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Sample records for potential cardioprotective factor

  1. Upregulation of vascular endothelial growth factor receptor-1 contributes to sevoflurane preconditioning–mediated cardioprotection

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    Qian B

    2018-04-01

    Full Text Available Bin Qian,1 Yang Yang,2 Yusheng Yao,3 Yanling Liao,3 Ying Lin3 1Department of Anesthesiology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China; 2Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; 3Department of Anesthesiology, The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China Purpose: Sevoflurane preconditioning (SPC can provide myocardial protective effects similar to ischemic preconditioning. However, the exact mechanism of SPC remains unclear. Previous studies indicate that vascular endothelial growth factor receptor 1 (VEGFR-1 is involved in ischemic preconditioning-mediated cardioprotection. This study was designed to determine the significance of VEGFR-1 signaling in SPC-mediated cardioprotection.Materials and methods: Myocardial ischemia–reperfusion (I/R rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, after 15 min of baseline equilibration, the isolated hearts were pretreated with 2.5% sevoflurane, 2.5% sevoflurane+MF1 10 µmol/L, or 2.5% sevoflurane+placental growth factor 10 µmol/L, and then subjected to 30 min of global ischemia and 120 min of reperfusion. The changes in hemodynamic parameters, myocardial infarct size, and the levels of creatine kinase-MB, lactate dehydrogenase, cardiac troponin-I, tumor necrosis factor-α, and interleukin 6 in the myocardium were evaluated.Results: Compared to the I/R group, pretreatment with 2.5% sevoflurane significantly improved the cardiac function, limited myocardial infarct size, reduced cardiac enzyme release, upregulated VEGFR-1 expression, and decreased inflammation. In addition, the selective VEGFR-1 agonist, placental growth factor, did not enhance the cardioprotection and anti-inflammation effects of sevoflurane, while the specific VEGFR-1 inhibitor, MF1, completely reversed these effects

  2. Evaluation of the potential cardioprotective activity of some Saudi plants against doxorubicin toxicity.

    Science.gov (United States)

    Ashour, Osama M; Abdel-Naim, Ashraf B; Abdallah, Hossam M; Nagy, Ayman A; Mohamadin, Ahmed M; Abdel-Sattar, Essam A

    2012-01-01

    Doxorubicin (DOX) is an anthracycline antibiotic widely used as a chemotherapeutic agent in the treatment of several tumours. However, its cardiac toxicity limits its use at maximum therapeutic doses. Most studies implicated increased oxidative stress as the major determinant of DOX cardiotoxicity. The local Saudi flora is very rich in a variety of plants of quite known folkloric or traditional medicinal uses. Tribulus macropterus Boiss., Olea europaea L. subsp. africana (Mill.) P. S. Green, Tamarix aphylla (L.) H. Karst., Cynomorium coccineum L., Cordia myxa L., Calligonum comosum L' Hér, and Withania somnifera (L.) Dunal are Saudi plants known to have antioxidant activities. The aim of the current study was to explore the potential protective effects of methanolic extracts of these seven Saudi plants against DOX-induced cardiotoxicity in rats. Two plants showed promising cardioprotective potential in the order Calligonum comosum > Cordia myxa. The two plant extracts showed potent in vitro radical scavenging and antioxidant properties. They significantly protected against DOX-induced alterations in cardiac oxidative stress markers (GSH and MDA) and cardiac serum markers (CK-MB and LDH activities). Additionally, histopathological examination indicated a protection against DOX-induced cardiotoxicity. In conclusion, C. comosum and C. myxa exerted protective activity against DOX-induced cardiotoxicity, which is, at least partly, due to their antioxidant effect.

  3. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

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    Heera Ram

    2014-01-01

    Full Text Available Acacia senegal L. (Fabaceae seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil for 15 days. Circulating total cholesterol (TC, HDL-cholesterol (HDL-C, LDL-cholesterol (LDL-C, triglycerides, and VLDL-cholesterol (VLDL-C levels; atherogenic index (AI; cardiac lipid peroxidation (LPO; planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34±0.72 and increased lumen volume (51.65±3.66, administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o. for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics.

  4. Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits

    International Nuclear Information System (INIS)

    Jirkovský, Eduard; Lenčová-Popelová, Olga; Hroch, Miloš; Adamcová, Michaela; Mazurová, Yvona; Vávrová, Jaroslava

    2013-01-01

    Despite incomplete understanding to its mechanism of action, dexrazoxane (DEX) is still the only clearly effective cardioprotectant against chronic anthracycline (ANT) cardiotoxicity. However, its clinical use is currently restricted to patients exceeding significant ANT cumulative dose (300 mg/m 2 ), although each ANT cycle may induce certain potentially irreversible myocardial damage. Therefore, the aim of this study was to compare early and delayed DEX intervention against chronic ANT cardiotoxicity and study the molecular events involved. The cardiotoxicity was induced in rabbits with daunorubicin (DAU; 3 mg/kg/week for 10 weeks); DEX (60 mg/kg) was administered either before the 1st or 7th DAU dose (i.e. after ≈300 mg/m 2 cumulative dose). While both DEX administration schedules prevented DAU-induced premature deaths and severe congestive heart failure, only the early intervention completely prevented the left ventricular dysfunction, myocardial morphological changes and mitochondrial damage. Further molecular analyses did not support the assumption that DEX cardioprotection is based and directly proportional to protection from DAU-induced oxidative damage and/or deletions in mtDNA. Nevertheless, DAU induced significant up-regulation of heme oxygenase 1 pathway while heme synthesis was inversely regulated and both changes were schedule-of-administration preventable by DEX. Early and delayed DEX interventions also differed in ability to prevent DAU-induced down-regulation of expression of mitochondrial proteins encoded by both nuclear and mitochondrial genome. Hence, the present functional, morphological as well as the molecular data highlights the enormous cardioprotective effects of DEX and provides novel insights into the molecular events involved. Furthermore, the data suggests that currently recommended delayed intervention may not be able to take advantage of the full cardioprotective potential of the drug

  5. Molecular Mechanisms in Exercise-Induced Cardioprotection

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    Saeid Golbidi

    2011-01-01

    Full Text Available Physical inactivity is increasingly recognized as modifiable behavioral risk factor for cardiovascular diseases. A partial list of proposed mechanisms for exercise-induced cardioprotection include induction of heat shock proteins, increase in cardiac antioxidant capacity, expression of endoplasmic reticulum stress proteins, anatomical and physiological changes in the coronary arteries, changes in nitric oxide production, adaptational changes in cardiac mitochondria, increased autophagy, and improved function of sarcolemmal and/or mitochondrial ATP-sensitive potassium channels. It is currently unclear which of these protective mechanisms are essential for exercise-induced cardioprotection. However, most investigations focus on sarcolemmal KATP channels, NO production, and mitochondrial changes although it is very likely that other mechanisms may also exist. This paper discusses current information about these aforementioned topics and does not consider potentially important adaptations within blood or the autonomic nervous system. A better understanding of the molecular basis of exercise-induced cardioprotection will help to develop better therapeutic strategies.

  6. Cardioprotection by gene therapy: A review paper on behalf of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology.

    Science.gov (United States)

    Madonna, Rosalinda; Cadeddu, Christian; Deidda, Martino; Giricz, Zoltán; Madeddu, Clelia; Mele, Donato; Monte, Ines; Novo, Giuseppina; Pagliaro, Pasquale; Pepe, Alessia; Spallarossa, Paolo; Tocchetti, Carlo Gabriele; Varga, Zoltán V; Zito, Concetta; Geng, Yong-Jian; Mercuro, Giuseppe; Ferdinandy, Peter

    2015-07-15

    Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood. This is due to the targeted approach that allowed identifying one or a few genes associated with IRI and cardioprotection. Genes critical for signaling pathways in cardioprotection include protectomiRs (e.g., microRNA 125b*), ZAC1 transcription factor, pro-inflammatory genes such as cycloxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), antioxidant enzymes such as hemoxygenase (HO)-1, extracellular and manganese superoxidase dismutases (ec-SOD and Mg-SOD), heat shock proteins (HSPs), growth factors such as insulin like growth factor (IGF)-1 and hepatocyte growth factor (HGF), antiapoptotic proteins such as Bcl-2 and Bcl-xL, pro-apoptotic proteins such as FasL, Bcl-2, Bax, caspase-3 and p53, and proangiogenic genes such as TGFbeta, sphingosine kinase 1 (SPK1), and PI3K-Akt. By identifying the gene expression profiles of IRI and ischemic conditioning, one may reveal potential gene targets responsible for cardioprotection. In this manuscript, we review the current state of the art of gene therapy in cardioprotection and propose that gene expression analysis facilitates the identification of individual genes associated with cardioprotection. We discuss signaling pathways associated with cardioprotection that can be targeted by gene therapy to achieve cardioprotection. Copyright © 2015. Published by Elsevier Ireland Ltd.

  7. Effects of Brazilian Cardioprotective Diet Program on risk factors in patients with coronary heart disease: a Brazilian Cardioprotective Diet randomized pilot trial

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    Bernardete Weber

    2012-12-01

    Full Text Available OBJECTIVE: To evaluate the effectiveness of the Brazilian Cardioprotective Diet Program in reducing blood pressures, fasting glucose levels and body mass indices in patients with established atherothrombotic disease. METHOD: This randomized controlled pilot trial included outpatients who were over 45 years of age with atherothrombotic cardiovascular disease. Group A, who received the Brazilian Cardioprotective Diet Program, had weekly sessions with dietitians. Groups B and C received the usual dietary therapy that is given to patients with cardiovascular diseases as proposed by the Brazilian guidelines. This diet had the same nutrient profile as that given to Group A, but it was customized by the integration of typical Mediterranean foods. The difference between Groups B and C was the number of sessions with the dietitian. Group B received weekly sessions, while group C only had monthly sessions. ClinicalTrials.gov: NCT 01453166. RESULTS: There was a greater reduction in systolic (7.8% and diastolic (10.8% blood pressures in Group A compared with Group B (2.3% and 7.3%, and Group C (3.9% and 4.9%, respectively. Fasting glucose decreased by 5.3% and 2% in Groups A and B, respectively. Fasting glucose increased by 3.7% in Group C. The BMIs decreased by 3.5% and 3.3% in Groups A and B, respectively. Group C did not present with any changes in BMI. However, none of these data showed statistical differences between the groups, which is methodologically acceptable in pilot trials. CONCLUSIONS: The Brazilian Cardioprotective Diet Program seems to be more effective in reducing blood pressures, fasting glucose levels, weights and BMIs in patients with previous cardiovascular disease compared with the diet that has been proposed by the Brazilian guidelines.

  8. Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

    International Nuclear Information System (INIS)

    Zhao, Liyan; Liu, Xiaolin; Zhang, Yuelin; Liang, Xiaoting; Ding, Yue; Xu, Yan; Fang, Zhen; Zhang, Fengxiang

    2016-01-01

    Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease.

  9. Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

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    Zhao, Liyan; Liu, Xiaolin [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zhang, Yuelin [Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong (China); Liang, Xiaoting; Ding, Yue [Pudong District Clinical Translational Medical Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai (China); Xu, Yan; Fang, Zhen [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zhang, Fengxiang, E-mail: njzfx6@njmu.edu.cn [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2016-05-15

    Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease.

  10. Eat healthy? Attitudes of the German population towards industrially produced cardioprotective food.

    Science.gov (United States)

    Jung, F U C E; Luck-Sikorski, C; Krüger, M; Wiacek, C; Braun, P G; Engeli, S; Riedel-Heller, S G

    2018-05-01

    Cardiovascular disease (CVD) is likely to increase in incidence. Foods with cardioprotective functions, e.g. specific functional food, could reduce CVD risk factors and hence CVD incidence. Little is known about industrially modified foods with cardioprotective functions. In a large German sample (n = 1007), attitudes of consumers in Germany towards industrially produced cardioprotective food were assessed using Cluster analyses. Consumers were contacted via telephone and interviewed using questionnaires. Overall, about 25% knew about industrially produced food with cardioprotective function. Our analysis revealed a small but determined group of consumers who think very skeptical about cardioprotective products, but we also identified a favorable group. These two groups only differed in age, with the skeptical group being ten years older. The rising number of industrially modified products with potential cardioprotective benefit is met by skepticism and a lack of knowledge by German costumers. If large scale studies show health benefits of these products, these will need to be better communicated to German customers in order to address possible doubts or concerns and to encourage healthy eating habits in consumer eating behavior. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  11. Cardioprotection by modulation of mitochondrial respiration during ischemia–reperfusion: Role of apoptosis-inducing factor

    International Nuclear Information System (INIS)

    Xu, Aijun; Szczepanek, Karol; Hu, Ying; Lesnefsky, Edward J.; Chen, Qun

    2013-01-01

    Highlights: •Blockade of electron transport prevents the loss of AIF from mitochondria during IR. •Blockade of electron transport decreases caspase-independent cell death during IR. •Mitochondrial AIF content is down-regulated in Harlequin mice. •Blockade of electron transport protects Harlequin mouse hearts during IR. •Amobarbital protection is partially dependent on mitochondrial AIF content. -- Abstract: The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia–reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia–reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in

  12. Cardioprotection by modulation of mitochondrial respiration during ischemia–reperfusion: Role of apoptosis-inducing factor

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Aijun [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030 (China); Szczepanek, Karol; Hu, Ying [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Lesnefsky, Edward J. [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298 (United States); McGuire Department of Veterans Affairs Medical Center, Richmond, VA 23249 (United States); Chen, Qun, E-mail: qchen8@vcu.edu [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States)

    2013-06-14

    Highlights: •Blockade of electron transport prevents the loss of AIF from mitochondria during IR. •Blockade of electron transport decreases caspase-independent cell death during IR. •Mitochondrial AIF content is down-regulated in Harlequin mice. •Blockade of electron transport protects Harlequin mouse hearts during IR. •Amobarbital protection is partially dependent on mitochondrial AIF content. -- Abstract: The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia–reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia–reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in

  13. Cardioprotection by Conditioning Mimetic Drugs.

    Science.gov (United States)

    Santillo, Elpidio; Migale, Monica; Postacchini, Demetrio; Balestrini, Fabrizio; Incalzi, Raffaele Antonelli

    2016-01-01

    At present, ischemic heart disease (IHD) is one of the main causes of morbidity and mortality world-wide. An important insight into both IHD pathophysiology and cardioprotection was achieved in 1986 when Murry et al. described for the first time the ischemic preconditioning (IP). IP can be defined as an innate phenomenon by which brief episodes of ischemia confer protection to a tissue from a subsequent more protracted ischemic insult. Suggested mechanisms explaining IP comprise the action of circulating substances (e.g. adenosine, bradykinin, nitric oxide). These mediators are released after a prolonged ischemic stress, causing activation of molecular pathways that induce favorable posttranslational changes of proteins and adaptive modifications in genetic expression. Briefly review evidences from clinical studies on drugs that exert their effects by mimicking IP, discussing their therapeutic properties and the potential clinical employment in order to obtain cardioprotection. Literature regarding IP mimicking pharmacological agents was searched in Medline and Google Scholar. Authors reviewed relevant researches in English language including both clinical studies and reviews of clinical studies published from 1986 to 2016. Several pharmacological agents reproducing IP protective actions have been evaluated in many clinical trials. Examined molecules include adenosine, nicorandil and atrial natriuretic peptide. Interestingly IP mimicking effects of drugs have been also analyzed perioperatively in the context of ischaemia-reperfusion heart injury. Moreover evidences suggest that also some anaesthetic drugs (especially volatile agents) are able to provide myocardial protection by inducing IP. Drugs capable of mimicking IP exhibit a high therapeutic potential because of their properties of eliciting an effective cardioprotective signaling. Future studies should clarify the optimal doses and timing of administration of IP mimetic agents in order to favor the advent of

  14. The Brazilian Cardioprotective Nutritional Program to reduce events and risk factors in secondary prevention for cardiovascular disease: study protocol (The BALANCE Program Trial).

    Science.gov (United States)

    Weber, Bernardete; Bersch-Ferreira, Ângela Cristine; Torreglosa, Camila Ragne; Ross-Fernandes, Maria Beatriz; da Silva, Jacqueline Tereza; Galante, Andrea Polo; Lara, Enilda de Sousa; Costa, Rosana Perim; Soares, Rafael Marques; Cavalcanti, Alexandre Biasi; Moriguchi, Emilio H; Bruscato, Neide M; Kesties; Vivian, Lilian; Schumacher, Marina; de Carli, Waldemar; Backes, Luciano M; Reolão, Bruna R; Rodrigues, Milena P; Baldissera, Dúnnia M B; Tres, Glaucia S; Lisbôa, Hugo R K; Bem, João B J; Reolão, Jose B C; Deucher, Keyla L A L; Cantarelli, Maiara; Lucion, Aline; Rampazzo, Daniela; Bertoni, Vanessa; Torres, Rosileide S; Verríssimo, Adriana O L; Guterres, Aldair S; Cardos, Andrea F R; Coutinho, Dalva B S; Negrão, Mayara G; Alencar, Mônica F A; Pinho, Priscila M; Barbosa, Socorro N A A; Carvalho, Ana P P F; Taboada, Maria I S; Pereira, Sheila A; Heyde, Raul V; Nagano, Francisca E Z; Baumgartner, Rebecca; Resende, Fernanda P; Tabalipa, Ranata; Zanini, Ana C; Machado, Michael J R; Araujo, Hevila; Teixeira, Maria L V; Souza, Gabriela C; Zuchinali, Priccila; Fracasso, Bianca M; Ulliam, Karen; Schumacher, Marina; Pierotto, Moara; Hilário, Thamires; Carlos, Daniele M O; Cordeiro, Cintia G N C; Carvalho, Daniele A; Gonçalves, Marília S; Vasconcelos, Valdiana B; Bosquetti, Rosa; Pagano, Raira; Romano, Marcelo L P; Jardim, César A; de Abreu, Bernardo N A; Marcadenti, Aline; Schmitt, Alessandra R; Tavares, Angela M V; Faria, Christiane C; Silva, Flávia M; Fink, Jaqueline S; El Kik, Raquel M; Prates, Clarice F; Vieira, Cristiane S; Adorne, Elaine F; Magedanz, Ellen H; Chieza, Fernanda L; Silva, Ingrid S; Teixeira, Joise M; Trescastro, Eduardo P; Pellegrini, Lívia A; Pinto, Jéssika C; Telles, Cristina T; Sousa, Antonio C S; Almeida, Andreza S; Costa, Ariane A; Carmo, José A C; Silva, Juliana T; Alves, Luciana V S; Sales, Saulo O C; Ramos, Maria E M; Lucas, Marilia C S; Damiani, Monica; Cardoso, Patricia C; Ramos, Salvador S; Dantas, Clenise F; Lopes, Amanda G; Cabral, Ana M P; Lucena, Ana C A; Medeiros, Auriene L; Terceiro, Bernardino B; Leda, Neuma M F S; Baía, Sandra R D; Pinheiro, Josilene M F; Cassiano, Alexandra N; Melo, Andressa N L; Cavalcanti, Anny K O; Souza, Camila V S; Queiroz, Dayanna J M; Farias, Hercilla N C F; Souza, Larissa C F; Santos, Letícia S; Lima, Luana R M; Hoffmann, Meg S; Ribeiro, Átala S Silva; Vasconcelos, Daniel F; Dutra, Eliane S; Ito, Marina K; Neto, José A F; Santos, Alexsandro F; Sousa, Rosângela M L; Dias, Luciana Pereira P; Lima, Maria T M A; Modanesi, Victor G; Teixeira, Adriana F; Estrada, Luciana C N C D; Modanesi, Paulo V G; Gomes, Adriana B L; Rocha, Bárbara R S; Teti, Cristina; David, Marta M; Palácio, Bruna M; Junior, Délcio G S; Faria, Érica H S; Oliveira, Michelle C F; Uehara, Rose M; Sasso, Sandramara; Moreira, Annie S B; Cadinha, Ana C A H; Pinto, Carla W M; Castilhos, Mariana P; Costa, Mariana; Kovacs, Cristiane; Magnoni, Daniel; Silva, Quênia; Germini, Michele F C A; da Silva, Renata A; Monteiro, Aline S; dos Santos, Karina G; Moreira, Priscila; Amparo, Fernanda C; Paiva, Catharina C J; Poloni, Soraia; Russo, Diana S; Silveira, Izabele V; Moraes, Maria A; Boklis, Mirena; Cardoso, Quinto I; Moreira, Annie S B; Damaceno, Aline M S; Santos, Elisa M; Dias, Glauber M; Pinho, Cláudia P S; Cavalcanti, Adrilene C; Bezerra, Amanda S; Queiroga, Andrey V; Rodrigues, Isa G; Leal, Tallita V; Sahade, Viviane; Amaral, Daniele A; Souza, Diana S; Araújo, Givaldo A; Curvello, Karine; Heine, Manuella; Barretto, Marília M S; Reis, Nailson A; Vasconcelos, Sandra M L; Vieira, Danielly C; Costa, Francisco A; Fontes, Jessica M S; Neto, Juvenal G C; Navarro, Laís N P; Ferreira, Raphaela C; Marinho, Patrícia M; Abib, Renata Torres; Longo, Aline; Bertoldi, Eduardo G; Ferreira, Lauren S; Borges, Lúcia R; Azevedo, Norlai A; Martins, Celma M; Kato, Juliana T; Izar, Maria C O; Asoo, Marina T; de Capitani, Mariana D; Machado, Valéria A; Fonzar, Waléria T; Pinto, Sônia L; Silva, Kellen C; Gratão, Lúcia H A; Machado, Sheila D; de Oliveira, Susane R U; Bressan, Josefina; Caldas, Ana P S; Lima, Hatanne C F M; Hermsdorff, Helen H M; Saldanha, Tânia M; Priore, Sílvia E; Feres, Naoel H; Neves, Adila de Queiroz; Cheim, Loanda M G; Silva, Nilma F; Reis, Silvia R L; Penafort, Andreza M; de Queirós, Ana Paula O; Farias, Geysa M N; de los Santos, Mônica L P; Ambrozio, Cíntia L; Camejo, Cirília N; dos Santos, Cristiano P; Schirmann, Gabriela S; Boemo, Jorge L; Oliveira, Rosane E C; Lima, Súsi M B; Bortolini, Vera M S; Matos, Cristina H; Barretta, Claiza; Specht, Clarice M; de Souza, Simone R; Arruda, Cristina S; Rodrigues, Priscila A; Berwanger, Otávio

    2016-01-01

    This article reports the rationale for the Brazilian Cardioprotective Nutritional Program (BALANCE Program) Trial. This pragmatic, multicenter, nationwide, randomized, concealed, controlled trial was designed to investigate the effects of the BALANCE Program in reducing cardiovascular events. The BALANCE Program consists of a prescribed diet guided by nutritional content recommendations from Brazilian national guidelines using a unique nutritional education strategy, which includes suggestions of affordable foods. In addition, the Program focuses on intensive follow-up through one-on-one visits, group sessions, and phone calls. In this trial, participants 45 years or older with any evidence of established cardiovascular disease will be randomized to the BALANCE or control groups. Those in the BALANCE group will receive the afore mentioned program interventions, while controls will be given generic advice on how to follow a low-fat, low-energy, low-sodium, and low-cholesterol diet, with a view to achieving Brazilian nutritional guideline recommendations. The primary outcome is a composite of death (any cause), cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, or hospitalization for unstable angina. A total of 2468 patients will be enrolled in 34 sites and followed up for up to 48 months. If the BALANCE Program is found to decrease cardiovascular events and reduce risk factors, this may represent an advance in the care of patients with cardiovascular disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Canned bluefin tuna, an in vitro cardioprotective functional food potentially safer than commercial fish oil based pharmaceutical formulations.

    Science.gov (United States)

    Tenore, Gian Carlo; Calabrese, Giorgio; Ritieni, Alberto; Campiglia, Pietro; Giannetti, Daniela; Novellino, Ettore

    2014-09-01

    Commercial canned fish species typical in the Italian market were evaluated for their lipid profile. Bluefin tuna samples showed the highest content in omega-3 fatty acids (n-3 PUFA) among the canned fish samples analyzed. Tests on H9C2 cardiomyocytes revealed that bluefin tuna n-3 PUFA may responsible for a significant cell protection against both physiological and doxorubicin-induced oxidative stress. Analogous tests performed by incubating cardiac cells with n-3 PUFA ethyl esters, of which most of fish oil pharmaceutical formulations (FOPF) are based, showed cytotoxicity at high doses. Our results highlighted that n-3 PUFA contents in a 50 g canned bluefin tuna portion would be almost equivalent to and potentially safer than those of 1 FOPF capsule (1000 mg)/die usually suggested for hyperlipidaemic subjects. Thus, Italian commercial canned bluefin tuna could be indicated as a functional food with potential health benefits for the prevention and care of cardiovascular disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Cardioprotective peptides from marine sources.

    Science.gov (United States)

    Harnedy, Padraigín A; FitzGerald, Richard J

    2013-05-01

    Elevated blood pressure or hypertension is one of the fastest growing health problems worldwide. Although the etiology of essential hypertension has a genetic component, dietary factors play an important role. With the high costs and adverse side-effects associated with synthetic antihypertensive drugs and the awareness of the link between diet and health there has been increased focus on identification of food components that may contribute to cardiovascular health. In recent years special interest has been paid to the cardioprotective activity of peptides derived from food proteins including marine proteins. These peptides are latent within the sequence of the parent protein and only become active when released by proteolytic digestion during gastrointestinal digestion or through food processing. Current data on antihypertensive activity of marine-derived protein hydrolysates/peptides in animal and human studies is reviewed herein. Furthermore, products containing protein hydrolysates/peptides from marine origin with antihypertensive effects are discussed.

  17. Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

    Science.gov (United States)

    Borges, Juliana Pereira; Lessa, Marcos Adriano

    2015-01-01

    Background Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate. Objective To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury. Methods A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies. Results The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review. Conclusion On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions. PMID:25830711

  18. Adjuvant Cardioprotection in Cardiac Surgery: Update

    Directory of Open Access Journals (Sweden)

    Robert Wagner

    2014-01-01

    Full Text Available Cardiac surgery patients are now more risky in terms of age, comorbidities, and the need for complex procedures. It brings about reperfusion injury, which leads to dysfunction and/or loss of part of the myocardium. These groups of patients have a higher incidence of postoperative complications and mortality. One way of augmenting intraoperative myocardial protection is the phenomenon of myocardial conditioning, elicited with brief nonlethal episodes of ischaemia-reperfusion. In addition, drugs are being tested that mimic ischaemic conditioning. Such cardioprotective techniques are mainly focused on reperfusion injury, a complex response of the organism to the restoration of coronary blood flow in ischaemic tissue, which can lead to cell death. Extensive research over the last three decades has revealed the basic mechanisms of reperfusion injury and myocardial conditioning, suggesting its therapeutic potential. But despite the enormous efforts that have been expended in preclinical studies, almost all cardioprotective therapies have failed in the third phase of clinical trials. One reason is that evolutionary young cellular mechanisms of protection against oxygen handling are not very robust. Ischaemic conditioning, which is among these, is also limited by this. At present, the prevailing belief is that such options of treatment exist, but their full employment will not occur until subquestions and methodological issues with the transfer into clinical practice have been resolved.

  19. Regulation of Sirtuin-Mediated Protein Deacetylation by Cardioprotective Phytochemicals

    Directory of Open Access Journals (Sweden)

    Niria Treviño-Saldaña

    2017-01-01

    Full Text Available Modulation of posttranslational modifications (PTMs, such as protein acetylation, is considered a novel therapeutic strategy to combat the development and progression of cardiovascular diseases. Protein hyperacetylation is associated with the development of numerous cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction. Several phytochemicals exert cardioprotective effects by regulating protein acetylation levels. These effects are mainly exerted via activation of Sirt1 and Sirt3 and inhibition of acetyltransferases. Numerous studies support a cardioprotective role for sirtuin activators (e.g., resveratrol, as well as other emerging modulators of protein acetylation, including curcumin, honokiol, oroxilyn A, quercetin, epigallocatechin-3-gallate, bakuchiol, tyrosol, and berberine. Studies also point to a cardioprotective role for various nonaromatic molecules, such as docosahexaenoic acid, alpha-lipoic acid, sulforaphane, and caffeic acid ethanolamide. Here, we review the vast evidence from the bench to the clinical setting for the potential cardioprotective roles of various phytochemicals in the modulation of sirtuin-mediated deacetylation.

  20. Regulation of Sirtuin-Mediated Protein Deacetylation by Cardioprotective Phytochemicals

    Science.gov (United States)

    2017-01-01

    Modulation of posttranslational modifications (PTMs), such as protein acetylation, is considered a novel therapeutic strategy to combat the development and progression of cardiovascular diseases. Protein hyperacetylation is associated with the development of numerous cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction. Several phytochemicals exert cardioprotective effects by regulating protein acetylation levels. These effects are mainly exerted via activation of Sirt1 and Sirt3 and inhibition of acetyltransferases. Numerous studies support a cardioprotective role for sirtuin activators (e.g., resveratrol), as well as other emerging modulators of protein acetylation, including curcumin, honokiol, oroxilyn A, quercetin, epigallocatechin-3-gallate, bakuchiol, tyrosol, and berberine. Studies also point to a cardioprotective role for various nonaromatic molecules, such as docosahexaenoic acid, alpha-lipoic acid, sulforaphane, and caffeic acid ethanolamide. Here, we review the vast evidence from the bench to the clinical setting for the potential cardioprotective roles of various phytochemicals in the modulation of sirtuin-mediated deacetylation. PMID:29234485

  1. CARDIOPROTECTIVE EFFECTS OF PHYTOSTEROLS

    OpenAIRE

    Jyotika Dhankhar

    2013-01-01

    Foods and nutrients play a vital role in normal functioning of the body. They are helpful in maintaining the health of the individual and in reducing the risk of various diseases. Worldwide acceptance of this fact formed a recognition link between "nutrition" and "health" and the concept of "nutraceuticals" has evolved. More than any other disease, the etiology of cardiovascular disease reveals many risk factors that are amenable to nutraceutical intervention. The scientific literature shows ...

  2. Kleptomania and Potential Exacerbating Factors

    Science.gov (United States)

    2011-01-01

    Kleptomania is an impulse control disorder that can cause significant impairment and serious consequences. Often, the condition is kept secret by the patient, and usually help is sought only when confronted by the legal consequences of the impulsive behaviors. Historically, kleptomania has been viewed from a psychodynamic perspective, and the mainstay of treatment has been psychotherapy. Recently, attempts to explain kleptomania within a neuropsychiatric paradigm have highlighted the possible links between mood disorders, addictive behaviors, and brain injury with kleptomania. These associations with kleptomania can be extrapolated to pharmacological strategies that can potentially help in treating kleptomania. A case of kleptomania, which was potentially exacerbated by multiple factors, will be reviewed. Treatment modalities used in this case, including the use of the Yale-Brown Obsessive Compulsive Scale as a surrogate marker to gauge response to treatment, will be discussed. PMID:22132369

  3. Cardioprotective effect of valsartan in mice with short-term high-salt diet by regulating cardiac aquaporin 1 and angiogenic factor expression.

    Science.gov (United States)

    Jiang, Yong; Wang, Hui-Yan; Zheng, Sheng; Mu, Shang-Qiang; Ma, Meng-Ni; Xie, Xin; Zhang, Yang-Yang; Zhang, Chun-Xue; Cai, Jian-Hui

    2015-01-01

    Hypertension is the most common risk factor for various cardiovascular and cerebrovascular diseases that affects approximately 61 million, or 25% of the population in United States. The dietary salt intake is one of the most important but modifiable factors for hypertension. In the current study, we aim to elucidate the role of aquaporin 1 in high-salt-induced hypertension and cardiac injuries and whether angiotensin II receptor blocker valsartan could ameliorate the effect of high salt on blood pressure. Mice were fed with normal diet, high-salt diet in the presence or absence of valsartan for 4 weeks. The body weight gain, feeding behavior, blood pressure, and cardiac pathology changes were monitored after 4 weeks. The expression of aquaporin 1, vascular endothelial growth factor, transforming growth factor β1, and basic fibroblast growth factor were analyzed using quantitative real-time polymerase chain reaction, Western blot, and immunohistochemical staining. Valsartan partially reversed the effects of high-salt diet on hypertension, cardiac injuries such as fibrosis and inflammatory cell infiltration, and inhibition of aquaporin 1 and angiogenic factors; valsartan alone did not exert such effects. The current data demonstrated that the reduction of cardiac aquaporin 1 and angiogenic factor expression level might be associated with high-salt-induced hypertension and cardiac injuries in mice, which could be ameliorated by angiotensin II receptor blocker treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Potential success factors in brand development

    DEFF Research Database (Denmark)

    Esbjerg, Lars; Grunert, Klaus G.; Poulsen, Carsten Stig

    2005-01-01

    to the marketing of the brand." The branding literature mentions many important aspects, factors, issues, brand requirements, steps, building blocks or guidelines for building strong brands. However, these are all quite general and abstract. Given the substantial body of literature on branding, surprisingly few......? This is the question we want to answer. More specifically, we want to identify potential success factors in building strong brands, understood as brands with high consumer-based brand equity. Keller (1993, p. 2) defined customer-based brand equity as "the differential effect of brand knowledge on consumer response...... of this paper is to identify potential success factors in developing strong brands and to test whether these factors can be used to discriminate between strong and weak brands. It does so through a review of the literature for potential success factors. Furthermore, to ensure that important factors have...

  5. Development of fluorescence imaging-based assay for screening cardioprotective compounds from medicinal plants.

    Science.gov (United States)

    Wang, Yi; Zhao, Xiaoping; Gao, Xiumei; Nie, Xiaojing; Yang, Yingxin; Fan, Xiaohui

    2011-09-19

    Medicinal plants have been widely recognized as a renewable resource for the discovery of novel leads and drug. In this study, an approach for screening and identification compounds with cardioprotective activity from medicinal plant extracts by cellular-fluorescence imaging technique was developed. It is a cell-based assay for measuring mitochondrial membrane potential changes in H9c2 cardiac muscle cells exposed to H(2)O(2) by using a fluorescence automatic microscopy screening platform. Rhodamine 123 was used as the fluorescent dye to indicate the change of mitochondrial membrane potential. The sensitivity and linear range of the proposed approach were evaluated and validated using vitamin C, an antioxidative compound. The method was applied to screen active components with potent cardioprotective effects from a traditional Chinese formula. The potential cardioprotective components were identified by liquid chromatography coupled with mass spectrometry (LC/MS). Moreover, the utility of the proposed approach was further validated by three compounds (salvianolic acid B, protocatechuic aldehyde, and tanshinone II A) identified from the formula which showed cardioprotective effects in a dose-dependent manner. These applications suggested that the proposed rapid and sensitive screening approach offers an efficient way to discover active components or compounds from medicinal plants. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Potential effect of opium consumption on controlling diabetes and some cardiovascular risk factors in diabetic patients.

    Science.gov (United States)

    Rahimi, Najmeh; Gozashti, Mohamad Hossain; Najafipour, Hamid; Shokoohi, Mostafa; Marefati, Hamid

    2014-01-01

    Due to this belief that opium may have beneficial effects on diabetes or cardiovascular risk factors, the present study aimed to assess the potential and possible effects of opium consumption on diabetes control and some cardiovascular risk factors in diabetic patients. This study enrolled 374 diabetic subjects from diabetes care centers in Kerman, Iran, including opium user group (n = 179) and a non-opium user group (n = 195). The data were collected through a questionnaire completed by interviewing, physical examination and laboratory assessment. Opium did not show any statistically significant effect on blood glucose, glycated hemoglobin (HbA1C), fasting blood sugar (FBS), low-density lipoprotein (LDL) and diastolic blood pressure. However, systolic blood pressure (SBP) and prevalence of high SBP were significantly higher in opium user group (P opium user group (P opium does not seem to have beneficial effects on diabetes control or cardiovascular risk factors. Therefore, it would not be advisable to consume opium as an anti-diabetes or cardioprotective agent.

  7. Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection.

    Science.gov (United States)

    Lamont, Kim T; Somers, Sarin; Lacerda, Lydia; Opie, Lionel H; Lecour, Sandrine

    2011-05-01

    Epidemiological studies suggest that regular moderate consumption of red wine confers cardioprotection but the mechanisms involved in this effect remain unclear. Recent studies demonstrate the presence of melatonin in wine. We propose that melatonin, at a concentration found in red wine, confers cardioprotection against ischemia-reperfusion injury. Furthermore, we investigated whether both melatonin and resveratrol protect via the activation of the newly discovered survivor activating factor enhancement (SAFE) prosurvival signaling pathway that involves the activation of tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Isolated perfused male mouse (wild type, TNFα receptor 2 knockout mice, and cardiomyocyte-specific STAT3-deficient mice) or rat hearts (Wistars) were subjected to ischemia-reperfusion. Resveratrol (2.3 mg/L) or melatonin (75 ng/L) was perfused for 15 min with a 10-min washout period prior to an ischemia-reperfusion insult. Infarct size was measured at the end of the protocol, and Western blot analysis was performed to evaluate STAT3 activation prior to the ischemic insult. Both resveratrol and melatonin, at concentrations found in red wine, significantly reduced infarct size compared with control hearts in wild-type mouse hearts (25 ± 3% and 25 ± 3% respectively versus control 69 ± 3%, P < 0.001) but failed to protect in TNF receptor 2 knockout or STAT3-deficient mice. Furthermore, perfusion with either melatonin or resveratrol increased STAT3 phosphorylation prior to ischemia by 79% and 50%, respectively (P < 0.001 versus control). Our data demonstrate that both melatonin and resveratrol, as found in red wine, protect the heart in an experimental model of myocardial infarction via the SAFE pathway. © 2011 John Wiley & Sons A/S.

  8. Cardioprotective and Metabolomic Profiling of Selected Medicinal Plants against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Nadia Afsheen

    2018-01-01

    Full Text Available In this research work, the antioxidant and metabolomic profiling of seven selected medicinally important herbs including Rauvolfia serpentina, Terminalia arjuna, Coriandrum sativum, Elettaria cardamom, Piper nigrum, Allium sativum, and Crataegus oxyacantha was performed. The in vivo cardioprotective potential of these medicinal plants was evaluated against surgically induced oxidative stress through left anterior descending coronary artery ligation (LADCA in dogs. The antioxidant profiling of these plants was done through DPPH and DNA protection assay. The C. oxyacantha and T. arjuna showed maximum antioxidant potential, while the E. cardamom showed poor antioxidative strength even at its high concentration. Different concentrations of extracts of the said plants exhibited the protection of plasmid DNA against H2O2 damage as compared to the plasmid DNA merely treated with H2O2. The metabolomic profiling through LC-MS analysis of these antioxidants revealed the presence of active secondary metabolites responsible for their antioxidant potential. During in vivo analysis, blood samples of all treatment groups were drawn at different time intervals to analyze the cardiac and hemodynamic parameters. The results depicted that the group pretreated with HC4 significantly sustained the level of CK-MB, SGOT, and LDH as well as hemodynamic parameters near to normal. The histopathological examination also confirmed the cardioprotective potential of HC4. Thus, the HC4 being safe and inexpensive cardioprotective herbal combination could be considered as an alternate of synthetic drugs.

  9. Cardioprotective and Metabolomic Profiling of Selected Medicinal Plants against Oxidative Stress

    Science.gov (United States)

    Afsheen, Nadia; Jahan, Nazish; Ijaz, Misbah; Manzoor, Asad; Khan, Khalid Mahmood; Hina, Saman

    2018-01-01

    In this research work, the antioxidant and metabolomic profiling of seven selected medicinally important herbs including Rauvolfia serpentina, Terminalia arjuna, Coriandrum sativum, Elettaria cardamom, Piper nigrum, Allium sativum, and Crataegus oxyacantha was performed. The in vivo cardioprotective potential of these medicinal plants was evaluated against surgically induced oxidative stress through left anterior descending coronary artery ligation (LADCA) in dogs. The antioxidant profiling of these plants was done through DPPH and DNA protection assay. The C. oxyacantha and T. arjuna showed maximum antioxidant potential, while the E. cardamom showed poor antioxidative strength even at its high concentration. Different concentrations of extracts of the said plants exhibited the protection of plasmid DNA against H2O2 damage as compared to the plasmid DNA merely treated with H2O2. The metabolomic profiling through LC-MS analysis of these antioxidants revealed the presence of active secondary metabolites responsible for their antioxidant potential. During in vivo analysis, blood samples of all treatment groups were drawn at different time intervals to analyze the cardiac and hemodynamic parameters. The results depicted that the group pretreated with HC4 significantly sustained the level of CK-MB, SGOT, and LDH as well as hemodynamic parameters near to normal. The histopathological examination also confirmed the cardioprotective potential of HC4. Thus, the HC4 being safe and inexpensive cardioprotective herbal combination could be considered as an alternate of synthetic drugs. PMID:29576858

  10. Cardioprotective and nonprotective regimens of chronic hypoxia diversely affect the myocardial antioxidant systems

    Czech Academy of Sciences Publication Activity Database

    Kašparová, D.; Neckář, Jan; Dabrowská, L.; Novotný, J.; Mráz, J.; Kolář, František; Žurmanová, J.

    2015-01-01

    Roč. 47, č. 12 (2015), s. 612-620 ISSN 1094-8341 R&D Projects: GA ČR(CZ) GAP303/12/1162; GA ČR(CZ) GA13-10267S Institutional support: RVO:67985823 Keywords : adaptation to hypoxia * cardioprotection * ischemia-reperfusion injury * oxidative stress * antioxidant defense Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.615, year: 2015

  11. Hypertrophied hearts: what of sevoflurane cardioprotection?

    DEFF Research Database (Denmark)

    Larsen, Jens Kjærgaard Rolighed; Smerup, Morten Holdgaard; Hasenkam, John Michael

    2009-01-01

    pigs (n=7-12/group) were subjected to 45 min distal coronary artery balloon occlusion, followed by 120 min of reperfusion. Controls were given pentobarbital, while sevoflurane cardioprotection was achieved by 3.2% inhalation throughout the experiment. Chronic banding of the ascending aorta resulted......-at-risk) was reduced from mean 55.0 (13.6%) (+/-SD) in controls to 17.5 (13.2%) by sevoflurane (P=0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) (P=0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) (P=0.001). CONCLUSION: Sevoflurane abrogated...

  12. Cardioprotective adaptation of rats to intermittent hypobaric hypoxia is accompanied by the increased association of hexokinase with mitochondria

    Czech Academy of Sciences Publication Activity Database

    Wasková-Arnoštová, P.; Elsnicová, B.; Kašparová, D.; Horníková, D.; Kolář, František; Novotný, J.; Žurmanová, J.

    2015-01-01

    Roč. 119, č. 12 (2015), s. 1487-1493 ISSN 8750-7587 Institutional support: RVO:67985823 Keywords : hexokinase * mitochondrial colocalization * cardioprotection * chronic hypoxia * rat heart Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.004, year: 2015

  13. Association of Exercise Preconditioning With Immediate Cardioprotection: A Review.

    NARCIS (Netherlands)

    Thijssen, D.H.J.; Redington, A.; George, K.P.; Hopman, M.T.E.; Jones, H.

    2018-01-01

    Importance: Exercise reduces the risk of cardiovascular events, including through an underrecognized, clinically useful form of acute cardioprotection accessible after a single episode of exercise, which is called cardiovascular preconditioning. Observations: Preclinical evidence shows that 1 to 3

  14. Estrogen replacement therapy and cardioprotection: mechanisms and controversies

    Directory of Open Access Journals (Sweden)

    M.T.R. Subbiah

    2002-03-01

    Full Text Available Epidemiological and case-controlled studies suggest that estrogen replacement therapy might be beneficial in terms of primary prevention of coronary heart disease (CHD. This beneficial effect of estrogens was initially considered to be due to the reduction of low density lipoproteins (LDL and to increases in high density lipoproteins (HDL. Recent studies have shown that estrogens protect against oxidative stress and decrease LDL oxidation. Estrogens have direct effects on the arterial tissue and modulate vascular reactivity through nitric oxide and prostaglandin synthesis. While many of the effects of estrogen on vascular tissue are believed to be mediated by estrogen receptors alpha and ß, there is evidence for `immediate non-genomic' effects. The role of HDL in interacting with 17ß-estradiol including its esterification and transfer of esterified estrogens to LDL is beginning to be elucidated. Despite the suggested positive effects of estrogens, two recent placebo-controlled clinical trials in women with CHD did not detect any beneficial effects on overall coronary events with estrogen therapy. In fact, there was an increase in CHD events in some women. Mutations in thrombogenic genes (factor V Leiden, prothrombin mutation, etc. in a subset of women may play a role in this unexpected finding. Thus, the cardioprotective effect of estrogens appears to be more complicated than originally thought and requires more research.

  15. Mast cells, peptides and cardioprotection - an unlikely marriage?

    LENUS (Irish Health Repository)

    Walsh, S K

    2012-01-31

    1 Mast cells have classically been regarded as the \\'bad guys\\' in the setting of acute myocardial ischaemia, where their released contents are believed to contribute both to tissue injury and electrical disturbances resulting from ischaemia. Recent evidence suggests, however, that if mast cell degranulation occurs in advance of ischaemia onset, this may be cardioprotective by virtue of the depletion of mast cell contents that can no longer act as instruments of injury when the tissue becomes ischaemic. 2 Many peptides, such as ET-1, adrenomedullin, relaxin and atrial natriuretic peptide, have been demonstrated to be cardioprotective when given prior to the onset of myocardial ischaemia, although their physiological functions are varied and the mechanisms of their cardioprotective actions appear to be diverse and often ill defined. However, one common denominator that is emerging is the ability of these peptides to modulate mast cell degranulation, raising the possibility that peptide-induced mast cell degranulation or stabilization may hold the key to a common mechanism of their cardioprotection. 3 The aim of this review was to consolidate the evidence implying that mast cell degranulation could play both a detrimental and protective role in myocardial ischaemia, depending upon when it occurs, and that this may underlie the cardioprotective effects of a range of diverse peptides that exerts physiological effects within the cardiovascular system.

  16. Anti-hypertensive and cardioprotective effects of a novel apitherapy formulation via upregulation of peroxisome proliferator-activated receptor-α and -γ in spontaneous hypertensive rats.

    Science.gov (United States)

    Sun, Yanru; Han, Mingfeng; Shen, Zhenhuang; Huang, Haibo; Miao, Xiaoqing

    2018-02-01

    Ventricular remodeling is associated with many heart diseases, and ventricular remodeling induced by hypertension can be fatal independent of hypertension. In this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling (BYL), which contained propolis, royal jelly, and bee venom, to treat spontaneous hypertensive rats (SHRs). We then evaluated the pharmacology of BYL and the potential mechanisms through which BYL affects hypertension and ventricular remodeling. We found that BYL treatment could reduce blood pressure in SHRs. Thereafter, we found that BYL treatment reduced serum levels of angiotensin II, endothelin 1, and transforming growth factor-β and improved the myocardial structure. Moreover, the results of quantitative real-time polymerase chain reaction indicated that BYL treatment could upregulate the mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. Thus, we could conclude that BYL had hypotensive and cardioprotective effects in SHRs, potentially through improvement of myocardial energy metabolism.

  17. Anti-hypertensive and cardioprotective effects of a novel apitherapy formulation via upregulation of peroxisome proliferator-activated receptor-α and -γ in spontaneous hypertensive rats

    Directory of Open Access Journals (Sweden)

    Yanru Sun

    2018-02-01

    Full Text Available Ventricular remodeling is associated with many heart diseases, and ventricular remodeling induced by hypertension can be fatal independent of hypertension. In this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling (BYL, which contained propolis, royal jelly, and bee venom, to treat spontaneous hypertensive rats (SHRs. We then evaluated the pharmacology of BYL and the potential mechanisms through which BYL affects hypertension and ventricular remodeling. We found that BYL treatment could reduce blood pressure in SHRs. Thereafter, we found that BYL treatment reduced serum levels of angiotensin II, endothelin 1, and transforming growth factor-β and improved the myocardial structure. Moreover, the results of quantitative real-time polymerase chain reaction indicated that BYL treatment could upregulate the mRNA expression of peroxisome proliferator-activated receptor (PPAR-α and PPAR-γ. Thus, we could conclude that BYL had hypotensive and cardioprotective effects in SHRs, potentially through improvement of myocardial energy metabolism.

  18. Levosimendan for Perioperative Cardioprotection: Myth or Reality?

    Science.gov (United States)

    Santillo, Elpidio; Migale, Monica; Massini, Carlo; Incalzi, Raffaele Antonelli

    2018-03-21

    Levosimendan is a calcium sensitizer drug causing increased contractility in the myocardium and vasodilation in the vascular system. It is mainly used for the therapy of acute decompensated heart failure. Several studies on animals and humans provided evidence of the cardioprotective properties of levosimendan including preconditioning and anti-apoptotic. In view of these favorable effects, levosimendan has been tested in patients undergoing cardiac surgery for the prevention or treatment of low cardiac output syndrome. However, initial positive results from small studies have not been confirmed in three recent large trials. To summarize levosimendan mechanisms of action and clinical use and to review available evidence on its perioperative use in cardiac surgery setting. We searched two electronic medical databases for randomized controlled trials studying levosimendan in cardiac surgery patients, ranging from January 2000 to August 2017. Meta-analyses, consensus documents and retrospective studies were also reviewed. In the selected interval of time, 54 studies on the use of levosimendan in heart surgery have been performed. Early small size studies and meta-analyses have suggested that perioperative levosimendan infusion could diminish mortality and other adverse outcomes (i.e. intensive care unit stay and need for inotropic support). Instead, three recent large randomized controlled trials (LEVO-CTS, CHEETAH and LICORN) showed no significant survival benefits from levosimendan. However, in LEVO-CTS trial, prophylactic levosimendan administration significantly reduced the incidence of low cardiac output syndrome. Based on most recent randomized controlled trials, levosimendan, although effective for the treatment of acute heart failure, can't be recommended as standard therapy for the management of heart surgery patients. Further studies are needed to clarify whether selected subgroups of heart surgery patients may benefit from perioperative levosimendan

  19. Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion: a fibroblast growth factor receptor, protein kinase C, and tyrosine kinase-dependent mechanism

    NARCIS (Netherlands)

    Palmen, Meindert; Daemen, Mat J. A. P.; de Windt, Leon J.; Willems, Jodil; Dassen, Willem R. M.; Heeneman, Sylvia; Zimmermann, Rene; van Bilsen, Marc; Doevendans, Pieter A.

