerwe, L.

    2008-04-15

    With the increasing application of self-compacting concrete (SCC) in construction and infrastructure, the fire spalling behavior of SCC has been attracting due attention. In high performance concrete (HPC), addition of polypropylene fibers (PP fibers) is widely used as an effective method to prevent explosive spalling. Hence, it would be useful to investigate whether the PP fibers are also efficient in SCC to avoid explosive spalling. However, no universal agreement exists concerning the fundamental mechanism of reducing the spalling risk by adding PP fiber. For SCC, the reduction of flowability should be considered when adding a significant amount of fibres. In this investigation, both the micro-level and macro-level properties of pastes with different fiber contents were studied in order to investigate the role of PP fiber at elevated temperature in self-compacting cement paste samples. The micro properties were studied by backscattering electron microscopy (BSE) and mercury intrusion porosimetry (MIP) tests. The modification of the pore structure at elevated temperature was investigated as well as the morphology of the PP fibers. Some macro properties were measured, such as the gas permeability of self-compacting cement paste after heating at different temperatures. The factors influencing gas permeability were analyzed. It is shown that with the melting of PP fiber, no significant increase in total pore volume is obtained. However, the connectivity of isolated pores increases, leading to an increase of gas permeability. With the increase of temperature, the addition of PP fibers reduces the damage of cement pastes, as seen from the total pore volume and the threshold pore diameter changes. From this investigation, it is concluded that the connectivity of pores as well as the creation of micro cracks are the major factors which determine the gas permeability after exposure to high temperatures. Furthermore, the connectivity of the pores acts as a dominant factor

  4. Is the GnRH Antagonist Protocol Effective at Preventing OHSS for Potentially High Responders Undergoing IVF/ICSI?

    PubMed Central

    Xing, Weijie; Lin, Haiyan; Li, Yu; Yang, Dongzi; Wang, Wenjun; Zhang, Qingxue

    2015-01-01

    Objective To determine if the GnRH antagonist protocol is effective in preventing ovarian hyperstimulation syndrome (OHSS) in potentially high responders. Methods A total of 660 IVF-ET/ICSI cycles were retrospectively identified. The inclusion criterion was age ≤ 30 years. Cycles were divided into two groups: a GnRHa group and a GnRHant group. In the GnRHa group, the patients received one single injection of 1.0mg-1.3mg Triptorelin in previous mid-luteal phase. In the GnRHant group, a daily dose of 0.25 mg Cetrotide was initiated when a lead follicle obtained a mean diameter of 14 mm, continued up until the day of hCG administration. The duration of stimulation, total dose of Gn, implantation rate, pregnancy rate, and OHSS rate were compared. Results The duration of stimulation, E2 level on hCG day, numbers of oocytes retrieved, MII oocytes, and high-quality embryos in the GnRHa group were all significantly more than those in the GnRHant group. In the GnRHa group, 83.53% of cancelled fresh-transferred cycles were cancelled because of high risk of OHSS, which was significantly higher than that in the GnRHant group (43.55%, P<0.05). The incidence of OHSS in the GnRHa group was slightly higher than that in the GnRHant group. The implantation and clinical pregnancy rates in the GnRHa group were significantly higher than those in the GnRHant group (37.36% VS 19.25%, 62.78% VS 31.06%; P<0.05). Conclusions Our study demonstrated that for potentially high responders, the GnRHant protocol can, to some extent, lower the cancellation and incidence rates of OHSS. The GnRHa protocol was superior to the GnRHant protocol in terms of implantation and clinical pregnancy rates. PMID:26468951

  5. 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/ ...

  6. 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

  7. High concentrations of glucose suppress etoposide-induced cell death of B-cell lymphoma through BCL-6.

    PubMed

    Shao, Yan; Ling, Chang Chun; Liu, Xu Qing

    2014-07-18

    Glucose is potentially a factor in the resistance to chemotherapy of B-cell lymphomas. In this study we investigated the expression of the glucose induced transcription factor Bcl-6 and the underlying mechanism by which it suppresses B-cell lymphoma cell death. Glucose was found to prevent etoposide-induced tumor cell death. BCL-6 expression was induced by glucose but down-regulated by etoposide. BCL-6 expression was regulated by the interaction of VDUP1 and p53. The molecular mechanism by which glucose prevented etoposide-induced tumor cell death was shown to involve the BCL-6 mediated caspase pathway. Our data suggest that glucose-induced BCL-6 overexpression could abrogate the etoposide chemotherapy effect on tumor cell death. PMID:24878528

  8. 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.

  9. Determination of preventive behaviors for pandemic influenza A/H1N1 based on protection motivation theory among female high school students in Isfahan, Iran

    PubMed Central

    Sharifirad, Gholamreza; Yarmohammadi, Parastoo; Sharifabad, Mohammad Ali Morowati; Rahaei, Zohreh

    2014-01-01

    Introduction: Influenza A/H1N1 pandemic has recently threatened the health of world's population more than ever. Non-pharmaceutical measures are important to prevent the spread of influenza A/H1N1 and to prevent a pandemic. Effective influenza pandemic management requires understanding of the factors influencing preventive behavioral. This study reports on predictors of students’ preventive behaviors for pandemic influenza A/H1N1 using variables based on the protection motivation theory (PMT). Materials and Methods: In a cross-sectional study, multiple-stage randomized sampling was used to select 300 female students in Isfahan who completed a questionnaire in December 2009. Data were collected using a self-report questionnaire based on PMT. The statistical analysis of the data included bivariate correlations, Mann-Whitney, Kruskal-Wallis, and linear regression. Results: The mean age of participants was 15.62 (SE = 1.1) years old. Majority of participants were aware regarding pandemic influenza A/H1N1 (87.3%, 262 out of 300). Results showed that, protection motivation was highly significant relationship with preventive behavior and predicted 34% of its variance. We found all of the variables with the exception of perceived susceptibility, perceived severity, and response cost were related with protection motivation and explained 22% of its variance. Conclusion: Promotion of students’ self-efficacy, and intention to protect themselves from a health threat should be priorities of any programs aimed at promoting preventive behaviors among students. It is also concluded that the protection motivation theory may be used in developing countries, like Iran, as a framework for prevention interventions in an attempt to improve the preventive behaviors of students. PMID:24741647

  10. 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. PMID:26514092

  11. Highly purified omega-3 polyunsaturated fatty acids are effective as adjunct therapy for secondary prevention of myocardial infarction.

    PubMed

    Verboom, Cees N

    2006-12-01

    Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione was the first large randomized trial to produce evidence that a pharmaceutical preparation of highly purified omega-3 polyunsaturated fatty acids (PUFAs), administered as an adjunct to other accepted interventions, had a favorable effect on hard clinical end-points in post-myocardial infarction patients. Much of the 20% all-cause mortality benefit recorded during the study could be attributed to a 45% reduction in sudden death--a fatal outcome that traditionally has proved resistant to medical intervention. These results were obtained with an omega-3 PUFA dose of 1 g/day, which is much lower than was routinely being used at the time the study was initiated (e.g. 4 g/day for hypertriglyceridemia). One consequence of this low-dose regimen was that the tolerability profile of omega-3 PUFAs during GISSI-Prevenzione was considered highly satisfactory, with low adverse event incidence rates and low rates of discontinuation due to adverse events. Time-course analysis established that much of the survival benefit of omega-3 PUFA treatment in GISSI-Prevenzione was realized during the early months of the trial. The beneficial effects of omega-3 PUFA treatment were observed on top of standard, secondary pharmacological prevention therapy like anti-platelet agents, statins, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors. The benefits of omega-3 PUFA therapy were also apparent in patients at all standards of adherence to a healthy diet and may have been augmented in patients with the best dietary profile. Patients with diabetes mellitus (approximately 15% of the study cohort) appeared to benefit from omega-3 PUFAs to at least the same extent as the general study population; the treatment effect on sudden death was progressively more pronounced as left ejection fraction declined. Cost-effectiveness analyses undertaken from a third-party payer perspective for Italy