    2004-01-01

    We sought to investigate the role of fibroblast growth factor (FGF)-1 during acute myocardial ischemia and reperfusion. The FGFs display cardioprotective effects during ischemia and reperfusion. We investigated FGF-1-induced cardioprotection during ischemia and reperfusion and the intracellular

  20. Experimental evidence for the cardioprotective effects of red wine.

    Science.gov (United States)

    Das, Samarjit; Santani, Dev D; Dhalla, Naranjan S

    2007-01-01

    Both epidemiological and experimental studies have revealed that intake of wine, particularly red wine, in moderation protects cardiovascular health; however, the experimental basis for such an action is not fully understood. Because all types of red wine contain varying amounts of alcohol and antioxidants, it is likely that the cardioprotective effect of red wine is due to both these constituents. In view of its direct action on the vascular smooth muscle cells, alcohol may produce coronary vasodilation in addition to attenuating oxidative stress by its action on the central nervous system. The antioxidant components of red wine may provide cardioprotection by their ability to reduce oxidative stress in the heart under different pathological conditions. Mild-to-moderate red wine consumption improves cardiac function in the ischemic myocardium through the protection of endothelial function, the expression of several cardioprotective oxidative stress-inducible proteins, as well as the activation of adenosine receptors and nitrous oxide synthase mechanisms.

  1. Experimental evidence for the cardioprotective effects of red wine

    Science.gov (United States)

    Das, Samarjit; Santani, Dev D; Dhalla, Naranjan S

    2007-01-01

    Both epidemiological and experimental studies have revealed that intake of wine, particularly red wine, in moderation protects cardiovascular health; however, the experimental basis for such an action is not fully understood. Because all types of red wine contain varying amounts of alcohol and antioxidants, it is likely that the cardioprotective effect of red wine is due to both these constituents. In view of its direct action on the vascular smooth muscle cells, alcohol may produce coronary vasodilation in addition to attenuating oxidative stress by its action on the central nervous system. The antioxidant components of red wine may provide cardioprotection by their ability to reduce oxidative stress in the heart under different pathological conditions. Mild-to-moderate red wine consumption improves cardiac function in the ischemic myocardium through the protection of endothelial function, the expression of several cardioprotective oxidative stress-inducible proteins, as well as the activation of adenosine receptors and nitrous oxide synthase mechanisms. PMID:18650973

  2. HUMAN POTENTIAL AS A STRATEGIC FACTOR OF REGIONAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    A.M. Korobeynikov

    2008-12-01

    Full Text Available The article gives an insight of human potential as the strategic factor of regional development. The matter of human potential and its role in regional reproducing process is considered; regional intellectual potential as an integral part of human potential is analysed. The author outlines major directions of active social policy, aimed to develop regional human potential.

  3. Subconjunctival hemorrhage: risk factors and potential indicators

    Directory of Open Access Journals (Sweden)

    Tarlan B

    2013-06-01

    Full Text Available Bercin Tarlan,1 Hayyam Kiratli21Department of Ophthalmology, Kozluk State Hospital, Batman, Turkey; 2Ocular Oncology Service, Hacettepe University Schoolof Medicine, Ankara, TurkeyAbstract: Subconjunctival hemorrhage is a benign disorder that is a common cause of acute ocular redness. The major risk factors include trauma and contact lens usage in younger patients, whereas among the elderly, systemic vascular diseases such as hypertension, diabetes, and arteriosclerosis are more common. In patients in whom subconjunctival hemorrhage is recurrent or persistent, further evaluation, including workup for systemic hypertension, bleeding disorders, systemic and ocular malignancies, and drug side effects, is warranted.Keywords: subconjunctival hemorrhage, contact lens, hypertension, red eye

  4. Pleiotropic preconditioning-like cardioprotective effects of hypolipidemic drugs in acute ischemia–reperfusion in normal and hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Ravingerová, T.; Ledvényiová-Farkašová, V.; Ferko, M.; Barteková, M.; Bernátová, I.; Pecháňová, O.; Adameová, A.; Kolář, František; Lazou, A.

    2015-01-01

    Roč. 93, č. 7 (2015), s. 495-503 ISSN 0008-4212 R&D Projects: GA MŠk(CZ) 7AMB14SK115 Grant - others:AV ČR(CZ) SAV-15-15 Program:Bilaterální spolupráce Institutional support: RVO:67985823 Keywords : myocardial ischemia * cardioprotection * hypolipidemic drugs Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.704, year: 2015

  5. Incidence And Potential Risk Factors Of Low Birth Weight Among ...

    African Journals Online (AJOL)

    Incidence And Potential Risk Factors Of Low Birth Weight Among Full Term Deliveries. ... (LBW) is a reliable indicator in monitoring and evaluating the success of maternal and child ... Key words: Low birth weight- incidence- associated factors.

  6. The cardioprotective efficacy of TVP1022 in a rat model of ischaemia/reperfusion.

    Science.gov (United States)

    Ertracht, Offir; Liani, Esti; Bachner-Hinenzon, Noa; Bar-Am, Orit; Frolov, Luba; Ovcharenko, Elena; Awad, Huda; Blum, Shany; Barac, Yaron; Amit, Tamar; Adam, Dan; Youdim, Moussa; Binah, Ofer

    2011-06-01

    Because myocardial infarction is a major cause of morbidity and mortality worldwide, protecting the heart from the ischaemia and reperfusion (I/R) damage is the focus of intense research. Based on our in vitro findings showing that TVP1022 (the S-enantiomer of rasagiline, an anti-Parkinsonian drug) possesses cardioprotective effects, in the present study we investigated the hypothesis that TVP1022 can attenuate myocardial damage in an I/R model in rats. The model consisted of 30-min occlusion of the left anterior descending artery followed by 4 or 24 h reperfusion. In addition, we investigated the possible mechanisms of cardioprotection in H9c2 cells and neonatal rat ventricular myocytes (NRVM) exposed to oxidative stress induced by H(2) O(2) . TVP1022 (20 and 40 mg·kg(-1) ) administered 5 min before reperfusion followed by an additional dose 4 h after reperfusion reduced the infarct size and attenuated the decline in ventricular function. TVP1022 also attenuated I/R-induced deterioration in cardiac mitochondrial integrity evaluated by mitochondrial swelling capacity. In vitro, using H9c2 cells and NRVM, TVP1022 attenuated both serum free- and H(2) O(2) -induced damage, preserved mitochondrial membrane potential and Bcl-2 levels, inhibited mitochondrial cytochrome c release and the increase in cleaved caspase 9 and 3 levels, and enhanced the phosphorylation of protein kinase C and glycogen synthase kinase-3β. TVP1022 provided cardioprotection in a model of myocardial infarction, and therefore should be considered as a novel adjunctive therapy for attenuating myocardial damage resulting from I/R injuries. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  7. Cnidoscolus chayamansa Mc Vaugh, an important antioxidant, anti-inflammatory and cardioprotective plant used in Mexico.

    Science.gov (United States)

    García-Rodríguez, Rosa Virginia; Gutiérrez-Rebolledo, Gabriel Alfonso; Méndez-Bolaina, Enrique; Sánchez-Medina, Alberto; Maldonado-Saavedra, Octavio; Domínguez-Ortiz, Miguel Ángel; Vázquez-Hernández, Maribel; Muñoz-Muñiz, Omar David; Cruz-Sánchez, Jesús Samuel

    2014-02-03

    Cnidoscolus chayamansa Mc Vaugh (Euphorbiaceae) is commonly known as 'chaya' in Central America. In South East Mexico, because of its high nutritional values, is an important part of the diet of many indigenous communities. Chaya is also used as a traditional remedy for the treatment of diabetes, rheumatism, gastrointestinal disorders and inflammation-related diseases. Although Cnidoscolus chayamansa is one of most used and valued medicinal plants, only few studies on documenting its pharmacological properties can be found. Dried leaves of Cnidoscolus chayamansa were subjected to a successive maceration using Hex, EtOAc and EtOH. The antioxidant activities of the extracts were tested using the DPPH radical scavenging, Ferric reducing/antioxidant power and total phenolic content assays. To determine the anti-inflammatory activity, the TPA-induced mouse ear edema and the carrageenan-induced mouse paw edema assays were used. The cardioprotective effects of the EtOH extract was determined using the ischemia/reperfusion (I/R) rat model. Finally, the acute toxicity was determined using Lorke's method. The results showed a similar anti-inflammatory activity (≈30%) for all extracts but only the EtOAc extract showed relevant activity when applied intraperitoneally. When tested for their antioxidant activity none of the extracts showed a significant activity suggesting that the antinflammatory activity is not related to a direct free radical scavenging of the extracts. Additionally, the EtOH extract showed a strong cardioprotective effect at 500mg/kg when given orally. Both the EtOAc and the EtOH extract have a LD50 >5g/kg, confirming their safety in acute oral administration. All these results are relevant for a better understanding of the therapeutic used of Cnidoscolus chayamansa in the Mexican traditional medicine and highlights its cardioprotective potential. © 2013 Published by Elsevier Ireland Ltd.

  8. Characterization and cardioprotective activity of anthocyanins from Nitraria tangutorum Bobr. by-products.

    Science.gov (United States)

    Zhang, Ming; Ma, Jianbin; Bi, Hongtao; Song, Jiayin; Yang, Hongxia; Xia, Zhenghua; Du, Yuzhi; Gao, Tingting; Wei, Lixin

    2017-08-01

    The Nitraria tangutorum Bobr. fruit is an indigenous berry of the shrub belonging to the Zygophyllaceae family which grows at an altitude of over 3000 m in the Tibetan Plateau, and has been used as a native medicinal food for treating weakness of the spleen, stomach syndrome, dyspepsia, neurasthenia, dizziness, etc. for thousands of years. Nowadays, N. tangutorum industrial juice by-products generated from health food production can be a potential low cost source of some unique bioactive ingredients. In a prior study, we established a simultaneous microwave/ultrasonic assisted enzymatic extraction method for extracting antioxidant ingredients from the industrial by-products of N. tangutorum juice. In this study, these ingredients were selectively fractionated by cation-exchange resin chromatography to obtain an anthocyanin fraction namely NJBAE. NJBAE was found to be composed of 16 anthocyanins derived from six anthocyanidins by HPLC-ESI-MS, and has an appreciable cardioprotective effect on doxorubicin-induced injured H9c2 cardiomyocytes. The cardioprotective mechanism research showed that NJBAE could directly scavenge ROS, restrict further generation of ROS, promote the activity of key antioxidase, enhance glutathione redox cycling, then affect the apoptotic signaling changes in a positive way, and finally mediate caspase-dependent cell death pathways. Therefore, NJBAE has great potential to be used for preventing and treating cardiovascular disease in the food, pharmaceutical and other emerging industries.

  9. The effect of cardioprotective diet rich with natural antioxidants on chronic inflammation and oxidized LDL during cardiac rehabilitation in patients after acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Polona Mlakar

    2015-06-01

    Conclusions: The addition of cardioprotective diet, rich with natural antioxidants, to physical activity as a part of a CR program, positively modifies not just classic risk factors and exercise capacity, but also diminishes chronic inflammation markers. These effects, and oxLDL decline were most prominent in nonsmoking patients.

  10. Categorization of potential project cost overrun factors in construction industry

    Science.gov (United States)

    Karunakaran, P.; Abdullah, A. H.; Nagapan, S.; Sohu, S.; Kasvar, K. K.

    2018-04-01

    Cost overrun has been severely hit down the economy and reputations for many construction industry around the world. Many project management tools developed to control the budget of a project. However, the cost management is still considered poor as there are many cost overrun issues occurred in the construction industry. Thus, this paper aims to identify and cluster the potential construction project cost overrun factors according to their originating groups using the thematic approach. Basically, through literature review, all the potential factors that may cause cost overrun were screened thoroughly before they were clustered into seven (7) groups of the originating factors, namely project, contract, client, contractor, consultant, labour and external. Each potential factor was explained clearly with some examples based on the Malaysian case studies to illustrate the cost overrun scenario. These findings may aid in the future to highlight on how to mitigate the critical potential factors of cost overrun to reduce or overcome its impact on all the stakeholders involved.

  11. Comparison of cardioprotective effects of salvianolic acid B and benazepril on large myocardial infarction in rats.

    Science.gov (United States)

    He, Hai-Bo; Yang, Xian-Zhe; Shi, Meng-Qiong; Zeng, Xiao-Wei; Wu, Li-Mao; Li, Lian-Da

    2008-01-01

    In the present study, we compared cardioprotective effects of salvianolic acid B (Sal B) and the angiotension-converting enzyme inhibitor, benazepril, in rats with large myocardial infarction (MI). The large MI was produced by coronary artery ligation for 4 weeks in rats. The rats were divided into the following groups: sham operation; MI; MI + Sal B (100 mg/kg by a gavage, once a day for 4 weeks) and MI + benazepril (1 mg/kg by a gavage, once a day for 4 weeks). Echocardiogram, hemodynamic and hemorheological changes, angiogenesis, infarct size and cardiac remodeling, as well as messenger ribonucleic acid (mRNA) of vascular endothelium growth factor (VEGF) were measured. The following similar effects were observed in MI rats treated with Sal B and benazepril: (1) a marked improvement of echocardiographic, hemodynamic and hemorheological parameters, (2) significant reduction of infarct size, (3) significantly attenuated heart hypertrophy, left ventricular (LV) dilatation and fibrosis. The unique effects of Sal B were: angiogenesis and augmented VEGF expression in the border and remote noninfarcted LV area. These results suggest that Sal B and benazepril exerted beneficial cardioprotective effects. However, Sal B enforced some different modality than benazepril, which might improve myocardial microcirculation by augmenting VEGF expression and promoting angiogenesis besides similar effects to benazepril.

  12. Risk factors for potential drug interactions in general practice

    DEFF Research Database (Denmark)

    Bjerrum, Lars; Gonzalez Lopez-Valcarcel, Beatriz; Petersen, Gert

    2008-01-01

    interactions during 1 year. Patient factors associated with increased risk of potential drug interactions were high age, a high number of concurrently used drugs, and a high number of prescribers. Practice factors associated with potential drug interactions were a high percentage of elderly patients and a low......Objective: To identify patient- and practice-related factors associated with potential drug interactions. Methods: A register analysis study in general practices in the county of Funen, Denmark. Prescription data were retrieved from a population-based prescription database (Odense University......, depending on the severity of outcome and the quality of documentation. A two-level random coefficient logistic regression model was used to investigate factors related to potential drug interactions. Results: One-third of the population was exposed to polypharmacy, and 6% were exposed to potential drug...

  13. Experimental evidence for the cardioprotective effects of red wine

    OpenAIRE

    Das, Samarjit; Santani, Dev D; Dhalla, Naranjan S

    2007-01-01

    Both epidemiological and experimental studies have revealed that intake of wine, particularly red wine, in moderation protects cardiovascular health; however, the experimental basis for such an action is not fully understood. Because all types of red wine contain varying amounts of alcohol and antioxidants, it is likely that the cardioprotective effect of red wine is due to both these constituents. In view of its direct action on the vascular smooth muscle cells, alcohol may produce coronary ...

  14. Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection

    OpenAIRE

    Mukherjee, Uma A.; Ong, Sang-Bing; Ong, Sang-Ging; Hausenloy, Derek J.

    2015-01-01

    Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotect...

  15. The Lipid Lowering and Cardioprotective Effects of Vernonia calvoana Ethanol Extract in Acetaminophen-Treated Rats

    Directory of Open Access Journals (Sweden)

    Godwin Eneji Egbung

    2017-12-01

    Full Text Available Background: Paracetamol overdose/abuse as a result of self-medication is a common occurrence amongst people living in low/middle income countries. The present study was designed to investigate the hypolipidemic and cardioprotective potentials of Vernonia calvoana (VC ethanol extract in acetaminophen (paracetamol-treated rats. Methods: Thirty-five Wistar rats weighing 100–150 g were randomly assigned into five groups of seven rats each. Groups 2–5 received high doses of paracetamol to induce liver damage, while group 1 was used as normal control. Afterwards, they were allowed to receive varying doses of VC (group 3 and 4 or vitamin E (group 5, whilst groups 1 and 2 were left untreated. The treatment period lasted for twenty one days after which sera were harvested and assayed for serum lipid indices using standard methods. Results: Groups 3 to 5 treated animals indicated significant decrease (p < 0.001 in low density lipoprotein cholesterol (LDL-c, total cholesterol (TC and triacylglycerol (TG levels relative to the normal and acetaminophen-treated controls, the atherogenic index showed a significant decrease (p < 0.001 in all treated groups compared with normal and acetaminophen-treated controls. However, the VC- and vitamin E-treated groups showed significant (p < 0.001 increase in high density lipoprotein cholesterol (HDL-C relative to the controls. Conclusions: Data from our study suggest that ethanol leaf extract of VC possesses probable hypolipidemic and cardioprotective effects.

  16. Minoxidil opens mitochondrial KATP channels and confers cardioprotection

    Science.gov (United States)

    Sato, Toshiaki; Li, Yulong; Saito, Tomoaki; Nakaya, Haruaki

    2003-01-01

    ATP-sensitive potassium channel in the mitochondrial inner membrane (mitoKATP channel) rather than in the sarcolemma (sarcKATP channel) appears to play an important role in cardioprotection. We examined the effect of minoxidil, a potent antihypertensive agent and hair growth stimulator, on sarcKATP and mitoKATP channels in guinea-pig ventricular myocytes. Minoxidil activated a glybenclamide-sensitive sarcKATP channel current in the whole-cell recording mode with an EC50 of 182.6 μM. Minoxidil reversibly increased the flavoprotein oxidation, an index of mitoKATP channel activity, in a concentration-dependent manner. The EC50 for mitoKATP channel activation was estimated to be 7.3 μM; this value was notably ≈25-fold lower than that for sarcKATP channel activation. Minoxidil (10 μM) significantly attenuated the ouabain-induced increase of mitochondrial Ca2+ concentration, which was measured by loading cells with rhod-2 fluorescence. Furthermore, pretreatment with minoxidil (10 μM) before 20-min no-flow ischaemia significantly improved the recovery of developed tension measured after 60 min of reperfusion in coronary perfused guinea-pig ventricular muscles. These cardioprotective effects of minoxidil were completely abolished by the mitoKATP channel blocker 5-hydroxydecanoate (500 μM). Our results indicate that minoxidil exerts a direct cardioprotective effect on heart muscle cells, an effect mediated by the selective activation of mitoKATP channels. PMID:14691056

  17. Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles.

    Science.gov (United States)

    Lai, Ruenn Chai; Arslan, Fatih; Tan, Soon Sim; Tan, Betty; Choo, Andre; Lee, May May; Chen, Tian Sheng; Teh, Bao Ju; Eng, John Kun Long; Sidik, Harwin; Tanavde, Vivek; Hwang, Wei Sek; Lee, Chuen Neng; El Oakley, Reida Menshawe; Pasterkamp, Gerard; de Kleijn, Dominique P V; Tan, Kok Hian; Lim, Sai Kiang

    2010-06-01

    The therapeutic effects of mesenchymal stem cells (MSCs) transplantation are increasingly thought to be mediated by MSC secretion. We have previously demonstrated that human ESC-derived MSCs (hESC-MSCs) produce cardioprotective microparticles in pig model of myocardial ischemia/reperfusion (MI/R) injury. As the safety and availability of clinical grade human ESCs remain a concern, MSCs from fetal tissue sources were evaluated as alternatives. Here we derived five MSC cultures from limb, kidney and liver tissues of three first trimester aborted fetuses and like our previously described hESC-derived MSCs; they were highly expandable and had similar telomerase activities. Each line has the potential to generate at least 10(16-19) cells or 10(7-10) doses of cardioprotective secretion for a pig model of MI/R injury. Unlike previously described fetal MSCs, they did not express pluripotency-associated markers such as Oct4, Nanog or Tra1-60. They displayed a typical MSC surface antigen profile and differentiated into adipocytes, osteocytes and chondrocytes in vitro. Global gene expression analysis by microarray and qRT-PCR revealed a typical MSC gene expression profile that was highly correlated among the five fetal MSC cultures and with that of hESC-MSCs (r(2)>0.90). Like hESC-MSCs, they produced secretion that was cardioprotective in a mouse model of MI/R injury. HPLC analysis of the secretion revealed the presence of a population of microparticles with a hydrodynamic radius of 50-65 nm. This purified population of microparticles was cardioprotective at approximately 1/10 dosage of the crude secretion. (c) 2009 Elsevier Ltd. All rights reserved.

  18. Molecular mechanisms of the antiglycative and cardioprotective activities of Psidium guajava leaves in the rat diabetic myocardium.

    Science.gov (United States)

    Soman, Sowmya; Rajamanickam, Chellam; Rauf, Arun A; Madambath, Indira

    2016-12-01

    Antiglycative potential of Psidium guajava L. (Myrtaceae) leaves has been established. However, the molecular basis of its antiglycative potential remains unknown. The ethyl acetate fraction of P. guajava leaves (PGEt) was evaluated to determine the cardioprotective effect and its mechanism of action compared to quercetin. After the induction of diabetes by streptozotocin (55 mg/kg body weight), PGEt and quercetin (50 mg/kg body weight) was administered for 60 days. Rats were grouped as follows: Group C: Control, Group D: Diabetic, Group D + E: Diabetic rats treated with PGEt, Group D + Q: Diabetic rats treated with quercetin. The antiglycative potential was evaluated by assaying glycosylated haemoglobin, serum fructosamine and advanced glycation end product levels. The differential receptor for advanced glycation end products and nuclear factor kappa B (NFκB) protein levels was determined by western blot and the transcript level changes of connective tissue growth factor (CTGF), brain natriuretic peptide (BNP) and TGF-β1 in heart tissue were assessed by RT-PCR analysis. Glycated haemoglobin and serum fructosamine levels were found to be enhanced in diabetic rats when compared with control. Administration of PGEt significantly reduced the glycated haemoglobin and fructosamine levels to a larger extent than quercetin treated diabetic rats. PGEt reduced the translocation of NFκB from cytosol to nucleus when compared with diabetic rats. Expression of TGF-β1, CTGF and BNP was downregulated in PGEt treated groups compared with diabetic controls. Administration of PGEt ameliorated diabetes associated changes in the myocardium to a greater extent than quercetin.

  19. Cardioprotection and Anticholinesterases in Patients with Alzheimer's Disease: Time for Reappraisal

    Directory of Open Access Journals (Sweden)

    Fiammetta Monacelli

    2014-02-01

    Full Text Available Background/Aim: Traditional risk factors, like impaired transmitral flow in diastolic filling [vortex formation time (VFT as echocardiographic parameter], contribute to Alzheimer's disease (AD. Moreover, we observed that acetylcholinesterase inhibitors provide a significant cardioprotection. We assessed the pathogenetic role of VFT as early cardiovascular risk factor in 23 AD patients and 24 controls. Results: The results showed no statistical difference between the two groups, but the VFT values were significantly lower in nontreated AD patients, and higher value were observed in AD patients treated with anticholinesterases. Conclusions: The results support the beneficial effects of anticholinesterases on the cardiovascular system of AD patients. Thus, the transition to evidence-based medicine and an in vivo model of cardiomyocytes might strengthen these results.

  20. Factorization method and new potentials from the inverted oscillator

    International Nuclear Information System (INIS)

    Bermudez, David; Fernández C, David J.

    2013-01-01

    In this article we will apply the first- and second-order supersymmetric quantum mechanics to obtain new exactly-solvable real potentials departing from the inverted oscillator potential. This system has some special properties; in particular, only very specific second-order transformations produce non-singular real potentials. It will be shown that these transformations turn out to be the so-called complex ones. Moreover, we will study the factorization method applied to the inverted oscillator and the algebraic structure of the new Hamiltonians. -- Highlights: •We apply supersymmetric quantum mechanics to the inverted oscillator potential. •The complex second-order transformations allow us to build new non-singular potentials. •The algebraic structure of the initial and final potentials is analyzed. •The initial potential is described by a complex-deformed Heisenberg–Weyl algebra. •The final potentials are described by polynomial Heisenberg algebras

  1. Risk factors for addiction potential among college students

    Directory of Open Access Journals (Sweden)

    Mehdi Ranjbaran

    2018-01-01

    Full Text Available Background: Tendency toward addiction is provided before drug use begins. The present study aimed to identify the risk factors for addiction potential in the students of Arak University of Medical Sciences. Methods: We conducted this cross-sectional study among 305 students from Arak University of Medical Sciences, Iran in 2016. We selected the students by stratified random sampling and collected the data by family and sociodemographic factors questionnaires and Addiction Potential Scale. Results: Male students, students with low economic status and high family members were more prone to addiction. We identified variable; addiction in close friends, adverse family conditions (dispute with the family, poor economic condition of families, and family size by controlling the effect of other variables, as risk factors for addiction potential. Conclusions: Preventive and intervention actions appear necessary considering the mentioned factors.

  2. Erythropoietin: ready for prime-time cardioprotection.

    NARCIS (Netherlands)

    Riksen, N.P.; Hausenloy, D.J.; Yellon, D.

    2008-01-01

    To improve clinical outcomes in patients presenting with an acute myocardial infarction, new strategies to limit infarct size and postinfarct remodelling are warranted. Recent animal studies have revealed that erythropoietin has the potential to achieve both these goals. Even more intriguing is the

  3. Parathyroid Hormone-Related Peptide: A Novel Endocrine Cardioprotective "Conditioning Mimetic".

    Science.gov (United States)

    Datta, Tanuka; Przyklenk, Karin; Datta, Nabanita S

    2017-11-01

    An as-yet limited body of evidence suggests that calcium-regulating endocrine hormones-in particular, parathyroid hormone-related peptide (PTHrP)-may have unappreciated cardioprotective effects. The current review focuses on the concept that PTHrP may, via modulation of classic cardioprotective signaling pathways, provide a novel strategy to attenuate myocardial ischemia-reperfusion injury.

  4. FACTORS AFFECTING THE PRODUCTIVE POTENTIAL OF THE ENTERPRISE

    Directory of Open Access Journals (Sweden)

    Ileana ANASTASE (BĂDULESCU

    2013-06-01

    Full Text Available The paper enumerates the factors that determine the production potential of the company, points out the references to the opinions of economic experts in terms of productive investment. The criteria are "inferred" and economically interpreted. Decision making is based on initial information, on a number of criteria that must be led by the manager of the company. Productive potential of the enterprise can be determined only conditionally. Business potential depends on a number of exogenous and endogenous factors including professional qualities of the entrepreneur. In this context, the potential success of the company is determined by the entrepreneur, which is the "motoric" force of the enterprise and needs to possess certain professional, psychological and analytical qualities.

  5. Cardioprotection against Heart Failure by Shenfu Injection via TGF-β/Smads Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jingyu Ni

    2017-01-01

    Full Text Available Objective. To explore the potential cardioprotective mechanism of Shenfu injection (SFI against heart failure (HF by attenuating myocardial fibrosis and cardiac remodeling. Methods and Results. Four weeks after myocardial infarction (MI, adult male Sprague Dawley rats were randomized for 4-week treatment with Valsartan, SFI, or vehicle. Echocardiography and hemodynamics were applied to evaluate cardiac functions. Myocardia of coronary artery ligated (CAD rats were observed to investigate changes in cardiac structure and function. Our findings suggest that treatment with SFI could inhibit progression of myocardial fibrosis and attenuate cardiac remodeling. In addition, SFI decreased expression of Smad2 and Smad3, while increasing the expression of Smad7 through regulation of TGF-β/Smads signaling pathway. Conclusion. Treatment with SFI in Sprague Dawley rats improves ventricular structure and function and reduces cardiac fibrosis by ameliorating TGF-β/Smads signaling pathway after ventricular remodeling.

  6. Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells.

    Science.gov (United States)

    Yang, Bin; Wang, Fei; Cao, Huili; Liu, Guifang; Zhang, Yuean; Yan, Ping; Li, Bao

    2017-11-01

    Caffeoylxanthiazonoside (CYT) is an active constituent isolated from the fruit of the Xanthium strumarium L plant. The aim of the present study was to investigate the cardioprotective effects of oral administration of CYT on chronic heart failure (CHF) and its underlying mechanisms. A rat model of CHF was first established, and cardiac function indices, including the heart/body weight index, left heart/body weight index, fractional shortening (FS), ejection fraction (EF), cardiac output (CO) and heart rate (HR), were subsequently determined by cardiac ultrasound. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and the levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in heart tissues and cardiac microvascular endothelial cells (CMECs) were determined using ELISA. In addition, the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway members were determined by western blotting in CMECs. The results demonstrated that oral administration of 10, 20, 40 mg/kg CYT significantly reduced cardiac hypertrophy and reversed FS, EF, CO and HR when compared with CHF model rats. In addition, CYT administration significantly decreased the levels of TNF-α, IL-6 and IL-1β in heart tissues, as well as serum LDH and CK levels. Furthermore, exposure of CMECs to 20, 40 and 80 µg/ml CYT significantly decreased the production of TNF-α, IL-1β and IL-6. The protein expression levels of cytoplasmic NF-κB p65 and IκB were upregulated, while nuclear NF-κB p65 was downregulated following treatment of CMECs with 20, 40 and 80 µg/ml CYT when compared with untreated CHF model controls. In conclusion, the results of the current study suggest that CYT demonstrates cardioprotective effects in CHF model rats by suppressing the expression of pro-inflammatory cytokines and the NF-κB signaling pathway.

  7. Reconstruction of atomic effective potentials from isotropic scattering factors

    International Nuclear Information System (INIS)

    Romera, E.; Angulo, J.C.; Torres, J.J.

    2002-01-01

    We present a method for the approximate determination of one-electron effective potentials of many-electron systems from a finite number of values of the isotropic scattering factor. The method is based on the minimum cross-entropy technique. An application to some neutral ground-state atomic systems has been done within a Hartree-Fock framework

  8. Antioxidant Properties and Cardioprotective Mechanism of Malaysian Propolis in Rats

    Science.gov (United States)

    Ahmed, Romana; Hossen, Md. Sakib; Ahmmed, Istiyak; Rumpa, Nur-E-Noushin; Sulaiman, Siti Amrah

    2017-01-01

    Propolis contains high concentrations of polyphenols, flavonoids, tannins, ascorbic acid, and reducing sugars and proteins. Malaysian Propolis (MP) has been reported to exhibit high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and ferric reducing antioxidant power (FRAP) values. Herein, we report the antioxidant properties and cardioprotective properties of MP in isoproterenol- (ISO-) induced myocardial infarction in rats. Male Wistar rats (n = 32) were pretreated orally with an ethanol extract of MP (100 mg/kg/day) for 30 consecutive days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes and cardiac troponin I levels and altered serum lipid profiles. In addition significantly increased lipid peroxides and decreased activities of cellular antioxidant defense enzymes were observed in the myocardium. However, pretreatment of ischemic rats with MP ameliorated the biochemical parameters, indicating the protective effect of MP against ISO-induced ischemia in rats. Histopathological findings obtained for the myocardium further confirmed the biochemical findings. It is concluded that MP exhibits cardioprotective activity against ISO-induced oxidative stress through its direct cytotoxic radical-scavenging activities. It is also plausible that MP contributed to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation. PMID:28261310

  9. Antioxidant Properties and Cardioprotective Mechanism of Malaysian Propolis in Rats

    Directory of Open Access Journals (Sweden)

    Romana Ahmed

    2017-01-01

    Full Text Available Propolis contains high concentrations of polyphenols, flavonoids, tannins, ascorbic acid, and reducing sugars and proteins. Malaysian Propolis (MP has been reported to exhibit high 1,1-diphenyl-2-picrylhydrazyl (DPPH radical-scavenging activity and ferric reducing antioxidant power (FRAP values. Herein, we report the antioxidant properties and cardioprotective properties of MP in isoproterenol- (ISO- induced myocardial infarction in rats. Male Wistar rats (n=32 were pretreated orally with an ethanol extract of MP (100 mg/kg/day for 30 consecutive days. Subcutaneous injection of ISO (85 mg/kg in saline for two consecutive days caused a significant increase in serum cardiac marker enzymes and cardiac troponin I levels and altered serum lipid profiles. In addition significantly increased lipid peroxides and decreased activities of cellular antioxidant defense enzymes were observed in the myocardium. However, pretreatment of ischemic rats with MP ameliorated the biochemical parameters, indicating the protective effect of MP against ISO-induced ischemia in rats. Histopathological findings obtained for the myocardium further confirmed the biochemical findings. It is concluded that MP exhibits cardioprotective activity against ISO-induced oxidative stress through its direct cytotoxic radical-scavenging activities. It is also plausible that MP contributed to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

  10. Mitochondrial events responsible for morphine's cardioprotection against ischemia/reperfusion injury

    International Nuclear Information System (INIS)

    He, Haiyan; Huh, Jin; Wang, Huihua; Kang, Yi; Lou, Jianshi; Xu, Zhelong

    2016-01-01

    Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30 min ischemia and 2 h of reperfusion. Morphine was given before the onset of ischemia. Infarct size and troponin I release were measured to evaluate cardiac injury. Oxidative stress was evaluated by measuring mitochondrial protein carbonylation and mitochondrial ROS generation. HL-1 cells were subjected to simulated ischemia/reperfusion and LDH release and mitochondrial membrane potential (ΔΨm) were measured. Morphine reduced infarct size as well as cardiac troponin I release which were aborted by the selective Src tyrosine kinase inhibitors PP2 and Src-I1. Morphine also attenuated LDH release and prevented a loss of ΔΨm at reperfusion in a Src tyrosine kinase dependent manner in HL-1 cells. However, morphine failed to reduce LDH release in HL-1 cells transfected with Src siRNA. Morphine increased mitochondrial Src phosphorylation at reperfusion and this was abrogated by PP2. Morphine attenuated mitochondrial protein carbonylation and mitochondrial superoxide generation at reperfusion through Src tyrosine kinase. The inhibitory effect of morphine on the mitochondrial complex I activity was reversed by PP2. These data suggest that morphine induces cardioprotection by preventing mitochondrial oxidative stress through mitochondrial Src tyrosine kinase. Inhibition of mitochondrial complex I at reperfusion by Src tyrosine kinase may account for the prevention of mitochondrial oxidative stress by morphine. - Highlights: • Morphine induced mito-Src phosphorylation and reduced infarct size in rat hearts. • Morphine failed to reduce I/R-induced LDH release in Src-silencing HL-1 cells. • Morphine prevented mitochondria damage caused by I/R through Src. • Morphine reduced

  11. Mitochondrial events responsible for morphine's cardioprotection against ischemia/reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    He, Haiyan [Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin 300070 (China); Department of Pharmacology, Tianjin Medical University, Tianjin 300070 (China); Huh, Jin [Department of Anesthesia and Pain Medicine, Medical College, Kangwon National University, Chuncheon City (Korea, Republic of); Wang, Huihua [Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang Province (China); Kang, Yi; Lou, Jianshi [Department of Pharmacology, Tianjin Medical University, Tianjin 300070 (China); Xu, Zhelong, E-mail: zxu@tmu.edu.cn [Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin 300070 (China)

    2016-01-01

    Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30 min ischemia and 2 h of reperfusion. Morphine was given before the onset of ischemia. Infarct size and troponin I release were measured to evaluate cardiac injury. Oxidative stress was evaluated by measuring mitochondrial protein carbonylation and mitochondrial ROS generation. HL-1 cells were subjected to simulated ischemia/reperfusion and LDH release and mitochondrial membrane potential (ΔΨm) were measured. Morphine reduced infarct size as well as cardiac troponin I release which were aborted by the selective Src tyrosine kinase inhibitors PP2 and Src-I1. Morphine also attenuated LDH release and prevented a loss of ΔΨm at reperfusion in a Src tyrosine kinase dependent manner in HL-1 cells. However, morphine failed to reduce LDH release in HL-1 cells transfected with Src siRNA. Morphine increased mitochondrial Src phosphorylation at reperfusion and this was abrogated by PP2. Morphine attenuated mitochondrial protein carbonylation and mitochondrial superoxide generation at reperfusion through Src tyrosine kinase. The inhibitory effect of morphine on the mitochondrial complex I activity was reversed by PP2. These data suggest that morphine induces cardioprotection by preventing mitochondrial oxidative stress through mitochondrial Src tyrosine kinase. Inhibition of mitochondrial complex I at reperfusion by Src tyrosine kinase may account for the prevention of mitochondrial oxidative stress by morphine. - Highlights: • Morphine induced mito-Src phosphorylation and reduced infarct size in rat hearts. • Morphine failed to reduce I/R-induced LDH release in Src-silencing HL-1 cells. • Morphine prevented mitochondria damage caused by I/R through Src. • Morphine

  12. Human factors in waste management - potential and reality

    International Nuclear Information System (INIS)

    Thompson, J.S.

    1996-01-01

    There is enormous potential for human factors contributions in the realm of waste management. The reality, however, is very different from the potential. This is particularly true for low-level and low-level mixed-waste management. The hazards are less severe; therefore, health and safety requirements (including human factors) are not as rigorous as for high-level waste. High-level waste management presents its own unique challenges and opportunities. Waste management is strongly driven by regulatory compliance. When regulations are flexible and open to interpretation and the environment is driven so strongly by regulatory compliance, standard practice is to drop open-quotes nice to haveclose quotes features, like a human factors program, to save money for complying with other requirements. The challenge is to convince decision makers that human factors can help make operations efficient and cost-effective, as well as improving safety and complying with regulations. A human factors program should not be viewed as competing with compliance efforts; in fact, it should complement them and provide additional cost-effective means of achieving compliance with other regulations. Achieving this synergy of human factors with ongoing waste management operations requires educating program and facility managers and other technical specialists about human factors and demonstrating its value open-quotes through the back doorclose quotes on existing efforts. This paper describes ongoing projects at Los Alamos National Laboratory (LANL) in support of their waste management groups. It includes lessons learned from hazard and risk analyses, safety analysis reports, job and task analyses, operating procedure development, personnel qualification/certification program development, and facility- and job-specific training program and course development

  13. Pair potentials and structure factors of liquid alkali metals

    International Nuclear Information System (INIS)

    Kumaravadivel, R.; Tosi, M.P.

    1984-03-01

    Measured structure factors of liquid alkali metals are examined in the framework of screened-pair-potentials theory. Information on the main attractive well in the effective pair potential is obtained from the structural data by an approximate method stemming from an optimized random phase treatment of the indirect ion-ion attraction. The results are compared with a variety of theoretical pair potentials in the cases of sodium and potassium, after a test of the method against computer simulation data on a model for rubidium. Results for the other alkali metals are also given and discussed. The small-angle scattering region is then examined in considerable detail, with special attention to the possibility of a linear term in a series expansion of the structure factor at very small momentum transfer. Although sensitivity to both the bare electron-ion coupling and the local field factor in the screening function is demonstrated and analyzed, no linear term of the magnitude reported in recent X-ray diffraction experiments is found in the present theoretical framework. (author)

  14. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    Directory of Open Access Journals (Sweden)

    Luisa Vicari

    2016-01-01

    Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  15. Potential Role of Activating Transcription Factor 5 during Osteogenesis.

    Science.gov (United States)

    Vicari, Luisa; Calabrese, Giovanna; Forte, Stefano; Giuffrida, Raffaella; Colarossi, Cristina; Parrinello, Nunziatina Laura; Memeo, Lorenzo

    2016-01-01

    Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB) family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2), encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  16. Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules.

    Directory of Open Access Journals (Sweden)

    Takanobu Nagata

    Full Text Available Myocardial ischemia reperfusion injury (IRI adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS-3, an intrinsic negative feedback regulator of the Janus kinase (JAK-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT-activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO. The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1 was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI.

  17. Intense light-elicited upregulation of miR-21 facilitates glycolysis and cardioprotection through Per2-dependent mechanisms.

    Directory of Open Access Journals (Sweden)

    Colleen Marie Bartman

    Full Text Available A wide search for ischemic preconditioning (IPC mechanisms of cardioprotection identified the light elicited circadian rhythm protein Period 2 (Per2 to be cardioprotective. Studies on cardiac metabolism found a key role for light elicited Per2 in mediating metabolic dependence on carbohydrate metabolism. To profile Per2 mediated pathways following IPC of the mouse heart, we performed a genome array and identified 352 abundantly expressed and well-characterized Per2 dependent micro RNAs. One prominent result of our in silico analysis for cardiac Per2 dependent micro RNAs revealed a selective role for miR-21 in the regulation of hypoxia and metabolic pathways. Based on this Per2 dependency, we subsequently found a diurnal expression pattern for miR-21 with higher miR-21 expression levels at Zeitgeber time (ZT 15 compared to ZT3. Gain or loss of function studies for miR-21 using miRNA mimics or miRNA inhibitors and a Seahorse Bioanalyzer uncovered a critical role of miR-21 for cellular glycolysis, glycolytic capacity, and glycolytic reserve. Exposing mice to intense light, a strategy to induce Per2, led to a robust induction of cardiac miR-21 tissue levels and decreased infarct sizes, which was abolished in miR-21-/- mice. Similarly, first translational studies in humans using intense blue light exposure for 5 days in healthy volunteers resulted in increased plasma miR-21 levels which was associated with increased phosphofructokinase activity, the rate-limiting enzyme in glycolysis. Together, we identified miR-21 as cardioprotective downstream target of Per2 and suggest intense light therapy as a potential strategy to enhance miR-21 activity and subsequent carbohydrate metabolism in humans.

  18. CARDIOPROTECTIVE EFFECT OF NATIVE ANTIHYPOXANTS IN EXPERIMENTAL COBALT CARDIOMYOPATHY

    Directory of Open Access Journals (Sweden)

    I. V. Zadnipryany

    2016-01-01

    Full Text Available The aim of research – the study of cardioprotective properties of antioxidants in terms of histotoxic hypoxia under experimental conditions.Materials and methods. The study was conducted on 20 adult male Wistar rats divided into 3 experimental groups, which for 7 days were intraperitoneally injected aqueous CoCl2 solution at a dose of 60 mg/kg. Rats of the first experimental group (n = 6 had no administered drug correction, a the second group of animals (n = 7 after the cobalt chloride daily injections was administered intragastrically Enoant Premium aqueous solution at a dose of 2.5 ml / kg, along with 0.05 ml of water, the rats the third test group (n = 7 after the administration of cobalt chloride were exposed to cytoflavin correction concentrate and grape polyphenols administered simultaneously. Studies of myocardium were conducted using light and electron microscopy.Results of the research. The result of the cobalt toxic effect on the heart of animals in experiments lead to the development of cardiomyopathy, which required timely cardioprotection. Morphological changes in the second group of rats, despite a slight improvement compared with the group without correction,were characterized, above all, by uneven from mild to severe edema of the myocardium. Structure of myocardium observed in the third group of male rats after cobalt intoxication, generally reflected a tendency to minimization of the extent of the damage, which was manifested in the form of normalization of cell structures and muscle fibers.Conclusion. The administration of succinic acid derivatives combined with the grape polyphenols demonstrated vivid cytoprotective properties evidenced by mostly preserved myocardium structure in rats exposed to histotoxic hypoxia in comparison to only administration of plant polyphenols group. 

  19. Cardioprotective Signature of Short-Term Caloric Restriction.

    Directory of Open Access Journals (Sweden)

    Hossein Noyan

    Full Text Available To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR.Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we reveal the pathways that are modulated by short-term CR, which are associated with protection of the mouse heart from ischemia.Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL diet with free access to regular chow, or CR, receiving 30% less food for 7 days (d, prior to myocardial infarction (MI via permanent coronary ligation. At d8, the left ventricles (LV of AL and CR mice were collected for Western blot, mRNA and microRNA (miR analyses to identify cardioprotective gene expression signatures. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI.This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01. mRNA and miR profiles pre-MI (N=5/group identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM. Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38. CR regimen was also associated with reduced protein abundance of cleaved caspase 3 in the infarcted heart and improved cardiac function.

  20. Buzz Factor or Innovation Potential: What Explains Cryptocurrencies’ Returns?

    Science.gov (United States)

    Wang, Sha

    2017-01-01

    Cryptocurrencies have become increasingly popular since the introduction of bitcoin in 2009. In this paper, we identify factors associated with variations in cryptocurrencies’ market values. In the past, researchers argued that the “buzz” surrounding cryptocurrencies in online media explained their price variations. But this observation obfuscates the notion that cryptocurrencies, unlike fiat currencies, are technologies entailing a true innovation potential. By using, for the first time, a unique measure of innovation potential, we find that the latter is in fact the most important factor associated with increases in cryptocurrency returns. By contrast, we find that the buzz surrounding cryptocurrencies is negatively associated with returns after controlling for a variety of factors, such as supply growth and liquidity. Also interesting is our finding that a cryptocurrency’s association with fraudulent activity is not negatively associated with weekly returns—a result that further qualifies the media’s influence on cryptocurrencies. Finally, we find that an increase in supply is positively associated with weekly returns. Taken together, our findings show that cryptocurrencies do not behave like traditional currencies or commodities—unlike what most prior research has assumed—and depict an industry that is much more mature, and much less speculative, than has been implied by previous accounts. PMID:28085906

  1. Buzz Factor or Innovation Potential: What Explains Cryptocurrencies' Returns?

    Science.gov (United States)

    Wang, Sha; Vergne, Jean-Philippe

    2017-01-01

    Cryptocurrencies have become increasingly popular since the introduction of bitcoin in 2009. In this paper, we identify factors associated with variations in cryptocurrencies' market values. In the past, researchers argued that the "buzz" surrounding cryptocurrencies in online media explained their price variations. But this observation obfuscates the notion that cryptocurrencies, unlike fiat currencies, are technologies entailing a true innovation potential. By using, for the first time, a unique measure of innovation potential, we find that the latter is in fact the most important factor associated with increases in cryptocurrency returns. By contrast, we find that the buzz surrounding cryptocurrencies is negatively associated with returns after controlling for a variety of factors, such as supply growth and liquidity. Also interesting is our finding that a cryptocurrency's association with fraudulent activity is not negatively associated with weekly returns-a result that further qualifies the media's influence on cryptocurrencies. Finally, we find that an increase in supply is positively associated with weekly returns. Taken together, our findings show that cryptocurrencies do not behave like traditional currencies or commodities-unlike what most prior research has assumed-and depict an industry that is much more mature, and much less speculative, than has been implied by previous accounts.

  2. Buzz Factor or Innovation Potential: What Explains Cryptocurrencies' Returns?

    Directory of Open Access Journals (Sweden)

    Sha Wang

    Full Text Available Cryptocurrencies have become increasingly popular since the introduction of bitcoin in 2009. In this paper, we identify factors associated with variations in cryptocurrencies' market values. In the past, researchers argued that the "buzz" surrounding cryptocurrencies in online media explained their price variations. But this observation obfuscates the notion that cryptocurrencies, unlike fiat currencies, are technologies entailing a true innovation potential. By using, for the first time, a unique measure of innovation potential, we find that the latter is in fact the most important factor associated with increases in cryptocurrency returns. By contrast, we find that the buzz surrounding cryptocurrencies is negatively associated with returns after controlling for a variety of factors, such as supply growth and liquidity. Also interesting is our finding that a cryptocurrency's association with fraudulent activity is not negatively associated with weekly returns-a result that further qualifies the media's influence on cryptocurrencies. Finally, we find that an increase in supply is positively associated with weekly returns. Taken together, our findings show that cryptocurrencies do not behave like traditional currencies or commodities-unlike what most prior research has assumed-and depict an industry that is much more mature, and much less speculative, than has been implied by previous accounts.

  3. Cyclosporine A administered during reperfusion fails to restore cardioprotection in prediabetic Zucker obese rats in vivo

    NARCIS (Netherlands)

    Huhn, R.; Heinen, A.; Hollmann, M. W.; Schlack, W.; Preckel, B.; Weber, N. C.

    2010-01-01

    Background and aims: Hyperglycaemia blocks sevoflurane-induced postconditioning, and cardioprotection in hyperglycaemic myocardium can be restored by inhibition of the mitochondrial permeability transition pore (mPTP). We investigated whether sevoflurane-induced postconditioning is also blocked in

  4. Factors Potentially Influencing Student Acceptance of Biological Evolution

    Science.gov (United States)

    Wiles, Jason R.

    This investigation explored scientific, religious, and otherwise nonscientific factors that may influence student acceptance of biological evolution and related concepts, how students perceived these factors to have influenced their levels of acceptance of evolution and changes therein, and what patterns arose among students' articulations of how their levels of acceptance of evolution may have changed. This exploration also measured the extent to which students' levels of acceptance changed following a treatment designed to address factors identified as potentially affecting student acceptance of evolution. Acceptance of evolution was measured using the MATE instrument (Rutledge and Warden, 1999; Rutledge and Sadler, 2007) among participants enrolled in a secondary-level academic program during the summer prior to their final year of high school and as they transitioned to the post-secondary level. Student acceptance of evolution was measured to be significantly higher than pre-treatment levels both immediately following and slightly over one year after treatment. Qualitative data from informal questionnaires, from formal course evaluations, and from semi-structured interviews of students engaged in secondary level education and former students at various stages of post-secondary education confirmed that the suspected factors were perceived by participants to have influenced their levels of acceptance of evolution. Furthermore, participant reports provided insight regarding the relative effects they perceived these factors to have had on their evolution acceptance levels. Additionally, many participants reported that their science teachers in public schools had avoided, omitted, or denigrated evolution during instruction, and several of these students expressed frustration regarding what they perceived to have been a lack of education of an important scientific principle. Finally, no students expressed feelings of being offended by having been taught about

  5. Established and potential risk factors for clostridum difficile infection

    Directory of Open Access Journals (Sweden)

    Vaishnavi C

    2009-01-01

    Full Text Available Clostridium difficile is the aetiological agent for almost all cases of pseudo membranous colitis and 15-25% of antibiotic associated diarrhoea. In recent years, C. difficile associated disease (CDAD has been increasing in frequency and severity due to the emergence of virulent strains. Severe cases of toxic mega colon may be associated with mortality rates of 24-38%. The prevalence of CDAD is global and the incidence varies considerably from place to place. In the initial stages of its discovery, C. difficile infection was regarded mainly as an outcome of antibiotic intake and not as a life threatening disease. Intervention by man has produced conditions making C. difficile a significant cause of morbidity and mortality. The recent outbreak of CDAD in Quebec has sent the alarm bells ringing. Apart from a threefold increase in the incidence of CDAD, clinicians have also reported a higher number of cases involving toxic mega colon, colectomy or death. Among all the risk factors, inclusive of the host and the environmental factors, antibiotics are the most important ones. Surgical patients comprise 55-75% of all patients with CDAD due to the fact that perioperative prophylaxis requires the use of antibiotics. However, other drugs such as immunosuppressants and proton pump inhibitors are also important risk factors. Thus CDAD is a growing nosocomial and public health challenge. Additionally, the recognition of community acquired CDAD signals the presence of several risk factors. In this review, the established and potential risk factors of CDAD, along with the epidemiology, diagnostic modalities, management and preventive measures of the disease have been elaborated.