  12. 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

  13. Antioxidative Activity of Blueberry Leaf Extract Prevents High-fat Diet-induced Obesity in C57BL/6 Mice

    PubMed Central

    Lee, In-Chul; Kim, Dae Yong; Choi, Bu Young

    2014-01-01

    Background: Health beneficial effects of blueberry have been well documented. Obesity is health hazard that is associated with metabolic abnormalities. We investigated the effect of blueberry leaf extract (BBLE) on high-fat diet (HFD)-induced obesity in C57BL/6J mice. Methods: C57BL/6 mice were fed HFD with or without BBLE for 10 weeks. Body weight, serum parameter, and adipose tissues morphology were assessed. The expression of mRNA associated with adipogenesis was measured using real-time polymerase chain reaction (RT-PCR) analysis. Results: Administration of BBLE to mice challenged with HFD significantly decreased the body weight gain, the levels of plasma triglyceride (TG) and liver lipid peroxidation, and reduced the adipocyte size and improved hepatic status compared with the group treated with HFD only. BBLE treatment significantly improved glucose control compared with the HFD group. Moreover, BBLE showed an inhibitory effect on adipocyte differentiation in obese mice together with significant decrease in the lipid accumulation by downregulating gene expression of adipocyte-specific transcription factors, such as peroxisome proliferation-activity receptor and acetyl coenzyme A carboxylase and upregulating the mRNA expression of adiponectin, which are critical for adipogenesis. Conclusion: BBLE suppressed the body weight gain in the HFD-fed C57BL/6 mice. Intake of BBLE reduced body weight in HFD-fed mice by 20%. Furthermore, BBLE supplementation significantly decreased the TG level in the liver and inhibited leptin secretion. BBLE supplementation also improved insulin resistance. Therefore, BBLE is a possible agent to prevent obesity. PMID:25337590

  14. 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

  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. 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…

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. Preventive and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity.

    PubMed

    Jing, Li; Zhang, Yu; Fan, Shengjie; Gu, Ming; Guan, Yu; Lu, Xiong; Huang, Cheng; Zhou, Zhiqin

    2013-09-01

    D-limonene is a major constituent in citrus essential oil, which is used in various foods as a flavoring agent. Recently, d-limonene has been reported to alleviate fatty liver induced by a high-fat diet. Here we determined the preventive and therapeutic effects of d-limonene on metabolic disorders in mice with high-fat diet-induced obesity. In the preventive treatment, d-limonene decreased the size of white and brown adipocytes, lowered serum triglyceride (TG) and fasting blood glucose levels, and prevented liver lipid accumulations in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, d-limonene reduced serum TG, low-density lipoprotein cholesterol (LDL-c) and fasting blood glucose levels and glucose tolerance, and increased serum high-density lipoprotein cholesterol (HDL-c) in obese mice. Using a reporter assay and gene expression analysis, we found that d-limonene activated peroxisome proliferator-activated receptor (PPAR)-α signaling, and inhibited liver X receptor (LXR)-β signaling. Our data suggest that the intake of d-limonene may benefit patients with dyslipidemia and hyperglycemia and is a potential dietary supplement for preventing and ameliorating metabolic disorders.

  3. 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.

  4. 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. PMID:27195666

  5. Understanding the Importance of Gene and Environment in the Etiology and Prevention of Type 2 Diabetes Mellitus in High-Risk Populations

    PubMed Central

    Samsom, Marsha; Trivedi, Tushar; Orekoya, Olubunmi; Vyas, Shraddha

    2016-01-01

    Current literature focuses on the complications and treatment of Type 2 Diabetes Mellitus (T2DM) while clustering environmental and genetic factors to explain the disease. Interventions proposed to reduce diabetes prevalence should focus predominantly on initiating active rapports of family members and promoting a more communication-oriented preventative approach between diabetics and non-diabetics. Due to varying risks in T2DM by race and ethnicity, these populations should follow race-appropriate guidelines to prevent further T2DM occurrence and complications. The review consists of information related to the genetic component of T2DM to help identify high-risk groups and focuses on the environmental aspect of the disease to help consider appropriate techniques to reduce disease burden. Genetic factors play important roles in the pathogenesis of diabetes and thus are an essential element of understanding the cause of the disease and possible methods of prevention. Focusing on high-risk groups with T2DM could have profound effects on the current health care situation. In this review, we discuss the epidemiology of diabetes in the United States and propose methods of preventing and delaying the development of T2DM in high-risk individuals. PMID:27376154

  6. 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…

  7. 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…

  8. Strengthening Head Start Families: Reducing High Risk through Mental Health Prevention/Intervention (MHP/IP). Overview and Final Report.

    ERIC Educational Resources Information Center

    Hutchison, Mary Ann; And Others

    The Mental Health Prevention/Intervention Project (MHP/IP) was designed to provide and assess comprehensive and effective mental health services to Head Start children, parents, families, and staff. Sponsored by the Latin American Civic Association (LACA) in Los Angeles, the 14-month intervention was implemented and assessed on three levels: (1)…

  9. 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…

  10. 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…

  11. 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. PMID:26595265

  12. 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 fo