  6. Potential for use of environmental factors in urban planning

    Science.gov (United States)

    Teixeira da Silva, Ricardo; van der Ploeg, Martine; van Delden, Hedwig; Fleskens, Luuk

    2016-04-01

    Projections for population growth estimate, on top of the current 7.4 billion world population, an increase of 2 billion people for the next 40 years. It is also projected that 66 per cent of the world population in 2050 will live in urban areas. To accommodate the urban population growth cities are changing continuously land cover to urban areas. Such changes are a threat for natural resources and food production systems stability and capability to provide food and other functions. However, little has been done concerning a rational soil management for food production in urban and peri-urban areas. This study focuses on the assessment of soil lost due to urban expansion and discusses the potential loss regarding the quality of the soil for food production and environmental functions. It is relevant to increase the knowledge on the role of soils in peri-urban areas and in the interaction of physical, environmental and social factors. The methodology consists of assessing the soil quality in and around urban and peri-urban areas. It focuses particularly on the physical properties and the environmental factors, for two periods of time and account the potential losses due to urban expansion. This project is on-going, therefore current advances will be presented and will look for a discussion on the contribution of soil quality for decision-making and land management in urban and peri-urban areas.

  7. The potential contribution of dietary factors to breast cancer prevention.

    Science.gov (United States)

    Shapira, Niva

    2017-09-01

    Breast cancer (BC), the leading cancer in women, is increasing in prevalence worldwide, concurrent with western metabolic epidemics, that is, obesity, metabolic syndrome, and diabetes, and shares major risk factors with these diseases. The corresponding potential for nutritional contributions toward BC prevention is reviewed and related to critical stages in the life cycle and their implications for carcinogenic and pathometabolic trajectories. BC initiation potentially involves diet-related pro-oxidative, inflammatory, and procarcinogenic processes, that interact through combined lipid/fatty acid peroxidation, estrogen metabolism, and related DNA-adduct/depurination/mutation formation. The pathometabolic trajectory is affected by high estrogen, insulin, and growth factor cascades and resultant accelerated proliferation/progression. Anthropometric risk factors - high birth weight, adult tallness, adiposity/BMI, and weight gain - are often reflective of these trends. A sex-based nutritional approach targets women's specific risk in western obesogenic environments, associated with increasing fatness, estrogen metabolism, n-6 : n-3 polyunsaturated fatty acid ratio, and n-6 polyunsaturated fatty acid conversion to proinflammatory/carcinogenic eicosanoids, and effects of timing of life events, for example, ages at menarche, full-term pregnancy, and menopause. Recent large-scale studies have confirmed the effectiveness of the evidence-based recommendations against BC risk, emphasizing low-energy density diets, highly nutritious plant-based regimes, physical activity, and body/abdominal adiposity management. Better understanding of dietary inter-relationships with BC, as applied to food intake, selection, combination, and processing/preparation, and recommended patterns, for example, Mediterranean, DASH, plant-based, low energy density, and low glycemic load, with high nutrient/phytonutrient density, would increase public motivation and authoritative support for early

  8. Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

    International Nuclear Information System (INIS)

    Thonel, Aurelie de; Mezger, Valerie; Garrido, Carmen

    2011-01-01

    Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents

  9. Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

    Energy Technology Data Exchange (ETDEWEB)

    Thonel, Aurelie de [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); Mezger, Valerie, E-mail: valerie.mezger@univ-paris-diderot.fr [CNRS, UMR7216 Epigenetics and Cell Fate, Paris (France); University Paris Diderot, 75013 Paris (France); Garrido, Carmen, E-mail: valerie.mezger@univ-paris-diderot.fr [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); CHU, Dijon BP1542, Dijon (France)

    2011-03-07

    Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents.

  10. Comparison of cardioprotective effects using salvianolic acid B and benazepril for the treatment of chronic myocardial infarction in rats.

    Science.gov (United States)

    He, Haibo; Shi, Mengqiong; Yang, Xianzhe; Zeng, Xiaowei; Wu, Limao; Li, Lianda

    2008-09-01

    The aim of this study was to compare the cardioprotective effects of salvianolic acid B (Sal B) and the angiotension-converting enzyme inhibitor, benazepril, in rats with chronic myocardial infarction (MI) that resulted from a coronary artery ligation for 4 weeks. The rats were divided into four groups: those undergoing a sham operation; a MI group; a MI+SalB group (100 mg/kg by a gavage, once a day for 4 weeks); a MI+benazepril group (10 mg/kg by a gavage, once a day for 4 weeks). The following parameters were measured: echocardiographic, hemodynamic and hemorheological changes, angiogenesis, infarct size and cardiac remodeling and the messenger ribonucleic acid (mRNA) of vascular endothelium growth factor (VEGF). Rats treated with SalB or benazepril manifested the following: (1) marked improvements in echocardiographic, hemodynamic and hemorheological parameters; (2) significant reduction of infarct size; (3) significantly attenuated heart, kidney and lung hypertrophies, left ventricular (LV) dilatation and fibrosis. The unique effects of SalB were angiogenesis and augmented VEGF expression in the border and remote noninfarcted left ventricular area. These results suggest that both SalB and benazepril exerted beneficial cardioprotective effects in our experimental system, but that the modality of Sal B was different from that of benazepril. The additional beneficial effects of Sal B relative to benazpril, augmenting VEGF expression and promoting angiogenesis, may result in improved myocardial microcirculation.

  11. Cardioprotective Effect of Aloe vera Biomacromolecules Conjugated with Selenium Trace Element on Myocardial Ischemia-Reperfusion Injury in Rats.

    Science.gov (United States)

    Yang, Yang; Yang, Ming; Ai, Fen; Huang, Congxin

    2017-06-01

    The present study was undertaken to evaluate the cardioprotection potential and underlying molecular mechanism afforded by a selenium (Se) polysaccharide (Se-AVP) from Aloe vera in the ischemia-reperfusion (I/R) model of rats in vivo. Myocardial I/R injury was induced by occluding the left anterior descending coronary artery (LAD) for 30 min followed by 2-h continuous reperfusion. Pretreatment with Se-AVP (100, 200, and 400 mg/kg) attenuated myocardial damage, as evidenced by reduction of the infarct sizes, increase in serum and myocardial endogenous antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT)), and decrease in the malondialdehyde (MDA) level in the rats suffering I/R injury. This cardioprotective activity afforded by Se-AVP is further supported by the decreased levels of cardiac marker enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as the rise of myocardial Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase activities in I/R rats. Additionally, cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining and the result showed that the percent of TUNEL-positive cells in myocardium of Se-AVP-treated groups was lower than I/R rats. In conclusion, we clearly demonstrated that Se-AVP had a protective effect against myocardial I/R injury in rats by augmenting endogenous antioxidants and protecting rat hearts from oxidative stress-induced myocardial apoptosis.

  12. Cardioprotective effects of cocoa: clinical evidence from randomized clinical intervention trials in humans.

    Science.gov (United States)

    Arranz, Sara; Valderas-Martinez, Palmira; Chiva-Blanch, Gemma; Casas, Rosa; Urpi-Sarda, Mireia; Lamuela-Raventos, Rosa M; Estruch, Ramon

    2013-06-01

    Cocoa is an important source of polyphenols, which comprise 12-18% of its total dry weight. The major phenolic compounds in cocoa and cocoa products are mainly flavonoids such as epicatechin, catechin, and proanthocyanidins. These products contain higher amounts of flavonoids than other polyphenol-rich foods. However, the bioavailability of these compounds depends on other food constituents and their interactions with the food matrix. Many epidemiological and clinical intervention trials have concluded that the ingestion of flavonoids reduces the risk factors of developing cardiovascular disease. This review summarizes the new findings regarding the effects of cocoa and chocolate consumption on cardiovascular risk factors. The mechanisms involved in the cardioprotective effects of cocoa flavonoids include reduction of oxidative stress, inhibition of low-density lipoproteins oxidation and platelet aggregation, vasodilatation of blood vessels, inhibition of the adherence of monocytes to vascular endothelium, promotion of fibrinolysis, and immunomodulatory and anti-inflammatory activity. Scientific evidence supports a cause and effect relationship between consumption of cocoa flavonoids and the maintenance of normal endothelium-dependent vasodilation, which contributes to normal blood flow. However, larger randomized trials are required to definitively establish the impact of cocoa and cocoa products consumption on hard cardiovascular outcomes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.

    Science.gov (United States)

    Moreira-Gonçalves, Daniel; Ferreira, Rita; Fonseca, Hélder; Padrão, Ana Isabel; Moreno, Nuno; Silva, Ana Filipa; Vasques-Nóvoa, Francisco; Gonçalves, Nádia; Vieira, Sara; Santos, Mário; Amado, Francisco; Duarte, José Alberto; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

    2015-11-01

    Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

  14. Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments

    Science.gov (United States)

    Landi, Francesco; Calvani, Riccardo; Tosato, Matteo; Martone, Anna Maria; Ortolani, Elena; Savera, Giulia; Sisto, Alex; Marzetti, Emanuele

    2016-01-01

    Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an “ageist” approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons. PMID:26828516

  15. Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments.

    Science.gov (United States)

    Landi, Francesco; Calvani, Riccardo; Tosato, Matteo; Martone, Anna Maria; Ortolani, Elena; Savera, Giulia; Sisto, Alex; Marzetti, Emanuele

    2016-01-27

    Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an "ageist" approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons.

  16. Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments

    Directory of Open Access Journals (Sweden)

    Francesco Landi

    2016-01-01

    Full Text Available Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an “ageist” approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons.

  17. Potentially modifiable factors contributing to sepsis-associated encephalopathy.

    Science.gov (United States)

    Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

    2017-08-01

    Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia 10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

  18. Cardioprotective effect of mumie (shilajit) on experimentally induced myocardial injury.

    Science.gov (United States)

    Joukar, Siyavash; Najafipour, Hamid; Dabiri, Shahriar; Sheibani, Mohammad; Sharokhi, Nader

    2014-09-01

    This study assessed the effects of mumie (shilajit) pre-treatment, a traditional drug which is well known in the ancient medicine of both east and west, on cardiac performance of rats subjected to myocardial injury. Animals were divided into control, M250, and M500 (received mumie at dosages of 250 and 500 mg/kg/day, orally for 7 days, respectively) main groups each consisting of two subgroups-with and without heart injury. On the 6th and 7th days, isoproterenol (ISO) (85 mg/kg i.p.) was injected (s.c.) to half of the animal subgroups to induce myocardial damage. On the 8th day, after hemodynamic parameter recordings, hearts were removed for further evaluation. Mumie pre-treatment had no significant effects on hemodynamic and cardiac indices of normal animals. When the cardiac injury was induced, mumie maintained the ±dp/dt maximum, attenuated the serum cardiac troponin I, and reduced the severity of cardiac lesions. Despite the mild positive effects of mumie on total antioxidant capacity and lipid proxidation index, no significant difference was observed among animal groups. The findings suggest the prominent cardioprotective effect of mumie against destructive effects of ISO. It seems that other mechanisms than reinforcements of antioxidant system are involved in this beneficial effect.

  19. Removing the cells from adult bone marrow derived stem cell therapy does not eliminate cardioprotection.

    Science.gov (United States)

    Yasin, Mohammed

    2013-04-01

    .8-fold), tumour necrosis factor receptor-1 associated protein (2.3-fold), ischaemia responsive protein-94 (1.6-fold); (iv) glycolytic protein: glyceraldehyde-3-phosphate dehydrogenase (2.3-fold); (v) mitochondrial respiratory proteins: mitochondrial aconitase (4.7-fold), voltage-dependent anion-selective channel protein-1 (VDAC-1) (2.7-fold). Regional myocardial reperfusion injury can be attenuated by intravenous administration of either BMMNC or BMS at the onset of reperfusion, which suggests adult stem cells mediate non-regenerative cardioprotection.

  20. Cardioprotective Effects of Quercetin in Cardiomyocyte under Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Yi-Wen Chen

    2013-01-01

    Full Text Available Quercetin, a polyphenolic compound existing in many vegetables, fruits, has antiinflammatory, antiproliferation, and antioxidant effect on mammalian cells. Quercetin was evaluated for protecting cardiomyocytes from ischemia/reperfusion injury, but its protective mechanism remains unclear in the current study. The cardioprotective effects of quercetin are achieved by reducing the activity of Src kinase, signal transducer and activator of transcription 3 (STAT3, caspase 9, Bax, intracellular reactive oxygen species production, and inflammatory factor and inducible MnSOD expression. Fluorescence two-dimensional differential gel electrophoresis (2D-DIGE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS can reveal the differentially expressed proteins of H9C2 cells treated with H2O2 or quercetin. Although 17 identified proteins were altered in H2O2-induced cells, these proteins such as alpha-soluble NSF attachment protein (α-SNAP, Ena/VASP-like protein (Evl, and isopentenyl-diphosphate delta-isomerase 1 (Idi-1 were reverted by pretreatment with quercetin, which correlates with kinase activation, DNA repair, lipid, and protein metabolism. Quercetin dephosphorylates Src kinase in H2O2-induced H9C2 cells and likely blocks the H2O2-induced inflammatory response through STAT3 kinase modulation. This probably contributes to prevent ischemia/reperfusion injury in cardiomyocytes.

  1. Dynamic Action of Carotenoids in Cardioprotection and Maintenance of Cardiac Health

    Directory of Open Access Journals (Sweden)

    Dipak K. Das

    2012-04-01

    Full Text Available Oxidative stress has been considered universally and undeniably implicated in the pathogenesis of all major diseases, including those of the cardiovascular system. Oxidative stress activate transcriptional messengers, such as nuclear factor—κB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Evidence is rapidly accumulating to support the role of reactive oxygen species (ROS and reactive nitrogen species (RNS as intracellular signaling molecules. Despite this connection between oxidative stress and cardiovascular disease (CVD, there are currently no recognized therapeutic interventions to address this important unmet need. Antioxidants that provide a broad, “upstream” approach via ROS/RNS quenching or free radical chain breaking seem an appropriate therapeutic option based on epidemiologic, dietary, and in vivo animal model data. Short-term dietary intervention trials suggest that diets rich in fruit and vegetable intake lead to improvements in coronary risk factors and reduce cardiovascular mortality. Carotenoids are such abundant, plant-derived, fat-soluble pigments that functions as antioxidants. They are stored in the liver or adipose tissue, and are lipid soluble by becoming incorporated into plasma lipoprotein particles during transport. For these reasons, carotenoids may represent one plausible mechanism by which fruits and vegetables reduce the risk of chronic diseases as cardiovascular disease (CVD. This review paper outlines the role of carotenoids in maintaining cardiac health and cardioprotection mediated by several mechanisms including redox signaling.

  2. Cardioprotective Effects of Pomegranate (Punica granatum) Juice in Patients with Ischemic Heart Disease.

    Science.gov (United States)

    Razani, Zahra; Dastani, Mostafa; Kazerani, Hamid Reza

    2017-11-01

    Ischemic heart disease is the leading cause of mortality worldwide. The purpose of this study was to evaluate the cardioprotective effects of pomegranate juice in patients with ischemic heart disease. One hundred patients, diagnosed with unstable angina or myocardial infarction, were randomly assigned to the test and the control groups (n = 50, each). During 5 days of hospitalization, in addition to the conventional medical therapies, the test groups received 220 mL pomegranate juice, daily. During the hospitalization period, the blood pressure, heart rate, as well as the intensity, occurrence, and duration of the angina were evaluated on a regular basis. At the end of the hospitalization period, the serum levels of malondialdehyde, interleukin-6, and tumor necrosis factor alpha were measured in all patients. The levels of serum troponin and high-sensitive C-reactive protein levels were also assayed in patients diagnosed with myocardial infarction. Pomegranate juice caused significant reductions in the intensity, occurrence, and duration of angina pectoris in patients with unstable angina. Consistently, the test patients had significantly lower levels of serum troponin and malondialdehyde. Other studied parameters did not change significantly. The results of this study suggest protective effects of pomegranate juice against myocardial ischemia and reperfusion injury. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Cardioprotective Effect of Intermittent Fasting is Associated with an Elevation of Adiponectin Levels in Rats

    Science.gov (United States)

    Wan, Ruiqian; Ahmet, Ismayil; Brown, Martin; Cheng, Aiwu; Kamimura, Naomi; Talan, Mark; Mattson, Mark P.

    2009-01-01

    It has been reported that dietary energy restriction, including intermittent fasting (IF), can protect heart and brain cells against injury and improve functional outcome in animal models of myocardial infarction and stroke. Here we report that IF improves glycemic control and protects the myocardium against ischemia-induced cell damage and inflammation in rats. Echocardiographic analysis of heart structural and functional variables revealed that IF attenuates the growth-related increase in posterior ventricular wall thickness, , end systolic and diastolic volumes, and reduces the ejection fraction. The size of the ischemic infarct 24 hours following permanent ligation of a coronary artery was significantly smaller, and markers of inflammation (infiltration of leukocytes in the area at risk and plasma IL-6 levels) were less, in IF rats compared to rats on the control diet. IF resulted in increased levels of circulating adiponectin prior to and after myocardial infarction. Because recent studies have shown that adiponectin can protect the heart against ischemic injury, our findings suggest a potential role for adiponectin as a mediator of the cardioprotective effect of IF. PMID:19423320

  4. Cardioprotective Effect of the Compound Yangshen Granule in Rat Models with Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Xie Ming

    2012-01-01

    Full Text Available The protective effect of Compound Yangshen Granules was observed in myocardial infarction rat model. Rats were randomly divided into 6 groups: the model group, the control group (sham operated, the positive drug group, and small, medium, and large dosage of the Yangshen granule groups, respectively. The rats in the 3 Yangshen granule groups were orally administrated with 0.7 g/kg, 1.4 g/kg, and 2.8 g/kg for 7 consecutive days, whereas the rats of the positive drug group treated with 0.14 g/kg of Danshen Dropping Pills, and rats in the control and model groups orally administrated with saline. The rat model of acute myocardial infarction was established with ligation of coronary artery. Electrocardiograms at different time points, the blood rheology, myocardial enzymes, infarct size, and myocardial morphologic changes were measured. The results demonstrated that the granules could improve blood rheology, decrease st-segment of electrocardiograms and the activities of LDH and CK in serum, reduce myocardial infarction size, and alleviate myocardial histopathologic changes. In addition, the effect of the granules depended on the dose administrated orally. The results suggest that the Yangshen granules could produce cardioprotection effect and have potential benefits in the prevention of ischemic heart disease.

  5. Cardioprotection by controlling hyperamylinemia in a "humanized" diabetic rat model.

    Science.gov (United States)

    Despa, Sanda; Sharma, Savita; Harris, Todd R; Dong, Hua; Li, Ning; Chiamvimonvat, Nipavan; Taegtmeyer, Heinrich; Margulies, Kenneth B; Hammock, Bruce D; Despa, Florin

    2014-08-21

    Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart. By Western blot, we found abundant amylin aggregates in lysates of cardiac myocytes from obese patients, but not in controls. Aggregated amylin was elevated in failing hearts, suggesting a role in myocyte injury. Using rats overexpressing human amylin in the pancreas (HIP rats) and control myocytes incubated with human amylin, we show that amylin aggregation at the sarcolemma induces oxidative stress and Ca(2+) dysregulation. In time, HIP rats developed cardiac hypertrophy and left-ventricular dilation. We then tested whether metabolites with antiaggregation properties, such as eicosanoid acids, limit myocardial amylin deposition. Rats were treated with an inhibitor of soluble epoxide hydrolase, the enzyme that degrades endogenous eicosanoids. Treatment doubled the blood concentration of eicosanoids, which drastically reduced incorporation of aggregated amylin in cardiac myocytes and blood cells, without affecting pancreatic amylin secretion. Animals in the treated group showed reduced cardiac hypertrophy and left-ventricular dilation. The cardioprotective mechanisms included the mitigation of amylin-induced cardiac oxidative stress and Ca(2+) dysregulation. The results suggest blood amylin as a novel therapeutic target in diabetic heart disease and elevating blood levels of antiaggregation metabolites as a pharmacological strategy to reduce amylin aggregation and amylin-mediated cardiotoxicity. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  6. Antihypertensive and cardioprotective effects of pumpkin seed oil.

    Science.gov (United States)

    El-Mosallamy, Aliaa E M K; Sleem, Amany A; Abdel-Salam, Omar M E; Shaffie, Nermeen; Kenawy, Sanaa A

    2012-02-01

    Pumpkin seed oil is a natural product commonly used in folk medicine for treatment of prostatic hypertrophy. In the present study, the effects of treatment with pumpkin seed oil on hypertension induced by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg /kg/day) in rats were studied and compared with those of the calcium channel blocker amlodipine. Pumpkin seed oil (40 or 100 mg/kg), amlodipine (0.9 mg/kg), or vehicle (control) was given once daily orally for 6 weeks. Arterial blood pressure (BP), heart rate, electrocardiogram (ECG) changes, levels of serum nitric oxide (NO) (the concentrations of nitrite/nitrate), plasma malondialdehyde (MDA), blood glutathione, and erythrocytic superoxide dismutase activity were measured. Histopathological examination of heart and aorta was conducted as well. L-NAME administration resulted in a significant increase in BP starting from the second week. Pumpkin seed oil or amlodipine treatment significantly reduced the elevation in BP by L-NAME and normalized the L-NAME-induced ECG changes-namely, prolongation of the RR interval, increased P wave duration, and ST elevation. Both treatments significantly decreased the elevated levels of MDA and reversed the decreased levels of NO metabolites to near normal values compared with the L-NAME-treated group. Amlodipine also significantly increased blood glutathione content compared with normal (but not L-NAME-treated) rats. Pumpkin seed oil as well as amlodipine treatment protected against pathological alterations in heart and aorta induced by L-NAME. In conclusion, this study has shown that pumpkin seed oil exhibits an antihypertensive and cardioprotective effects through a mechanism that may involve generation of NO.

  7. Development of Matrix Metalloproteinase-2 Inhibitors for Cardioprotection

    Directory of Open Access Journals (Sweden)

    Péter Bencsik

    2018-04-01

    Full Text Available The objective of our present study is to develop novel inhibitors for MMP-2 for acute cardioprotection. In a series of pilot studies, novel substituted carboxylic acid derivatives were synthesized based on imidazole and thiazole scaffolds and then tested in a screeening cascade for MMP inhibition. We found that the MMP-inhibiting effects of imidazole and thiazole carboxylic acid-based compounds are superior in efficacy in comparison to the conventional hydroxamic acid derivatives of the same molecules. Based on these results, a 568-membered focused library of imidazole and thiazole compounds was generated in silico and then the library members were docked to the 3D model of MMP-2 followed by an in vitro medium throughput screening (MTS based on a fluorescent assay employing MMP-2 catalytic domain. Altogether 45 compounds showed a docking score of >70, from which 30 compounds were successfully synthesized. Based on the MMP-2 inhibitory tests using gelatin zymography, 7 compounds were then selected and tested in neonatal rat cardiac myocytes subjected to simulated I/R injury. Six compounds showed significant cardio-cytoprotecion and the most effective compound (MMPI-1154 significantly decreased infarct size when applied at 1 μM in an ex vivo model for acute myocardial infarction. This is the first demonstration that imidazole and thiazole carboxylic acid-based compounds are more efficacious MMP-2 inhibitor than their hydroxamic acid derivatives. MMPI-1154 is a promising novel cardio-cytoprotective imidazole-carboxylic acid MMP-2 inhibitor lead candidate for the treatment of acute myocardial infarction.

  8. Development of Matrix Metalloproteinase-2 Inhibitors for Cardioprotection

    Science.gov (United States)

    Bencsik, Péter; Kupai, Krisztina; Görbe, Anikó; Kenyeres, Éva; Varga, Zoltán V.; Pálóczi, János; Gáspár, Renáta; Kovács, László; Weber, Lutz; Takács, Ferenc; Hajdú, István; Fabó, Gabriella; Cseh, Sándor; Barna, László; Csont, Tamás; Csonka, Csaba; Dormán, György; Ferdinandy, Péter

    2018-01-01

    The objective of our present study is to develop novel inhibitors for MMP-2 for acute cardioprotection. In a series of pilot studies, novel substituted carboxylic acid derivatives were synthesized based on imidazole and thiazole scaffolds and then tested in a screeening cascade for MMP inhibition. We found that the MMP-inhibiting effects of imidazole and thiazole carboxylic acid-based compounds are superior in efficacy in comparison to the conventional hydroxamic acid derivatives of the same molecules. Based on these results, a 568-membered focused library of imidazole and thiazole compounds was generated in silico and then the library members were docked to the 3D model of MMP-2 followed by an in vitro medium throughput screening (MTS) based on a fluorescent assay employing MMP-2 catalytic domain. Altogether 45 compounds showed a docking score of >70, from which 30 compounds were successfully synthesized. Based on the MMP-2 inhibitory tests using gelatin zymography, 7 compounds were then selected and tested in neonatal rat cardiac myocytes subjected to simulated I/R injury. Six compounds showed significant cardio-cytoprotecion and the most effective compound (MMPI-1154) significantly decreased infarct size when applied at 1 μM in an ex vivo model for acute myocardial infarction. This is the first demonstration that imidazole and thiazole carboxylic acid-based compounds are more efficacious MMP-2 inhibitor than their hydroxamic acid derivatives. MMPI-1154 is a promising novel cardio-cytoprotective imidazole-carboxylic acid MMP-2 inhibitor lead candidate for the treatment of acute myocardial infarction. PMID:29674965

  9. Inhibitors in haemophilia A: a perspective on clotting factor products as a potential contributing factor.

    Science.gov (United States)

    Mathew, P; Dinter, H; Church, N; Humphries, T J; Kulkarni, R

    2016-05-01

    The occurrence of a neutralizing antibody in previously untreated patients (PUPs) with haemophilia A appears to be the result of an intricate interplay of both genetic and environmental factors. Recently, the type of factor VIII (FVIII) product used in the PUPs population has been implicated as a risk factor for inhibitor development. The aim of this review was to explore in a systematic manner potential hypotheses for the product-related findings in these studies (i.e. differences in the expression system of the cell lines used to produce recombinant FVIII [rFVIII], differences in the administered antigen load or changes in clinical practice over time). Review of the available clinical studies illustrates the high degree of variability for the risk of inhibitor development for the same products across different studies. Differences in cell lines or antigen load were not found to provide a reasonable explanation. The possibility of changes in clinical practice over time and patient selection bias (i.e. the preferential use of one product over another in patients at higher risk for inhibitors) offers a potential explanation and should be carefully considered when evaluating the studies. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  10. Cardiotoxic effects of the novel approved anti-ErbB2 agents and reverse cardioprotective effects of ranolazine

    Directory of Open Access Journals (Sweden)

    De Lorenzo C

    2018-04-01

    Full Text Available Claudia De Lorenzo,1,2,* Rolando Paciello,1,2,* Gennaro Riccio,3 Domenica Rea,4 Antonio Barbieri,4 Carmela Coppola,4 Nicola Maurea4 1Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy; 2Ceinge, Biotecnologie Avanzate s.c.a.r.l., Naples, Italy; 3Department of Pharmacy, Federico II University, Naples, Italy; 4Division of Cardiology, Istituto Nazionale Tumori – Irccs Fondazione G. Pascale, Naples, Italy *These authors contributed equally to this work Purpose: Pertuzumab, a novel anti-epidermal growth factor receptor 2 humanized monoclonal antibody, and trastuzumab-emtansine (TDM1, a novel antibody–drug conjugate made up of trastuzumab covalently linked to the highly potent microtubule inhibitory agent DM1, have been recently approved by the US Food and Drug Administration for increasing the efficiency and safety of breast cancer therapy with trastuzumab. We investigated for the first time the potential cardiotoxic effects of pertuzumab and TDM1, which are not yet fully elucidated, and we tested whether ranolazine could blunt their cardiotoxicity.Methods: The cardiotoxic effects were tested in vitro on rat cardiomyoblasts, human fetal cardiomyocytes, adult-like cardiomyocytes, and in vivo on a mouse model.Results: All the treated cardiac cell lines were significantly affected by treatment with the tested drugs. Surprisingly, TDM1 showed stronger inhibitory effects on cardiac cells with respect to trastuzumab and pertuzumab by more significantly reducing the cell viability and by changing the morphology of these cells. TDM1 also affected the beating phenotype of adult-like cardiomyocytes in vitro and reduced fractional shortening and ejection fraction in vivo in a mouse model. We also found that ranolazine attenuated not only the cardiotoxic side effects of trastuzumab but also those of pertuzumab and TDM1, when used in combinatorial treatments both in vitro and in vivo, as

  11. Factors potentially influencing academic performance among medical students

    Directory of Open Access Journals (Sweden)

    Al Shawwa L

    2015-01-01

    Full Text Available Lana Al Shawwa,1 Ahmad A Abulaban,2 Abdulrhman A Abulaban,3 Anas Merdad,3 Sara Baghlaf,3 Ahmed Algethami,3 Joullanar Abu-shanab,3 Abdulrahman Balkhoyor3 1Department of Medical Education, College of Medicine, King Abdulaziz University, Jeddah, 2Department of Medicine-Neurology, King Fahad National Guard Hospital, King Abdulziz Medical City, Riyadh, 3Department of Medical Education, College of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia Background: Studies are needed to examine predictors of success in medical school. The aim of this work is to explore factors that potentially influence excellence of medical students. Methods: The study was conducted in the Medical Faculty of King Abdulaziz University during October 2012. A self-administered questionnaire was used. Medical students with a grade point average (GPA ≥4.5 (out of 5 were included and compared to randomly selected medical students with a GPA <4.5, who were available at the time of the study. Results: A total of 359 undergraduate students participated in the study. 50.4% of the sample was students with a GPA ≥4.5. No statistically significant difference regarding the time spent on outings and social events was found. However, 60.7% of high GPA students spend less than 2 hours on social networking per day as compared to 42.6% of the lower GPA students (P<0.01. In addition, 79% of high GPA students prefer to study alone (P=0.02, 68.0% required silence and no interruptions during studying time (P=0.013, and 47% revise their material at least once before an exam (P=0.02. Conclusion: Excellent medical students have many different characteristics. For example, they do not use social networking for prolonged periods of time, and they have strong motivation and study enjoyment. Further studies are needed to examine whether these differences have a real impact on GPA or not. Keyword: King Abdulaziz University KAU, medical school, study habits, exam habits 

  12. Urban air pollution produces up-regulation of myocardial inflammatory genes and dark chocolate provides cardioprotection.

    Science.gov (United States)

    Villarreal-Calderon, Rodolfo; Reed, William; Palacios-Moreno, Juan; Keefe, Sheyla; Herritt, Lou; Brooks, Diane; Torres-Jardón, Ricardo; Calderón-Garcidueñas, Lilian

    2012-05-01

    Air pollution is a serious environmental problem. Elderly subjects show increased cardiac morbidity and mortality associated with air pollution exposure. Mexico City (MC) residents are chronically exposed to high concentrations of fine particulate matter (PM(2.5)) and PM-associated lipopolysaccharides (PM-LPS). To test the hypothesis that chronic exposure to urban pollution produces myocardial inflammation, female Balb-c mice age 4 weeks were exposed for 16 months to two distinctly different polluted areas within MC: southwest (SW) and northwest (NW). SW mice were given either no treatment or chocolate 2g/9.5 mg polyphenols/3 times per week. Results were compared to mice kept in clean air. Key inflammatory mediator genes: cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the LPS receptor CD14 (cluster of differentiation antigen 14) were measured by real-time polymerase chain reaction. Also explored were target NFκB (nuclear factor κB), oxidative stress and antioxidant defense genes. TNF-α, IL-6, and COX-2 were significantly increased in both NW and SWMC mice (p=0.0001). CD14 was up-regulated in SW mice in keeping with the high exposures to particulate matter associated endotoxin. Chocolate administration resulted in a significant down-regulation of TNF-α (p<0.0001), IL-6 (p=0.01), and IL-1β (p=0.02). The up-regulation of antioxidant enzymes and the down-regulation of potent oxidases, toll-like receptors, and pro-apoptotic signaling genes completed the protective profile. Exposure to air pollution produces up-regulation of inflammatory myocardial genes and endotoxin plays a key role in the inflammatory response. Regular consumption of dark chocolate may reduce myocardial inflammation and have cardioprotective properties in the setting of air pollution exposures. Copyright © 2010 Elsevier GmbH. All rights reserved.

  13. Psychological Factors and Reference Potential of Market Mavens

    Directory of Open Access Journals (Sweden)

    Jofi Puspa

    2009-09-01

    Full Text Available The function of a market maven in the information transfer processes is apparently related to one’s psychological states such as inherent knowledge and involvement level. Understanding reference potential of mavens seems to be relevant to comprehend the implicit value of a maven in the communication process. This study shows that (1 apparently, maven groups can be clearly distinguished from a non-maven group on the basis on inherent personal knowledge level and involvement level; (2 market mavens have a high reference potential which confirmed their function in WOM-information.

  14. Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics.

    Science.gov (United States)

    Suleiman, M-S; Zacharowski, K; Angelini, G D

    2008-01-01

    Open-heart surgery triggers an inflammatory response that is largely the result of surgical trauma, cardiopulmonary bypass, and organ reperfusion injury (e.g. heart). The heart sustains injury triggered by ischaemia and reperfusion and also as a result of the effects of systemic inflammatory mediators. In addition, the heart itself is a source of inflammatory mediators and reactive oxygen species that are likely to contribute to the impairment of cardiac pump function. Formulating strategies to protect the heart during open heart surgery by attenuating reperfusion injury and systemic inflammatory response is essential to reduce morbidity. Although many anaesthetic drugs have cardioprotective actions, the diversity of the proposed mechanisms for protection (e.g. attenuating Ca(2+) overload, anti-inflammatory and antioxidant effects, pre- and post-conditioning-like protection) may have contributed to the slow adoption of anaesthetics as cardioprotective agents during open heart surgery. Clinical trials have suggested at least some cardioprotective effects of volatile anaesthetics. Whether these benefits are relevant in terms of morbidity and mortality is unclear and needs further investigation. This review describes the main mediators of myocardial injury during open heart surgery, explores available evidence of anaesthetics induced cardioprotection and addresses the efforts made to translate bench work into clinical practice.

  15. Targets Involved in Cardioprotection by the Non-Anesthetic Noble Gas Helium

    NARCIS (Netherlands)

    Weber, Nina C.; Smit, Kirsten F.; Hollmann, Markus W.; Preckel, Benedikt

    2015-01-01

    Research data from the past decade indicate that noble gases like xenon and helium exert profound cardioprotection when applied before, during or after organ ischemia. Of all noble gases, especially helium, has gained interest in the past years because it does not have an anesthetic "side effect"

  16. Motivating Factors for Sustainable Accountant Potentials in Malaysia

    Directory of Open Access Journals (Sweden)

    Syed Ibrahim Sharifah Norhafiza

    2017-01-01

    Full Text Available Economic Transformation Plan (ETP emphasizes that the country has a pool of resources to steer towards Malaysia’s aspirations to become a developed and high-income nation. The ETP Roadmap highlights accountancy, an integral function in all businesses as part of the significant ETP driver. However, Malaysia still lacks the required number of qualified accountants by the year 2020. This challenges higher learning institutions to produce suitable accounting graduates. Despite taking an accounting subject in schools, not all these students later opt to enrol accounting in higher learning institutions as many factors influence their career choices. This study aims to explore these motivating factors. A quantitative approach was applied whereby primary data were collected through a questionnaire survey. Respondents were students from seven elite schools in Melaka. The study found eight motivating factors; family members in the accounting profession, public accountant as a career choice, students’ interest in receiving relevant information, choosing private accountants as a career, parents, school counsellor and career talk. However, only four of these factors were significant to students’ decisions to pursue professional accounting courses. In addition, parents’ influence plays a greater role in motivating students to opt for professional accounting courses as compared to an accounting degree.

  17. Potential predictive factors of positive prostate biopsy in the Chinese ...

    African Journals Online (AJOL)

    Yomi

    2012-01-16

    Jan 16, 2012 ... Therefore, it might be inappropriate that we apply these western models to the. Chinese population that has a lower incidence of PCa. Therefore, this retrospective study aimed to determine predictive factors for a positive prostate biopsy in Chinese men. Our ultimate goal is to develop a simple model for ...

  18. Osteogenic Potential of the Transcription Factor c-MYB

    Czech Academy of Sciences Publication Activity Database

    Oralová, Veronika; Matalová, Eva; Killinger, Michael; Knopfová, L.; Šmarda, J.; Buchtová, Marcela

    2017-01-01

    Roč. 100, č. 3 (2017), s. 311-322 ISSN 0171-967X R&D Projects: GA ČR(CZ) GB14-37368G Institutional support: RVO:67985904 Keywords : mineralised matrix * micromass cultures * mouse limbs Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Developmental biology Impact factor: 3.124, year: 2016

  19. Interionic pair potentials and partial structure factors of compound ...

    Indian Academy of Sciences (India)

    Hiroike. Formulae are applied to NaSn (Na, Sn, NaSn, Na3Sn) which is considered as a ... for not only physicists but also chemists and engineers. This study is ... alizing Harrison's [18] approach of pair-wise potential between the metallic ions.

  20. Alcohol in moderation, cardioprotection, and neuroprotection: epidemiological considerations and mechanistic studies.

    Science.gov (United States)

    Collins, Michael A; Neafsey, Edward J; Mukamal, Kenneth J; Gray, Mary O; Parks, Dale A; Das, Dipak K; Korthuis, Ronald J

    2009-02-01

    In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions-pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, beta-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol

  1. Fibroblast Growth Factor-23—A Potential Uremic Toxin

    Directory of Open Access Journals (Sweden)

    Piotr Kuczera

    2016-12-01

    Full Text Available Fibroblast growth factor-23 (FGF23 is a circulating member of the FGF family produced mainly by the osteocytes and osteoblasts that can act as a hormone. The main action of FGF23 is to lower phosphatemia via the reduction of urinary phosphate reabsorption and the decrease of 1,25(OH2-D generation in the kidney. In the course of chronic kidney disease (CKD, plasma FGF23 concentration rises early, most probably to compensate the inability of the deteriorating kidneys to excrete an adequate amount of phosphate. However, this comes at the cost of FGF23-related target organ toxicity. Results of clinical studies suggest that elevated plasma FGF23 concentration is independently associated with the increased risk of CKD progression, occurrence of cardio-vascular complications, and mortality in different stages of CKD. FGF23 also contributes to cardiomyocyte hypertrophy, vascular calcification, and endothelial dysfunction. The impact of FGF23 on heart muscle is not dependent on Klotho, but rather on the PLCγ–calcineurin–NFAT (nuclear factor of activated T-cells pathway. Among the factors increasing plasma FGF23 concentration, active vitamin D analogues play a significant role. Additionally, inflammation and iron deficiency can contribute to the increase of plasma FGF23. Among the factors decreasing plasma FGF23, dietary phosphate restriction, some intestinal phosphate binders, cinacalcet (and other calcimimetics, and nicotinamide can be enumerated. Anti-FGF23 antibodies have also recently been developed to inhibit the action of FGF23 in target organs. Still, the best way to normalize plasma FGF23 in maintenance hemodialysis patients is restoring kidney function by successful kidney transplantation.

  2. Human Resource – Potential Factor of Organiztional Crisis

    Directory of Open Access Journals (Sweden)

    Mihail Cristian Negrulescu

    2008-10-01

    Full Text Available At the level of any economic system, the change brings about the modification of the internal operating method of the relations between the actors and of the work habits. In other words, the substance (main, important modifications can be shaped on each of the organizational dominant of the system at a structural, functional or cultural level, in which the main actor, the human resource, intends to be part of this equation of changes. In this context, significant is the role played by the main organization actors, a role which can be materialized either as a factor of innovation, prevention and even progress, or as a conflict promoting factor, which, in time, generates a state of abnormality, of crisis. That is why major importance must be allotted to the human resources at the level of each organisation, considering the progress focused on knowledge, experience, experiments, attitude, behaviour and competences, these implying factors of correction and efficient reaction for the administration of the organizational crises.

  3. Potential risk factors for diabetic neuropathy: a case control study

    Directory of Open Access Journals (Sweden)

    Nooraei Mahdi

    2005-12-01

    Full Text Available Abstract Background Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression. Methods In this case-control study, 110 diabetic patients were selected from the Shariati Hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS was used to differentiate cases from controls. The diagnosis of neuropathy was confirmed by nerve conduction studies (nerve conduction velocity and electromyography. The multiple factors compared between the two groups included consumption of angiotensin converting enzyme inhibitors (ACEI, blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality. Results Statistically significant relationships were found between neuropathy and age, gender, quality of diabetes control and duration of disease (P values in the order: 0.04, 0.04, Conclusion In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control reduces the incidence of neuropathy, slows its progression and improves the diabetic patient's quality of life. More attention must be paid to elderly male diabetic patients with poor diabetes control with regard to regular foot examinations and more practical education.

  4. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  5. Factors affecting potential market penetration of laser fusion power plants

    International Nuclear Information System (INIS)

    Deonigi, D.E.; Fraley, D.W.

    1979-08-01

    A mini-model has been constructed to estimate the optimal size of laser fusion power plants and to estimate the allowable cost of the first such plant in relation to the next best alternative. In estimating the costs of laser fusion, the mini-model incorporates such factors as market penetration, learning, economies of scale, system size, transmission costs, reserve requirements, development and licensing costs and site costs. The results of the mini-model simulations indicate that the optimal laser fusion plant size is approximately 3 GWe; risk considerations unincorporated in the mini-model suggest an optimal size closer to 2.5 GWe

  6. Recognizing influencing factors on students' leadership trait potential

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Hosseini Moghadam

    2013-05-01

    Full Text Available This paper presents a study to investigate the effect of university education on leadership capacity of both male and female management students of Ferdowsi University of Mashhad. The data were collected from the first and the last year students using classified sampling method. The results of 116 questionnaires analyzed using SPSS software indicate that university education had a different effect on both male and female students' leadership capacity. Comparing the results of this study with other countries shows that the role of culture should be considered as an effective factor, while evaluating and comparing students' leadership capacity among communities.

  7. Balneotherapy is a potential risk factor for Pseudomonas aeruginosa colonization

    Directory of Open Access Journals (Sweden)

    Gabriela Deutsch

    Full Text Available ABSTRACT The practice of immersion in burn patient has been abandoned in many parts of the world but in Brazil it is still common. The aim of this study was to ascertain if balneotherapy is a risk factor for Pseudomonas aeruginosa colonization in thermally injured patients. Eighteen patients from a Burn Center were studied for 14 weeks for Pseudomonas aeruginosa. Samples were collected by swabbing the exudate of wounds, before and after giving bath to the patients and from balneotherapy table. Pulsed-field gel electrophoresis was used to determine bacterial genetic relatedness. Thirty-seven P. aeruginosa isolates were detected from 292 swabs collected from patients' burn surface area and from the balneotherapy table. Profile analysis of P. aeruginosa DNA fragmentation showed 10 clones among the 37 strains analyzed. Type A is the most prevalent clone, with 23 strains distributed into eight subtypes. These were present in the swabs collected, before and after the patients' bath, from the surface of the bath table, suggesting that there was cross-contamination between the patients in different ways. This work demonstrates that balneotherapy is a risk factor in the Burn Center studied, because the same clone was found among P. aeruginosa isolates collected at various points and times.

  8. Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

    Energy Technology Data Exchange (ETDEWEB)

    Toyonaga, Takuya; Hirata, Kenji; Kobayashi, Kentaro; Manabe, Osamu; Watanabe, Shiro; Hattori, Naoya; Shiga, Tohru; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Yamaguchi, Shigeru [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki [Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Tanaka, Shinya [Hokkaido University Graduate School of Medicine, Department of Cancer Pathology, Sapporo (Japan); Ito, Yoichi M. [Hokkaido University Graduate School of Medicine, Department of Biostatistics, Sapporo (Japan)

    2017-04-15

    Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV x FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV

  9. Potential risk factors for psychiatric disorders in patients with headache.

    Science.gov (United States)

    Nimnuan, Chaichana; Asawavichienjinda, Thanin; Srikiatkhachorn, Anan

    2012-01-01

    Psychiatric comorbidities are common among patients with headache. These can compromise the quality of life of patients and may affect the result of treatment. No available systematic study concerning this problem has been conducted in Thailand. The study aimed to determine the prevalence and risk factors of psychiatric disorders in patients with headache in tertiary care facility. The study was conducted at the Headache Clinic, King Chulalongkorn Memorial Hospital in Bangkok, Thailand. One hundred and thirteen patients were enrolled. Diagnosis of headache was made based on International Classification of Headache Disorders II system. Mental disorders were assessed using Primary Care Evaluation of Mental Disorders. Other possible risk factors were extracted using significant physical symptoms count and accumulated risk for mental disorder. Of the 113 samples analyzed, the prevalence of depression, anxiety, and somatoform disorder was found to be 29.2%, 9.7%, and 27.4%, respectively. No definite relationship between headache types and mental disorders was observed. High number of significant physical complaints and health concerns significantly increased the risk for depression (OR = 4.6, 95% CI = 1.6 to 13.5) while the level of possible risk for mental disorder was associated with an increased risk for somatoform disorder (OR = 1.6, 95% CI = 1.2 to 2.2). The study confirmed high prevalence of psychiatric comorbidities in patients with headache. The results of this study will raise the awareness of physicians to possible underlying mental disorders in patients with headache and facilitate appropriate treatment or psychiatric referral. © 2011 American Headache Society.

  10. Factors affecting the reproductive potential of dairy cows

    International Nuclear Information System (INIS)

    Folman, Y.; Rosenberg, M.; Kaim, M.

    1990-01-01

    Various factors that affect fertility were examined in high yielding dairy cows. In cows treated for the synchronization of oestrous cycles, manifestation of oestrus following synchronization treatment was affected by the body condition score in the winter; 74% of the cows had a low score. Primiparous cows that were thin or fat had a low conception rate. The conception rate of multiparous cows with different body condition scores did not differ in the winter. However, in the summer, thin, medium-low, medium-high and fat cows had a conception rate of 15, 36, 48 and 27%, respectively (P 4 ) levels five days before the first post-partum AI affected conception rates. Primiparous cows with low (≤2 ng/mL), medium (2.1-4.0 ng/mL) and high (≥4.1 ng/mL) P 4 levels had a conception rate of 28, 17 and 61%, respectively (P 4 had a conception rate of 25, 46 and 52%, respectively (P<0.02). Cows in their fifth or later lactation that were fed straw as their sole roughage had a conception rate of 23% and a 120 day pregnancy rate of 23%. Cows of the same parities that were fed hay had a conception rate of 50% (P<0.05) and a pregnancy rate of 80% (P<0.005). (author). 15 refs, 5 tabs

  11. Potential factors that may promote successful cognitive aging

    Directory of Open Access Journals (Sweden)

    Vance DE

    2012-06-01

    Full Text Available David E VanceCenter for Nursing Research, School of Nursing, Edward R Roybal Center for Translational Research in Aging and Mobility, University of Alabama at Birmingham (UAB, Birmingham, AL, USAAbstract: With the unprecedented number of older adults worldwide, it is important to consider ways of facilitating successful cognitive aging. One way to think of this is by augmenting or bolstering cognitive reserve. Loosely defined, cognitive reserve is considered a neurological reservoir that can be depleted by physiological insults (eg, white matter hyperintensities, oxidative stress to the brain but yet maintain optimal cognitive functioning. Cognitive reserve is built up or depleted by processes of positive and negative neuroplasticity, respectively. Lifestyle factors such as physical exercise (+, mental stimulation (+, good sleep hygiene (+, substance abuse (-, sedentary lifestyle (-, chronic stress and depression (-, social isolation (-, and poor health (- can either promote or discourage positive and negative neuroplasticity, which in turn impacts cognitive reserve. Nurses are encouraged to understand these processes so they can help facilitate successful cognitive aging in their patients.Keywords: cognitive reserve, Alzheimer's disease, neuroplasticity

  12. Potential factors affecting accumulation of unsupported 210Pb in soil

    International Nuclear Information System (INIS)

    Mihailović, Aleksandra; Vučinić Vasić, Milica; Todorović, Nataša; Hansman, Jan; Vasin, Jovica; Krmar, Miodrag

    2014-01-01

    Airborne 210 Pb, daughter of 222 Rn, is frequently used as a tracer in different studies concerning atmospheric transport, sedimentation, soil erosion, dating, etc. Concentration of 210 Pb was measured in 40 soil samples collected in urban and industrial areas in order to get evidence of possible influence of some factors on accumulation of airborne 210 Pb in soil. Different soil properties such as the content of organic matter, free CaCO 3 , and available phosphorus (P 2 O 5 ) were measured to explore their possible correlation with the amount of 210 Pb. Special attention was given to the correlation between 210 Pb and stable lead accumulated in the soil. Several samples were taken near a battery manufacturer to check if extremely high concentrations of lead can affect the uptake of the airborne 210 Pb in soil. Soil samples were also taken at different depths to investigate the penetration of lead through the soil. - Highlights: • 210 Pb and 137 Cs were measured in samples of urban soil. • Organic matter, free CaCO 3 content, available phosphorus, and lead were measured in soil samples. • There is no statistically significant correlation between 210 Pb and lead, CaCO 3 and phosphorus. • A strong positive correlation between 210 Pb and organic matter was observed

  13. Periodontal disease as a potential factor of migraine chronification.

    Science.gov (United States)

    Ameijeira, Pablo; Leira, Yago; Blanco, Juan; Leira, Rogelio

    2017-05-01

    Migraine is a hereditary constitutional base disorder, which is characterized by recurrent episodes of headache pulsatile characteristics associated with photophobia/phonophobia, nausea and/or vomiting. The main complication in migraine is the chronicity of the process, now recognized as a chronic migraine. Although pathogenic mechanisms that may influence the pathophysiology of migraine and its possible chronicity are not fully understood, previous studies have shown in patients with migraine molecular alterations of systemic inflammation, neurogenic inflammation, endothelial dysfunction, innate immunity, dysfunction of matrix proteases and blood-brain barrier. Periodontal disease is an inflammatory lesion caused by bacteria. After the bacterial infection begins, an immune response that will be responsible for individual susceptibility appears. More advanced forms of periodontitis have demonstrated molecular alterations of inflammation, endothelial dysfunction, dysfunction of matrix proteases and innate immunity, similar to those observed in migraine. Furthermore, the main molecular mediators of neurogenic inflammation related to activation of the trigeminovascular system, which are characteristic of migraine, are overexpressed in gingival crevicular fluid and mucosa in patients with periodontal disease. Hypertension, hypercholesterolemia, insulin resistance, stroke or coronary artery disease are comorbidities that periodontal disease and migraine could share. Therefore, several mechanisms and hypotheses could explain the possible association between both diseases. However, epidemiological and molecular studies will be necessary to provide a better understanding of this potential association, which could be implicated in the chronification of migraine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Tehran Survey of Potential Risk Factors for Multiple Births

    Directory of Open Access Journals (Sweden)

    Reza Omani Samani

    2017-09-01

    Full Text Available Background The multiple pregnancy incidence is increasing worldwide. This increased incidence is concerning to the health care system. This study aims to determine the frequency of multiple pregnancy and identify factors that affect this frequency in Tehran, Iran. Materials and Methods This cross-sectional study included 5170 mothers in labor between July 6-21, 2015 from 103 hospitals with Obstetrics and Gynecology Wards. The questionnaire used in this study consisted of five parts: demographic characteristics; information related to pregnancy; information related to the infant; information regarding the multiple pregnancy; and information associated with infertility. We recruited 103 trained midwives to collect data related to the questionnaire from eligible participants through an interview and medical records review. Frequencies and odds ratios (OR for the association between multiple pregnancy and the selected characteristics (maternal age, economic status, history of multiple pregnancy in first-degree relatives, and reproductive history were computed by multiple logistic regression. Stata software, version 13 (Stata Corp, College Station, TX, USA was used for all statistical analyses. Results Multiple pregnancy had a prevalence of 1.48% [95% confidence interval (CI: 1.19-1.85]. After controlling for confounding variables, we observed a significant association between frequency of multiple pregnancy and mother’s age (OR=1.04, 95% CI: 1.001-1.09, P=0.044, assisted reproductive technique (ART, OR=6.11, 95% CI: 1.7- 21.97, P=0.006, and history of multiple pregnancy in the mother’s family (OR=5.49, 95% CI: 3.55-9.93, P=0.001. Conclusion The frequency of multiple pregnancy approximated results reported in previous studies in Iran. Based on the results, we observed significantly greater frequency of multiple pregnancy in older women, those with a history of ART, and a history of multiple pregnancy in the mother’s family compared to the other

  15. Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart

    Directory of Open Access Journals (Sweden)

    Singh Manjeet

    2011-07-01

    Full Text Available Abstract Background Nitric oxide (NO has been noted to produce ischemic preconditioning (IPC-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM. The present study was designed to investigate the involvement of caveolin in attenuation of the cardioprotective effect of IPC during DM in rat. Methods Experimental DM was induced by single dose of streptozotocin (50 mg/Kg, i.p, and animals were used for experiments four weeks later. Isolated heart was mounted on Langendorff's apparatus, and was subjected to 30 min of global ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Kreb's-Henseleit solution (K-H. Extent of injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC staining, and release of lactate dehydrogenase (LDH and creatin kinase-MB (CK-MB in coronary effluent. The cardiac release of NO was noted by measuring the level of nitrite in coronary effluent. Results IPC- induced cardioprotection and release of NO was significantly decreased in diabetic rat heart. Pre-treatment of diabetic rat with daidzein (DDZ a caveolin inhibitor (0.2 mg/Kg/s.c, for one week, significantly increased the release of NO and restored the attenuated cardioprotective effect of IPC. Also perfusion of sodium nitrite (10 μM/L, a precursor of NO, significantly restored the lost effect of IPC, similar to daidzein in diabetic rat. Administration of 5-hydroxy deaconate (5-HD, a mito KATP channel blocker, significantly abolished the observed IPC-induced cardioprotection in normal rat or daidzein and sodium nitrite perfused diabetic rat heart alone or in combination. Conclusions Thus, it is suggested that attenuation of the cardioprotection in diabetic heart may be due to decrease the IPC mediated release of NO in

  16. Increased F3-Isoprostanes in the Canadian Inuit Population Could Be Cardioprotective by Limiting F2-Isoprostane Production.

    Science.gov (United States)

    Alkazemi, Dalal; Jackson, Robert L; Chan, Hing Man; Kubow, Stan

    2016-09-01

    F3-isoprostanes (F3-IsoPs), derived from peroxidation of eicosapentaenoic acid (C20:5n-3), could be cardioprotective by limiting production of F2-isoprostanes (F2-IsoPs), a cardiovascular disease risk factor. The objective of the study was to determine whether the n-3-polyunsaturated (PUFA)-rich Inuit diet is associated with a lower plasma ratio of F2-IsoPs to F3-IsoPs. This was a cross-sectional observational study. The study was conducted in 36 Canadian Arctic Inuit communities. Participants included a random subset (n = 233) of Inuit adults taken from a population-based survey. Plasma F2-IsoPs and F3-IsoPs, cardiometabolic risk factors (blood lipids, C-reactive protein, blood pressure, fasting glucose) and markers of dietary exposure (erythrocyte n-3 and n-6 PUFA, blood levels of Se, mercury, polychlorinated biphenyls) were measured. Inuit aged 40 years old and older vs younger Inuit showed higher concentrations of plasma F3-IsoPs and erythrocyte n-3 PUFA and lower plasma F2-IsoPs concentrations despite having higher blood lipids, fasting glucose, systolic blood pressure, and percentage body fat. Plasma F3-IsoPs were not associated with any cardiometabolic measures. When subjects were categorized into tertiles according to total n-3 PUFA erythrocyte concentrations, F3-IsoPs increased with increasing tertiles, whereas the F2-IsoP to F3-IsoP ratio was lowest at the highest n-3 tertile. The F2-IsoP to F3-IsoP ratio was significantly predicted by C20:5n-3 (β= -.365, P = .002); C20:4n-6:C20:5n-3 (β = .056, P = .006), blood mercury (β = -.812, P =.015), blood Se (β = -1.95, P = .015), and smoking (β = .745, P = .025). Plasma F3-IsoPs were not associated with cardiometabolic risk factors previously seen with F2-IsoPs. Higher n-3 fatty acid status was associated with lower plasma F2-IsoPs and higher plasma F3-IsoPs, which provides partial explanation to the cardioprotective effects of the n-3 PUFA-rich Inuit diet.

  17. Macrophage migration inhibitory factor as a potential prognostic factor in gastric cancer

    Science.gov (United States)

    He, Long-Jun; Xie, Dan; Hu, Pin-Jin; Liao, Yi-Ji; Deng, Hai-Xia; Kung, Hsiang-Fu; Zhu, Sen-Lin

    2015-01-01

    AIM: To investigate macrophage migration inhibitory factor (MIF) expression and its clinical relevance in gastric cancer, and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS: Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry (IHC) semiquantitatively, and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Two pairs of siRNA targeting the MIF gene (MIF si-1 and MIF si-2) and one pair of scrambled siRNA as a negative control (NC) were designed and chemically synthesized. All siRNAs were transiently transfected in AGS cells with OligofectamineTM to knock down the MIF expression, with the NC group and mock group (OligofectamineTM alone) as controls. At 24, 48, and 72 h after transfection, MIF mRNA was analyzed by RT-PCR, and MIF and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot. The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium (MTT) assay and colony forming assay. RESULTS: The tissue microarray was informative for IHC staining, in which the MIF expression in gastric cancer tissues was higher than that in adjacent non-cancer normal tissues (P < 0.001), and high level of MIF was related to poor tumor differentiation, advanced T stage, advanced tumor stage, lymph node metastasis, and poor patient survival (P < 0.05 for all). After siRNA transfection, MIF mRNA was measured by real-time PCR, and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group, MIF expression was knocked down successfully in gastric cancer cells, and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection, and

  18. Cardioprotective effect of Erythrina stricta leaves on isoproterenol-induced myocardial infarction in rat

    Directory of Open Access Journals (Sweden)

    Asokkumar Kuppusamy

    2010-03-01

    Full Text Available The cardioprotective activity of Erythrina stricta leaves against isoproterenol- induced myocardial infarction was studied. Wistar albino rats were pretreated with leaf extract (200 mg/kg daily for 28 days. After treatment, isoproterenol (8.5 mg/kg body weight, orally was injected to rats at an interval of 24 hours for two days to induce myocardial injury. Cardioprotection was investigated by estimating the activities of serum aminotransferase, lactate dehydrogenase and creatinine kinase. Antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and thiobarbituric acid reactive substances were determined. The activities of serum marker enzymes were increased significantly (p<0.05 in isoproterenol-induced rats. E. stricta leaf extract showed a decrease in serum enzyme levels and increase of antioxidant status. The results were confirmed by histopathological evidences. The present study concludes that E. stricta leaf extract has a prophylactic value in myocardial infarction.

  19. Cardioprotective effect of Erythrina stricta leaves on isoproterenol-induced myocardial infarction in rat

    Directory of Open Access Journals (Sweden)

    Divia Chirakkan

    2010-06-01

    Full Text Available The cardioprotective activity of Erythrina stricta leaves against isoproterenol- induced myocardial infarction was studied. Wistar albino rats were pretreated with leaf extract (200 mg/kg daily for 28 days. After treatment, isoproterenol (8.5 mg/kg body weight, orally was injected to rats at an interval of 24 hours for two days to induce myocardial injury. Cardioprotection was investigated by estimating the activities of serum aminotransferase, lactate dehydrogenase and creatinine kinase. Antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and thiobarbituric acid reactive substances were determined. The activities of serum marker enzymes were increased significantly (p<0.05 in isoproterenol-induced rats. E. stricta leaf extract showed a decrease in serum enzyme levels and increase of antioxidant status. The results were confirmed by histopathological evidences. The present study concludes that E. stricta leaf extract has a prophylactic value in myocardial infarction.

  20. Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

    DEFF Research Database (Denmark)

    Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

    2009-01-01

    (Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative...... was downregulated in hearts from ZDF rats at both the mRNA and protein levels (P diabetic hearts (P obese diabetic rats have......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...

  1. Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

    DEFF Research Database (Denmark)

    Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

    2009-01-01

    (Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...... mimics IPC. 2. Rat hearts were studied in a Langendorff preparation perfused with Krebs'-Henseleit solution and subjected to 40 min global no-flow ischaemia, followed by 120 min reperfusion. L-Glutamate (0, 15 and 30 mmol/L) was added to the perfusate during reperfusion of hearts from non-diabetic...

  2. Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

    Science.gov (United States)

    See Hoe, Louise E.; Schilling, Jan M.; Tarbit, Emiri; Kiessling, Can J.; Busija, Anna R.; Niesman, Ingrid R.; Du Toit, Eugene; Ashton, Kevin J.; Roth, David M.; Headrick, John P.; Patel, Hemal H.

    2014-01-01

    Cholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemia-reperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-β-cyclodextrin (MβCD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function, I/R tolerance, and opioid receptor (OR)-mediated protection. Langendorff-perfused hearts from young male C57Bl/6 mice were untreated or treated with 0.02–1.0 mM MβCD for 25 min to deplete membrane cholesterol and disrupt caveolae. Hearts were subjected to 25-min ischemia/45-min reperfusion, and the cardioprotective effects of morphine applied either acutely or chronically [sustained ligand-activated preconditioning (SLP)] were assessed. MβCD concentration dependently reduced normoxic contractile function and postischemic outcomes in association with graded (10–30%) reductions in sarcolemmal cholesterol. Cardioprotection with acute morphine was abolished with ≥20 μM MβCD, whereas SLP was more robust and only inhibited with ≥200 μM MβCD. Deletion of Cav-3 also reduced, whereas Cav-3 OE improved, myocardial I/R tolerance. Protection via SLP remained equally effective in Cav-3 KO mice and was additive with innate protection arising with Cav-3 OE. These data reveal the membrane cholesterol dependence of normoxic myocardial and coronary function, I/R tolerance, and OR-mediated cardioprotection in murine hearts (all declining with cholesterol depletion). In contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R tolerance parallels Cav-3 expression. Novel SLP appears unique, being less sensitive to cholesterol depletion than acute OR protection and arising independently of Cav-3 expression. PMID:25063791

  3. Lowering the alcohol content of red wine does not alter its cardioprotective properties

    OpenAIRE

    Lamont, Kim; Blackhurst, Dee; Albertyn, Zulfah; Marais, David; Lecour, Sandrine

    2012-01-01

    BACKGROUND: Many epidemiological, clinical and laboratory studies suggest that chronic and moderate consumption of red wine benefits cardiovascular health, because of the alcoholic content or the polyphenols/flavonoids. Aims. The antioxidant and cardioprotective properties of a French red wine (cabernet sauvignon, 12% alcohol by volume) were compared with those of the same wine subjected to reverse osmosis for partial removal of alcohol (6% alcohol by volume). METHODS: Antioxidant capacity wa...

  4. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

    OpenAIRE

    Khalil, Md. Ibrahim; Tanvir, E. M.; Afroz, Rizwana; Sulaiman, Siti Amrah; Gan, Siew Hua

    2015-01-01

    The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey...

  5. Metabolites derived from omega-3 polyunsaturated fatty acids are important for cardioprotection.

    Science.gov (United States)

    Gilbert, Kim; Malick, Mandy; Madingou, Ness; Touchette, Charles; Bourque-Riel, Valérie; Tomaro, Leandro; Rousseau, Guy

    2015-12-15

    Although controversial, some data suggest that omega-3 polyunsaturated fatty acids (PUFA) are beneficial to cardiovascular diseases, and could reduce infarct size. In parallel, we have reported that the administration of Resolvin D1 (RvD1), a metabolite of docosahexaenoic acid, an omega-3 PUFA, can reduce infarct size. The present study was designed to determine if the inhibition of two important enzymes involved in the formation of RvD1 from omega-3 PUFA could reduce the cardioprotective effect of omega-3 PUFA. Sprague-Dawley rats were fed with a diet rich in omega-3 PUFA during 10 days before myocardial infarction (MI). Two days before MI, rats received a daily dose of Meloxicam, an inhibitor of cyclooxygenase-2, PD146176, an inhibitor of 15-lipoxygenase, both inhibitors or vehicle. MI was induced by the occlusion of the left coronary artery for 40min followed by reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion while caspase-3, -8 and Akt activities were assessed at 30min of reperfusion. Rats receiving inhibitors, alone or in combination, showed a larger infarct size than those receiving omega-3 PUFA alone. Caspase-3 and -8 activities are higher in ischemic areas with inhibitors while Akt activity is diminished in groups treated with inhibitors. Moreover, the study showed that RvD1 restores cardioprotection when added to the inhibitors. Results from this study indicate that the inhibition of the metabolism of Omega-3 PUFA attenuate their cardioprotective properties. Then, resolvins seem to be an important mediator in the cardioprotection conferred by omega-3 PUFA in our experimental model of MI. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Two new phenolic constituents from the root bark of Morus alba L. and their cardioprotective activity.

    Science.gov (United States)

    Cao, Yan-Gang; Zheng, Xiao-Ke; Yang, Fang-Fang; Li, Fang; Qi, Man; Zhang, Yan-Li; Zhao, Xuan; Kuang, Hai-Xue; Feng, Wei-Sheng

    2018-02-01

    A new biphenyl-furocoumarin, named morescoumarin A (1), and a new prenylated flavanone, named morflavanone A (2) were isolated from the root bark of Morus alba L., together with four known compounds (3-6). Their structures were determined by extensive spectroscopic analyses and comparison with literature data. The cardioprotective effects of these compounds against doxorubicin-induced cell death were evaluated by MTT method.

  7. Lowering the alcohol content of red wine does not alter its cardioprotective properties.

    Science.gov (United States)

    Lamont, Kim; Blackhurst, Dee; Albertyn, Zulfah; Marais, David; Lecour, Sandrine

    2012-05-23

    Many epidemiological, clinical and laboratory studies suggest that chronic and moderate consumption of red wine benefits cardiovascular health, because of the alcoholic content or the polyphenols/flavonoids. The antioxidant and cardioprotective properties of a French red wine (cabernet sauvignon, 12% alcohol by volume) were compared with those of the same wine subjected to reverse osmosis for partial removal of alcohol (6% alcohol by volume). Antioxidant capacity was assessed in vitro using the oxygen radical absorbance capacity (ORAC) assay. To test the cardioprotective effect of 12% v. 6% wine, the drinking water of rats used for controls was supplemented with red wine (12% or 6%). After 10 days, hearts were isolated on a Langendorff system and subjected to 30 minutes of global ischaemia plus 30 minutes of reperfusion (I/R). No differences in antioxidant capacity were observed between wine of 12% and 6% alcohol content (n=8 per group). Control hearts subjected to I/R presented a rate pressure product (heart rate x left ventricular developed pressure, expressed as a percentage of baseline value) of 16±4% (mean±standard error). Pretreatment with wine 12% or 6% improved the rate pressure product to 40±6% and 43±6%, respectively (pwine did not alter its antioxidant and cardioprotective properties. Moderate and regular consumption of lower alcohol content wines may confer beneficial effects without the risks associated with traditional wines of higher alcohol content.

  8. A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

    Directory of Open Access Journals (Sweden)

    Andrew P. Wojtovich

    2013-03-01

    Full Text Available Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.

  9. High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

    International Nuclear Information System (INIS)

    Landim, M.B.P.; Dourado, P.M.M.; Casella-Filho, A.; Chagas, A.C.P.; Luz, P.L. da

    2013-01-01

    A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats

  10. High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Landim, M.B.P.; Dourado, P.M.M.; Casella-Filho, A.; Chagas, A.C.P.; Luz, P.L. da [Unidade de Aterosclerose, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-05-10

    A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.

  11. Cyclosporine A administered during reperfusion fails to restore cardioprotection in prediabetic Zucker obese rats in vivo.

    Science.gov (United States)

    Huhn, R; Heinen, A; Hollmann, M W; Schlack, W; Preckel, B; Weber, N C

    2010-12-01

    Hyperglycaemia blocks sevoflurane-induced postconditioning, and cardioprotection in hyperglycaemic myocardium can be restored by inhibition of the mitochondrial permeability transition pore (mPTP). We investigated whether sevoflurane-induced postconditioning is also blocked in the prediabetic heart and if so, whether cardioprotection could be restored by inhibiting mPTP. Zucker lean (ZL) and Zucker obese (ZO) rats were assigned to one of seven groups. Animals underwent 25 min of ischaemia and 120 min of reperfusion. Control (ZL-/ZO Con) animals were not further treated. postconditioning groups (ZL-/ZO Sevo-post) received sevoflurane for 5 min starting 1min prior to the onset of reperfusion. The mPTP inhibitor cyclosporine A (CsA) was administered intravenously in a concentration of 5 (ZO CsA and ZO CsA+Sevo-post) or 10 mg/kg (ZO CsA10+Sevo-post) 5 min before the onset of reperfusion. At the end of reperfusion, infarct sizes were measured by TTC staining. Blood samples were collected to measure plasma levels of insulin, cholesterol and triglycerides. Sevoflurane postconditioning reduced infarct size in ZL rats to 35±12% (pfailed to restore cardioprotection in the prediabetic but normoglycaemic heart of Zucker obese rats in vivo. Copyright © 2009 Elsevier B.V. All rights reserved.

  12. Fenofibrate plus Metformin Produces Cardioprotection in a Type 2 Diabetes and Acute Myocardial Infarction Model

    Directory of Open Access Journals (Sweden)

    Víctor Hugo Oidor-Chan

    2016-01-01

    Full Text Available We investigated whether fenofibrate, metformin, and their combination generate cardioprotection in a rat model of type 2 diabetes (T2D and acute myocardial infarction (AMI. Streptozotocin-induced diabetic- (DB- rats received 14 days of either vehicle, fenofibrate, metformin, or their combination and immediately after underwent myocardial ischemia/reperfusion (I/R. Fenofibrate plus metformin generated cardioprotection in a DBI/R model, reported as decreased coronary vascular resistance, compared to DBI/R-Vehicle, smaller infarct size, and increased cardiac work. The subchronic treatment with fenofibrate plus metformin increased, compared with DBI/R-Vehicle, total antioxidant capacity, manganese-dependent superoxide dismutase activity (MnSOD, guanosine triphosphate cyclohydrolase I (GTPCH-I expression, tetrahydrobiopterin : dihydrobiopterin (BH4 : BH2 ratio, endothelial nitric oxide synthase (eNOS activity, nitric oxide (NO bioavailability, and decreased inducible NOS (iNOS activity. These findings suggest that PPARα activation by fenofibrate + metformin, at low doses, generates cardioprotection in a rat model of T2D and AMI and may represent a novel treatment strategy to limit I/R injury in patients with T2D.

  13. A study of new potential risk factors for Down syndrome in Upper Egypt

    African Journals Online (AJOL)

    The well-established risk factor, advanced maternal age, was not found in many of the Down syndrome cases in Egypt, while other possible risk factors have not been well studied yet. In view of this, we have conducted the present study to clarify that issue and throw some lights on other potential risk factors in Down ...

  14. Fruitflow®: the first European Food Safety Authority-approved natural cardio-protective functional ingredient.

    Science.gov (United States)

    O'Kennedy, Niamh; Raederstorff, Daniel; Duttaroy, Asim K

    2017-03-01

    Hyperactive platelets, in addition to their roles in thrombosis, are also important mediators of atherogenesis. Antiplatelet drugs are not suitable for use where risk of a cardiovascular event is relatively low. It is therefore important to find alternative safe antiplatelet inhibitors for the vulnerable population who has hyperactive platelets in order to reduce the risk of cardiovascular disease. Potent antiplatelet factors were identified in water-soluble tomato extract (Fruitflow ® ), which significantly inhibited platelet aggregation. Human volunteer studies demonstrated the potency and bioavailability of active compounds in Fruitflow ® . Fruitflow ® became the first product in Europe to obtain an approved, proprietary health claim under Article 13(5) of the European Health Claims Regulation 1924/2006 on nutrition and health claims made on foods. Fruitflow ® is now commercially available in different countries worldwide. In addition to its reduction in platelet reactivity, Fruitflow ® contains anti-angiotensin-converting enzyme and anti-inflammatory factors, making it an effective and natural cardio-protective functional food.

  15. Andrographolide inhibits arrhythmias and is cardioprotective in rabbits

    OpenAIRE

    Zeng, Mengliu; Jiang, Wanzhen; Tian, Youjia; Hao, Jie; Cao, Zhenzhen; Liu, Zhipei; Fu, Chen; Zhang, Peihua; Ma, Jihua

    2017-01-01

    Andrographolide has a protective effect on the cardiovascular system. To study its cardic-electrophysiological effects, action potentials and voltage-gated Na+ (INa), Ca2+ (ICaL), and K+ (IK1, IKr, Ito and IKur) currents were recorded using whole-cell patch clamp and current clamp techniques. Additionally, the effects of andrographolide on aconitine-induced arrhythmias were assessed on electrocardiograms in vivo. We found that andrographolide shortened action potential duration and reduced ma...

  16. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease : A Mendelian Randomization Study

    NARCIS (Netherlands)

    Ostergaard, Soren D.; Mukherjee, Shubhabrata; Sharp, Stephen J.; Proitsi, Petroula; Lotta, Luca A.; Day, Felix; Perry, John R. B.; Boehme, Kevin L.; Walter, Stefan; Kauwe, John S.; Gibbons, Laura E.; Larson, Eric B.; Powell, John F.; Langenberg, Claudia; Crane, Paul K.; Wareham, Nicholas J.; Scott, Robert A.; van der Schouw, YT

    Background Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these

  17. Mitochondrial reactive oxygen species: which ROS signals cardioprotection?

    Czech Academy of Sciences Publication Activity Database

    Garlid, A. O.; Jabůrek, Martin; Jacobs, J. P.; Garlid, K. D.

    2013-01-01

    Roč. 305, č. 7 (2013), H960-H968 ISSN 0363-6135 R&D Projects: GA MŠk(CZ) ME09018; GA ČR(CZ) GAP301/11/0662 Institutional support: RVO:67985823 Keywords : KATP channels * ROS signaling * cardiac ischemia * cardioportection * mitochondria Subject RIV: ED - Physiology Impact factor: 4.012, year: 2013

  18. Histone deacetylase inhibition enhances self renewal and cardioprotection by human cord blood-derived CD34 cells.

    Directory of Open Access Journals (Sweden)

    Ilaria Burba

    Full Text Available BACKGROUND: Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs, have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of "enhancement" strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit. PRINCIPAL FINDINGS: Pharmacologic inhibition of histone deacetylases (HDACs is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34(+ were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction. CONCLUSIONS: Our results show that HDAC blockade leads to phenotype changes in CD34(+ cells with enhanced self renewal and cardioprotection.

  19. Cardioprotective effect of melatonin-standardized ethanol extract of ...

    African Journals Online (AJOL)

    Results: ISO-treated group demonstrated a significant (p < 0.05) elevation in the level of ... Journal Citation Reports/Science Edition, Directory of Open Access Journals ... water, dried and were grinded to make powder. .... radicals and antioxidative defense system, .... Potentials of Seaweed Biomass Ulva lactuca and.

  20. Brain derived neurotrophic factor contributes to the cardiogenic potential of adult resident progenitor cells in failing murine heart.

    Directory of Open Access Journals (Sweden)

    Rasmita Samal

    Full Text Available Resident cardiac progenitor cells show homing properties when injected into the injured but not to the healthy myocardium. The molecular background behind this difference in behavior needs to be studied to elucidate how adult progenitor cells can restore cardiac function of the damaged myocardium. Since the brain derived neurotrophic factor (BDNF moderates cardioprotection in injured hearts, we focused on delineating its regulatory role in the damaged myocardium.Comparative gene expression profiling of freshly isolated undifferentiated Sca-1 progenitor cells derived either from heart failure transgenic αMHC-CyclinT1/Gαq overexpressing mice or wildtype littermates revealed transcriptional variations. Bdnf expression was up regulated 5-fold during heart failure which was verified by qRT-PCR and confirmed at protein level. The migratory capacity of Sca-1 cells from transgenic hearts was improved by 15% in the presence of 25 ng/ml BDNF. Furthermore, BDNF-mediated effects on Sca-1 cells were studied via pulsed Stable Isotope Labeling of Amino acids in Cell Culture (pSILAC proteomics approach. After BDNF treatment significant differences between newly synthesized proteins in Sca-1 cells from control and transgenic hearts were observed for CDK1, SRRT, HDGF, and MAP2K3 which are known to regulate cell cycle, survival and differentiation. Moreover BDNF repressed the proliferation of Sca-1 cells from transgenic hearts.Comparative profiling of resident Sca-1 cells revealed elevated BDNF levels in the failing heart. Exogenous BDNF (i stimulated migration, which might improve the homing ability of Sca-1 cells derived from the failing heart and (ii repressed the cell cycle progression suggesting its potency to ameliorate heart failure.

  1. The Cardioprotective Effects of Citric Acid and L-Malic Acid on Myocardial Ischemia/Reperfusion Injury

    Science.gov (United States)

    Tang, Xilan; Liu, Jianxun; Dong, Wei; Li, Peng; Li, Lei; Lin, Chengren; Zheng, Yongqiu; Hou, Jincai; Li, Dan

    2013-01-01

    Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components of Fructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. In in vivo rat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation. In vitro experiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient of Fructus Choerospondiatis responsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease. PMID:23737849

  2. Andrographolide inhibits arrhythmias and is cardioprotective in rabbits.

    Science.gov (United States)

    Zeng, Mengliu; Jiang, Wanzhen; Tian, Youjia; Hao, Jie; Cao, Zhenzhen; Liu, Zhipei; Fu, Chen; Zhang, Peihua; Ma, Jihua

    2017-09-22

    Andrographolide has a protective effect on the cardiovascular system. To study its cardic-electrophysiological effects, action potentials and voltage-gated Na + (I Na ), Ca 2+ (I CaL ), and K + (I K1 , I Kr , I to and I Kur ) currents were recorded using whole-cell patch clamp and current clamp techniques. Additionally, the effects of andrographolide on aconitine-induced arrhythmias were assessed on electrocardiograms in vivo . We found that andrographolide shortened action potential duration and reduced maximum upstroke velocity in rabbit left ventricular and left atrial myocytes. Andrographolide attenuated rate-dependence of action potential duration, and reduced or abolished delayed afterdepolarizations and triggered activities induced by isoproterenol (1 μM) and high calcium ([Ca 2+ ] o =3.6 mM) in left ventricular myocytes. Andrographolide also concentration-dependently inhibited I Na and I CaL , but had no effect on I to , I Kur , I K1 , or I Kr in rabbit left ventricular and left atrial myocytes. Andrographolide treatment increased the time and dosage thresholds of aconitine-induced arrhythmias, and reduced arrhythmia incidence and mortality in rabbits. Our results indicate that andrographolide inhibits cellular arrhythmias (delayed afterdepolarizations and triggered activities) and aconitine-induced arrhythmias in vivo , and these effects result from I Na and I CaL inhibition. Andrographolide may be useful as a class I and IV antiarrhythmic therapeutic.

  3. Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-κB pathway in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Dejuan Li

    2018-05-01

    Full Text Available Caffeic acid phenethyl ester (CAPE could ameliorate myocardial ischemia/reperfusion injury (MIRI by various mechanisms, but there hadn’t been any reports on that CAPE could regulate silent information regulator 1 (SIRT1 and endothelial nitric oxide synthase (eNOS to exert cardioprotective effect. The present study aimed to investigate the cardioprotective potential of caffeic acid o-nitro phenethyl ester (CAPE-oNO2 on MIRI and the possible mechanism based on the positive control of CAPE. The SD rats were subjected to left coronary artery ischemia /reperfusion (IR and the H9c2 cell cultured in hypoxia/reoxygenation (HR to induce the MIRI model. Prior to the procedure, vehicle, CAPE or CAPE-oNO2 were treated in the absence or presence of a SIRT1 inhibitor nicotinamide (NAM and an eNOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME. In vivo, CAPE and CAPE-oNO2 conferred a cardioprotective effect as shown by reduced myocardial infarct size, cardiac marker enzymes and structural abnormalities. From immunohistochemical and sirius red staining, above two compounds ameliorated the TNF-α release and collagen deposition of IR rat hearts. They could agitate SIRT1 and eNOS expression, and consequently enhance NO release and suppress NF-κB signaling, to reduce the malondialdehyde content and cell necrosis. In vitro, they could inhibit HR-induced H9c2 cell apoptosis and ROS generation by activating SIRT1/eNOS pathway and inhabiting NF-κB expression. Emphatically, CAPE-oNO2 presented the stronger cardioprotection than CAPE both in vivo and in vitro. However, NAM and L-NAME eliminated the CAPE-oNO2-mediated cardioprotection by restraining SIRT1 and eNOS expression, respectively. It suggested that CAPE-oNO2 ameliorated MIRI by suppressing the oxidative stress, inflammatory response, fibrosis and necrocytosis via the SIRT1/eNOS/NF-κB pathway.

  4. Cardioprotective potential of Punica granatum extract in isoproterenol-induced myocardial infarction in Wistar rats.

    Science.gov (United States)

    Mohan, Mahalaxmi; Patankar, Pankaj; Ghadi, Prakash; Kasture, Sanjay

    2010-01-01

    To determine the protective role of Punica granatum L. (Punicaceae) seed juice extract and its butanolic fraction on heart rate, electrocardiographic patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphologic and histopathological changes in isoproterenol-induced myocardial infarction in male Wistar rats. The effects of Punica granatum seed juice extract (100 mg/kg, p.o. and 300 mg/kg, p.o.) and butanolic fraction of Punica granatum seed juice extract (100 mg/kg., p.o.) on cardiac parameters were studied. Isoproterenol hydrochloride was used to induce myocardial infarction in Wistar rats. At the end of the experiment, heart rate, ECG, pressure rate index and cardiac marker enzyme levels were assessed. Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate, ST elevation in ECG, pressure rate index and a significant increase in the levels of cardiac marker enzymes- lactate dehydrogenase, and creatine kinase in serum. Isoproterenol significantly reduced superoxide dismutase and catalase activity and increased vascular reactivity to various catecholamines. Pretreatment with PJ (100 mg/kg, p.o. and 300 mg/kg, p.o.) and B-PJ (100 mg/kg., p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, PRI, ECG patterns, levels of LDH, CK, SOD, CAT, and vascular reactivity changes. Treatment with PJ (100 mg/kg and 300 mg/kg) and B-PJ (100 mg/kg., p.o.) alone did not alter any of the parameters as compared to vehicle-treated Wistar rats. Punica granatum-treated animals showed a lesser degree of cellular infiltration in histopathological studies. Punica granatum ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of MI.

  5. The factors in the development of marketing potential of trading enterprises

    Directory of Open Access Journals (Sweden)

    Bubenets Iryna

    2016-03-01

    Full Text Available The purpose of this article is the selection and systematization of the influence factors the formation and development of marketing potential of trading enterprises. Currently, when enterprises have experienced an acute shortage of financial resources the value of the marketing potential of the enterprise increases. Since the marketing potential is determined by the possibility of using their own marketing resources, taking into account external and internal factors, their concretization and systematization for increasing the total effective functioning of the economic subsystems of the enterprise are now becoming ever more relevant. Taking into consideration the content of the main functions of business enterprises the author distinguishes the following groups of factors of formation and development of marketing potential of an enterprise: external (external development resources and market opportunities, external marketing environment; internal (internal marketing environment marketing reflects the tangible and intangible resources and capabilities internal development of commercial enterprise. The author has researched and identified the factors-activators of marketing potential of the trading enterprises, which influence greatly on the current and future state of the management system of the marketing potential of the enterprise and help define the desired strategy for the development of marketing potential.

  6. Factors of Formation of the tax Potential of the Securities Market

    Directory of Open Access Journals (Sweden)

    Gumenniy Anatoliy A.

    2014-02-01

    Full Text Available The article is devoted to the problems of identification of factors that influence volumes and dynamics of the tax potential of the securities market. The goal of the article is detection and systematisation of factors of formation and realisation of the tax potential of the securities market. In the result of the conducted study it systemises factors of formation and realisation of the tax potential of the securities market by two groups: economic and legislatory organisational. The main of the economic factors are: state of economic development, degree of the shadow economy, level of savings of the population, level of trust of the population and level of inflation. The article justifies interconnection that exist between the said factors and volumes of the tax potential of the securities market. In particular, it proves that increase of volumes of the shadow economy facilitates reduction of the tax potential of the securities market, since it facilitates outflow of capital from the official sector of economy. Growth of unorganised savings of the population, the volume of which grows proportionally to the growth of the level of distrust of the population to the securities market, has a negative impact on formation of the tax potential of the securities market. Degree of the negative impact of the said factors grows in the event of deterioration of the state of the macro-economic situation and growth of inflation. The legislatory organisational factors are: object, base, rates of taxation of securities trading and the securities market infrastructure. The article proves that low level of infrastructure development could significantly reduce the tax potential of the securities market. The proposed approach to the study of factors of formation of the tax potential gives a possibility to mark out, apart from de-shadowing of operations and expansion of the taxation base, one more direction on increase of the tax potential of the securities market

  7. Cardioprotective effects of 70-kDa heat shock protein in transgenic mice.

    Science.gov (United States)

    Radford, N B; Fina, M; Benjamin, I J; Moreadith, R W; Graves, K H; Zhao, P; Gavva, S; Wiethoff, A; Sherry, A D; Malloy, C R; Williams, R S

    1996-03-19

    Heat shock proteins are proposed to limit injury resulting from diverse environmental stresses, but direct metabolic evidence for such a cytoprotective function in vertebrates has been largely limited to studies of cultured cells. We generated lines of transgenic mice to express human 70-kDa heat shock protein constitutively in the myocardium. Hearts isolated from these animals demonstrated enhanced recovery of high energy phosphate stores and correction of metabolic acidosis following brief periods of global ischemia sufficient to induce sustained abnormalities of these variables in hearts from nontransgenic littermates. These data demonstrate a direct cardioprotective effect of 70-kDa heat shock protein to enhance postischemic recovery of the intact heart.

  8. Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    Sudhira Begum

    2007-12-01

    Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

  9. EVALUATION OF CARDIOPROTECTIVE ACTIVITY OF MEDOHAR VATI BY ISOPROTERENOL INDUCED MYOCARDIAL DAMAGE IN RATS

    OpenAIRE

    Patel Jignasa S; Setty Seema K; Chakraborty Manodeep; Kamath Jagadish V

    2012-01-01

    This study was designed to investigate the cardioprotective activity of poly herbal formulation Medohar vati in isoproterenol (ISO)- induced myocardial necrosis in rats. Animals were treated with Medohar vati (150 and 300 mg/kg for 21 days) and Carvedilol (10mg/kg for 7 days) to the rats treated with ISO (85 mg/kg, sc) on the 22th and 23rd days. The group only treated with ISO demonstrated elevated level of Lactate dehydrogenasa (LDH), Creatine kinase (CK-MB) and CK- NAC in serum which was r...

  10. Cardioprotective effects of lipoic acid, quercetin and resveratrol on oxidative stress related to thyroid hormone alterations in long-term obesity.

    Science.gov (United States)

    Cheserek, Maureen Jepkorir; Wu, Guirong; Li, Longnan; Li, Lirong; Karangwa, Eric; Shi, Yonghui; Le, Guowei

    2016-07-01

    This study investigated possible mechanisms for cardioprotective effects of lipoic acid (LA), quercetin (Q) and resveratrol (R) on oxidative stress related to thyroid hormone alterations in long-term obesity. Female C57BL/6 mice were fed on high-fat diet (HFD), HFD+LA, HFD+R, HFD+Q and normal diet for 26weeks. Body weight, blood pressure, thyroid hormones, oxidative stress markers, angiotensin converting enzyme (ACE), nitric oxide synthase (NOS) and ion pump activities were measured, and expression of cardiac genes was analyzed by real-time polymerase chain reaction. HFD induced marked increase (Pstress, while plasma triidothyronine levels reduced. ACE activity increased (Pobesity thereby restoring plasma thyroid hormone levels and attenuating oxidative stress in the heart and thus may have therapeutic potential in heart diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Rhizoma coptidis: A potential cardiovascular protective agent

    Directory of Open Access Journals (Sweden)

    Hui-Li Tan

    2016-10-01

    Full Text Available Cardiovascular diseases (CVDs are among the leading causes of morbidity and mortality in both the developed and developing world. Rhizoma coptidis (RC, known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae, such as Coptis chinensis Franch, C. deltoidea C.Y. Cheng et Hsiao, and C. teeta Wall which has been used by Chinese medicinal physicians for more than 2000 years. In China, RC is a common component in traditional medicines used to treat CVD associated problems including obesity, diabetes mellitus, hyperlipidemia, hyperglycemia and disorders of lipid metabolism. In recent years, numerous scientific studies have sought to investigate the biological properties of RC to provide scientific evidence for its traditional medical uses. RC has been found to exert significant beneficial effects on major risk factors for CVDs including anti-atherosclerotic effect, protection from myocardial ischemia-reperfusion injury, lipid-lowering effect, anti-obesity effect and anti-hepatic steatosis effect. These properties have been attributed to the presence of bioactive compounds contained in RC such as berberine, coptisine, palmatine, epiberberine, jatrorrhizine and magnoflorine; all of which have been demonstrated to have cardioprotective effects on the various parameters contributing to the occurrence of CVD through a variety of pathways. The evidence available in the published literature indicates that RC is a herb with tremendous potential to reduce the risks of CVDs, and this review aims to summarize the cardioprotective properties of RC with reference to the published literature which overall indicates that RC is a herb with remarkable potential to reduce the risks of CVDs.

  12. Cardioprotection against experimental myocardial ischemic injury using cornin

    Directory of Open Access Journals (Sweden)

    Y. Xu

    2016-01-01

    Full Text Available Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

  13. Sarcolemmal cardiac K(ATP) channels as a target for the cardioprotective effects of the fluorine-containing pinacidil analogue, flocalin.

    Science.gov (United States)

    Voitychuk, Oleg I; Strutynskyi, Ruslan B; Yagupolskii, Lev M; Tinker, Andrew; Moibenko, Olexiy O; Shuba, Yaroslav M

    2011-02-01

    A class of drugs known as K(ATP) -channel openers induce cardioprotection. This study examined the effects of the novel K(ATP) -channel opener, the fluorine-containing pinacidil derivative, flocalin, on cardiac-specific K(ATP) -channels, excitability of native cardiac myocytes and on the ischaemic heart. The action of flocalin was investigated on: (i) membrane currents through cardiac-specific K(ATP) -channels (I(KATP) ) formed by K(IR) 6.2/SUR2A heterologously expressed in HEK-293 cells (HEK-293(₆.₂/₂A) ); (ii) excitability and intracellular Ca²(+) ([Ca²(+) ](i) ) transients of cultured rat neonatal cardiac myocytes; and (iii) functional and ultrastructural characteristics of isolated guinea-pig hearts subjected to ischaemia-reperfusion. Flocalin concentration-dependently activated a glibenclamide-sensitive I(KATP) in HEK-293(₆.₂/₂A) cells with an EC₅₀= 8.1 ± 0.4 µM. In cardiac myocytes, flocalin (5 µM) hyperpolarized resting potential by 3-5 mV, markedly shortened action potential duration, reduced the amplitude of [Ca²(+) ](i) transients by 2-3-fold and suppressed contraction. The magnitude and extent of reversibility of these effects depended on the type of cardiac myocytes. In isolated hearts, perfusion with 5 µmol·L⁻¹ flocalin, before inducing ischaemia, facilitated restoration of contraction during reperfusion, decreased the number of extrasystoles, prevented the appearance of coronary vasoconstriction and reduced damage to the cardiac tissue at the ultrastructural level (state of myofibrils, membrane integrity, mitochondrial cristae structure). Flocalin induced potent cardioprotection by activating cardiac-type K(ATP) -channels with all the benefits of the presence of fluorine group in the drug structure: higher lipophilicity, decreased toxicity, resistance to oxidation and thermal degradation, decreased metabolism in the organism and prolonged therapeutic action. © 2011 The Authors. British Journal of Pharmacology © 2011 The

  14. Potential human factors research relating to modern technology in nuclear power plants

    International Nuclear Information System (INIS)

    Ketchel, J.; Fink, R.; Hanes, L.; Williges, R.; Williges, B.

    1994-01-01

    This paper discusses proposed human factors research to address advanced human-machine interface technology in nuclear power plants. It relates to a current EPRI project to identify a prioritized list of specific research issues that could be assessed to improve control room and other user interface areas. The project seeks to bridge the gap between the functional requirements of advanced design initiatives and the human factors research needed to support them. It seeks to identify potential benefits to be expected, as well as potential problems that might be introduced by advanced technology. It provides an organized approach to identifying human factors research needs, information already available, and measures of performance and effectiveness that might be used to assess the value of potential improvements. Those parts of the proposed plan that are subsequently approved by EPRI management and by the utility advisory committee will provide a basis for recommending research priorities

  15. Cardioprotective effect of Sida rhomboidea. Roxb extract against isoproterenol induced myocardial necrosis in rats.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Ansarullah; Karn, Sanjay S; Shah, Jigar D; Patel, Dipak K; Salunke, Sunita P; Padate, Geeta S; Devkar, Ranjitsinh V; Ramachandran, A V

    2011-05-01

    The present study investigates cardioprotective effect of Sida rhomboidea. Roxb (SR) extract on heart weight, plasma lipid profile, plasma marker enzymes, lipid peroxidation, endogenous enzymatic and non-enzymatic antioxidants and membrane bound ATPases against isoproterenol (IP) induced myocardial necrosis (MN) in rats. Rats treated with IP (85 mg/kg, s.c.) recorded significant (p<0.05) increment in heart weight, plasma lipid profile, plasma marker enzymes of cardiac damage, cardiac lipid peroxidation (LPO) and activity levels of Ca(+2) ATPase whereas there was significant (p<0.05) decrease in plasma HDL, cardiac endogenous enzymatic and non-enzymatic antioxidants, Na(+)-K(+) ATPase and Mg(+2) ATPase. Pre-treatment with SR extract (400 mg/kg per day, p.o.) for 30 consecutive days followed by IP injections on days 29th and 30th, showed significant (p<0.05) decrease in heart weight, plasma lipid profile, plasma marker enzymes of cardiac damage, cardiac lipid peroxidation, Ca(+2) ATPase and significant increase in plasma HDL, cardiac endogenous enzymatic and non-enzymatic antioxidants, Na(+)-K(+) ATPase and Mg(+2) ATPase compared to IP treated group. Hence, this study is the first scientific report on cardioprotective effect of SR against IP induced MN in rats. Copyright © 2010 Elsevier GmbH. All rights reserved.

  16. Roles of Endoplasmic Reticulum Stress in NECA-Induced Cardioprotection against Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Fengmei Xing

    2017-01-01

    Full Text Available Objective. This study aimed to investigate whether the nonselective A2 adenosine receptor agonist NECA induces cardioprotection against myocardial ischemia/reperfusion (I/R injury via glycogen synthase kinase 3β (GSK-3β and the mitochondrial permeability transition pore (mPTP through inhibition of endoplasmic reticulum stress (ERS. Methods and Results. H9c2 cells were exposed to H2O2 for 20 minutes. NECA significantly prevented H2O2-induced TMRE fluorescence reduction, indicating that NECA inhibited the mPTP opening. NECA blocked H2O2-induced GSK-3β phosphorylation and GRP94 expression. NECA increased GSK-3β phosphorylation and decreased GRP94 expression, which were prevented by both ERS inductor 2-DG and PKG inhibitor KT5823, suggesting that NECA may induce cardioprotection through GSK-3β and cGMP/PKG via ERS. In isolated rat hearts, both NECA and the ERS inhibitor TUDCA decreased myocardial infarction, increased GSK-3β phosphorylation, and reversed GRP94 expression at reperfusion, suggesting that NECA protected the heart by inhibiting GSK-3β and ERS. Transmission electron microscopy showed that NECA and TUDCA reduced mitochondrial swelling and endoplasmic reticulum expansion, further supporting that NECA protected the heart by preventing the mPTP opening and ERS. Conclusion. These data suggest that NECA prevents the mPTP opening through inactivation of GSK-3β via ERS inhibition. The cGMP/PKG signaling pathway is responsible for GSK-3β inactivation by NECA.

  17. Screening of cardioprotective activity of leaves of Andrographis paniculata against isoproterenol induced myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    Dipendra Kumar Sah

    2016-01-01

    Full Text Available Objective: The objective of the present study was to investigate the cardioprotective effects of methanolic extract of leaves of Andrographis paniculata against Isoproterenol-induced myocardial infarction (MI in rats.Method: The rats were divided into five experimental groups viz., Normal control, ISO-treated (Disease control, Propranolol (10 mg/kg + ISO, Andrographis paniculata (100 mg/kg +ISO and Andrographis paniculata (200 mg/kg + ISO. Myocardial infarction in rats was induced by the administration of isoproterenol at a dose of 85mg/kg i.p., the rats in group IV and group V were pretreated with methanolic extract of Andrographis paniculata in the dose of 100mg/kg b.w. and 200mg/kg b.w. through oral route. Cardiac marker enzymes, lipid profile and antioxidant enzymes as biomarker of cardiotoxicity were determined in experimental animals.Result: Animals treated with flavonoid of leaves of Andrographis paniculata showed significant decrease in LDL-Cholesterol, total cholesterol, Triglycerides, AST, ALT, ALP, antioxidant enzymes viz., superoxide dismutase, catalase LPO and increase in HDL-Cholesterol and further was confirmed by histopathological study.Conclusion: The results of the study demonstrate that Andrographis paniculata strongly protected the myocardium against isoproterenol-induced infarction and suggest that the cardioprotective effects could be related to antioxidant activities.

  18. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels.

    Science.gov (United States)

    Khalil, Md Ibrahim; Tanvir, E M; Afroz, Rizwana; Sulaiman, Siti Amrah; Gan, Siew Hua

    2015-01-01

    The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

  19. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

    Directory of Open Access Journals (Sweden)

    Md. Ibrahim Khalil

    2015-01-01

    Full Text Available The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO- induced myocardial infarction (MI in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI, triglycerides (TG, total cholesterol (TC, lipid peroxidation (LPO products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40 were pretreated orally with Tualang honey (3 g/kg/day for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB, lactate dehydrogenase (LDH, and aspartate transaminase (AST, cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO products (TBARS and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST. Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

  20. Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I.

    Science.gov (United States)

    Chouchani, Edward T; Methner, Carmen; Nadtochiy, Sergiy M; Logan, Angela; Pell, Victoria R; Ding, Shujing; James, Andrew M; Cochemé, Helena M; Reinhold, Johannes; Lilley, Kathryn S; Partridge, Linda; Fearnley, Ian M; Robinson, Alan J; Hartley, Richard C; Smith, Robin A J; Krieg, Thomas; Brookes, Paul S; Murphy, Michael P

    2013-06-01

    Oxidative damage from elevated production of reactive oxygen species (ROS) contributes to ischemia-reperfusion injury in myocardial infarction and stroke. The mechanism by which the increase in ROS occurs is not known, and it is unclear how this increase can be prevented. A wide variety of nitric oxide donors and S-nitrosating agents protect the ischemic myocardium from infarction, but the responsible mechanisms are unclear. Here we used a mitochondria-selective S-nitrosating agent, MitoSNO, to determine how mitochondrial S-nitrosation at the reperfusion phase of myocardial infarction is cardioprotective in vivo in mice. We found that protection is due to the S-nitrosation of mitochondrial complex I, which is the entry point for electrons from NADH into the respiratory chain. Reversible S-nitrosation of complex I slows the reactivation of mitochondria during the crucial first minutes of the reperfusion of ischemic tissue, thereby decreasing ROS production, oxidative damage and tissue necrosis. Inhibition of complex I is afforded by the selective S-nitrosation of Cys39 on the ND3 subunit, which becomes susceptible to modification only after ischemia. Our results identify rapid complex I reactivation as a central pathological feature of ischemia-reperfusion injury and show that preventing this reactivation by modification of a cysteine switch is a robust cardioprotective mechanism and hence a rational therapeutic strategy.

  1. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats.

    Directory of Open Access Journals (Sweden)

    Tsung-I Chen

    Full Text Available In obstructive sleep apnea (OSA, recurrent obstruction of the upper airway leads to intermittent hypoxia (IH during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON or to a group receiving 10 weeks of exercise training (EXE. During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE, whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl ethylenediamine (TPEN, or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

  2. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

    Science.gov (United States)

    Chen, Michael Yu-Chih

    2016-01-01

    In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect. PMID:27977796

  3. Potential Effect of Opium Consumption on Controlling Diabetes and Some Cardiovascular Risk Factors in Diabetic Patients

    OpenAIRE

    Rahimi, Najmeh; Gozashti, Mohamad Hossain; Najafipour, Hamid; Shokoohi, Mostafa; Marefati, Hamid

    2014-01-01

    Background Due to this belief that opium may have beneficial effects on diabetes or cardiovascular risk factors, the present study aimed to assess the potential and possible effects of opium consumption on diabetes control and some cardiovascular risk factors in diabetic patients. Methods This study enrolled 374 diabetic subjects from diabetes care centers in Kerman, Iran, including opium user group (n = 179) and a non-opium user group (n = 195). The data were collected through a questionnair...

  4. Proximity formulae for folding potentials. [Saxon-Woods form factors, first order corrections

    Energy Technology Data Exchange (ETDEWEB)

    Schechter, H; Canto, L F [Rio de Janeiro Univ. (Brazil). Inst. de Fisica

    1979-03-05

    The proximity formulae of Brink and Stancu are applied to folding potentials. A numerical study is made for the case of single folding potentials with Saxon-Woods form factors. It is found that a proximity formula is accurate to 1-2% at separations of the order of the radius of the Coulomb barrier and that first order corrections due to first curvature are important. The approximations involved are discussed.

  5. The sea surface currents as a potential factor in the estimation and monitoring of wave energy potential

    Science.gov (United States)

    Zodiatis, George; Galanis, George; Nikolaidis, Andreas; Stylianoy, Stavros; Liakatas, Aristotelis

    2015-04-01

    The use of wave energy as an alternative renewable is receiving attention the last years under the shadow of the economic crisis in Europe and in the light of the promising corresponding potential especially for countries with extended coastline. Monitoring and studying the corresponding resources is further supported by a number of critical advantages of wave energy compared to other renewable forms, like the reduced variability and the easier adaptation to the general grid, especially when is jointly approached with wind power. Within the framework, a number of countries worldwide have launched research and development projects and a significant number of corresponding studies have been presented the last decades. However, in most of them the impact of wave-sea surface currents interaction on the wave energy potential has not been taken into account neglecting in this way a factor of potential importance. The present work aims at filling this gap for a sea area with increased scientific and economic interest, the Eastern Mediterranean Sea. Based on a combination of high resolution numerical modeling approach with advanced statistical tools, a detailed analysis is proposed for the quantification of the impact of sea surface currents, which produced from downscaling the MyOcean-FO regional data, to wave energy potential. The results although spatially sensitive, as expected, prove beyond any doubt that the wave- sea surface currents interaction should be taken into account for similar resource analysis and site selection approaches since the percentage of impact to the available wave power may reach or even exceed 20% at selected areas.

  6. Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors.

    Science.gov (United States)

    Janssens, Derek H; Komori, Hideyuki; Grbac, Daniel; Chen, Keng; Koe, Chwee Tat; Wang, Hongyan; Lee, Cheng-Yu

    2014-03-01

    Despite expressing stem cell self-renewal factors, intermediate progenitor cells possess restricted developmental potential, which allows them to give rise exclusively to differentiated progeny rather than stem cell progeny. Failure to restrict the developmental potential can allow intermediate progenitor cells to revert into aberrant stem cells that might contribute to tumorigenesis. Insight into stable restriction of the developmental potential in intermediate progenitor cells could improve our understanding of the development and growth of tumors, but the mechanisms involved remain largely unknown. Intermediate neural progenitors (INPs), generated by type II neural stem cells (neuroblasts) in fly larval brains, provide an in vivo model for investigating the mechanisms that stably restrict the developmental potential of intermediate progenitor cells. Here, we report that the transcriptional repressor protein Earmuff (Erm) functions temporally after Brain tumor (Brat) and Numb to restrict the developmental potential of uncommitted (immature) INPs. Consistently, endogenous Erm is detected in immature INPs but undetectable in INPs. Erm-dependent restriction of the developmental potential in immature INPs leads to attenuated competence to respond to all known neuroblast self-renewal factors in INPs. We also identified that the BAP chromatin-remodeling complex probably functions cooperatively with Erm to restrict the developmental potential of immature INPs. Together, these data led us to conclude that the Erm-BAP-dependent mechanism stably restricts the developmental potential of immature INPs by attenuating their genomic responses to stem cell self-renewal factors. We propose that restriction of developmental potential by the Erm-BAP-dependent mechanism functionally distinguishes intermediate progenitor cells from stem cells, ensuring the generation of differentiated cells and preventing the formation of progenitor cell-derived tumor-initiating stem cells.

  7. A questionnaire study of associations between potential risk factors and salmonella status in Swedish dairy herds.

    Science.gov (United States)

    Ågren, Estelle C C; Frössling, Jenny; Wahlström, Helene; Emanuelson, Ulf; Sternberg Lewerin, Susanna

    2017-08-01

    In this study associations between potential risk factors and salmonella status in Swedish dairy herds were investigated. A case-control study design was used, including existing as well as new cases. Herds were assigned a salmonella status on the basis of antibody analysis of bulk milk samples. Information on potential risk factors was collected from registry data and from farmers via a questionnaire. Univariable and multivariable logistic regression analyses were used to investigate associations between salmonella status and potential risk factors. In addition, multivariate analysis with Additive Bayesian Network (ABN) modelling was performed to improve understanding of the complex relationship between all the variables. Because of the difficulty in identifying associations between potential risk factors and infections with low prevalence and a large regional variation, exposure of potential risk factors in the high-prevalence region (Öland) were compared to exposure in other regions in Sweden. In total 483 of 996 (48%) farmers responded to the questionnaire, 69 herds had test-positive bulk milk samples. The strongest association with salmonella status was 'presence of salmonella test-positive herds pastures and providing protective clothing for visitors. The latter is probably a reflection of increased disease awareness in Öland. The ABN model showed associations between herd size and housing as well as several management procedures. This provides an explanation why herd size frequently has been identified as a risk factor for salmonella by other studies. The study confirms the importance of local transmission routes for salmonella, but does not identify specific components in this local spread. Therefore, it supports the use of a broad biosecurity approach in the prevention of salmonella. In Öland, some potential risk factors are more common than in other parts of Sweden. Theoretically these could contribute to the spread of salmonella, but this was not

  8. Potential roles of WRKY transcription factors in resistance to Aspergillus flavus colonization of immature maize kernels

    Science.gov (United States)

    Resistance to Aspergillus flavus by maize (Zea mays L.) is mediated by several defense proteins; however the mechanism regulating the expression of these defenses is poorly understood. This study examined the potential roles of six maize WRKY transcription factors, ZmWRKY19, ZmWRKY21, ZmWRKY53, ZmW...

  9. Proteomic identification of CIB1 as a potential diagnostic factor in ...

    Indian Academy of Sciences (India)

    Proteomic identification of CIB1 as a potential diagnostic factor in hepatocellular carcinoma. Tong Junrong Zhou Huancheng H E Feng Gao Yi Yang Xiaoqin Luo Zhengmao Zhang Hong Zeng Jianying Wang Yin Huang Yuanhang Zhang Jianlin Sun Longhua He Guolin. Articles Volume 36 Issue 4 September 2011 pp 659- ...

  10. A review of potential factors relevant to coping in patients with advanced cancer

    DEFF Research Database (Denmark)

    Thomsen, Thora G.; Rydahl-Hansen, Susan; Wagner, Lis

    2010-01-01

    The aim was to identify characteristics that are considered to describe coping in patients with advanced cancer, as seen from a patient perspective. Based on the identified characteristics, the second aim was to identify potential factors that are relevant to coping in patients with advanced cancer....

  11. PHO-ERK1/2 interaction with mitochondria regulates the permeability transition pore in cardioprotective signaling.

    Science.gov (United States)

    Hernández-Reséndiz, Sauri; Zazueta, Cecilia

    2014-07-11

    The molecular mechanism(s) by which extracellular signal-regulated kinase 1/2 (ERK1/2) and other kinases communicate with downstream targets have not been fully determined. Multiprotein signaling complexes undergoing spatiotemporal redistribution may enhance their interaction with effector proteins promoting cardioprotective response. Particularly, it has been proposed that some active kinases in association with caveolae may converge into mitochondria. Therefore, in this study we investigate if PHO-ERK1/2 interaction with mitochondria may provide a mechanistic link in the regulation of these organelles in cardioprotective signaling. Using a model of dilated cardiomyopathy followed by ischemia-reperfusion injury, we determined ERK1/2 signaling at the level of mitochondria and evaluated its effect on the permeability transition pore. The most important finding of the present study is that, under cardioprotective conditions, a subpopulation of activated ERK1/2 was directed to the mitochondrial membranes through vesicular trafficking, concurring with increased phosphorylation of mitochondrial proteins and inhibition of the mitochondrial permeability transition pore opening. In addition, our results suggest that vesicles enriched with caveolin-3 could form structures that may drive ERK1/2, GSK3β and Akt to mitochondria. Signaling complexes including PHO-ERK, PHO-Akt, PHO-eNOS and caveolin-3 contribute to cardioprotection by directly targeting the mitochondrial proteome and regulating the opening of the permeability transition pore in this model. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Modification of transition's factor in the compact surface-potential-based MOSFET model

    Directory of Open Access Journals (Sweden)

    Kevkić Tijana

    2016-01-01

    Full Text Available The modification of an important transition's factor which enables continual behavior of the surface potential in entire useful range of MOSFET operation is presented. The various modifications have been made in order to obtain an accurate and computationally efficient compact MOSFET model. The best results have been achieved by introducing the generalized logistic function (GL in fitting of considered factor. The smoothness and speed of the transition of the surface potential from the depletion to the strong inversion region can be controlled in this way. The results of the explicit model with this GL functional form for transition's factor have been verified extensively with the numerical data. A great agreement was found for a wide range of substrate doping and oxide thickness. Moreover, the proposed approach can be also applied on the case where quantum mechanical effects play important role in inversion mode.

  13. Mapping Soil Erosion Factors and Potential Erosion Risk for the National Park "Central Balkan"

    Science.gov (United States)

    Ilieva, Diliana; Malinov, Ilia

    2014-05-01

    Soil erosion is widely recognised environmental problem. The report aims at presenting the main results from assessment and mapping of the factors of sheet water erosion and the potential erosion risk on the territory of National Park "Central Balkan". For this purpose, the Universal Soil Loss Equation (USLE) was used for predicting soil loss from erosion. The influence of topography (LS-factor) and soil erodibility (K-factor) was assessed using small-scale topographic and soil maps. Rainfall erosivity (R-factor) was calculated from data of rainfalls with amounts exceeding 9.5 mm from 14 hydro-meteorological stations. The values of the erosion factors (R, K and LS) were presented for the areas of forest, sub-alpine and alpine zones. Using the methods of GIS, maps were plotted presenting the area distribution among the classes of the soil erosion factors and the potential risk in the respective zones. The results can be used for making accurate decisions for soil conservation and sustainable land management in the park.

  14. Hyaluronic Acid Gel-Based Scaffolds as Potential Carrier for Growth Factors: An In Vitro Bioassay on Its Osteogenic Potential

    Directory of Open Access Journals (Sweden)

    Masako Fujioka-Kobayashi

    2016-11-01

    Full Text Available Hyaluronic acid (HA has been utilized for a variety of regenerative medical procedures due to its widespread presence in connective tissue and perceived biocompatibility. The aim of the present study was to investigate HA in combination with recombinant human bone morphogenetic protein 9 (rhBMP9, one of the most osteogenic growth factors of the BMP family. HA was first combined with rhBMP9 and assessed for the adsorption and release of rhBMP9 over 10 days by ELISA. Thereafter, ST2 pre-osteoblasts were investigated by comparing (1 control tissue culture plastic, (2 HA alone, and (3 HA with rhBMP9 (100 ng/mL. Cellular proliferation was investigated by a MTS assay at one, three and five days and osteoblast differentiation was investigated by alkaline phosphatase (ALP activity at seven days, alizarin red staining at 14 days and real-time PCR for osteoblast differentiation markers. The results demonstrated that rhBMP9 adsorbed within HA scaffolds and was released over a 10-day period in a controlled manner. While HA and rhBMP9 had little effect on cell proliferation, a marked and pronounced effect was observed for cell differentiation. rhBMP9 significantly induced ALP activity, mRNA levels of collagen1α2, and ALP and osteocalcin (OCN at three or 14 days. HA also demonstrated some ability to induce osteoblast differentiation by increasing mRNA levels of OCN and increasing alizarin red staining at 14 days. In conclusion, the results from the present study demonstrate that (1 HA may serve as a potential carrier for various growth factors, and (2 rhBMP9 is a potent and promising inducer of osteoblast differentiation. Future animal studies are now necessary to investigate this combination approach in vivo.

  15. Analysis of transactivation potential of rice (Oryza sativa L.) heat shock factors.

    Science.gov (United States)

    Lavania, Dhruv; Dhingra, Anuradha; Grover, Anil

    2018-06-01

    Based on yeast one-hybrid assays, we show that the presence of C-terminal AHA motifs is not a prerequisite for transactivation potential in rice heat shock factors. Transcriptional activation or transactivation (TA) of heat stress responsive genes takes place by binding of heat shock factors (Hsfs) to heat shock elements. Analysis of TA potential of thirteen rice (Oryza sativa L.) Hsfs (OsHsfs) carried out in this study by yeast one-hybrid assay showed that OsHsfsA3 possesses strong TA potential while OsHsfs A1a, A2a, A2b, A4a, A4d, A5, A7b, B1, B2a, B2b, B2c and B4d lack TA potential. From a near complete picture of TA potential of the OsHsf family (comprising of 25 members) emerging from this study and an earlier report from our group (Mittal et al. in FEBS J 278(17):3076-3085, 2011), it is concluded that (1) overall, six OsHsfs, namely A3, A6a, A6b, A8, C1a and C1b possess TA potential; (2) four class A OsHsfs, namely A3, A6a, A6b and A8 have TA potential out of which A6a and A6b contain AHA motifs while A3 and A8 lack AHA motifs; (3) nine class A OsHsfs, namely A1a, A2a, A2b, A2e, A4a, A4d, A5, A7a and A7b containing AHA motif(s) lack TA function in the yeast assay system; (4) all class B OsHsfs lack AHA motifs and TA potential (B4a not analyzed) and (5) though all class C OsHsf members lack AHA motifs, two members C1a and C1b possess TA function, while one member C2a lacks TA potential (C2b not analyzed). Thus, the presence or absence of AHA motif is possibly not the only factor determining TA potential of OsHsfs. Our findings will help to identify the transcriptional activators of rice heat shock response.

  16. CONTROLLING FACTORS OF POTENTIAL EVAPOTRANSPIRATION ABOVE GRASSLAND IN HUMID AND ARID AREA

    Directory of Open Access Journals (Sweden)

    . Yanto

    2013-05-01

    Full Text Available Potential evapotranspiration (PET is an importance process in water balance studies controlled by a number of meteorological factors such as temperature, wind speed, atmospheric pressure, solar radiation, vapor pressure gradient, relative humidity and biological factors such as vegetation type, canopy height and plant density that varied in time-scale and in spatial scale. Of all those variables, determining the most controlling factors of evapotranspiration in humid and arid area is of interest of this paper. Two sites representing humid and arid area i.e. Fermi Prairie site in Illinois and Audubon Research Ranch in Arizona respectively were investigated in this study.  The flux data employed in this study was acquired from Ameriflux Netwotk. Penmann-Monteith formula is employed in to estimate evapotranspiration rate in both sites. The result shows that the PET is in dependence on the considered meteorological factor such as shortwave radiation, vapor pressure, air temperature, wind speed, net radiation and vapor pressure deficit. It is also can be inferred from the analysis that PET is also strongly controlled by vegetation factors represented as stomatal resistance. Keywords: Potential evapotranspiration, Penmann-Monteith, humid, arid.

  17. Biotransformation of Dioscorea nipponica by Rat Intestinal Microflora and Cardioprotective Effects of Diosgenin

    Directory of Open Access Journals (Sweden)

    Jia-Fu Feng

    2017-01-01

    Full Text Available Studying the biotransformation of natural products by intestinal microflora is an important approach to understanding how and why some medicines—particularly natural medicines—work. In many cases, the active components are generated by metabolic activation. This is critical for drug research and development. As a means to explore the therapeutic mechanism of Dioscorea nipponica (DN, a medicinal plant used to treat myocardial ischemia (MI, metabolites generated by intestinal microflora from DN were identified, and the cardioprotective efficacy of these metabolites was evaluated. Our results demonstrate that diosgenin is the main metabolite produced by rat intestinal microflora from DN. Further, our results show that diosgenin protects the myocardium against ischemic insult through increasing enzymatic and nonenzymatic antioxidant levels in vivo and by decreasing oxidative stress damage. These mechanisms explain the clinical efficacy of DN as an anti-MI drug.

  18. Mitochondria as key targets of cardioprotection in cardiac ischemic disease: role of thyroid hormone triiodothyronine.

    Science.gov (United States)

    Forini, Francesca; Nicolini, Giuseppina; Iervasi, Giorgio

    2015-03-19

    Ischemic heart disease is the major cause of mortality and morbidity worldwide. Early reperfusion after acute myocardial ischemia has reduced short-term mortality, but it is also responsible for additional myocardial damage, which in the long run favors adverse cardiac remodeling and heart failure evolution. A growing body of experimental and clinical evidence show that the mitochondrion is an essential end effector of ischemia/ reperfusion injury and a major trigger of cell death in the acute ischemic phase (up to 48-72 h after the insult), the subacute phase (from 72 h to 7-10 days) and chronic stage (from 10-14 days to one month after the insult). As such, in recent years scientific efforts have focused on mitochondria as a target for cardioprotective strategies in ischemic heart disease and cardiomyopathy. The present review discusses recent advances in this field, with special emphasis on the emerging role of the biologically active thyroid hormone triiodothyronine (T3).

  19. Sensitivity of reproductive potential to environmental factors in sheep and goats

    International Nuclear Information System (INIS)

    Chemineau, P.; Terqui, M.

    1986-01-01

    Ovulation rate, embryo survival, postnatal mortality, interval from parturition to conception, age at first parturition, number of parturitions before culling, and age at culling collectively declineate the ability of a breed to cope with the local environment and management which are often harsh and suboptimal. In tropical and subtropical countries, the reproductive performance of goat and sheep is low and far from their maximum potential. Identification of the main limiting factors and determination of the breed's sensitivity to these factors are essential preliminary steps before choosing the method(s) to improve reproductive performance in such countries. (author)

  20. The cardioprotective efficacy of TVP1022 against ischemia/reperfusion injury and cardiac remodeling in rats.

    Science.gov (United States)

    Malka, Assaf; Ertracht, Offir; Bachner-Hinenzon, Noa; Reiter, Irina; Binah, Ofer

    2016-12-01

    Following acute myocardial infarction (MI), early and successful reperfusion is the most effective strategy for reducing infarct size and improving the clinical outcome. However, immediate restoration of blood flow to the ischemic zone results in myocardial damage, defined as "reperfusion-injury". Whereas we previously reported that TVP1022 (the S-isomer of rasagiline, FDA-approved anti-Parkinson drug) decreased infarct size 24 h post ischemia reperfusion (I/R) in rats, in this study we investigated the chronic cardioprotective efficacy of TVP1022 14 days post-I/R. To simulate the clinical settings of acute MI followed by reperfusion therapy, we employed a rat model of left anterior descending artery occlusion for 30 min followed by reperfusion and a follow-up for 14 days. TVP1022 was initially administered postocclusion-prereperfusion, followed by chronic daily administrations. Cardiac performance and remodeling were evaluated using customary and advanced echocardiographic methods, hemodynamic measurements by Millar Mikro-Tip ® catheter, and histopathological techniques. TVP1022 administration markedly decreased the remodeling process as illustrated by attenuation of left ventricular enlargement and cardiac hypertrophy (both at the whole heart and the cellular level). Furthermore, TVP1022 inhibited cardiac fibrosis and reduced ventricular BNP levels. Functionally, TVP1022 treatment preserved cardiac wall motion. Specifically, the echocardiographic and most of the direct hemodynamic measures were pronouncedly improved by TVP1022. Collectively, these findings indicate that TVP1022 provides prominent cardioprotection against I/R injury and post-MI remodeling in this I/R model.

  1. Cardioprotection after acute exposure to simulated high altitude in rats. Role of nitric oxide.

    Science.gov (United States)

    La Padula, Pablo H; Etchegoyen, Melisa; Czerniczyniec, Analia; Piotrkowski, Barbara; Arnaiz, Silvia Lores; Milei, Jose; Costa, Lidia E

    2018-02-28

    In previous studies, upregulation of NOS during acclimatization of rats to sustained hypobaric hypoxia was associated to cardioprotection, evaluated as an increased tolerance of myocardium to hypoxia/reoxygenation. The objective of the present work was to investigate the effect of acute hypobaric hypoxia and the role of endogenous NO concerning cardiac tolerance to hypoxia/reoxygenation under β-adrenergic stimulation. Rats were submitted to 58.7 kPa in a hypopressure chamber for 48 h whereas their normoxic controls remained at 101.3 kPa. By adding NOS substrate L-arg, or blocker L-NNA, isometric mechanical activity of papillary muscles isolated from left ventricle was evaluated at maximal or minimal production of NO, respectively, under β-adrenergic stimulation by isoproterenol, followed by 60/30 min of hypoxia/reoxygenation. Activities of NOS and cytochrome oxidase were evaluated by spectrophotometric methods and expression of HIF1-α and NOS isoforms by western blot. Eosin and hematoxiline staining were used for histological studies. Cytosolic expression of HIF1-α, nNOS and eNOS, and NO production were higher in left ventricle of hypoxic rats. Mitochondrial cytochrome oxidase activity was decreased by hypobaric hypoxia and this effect was reversed by L-NNA. After H/R, recovery of developed tension in papillary muscles from normoxic rats was 51-60% (regardless NO modulation) while in hypobaric hypoxia was 70% ± 3 (L-arg) and 54% ± 1 (L-NNA). Other mechanical parameters showed similar results. Preserved histological architecture was observed only in L-arg papillary muscles of hypoxic rats. Exposure of rats to hypobaric hypoxia for only 2 days increased NO synthesis leading to cardioprotection. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Is ADH1C genotype relevant for the cardioprotective effect of alcohol?

    Science.gov (United States)

    Høiseth, Gudrun; Magnus, Per; Knudsen, Gun Peggy; Jansen, Mona Dverdal; Næss, Oyvind; Tambs, Kristian; Mørland, Jørg

    2013-03-01

    The cardioprotective effect of ethanol has been suggested to be linked to one of the ethanol metabolizing enzymes (ADH1C), which constitutes a high V(max) and a low V(max) variant. This has been demonstrated in some studies, while others have not been able to replicate the findings. The aim of the present study was to investigate the relation between the different ADH1C genotypes, death from coronary heart disease (CHD) and alcohol in a material larger than the previously published studies. Eight hundred CHD deaths as well as 1303 controls were genotyped for the high V(max) (γ1) and the low V(max) (γ2) ADH1C variant. Information of alcohol use was available for all subjects. Multiple logistic regression analyses was used to study if the decreased risk of death from CHD in alcohol consuming subjects was more pronounced in subjects homozygous for the γ2 allele (γ2γ2 subjects) compared to γ1γ1 and γ1γ2 subjects. The odds ratio (OR) for death from CHD in alcohol consumers compared to abstainers was similar in the genotype groups, i.e., 0.62 (95% CI: 0.43-0.88) in γ1γ1 subjects and 0.62 (95% CI: 0.42-0.91) in γ2γ2 subjects. Also when stratifying the results by gender and when dividing alcohol consumers into different alcohol consumption groups, there was no difference in the OR between the different genotype groups. This study, which included the largest study group published so far, failed to find any link between the ADH1C genotype and the cardioprotective effects of alcohol. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Nitric oxide fails to confer endogenous antiarrhythmic cardioprotection in the primate heart in vitro.

    Science.gov (United States)

    Pabla, R; Curtis, M J

    2007-04-01

    The role of nitric oxide (NO) in cardiac pathophysiology remains controversial. According to data from several studies using rat and rabbit isolated hearts, NO is an endogenous cardioprotectant against reperfusion-induced ventricular fibrillation (VF). Thus, if cardiac NO production is abolished by perfusion with L-N(G)-nitro-L-arginine methylester (L-NAME) (100 microM) there is a concomittant increase in the incidence of reperfusion-induced VF, with L-NAME's effects on NO and VF prevented by L- (but not D-) arginine co-perfusion. To make a better estimate of the clinical relevance of these findings, 100 microM L-NAME was tested in primate hearts under similar conditions. Marmoset (Callithrix jaccus) hearts, isolated and perfused, were subjected to 60 min left regional ischaemia followed by 10 min reperfusion in vitro. The ECG was recorded and NO in coronary effluent measured by chemiluminescence. L-NAME (100 micro M) decreased NO in coronary effluent throughout ischaemia and reperfusion (e.g. from 3720+/-777 pmol min(-1) g(-1) in controls to 699+/-98 pmol min(-1) g(-1) after 5 min of ischaemia) and, during ischaemia, lowered coronary flow and reduced heart rate, actions identical to those seen in rat and rabbit hearts. However, the incidence of reperfusion-induced VF was unchanged (20%, with or without L-NAME). A species difference exists in the effectiveness of endogenous NO to protect hearts against reperfusion-induced VF. The present primate data, which presumably take precedence over rat and rabbit data, cast doubt on the clinical relevance of NO as an endogenous, antiarrhythmic, cardioprotectant.

  4. Cardioprotective role of tadalafil against cisplatin-induced cardiovascular damage in rats.

    Science.gov (United States)

    Saleh, Rasha M; Awadin, Walaa F; El-Shafei, Reham A; Elseady, Yousef Y; Wehaish, Faheim E; Elshal, Mohamed F

    2015-10-15

    The present study investigated the possible cardioprotective effect of tadalafil (Tad) on cisplatin (CDDP)-induced cardiac and vascular damages in rats. A total number of seventy two healthy male albino rats initially weighting between 200 and 220 g were used and randomly divided into four groups,18 rats in each. The control group received no treatment; CDDP group received a single dose of CDDP (4 mg/kg) intraperitoneal (i.p.) per week for 4 weeks the duration of the experiment; Tad group received 0.4 mg/kg BW Tad i.p. daily and Tad +CDDP group received 0.4 mg/kg BW Tad i.p. +4 mg/kg BW CDDP i.p. The results showed that Tad was able to decrease blood pressure, heart rate, levels of serum cardiac troponin (cTn-I), malondialdehyde (MDA) and increased levels of reduced glutathione (GSH) and nitric oxide (NO) in the heart homogenate sample from CDDP treated rats. Semi-quantitative analysis showed that Tad was able to decrease the histopathological scores of cardiac muscular hyalinzation and fibrosis in three sacrifices in CDDP treated rats. CDDP treated rats showed significantly increased thickening in wall of aorta with an irregular luminal layer of endothelial cell linings in three sacrifices when it was compared to other groups. Moreover, immunohistochemical labeling of α- smooth muscle actin (α-SMA) in aorta revealed significant lower scores in Tad +CDDP group when they were compared to CDDP group. In conclusion, Tad alone did not induce any harmful effects on blood pressure, selective antioxidant, peroxidation markers or cardiac histology, in addition, Tad has a cardio-protective role against CDDP. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Glucoseinsulin Mixture as a Cardioprotective Agent in Cardiology and Cardiac Surgery (Review

    Directory of Open Access Journals (Sweden)

    I. A. Kozlov

    2017-01-01

    Full Text Available The literature review presents an analysis of publications describing the use of a glucose%insulin mixture as a cardioprotective agent in acute myocardial infarction and in cardiac surgeries with extracorporeal circulation (ECC. It summarizes historical aspects of implementation of the glucose%insulin therapy in cardiology and car%diac surgery. Possible mechanisms of action of the glucose-insulin-potassium mixture in acute ischemia and myocardial infarction were analyzed (normalization of electrical processes on the cardiomyocyte membrane, replenishment of metabolic substrates and increased production rate of adenosine triphosphoric acid due to glycolysis, decreased intensity of non%esterified fatty acid oxidation, decreased apoptosis, etc.. It discusses results of clinical studies evaluating prescription of the mixture for acute myocardial infarction, including data from metaanalyses. It demonstrated that the role and the clinical efficacy of the preventive and therapeutic measure under consideration in acute myocardial infarction are still the subject of discussion and require further research. It also analyzed modern concepts explaining the cardioprotective effects of insulin and glucose during surgeries with ECC (decreased insulin resistance, activation of anaplerosis, stimulation of intracellular signaling pathways maintaining the viability of cells, reduction of the severity of systemic inflammatory response, immunomodulatingeffect, etc.. Review discusses results of clinical studies including data from randomized clinical trials and metaanalyses performed over the last 5 years that demonstrated the absence of the effect of the glucose%insulin therapy on the hospital mortality. Various studies demonstrated its positive effects including decreased incidence of peri%operative myocardial infarctions and intensity of inotropic support, increased values of postoperative cardiac index, decreased duration of postoperative mechanical ventilation

  6. Unintended benefits: the potential economic impact of addressing risk factors to prevent Alzheimer's disease.

    Science.gov (United States)

    Lin, Pei-Jung; Yang, Zhou; Fillit, Howard M; Cohen, Joshua T; Neumann, Peter J

    2014-04-01

    Certain chronic conditions appear to be modifiable risk factors of Alzheimer's disease and related dementias. To understand the potential health and economic impacts of addressing those risk factors, we used data on a Medicare cohort to simulate four scenarios: a 10 percent reduction in the prevalence of diabetes, hypertension, cardiovascular diseases, respectively, and a 10 percent reduction in body mass index among beneficiaries who were overweight or obese. Our simulation demonstrated that reducing the prevalence of these conditions may yield "unintended benefits" by lowering the risk, delaying the onset, reducing the duration, and lowering the costs of dementia. More research is needed to clarify the exact relationship between various other chronic diseases and dementia. However, our findings highlight potential health gains and savings opportunities stemming from the better management of other conditions associated with dementia.

  7. Vitamin-D Deficiency As a Potential Environmental Risk Factor in Multiple Sclerosis, Schizophrenia, and Autism.

    Science.gov (United States)

    Kočovská, Eva; Gaughran, Fiona; Krivoy, Amir; Meier, Ute-Christiane

    2017-01-01

    In this short review, we want to summarize the current findings on the role of vitamin-D in multiple sclerosis (MS), schizophrenia, and autism. Many studies have highlighted hypovitaminosis-D as a potential environmental risk factor for a variety of conditions such as MS, asthma, cardiovascular disease, and, more recently, psychiatric diseases. However, whether hypovitaminosis-D is a potential causative factor for the development or activity in these conditions or whether hypovitaminosis-D may be due to increased vitamin-D consumption by an activated immune system (reverse causation) is the focus of intense research. Here, we will discuss current evidence exploring the role of vitamin-D in MS, schizophrenia, and autism and its impact on adaptive and innate immunity, antimicrobial defense, the microbiome, neuroinflammation, behavior, and neurogenesis. More work is needed to gain insight into its role in the underlying pathophysiology of these conditions as it may offer attractive means of intervention and prevention.

  8. Weight loss, Mortality and associated potentially modifiable nutritional risk factors among nursing home residents

    DEFF Research Database (Denmark)

    Beck, Anne Marie

    2015-01-01

    Objectives The objective of this follow-up study is to assess the association between different potentially modifiable nutritional risk factors; weight loss after six and 12 months and mortality. Design and setting A one year follow-up project among Danish nursing home residents. Participants...... A total of 441 nursing home resident living in 11 nursing homes. Measurements Odds ratio was calculated and used to assess the strength of association between different potentially modifiable nutritional risk factors and nutritional status of the participants. The difference in mortality between those who...... at most meals, chewing and swallowing problems. The prevalence of eating dependency; leaves 25% or more of food uneaten at most meals; swallowing problems and enteral nutrition were higher among those who died than among survivors. Conclusion A high percentage of old nursing home residents suffer from...

  9. Registered report: Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors2

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Edward Greenfield, Erin Griner, The Reproducibility Project: Cancer Biology† ### Abstract The [Reproducibility Project: Cancer Biology](https://osf.io/e81xl/wiki/home/) seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from “Widespread potential for growth-factor-d...

  10. INNOVATION POTENTIAL AS A DETERMINING FACTOR IN THE GROWTH OF COMPETITIVE ADVANTAGES BUILDING PRODUCTS

    OpenAIRE

    T. U. Levitsky; A. M. Esetova

    2014-01-01

    It is stipulated that the construction company, chosen the strategy of economic growth, should have some competitive advantages, determining opportunities for sustainable development and effective improving, and operational efficiency increase. One of the factors of the competitiveness increase of construction products is the innovative potential of construction industry. Methodical approaches to the evaluation of innovative capacity and its effect on the growth of competitive advantages have...

  11. INNOVATION POTENTIAL AS A DETERMINING FACTOR IN THE GROWTH OF COMPETITIVE ADVANTAGES BUILDING PRODUCTS

    Directory of Open Access Journals (Sweden)

    T. U. Levitsky

    2014-01-01

    Full Text Available It is stipulated that the construction company, chosen the strategy of economic growth, should have some competitive advantages, determining opportunities for sustainable development and effective improving, and operational efficiency increase. One of the factors of the competitiveness increase of construction products is the innovative potential of construction industry. Methodical approaches to the evaluation of innovative capacity and its effect on the growth of competitive advantages have been proposed. 

  12. Potential microbial risk factors related to soil amendments and irrigation water of potato crops.

    Science.gov (United States)

    Selma, M V; Allende, A; López-Gálvez, F; Elizaquível, P; Aznar, R; Gil, M I

    2007-12-01

    This study assesses the potential microbial risk factors related to the use of soil amendments and irrigation water on potato crops, cultivated in one traditional and two intensive farms during two harvest seasons. The natural microbiota and potentially pathogenic micro-organisms were evaluated in the soil amendment, irrigation water, soil and produce. Uncomposted amendments and residual and creek water samples showed the highest microbial counts. The microbial load of potatoes harvested in spring was similar among the tested farms despite the diverse microbial levels of Listeria spp. and faecal coliforms in the potential risk sources. However, differences in total coliform load of potato were found between farms cultivated in the autumn. Immunochromatographic rapid tests and the BAM's reference method (Bacteriological Analytical Manual; AOAC International) were used to detect Escherichia coli O157:H7 from the potential risk sources and produce. Confirmation of the positive results by polymerase chain reaction procedures showed that the immunochromatographic assay was not reliable as it led to false-positive results. The potentially pathogenic micro-organisms of soil amendment, irrigation water and soil samples changed with the harvest seasons and the use of different agricultural practices. However, the microbial load of the produce was not always influenced by these risk sources. Improvements in environmental sample preparation are needed to avoid interferences in the use of immunochromatographic rapid tests. The potential microbial risk sources of fresh produce should be regularly controlled using reliable detection methods to guarantee their microbial safety.

  13. ABO blood grouping: A potential risk factor for early childhood caries - A cross-sectional study.

    Science.gov (United States)

    Govindaraju, Lavanya; Jeevanandan, Ganesh; Subramanian, E M G

    2018-01-01

    The paradigm of etiology of early childhood caries (ECC) is shifting toward genetics. Of various inherited factors, blood group of an individual is genetically determined. The aim of the study is to determine if blood group of an individual will serve as a potential risk factor in the development of ECC. A cross-sectional study was conducted in Chennai. Blood samples were collected from a total of 500 children age for determination of the blood group. Of which 96 children (24 per blood group) were randomly selected and were included in the study. Oral screening of the selected children was done by a pediatric dentist who was blinded to the blood group of the children. Decayed, extracted, and filling index was noted. Details on other associated factors for the development of ECC such as the socioeconomic status, oral hygiene measures, diet, and feeding practices were collected by directly interviewing the parents through a questionnaire. Statistical analysis was done using Chi-square and Kruskal-Wallis test and post hoc Tukey test with significance level set at 0.05. Intergroup analysis of the associated factors showed no significant differences between the children of different blood groups. A statistically significant relation was noted between the blood groups and development of ECC (P = 0.025). Blood group is a potential risk indicator for the development of ECC.

  14. Ozone dosing alters the biological potential and therapeutic outcomes of plasma rich in growth factors.

    Science.gov (United States)

    Anitua, E; Zalduendo, M M; Troya, M; Orive, G

    2015-04-01

    Until now, ozone has been used in a rather empirical way. This in-vitro study investigates, for the first time, whether different ozone treatments of plasma rich in growth factors (PRGF) alter the biological properties and outcomes of this autologous platelet-rich plasma. Human plasma rich in growth factors was treated with ozone using one of the following protocols: a continuous-flow method; or a syringe method in which constant volumes of ozone and PRGF were mixed. In both cases, ozone was added before, during and after the addition of calcium chloride. Three ozone concentrations, of the therapeutic range 20, 40 and 80 μg/mL, were tested. Fibrin clot properties, growth factor content and the proliferative effect on primary osteoblasts and gingival fibroblasts were evaluated. Ozone treatment of PRGF using the continuous flow protocol impaired formation of the fibrin scaffold, drastically reduced the levels of growth factors and significantly decreased the proliferative potential of PRGF on primary osteoblasts and gingival fibroblasts. In contrast, treatment of PRGF with ozone using the syringe method, before, during and after the coagulation process, did not alter the biological outcomes of the autologous therapy. These findings suggest that ozone dose and the way that ozone combines with PRGF may alter the biological potential and therapeutic outcomes of PRGF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion.

    Science.gov (United States)

    Yamamoto, Tsunehisa; Tamaki, Kayoko; Shirakawa, Kohsuke; Ito, Kentaro; Yan, Xiaoxiang; Katsumata, Yoshinori; Anzai, Atsushi; Matsuhashi, Tomohiro; Endo, Jin; Inaba, Takaaki; Tsubota, Kazuo; Sano, Motoaki; Fukuda, Keiichi; Shinmura, Ken

    2016-04-15

    Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.Am J Physiol Heart Circ Physiol 308: H894-H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (CM-Sirt1(-/-)) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM-Sirt1(-/-)mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM-Sirt1(-/-)mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventional C3 knockout (C3(-/-)) mice treated with CR was similar to that in the ad libitum-fed C3(-/-)mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting

  16. Cardioprotection by minocycline in a rabbit model of ischemia/reperfusion injury : Detection of cell death by in vivo (111)In-GSAO SPECT

    NARCIS (Netherlands)

    Yamaki, Takayoshi; de Haas, Hans J; Tahara, Nobuhiro; Petrov, Artiom; Mohar, Dilbahar; Haider, Nezam; Zhou, Jun; Tahara, Atsuko; Takeishi, Yasuchika; Boersma, Hendrikus H; Scarabelli, Tiziano; Kini, Annapoorna; Strauss, H William; Narula, Jagat

    BACKGROUND: Preclinical studies indicate that minocycline protects against myocardial ischemia/reperfusion injury. In these studies, minocycline was administered before ischemia, which can rarely occur in clinical practice. The current study aimed to evaluate cardioprotection by minocycline

  17. Prevalence and Potential Risk Factors for Bartonella Infection in Tunisian Stray Dogs.

    Science.gov (United States)

    Belkhiria, Jaber; Chomel, Bruno B; Ben Hamida, Taoufik; Kasten, Rickie W; Stuckey, Matthew J; Fleischman, Drew A; Christopher, Mary M; Boulouis, Henri-Jean; Farver, Thomas B

    2017-06-01

    Bartonellae are blood-borne and vector-transmitted pathogens, some are zoonotic, which have been reported in several Mediterranean countries. Transmission from dogs to humans is suspected, but has not been clearly demonstrated. Our objectives were to determine the seroprevalence of Bartonella henselae, Bartonella vinsonii subsp. berkhoffii, Bartonella clarridgeiae, and Bartonella bovis (as a proxy for Candidatus Bartonella merieuxii) in stray dogs from Tunisia, identify the Bartonella species infecting the dogs and evaluate potential risk factors for canine infection. Blood samples were collected between January and November 2013 from 149 dogs in 10 Tunisian governorates covering several climatic zones. Dog-specific and geographic variables were analyzed as potential risk factors for Bartonella spp. seropositivity and PCR-positivity. DNA was extracted from the blood of all dogs and tested by PCR for Bartonella, targeting the ftsZ and rpoB genes. Partial sequencing was performed on PCR-positive dogs. Twenty-nine dogs (19.5%, 95% confidence interval: 14-27.4) were seropositive for one or more Bartonella species, including 17 (11.4%) for B. vinsonii subsp. berkhoffii, 14 (9.4%) for B. henselae, 13 (8.4%) for B. clarridgeiae, and 7 (4.7%) for B. bovis. Statistical analysis revealed a few potential risk factors, mainly dog's age and breed, latitude and average winter temperature. Twenty-two (14.8%) dogs, including 8 of the 29 seropositive dogs, were PCR-positive for Bartonella based on the ftsZ gene, with 18 (81.8%) of these 22 dogs also positive for the rpoB gene. Partial sequencing showed that all PCR-positive dogs were infected with Candidatus B. merieuxii. Dogs from arid regions and regions with cold average winter temperatures were less likely to be PCR-positive than dogs from other climatic zones. The widespread presence of Bartonella spp. infection in Tunisian dogs suggests a role for stray dogs as potential reservoirs of Bartonella species in Tunisia.

  18. Influence of obstetric factors on osteogenic potential of umbilical cord-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Canella Alessandro

    2009-10-01

    Full Text Available Abstract Wharton's jelly from the umbilical cord is a noncontroversial source of mesenchymal stem cells (WJMSCs with high plasticity, proliferation rate and ability to differentiate towards multiple lineages. WJMSCs from different donors have been characterized for their osteogenic potential. Although there is large evidence of WJMSCs plasticity, recently scientific debate has focused on MSCs selection, establishing predictable elements to discriminate the cells with most promising osteoprogenitor cell potential. In the present study a comparative study between the presence of osteoblastic markers and different parameters that pertain to both the newborn and the mother was performed. Umbilical cords were collected after all patients signed the informed consent and local ethical commettee approved the study. Obstetric parameters, including baby's gender and birth weight, mother's age at delivery, gestational stage at parturition and mode of delivery were examined. After characterization and expansion, WJMSCs were analyzed for two osteoblastic markers, alkaline phosphatase (ALP activity, and the expression level of RUNX-2 transcription factor, and for their ability to deposit mineralized matrix after osteogenic induction. We found that osteoblastic potential was not influenced by baby's gender and mode of delivery. On the contrary, the highest degree of osteoblastic potential has been shown by WJMSCs with RUNX-2 high basal levels, selected from umbilical cords of the heaviest term babies. Even if further evaluation is required, our hypothesis is that our findings may help in selecting the optimal umbilical cord donors and in collecting high potential Wharton's jelly-derived osteoprogenitors efficiently.

  19. In Silico discovery of transcription factors as potential diagnostic biomarkers of ovarian cancer

    KAUST Repository

    Kaur, Mandeep

    2011-09-19

    Background: Our study focuses on identifying potential biomarkers for diagnosis and early detection of ovarian cancer (OC) through the study of transcription regulation of genes affected by estrogen hormone.Results: The results are based on a set of 323 experimentally validated OC-associated genes compiled from several databases, and their subset controlled by estrogen. For these two gene sets we computationally determined transcription factors (TFs) that putatively regulate transcription initiation. We ranked these TFs based on the number of genes they are likely to control. In this way, we selected 17 top-ranked TFs as potential key regulators and thus possible biomarkers for a set of 323 OC-associated genes. For 77 estrogen controlled genes from this set we identified three unique TFs as potential biomarkers.Conclusions: We introduced a new methodology to identify potential diagnostic biomarkers for OC. This report is the first bioinformatics study that explores multiple transcriptional regulators of OC-associated genes as potential diagnostic biomarkers in connection with estrogen responsiveness. We show that 64% of TF biomarkers identified in our study are validated based on real-time data from microarray expression studies. As an illustration, our method could identify CP2 that in combination with CA125 has been reported to be sensitive in diagnosing ovarian tumors. 2011 Kaur et al; licensee BioMed Central Ltd.

  20. In Silico discovery of transcription factors as potential diagnostic biomarkers of ovarian cancer

    KAUST Repository

    Kaur, Mandeep; MacPherson, Cameron R; Schmeier, Sebastian; Narasimhan, Kothandaraman; Choolani, Mahesh; Bajic, Vladimir B.

    2011-01-01

    Background: Our study focuses on identifying potential biomarkers for diagnosis and early detection of ovarian cancer (OC) through the study of transcription regulation of genes affected by estrogen hormone.Results: The results are based on a set of 323 experimentally validated OC-associated genes compiled from several databases, and their subset controlled by estrogen. For these two gene sets we computationally determined transcription factors (TFs) that putatively regulate transcription initiation. We ranked these TFs based on the number of genes they are likely to control. In this way, we selected 17 top-ranked TFs as potential key regulators and thus possible biomarkers for a set of 323 OC-associated genes. For 77 estrogen controlled genes from this set we identified three unique TFs as potential biomarkers.Conclusions: We introduced a new methodology to identify potential diagnostic biomarkers for OC. This report is the first bioinformatics study that explores multiple transcriptional regulators of OC-associated genes as potential diagnostic biomarkers in connection with estrogen responsiveness. We show that 64% of TF biomarkers identified in our study are validated based on real-time data from microarray expression studies. As an illustration, our method could identify CP2 that in combination with CA125 has been reported to be sensitive in diagnosing ovarian tumors. 2011 Kaur et al; licensee BioMed Central Ltd.

  1. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act.

    Science.gov (United States)

    Johnson, Matthew W; Griffiths, Roland R; Hendricks, Peter S; Henningfield, Jack E

    2018-06-05

    This review assesses the abuse potential of medically-administered psilocybin, following the structure of the 8 factors of the US Controlled Substances Act (CSA). Research suggests the potential safety and efficacy of psilocybin in treating cancer-related psychiatric distress and substance use disorders, setting the occasion for this review. A more extensive assessment of abuse potential according to an 8-factor analysis would eventually be required to guide appropriate schedule placement. Psilocybin, like other 5-HT2A agonist classic psychedelics, has limited reinforcing effects, supporting marginal, transient non-human self-administration. Nonetheless, mushrooms with variable psilocybin content are used illicitly, with a few lifetime use occasions being normative among users. Potential harms include dangerous behavior in unprepared, unsupervised users, and exacerbation of mental illness in those with or predisposed to psychotic disorders. However, scope of use and associated harms are low compared to prototypical abused drugs, and the medical model addresses these concerns with dose control, patient screening, preparation and follow-up, and session supervision in a medical facility. (1) psilocybin has an abuse potential appropriate for CSA scheduling if approved as medicine; (2) psilocybin can provide therapeutic benefits that may support the development of an approvable New Drug Application (NDA) but further studies are required which this review describes; (3) adverse effects of medical psilocybin are manageable when administered according to risk management approaches; and (4) although further study is required, this review suggests that placement in Schedule IV may be appropriate if a psilocybin-containing medicine is approved. Copyright © 2018. Published by Elsevier Ltd.

  2. A multidimensional approach to understanding the potential risk factors and covariates of adult picky eating.

    Science.gov (United States)

    Ellis, Jordan M; Schenk, Rebecca R; Galloway, Amy T; Zickgraf, Hana F; Webb, Rose Mary; Martz, Denise M

    2018-06-01

    Adult picky eating (PE) has received increased attention in the eating behavior literature due to its important association with adult avoidant-restrictive food intake disorder (ARFID). The current study tested a model of potential risk factors of adult PE behavior, including perceived early parental feeding practices. An exploratory model was also utilized to understand associations with different aspects of adult PE behaviors. A sample of 1339 US adults recruited through Amazon's MTurk completed an online survey that included the recently developed Adult Picky Eating Questionnaire (APEQ), retrospective reports of parental feeding practices, and other measures of eating behavior and demographic variables. A structural equation modeling procedure tested a series of regression models that included BMI and disordered eating behaviors as covariates. SEM modeling indicated that retrospective reports of greater parental pressure to eat, higher disgust sensitivity, lower PE age of onset, and experiencing an aversive food event were associated with general adult PE behavior. Results also indicated parental encouragement of healthy eating may be a protective factor, and that men endorsed higher levels of adult PE. Exploratory analyses indicated that cross-sectional predictors and covariates were differentially related to specific aspects of PE as measured by the APEQ subscales. Early experiences, including parental approaches to feeding, appear to be potential risk factors of PE behavior in adults. A nuanced understanding of adult PE is important for the prevention and treatment of severe PE behaviors, related psychosocial impairment, and ARFID. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

    Science.gov (United States)

    Papagiorgis, Petros Christakis

    2016-05-01

    Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

  4. Identification and assessment of potential water quality impact factors for drinking-water reservoirs.

    Science.gov (United States)

    Gu, Qing; Deng, Jinsong; Wang, Ke; Lin, Yi; Li, Jun; Gan, Muye; Ma, Ligang; Hong, Yang

    2014-06-10

    Various reservoirs have been serving as the most important drinking water sources in Zhejiang Province, China, due to the uneven distribution of precipitation and severe river pollution. Unfortunately, rapid urbanization and industrialization have been continuously challenging the water quality of the drinking-water reservoirs. The identification and assessment of potential impacts is indispensable in water resource management and protection. This study investigates the drinking water reservoirs in Zhejiang Province to better understand the potential impact on water quality. Altogether seventy-three typical drinking reservoirs in Zhejiang Province encompassing various water storage levels were selected and evaluated. Using fifty-two reservoirs as training samples, the classification and regression tree (CART) method and sixteen comprehensive variables, including six sub-sets (land use, population, socio-economy, geographical features, inherent characteristics, and climate), were adopted to establish a decision-making model for identifying and assessing their potential impacts on drinking-water quality. The water quality class of the remaining twenty-one reservoirs was then predicted and tested based on the decision-making model, resulting in a water quality class attribution accuracy of 81.0%. Based on the decision rules and quantitative importance of the independent variables, industrial emissions was identified as the most important factor influencing the water quality of reservoirs; land use and human habitation also had a substantial impact on water quality. The results of this study provide insights into the factors impacting the water quality of reservoirs as well as basic information for protecting reservoir water resources.

  5. Identification of pathogenic factors potentially involved in Staphylococcus aureus keratitis using proteomics.

    Science.gov (United States)

    Khan, Shamila; Cole, Nerida; Hume, Emma B H; Garthwaite, Linda L; Nguyen-Khuong, Terry; Walsh, Bradley J; Willcox, Mark D P

    2016-10-01

    Staphylococcus is a leading cause of microbial keratitis, characterized by destruction of the cornea by bacterial exoproteins and host-associated factors. The aim of this study was to compare extracellular and cell-associated proteins produced by two different isolates of S. aureus, a virulent clinical isolate (Staph 38) and a laboratory strain (Staphylococcus aureus 8325-4) of weaker virulence in the mouse keratitis model. Proteins were analyzed using 2D polyacrylamide gel electrophoresis and identified by subsequent mass spectrometry. Activity of staphylococcal adhesins was assessed by allowing strains to bind to various proteins adsorbed onto polymethylmethacrylate squares. Thirteen proteins in the extracellular fraction and eight proteins in the cell-associated fractions after bacterial growth were produced in increased amounts in the clinical isolate Staph 38. Four of these proteins were S. aureus virulence factor adhesins, fibronectin binding protein A, staphopain, glyceraldehyde-3-phosphate dehydrogenase 2 and extracellular adherence protein. The clinical isolate Staph 38 adhered to a greater extent to all mammalian proteins tested, indicating the potential of the adhesins to be active on its surface. Other proteins with increased expression in Staph 38 included potential moonlighting proteins and proteins involved in transcription or translation. This is the first demonstration of the proteome of S. aureus isolates from keratitis. These results indicate that the virulent clinical isolate produces more potentially important virulence factors compared to the less virulent laboratory strain and these may be associated with the ability of a S. aureus strain to cause more severe keratitis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Ionization-potential depression and dynamical structure factor in dense plasmas

    Science.gov (United States)

    Lin, Chengliang; Röpke, Gerd; Kraeft, Wolf-Dietrich; Reinholz, Heidi

    2017-07-01

    The properties of a bound electron system immersed in a plasma environment are strongly modified by the surrounding plasma. The modification of an essential quantity, the ionization energy, is described by the electronic and ionic self-energies, including dynamical screening within the framework of the quantum statistical theory. Introducing the ionic dynamical structure factor as the indicator for the ionic microfield, we demonstrate that ionic correlations and fluctuations play a critical role in determining the ionization potential depression. This is, in particular, true for mixtures of different ions with large mass and charge asymmetry. The ionization potential depression is calculated for dense aluminum plasmas as well as for a CH plasma and compared to the experimental data and more phenomenological approaches used so far.

  7. Structure factor of polymers interacting via a short range repulsive potential: Application to hairy wormlike micelles

    International Nuclear Information System (INIS)

    Massiera, Gladys; Ramos, Laurence; Ligoure, Christian; Pitard, Estelle

    2003-01-01

    We use the random phase approximation to compute the structure factor S(q) of a solution of chains interacting through a soft and short range repulsive potential V. Above a threshold polymer concentration, whose magnitude is essentially controlled by the range of the potential, S(q) exhibits a peak whose position depends on the concentration. We take advantage of the close analogy between polymers and wormlike micelles and apply our model, using a Gaussian function for V, to quantitatively analyze experimental small angle neutron scattering profiles of solutions of hairy wormlike micelles. These samples, which consist in surfactant self-assembled flexible cylinders decorated by amphiphilic copolymer, provide indeed an appropriate experimental model system to study the structure of sterically interacting polymer solutions

  8. ANALYSIS OF FACTORS AFFECTING WIND-ENERGY POTENTIAL IN LOW BUILT-UP URBAN ENVIRONMENTS

    Directory of Open Access Journals (Sweden)

    LÁZÁR I.

    2014-03-01

    Full Text Available his study is concerned with the examination of roughness factor affecting wind potential in low built-up urban areas (e.g. subdivision, light industrial area. The test interval is the transition between summer and winter, as a secondary wind maximum period. The ten-minute data-pairs empirical distribution was approached by several theoretical distributions where a fitting test research was also performed. Extrapolation to higher levels is possible by defining the Hellmann exponent. The wind speed in respective height and the specific wind power are derived from it. Knowing the daily progress of the Hellmann exponent value, more accurate estimation can be given of the wind potential calculated to different heights according to the measuring point. The results were compared to the surface cover of the surrounding area as well as to the literary alpha values.

  9. Potential safety issues and other factors that may affect the introduction and uptake of rotavirus vaccines

    Science.gov (United States)

    Aliabadi, N.; Tate, J.E.; Parashar, U.D.

    2018-01-01

    Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally. PMID:27129416

  10. Potential safety issues and other factors that may affect the introduction and uptake of rotavirus vaccines.

    Science.gov (United States)

    Aliabadi, N; Tate, J E; Parashar, U D

    2016-12-01

    Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally. Published by Elsevier Ltd.

  11. Application of positive matrix factorization to identify potential sources of PAHs in soil of Dalian, China

    International Nuclear Information System (INIS)

    Wang Degao; Tian Fulin; Yang Meng; Liu Chenlin; Li Yifan

    2009-01-01

    Soil derived sources of polycyclic aromatic hydrocarbons (PAHs) in the region of Dalian, China were investigated using positive matrix factorization (PMF). Three factors were separated based on PMF for the statistical investigation of the datasets both in summer and winter. These factors were dominated by the pattern of single sources or groups of similar sources, showing seasonal and regional variations. The main sources of PAHs in Dalian soil in summer were the emissions from coal combustion average (46%), diesel engine (30%), and gasoline engine (24%). In winter, the main sources were the emissions from coal-fired boiler (72%), traffic average (20%), and gasoline engine (8%). These factors with strong seasonality indicated that coal combustion in winter and traffic exhaust in summer dominated the sources of PAHs in soil. These results suggested that PMF model was a proper approach to identify the sources of PAHs in soil. - PMF model is a proper approach to identify potential sources of PAHs in soil based on the PAH profiles measured in the field and those published in the literature.

  12. What practice can learn from theory: The potential impact of disposition decision factors on organisational performance

    Directory of Open Access Journals (Sweden)

    Amanda Badenhorst

    2018-02-01

    Full Text Available Background: Effective disposition decisions can lead to a number of value-adding benefits including economic, environmental and marketing benefits. Despite this, many organisations are not aware of the importance of disposition decisions and the impact they can have on organisational performance. Objectives: The aim of this study was to demonstrate the potential impact of disposition decision factors on organisational performance. Method: This study made use of a qualitative content analysis method on previously published scientific articles on reverse logistics. The sample included 67 published scientific articles between 2006 and 2016. ATLAS.ti software was used to assist with the data analysis process. Findings: The findings showed a number of factors for disposition decision-making resulting in a number of value-adding benefits, which can improve organisational performance. From the findings, a conceptual framework was developed linking the disposition decision factors with the value-adding benefits and areas of organisational performance improvements. Conclusion: The framework developed in this article contributes to new insights and can help organisations to identify different performance improvement areas associated with certain disposition decision factors.

  13. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

    Science.gov (United States)

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-06-03

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

  14. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target

    International Nuclear Information System (INIS)

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo JA; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-01-01

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users

  15. Leptin-induced cardioprotection involves JAK/STAT signaling that may be linked to the mitochondrial permeability transition pore

    OpenAIRE

    Smith, Christopher C. T.; Dixon, Richard A.; Wynne, Abigail M.; Theodorou, Louise; Ong, Sang-Ging; Subrayan, Sapna; Davidson, Sean M.; Hausenloy, Derek J.; Yellon, Derek M.

    2010-01-01

    Leptin-induced protection against myocardial ischemia-reperfusion (I/R) injury involves the activation of the reperfusion injury salvage kinase pathway, incorporating phosphatidylinositol 3-kinase-Akt/protein kinase B and p44/42 MAPK, and the inhibition of the mitochondrial permeability transition pore (MPTP). Recently published data indicate that the JAK/STAT signaling pathway, which mediates the metabolic actions of leptin, also plays a pivotal role in cardioprotection. Consequently, in the...

  16. [Potential role of the angiogenic factor "EG-VEGF" in gestational trophoblastic diseases].

    Science.gov (United States)

    Boufettal, H; Feige, J-J; Benharouga, M; Aboussaouira, T; Nadifi, S; Mahdaoui, S; Samouh, N; Alfaidy, N

    2013-10-01

    Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Influence of potentially confounding factors on sea urchin porewater toxicity tests

    Science.gov (United States)

    Carr, R.S.; Biedenbach, J.M.; Nipper, M.

    2006-01-01

    The influence of potentially confounding factors has been identified as a concern for interpreting sea urchin porewater toxicity test data. The results from >40 sediment-quality assessment surveys using early-life stages of the sea urchin Arbacia punctulata were compiled and examined to determine acceptable ranges of natural variables such as pH, ammonia, and dissolved organic carbon on the fertilization and embryological development endpoints. In addition, laboratory experiments were also conducted with A. punctulata and compared with information from the literature. Pore water with pH as low as 6.9 is an unlikely contributor to toxicity for the fertilization and embryological development tests with A. punctulata. Other species of sea urchin have narrower pH tolerance ranges. Ammonia is rarely a contributing factor in pore water toxicity tests using the fertilization endpoint, but the embryological development endpoint may be influenced by ammonia concentrations commonly found in porewater samples. Therefore, ammonia needs to be considered when interpreting results for the embryological development test. Humic acid does not affect sea urchin fertilization at saturation concentrations, but it could have an effect on the embryological development endpoint at near-saturation concentrations. There was no correlation between sediment total organic carbon concentrations and porewater dissolved organic carbon concentrations. Because of the potential for many varying substances to activate parthenogenesis in sea urchin eggs, it is recommended that a no-sperm control be included with every fertilization test treatment. ?? 2006 Springer Science+Business Media, Inc.

  18. Potential risk factors for onset of severe neck and shoulder discomfort (Katakori) in urban Japanese workers.

    Science.gov (United States)

    Sawada, Takayuki; Matsudaira, Ko; Muto, Yumiko; Koga, Tadashi; Takahashi, Masaya

    2016-06-10

    Katakori is a Japanese word, and there is no clear English translation. Katakori consists of two terms, Kata means neck and shoulder, kori means stiffness. Consequently, Katakori is defined as neck and shoulder discomfort or dull pain. Katakori is a major somatic complaint and has a large impact on workers. To examine the association between onset of severe Katakori and potential risk factors in Japanese workers, a prospective cohort study, entitled "Cultural and Psychosocial Influence on Disability (CUPID)", was conducted. Self-administered questionnaires were distributed twice: at baseline and 1 year after baseline. Logistic regression was used to explore the risk factors of onset of severe Katakori. Of those 1,398, the incidence of severe Katakori onset after 1 year was 3.0% (42 workers). Being female (adjusted odds ratio: 2.39, 95% confidence interval: 1.18-4.86), short sleep duration (adjusted odds ratio: 2.86, 95% confidence interval: 1.20-6.82) and depressed mood with some issues at work (adjusted odds ratio: 3.11, 95% confidence interval: 1.38-7.03) were significantly associated with onset of severe Katakori. Psychosocial factors as well as gender difference were associated with onset of severe Katakori. We suggest that mental health support at the workplace is important to prevent severe Katakori.

  19. Potential bias factors that affect the course evaluation of students in preclinical courses

    Directory of Open Access Journals (Sweden)

    Su Jin Chae

    2017-06-01

    Full Text Available Purpose We aim to identify what potential bias factors affected students’ overall course evaluation, and to observe what factors should be considered in the curriculum evaluation system of medical schools. Methods This study analyzed students’ ratings of preclinical instructions at the Ajou University School of Medicine. The ratings of instructions involved 41 first-year and 45 second-year medical students. Results There was a statistically significant difference between years of study and ratings’ scoring. Learning difficulty, learning amount, student assessment, and teacher preparation from second-year students were significantly higher than first-year students (p<0.05. The analysis results revealed that student assessment was the predictor of ratings from first-year students, while teacher preparation was the predictor of ratings from second-year students. Conclusion We found significant interactions between year of study and the students’ rating results. We were able to confirm that satisfaction of instructions factors perceived by medical students were different for the characteristics of courses. Our results may be an important resource for evaluating preclinical curriculums.

  20. Entrapment of ovalbumin into liposomes--factors affecting entrapment efficiency, liposome size, and zeta potential.

    Science.gov (United States)

    Brgles, Marija; Jurasin, Darija; Sikirić, Maja Dutour; Frkanec, Ruza; Tomasić, Jelka

    2008-01-01

    Various amounts of Ovalbumin (OVA) were encapsulated into positively and negatively charged multilamellar liposomes, with the aim to investigate the entrapment efficiency in different buffers and to study their effects on the liposome size and zeta potential. Results showed that the entrapment efficiency of OVA in anionic liposomes was the same in 10 mM Phosphate Buffer (PB) as in Phosphate-Buffered Saline (PBS; PB + 0.15 M NaCl). Also, liposome size was approximately 1200 nm for all anionic liposomes incorporating OVA. The entrapment efficiency of OVA in cationic liposomes was highly dependent on ionic strength. The size of cationic liposomes was approximately 1200 nm in PBS, regardless of protein content, but increased with the amount of the incorporated protein in PB. Aggregation of cationic liposomes in PB was observed when the mass of the protein was 2.5 mg or greater. The zeta potential of anionic liposomes was negative and of cationic liposomes positive in the whole range of protein mass tested. These results show how different compositions of lipid and aqueous phases can be used to vary the entrapment efficiency, liposome size, and zeta potential--the factors that are of great importance for the use of liposomes as drug carriers.

  1. Factors Influencing the Recurrence Potential of Benign Endometrial Polyps after Hysteroscopic Polypectomy.

    Directory of Open Access Journals (Sweden)

    Jehn-Hsiahn Yang

    Full Text Available An endometrial polyp is a frequently encountered gynecologic disease with abnormal uterine bleeding and infertility being the two common presenting problems, and hysteroscopic polypectomy is an effective method to remove them. The postoperative polyp recurrence might result in reappearance of abnormal uterine bleeding or infertility, whereas factors influencing the postoperative recurrence potential have limited data.This case-series report included 168 premenopausal women who suffered from endometrial polyps and underwent hysteroscopic polypectomy. All of them were awaiting a future pregnancy. Office hysteroscopy was done before and after hysteroscopic polypectomy, in which preoperative hysteroscopy examined the number, type, and location of endometrial polyps, and postoperative hysteroscopy checked the polyp recurrence. Surgical indications, either infertility or the presentation of abnormal uterine bleeding, and follow-up duration were recorded.Seventy-three out of 168 (43% women had polyp recurrence after hysteroscopic polypectomy. Multivariate logistic regression analysis revealed that more endometrial polyps (P = 0.015 and longer duration of follow-up (P = 0.004 were significantly associated with an increased risk of postoperative polyp recurrence. The type of endometrial polyps was not correlated with polyp recurrence potential, whereas pedunculated type endometrial polyps were closely related to the presentation of abnormal uterine bleeding (P = 0.001.A higher number of endometrial polyps and longer follow-up duration are associated with a greater potential of polyp recurrence after hysteroscopic polypectomy.

  2. Lack of acute cardioprotective effect from preischaemic erythropoietin administration in a porcine coronary occlusion model

    DEFF Research Database (Denmark)

    Kristensen, Jens; Mæng, Michael; Rehling, Michael

    2005-01-01

    preconditioning may be involved. Before clinical testing such possible cardioprotective effects needs assessment in an experimental large animal model with closer similarity to human ischaemic pathophysiology. METHODS: A control group and two rhEPO groups were studied. EPO1 pigs were given EPO corresponding...... by myocardial perfusion imaging (MPI) and postmortem by a histochemical procedure (at 150 min of reperfusion). RESULTS: IS/AAR did not differ significantly between control (C), EPO1 and EPO2 groups, neither measured by MPI (mean+/-SD for C: 0.87+/-0.13; EPO1: 0.92+/-0.08; EPO2: 0.87+/-0.11), nor histochemically...... (mean+/-SD for C: 0.64+/-0.20; EPO1: 0.75+/-0.17; EPO2: 0.80+/-0.07). In the EPO2 group mean arterial pulmonary pressure and dP/dtmax were increased compared with control group. CONCLUSION: Despite promising results from studies in rodents, rhEPO did not reduce infarct size measured after 2.5 h...

  3. Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

    Science.gov (United States)

    Rodrigo, Ramón; Feliú, Felipe; Hasson, Daniel

    2013-01-01

    Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA) have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress). These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage. PMID:23936799

  4. Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Ramón Rodrigo

    2013-01-01

    Full Text Available Acute myocardial infarction (AMI is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress. These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage.

  5. Gsk-3β Inhibitors Mimic the Cardioprotection Mediated by Ischemic Pre- and Postconditioning in Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Luisa F. González Arbeláez

    2013-01-01

    Full Text Available The aim of this study was to examine the effects of GSK-3β inhibitors compared with PRE and POS in spontaneously hypertensive rats (SHR. Isolated hearts were submitted to the following protocols: IC: 45 min global ischemia (GI and 1-hour reperfusion (R; PRE: a cycle of 5 min GI and 10 minutes of R prior to 45 min GI; POS: three cycles of 30 sec GI/30 sec R at the start of R. Other hearts received lithium chloride (LiCl or indirubin-3′-monoxime,5-iodo-(IMI as GSK-3β inhibitors. All interventions reduced the infarct size observed in IC group. The expressions of P-GSK-3β and P-Akt decreased in IC and were restored after PRE, POS, and GSK-3β inhibitors treatments. An increase of cytosolic MnSOD activity and lipid peroxidation and a decrease of GSH content observed in IC hearts were attenuated in PRE, POS, and LiCl or IMI treatments. An increase of P-GSK-3β/VDAC physical association and a partial recovery of mitochondrial permeability were also detected after interventions. These data show that, in SHR hearts, GSK-3β inhibitors mimic the cardioprotection afforded by PRE and POS and suggest that a decrease in mitochondrial permeability mediated by P-GSK-3β/VDAC interaction is a crucial event.

  6. Mitochondria as Key Targets of Cardioprotection in Cardiac Ischemic Disease: Role of Thyroid Hormone Triiodothyronine

    Directory of Open Access Journals (Sweden)

    Francesca Forini

    2015-03-01

    Full Text Available Ischemic heart disease is the major cause of mortality and morbidity worldwide. Early reperfusion after acute myocardial ischemia has reduced short-term mortality, but it is also responsible for additional myocardial damage, which in the long run favors adverse cardiac remodeling and heart failure evolution. A growing body of experimental and clinical evidence show that the mitochondrion is an essential end effector of ischemia/ reperfusion injury and a major trigger of cell death in the acute ischemic phase (up to 48–72 h after the insult, the subacute phase (from 72 h to 7–10 days and chronic stage (from 10–14 days to one month after the insult. As such, in recent years scientific efforts have focused on mitochondria as a target for cardioprotective strategies in ischemic heart disease and cardiomyopathy. The present review discusses recent advances in this field, with special emphasis on the emerging role of the biologically active thyroid hormone triiodothyronine (T3.

  7. [Role of restricted nitric oxide overproduction in the cardioprotective effect of adaptation to intermittent hypoxia].

    Science.gov (United States)

    goriacheva, A V; Belkina, L M; Terekhina, O L; Dawney, H F; Mallet, R T; Smirin, B V; Smirnova, E A; Mashina, S Iu; Manukhina, E B

    2012-01-01

    Adaptation to intermittent normobaric hypoxia is cardioprotective and can stimulate nitric oxide (NO) synthesis. However the role of nitric oxide (NO) in prevention of ischemia-reperfusion (IR) injury of myocardium is controversial. This study was focused on evaluating the effect of adaptation to hypoxia and IR on NO production and development of nitrative stress in the myocardium. Adaptation to hypoxia tended to increase NO production, which was determined by the total level of plasma nitrite and nitrate, and prevented IR-induced NO overproduction. The IR-induced NO overproduction was associated with significant 3-nitrotyrosine (3-NT) accumulation in the left ventricle but not in septum or aorta. In hypoxia-adapted rats, 3-NT after IR was similar to that of control rats without IR. IHC induced marked accumulation of HIF-1alpha in the left ventricle. We suggest that HIF-1alpha contributes to NO-synthase expression during adaptation to hypoxia and thereby facilitates the increase in NO production. NO, in turn, may subsequently prevent NO overproduction during IR by a negative feedback mechanism.

  8. Cardioprotective effect of hydroalcoholic extract of Tecoma stans flowers against isoproterenol induced myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    Shanmukha Ittagi

    2014-02-01

    Full Text Available Objective: To investigate the cardioprotective effect of 70% ethanolic extract of Tecoma stans (T. stans flowers against isoproterenol-induced myocardial infarction in rat myocardium. Methods: Wister rats were pretreated with 70% ethanolic extract of T. stans flowers (250 and 500 mg/kg orally for 14 d and then intoxicated with isoproterenol [200 mg/(kg · day, s.c.] for 2 consecutive d. The biochemical markers for myocardial infarction such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine kinase, total cholesterol, triglycerides, low density lipoproteins and high density lipoproteins were determined. In addition the antioxidant status on heart tissue is also evaluated by testing the activities of antioxidant enzymes such as lipid peroxidation, superoxide dismutase, reduced glutathione and catalase. Results: The results indicated that pretreatment with 70% ethanolic extract of T. stans flowers prevented fall in antioxidants and retarded elevation of cardiac damage markers in isoproterenol treated rats, significantly. In addition, these findings were evidently supported by the remarkable protection revealed in the histopathological studies, even GC-MS analysis data also substantiated out investigation. Conclusions: It was concluded that, in addition to poly phenolics, some of the phyto fragments found during GC-MS analysis might also contributed to the cardiac protection offered by the extract.

  9. Is there any cardioprotective role of Taurine during cold ischemic period following global myocardial ischemia?

    Directory of Open Access Journals (Sweden)

    Gamsizkan Mehmet

    2011-03-01

    Full Text Available Abstract Background The aim of the present study was to investigate the cardioprotective effect of Taurine on the donor hearts during cold ischemic period. Methods 32 rats were divided into four groups (sham, taurine, ischemia, treatment group, 8 rats in each. All rats were fed with rat food for three weeks. Taurine and treatment groups were given a 200 mg/kg/day dose of Taurine by oral gavage besides rat feed. Cardiectomy was performed in all rats after three weeks. In ischemia and treatment groups, harvested hearts were kept in 0.9% sodium chloride at +4 degrees C for 5 hours. Tissue samples were taken from left ventricle in all groups. These samples were evaluated by histopathologic and biochemical examination. Results In the present study results of the biochemical and histopathological examination reveals the protective effects of Taurine. As a marker of lipid peroxidation, Malondialdehyde (MDA levels in ischemia group were significantly higher than both Sham and Taurine groups. MDA values were recorded; 3.62 ± 0.197 in the sham group, 2.07 ± 0.751 in the Taurine group, 9.71 ± 1.439 in the ischemia group and 7.68 ± 1.365 in the treatment group. MDA levels decreased in treatment group. (p Conclusion Taurine decreased myocardial damage during cold ischemic period following global myocardial ischemia.

  10. Cardioprotective Effect of the Aqueous Extract of Lavender Flower against Myocardial Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Dong Wang

    2014-01-01

    Full Text Available This study was conducted to evaluate the cardioprotective property of the aqueous extract of lavender flower (LFAE. The myocardial ischemia/reperfusion (I/R injury of rat was prepared by Langendorff retrograde perfusion technology. The heart was preperfused with K-H solution containing LFAE for 10 min before 20 minutes global ischemia, and then the reperfusion with K-H solution was conducted for 45 min. The left ventricular developed pressure (LVDP and the maximum up/downrate of left ventricular pressure (±dp/dtmax were recorded by physiological recorder as the myocardial function and the myocardial infarct size was detected by TTC staining. Lactate dehydrogenase (LDH and creatine kinase (CK activities in the effluent were measured to determine the myocardial injury degree. The superoxide anion dismutase (SOD and malondialdehyde (MDA in myocardial tissue were detected to determine the oxidative stress degree. The results showed that the pretreatment with LFAE significantly decreased the myocardial infarct size and also decreased the LDH, CK activities, and MDA level, while it increased the LVDP, ±dp/dtmax, SOD activities, and the coronary artery flow. Our findings indicated that LFAE could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states.

  11. Use of Bioclimatic Factors to Determine Potential Niche of Vaccinia Virus, an Emerging and Zoonotic Pathogen

    Science.gov (United States)

    Quiner, C. A.; Nakazawa, Y.

    2017-12-01

    Emerging and understudied pathogens often lack information that most commonly used analytical tools require, such as negative controls or baseline data making public health control of emerging pathogens challenging. In lieu of opportunities to collect more data from larger outbreaks or formal epidemiological studies, new analytical strategies, merging case data with publically available datasets, can be used to understand transmission patterns and drivers of disease emergence. Zoonotic infections with Vaccinia virus (VACV) were first reported in Brazil in 1999, VACV is an emerging zoonotic Orthopoxvirus, which primarily infects dairy cattle and farmers in close contact with infected cows. Prospective studies of emerging pathogens could provide critical data that would inform public health planning and response to outbreaks. By using the location of 87-recorded outbreaks and publicly available bioclimatic data we demonstrate one such approach. Using an Ecological Niche Model (ENM), we identify the environmental conditions under which VACV outbreaks have occurred, and determine additional locations in two affected South American countries that may be susceptible to transmission. Further, we show how suitability for the virus responds to different levels of various environmental factors and highlight the most important climatic factors in determining its transmission. The final ENM predicted all areas where Brazilian outbreaks occurred, two out of five Colombian outbreaks and identified new regions within Brazil that are suitable for transmission based on bioclimatic factors. Further, the most important factors in determining transmission suitability are precipitation of the wettest quarter, annual precipitation, mean temperature of the coldest quarter and mean diurnal range. The analyses here provide a means by which to study patterns of an emerging infectious disease, and regions that are potentially at risk for it, in spite of the paucity of critical data. Policy

  12. Candida spp. airway colonization: A potential risk factor for Acinetobacter baumannii ventilator-associated pneumonia.

    Science.gov (United States)

    Tan, Xiaojiang; Zhu, Song; Yan, Dongxing; Chen, Weiping; Chen, Ruilan; Zou, Jian; Yan, Jingdong; Zhang, Xiangdong; Farmakiotis, Dimitrios; Mylonakis, Eleftherios

    2016-08-01

    This retrospective study was conducted to identify potential risk factors for Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) and evaluate the association between Candida spp. airway colonization and A. baumannii VAP. Intensive care unit (ICU) patients who were on mechanical ventilation (MV) for ≥48 hours were divided into the following groups: patients with and without Candida spp. airway colonization; colonized patients receiving antifungal treatment or not; patients with A. baumannii VAP and those without VAP. Logistic regression analysis and propensity score matching were used to identify factors independently associated with A. baumannii VAP. Among 618 eligible patients, 264 (43%) had Candida spp. airway colonization and 114 (18%) developed A. baumannii VAP. Along with MV for ≥7 days (adjusted odds ratio [aOR] 8.9, 95% confidence intervals [95% CI] 4.9-15.8) and presence of a central venous catheter (aOR 3.2, 95% CI 1.1-9), Candida spp. airway colonization (aOR 2.6, 95% CI 1.6-4.3) was identified as an independent risk factor for A. baumannii VAP. Patients with Candida spp. airway colonization were more likely to develop A. baumannii VAP than non-colonized patients (23% vs 15%, P=.01 and 34% vs. 15%, PCandida spp. airway colonization (43%) and A. baumannii VAP (18%) were common in ICU patients who were on mechanical ventilation for at least 48 hours. Candida spp. airway colonization was an independent risk factor for subsequent A. baumannii VAP. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. The potential estimation and factor analysis of China′s energy conservation on thermal power industry

    International Nuclear Information System (INIS)

    Lin, Boqiang; Yang, Lisha

    2013-01-01

    At present, researches about energy conservation are focused on prediction. But there are few researches focused on the estimation of effective input and energy conservation potential, and there has been even no research on energy conservation of thermal power industry of China. This paper will try to fill in such a blank. Panel data on Chinese thermal power industry over 2005–2010 are established, and we adopt the stochastic frontier analysis approach to estimate the energy saving potential of thermal power industry. The results are as follows: (1) the average efficiency of energy inputs in China′s thermal power industry over 2005–2010 was about 0.85, and cumulative energy saving potential equals to 551.04 (Mtce); (2) by improving the non-efficiency factors, the relatively backward inland cities could achieve higher energy saving in thermal power industry; (3) the energy input efficiency of Eastern China Grid is shown to be the highest; (4) in order to realize the energy-saving goal of thermal power industry, one important policy method the government should adopt is to conduct a market-oriented reform in power industry and break the state-owned monopoly to provide incentives for private and foreign direct investment in thermal power sector. -- Highlights: •We adopt SFA model to estimate the coal input efficiency of power sector in China. •We calculate the cumulative energy saving potential equals to 551.04 Mtce. •East China power grid has the highest energy input efficiency. •Some backward inland cities may be the main force for future energy conservation. •Encourage private and foreign direct investment in power sector might be effective

  14. Potential risk factors associated with human alveolar echinococcosis: Systematic review and meta-analysis.

    Science.gov (United States)

    Conraths, Franz J; Probst, Carolina; Possenti, Alessia; Boufana, Belgees; Saulle, Rosella; La Torre, Giuseppe; Busani, Luca; Casulli, Adriano

    2017-07-01

    Human alveolar echinococcosis (AE) is a severe zoonotic disease caused by the metacestode stage of Echinococcus multilocularis. AE is commonly associated with a long incubation period that may last for more than ten years. The objective of this systematic literature review was to identify and summarize the current knowledge on statistically relevant potential risk factors (PRFs) associated with AE in humans. Six bibliographic databases were searched, generating a total of 1,009 publications. Following the removal of duplicate records and the exclusion of papers that failed to meet the criteria of a previously agreed a priori protocol, 23 publications were retained; however, 6 of these did not contain data in a format that allowed their inclusion in the meta-analysis. The remaining 17 publications (6 case-control and 11 cross-sectional studies) were meta-analysed to investigate associations between AE and PRFs. Pooled odds ratios (OR) were used as a measure of effect and separately analysed for case-control and cross-sectional studies. In the case-control studies, the following PRFs for human AE showed higher odds of outcome: "dog ownership", "cat ownership", "have a kitchen garden", "occupation: farmer", "haymaking in meadows not adjacent to water", "went to forests for vocational reasons", "chewed grass" and "hunting / handling foxes". In the cross-sectional studies, the following PRFs showed higher odds of outcome: "dog ownership", "play with dogs", "gender: female", "age over 20 years", "ethnic group: Tibetan", "low income", "source of drinking water other than well or tap", "occupation: herding" and "low education". Our meta-analysis confirmed that the chance of AE transmission through ingestion of food and water contaminated with E. multilocularis eggs exists, but showed also that food- and water-borne PRFs do not significantly increase the risk of infection. This systematic review analysed international peer-reviewed articles that have over the years

  15. Potential risk factors associated with human alveolar echinococcosis: Systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Franz J Conraths

    2017-07-01

    Full Text Available Human alveolar echinococcosis (AE is a severe zoonotic disease caused by the metacestode stage of Echinococcus multilocularis. AE is commonly associated with a long incubation period that may last for more than ten years. The objective of this systematic literature review was to identify and summarize the current knowledge on statistically relevant potential risk factors (PRFs associated with AE in humans.Six bibliographic databases were searched, generating a total of 1,009 publications. Following the removal of duplicate records and the exclusion of papers that failed to meet the criteria of a previously agreed a priori protocol, 23 publications were retained; however, 6 of these did not contain data in a format that allowed their inclusion in the meta-analysis. The remaining 17 publications (6 case-control and 11 cross-sectional studies were meta-analysed to investigate associations between AE and PRFs. Pooled odds ratios (OR were used as a measure of effect and separately analysed for case-control and cross-sectional studies. In the case-control studies, the following PRFs for human AE showed higher odds of outcome: "dog ownership", "cat ownership", "have a kitchen garden", "occupation: farmer", "haymaking in meadows not adjacent to water", "went to forests for vocational reasons", "chewed grass" and "hunting / handling foxes". In the cross-sectional studies, the following PRFs showed higher odds of outcome: "dog ownership", "play with dogs", "gender: female", "age over 20 years", "ethnic group: Tibetan", "low income", "source of drinking water other than well or tap", "occupation: herding" and "low education". Our meta-analysis confirmed that the chance of AE transmission through ingestion of food and water contaminated with E. multilocularis eggs exists, but showed also that food- and water-borne PRFs do not significantly increase the risk of infection.This systematic review analysed international peer-reviewed articles that have over the

  16. Morphine preconditioning confers cardioprotection in doxorubicin-induced failing rat hearts via ERK/GSK-3β pathway independent of PI3K/Akt

    International Nuclear Information System (INIS)

    He, Shu-Fang; Jin, Shi-Yun; Wu, Hao; Wang, Bin; Wu, Yun-Xiang; Zhang, Shu-Jie; Irwin, Michael G.; Wong, Tak-Ming; Zhang, Ye

    2015-01-01

    Preconditioning against myocardial ischemia–reperfusion (I/R) injury can be suppressed in some pathological conditions. This study was designed to investigate whether morphine preconditioning (MPC) exerts cardioprotection in doxorubicin (DOX)-induced heart failure in rats and the mechanisms involved. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase (ERK) and glycogen synthase kinase (GSK)-3β pathways were examined. Normal and DOX-induced failing rat hearts were subjected to I/R injury using a Langendorff perfusion system with or without MPC or ischemic preconditioning (IPC). The PI3K inhibitor (wortmannin) or ERK inhibitor (PD98059) was infused before MPC. In normal hearts, both MPC and IPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by I/R injury. Pretreatment with wortmannin or PD98059 abrogated the protective effects of MPC and suppressed the phosphorylation of Akt, ERK and GSK-3β. In failing rat hearts, however, MPC retained its cardioprotection while IPC did not. This protective effect was abolished by PD98059 but not wortmannin. MPC increased the level of p-ERK rather than p-Akt. The phosphorylation of GSK-3β induced by MPC was reversed by PD98059 only. IPC did not elevate the expression of p-ERK, p-Akt and p-GSK-3β in failing rat hearts. We conclude that MPC is cardioprotective in rats with DOX-induced heart failure while IPC is not. The effect of MPC appears to be mediated via the ERK/GSK-3β pathway independent of PI3K/Akt. - Highlights: • Morphine and ischemic preconditioning are cardioprotective in normal rat hearts. • Ischemic preconditioning fails to confer cardioprotection in rats with heart failure. • Morphine retains cardioprotection in doxorubicin-induced heart failure. • Morphine exerts cardioprotection via the ERK/GSK-β pathway independent of PI3K/Akt.

  17. Morphine preconditioning confers cardioprotection in doxorubicin-induced failing rat hearts via ERK/GSK-3β pathway independent of PI3K/Akt

    Energy Technology Data Exchange (ETDEWEB)

    He, Shu-Fang; Jin, Shi-Yun; Wu, Hao; Wang, Bin; Wu, Yun-Xiang [Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601 (China); Zhang, Shu-Jie [Department of Ultrasound, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601 (China); Irwin, Michael G.; Wong, Tak-Ming [Department of Anesthesiology, University of Hong Kong (Hong Kong); Zhang, Ye, E-mail: zhangye_hassan@aliyun.com [Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601 (China)

    2015-11-01

    Preconditioning against myocardial ischemia–reperfusion (I/R) injury can be suppressed in some pathological conditions. This study was designed to investigate whether morphine preconditioning (MPC) exerts cardioprotection in doxorubicin (DOX)-induced heart failure in rats and the mechanisms involved. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase (ERK) and glycogen synthase kinase (GSK)-3β pathways were examined. Normal and DOX-induced failing rat hearts were subjected to I/R injury using a Langendorff perfusion system with or without MPC or ischemic preconditioning (IPC). The PI3K inhibitor (wortmannin) or ERK inhibitor (PD98059) was infused before MPC. In normal hearts, both MPC and IPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by I/R injury. Pretreatment with wortmannin or PD98059 abrogated the protective effects of MPC and suppressed the phosphorylation of Akt, ERK and GSK-3β. In failing rat hearts, however, MPC retained its cardioprotection while IPC did not. This protective effect was abolished by PD98059 but not wortmannin. MPC increased the level of p-ERK rather than p-Akt. The phosphorylation of GSK-3β induced by MPC was reversed by PD98059 only. IPC did not elevate the expression of p-ERK, p-Akt and p-GSK-3β in failing rat hearts. We conclude that MPC is cardioprotective in rats with DOX-induced heart failure while IPC is not. The effect of MPC appears to be mediated via the ERK/GSK-3β pathway independent of PI3K/Akt. - Highlights: • Morphine and ischemic preconditioning are cardioprotective in normal rat hearts. • Ischemic preconditioning fails to confer cardioprotection in rats with heart failure. • Morphine retains cardioprotection in doxorubicin-induced heart failure. • Morphine exerts cardioprotection via the ERK/GSK-β pathway independent of PI3K/Akt.

  18. Biomarkers Associated with Cognitive Impairment in Treated Cancer Patients: Potential Predisposition and Risk Factors

    Science.gov (United States)

    Castel, Hélène; Denouel, Angeline; Lange, Marie; Tonon, Marie-Christine; Dubois, Martine; Joly, Florence

    2017-01-01

    Purpose: Cognitive impairment in cancer patients induced, at least in part, by treatment are frequently observed and likely have negative impacts on patient quality of life. Such cognitive dysfunctions can affect attention, executive functions, and memory and processing speed, can persist after treatment, and their exact causes remain unclear. The aim of this review was to create an inventory and analysis of clinical studies evaluating biological markers and risk factors for cognitive decline in cancer patients before, during, or after therapy. The ultimate objectives were to identify robust markers and to determine what further research is required to develop original biological markers to enable prevention or adapted treatment management of patients at risk. Method: This review was guided by the PRISMA statement and included a search strategy focused on three components: “cognition disorders,” “predictive factors”/“biological markers,” and “neoplasms,” searched in PubMed since 2005, with exclusion criteria concerning brain tumors, brain therapy, and imaging or animal studies. Results: Twenty-three studies meeting the criteria were analyzed. Potential associations/correlations were identified between cognitive impairments and specific circulating factors, cerebral spinal fluid constituents, and genetic polymorphisms at baseline, during, and at the end of treatment in cancer populations. The most significant results were associations between cognitive dysfunctions and genetic polymorphisms, including APOE-4 and COMT-Val; increased plasma levels of the pro-inflammatory cytokine, IL-6; anemia; and hemoglobin levels during chemotherapy. Plasma levels of specific hormones of the hypothalamo-pituitary-adrenal axis are also modified by treatment. Discussion: It is recognized in the field of cancer cognition that cancer and comorbidities, as well as chemotherapy and hormone therapy, can cause persistent cognitive dysfunction. A number of biological

  19. Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.

    Science.gov (United States)

    Rivier, Jean E; Rivier, Catherine L

    2014-04-01

    Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Neurobehavioral deficits in premature graduates of intensive care--potential medical and neonatal environmental risk factors.

    Science.gov (United States)

    Perlman, J M

    2001-12-01

    There is growing evidence that a large number of very low birth weight infants are exhibiting neurobehavioral problems in the absence of cerebral palsy at follow-up that has extended into school age and adolescence. Many clinical factors (ie, chronic lung disease, recurrent apnea and bradycardia, transient hypothyroxemia of prematurity, hyperbilirubinemia, nutritional deficiencies, glucocorticoid exposure), as well as stressful environmental conditions, including infant-provider interaction, constant noise, and bright light, may act in combination to impact on the developing brain, even in the absence of overt hemorrhage and/or ischemia. Any potential intervention strategy designed to prevent cognitive and behavioral problems has to account for the numerous biological and clinical conditions and/or interventions, as well as postdischarge social and environmental influences.

  1. Potential factors associated with knee pain in cyclists: a systematic review

    Directory of Open Access Journals (Sweden)

    Bini RR

    2018-05-01

    Full Text Available Rodrigo Rico Bini, Alice Flores Bini La Trobe Rural Health School, La Trobe University, Flora Hill Campus, Bendigo, VIC, Australia Abstract: The potential factors associated with overuse injuries and pain in cyclists that are supported by evidence remain unclear. Our study aimed at assessing, using a systematic search of the most updated evidence, the main factors related to overuse knee-related pain and/or injuries in cyclists. The search assessed any potential mechanism related to knee pain or injury that could be used in the clinical practice. Databases were searched (i.e., PubMed, Scopus, Web of Science, and EBSCO. Studies were included if they presented results from original studies. They had to include, preferably but not limited to, recreational and/or competitive cyclists with or without knee pain. Quality of articles was assessed. Eleven articles were deemed eligible for full text appraisal. Studies involved generally the assessment of biomechanical outcomes associated with knee pain in cyclists. Overall, studies showed that cyclists with knee pain present larger knee adduction and larger ankle dorsiflexion and differences in activation for hamstrings and quadriceps muscles. Unclear results were observed for knee moments and no differences were observed for knee flexion angle, tibiofemoral and patellofemoral forces. It is important to state that varied types of knee pain were mixed in most studies, with 2 focused on anterior-related pain. Cyclists with overuse-related pain or injuries on their knees presented an increased medial projection of their knees and an altered activation of the Vastus Medialis and Vastus Lateralis muscles. However, this limited evidence is based on retrospective studies comparing cyclists with and without pain, which limits the conclusion on how cyclists develop knee pain and what are the main options for treatment of knee pain. Keywords: injury, cycling, overuse, biomechanics

  2. The account of sagging of wires at definition of specific potential factors of air High-Voltage Power Transmission Lines

    Directory of Open Access Journals (Sweden)

    Suslov V.M.

    2005-12-01

    Full Text Available The opportunity approached is shown, but more exact as it is usually accepted, the account of sagging of wires at definition of specific potential factors air High-Voltage Power Transmission Lines. The technique of reception of analytical expressions is resulted. For an opportunity of comparison traditional expressions for specific potential factors are resulted also. Communication of the offered and traditional analytical expressions is shown. Offered analytical expressions are not difficult for programming on a personal computer of any class and besides they allow to make an estimation of an error of traditional expressions by means of parallel definition of specific potential factors by both ways.

  3. PBDE levels in human milk: the situation in Germany and potential influencing factors - a controlled study

    Energy Technology Data Exchange (ETDEWEB)

    Vieth, B.; Mielke, H.; Ostermann, B.; Ruediger, T. [Federal Inst. for Risk Assessment, Berlin (Germany); Herrmann, T.; Paepke, O. [ERGO Forschungsgesellschaft mbH, Hamburg (Germany)

    2004-09-15

    An exponential increase of PBDE levels in breast milk from Sweden between 1972 and 1997 has been reported, which is in contrast to the continuous decline of other chlorinated POPs in breast milk. Also in blood samples from Germany, an increasing trend has been observed during the period from 1985 to 1999. The knowledge about human exposure pathways, which contribute to the PBDE body burden, is very limited. Consumption of food of animal origin, inhalation or ingestion of dust and further factors possibly influencing the PBDE levels in human matrices, like age, breast-feeding or smoking are under discussion. Only a few data on PBDE levels in breast milk from Germany have been published. To fill the data gaps, a controlled study was started in 2001 to characterise the PBDE levels in human milk from Germany with special efforts to identify and quantify deca-BDE-209. Furthermore, it was intended to verify potential factors possibly influencing PBDE levels. Two main hypotheses were proposed: (1) Are PBDE levels in breast milk from mothers consuming traditional food (omnivores) higher than those found in breast milk from mothers consuming vegetarian or vegan food? and (2) Are the PBDE levels found in human milk after a three-months period of breast-feeding lower than those detected at the beginning or does breast feeding result in a lower body burden, respectively? This paper summarises preliminary results. Further analytical data and results of data evaluation will be presented at the conference.

  4. Potential Factors Associated with Contraceptive Intention Among Adolescent Males in Taiwan

    Directory of Open Access Journals (Sweden)

    Ruey-Hsia Wang

    2004-03-01

    Full Text Available This study explored the predictors of contraceptive intention in adolescent males in Taiwan. It used a cross-sectional design and a sample of 1,000 vocational high school male students to determine the potential factors associated with contraceptive intention. Data were collected on an anonymous, self-administered questionnaire, including personal background variables, prior sexual experience, contraceptive knowledge, contraceptive attitude, contraceptive self-efficacy, perception of peers' contraceptive behavior, perception of support from significant others, and parental-adolescent communication about contraception. A total of 230 participants (23% had prior sexual experience, 13% (30 of whom reported being involved in their girlfriends' pregnancies. Of the participants, 45% recognized the use of condoms as the most favorable contraceptive method for future sexual intercourse. Second to condom use, the combination of the calendar method and condom use was also popular (13.1%. Multiple stepwise regression indicated that better contraceptive attitudes, higher contraceptive self-efficacy, no prior sexual experience, more perception of peers' contraceptive behavior, and higher perception of support from significant others were predictors of higher contraceptive intention. The above predicting factors explained 31.9% of the total variance for contraceptive intention among adolescents. These results provide health professionals with important information to understand the reality adolescents encounter and to design effective contraceptive programs for male adolescents.

  5. The Therapeutic Potential of Insulin-Like Growth Factor-1 in Central Nervous System Disorders

    Science.gov (United States)

    Costales, Jesse; Kolevzon, Alexander

    2016-01-01

    Central nervous system (CNS) development is a finely tuned process that relies on multiple factors and intricate pathways to ensure proper neuronal differentiation, maturation, and connectivity. Disruption of this process can cause significant impairments in CNS functioning and lead to debilitating disorders that impact motor and language skills, behavior, and cognitive functioning. Recent studies focused on understanding the underlying cellular mechanisms of neurodevelopmental disorders have identified a crucial role for insulin-like growth factor-1 (IGF-1) in normal CNS development. Work in model systems has demonstrated rescue of pathophysiological and behavioral abnormalities when IGF-1 is administered, and several clinical studies have shown promise of efficacy in disorders of the CNS, including autism spectrum disorder (ASD). In this review, we explore the molecular pathways and downstream effects of IGF-1 and summarize the results of completed and ongoing pre-clinical and clinical trials using IGF-1 as a pharmacologic intervention in various CNS disorders. This aim of this review is to provide evidence for the potential of IGF-1 as a treatment for neurodevelopmental disorders and ASD. PMID:26780584

  6. Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity

    International Nuclear Information System (INIS)

    Liu Wenjin; Sun Maoyun; Jiang Jianhai; Shen Xiaoyun; Sun Qing; Liu Weicheng; Shen Hailian; Gu Jianxin

    2004-01-01

    The Cyclin D3 protein is a member of the D-type cyclins. Besides serving as cell cycle regulators, D-type cyclins have been reported to be able to interact with several transcription factors and modulate their transcriptional activations. Here we report that human activating transcription factor 5 (hATF5) is a new interacting partner of Cyclin D3. The interaction was confirmed by in vivo coimmunoprecipitation and in vitro binding analysis. Neither interaction between Cyclin D1 and hATF5 nor interaction between Cyclin D2 and hATF5 was observed. Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. Cyclin D3 could potentiate hATF5 transcriptional activity independently of its Cdk4 partner. But Cyclin D1 and Cyclin D2 had no effect on hATF5 transcriptional activity. These data provide a new clue to understand the new role of Cyclin D3 as a transcriptional regulator

  7. Burnout and stress amongst interns in Irish hospitals: contributing factors and potential solutions.

    Science.gov (United States)

    Hannan, E; Breslin, N; Doherty, E; McGreal, M; Moneley, D; Offiah, G

    2018-05-01

    The transition from medical school to internship can be daunting for newly qualified doctors. High rates of stress and burnout have been reported, with negative impacts on patient care and physician wellbeing. We surveyed interns in our hospital group to evaluate rates of stress and burnout, as well as identify the causative factors and propose potential solutions to these. A hundred and one interns working in four different hospitals over a 2-year period were invited to participate in an anonymous survey. The survey collected basic demographic details and surveyed aspects of mental health using the burnout scale, Maslach Burnout Inventory (MBI) and the stress scale and 12-item General Health Questionnaire (GHQ-12). Interns were also asked to rate a variety of workplace factors on a Likert scale based on the degree of stress caused. Finally, they were surveyed on their awareness of support services available to them. Our results showed that 37% of interns met the criteria for psychological distress, high levels of emotional exhaustion, high depersonalisation and a low sense of personal accomplishment were reported in 55.4, 51.5 and 41.6%, respectively. Inadequate preparation for practice, financial worries, poor role definition and sleep deprivation were reported as significant stressors. Most were unaware of available support services and expressed interest in leaving Ireland after internship. Burnout and stress are significant problems amongst doctors in Irish hospitals. Ensuring better preparation for clinical practice and awareness of support services is vital to tackle this issue.

  8. Serological, molecular detection and potential risk factors associated with camel brucellosis in Pakistan.

    Science.gov (United States)

    Fatima, Sana; Khan, Iahtasham; Nasir, Amar; Younus, Muhammad; Saqib, Muhammad; Melzer, Falk; Neubauer, Heinrich; El-Adawy, Hosny

    2016-12-01

    Brucellosis is one of the most important zoonoses in developing countries and was considered the most widespread zoonosis in the world. Brucellosis was reported in camels and has been reported from all camel-keeping countries.The present study was performed in three districts (Jhang, Chiniot, and Bhakkar) of Punjab province of Pakistan. A total of 200 camel (Camelus bactrianus) sera were collected using random and multistage cluster sampling from different areas. Fifty samples were collected from one organized governmental farm. One hundred fifty samples were collected randomly from nomadic/pastoral production systems. All sera were tested with Rose Bengal plate agglutination test (RBPT) and confirmed by ELISA. Genomic DNA was extracted from all serum samples and tested by real-time PCR. Various potential risk factors (season, rearing with other animals, and abortion or orchitis history) recorded through questionnaires were statistically analyzed by Chi-square test.In total, 5 % of investigated sera were positive by RBPT. Only 2 % of the camel sera were CELISA positive. Brucella abortus DNA was detected in 1.5 % of the investigated animals. Season, rearing of camels with other ruminants, abortion, and orchitis history were found to be statistically significant (p brucellosis is a zoonotic disease in the Pakistani Punjab with various risk factors maintaining and perpetuating its spread. Therefore, there is a need for implementing control measures and raising public health awareness in prevention of brucellosis in Pakistan.

  9. The potential etiologic factors influencing tinnitus intensity in patients with temporomandibular disorders.

    Science.gov (United States)

    Demirkol, Nermin; Demirkol, Mehmet; Usumez, Aslihan; Sari, Fatih; Akcaboy, Cihan

    2017-08-30

    To investigate the potential relationships between the intensity of tinnitus associated with temporomandibular disorders (TMD) and potential etiologic factors, including age, gender, freeway space, sleep bruxism (SB), joint clicking, and headache. The sample was comprised of 90 patients without any hearing loss, as confirmed by otorhinolaryngology, who self-reported subjective tinnitus and simultaneous TMD, based on the Research Diagnostic Criteria for TMD (RDC/TMD). The results showed a positive, weak correlation between the intensity of tinnitus and age (r = 0.225, p = 0.033). The presence of SB and headache were seen in higher proportions in the present sample, at 75.5% (n = 68) and 66.6% (n = 60), respectively. In a population of patients with subjective tinnitus and TMD, no significant associations were found between tinnitus intensity and age, freeway space, SB, clicking presence, and headache, though gender did show a weak correlation with tinnitus intensity.

  10. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas

    International Nuclear Information System (INIS)

    Capala, J.; Barth, R.F.; Adams, D.M.; Bailey, M.Q.; Soloway, A.H.; Carlsson, J.

    1994-01-01

    The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of 10 B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10 5 -10 6 EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10 8 boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight (∼ 6 kD), this has allowed us to construct relatively small bioconjugates containing ∼ 900 boron atoms per EGF molecule 3 , which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using 131 I- or 99m T c -labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of the conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma

  11. Protective or pathogenic effects of vascular endothelial growth factor (VEGF) as potential biomarker in cerebral malaria.

    Science.gov (United States)

    Canavese, Miriam; Spaccapelo, Roberta

    2014-03-01

    Cerebral malaria (CM) is the major lethal complication of Plasmodium falciparum infection. It is characterized by persistent coma along with symmetrical motor signs. Several clinical, histopathological, and laboratory studies have suggested that cytoadherence of parasitized erythrocytes, neural injury by malarial toxin, and excessive inflammatory cytokine production are possible pathogenic mechanisms. Although the detailed pathophysiology of CM remains unsolved, it is thought that the binding of parasitized erythrocytes to the cerebral endothelia of microvessels, leading to their occlusion and the consequent angiogenic dysregulation play a key role in the disease pathogenesis. Recent evidences showed that vascular endothelial growth factor (VEGF) and its receptor-related molecules are over-expressed in the brain tissues of CM patients, as well as increased levels of VEGF are detectable in biologic samples from malaria patients. Whether the modulation of VEGF is causative agent of CM mortality or a specific phenotype of patients with susceptibility to fatal CM needs further evaluation. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify patients and potential risk for adverse outcomes would greatly enhance better intervention and clinical management to improve the outcomes. We review and discuss here what it is currently known in regard to the role of VEGF in CM as well as VEGF as a potential biomarker.

  12. Potential risk factors associated with stress urinary incontinence among Iranian women.

    Science.gov (United States)

    Vahdatpour, Babak; Zargham, Mahtab; Chatraei, Maryam; Bahrami, Faranak; Alizadeh, Farshid

    2015-01-01

    Stress urinary incontinence (SUI) is considered as one of the major hygienic problems among women. The main aim of the study is to assess the potential risk factors associated with SUI among Iranian women. This study was conducted on 90 married women with history of SUI diagnosed by an urologist and were selected randomly. Their pelvic muscles contraction (PMC) and the history of the subjects were assessed for some of risk factors such as age, height, weight, body mass index (BMI), pregnancy history, miscarriage, type of delivery (normal vaginal delivery or cesarean section), number of offspring born healthy in addition to other risk factors such as chronic cough, constipation and hypothyroidism by use of POP Questionnaire. Data were analyzed using Pearson correlation coefficient and SPSS version 18 Software. There was a significant relation between SUI and height (P < 0.05, r = 0.45), vaginal delivery (NVD) (P < 0.05, r = 0.2), number of genitourinary surgery (P < 0.05, r = 0.42), hypothyroidism and constipation (P < 0.05). An inverse relatively strong significant relation was found between SUI and cesarean section (P < 0.05, r = -0.50) No significant relation was found between SUI and weight, BMI, age, chronic cough and miscarriage, and other study parameters. An inverse significant relation between PMC and weight (P < 0.05, r = -0.52), BMI (P < 0.05, r = -0.42) and number of genitourinary surgery (P < 0.05, r = -0.18). Cesarean section had a preventive effect on SUI versus normal vaginal delivery. The rate of SUI was higher in taller women or those suffering from hypothyroidism or constipation or who had genitourinary surgery. The women with high BMI had lower pelvic floor muscles strength.

  13. Analysis of potential dynamic concealed factors in the difficulty of lower third molar extraction.

    Science.gov (United States)

    Singh, P; Ajmera, D-H; Xiao, S-S; Yang, X-Z; Liu, X; Peng, B

    2016-11-01

    The purpose of this study was to identify potential concealed variables associated with the difficulty of lower third molar (M3) extractions. To address the research purpose, we implemented a prospective study and enrolled a sample of subjects presenting for M3 removal. Predictor variables were categorized into Group-I and Group-II, based on predetermined criteria. The primary outcome variable was the difficulty of extraction, measured as extraction time. Appropriate univariate and multivariate statistics were computed using ordinal logistic regression. The sample comprised of 1235 subjects with a mean age of 29.49 +/- 8.92 years in Group-I and 26.20 +/- 11.55 years in Group-II subjects. The mean operating time per M3 extraction was 21.24 +/- 12.80 and 20.24 +/- 12.50 minutes for Group-I and Group-II subjects respectively. Three linear parameters including B-M2 height (distance between imaginary point B on the inferior border of mandibular body, and M2), lingual cortical thickness, bone density and one angular parameter including Rc-Cs angle (angle between ramus curvature and curve of spee), in addition to patient's age, profile type, facial type, cant of occlusal plane, and decreased overbite, were found to be statistically associated ( p < or = 0.05) with extraction difficulty under regression models. In conclusion, our study indicates that the difficulty of lower M3 extractions is possibly governed by morphological and biomechanical factors with substantial influence of myofunctional factors. Preoperative evaluation of dynamic concealed factors may not only help in envisaging the difficulty and planning of surgical approach but might also help in better time management in clinical practice.

  14. Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3β Activity

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    Karthi Shanmugam

    2018-01-01

    Full Text Available Acute myocardial infarction (AMI is the leading cause of morbidity and mortality worldwide. Timely reperfusion is considered an optimal treatment for AMI. Paradoxically, the procedure of reperfusion can itself cause myocardial tissue injury. Therefore, a strategy to minimize the reperfusion-induced myocardial tissue injury is vital for salvaging the healthy myocardium. Herein, we investigated the cardioprotective effects of fisetin, a natural flavonoid, against ischemia/reperfusion (I/R injury (IRI using a Langendorff isolated heart perfusion system. I/R produced significant myocardial tissue injury, which was characterized by elevated levels of lactate dehydrogenase and creatine kinase in the perfusate and decreased indices of hemodynamic parameters. Furthermore, I/R resulted in elevated oxidative stress, uncoupling of the mitochondrial electron transport chain, increased mitochondrial swelling, a decrease of the mitochondrial membrane potential, and induction of apoptosis. Moreover, IRI was associated with a loss of the mitochondrial structure and decreased mitochondrial biogenesis. However, when the animals were pretreated with fisetin, it significantly attenuated the I/R-induced myocardial tissue injury, blunted the oxidative stress, and restored the structure and function of mitochondria. Mechanistically, the fisetin effects were found to be mediated via inhibition of glycogen synthase kinase 3β (GSK3β, which was confirmed by a biochemical assay and molecular docking studies.

  15. Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3β Activity.

    Science.gov (United States)

    Shanmugam, Karthi; Ravindran, Sriram; Kurian, Gino A; Rajesh, Mohanraj

    2018-01-01

    Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. Timely reperfusion is considered an optimal treatment for AMI. Paradoxically, the procedure of reperfusion can itself cause myocardial tissue injury. Therefore, a strategy to minimize the reperfusion-induced myocardial tissue injury is vital for salvaging the healthy myocardium. Herein, we investigated the cardioprotective effects of fisetin, a natural flavonoid, against ischemia/reperfusion (I/R) injury (IRI) using a Langendorff isolated heart perfusion system. I/R produced significant myocardial tissue injury, which was characterized by elevated levels of lactate dehydrogenase and creatine kinase in the perfusate and decreased indices of hemodynamic parameters. Furthermore, I/R resulted in elevated oxidative stress, uncoupling of the mitochondrial electron transport chain, increased mitochondrial swelling, a decrease of the mitochondrial membrane potential, and induction of apoptosis. Moreover, IRI was associated with a loss of the mitochondrial structure and decreased mitochondrial biogenesis. However, when the animals were pretreated with fisetin, it significantly attenuated the I/R-induced myocardial tissue injury, blunted the oxidative stress, and restored the structure and function of mitochondria. Mechanistically, the fisetin effects were found to be mediated via inhibition of glycogen synthase kinase 3 β (GSK3 β ), which was confirmed by a biochemical assay and molecular docking studies.

  16. Cocoa Polyphenols: Can We Consider Cocoa and Chocolate as Potential Functional Food?

    OpenAIRE

    Ackar, Djurdjica; Valek Lendić, Kristina; Valek, Marina; Šubarić, Drago; Miličević, Borislav; Babić, Jurislav; Nedić, Ilija

    2013-01-01

    Chocolate has been consumed as confection, aphrodisiac, and folk medicine for many years before science proved its potential health benefiting effects. Main compounds of cocoa and chocolate which contribute to human health are polyphenols that act as antioxidants and have potential anti-inflammatory, cardioprotective, antihepatotoxic, antibacterial, antiviral, antiallergenic, and anticarcinogenic properties. This paper gives a short overview of scientific literature regarding cocoa polyph...

  17. Local arginase inhibition during early reperfusion mediates cardioprotection via increased nitric oxide production.

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    Adrian T Gonon

    Full Text Available Consumption of L-arginine contributes to reduced bioavailability of nitric oxide (NO that is critical for the development of ischemia-reperfusion injury. The aim of the study was to determine myocardial arginase expression and activity in ischemic-reperfusion myocardium and whether local inhibition of arginase within the ischemic myocardium results in increased NO production and protection against myocardial ischemia-reperfusion. Anesthetized pigs were subjected to coronary artery occlusion for 40 min followed by 4 h reperfusion. The pigs were randomized to intracoronary infusion of vehicle (n = 7, the arginase inhibitor N-hydroxy-nor-L-arginine (nor-NOHA, 2 mg/min, n = 7, the combination of nor-NOHA and the NO synthase inhibitor N(G-monomethyl-L-arginine (L-NMMA, 0.35 mg/min, n = 6 into the jeopardized myocardial area or systemic intravenous infusion of nor-NOHA (2 mg/min, n = 5 at the end of ischemia and start of reperfusion. The infarct size of the vehicle group was 80 ± 4% of the area at risk. Intracoronary nor-NOHA reduced infarct size to 46 ± 5% (P<0.01. Co-administration of L-NMMA abrogated the cardioprotective effect mediated by nor-NOHA (infarct size 72 ± 6%. Intravenous nor-NOHA did not reduce infarct size. Arginase I and II were expressed in cardiomyocytes, endothelial, smooth muscle and poylmorphonuclear cells. There was no difference in cytosolic arginase I or mitochondrial arginase II expression between ischemic-reperfused and non-ischemic myocardium. Arginase activity increased 2-fold in the ischemic-reperfused myocardium in comparison with non-ischemic myocardium. In conclusion, ischemia-reperfusion increases arginase activity without affecting cytosolic arginase I or mitochondrial arginase II expression. Local arginase inhibition during early reperfusion reduces infarct size via a mechanism that is dependent on increased bioavailability of NO.

  18. Antihypertensive and cardioprotective effects of the dipeptide isoleucine-tryptophan and whey protein hydrolysate.

    Science.gov (United States)

    Martin, M; Kopaliani, I; Jannasch, A; Mund, C; Todorov, V; Henle, T; Deussen, A

    2015-12-01

    Angiotensin-converting enzyme inhibitors are treatment of choice in hypertensive patients. Clinically used inhibitors exhibit a structural similarity to naturally occurring peptides. This study evaluated antihypertensive and cardioprotective effects of ACE-inhibiting peptides derived from food proteins in spontaneously hypertensive rats. Isoleucine-tryptophan (in vitro IC50 for ACE = 0.7 μm), a whey protein hydrolysate containing an augmented fraction of isoleucine-tryptophan, or captopril was given to spontaneously hypertensive rats (n = 60) over 14 weeks. Two further groups, receiving either no supplement (Placebo) or intact whey protein, served as controls. Systolic blood pressure age-dependently increased in the Placebo group, whereas the blood pressure rise was effectively blunted by isoleucine-tryptophan, whey protein hydrolysate and captopril (-42 ± 3, -38 ± 5, -55 ± 4 mm Hg vs. Placebo). At study end, myocardial mass was lower in isoleucine-tryptophan and captopril groups but only partially in the hydrolysate group. Coronary flow reserve (1 μm adenosine) was improved in isoleucine-tryptophan and captopril groups. Plasma ACE activity was significantly decreased in isoleucine-tryptophan, hydrolysate and captopril groups, but in aortic tissue only after isoleucine-tryptophan or captopril treatment. This was associated with lowered expression and activity of matrix metalloproteinase-2. Following isoleucine-tryptophan and captopril treatments, gene expression of renin was significantly increased indicating an active feedback within renin-angiotensin system. Whey protein hydrolysate and isoleucine-tryptophan powerfully inhibit plasma ACE resulting in antihypertensive effects. Moreover, isoleucine-tryptophan blunts tissue ACE activity, reduces matrix metalloproteinase-2 activity and improves coronary flow reserve. Thus, whey protein hydrolysate and particularly isoleucine-tryptophan may serve as innovative food additives with the goal of attenuating

  19. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

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    Søren D Østergaard

    2015-06-01

    Full Text Available Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR.We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49, fasting glucose (NSNPs = 36, insulin resistance (NSNPs = 10, body mass index (BMI, NSNPs = 32, total cholesterol (NSNPs = 73, HDL-cholesterol (NSNPs = 71, LDL-cholesterol (NSNPs = 57, triglycerides (NSNPs = 39, systolic blood pressure (SBP, NSNPs = 24, smoking initiation (NSNPs = 1, smoking quantity (NSNPs = 3, university completion (NSNPs = 2, and years of education (NSNPs = 1. We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3. Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8. Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3, although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28. We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1. Potential limitations of this study

  20. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Science.gov (United States)

    Østergaard, Søren D; Mukherjee, Shubhabrata; Sharp, Stephen J; Proitsi, Petroula; Lotta, Luca A; Day, Felix; Perry, John R B; Boehme, Kevin L; Walter, Stefan; Kauwe, John S; Gibbons, Laura E; Larson, Eric B; Powell, John F; Langenberg, Claudia; Crane, Paul K; Wareham, Nicholas J; Scott, Robert A

    2015-06-01

    Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this

  1. Potential risk factors for jaw osteoradionecrosis after radiotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Kuhnt, Thomas; Stang, Andreas; Wienke, Andreas; Vordermark, Dirk; Schweyen, Ramona; Hey, Jeremias

    2016-01-01

    To identify potential risk factors for the development of jaw osteoradionecrosis (ORN) after 3D-conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) among patients with newly diagnosed head and neck cancer. This study included 776 patients who underwent 3D-CRT or IMRT for head and neck cancer at the Department of Radiotherapy at the University Hospital Halle-Wittenberg between 2003 and 2013. Sex, dental status prior to radiotherapy, tumor site, bone surgery during tumor resection, concomitant chemotherapy, and the development of advanced ORN were documented for each patient. ORN was classified as grade 3, 4, or 5 according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer classification or grade 3 or 4 according to the late effects in normal tissues/subjective, objective, management, and analytic scale. The cumulative incidence of ORN was estimated. Cox regression analysis was used to identify prognostic risk factors for the development of ORN. Fifty-one patients developed advanced ORN (relative frequency 6.6 %, cumulative incidence 12.4 %). The highest risk was found in patients who had undergone primary bone surgery during tumor resection (hazard ratio [HR] = 5.87; 95 % confidence interval [CI]: 3.09–11.19) and in patients with tumors located in the oral cavity (HR = 4.69; 95 % CI: 1.33–16.52). Sex, dentition (dentulous vs. edentulous), and chemotherapy had no clinically relevant influence. In contrast to most previous studies, we noted a low cumulative incidence of advanced ORN. Patients with tumors located in the oral cavity and those who undergo bone surgery during tumor resection prior to RT may be considered a high-risk group for the development of ORN

  2. Change of water consumption and its potential influential factors in Shanghai: A cross-sectional study

    Science.gov (United States)

    2012-01-01

    Background Different water choices affect access to drinking water with different quality. Previous studies suggested social-economic status may affect the choice of domestic drinking water. The aim of this study is to investigate whether recent social economic changes in China affect residents’ drinking water choices. Methods We conducted a cross-sectional survey to investigate residents’ water consumption behaviour in 2011. Gender, age, education, personal income, housing condition, risk perception and personal preference of a certain type of water were selected as potential influential factors. Univariate and backward stepwise logistic regression analyses were performed to analyse the relation between these factors and different drinking water choices. Basic information was compared with that of a historical survey in the same place in 2001. Self-reported drinking-water-related diarrhoea was found correlated with different water choices and water hygiene treatment using chi-square test. Results The percentage of tap water consumption remained relatively stable and a preferred choice, with 58.99% in 2001 and 58.25% in 2011. The percentage of bottled/barrelled water consumption was 36.86% in 2001 and decreased to 25.75% in 2011. That of household filtrated water was 4.15% in 2001 and increased to 16.00% in 2011. Logistic regression model showed strong correlation between one’s health belief and drinking water choices (P water-related diarrhoea was found in all types of water and improper water hygiene behaviours still existed among residents. Conclusions Personal health belief, housing condition, age, personal income, education, taste and if worm ever founded in tap water affected domestic drinking water choices in Shanghai. PMID:22708830

  3. Potential risk factors for dental caries in Type 2 diabetic patients.

    Science.gov (United States)

    Almusawi, M A; Gosadi, I; Abidia, R; Almasawi, M; Khan, H A

    2018-05-11

    Diabetic patients are known to be at higher risk for dental caries. However, the role of potential risk factors such as blood glucose, salivary glucose and glycaemic control in the occurrence of dental caries in type 2 diabetes (T2D) is not clearly understood so far, and therefore, it was evaluated in this study. This cross-sectional study was conducted on 100 T2D patients from Saudi Arabia. The caries risk assessment was evaluated using the guidelines of Caries Management by Risk Assessment (CAMBRA). Cariogenic bacteria load in saliva was determined by a chair-side test kit. The levels of fasting blood glucose (FBG), salivary glucose and HbA1c were analysed. Majority of the patients had dental caries (84%), exposed root surfaces (92%) and heavy plaque (73%), whereas 66% of patients suffered from xerostomia. The frequency of patients with high counts of Streptococcus mutans and Lactobacilli (LB) were 78% and 42%, respectively. There were significant associations between dental caries risk and FBG, HbA1c and salivary glucose. After categorizing the patients into 3 categories of glycaemic control, we observed a significant association between glycaemic control and dental caries risk. Type 2 diabetes patients are at high risk for dental caries, which is directly associated with FBG, HbA1c and salivary glucose. This is the first study measuring dental caries and its risk factors in T2D patients from Saudi Arabia. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Elevated serum urate is a potential factor in reduction of total bilirubin: a Mendelian randomization study

    Science.gov (United States)

    Zhang, Hui; Liu, Jing; Dong, Zheng; Ding, Yue; Qian, Qiaoxia; Zhou, Jingru; Ma, Yanyun; Mei, Zhendong; Chen, Xiangxiang; Li, Yuan; Yuan, Ziyu; Zhang, Juan; Yang, Yajun; Chen, Xingdong; Jin, Li; Zou, Hejian; Wang, Xiaofeng; Wang, Jiucun

    2017-01-01

    Aim A Mendelian randomization study (MRS) can be linked to a “natural” randomized controlled trial in order to avoid potential bias of observational epidemiology. We aimed to study the possible association between serum urate (SU) and total bilirubin (TBIL) using MRS. Materials and Methods An observational epidemiological study using ordinary least squares (OLS) regression and MRS using two-stage least square (TLS) regression was conducted to assess the effect of SU on TBIL. The comparison between the OLS regression and the TLS regression was analyzed by the Durbin-Hausman test. If the p value is significant, it suggests that the OLS regression cannot evaluate the relationship between exposure and outcome, and the TLS regression is precise; while if the p value is not significant, there would be no significant difference between the two regressions. Results A total of 3,753 subjects were analyzed. In OLS regression, there was no significant association between SU and TBIL in all subjects and subgroup analysis (all p > 0.05). However, MRS revealed a negative correlation between SU and TBIL after adjustment for confounders (beta = –0.021, p = 0.010). Further analysis was conducted in different SU subgroups, and results show that elevated SU was associated with a significant reduction in TBIL after adjustment for hyperuricemic subjects (beta = –0.053, p = 0.027). In addition, the results using the Durbin-Hausman test further confirmed a negative effect of SU on TBIL (p = 0.002 and 0.010, respectively). Conclusions This research shows for the first time that elevated SU was a potential causal factor in the reduction of TBIL and it provides strong evidence to resolve the controversial association between SU and TBIL. PMID:29262606

  5. Association of Metronidazole with Cancer: A Potential Risk Factor or Inconsistent Deductions?

    Science.gov (United States)

    Adil, Muhammad; Iqbal, Waheed; Adnan, Fazal; Wazir, Shabnam; Khan, Imran; Khayam, Mohammad Umar; Kamal, Mohammad Amjad; Ahmad, Shafiq; Ahmad, Jawad; Khan, Ishaq N

    2018-03-29

    Metronidazole is a synthetic derivative of nitroimidazole that has been widely used for the treatment of several bacterial and protozoal parasitic infections including trichomoniasis, amoebiasis, giardiasis, liver abscess, acute ulcerative gingivitis, syphilis and tropical phagedena. In addition to its toxicity in the gastrointestinal tract and central/peripheral nervous system, metronidazole has been reported to cause mucosal imbalance by affecting the expression of mucin (Muc2 gene), which is responsible to form an insoluble mucous barrier that protects the gut lumen from microbial colonization. Since metronidazole is a nitro-group containing compound and used significantly for therapeutic purposes, scientists evaluated its carcinogenicity in different preclinical in-vitro and in-vivo studies. In addition to the preclinical in-vitro validation of DNA damage, metronidazole has been reported to induce cancer in the variety of animal models including lung cancer, malignant lymphomas, breast cancer, hepatocellular carcinoma, pituitary tumors, testicular neoplasms and uterine cancer. Several retrospective cohort studies have reported metronidazole as a potential risk factor for lung cancer (n = 771), cervical cancer (n = 2500), breast cancer (n = 2), cholangiocarcinoma (n = 1), and neuroblastoma (n = 28). So far, all the reported data have confirmed metronidazole carcinogenicity in animals; however, it is still controversial in humans. Based on previous observations, the oxidative metabolites from metronidazole metabolism are shown to have more carcinogenic effects than the parent drug itself. Since ~40% of drug metabolism is reliant on cytochromes, the inter-patient' differences in metronidazole metabolism potentially indicate the individual susceptibility to developing cancer. Due to these potent carcinogenic behaviors, use of metronidazole for animals treatment and its uses in animal food products are barred in the USA and European countries; however, its clinical

  6. Increased metastatic potential of tumor cells in von Willebrand factor-deficient mice.

    Science.gov (United States)

    Terraube, V; Pendu, R; Baruch, D; Gebbink, M F B G; Meyer, D; Lenting, P J; Denis, C V

    2006-03-01

    The key role played by von Willebrand factor (VWF) in platelet adhesion suggests a potential implication in various pathologies, where this process is involved. In cancer metastasis development, tumor cells interact with platelets and the vessel wall to extravasate from the circulation. As a potential mediator of platelet-tumor cell interactions, VWF could influence this early step of tumor spread and therefore play a role in cancer metastasis. To investigate whether VWF is involved in metastasis development. In a first step, we characterized the interaction between murine melanoma cells B16-BL6 and VWF in vitro. In a second step, an experimental metastasis model was used to compare the formation of pulmonary metastatic foci in C57BL/6 wild-type and VWF-null mice following the injection of B16-BL6 cells or Lewis lung carcinoma cells. In vitro adhesion assays revealed that VWF is able to promote a dose-dependent adhesion of B16-BL6 cells via its Arg-Gly-Asp (RGD) sequence. In the experimental metastasis model, we found a significant increase in the number of pulmonary metastatic foci in VWF-null mice compared with the wild-type mice, a phenotype that could be corrected by restoring VWF plasma levels. We also showed that increased survival of the tumor cells in the lungs during the first 24 h in the absence of VWF was the cause of this increased metastasis. These findings suggest that VWF plays a protective role against tumor cell dissemination in vivo. Underlying mechanisms remain to be investigated.

  7. Sirtuin 1 (SIRT1 activation mediates sildenafil induced delayed cardioprotection against ischemia-reperfusion injury in mice.

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    Mona Shalwala

    Full Text Available BACKGROUND: It has been well documented that phosphodiesterase-5 inhibitor, sildenafil (SIL protects against myocardial ischemia/reperfusion (I-R injury. SIRT1 is part of the class III Sirtuin family of histone deacetylases that deacetylates proteins involved in cellular stress response including those related to I-R injury. OBJECTIVE/HYPOTHESIS: We tested the hypothesis that SIL-induced cardioprotection may be mediated through activation of SIRT1. METHODS: Adult male ICR mice were treated with SIL (0.7 mg/kg, i.p., Resveratrol (RSV, 5 mg/kg, a putative activator of SIRT1 used as the positive control, or saline (0.2 mL. The hearts were harvested 24 hours later and homogenized for SIRT1 activity analysis. RESULTS: Both SIL- and RSV-treated mice had increased cardiac SIRT1 activity (P<0.001 as compared to the saline-treated controls 24 hours after drug treatment. In isolated ventricular cardiomyocytes, pretreatment with SIL (1 µM or RSV (1 µM for one hour in vitro also upregulated SIRT1 activity (P<0.05. We further examined the causative relationship between SIRT1 activation and SIL-induced late cardioprotection. Pretreatment with SIL (or RSV 24 hours prior to 30 min ischemia and 24 hours of reperfusion significantly reduced infarct size, which was associated with a significant increase in SIRT1 activity (P<0.05. Moreover, sirtinol (a SIRT1 inhibitor, 5 mg/kg, i.p. given 30 min before I-R blunted the infarct-limiting effect of SIL and RSV (P<0.001. CONCLUSION: Our study shows that activation of SIRT1 following SIL treatment plays an essential role in mediating the SIL-induced cardioprotection against I-R injury. This newly identified SIRT1-activating property of SIL may have enormous therapeutic implications.

  8. Cardioprotective Action of Ginkgo biloba Extract against Sustained β-Adrenergic Stimulation Occurs via Activation of M2/NO Pathway

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    Thássio R. R. Mesquita

    2017-05-01

    Full Text Available Ginkgo biloba is the most popular phytotherapic agent used worldwide for treatment of several human disorders. However, the mechanisms involved in the protective actions of Ginkgo biloba on cardiovascular diseases remain poorly elucidated. Taking into account recent studies showing beneficial actions of cholinergic signaling in the heart and the cholinergic hypothesis of Ginkgo biloba-mediated neuroprotection, we aimed to investigate whether Ginkgo biloba extract (GBE promotes cardioprotection via activation of cholinergic signaling in a model of isoproterenol-induced cardiac hypertrophy. Here, we show that GBE treatment (100 mg/kg/day for 8 days, v.o. reestablished the autonomic imbalance and baroreflex dysfunction caused by chronic β-adrenergic receptor stimulation (β-AR, 4.5 mg/kg/day for 8 days, i.p.. Moreover, GBE prevented the upregulation of muscarinic receptors (M2 and downregulation of β1-AR in isoproterenol treated-hearts. Additionally, we demonstrated that GBE prevents the impaired endothelial nitric oxide synthase activity in the heart. GBE also prevented the pathological cardiac remodeling, electrocardiographic changes and impaired left ventricular contractility that are typical of cardiac hypertrophy. To further investigate the mechanisms involved in GBE cardioprotection in vivo, we performed in vitro studies. By using neonatal cardiomyocyte culture we demonstrated that the antihypertrophic action of GBE was fully abolished by muscarinic receptor antagonist or NOS inhibition. Altogether, our data support the notion that antihypertrophic effect of GBE occurs via activation of M2/NO pathway uncovering a new mechanism involved in the cardioprotective action of Ginkgo biloba.

  9. Acute administration of n-3 rich triglyceride emulsions provides cardioprotection in murine models after ischemia-reperfusion.

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    Hylde Zirpoli

    Full Text Available Dietary n-3 fatty acids (FAs may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD, and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT. In the LAD model, mice treated with n-3 TG emulsion (1.5 g/kg body weight, immediately after ischemia and 1 h later during reperfusion, significantly reduced infarct size and maintained cardiac function (p<0.05. In the LT model, administration of n-3 TG emulsion (300 mg TG/100 ml during reperfusion significantly improved functional recovery (p<0.05. In both models, lactate dehydrogenase (LDH levels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (p<0.05. Acute n-3 TG emulsion treatment also increased Bcl-2 protein level and reduced an autophagy marker, Beclin-1 (p<0.05. Additionally, cardioprotection by n-3 TG emulsion was linked to changes in PPARγ protein expression (p<0.05. Rosiglitazone and p-AKT inhibitor counteracted the positive effect of n-3 TG; GSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction.

  10. Exercise training prevents the attenuation of anesthetic pre-conditioning-mediated cardioprotection in diet-induced obese rats.

    Science.gov (United States)

    Li, L; Meng, F; Li, N; Zhang, L; Wang, J; Wang, H; Li, D; Zhang, X; Dong, P; Chen, Y

    2015-01-01

    Obesity abolishes anesthetic pre-conditioning-induced cardioprotection due to impaired reactive oxygen species (ROS)-mediated adenosine monophosphate-activated protein kinase (AMPK) pathway, a consequence of increased basal myocardial oxidative stress. Exercise training has been shown to attenuate obesity-related oxidative stress. This study tests whether exercise training could normalize ROS-mediated AMPK pathway and prevent the attenuation of anesthetic pre-conditioning-induced cardioprotection in obesity. Male Sprague-Dawley rats were divided into lean rats fed with control diet and obese rats fed with high-fat diet. After 4 weeks of feeding, lean and obese rats were assigned to sedentary conditions or treadmill exercise for 8 weeks. There was no difference in infarct size between lean sedentary and obese sedentary rats after 25 min of myocardial ischemia followed by 120 min reperfusion. In lean rats, sevoflurane equally reduced infarct size in lean sedentary and lean exercise-trained rats. Molecular studies revealed that AMPK activity, endothelial nitric oxide synthase, and superoxide production measured at the end of ischemia in lean rats were increased in response to sevoflurane. In obese rats, sevoflurane increased the above molecular parameters and reduced infarct size in obese exercise-trained rats but not in obese sedentary rats. Additional study showed that obese exercise-trained rats had decreased basal oxidative stress than obese sedentary rats. The results indicate that exercise training can prevent the attenuation of anesthetic cardioprotection in obesity. Preventing the attenuation of this strategy may be associated with reduced basal oxidative stress and normalized ROS-mediated AMPK pathway, but the causal relationship remains to be determined. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Investigation of potential factors affecting the measurement of dew point temperature in oil-soaked transformers

    Science.gov (United States)

    Kraus, Adam H.

    Moisture within a transformer's insulation system has been proven to degrade its dielectric strength. When installing a transformer in situ, one method used to calculate the moisture content of the transformer insulation is to measure the dew point temperature of the internal gas volume of the transformer tank. There are two instruments commercially available that are designed for dew point temperature measurement: the Alnor Model 7000 Dewpointer and the Vaisala DRYCAPRTM Hand-Held Dewpoint Meter DM70. Although these instruments perform an identical task, the design technology behind each instrument is vastly different. When the Alnor Dewpointer and Vaisala DM70 instruments are used to measure the dew point of the internal gas volume simultaneously from a pressurized transformer, their differences in dew point measurement have been observed to vary as much as 30 °F. There is minimal scientific research available that focuses on the process of measuring dew point of a gas inside a pressurized transformer, let alone this observed phenomenon. The primary objective of this work was to determine what effect certain factors potentially have on dew point measurements of a transformer's internal gas volume, in hopes of understanding the root cause of this phenomenon. Three factors that were studied include (1) human error, (2) the use of calibrated and out-of-calibration instruments, and (3) the presence of oil vapor gases in the dry air sample, and their subsequent effects on the Q-value of the sampled gas. After completing this portion of testing, none of the selected variables proved to be a direct cause of the observed discrepancies between the two instruments. The secondary objective was to validate the accuracy of each instrument as compared to its respective published range by testing against a known dew point temperature produced by a humidity generator. In a select operating range of -22 °F to -4 °F, both instruments were found to be accurate and within their

  12. Cardioprotective Effects of LCZ696 (Sacubitril/Valsartan After Experimental Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Masanobu Ishii, MD

    2017-12-01

    Full Text Available LCZ696 (sacubitril/valsartan can lower the risk of cardiovascular events in chronic heart failure. However, it is unclear whether LCZ696 can improve prognosis in patients with acute myocardial infarction (MI. The present study shows that LCZ696 can prevent cardiac rupture after MI, probably due to the suppression of pro-inflammatory cytokines, matrix metalloproteinase-9 activity and aldosterone production, and enhancement of natriuretic peptides in mice. These findings suggest the mechanistic insight of cardioprotective effects of LCZ696 against acute MI, resulting in the belief that LCZ696 might be useful clinically to improve survival after acute MI.

  13. Cardioprotection of Electroacupuncture for Enhanced Recovery after Surgery on Patients Undergoing Heart Valve Replacement with Cardiopulmonary Bypass: A Randomized Control Clinical Trial

    Directory of Open Access Journals (Sweden)

    Fangxiang Zhang

    2017-01-01

    Full Text Available We attempted to investigate cardioprotection of electroacupuncture (EA for enhanced recovery after surgery on patients undergoing heart valve replacement with cardiopulmonary bypass. Forty-four patients with acquired heart valve replacement were randomly allocated to the EA group or the control group. Patients in the EA group received EA stimulus at bilateral Neiguan (PC6, Ximen (PC4, Shenting (GV24, and Baihui (GV20 acupoints twenty minutes before anesthesia induction to the end of surgery. The primary end point was cardioprotection effect of electroacupuncture postoperatively and the secondary endpoints were quality of recovery and cognitive functioning postoperatively. The present study demonstrated that electroacupuncture reduced the occurrence of complications and played a role of cardioprotective effect on patients after heart valve replacement surgery with cardiopulmonary bypass, and it benefits patients more comfortable and contributes to recovery after surgery. This trial is registered with ChiCTR-IOC-16009123.

  14. Factors which deter potential science/math teachers from teaching; changes necessary to ameliorate their concerns

    Science.gov (United States)

    Evans, Robert H.

    In light of the perceived national need for more science and math teachers, this study was conceived to:1.Identify teaching oriented students among freshmen at a mid-western engineering school, who have chosen NOT to become teachers;2.Find out what reasons these potential science and math teachers have for deciding not to pursue teaching careers;3.Determine what amelioration of these problems would be necessary for them to no longer be factors which would inhibit students from becoming teachers.Of a random sample of 110 students drawn from a freshman class, 98 participated fully in the study. Each participant took Holland's Self-Directed Search to determine teaching orientation and author-constructed instruments to assess their concerns about teaching.Results showed teaching oriented students avoided teaching due to low starting salaries, lack of job security, low maximum salaries, not wanting to do the work teacher's do, poor job availability and discouragement by family and friends. Starting salaries of 21,693 and salaries of 32,600 for a teacher with a B.A. and 10 years experience were among the changes deemed necessary to make teaching attractive.

  15. Chondrogenic potential of human mesenchymal stem cells and expression of Slug transcription factor.

    Science.gov (United States)

    Brini, Anna T; Niada, Stefania; Lambertini, Elisabetta; Torreggiani, Elena; Arrigoni, Elena; Lisignoli, Gina; Piva, Roberta

    2015-06-01

    The scientific literature rarely reports experimental failures or inconsistent outcomes in the induction of cell differentiation; however, researchers commonly experience poor or unsuccessful responses to differentiating agents when culturing stem cells. One way of investigating the underlying reasons for such responses is to look at the basal expression levels of specific genes in multipotent stem cells before the induction of differentiation. In addition to shedding light on the complex properties of stem cells and the molecular modulation of differentiation pathways, this strategy can also lead to the development of important time- and money-saving tools that aid the efficient selection of cellular specimens--in this case, stem cells that are more prone to differentiate towards specific lineages and are therefore more suitable for cell-based therapeutic protocols in regenerative medicine. To address this latter aspect, this study focused on understanding the reasons why some human mesenchymal stem cell (hMSC) samples are less efficient at differentiating towards chondrogenesis. This study shows that analysis of the basal expression levels of Slug, a negative regulator of chondrogenesis in hMSC, provides a rapid and simple tool for distinguishing stem cell samples with the potential to form a cartilage-like matrix, and that are therefore suitable for cartilage tissue engineering. It is shown that high basal levels of Slug prevent the chondrogenic differentiation of hMSCs, even in the presence of transforming growth factor-β and elevated levels of Sox9. Copyright © 2013 John Wiley & Sons, Ltd.

  16. [Investigation of potential toxic factors for fleece-flower root: from perspective of processing methods evolution].

    Science.gov (United States)

    Cui, He-Rong; Bai, Zhao-Fang; Song, Hai-Bo; Jia, Tian-Zhu; Wang, Jia-Bo; Xiao, Xiao-He

    2016-01-01

    In recent years, the rapid growth of reports on fleece-flower root-caused liver damages has drawn wide attention of both at home and abroad, however, there were rare literature on toxicology of fleece-flower root in ancient Chinese medicine. But why there are so many reports on toxicology of fleece-flower root now compared with the ancient literature? As a typical tonic medicine, the clinical utility of fleece-flower root was largely limited by its standardization and reliability of processing methods in ancient Chinese medicine. The ancient processing methods of fleece-flower root emphasized nine times of steaming and nine times of drying, while the modern processes have been simplified into one time of steaming. Whether the differences between ancient and modern processing methods are the potential cause of the increased events of fleece-flower root-caused liver damages. We will make deep analysis and provide new clues and perspectives for the research on its toxicity. This article, therefore, would discuss the affecting factors and key problems in toxicity attenuation of fleece-flower root on the basis of sorting out the processing methods of fleece-flower root in ancient medical books and modern standards, in order to provide the reference for establishing specification for toxicity attenuation of fleece-flower root. Copyright© by the Chinese Pharmaceutical Association.

  17. Outcome of Venom Bradykinin Potentiating Factor on Renin Angiotensin System in Irradiated Rats

    International Nuclear Information System (INIS)

    Ashry, O.; Farouk, H.; Moustafa, M.; Abu Sinn, G.; Abd ElBaset, A.

    2011-01-01

    Scorpion Venom contains a strong bradykinin potentiating factor (BPF) exhibiting angiotensin converting enzyme inhibition (ACEI). Irradiation and stimulation of renin-angiotensin system (RAS) induce oxidative stress. Interruption of the RAS by an ACEI or angiotensin II receptor blocker (ARB) losartan (LOS) and/or gamma-rays (4 Gy) were evaluated. Rats received 6 doses of BPF (1μg/g body wt) or of LOS (5 μg/g body wt). Treatment with BPF induced significant elevation in the level of potassium (K) and significant drop in the level of sodium (Na) and uric acid. Treatment with LOS significantly depressed the level of Na and uric acid compared to control. Irradiation discerned a significant elevation in malondialdehyde (MDA), advanced oxidative protein product (AOPP), aldosterone, Na, urea and creatinine, and a significant drop in the haematological values, glutathione (GSH), calcium (Ca) and uric acid. A significant decrease in MDA, aldosterone, urea, creatinine and uric acid compared to irradiated group was observed in irradiated treated groups. Irradiated animals treated with LOS showed a significant decrease in Na and chloride (Cl) compared to the irradiated group. Considerable amelioration of radiation-induced depression in haematopoiesis, improvement of oxidative stress and kidney function by BPF as ACEI or LOS as ARB are detected. Results add further identification to the properties of BPF

  18. Two factors important to the criticality potential of spent fuel in geologic repositories

    International Nuclear Information System (INIS)

    Gore, B.F.; Jenquin, U.P.

    1981-02-01

    Two factors important to the criticality potential of spent fuel in geologic repositories are: the residual fissile content of the fuel, and the extent to which geochemical processes might somehow separate and accumulate plutonium from other spent fuel materials. This paper presents the results of two calculational surveys defining conditions required for criticality. In the first, homogeneous spherical mixtures of spent fuel actinide oxides and water with water reflection are analyzed. Graphs of minimum critical mass vs duration of in-reactor exposure are presented. Parametric variations from a base case are explored, including the effects of initial enrichment, post exposure radioactive decay and addition of rock materials to the mixture. In the second study, homogeneous spherical mixtures devoid of water, containing plutonium and a neutronically optimized rock material, with a thick rock neutron reflector are analyzed. Graphs of Pu critical mass are presented as a function of concentration over the range from 2 to 100 g Pu/l. Parametric variations from a base case are explored, including effects of rock composition, 240 Pu content and uranium contamination of the plutonium

  19. Platelet Vascular Endothelial Growth Factor is a Potential Mediator of Transfusion-Related Acute Lung Injury.

    Science.gov (United States)

    Maloney, James P; Ambruso, Daniel R; Voelkel, Norbert F; Silliman, Christopher C

    The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors. Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak. There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, pproducts.

  20. Prevalence of and potential influencing factors for alcohol dependence in Europe.

    Science.gov (United States)

    Rehm, Jürgen; Anderson, Peter; Barry, Joe; Dimitrov, Plamen; Elekes, Zsuzsanna; Feijão, Fernanda; Frick, Ulrich; Gual, Antoni; Gmel, Gerrit; Kraus, Ludwig; Marmet, Simon; Raninen, Jonas; Rehm, Maximilien X; Scafato, Emanuele; Shield, Kevin D; Trapencieris, Marcis; Gmel, Gerhard

    2015-01-01

    Alcohol use disorders (AUDs), and alcohol dependence (AD) in particular, are prevalent and associated with a large burden of disability and mortality. The aim of this study was to estimate prevalence of AD in the European Union (EU), Iceland, Norway, and Switzerland for the year 2010, and to investigate potential influencing factors. The 1-year prevalence of AD in the EU was estimated at 3.4% among people 18-64 years of age in Europe (women 1.7%, men 5.2%), resulting in close to 11 million affected people. Taking into account all people of all ages, AD, abuse and harmful use resulted in an estimate of 23 million affected people. Prevalence of AD varied widely between European countries, and was significantly impacted by drinking cultures and social norms. Correlations with level of drinking and other drinking variables and with major known outcomes of heavy drinking, such as liver cirrhosis or injury, were moderate. These results suggest a need to rethink the definition of AUDs.

  1. Examining factors associated with elevated Lie Scale responding on the Child Abuse Potential Inventory.

    Science.gov (United States)

    Costello, Amanda H; Shook, Natalie J; Wallace, Nancy M; McNeil, Cheryl B

    2018-02-01

    Child maltreatment remains a serious public health issue in the United States. Therefore, it is important to engage in quality control of the assessment, prevention, and treatment services for families affected by maltreatment. Parenting capacity assessments (PCAs) are typically an integral part of service delivery for families affected by maltreatment and can carry serious consequences for the referred parent. The Child Abuse Potential Inventory (CAPI) is a measure that is widely used in PCAs; however, socially desirable responding on the CAPI can serve to invalidate the important information derived from this assessment, as well as lead to negative impressions of the parent. Using data collected via multiple methods (including a non-face valid behavioral measure, intelligence screening, and self-report) from a predominantly at-risk sample of parents, the aim of this study was to better understand factors that may predict socially desirable responding on the CAPI. Results indicated that lower parental intelligence, a "positivity bias" (i.e., the tendency to learn and attend to positive over negative information during the non-face valid behavioral task), and lower reported depressive symptoms were associated with higher socially desirable responding. These findings suggest that assessors should thoughtfully consider the possibility that invalid CAPI scores may be more related to low intelligence and a positivity bias than to psychopathy and manipulation (e.g., purposefully trying to present oneself in a positive light to gain favor in a PCA). Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Cardioprotective effect of breviscapine: inhibition of apoptosis in H9c2 cardiomyocytes via the PI3K/Akt/eNOS pathway following simulated ischemia/reperfusion injury.

    Science.gov (United States)

    Wang, Jun; Ji, Shu-Yun; Liu, Si-Zhu; Jing, Rui; Lou, Wei-Juan

    2015-09-01

    Breviscapine (BE) is a standardized Chinese herbal medicine extracted from Erigeron breviscapus (Vant.) Hand.-Mazz. It has been widely used to treat cardiovascular and cerebrovascular diseases. However, there are no reports on the protective effects and underlying molecular mechanisms of BE action on myocardial ischemia/reperfusion (MI/R)-induced cardiomyocyte apoptosis. In the present study, we aimed to confirm the cardioprotective effect of BE from MI/R injury in vivo, and investigate the potential molecular mechanisms against simulated ischemia/reperfusion (SI/R)-induced cardiomyocyte apoptosis in vitro. The rat model of MI/R injury was induced by 30 min of transient vessel occlusion followed by 3 h of reperfusion. BE significantly reduced the myocardium infarct size and production of cardiac troponin (cTnl) in serum. In an in vitro experiment, H9c2 cardiomyocytes were incubated with vehicle or ischemic buffer during hypoxia; then, they were reoxygenated with or without BE. BE markedly improved the cell viability and decreased lactate dehydrogenase (LDH) release. We confirmed the anti-apoptotic effect of BE with the Hoechst 33258 staining assay, and this effect was associated with an increase in Bcl-2 and a decrease in active caspase-3 expression. Western blot analysis also showed that BE increased the phosphorylation of Akt and eNOS in H9c2 cells, and the protective effects of BE were partially inhibited by the phosphatidylinositol 3'-kinase (PI3K) specific inhibitor LY294002. Our results suggested that BE could provide significant cardioprotection against MI/R injury, and the potential mechanisms might involve suppression of cardiomyocyte apoptosis through activating the PI3K/Akt/eNOS signaling pathway.

  3. Serotonin potentiates transforming growth factor-beta3 induced biomechanical remodeling in avian embryonic atrioventricular valves.

    Directory of Open Access Journals (Sweden)

    Philip R Buskohl

    Full Text Available Embryonic heart valve primordia (cushions maintain unidirectional blood flow during development despite an increasingly demanding mechanical environment. Recent studies demonstrate that atrioventricular (AV cushions stiffen over gestation, but the molecular mechanisms of this process are unknown. Transforming growth factor-beta (TGFβ and serotonin (5-HT signaling modulate tissue biomechanics of postnatal valves, but less is known of their role in the biomechanical remodeling of embryonic valves. In this study, we demonstrate that exogenous TGFβ3 increases AV cushion biomechanical stiffness and residual stress, but paradoxically reduces matrix compaction. We then show that TGFβ3 induces contractile gene expression (RhoA, aSMA and extracellular matrix expression (col1α2 in cushion mesenchyme, while simultaneously stimulating a two-fold increase in proliferation. Local compaction increased due to an elevated contractile phenotype, but global compaction appeared reduced due to proliferation and ECM synthesis. Blockade of TGFβ type I receptors via SB431542 inhibited the TGFβ3 effects. We next showed that exogenous 5-HT does not influence cushion stiffness by itself, but synergistically increases cushion stiffness with TGFβ3 co-treatment. 5-HT increased TGFβ3 gene expression and also potentiated TGFβ3 induced gene expression in a dose-dependent manner. Blockade of the 5HT2b receptor, but not 5-HT2a receptor or serotonin transporter (SERT, resulted in complete cessation of TGFβ3 induced mechanical strengthening. Finally, systemic 5-HT administration in ovo induced cushion remodeling related defects, including thinned/atretic AV valves, ventricular septal defects, and outflow rotation defects. Elevated 5-HT in ovo resulted in elevated remodeling gene expression and increased TGFβ signaling activity, supporting our ex-vivo findings. Collectively, these results highlight TGFβ/5-HT signaling as a potent mechanism for control of biomechanical

  4. Economic factors influencing potential use of cellulosic crop residues for electricity generation

    International Nuclear Information System (INIS)

    Maung, Thein A.; McCarl, Bruce A.

    2013-01-01

    This study examines cellulosic crop residues for biopower production in the context of (greenhouse gas) GHG emission mitigation. We employ sector modeling to simulate future market potential for biopower production from crop residues. Our findings suggest that in order for crop residues to have any role in electricity generation either the carbon or (carbon dioxide) CO 2 equivalent GHG price must rise to about 15 dollars per ton or the price of coal has to increase to about 43 dollars per ton. We find that crop residues with higher heat content have greater opportunities in biopower production than the residues with lower heat content. In addition, our evidence shows that improvements in crop yields do not have much impact on biopower production. However, the energy recovery efficiency does have significant positive impact but only if the CO 2 equivalent price rises substantially. Moreover, our analysis indicates the desirability of cofiring biomass as opposed to 100% replacement because this reduces transportation cost and increases the efficiency of heat recovery. In terms of policy implications, imposing carbon emission pricing could be an important step in inducing electric power producers to include biomass feedstocks in their fuel-mix power generation portfolios and achieve GHG emission reductions. - Highlights: • Crop residues with higher heat content have greater market opportunities. • Improvement in crop and residue yields does not have much impact on biopower production. • Advancement in biopower production technology does not encourage more use of crop residues. • The main factor that induces biopower production is an increase in future carbon prices

  5. Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease.

    Directory of Open Access Journals (Sweden)

    Juan A Rodriguez-Feo

    Full Text Available Caveolin-1 (Cav-1 is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice. This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target

  6. Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection.

    Science.gov (United States)

    Slavcev, Antonij; Lácha, Jiri; Honsová, Eva; Sajdlová, Helena; Lodererová, Alena; Vitko, Stefan; Skibová, Jelena; Striz, Ilja

    2005-06-01

    Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.

  7. The associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    Romani, Antonello A; Soliani, Paolo; Desenzani, Silvia; Borghetti, Angelo F; Crafa, Pellegrino

    2006-01-01

    Maspin, a member of the serpin family, is a suppressor of tumor growth, an inhibitor of angiogenesis and an inducer of apoptosis. Maspin induces apoptosis by increasing Bax, a member of the Bcl-2 family of apoptosis-regulating proteins. In this exploratory study, we investigated the associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma (IHCCA). Twenty-two paraffin-embedded samples were analyzed by immunohistochemical methods using Maspin, Bax and CD34 antibodies. Maspin was scored semiquantitatively (HSCORE). Apoptosis was assessed using an antibody against cleaved caspase-3. The strong relationship observed between the expression of Maspin and Bax, indicates that Bax is likely to be the key effector of Maspin-mediated induction of apoptosis as indicated by the activation of cleaved caspase-3. We categorized Maspin HSCORE by calculating the optimal cutpoint. A Maspin HSCORE above the cutpoint was inversely related with tumor dimension, depth of tumor and vascular invasion. Uni/multivariate analysis suggests that a Maspin HSCORE below the cutpoint significantly worsens the patients' prognosis. Tumors with Maspin HSCORE below the cutpoint had a shorter survival (11+/-5 months) than did patients with Maspin HSCORE above the cutpoint (27+/-4 months), whereas Kaplan-Meier analysis and logrank test showed no significant difference in overall survival between the patients. The associated expression of Maspin and Bax might delay tumor progression in IHCCA. Maspin above the cutpoint might counteract tumor development by increasing cell apoptosis, and by decreasing tumor mass and cell invasion. The combined expression of Maspin and Bax appears to influence the susceptibility of tumor cholangiocytes to apoptosis and thus may be involved in delaying IHCCA progression

  8. Urinary Nerve Growth Factor as a Potential Biomarker of Treatment Outcomes in Overactive Bladder Patients

    Directory of Open Access Journals (Sweden)

    Yoon Seok Suh

    2017-12-01

    Full Text Available Purpose The aim of this study was to investigate urinary nerve growth factor (NGF as a biomarker of treatment efficacy and recurrence in overactive bladder (OAB patients. Methods We enrolled 189 OAB subjects who visited our outpatient clinic from February 2010 to February 2015. All subjects with OAB received antimuscarinic treatment. A 3-day voiding diary and questionnaire were collected from each patient. Urinary levels of NGF were evaluated at baseline, the beginning of antimuscarinic treatment, and the end of antimuscarinic treatment. Urinary NGF was normalized to urine creatinine (Cr. Between-group comparisons of baseline characteristics were made using the Mann-Whitney U-test. Multivariate logistic regression analyses were used to predict responses to anticholinergic treatment and recurrence. The Wilcoxon signed-rank test with the Bonferroni correction was used for intragroup comparisons. A receiver operating characteristic curve was used to analyze the utility of this biomarker. Results Urinary levels of NGF/Cr tended to decrease in patients who responded to treatment (n=62, but this was not significant (P=0.260. Urinary NGF levels were higher at baseline in patients who did not experience recurrence than in those who did (P=0.047. In those who did not experience recurrence (n=29, urinary NGF/Cr decreased at the end of treatment compared to baseline, and this reduction was maintained at 12 weeks after the end of treatment (P<0.05. Conclusions Urinary NGF is a potential biomarker for predicting the outcome of antimuscarinic treatment in OAB patients. This may provide useful information when deciding to stop antimuscarinic treatment in responders.

  9. Transcription factor NF-kB as a potential biomarker for oxidative stress

    NARCIS (Netherlands)

    Berg, R. van den; Haenen, G.R.M.M.; Berg, H. van den; Bast, A.

    2001-01-01

    There is increasing interest in the involvement of transcription factors, such as of the transcription factor NF-κB (nuclear factor-κB), in the pathogenesis of various diseases. NF-κB is involved in the control of the transcription of a variety of cellular genes that regulate the inflammatory

  10. Identifying factors for optimal development of health-related websites: a delphi study among experts and potential future users.

    Science.gov (United States)

    Schneider, Francine; van Osch, Liesbeth; de Vries, Hein

    2012-02-14

    The Internet has become a popular medium for offering tailored and targeted health promotion programs to the general public. However, suboptimal levels of program use in the target population limit the public health impact of these programs. Optimizing program development is considered as one of the main processes to increase usage rates. To distinguish factors potentially related to optimal development of health-related websites by involving both experts and potential users. By considering and incorporating the opinions of experts and potential users in the development process, involvement in the program is expected to increase, consequently resulting in increased appreciation, lower levels of attrition, and higher levels of sustained use. We conducted a systematic three-round Delphi study through the Internet. Both national and international experts (from the fields of health promotion, health psychology, e-communication, and technical Web design) and potential users were invited via email to participate. During this study an extensive list of factors potentially related to optimal development of health-related websites was identified, by focusing on factors related to layout, general and risk information provision, questionnaire use, additional services, and ease of use. Furthermore, we assessed the extent to which experts and potential users agreed on the importance of these factors. Differences as well as similarities among experts and potentials users were deduced. In total, 20 of 62 contacted experts participated in the first round (32% response rate); 60 of 200 contacted experts (30% response rate) and 210 potential users (95% response rate) completed the second-round questionnaire, and 32 of 60 contacted experts completed the third round (53% response rate). Results revealed important factors consented upon by experts and potential users (eg, ease of use, clear structure, and detailed health information provision), as well as differences regarding

  11. Deuteron form factors and e-d polarization observables for the Paris and Graz-II potentials

    International Nuclear Information System (INIS)

    Schwarz, K.; Plessas, W.; Mathelitsch, L.

    1983-01-01

    Elastic e-d scattering is studied employing the meson-theoretical Paris potential and the non-local separable Graz-II potential. Electric and magnetic form factors are calculated with inclusion of meson-exchange currents and compared to existing experimental data. Deuteron vector and tensor polarizations are predicted and discussed in relation to the deuteron wave functions of the potential models considered. Thereby the off-shell behaviour of the Graz-II interaction is found to be close to that one of the Paris potential over the most important domain of low and moderate off-shell moments. (Author)

  12. Acute administration of n-3 rich triglyceride emulsions provides cardioprotection in murine models after ischemia-reperfusion.

    Science.gov (United States)

    Zirpoli, Hylde; Abdillahi, Mariane; Quadri, Nosirudeen; Ananthakrishnan, Radha; Wang, Lingjie; Rosario, Rosa; Zhu, Zhengbin; Deckelbaum, Richard J; Ramasamy, Ravichandran

    2015-01-01

    Dietary n-3 fatty acids (FAs) may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG) emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R) insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD), and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT). In the LAD model, mice treated with n-3 TG emulsion (1.5 g/kg body weight), immediately after ischemia and 1 h later during reperfusion, significantly reduced infarct size and maintained cardiac function (plevels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (plevel and reduced an autophagy marker, Beclin-1 (pGSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction.

  13. The impact of renal protection clinics on prescription of and adherence to cardioprotective drug therapy in chronic kidney disease patients.

    Science.gov (United States)

    Lepeytre, Fanny; Cardinal, Héloise; Fradette, Lorraine; Verhave, Jacobien; Dorais, Marc; LeLorier, Jacques; Pichette, Vincent; Madore, François

    2017-06-01

    Background: The aim of this study was to assess the impact of follow-up in renal protection clinics on the prescription of and adherence to cardioprotective drugs in patients with chronic kidney disease (CKD). Methods: We studied stage 4 and 5 CKD patients who initiated follow-up in three renal protection clinics. The prescription pattern of antihypertensive agents (AHA) and lipid-lowering agents (LLAs) was measured as the percentage of patients who are prescribed the agents of interest at a given time. Adherence to drug therapy was defined as the percentage of days, during a pre-defined observation period, in which patients have an on-hand supply of their prescribed medications. Results: A total of 259 CKD patients were enrolled and followed for up to 1 year after referral to renal protection clinics. There was a significant increase in the prescription of angiotensin-converting enzyme inhibitors (34-39%), angiotensin II receptor blockers (11-14%), beta-blockers (40-51%), calcium channel blockers (62-74%), diuretics (66-78%) and LLAs (39-47%) during follow-up in the renal protection clinic compared with baseline (P-values protection clinics. Conclusion: Our results suggest that referral and follow-up in a renal protection clinic may increase the prescription of cardioprotective agents in CKD patients, but does not appear to improve adherence to these medications.

  14. Discovery and cardioprotective effects of the first non-Peptide agonists of the G protein-coupled prokineticin receptor-1.

    Directory of Open Access Journals (Sweden)

    Adeline Gasser

    Full Text Available Prokineticins are angiogenic hormones that activate two G protein-coupled receptors: PKR1 and PKR2. PKR1 has emerged as a critical mediator of cardiovascular homeostasis and cardioprotection. Identification of non-peptide PKR1 agonists that contribute to myocardial repair and collateral vessel growth hold promises for treatment of heart diseases. Through a combination of in silico studies, medicinal chemistry, and pharmacological profiling approaches, we designed, synthesized, and characterized the first PKR1 agonists, demonstrating their cardioprotective activity against myocardial infarction (MI in mice. Based on high throughput docking protocol, 250,000 compounds were computationally screened for putative PKR1 agonistic activity, using a homology model, and 10 virtual hits were pharmacologically evaluated. One hit internalizes PKR1, increases calcium release and activates ERK and Akt kinases. Among the 30 derivatives of the hit compound, the most potent derivative, IS20, was confirmed for its selectivity and specificity through genetic gain- and loss-of-function of PKR1. Importantly, IS20 prevented cardiac lesion formation and improved cardiac function after MI in mice, promoting proliferation of cardiac progenitor cells and neovasculogenesis. The preclinical investigation of the first PKR1 agonists provides a novel approach to promote cardiac neovasculogenesis after MI.

  15. Factors Influencing Mean Inner Potentials As Studied Using Electron Holography and Density Functional Theory

    DEFF Research Database (Denmark)

    Pennington, Robert S.

    reflect properties of the specimen. The phase can yield quantitative measurements of nanoscale electric and magnetic potentials. One such electrostatic potential is called the mean inner potential. The mean inner potential is the average electrostatic potential measured between the bulk of a material...... to analyze diffraction effects on the amplitude and the phase. There is relatively good comparison between image simulation and experimental data, but the experimental absorption parameter is found to differ between strongly and weakly diffracting conditions. Density functional theory simulations of the mean...

  16. Correlation between Novel Potential Indoor Risk Factors and Frequency of Doctor's Visit for Respiratory Problem in Taiwan's Tropical Environment

    Directory of Open Access Journals (Sweden)

    Yu-Hao Wang

    2018-01-01

    Full Text Available Background: With a global rising trend in prevalence of allergic diseases, more attention has been paid to investigation of environmental risk factors. Many risk factors have so far been identified. However, novel risk factors specific to Taiwanese environment and lifestyle were still relatively unknown. Objective: To investigate the potential effects of a number of little-known indoor risk factors on the frequency of doctor's visit for respiratory problems in context of Taiwanese environment and lifestyle. Methods: A cross-sectional, population-based study was performed on a 861 participants around Kaohsiung area, Taiwan. Survey investigation was employed to assess the household environment and the frequency of doctor's visit for respiratory problems. Results: Participants who performed “daily cleaning” was shown to have a significantly (p=0.007 higher mean number of doctor's visits in comparison to those who did not. Similar observation was made for participants who periodically took out beddings (p=0.042. Age had a significant positive correlation (linear regression β 0.089 with frequency of respiratory problems. Conclusion: The habit of daily cleaning was implicated as a potential indoor risk factor due to the unique nature of Taiwanese cleaning habit and close contact with cleaning supplies, which could serve as chemical irritants. Bedding takeout was predicted to be an indicator of chronic allergies rather than an actual risk factor. However, both were controversial in their role as potential indoor risk factor, and required further examination.

  17. The Sustainable Office. An exploration of the potential for factor 20 environmental improvement of office accommodation

    OpenAIRE

    Van den Dobbelsteen, A.A.J.F.

    2004-01-01

    Sustainable development is the goal of a balance between economy and the environment, whilst establishing a better spread prosperity across the world. In order to make this possible, the environmental load of our commodities needs to be reduced by a factor of 20. This factor 20 can also be translated to the office market. The PhD research presented in this thesis focussed on finding solutions effectively contributing to factor 20 environmental improvement of office accommodation. In order to ...

  18. Potential effect of some environmental factors on the phage removal during wastewater treatment. Study in vitro

    International Nuclear Information System (INIS)

    Benhyahya, M.; Bohatier, J.; Laveran, H.; Ettayebi, M.; Senaud, J.

    2000-01-01

    Great quantities of enteric viruses and bacteriophages are included in wastewaters. They represent a contamination risk of natural water systems. But this viral burden is greatly reduced in the sewage treatment plants by the combined action of numerous environmental factors. To study water quality, some groups of bacteriophages as E. coli phages and Bacteroides fragilis phages have been proposed as model viruses. On an other hand, somatic and, in particular, F-specific coliphages have several morphological, structural and chemical composition ressemblances with the enteric viruses. Two different bacteriophages (øX-174 and MS2) were used as virus models in this in vitro study to evaluate the viral adsorption on suspended clay particles. Distilled sterile water was used as reactional medium to avoid the possible interactions with the considered substrates, the kaolinite (K) and the montmorillonite (M). Phage behaviour in the water and in the recommended diluent for phages, the saline peptone, was first compared. K and M suspensions were used at 300 mg/l for a contact time of 5, 30 and 60 min. In other series K and M suspensions were prepared at 600, 300 and 100 mg/l then used to determine the phage adsorption capacity in a fixed time 30 min. Results show that the phage titers for all samples were constant in the organic diluent. They were lower in the distilled sterile water and decrease with the time. Distilled water favours most likely the grouping of virions and leads aggregates formation. The adsorption of øX-174 and MS2 onto K or M particles was instantaneous and independent of the duration contact. The clay concentration had a slight significant influence on the phage adsorption rate. Using the same phages we have studied, in a second stage, the potential effect of the dissolved matters in a filtered polluted effluent, that of sunlight radiations and that of the protozoan Tetrahymena pyriformis on the phage removal. No soon significant phage inactivation was

  19. Myostatin and insulin-like growth factor I: potential therapeutic biomarkers for pompe disease.

    Directory of Open Access Journals (Sweden)

    Yin-Hsiu Chien

    Full Text Available OBJECTIVE: Myostatin and insulin-like growth factor 1 (IGF-1 are serum markers for muscle growth and regeneration. However, their value in the clinical monitoring of Pompe disease - a muscle glycogen storage disease - is not known. In order to evaluate their possible utility for disease monitoring, we assessed the levels of these serum markers in Pompe disease patients receiving enzyme replacement therapy (ERT. DESIGN: A case-control study that included 10 patients with Pompe disease and 10 gender- and age-matched non-Pompe disease control subjects was performed in a referral medical center. Average follow-up duration after ERT for Pompe disease patients was 11.7 months (range: 6-23 months. Measurements of serum myostatin, IGF-1, and creatine kinase levels were obtained, and examinations of muscle pathology were undertaken before and after ERT in the patient group. RESULTS: Compared with control subjects, Pompe disease patients prior to undergoing ERT had significantly lower serum IGF-1 levels (98.6 ng/ml vs. 307.9 ng/ml, p = 0.010 and lower myostatin levels that bordered on significance (1.38 ng/ml vs. 3.32 ng/ml, p = 0.075. After ERT, respective myostatin and IGF-1 levels in Pompe disease patients increased significantly by 129% (from 1.38 ng/ml to 3.16 ng/ml, p = 0.047 and 74% (from 98.6 ng/ml to 171.1 ng/ml, p = 0.013; these values fall within age-matched normal ranges. In contrast, myostatin and IGF-1 serum markers did not increase in age-matched controls. Follistatin, a control marker unrelated to muscle, increased in both Pompe disease patients and control subjects. At the same time, the percentage of muscle fibers containing intracytoplasmic vacuoles decreased from 80.0±26.4% to 31.6±45.3%. CONCLUSION: The increase in myostatin and IGF-1 levels in Pompe disease patients may reflect muscle regeneration after ERT. The role of these molecules as potential therapeutic biomarkers in Pompe disease and other neuromuscular

  20. UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes.

    Science.gov (United States)

    Adler, Amanda I; Stevens, Richard J; Neil, Andrew; Stratton, Irene M; Boulton, Andrew J M; Holman, Rury R

    2002-05-01

    To determine the role of hyperglycemia in prospective analyses of peripheral vascular disease (PVD) in type 2 diabetes, taking into account other potential risk factors. Potential risk factors for the development of PVD were examined in 3,834 of 5,102 individuals enrolled in the U.K. Prospective Diabetes Study (UKPDS) without PVD at diagnosis of diabetes, followed for 6 years, and for whom relevant data were available. PVD was defined as two of the following: ankle-arm blood pressure index < 0.8, absence of both dorsalis pedis and posterior tibial pulses to palpation in one or both legs, and intermittent claudication. Logistic regression was used to estimate the association between potential risk factors measured 3-4 months after diagnosis of diabetes and incident PVD. The prevalence of PVD at 3-year intervals to 18 years was determined. Hyperglycemia, assessed as HbA(1c), was associated with an increased risk for incident PVD, independent of other risk factors including age, increased systolic blood pressure, reduced HDL cholesterol, smoking, prior cardiovascular disease, peripheral sensory neuropathy, and retinopathy. Each 1% increase in HbA(1c) was associated with a 28% increased risk of PVD (95% CI 12-46), and each 10-mmHg increase in systolic blood pressure with a 25% increase in risk (95% CI 10-43). Hyperglycemia, as well as smoking, dyslipidemia, and blood pressure are potentially modifiable risk factors for the development of PVD.

  1. MEDIA ENVIRONMENT AS FACTOR OF REALIZATION OF CREATIVE POTENTIAL OF FUTURE TEACHERS` IN THE MOUNTAIN SCHOOLS OF THE UKRAINIAN CARPATHIANS

    Directory of Open Access Journals (Sweden)

    Alla Lebedieva

    2015-04-01

    Full Text Available The article shows up “media environment” as a factor of future teachers` creative potential realization in the mountainous schools of the Ukrainian Carpathians. The problem of using media environment as a factor of future teachers` creative potential in the mountainous schools of the Ukrainian Carpathians and the ways of its optimization is the main point of this research. Highlights ways to modernize social and professional orientation training of students in the creative process of nature is situates in information education and educational environment of high school. We consider the causal link use media environment as a factor of future teachers` creative potential and complexity of the teacher in the mountainous schools of the Ukrainian Carpathians. The basic function of the media environment are extensity, instrumental, communicative, interactive, multimedia. Reveals some aspects of training students to creatively active teaching process we describe subjects with objective possibilities in the formation of professional skills of future teachers` and which directly affect the realization of creative potential – “Ukrainian folk art”, “Basic recitation and rhetoric”, “The basis of pedagogical creativity”. The necessity of creating a full-fledged media environment in higher education is important condition of successful education as an important factor that allows the efficiency of the creative potential of future teachers` in the mountainous schools of the Ukrainian Carpathians.

  2. The Sustainable Office. An exploration of the potential for factor 20 environmental improvement of office accommodation

    NARCIS (Netherlands)

    Van den Dobbelsteen, A.A.J.F.

    2004-01-01

    Sustainable development is the goal of a balance between economy and the environment, whilst establishing a better spread prosperity across the world. In order to make this possible, the environmental load of our commodities needs to be reduced by a factor of 20. This factor 20 can also be

  3. The Insulin-like Growth Factor System in Cancer Prevention: Potential of Dietary intervention Strategies

    NARCIS (Netherlands)

    Voskuil, D.W.; Vrieling, A.; Veer, van 't L.J.; Kampman, E.; Rookus, M.A.

    2005-01-01

    The insulin-like growth factor (IGF) system is related to proliferation and tumor growth, and high levels of circulating IGF-I are thought to be a risk factor for several types of cancer. This review summarizes the epidemiologic evidence for an association between circulating IGF-I and cancer risk

  4. The insulin-like growth factor system in cancer prevention: potential of dietary intervention strategies.

    NARCIS (Netherlands)

    Voskuil, D.W.; Vrieling, A.; Veer, L.J. van 't; Kampman, E.; Rookus, M.A.

    2005-01-01

    The insulin-like growth factor (IGF) system is related to proliferation and tumor growth, and high levels of circulating IGF-I are thought to be a risk factor for several types of cancer. This review summarizes the epidemiologic evidence for an association between circulating IGF-I and cancer risk

  5. An investigation of potential success factors for an introductory model-driven programming course

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    In order to improve the course design of a CS1 model-driven programming course we study potential indicators of success for such a course. We explain our specific interpretation of objects-first. Of eight potential indicators of success, we have found only two to be significant at a 95% confidence...

  6. The Knowledge Potential as a Factor of Formation of Competitiveness of Transport Enterprise

    Directory of Open Access Journals (Sweden)

    Bonyar Svitlana M.

    2018-01-01

    Full Text Available The article is aimed at substantiating the importance of influence of the knowledge component of potential opportunities on the competitiveness of transport enterprises. The following functions of knowledge management in the transport enterprise are substantiated: stimulation, facilitating the development of cooperation, promotion and use of learning opportunities, attraction and preservation of human capital, increase of productivity, spreading the best experience, increasing the customer satisfaction level, creating a competitive advantage. Elements of the knowledge component of potential possibilities of transport enterprises have been defined as follows: professional knowledge; general knowledge; environmental knowledge; contracting potential; value characteristics of personality; qualities of personality; intuition; ability to logical thinking; communication potential; skill and ability to learn; ability to self-development; ability to work in a team; ability to use integrated knowledge; ability to reframing. The mechanism of influence of the knowledge component of potential opportunities on the competitiveness of transport enterprise has been formed.

  7. Hydroxytyrosol and its complex forms (secoiridoids) modulate aorta and heart proteome in healthy rats: Potential cardio-protective effects.

    Science.gov (United States)

    Catalán, Úrsula; Rubió, Laura; López de Las Hazas, Maria-Carmen; Herrero, Pol; Nadal, Pedro; Canela, Núria; Pedret, Anna; Motilva, Maria-José; Solà, Rosa

    2016-10-01

    Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in both free and complex forms (secoiridoids; SEC). Proteomics of cardiovascular tissues such as aorta or heart represents a promising tool to uncover the mechanisms of action of phenolic compounds in healthy animals. Twelve female Wistar rats were separated into three groups: a standard diet and two diets supplemented in phenolic compounds (HT and SEC) adjusted to 5 mg/kg/day during 21 days. Proteomic analyses of aorta and heart tissues were performed by nano-LC and MS. Ingenuity Pathway Analysis was used to generate interaction networks. HT or SEC modulated aorta and heart proteome compared to the standard diet. The top-scored networks were related to Cardiovascular System. HT and SEC downregulated proteins related to proliferation and migration of endothelial cells and occlusion of blood vessels in aorta and proteins related to heart failure in heart tissue. SEC showed higher fold change values compared to HT, attributed to higher concentration of HT detected in heart tissue. Changes at proteomic level in cardiovascular tissues may partially account for the underlying mechanisms of VOO phenols cardiovascular protection being the SEC effects higher than free HT. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment-Induced Cardioprotection against Ischemia-Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Hai-Jing Sun

    2017-01-01

    Full Text Available Propofol pretreatment before reperfusion, or propofol conditioning, has been shown to be cardioprotective, while its mechanism is unclear. The current study investigated the roles of endocannabinoid signaling in propofol cardioprotection in an in vivo model of myocardial ischemia/reperfusion (I/R injury and in in vitro primary cardiomyocyte hypoxia/reoxygenation (H/R injury. The results showed that propofol conditioning increased both serum and cell culture media concentrations of endocannabinoids including anandamide (AEA and 2-arachidonoylglycerol (2-AG detected by LC-MS/MS. The reductions of myocardial infarct size in vivo and cardiomyocyte apoptosis and death in vitro were accompanied with attenuations of oxidative injuries manifested as decreased reactive oxygen species (ROS, malonaldehyde (MDA, and MPO (myeloperoxidase and increased superoxide dismutase (SOD production. These effects were mimicked by either URB597, a selective endocannabinoids degradation inhibitor, or VDM11, a selective endocannabinoids reuptake inhibitor. In vivo study further validated that the cardioprotective and antioxidative effects of propofol were reversed by selective CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251. We concluded that enhancing endogenous endocannabinoid release and subsequent activation of CB2 receptor signaling represent a major mechanism whereby propofol conditioning confers antioxidative and cardioprotective effects against myocardial I/R injury.

  9. FACTORS THAT POTENTIALLY AFFECT THE FINANCIAL SUSTAINABILITY OF THE PENSION SYSTEM IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Luise Mladen

    2017-06-01

    Full Text Available In Romania, the State Social Security Budget spending exceeds the revenues, and this situation leads to a growing deficit of the public budget. This evolution is the result of a complex of factors, more or less difficult to be managed, which we analyze in this article. The phenomenon of ageing has a significant role in increasing the pressure on the social protection systems, in general, and on the pension system, in particular. Also, the labour market related factors and the economic factors have an important impact on the sustainability of the pension system. The design of the pension system is equally important.

  10. Transcription Factor Repertoire of Necrotrophic Fungal Phytopathogen Ascochyta rabiei: Predominance of MYB Transcription Factors As Potential Regulators of Secretome

    Directory of Open Access Journals (Sweden)

    Sandhya Verma

    2017-06-01

    Full Text Available Transcription factors (TFs are the key players in gene expression and their study is highly significant for shedding light on the molecular mechanisms and evolutionary history of organisms. During host–pathogen interaction, extensive reprogramming of gene expression facilitated by TFs is likely to occur in both host and pathogen. To date, the knowledge about TF repertoire in filamentous fungi is in infancy. The necrotrophic fungus Ascochyta rabiei, that causes destructive Ascochyta blight (AB disease of chickpea (Cicer arietinum, demands more comprehensive study for better understanding of Ascochyta-legume pathosystem. In the present study, we performed the genome-wide identification and analysis of TFs in A. rabiei. Taking advantage of A. rabiei genome sequence, we used a bioinformatic approach to predict the TF repertoire of A. rabiei. For identification and classification of A. rabiei TFs, we designed a comprehensive pipeline using a combination of BLAST and InterProScan software. A total of 381 A. rabiei TFs were predicted and divided into 32 fungal specific families of TFs. The gene structure, domain organization and phylogenetic analysis of abundant families of A. rabiei TFs were also carried out. Comparative study of A. rabiei TFs with that of other necrotrophic, biotrophic, hemibiotrophic, symbiotic, and saprotrophic fungi was performed. It suggested presence of both conserved as well as unique features among them. Moreover, cis-acting elements on promoter sequences of earlier predicted A. rabiei secretome were also identified. With the help of published A. rabiei transcriptome data, the differential expression of TF and secretory protein coding genes was analyzed. Furthermore, comprehensive expression analysis of few selected A. rabiei TFs using quantitative real-time polymerase chain reaction revealed variety of expression patterns during host colonization. These genes were expressed in at least one of the time points tested post

  11. Synergistic Cardioprotective Effects of Combined Chromium Picolinate and Atorvastatin Treatment in Triton X-100-Induced Hyperlipidemia in Rats: Impact on Some Biochemical Markers.

    Science.gov (United States)

    Shafik, Noha M; Baalash, Amal; Ebeid, Abla M

    2017-12-01

    Hyperlipidemia is one of the major risk factors for atherosclerosis and ischemic heart disease. Chromium (Cr) mineral is playing a crucial role in glucose and lipid homeostasis. The aim of this study was to evaluate the protective effects of combined chromium picolinate (CrPic) and atorvastatin treatment against hyperlipidemia-induced cardiac injury. Seventy-five male albino rats were divided into five groups (15 rats each). Hyperlipidemia was induced by intraperitoneal injection of a single dose of Triton X-100 (300 mg/kg body weight (b.w) (group ІІ). Treatment of hyperlipidemic rats was induced by daily administration of CrPic at a dose of 200 μg/kg b.w/day (group ІІІ), atorvastatin at a dose of 10 mg/kg/day (group IV), and combined treatment with both (group V) by gavage for 7 days. At the end of experiment, serum and heart tissues were obtained. Hyperlipidemia was confirmed by histopathology of heart tissues, marked serum dyslipidemia, increased atherogenic indices, and values of ischemia-modified albumin. In addition to increased values of proprotein convertase subtilisin/kexin type 9, activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme and high relative expression levels of pentraxin-3 were observed. However, paraoxonase-1 activity was markedly decreased in the hyperlipidemic group. Significant improvement in all assessed parameters was observed in the rat group treated with both CrPic and atorvastatin. It can be concluded that combined CrPic and atorvastatin treatments had synergistic cardioprotective effects against hyperlipidemia which may be through modulating atherosclerosis as well as cardiac and aortic damage and/or activation of anti-inflammatory and anti-oxidant pathways, thus reversing endothelial dysfunction.

  12. Heart rate variation and electroencephalograph--the potential physiological factors for thermal comfort study.

    Science.gov (United States)

    Yao, Y; Lian, Z; Liu, W; Jiang, C; Liu, Y; Lu, H

    2009-04-01

    Human thermal comfort researches mainly focus on the relation between the environmental factors (e.g. ambient temperature, air humidity, and air velocity, etc.) and the thermal comfort sensation based on a large amount of subjective field investigations. Although some physiological factors, such as skin temperature and metabolism were used in many thermal comfort models,they are not enough to establish a perfect thermal comfort model. In this paper,another two physiological factors, i.e. heart rate variation (HRV) and electroencephalograph (EEG), are explored for the thermal comfort study. Experiments were performed to investigate how these physiological factors respond to the environmental temperatures, and what is the relationship between HRV and EEG and thermal comfort. The experimental results indicate that HRV and EEG may be related to thermal comfort, and they may be useful to understand the mechanism of thermal comfort.

  13. Analysis of various risk factors affecting potentially malignant disorders and oral cancer patients of Central India

    Directory of Open Access Journals (Sweden)

    Vidya Kadashetti

    2015-01-01

    Conclusions: Chewing tobacco/betel quid is a strong risk factor in the development of PMD and oral cancer. Also age, gender, SES, education, and occupation influence the development of PMD and oral cancer.

  14. Feeding practices and potential risk factors for laminitis in dairy cows in Thailand

    OpenAIRE

    Pilachai, R.

    2013-01-01

    Laminitis is considered an important health problem facing the Thai dairy industry. Although the etiology of laminitis is multifactorial, nutrition is considered an important risk factor. Rumen acidosis, lipopolysaccharides (LPS) and histamine may play a role in the development of laminitis in dairy cattle. However, the relevancy of these risk factors in relation to the occurrence of laminitis under practical feeding conditions in Thailand is not clear. In Thailand, dairy rations are generall...

  15. Cardioprotection against ischemia/reperfusion injury by QiShenYiQi Pill® via ameliorate of multiple mitochondrial dysfunctions

    Directory of Open Access Journals (Sweden)

    Chen JR

    2015-06-01

    Full Text Available Jing Rui Chen,1–3 Jing Wei,1–3 Ling Yan Wang,1–3 Yan Zhu,1–3 Lan Li,1–3 Mary Akinyi Olunga,1–3 Xiu Mei Gao,1–3 Guan Wei Fan1–31Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, People’s Republic of China; 2Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Ministry of Education, 3Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of ChinaAim: To investigate the potential cardioprotective effects of QiShenYiQi Pill® (QSYQ on myocardial ischemia/reperfusion (I/R injury through antioxidative stress and mitochondrial protection.Methods and results: Sprague Dawley rats were pretreated with QSYQ or saline for 7 days and subjected to ischemia (30 minutes occlusion of the left anterior descending coronary artery and reperfusion (120 minutes. Cardiac functions were evaluated by echocardiogram and hemodynamics. Myocardial mitochondria were obtained to evaluate changes in mitochondrial structure and function, immediately after 120 minutes reperfusion. Pretreatment with QSYQ protected against I/R-induced myocardial structural injury and improved cardiac hemodynamics, as demonstrated by normalized serum creatine kinase and suppressed oxidative stress. Moreover, the impaired myocardial mitochondrial structure and function decreased level of ATP (accompanied by reduction of ATP5D and increase in the expression of cytochrome C. Myocardial fiber rupture, interstitial edema, and infiltrated leukocytes were all significantly ameliorated by pretreatment with QSYQ.Conclusion: Pretreatment of QSYQ in Sprague Dawley rats improves ventricular function and energy metabolism and reduces oxidative stress via ameliorating multiple mitochondrial dysfunctions during I/R injury.Keywords: QSYQ, ischemia/reperfusion injury, energy metabolism, mitochondria

  16. Medication Errors in Vietnamese Hospitals : Prevalence, Potential Outcome and Associated Factors

    NARCIS (Netherlands)

    Huong-Thao Nguyen, [Unknown; Tuan-Dung Nguyen, [No Value; van den Heuvel, Edwin R.; Haaijer-Ruskamp, Flora M.; Taxis, Katja

    2015-01-01

    Background Evidence from developed countries showed that medication errors are common and harmful. Little is known about medication errors in resource-restricted settings, including Vietnam. Objectives To determine the prevalence and potential clinical outcome of medication preparation and

  17. Effect of Interventions on Potential, Modifiable Risk Factors for Knee Injury in Team Ball Sports : A Systematic Review

    NARCIS (Netherlands)

    ter Stege, Marloes H. P.; Dallinga, Joan M.; Benjaminse, Anne; Lemmink, Koen A. P. M.

    2014-01-01

    Background Knee injuries are one of the most common types of injuries in team ball sports, and prevention is crucial because of health and economic implications. To set up effective prevention programs, these programs must be designed to target potential, modifiable risk factors. In addition, it is

  18. Risk indicators and potential risk factors for caries in 5-year-olds of different ethnic groups in Amsterdam.

    NARCIS (Netherlands)

    Verrips, G.H.; Frencken, J.E.; Kalsbeek, H.; Horst, G. ter; Filedt Kok-Weimar, T.L.

    1992-01-01

    The aim of this study was threefold: first, to assess the oral health of Turkish, Moroccan, Surinamese, Dutch and "other" 5-yr-old children living in Amsterdam; second, to identify risk indicators for caries, in addition to ethnicity; and third, to identify potential risk factors related to

  19. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE)

    DEFF Research Database (Denmark)

    O'Donnell, Martin J; Chin, Siu Lim; Rangarajan, Sumathy

    2016-01-01

    BACKGROUND: Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes o...

  20. Potential risk factors associated with contact dermatitis, lameness, negative emotional state, and fear of humans in broiler chicken flocks

    NARCIS (Netherlands)

    Bassler, A.; Arnould, C.; Butterworth, A.; Colin, L.; Jong, de I.C.; Ferrante, V.; Ferrari, P.; Haslam, S.A.; Wemelsfelder, F.; Blokhuis, H.J.

    2013-01-01

    The objectives of this study were to 1) identify determinants of poor welfare in commercial broiler chicken flocks by studying the associations between selected resource-based measures (RBM, potential risk factors), such as litter quality and dark period, and animal-based welfare indicators (ABM),

  1. Potential and emergence factors of biogas and by-product gas recovery. Synthesis

    International Nuclear Information System (INIS)

    Couturier, Ch.

    2004-11-01

    The aim of this study is to assess the energy potential of biomass (excluding energy crops), mainly biogas and biomass gases, for France, European Union, USA, China and India. The methodology is based on the identification of the organic matter flows, from agricultural and forestry areas, to their end use. This allows a limitation of double counts and forgotten flows, relevant to most usual methods. It has been tested successfully for France. Biogas potential for France is assumed to about 14 Mtoe, on a global biomass potential of about 51 Mtoe (accessible under 75 $ per barrel). Potential biomass resource in the industrialized countries is about one half of final consumption of fuels and electricity, among which a quarter from biogas. In China and India, biomass potential is of the same magnitude than final consumption of fuels and electricity. Forestry harvest is already intensive, and most of the increasing should be due to biogas, which is already a solution against deforestation. Most of biogas resources come from animal manure and crops residues. Anaerobic digestion allows the restitution of organic and mineral fertilizers to the soils. In the four areas of this study, biogas potential could rise from 11 Mtoe today, to 370 Mtoe in a long term perspective. (authors)

  2. Energy savings potential in China's industrial sector: From the perspectives of factor price distortion and allocative inefficiency

    International Nuclear Information System (INIS)

    Ouyang, Xiaoling; Sun, Chuanwang

    2015-01-01

    China's industrial energy consumption accounted for 70.82% of national and 14.12% of world energy usage in 2011. In the context of energy scarcity and environmental pollution, the industrial sector in China faces unsustainable growth problems. By adopting the stochastic frontier analysis (SFA) framework, this paper analyzes the factor allocative efficiency of China's industrial sector, and estimates the energy savings potential from the perspective of allocative inefficiency. This paper focuses on three issues. The first is examining the factor allocative inefficiency of China's industrial sector. The second is measuring factor price distortion by the shadow price model. The third is estimating the energy savings potential in China's industrial sector during 2001–2009. Major conclusions are thus drawn. First, factor prices of capital, labor and energy are distorted in China due to government regulations. Moreover, energy price is relatively low compared to capital price, while is relatively high compared to labor price. Second, the industry-wide energy savings potential resulted from energy allocative inefficiency was about 9.71% during 2001–2009. The downward trend of energy savings potential implies the increasing energy allocative efficiency in China's industrial sector. Third, a transparent and reasonable pricing mechanism is conducive to improving energy allocative efficiency. - Highlights: • We measure energy savings potential resulted from allocative inefficiency in China's industrial sector. • Allocative inefficiency is explained based on the theoretical and empirical models. • Factor prices of capital, labor and energy are distorted because of government regulations. • Energy pricing reform is conducive to improving energy allocative efficiency

  3. [Bruxism--confirmed and potential risk factors. A systematic review of the literature].

    Science.gov (United States)

    Kulis, Andreja; Türp, Jens Christoph

    2008-01-01

    Considering a point prevalence of up to 20% among adults, bruxism is a clinically significant phenomenon. It was the aim of the present work to systematically review the literature published until June 2007 in order to identify contributions on risk factors for bruxism in adults. Prerequisite for consideration were reported measures of risk assessment, such as odds ratios (OR). Seven relevant articles were found. Depending on the value of the OR and the position of the lower limit of the reported confidence interval (CI(LL)), we distinguished four risk groups (A to D). Three variables--severe stress experience; age between 25 and 44 years; age between 45 and 64 years--were grouped into category A (very strong indication for clinically relevant risk factor: OR >2; CI(LL) >2). Five variables fell into category B (strong indication for clinically relevant risk factor: OR >2; 1 1) was composed of 16 variables, while category D (possible indication for risk factor: 1 < OR < or = 2; CI(LL) < or = 1) embraced 11 variables. On the other hand, the presence of occlusal interferences was not a risk factor.

  4. Geogenic factors of radiation exposure with special regard of the radon potential

    International Nuclear Information System (INIS)

    Kemski, J.; Siehl, A.; Stegemann, R.; Valdivia-Manchego, M.

    1999-01-01

    Classification and mapping of geogenic radon potential in Germany is based on detailed field studies of radon activity in soil gas and in situ gas permeability, using GIS techniques. The distribution of the two parameters is combined in a ranking procedure to asses the geogenic radon potential, with regionalization based on a distance-weighted interpolation of the measurements on a regular grid and information on the corresponding geological unit as an attribute to every raster field. Thereby, the boundaries of the geological units are defined implicitly. In areas with rather homogeneous geological conditions, where lower to intermediate radon potential is present, the measuring sites are widely spaced (i.e. Meso- and Cenozoic sedimentary rocks, covering 80 % of the area). Areas with more complicated hard rock geology and suspected high geogenic radon potential, like the outcrop areas of the Palaeozoic and Precambrian basement, were mapped in detail with a higher density of the measurement grid. The data material at hand make it possible to design maps of different types of parameter combinations and classifications, taking into account also administrative units. As a result, a set of detailed maps of geogenic radon potential for selected test areas as well as a general map for Germany (1:2 000 000) are presented. (orig./SR) [de

  5. Haemophilia B caused by mutation of a potential thrombin cleavage site in factor IX

    Energy Technology Data Exchange (ETDEWEB)

    Winship, P.R. (Univ. of Oxford (England))

    1990-03-11

    Haemophilia B is a blood coagulation disorder caused by mutations in the factor IX gene giving functionally defective or reduced levels of factor IX protein circulating in the plasma. The mutation in the Caucasian patient under investigation, Haemophilia B Oxford h5 (Oxh5), was characterized at the DNA level by constructing a genomic library using leucocyte-derived DNA from the patient. Overlapping recombinant clones spanning the entire factor IX locus were isolated which then allowed the generation of a series of sub-clones across all eight exons (a-h) plus the 5{prime} and 3{prime} flanking sequences known to be important in regulation of the gene and polyadenylation of the mRNA species.

  6. Potential Success and Barrier Factors for Implementation of the Transition to Independence (TIP Model

    Directory of Open Access Journals (Sweden)

    Christopher M. Kalinyak

    2017-01-01

    Full Text Available In this qualitative study, 28 key stakeholders who work with transition-aged youth participated in focus group discussions addressing success and barrier factors regarding implementation of a transition to independence process (TIP program for youth, ages 14–29, in three Midwestern cities. All participants had prior knowledge of TIP. The paradigm shift to client-oriented goals and services was acknowledged by respondents as the prime benefit of TIP; youth are more motivated to follow through on self-determined goals. Barrier factors for providers involved collaboration with agencies adhering to provider-oriented interventions, provision of TIP methods training, and reallocation of time and money. Barrier factors for youth involved mistrust of service providers, overcoming maturational deficits, and acquiring and maintaining relationships, reputations, and social supports.

  7. Soil salinity and matric potential interaction on water use, water use efficiency and yield response factor of bean and wheat.

    Science.gov (United States)

    Khataar, Mahnaz; Mohhamadi, Mohammad Hossien; Shabani, Farzin

    2018-02-08

    We studied the effects of soil matric potential and salinity on the water use (WU), water use efficiency (WUE) and yield response factor (Ky), for wheat (Triticum aestivum cv. Mahdavi) and bean (Phaseoulus vulgaris cv. COS16) in sandy loam and clay loam soils under greenhouse conditions. Results showed that aeration porosity is the predominant factor controlling WU, WUE, Ky and shoot biomass (Bs) at high soil water potentials. As matric potential was decreased, soil aeration improved, with Bs, WU and Ky reaching maximum value at -6 to -10 kPa, under all salinities. Wheat WUE remained almost unchanged by reduction of matric potential under low salinities (EC ≤ 8 dSm -1 ), but increased under higher salinities (EC ≥ 8 dSm -1 ), as did bean WUE at all salinities, as matric potential decreased to -33 kPa. Wheat WUE exceeds that of bean in both sandy loam and clay loam soils. WUE of both plants increased with higher shoot/root ratio and a high correlation coefficient exists between them. Results showed that salinity decreases all parameters, particularly at high potentials (h = -2 kPa), and amplifies the effects of waterlogging. Further, we observed a strong relationship between transpiration (T) and root respiration (Rr) for all experiments.

  8. Development and evaluation of the McKnight Risk Factor Survey for assessing potential risk and protective factors for disordered eating in preadolescent and adolescent girls.

    Science.gov (United States)

    Shisslak, C M; Renger, R; Sharpe, T; Crago, M; McKnight, K M; Gray, N; Bryson, S; Estes, L S; Parnaby, O G; Killen, J; Taylor, C B

    1999-03-01

    To describe the development, test-retest reliability, internal consistency, and convergent validity of the McKnight Risk Factor Survey-III (MRFS-III). The MRFS-III was designed to assess a number of potential risk and protective factors for the development of disordered eating in preadolescent and adolescent girls. Several versions of the MRFS were pilot tested before the MRFS-III was administered to a sample of 651 4th through 12th- grade girls to establish its psychometric properties. Most of the test-retest reliability coefficients of individual items on the MRFS-III were r > .40. Alpha coefficients for each risk and protective factor domain on the MRFS-III were also computed. The majority of these coefficients were r > .60. High convergent validity coefficients were obtained for specific items on the MRFS-III and measures of self-esteem (Rosenberg Self-Esteem Scale) and weight concerns (Weight Concerns Scale). The test-retest reliability, internal consistency, and convergent validity of the MRFS-III suggest that it is a useful new instrument to assess potential risk and protective factors for the development of disordered eating in preadolescent and adolescent girls.

  9. Feeding practices and potential risk factors for laminitis in dairy cows in Thailand

    NARCIS (Netherlands)

    Pilachai, R.

    2013-01-01

    Laminitis is considered an important health problem facing the Thai dairy industry. Although the etiology of laminitis is multifactorial, nutrition is considered an important risk factor. Rumen acidosis, lipopolysaccharides (LPS) and histamine may play a role in the development of laminitis in dairy

  10. Temperament as a Potential Factor in the Development and Treatment of Conduct Disorders.

    Science.gov (United States)

    Center, David; Kemp, Dawn

    This report examines the development of Conduct Disorder (CD) in children and adolescents from the perspective of Hans Eysenck's bio-social theory of personality. The theory views personality as a product of the interaction of temperament and socialization. Eysenck's three-factor model of personality is comprised of Extroversion (E), Neuroticism…

  11. Microcystins: Potential risk factors in carcinogenesis of primary liver cancer in Serbia

    Directory of Open Access Journals (Sweden)

    Drobac Damjana

    2011-01-01

    Full Text Available The Primary Liver Carcinoma (PLC is one of the most common malignant diseases in the world. In Central Serbia during the period from 2000 to 2006 the average incidence was 16.9/100 000 that complies to the European epidemiology. The main risk factors for PLC are considered to be cirrhosis of liver and viral chronic Hepatitis B and C. The goal of this research was to analyze epidemiological data of these diseases and to state the correlation between PLC, liver cirrhosis and Hepatitis B and C in Serbia. During the research period of 6 years the correlations between PLC and the corresponding risk factors were negative. For this reason it was necessary to examine other risk factors. The high incidence of PLC in Nišavski, Toplički and Šumadijski region correlate with emerging blooms of Cyanobacteria in water reservoirs supplying these areas with drinking water. Since we examined only 7 years span and have no completed cyanotoxin analysis, it is necessary to complete more research in this field. The identification of cyanotoxins as risk factors that contribute to the development of liver cancer will help in the prevention of this disease.

  12. Prevalence and Potential Factors Associated with Overweight and Obesity Status in Adults with Intellectual Developmental Disorders

    Science.gov (United States)

    Ranjan, Sobhana; Nasser, Jennifer A.; Fisher, Kathleen

    2018-01-01

    Background: The prevalence of being overweight and obese is increasing not just in the general population but also in individuals with intellectual disability (ID). Therefore, a need to identify factors contributing to overweight/obesity arises as this population is escalating. Materials and Methods: This narrative review article summarizes…

  13. [Limiting factors in the class III camouflage treatment: a potential protocol].

    Science.gov (United States)

    Chaques Asensi, José

    2016-06-01

    The Class III skeletal malocclusion has been traditionally treated with a combined approach of orthodontics and orthognathic surgery or with a strategy of orthodontic camouflage. Some severe cases can be identified as ideal candidates for a surgical treatment whereas some others can be handled with orthodontics alone, with a reasonable expectation of an acceptable result. However, the problem remains for the borderline patient. In fact, limited information is available in the literature regarding the identification of the factors that can help in establishing the limits for one treatment modality or the other. Furthermore, the quantification of some of these factors, for practical purposes, is practically missing or very seldom suggested. Therefore, the decision making process remains a subjective reflection based on the "good clinical sense" of the orthodontist or just reduced to an "educated guess". In order to add some information, hopefully useful in deciding the most suitable treatment option for the individual patient, we propose a clinical protocol based on four different factors. Namely: the skeletal discrepancy, the occlusal discrepancy, the periodontal condition and facial aesthetics. For each one of these factors several parameters will be evaluated and, for some of them, an attempt to provide some reference numerical values will be made. Finally, clinical examples will be presented to illustrate the concepts discussed and the treatment alternatives, final treatment plan and treatment outcome will be analyzed for each one of them. © EDP Sciences, SFODF, 2016.

  14. Psychosocial factors influencing parental decision to allow or refuse potentially lifesaving enucleation in children with retinoblastoma

    Directory of Open Access Journals (Sweden)

    Rolando Enrique D. Domingo

    2017-01-01

    Full Text Available Objective: Retinoblastoma is the most common malignancy of the eye and ocular adnexa in the Philippines. It is curable when treated early, but delay in enucleation is common due to the parental refusal of surgery for varied reasons. The aim of this study is to identify the psychosocial barriers and facilitating factors for accepting versus refusing enucleation as treatment for retinoblastoma. Methods: This is a cross-sectional descriptive study utilizing structured interviews and a questionnaire. It was conducted at the Retinoblastoma Clinic of the Philippine General Hospital. A questionnaire using the Likert scale was constructed after performing key informant interviews and focus group discussions. It was pretested and revised before parents of patients with retinoblastoma were invited to participate in the study. Descriptive statistics, quantitative item analyses using inter-item correlations and item-total correlations was performed. Results: Factors that correlate with refusal to enucleate are the beliefs that cancer is a fatal illness, the fear of unacceptable esthetic outcome of the surgery, and the cost of treatment. Favorable factors include value of life, high regard for the opinion of medical practitioners, and appreciation of the efficacy of treatment. Conclusions: There are several favorable factors and barriers that health practitioners must consider in facilitating parental decision-making toward enucleation for retinoblastoma.

  15. Advanced REACH Tool : Development and application of the substance emission potential modifying factor

    NARCIS (Netherlands)

    Tongeren, M. van; Fransman, W.; Spankie, S.; Tischer, M.; Brouwer, D.; Schinkel, J.; Cherrie, J.W.; Tielemans, E.

    2011-01-01

    The Advanced REACH Tool (ART) is an exposure assessment tool that combines mechanistically modelled inhalation exposure estimates with available exposure data using a Bayesian approach. The mechanistic model is based on nine independent principal modifying factors (MF). One of these MF is the

  16. Fasting-induced adipose factor/angiopoietin-like protein 4: a potential target for dyslipidemia?

    NARCIS (Netherlands)

    Zandbergen, F.J.; Dijk, van S.; Müller, M.R.; Kersten, A.H.

    2006-01-01

    Recently, several proteins with homology to angiopoietins have been discovered. Three members of this new group, designated angiopoietin-like proteins (ANGPTLs), have been linked to regulation of energy metabolism. This review will focus on the fasting-induced adipose factor (FIAF)/ANGPTL4 as an

  17. General biological character of mammal adaptive potential in the response to diverse extreme environmental factors

    International Nuclear Information System (INIS)

    Graevskaya, B.M.; Zolotareva, N.N.

    1986-01-01

    Method for evaluating individual response and its prediction to extreme effect was developed. Experiments with different mammal types show that ranking (dominancy or subordination) are tightly related to radiosensitivity. It is confirmed that organism sensitivity, independen of effect factors, is determined with homeostasis capacity characterizing mammal genotype. Variation limits of ogranism mobilization possibilities depending on species differences were determined as well

  18. Factors associated with duration of breastfeeding in ireland: potential areas for improvement.

    LENUS (Irish Health Repository)

    Tarrant, R C

    2011-08-01

    There is a need to comprehensively examine why mothers in Ireland discontinue breastfeeding early and to explore the factors influencing duration of breastfeeding during the first 6 months postpartum. Findings from this study provide valuable direction for future strategies and interventions aimed at increasing breastfeeding duration rates in Ireland.

  19. A Global Assessment of Runoff Sensitivity to Changes in Precipitation, Potential Evaporation, and Other Factors

    NARCIS (Netherlands)

    Berghuijs, W.R.; Larsen, Joshua R.; van Emmerik, T.H.M.; Woods, Ross A.

    2017-01-01

    Precipitation (P) and potential evaporation (Ep) are commonly studied drivers of changing freshwater availability, as aridity (Ep/P) explains ∼90% of the spatial differences in mean runoff across the globe. However, it is unclear if changes in aridity over time are also the

  20. Dystrophin is required for the normal function of the cardio-protective K(ATP channel in cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Laura Graciotti

    Full Text Available Duchenne and Becker muscular dystrophy patients often develop a cardiomyopathy for which the pathogenesis is still unknown. We have employed the murine animal model of Duchenne muscular dystrophy (mdx, which develops a cardiomyopathy that includes some characteristics of the human disease, to study the molecular basis of this pathology. Here we show that the mdx mouse heart has defects consistent with alteration in compounds that regulate energy homeostasis including a marked decrease in creatine-phosphate (PC. In addition, the mdx heart is more susceptible to anoxia than controls. Since the cardio-protective ATP sensitive potassium channel (K(ATP complex and PC have been shown to interact we investigated whether deficits in PC levels correlate with other molecular events including K(ATP ion channel complex presence, its functionality and interaction with dystrophin. We found that this channel complex is present in the dystrophic cardiac cell membrane but its ability to sense a drop in the intracellular ATP concentration and consequently open is compromised by the absence of dystrophin. We further demonstrate that the creatine kinase muscle isoform (CKm is displaced from the plasma membrane of the mdx cardiac cells. Considering that CKm is a determinant of K(ATP channel complex function we hypothesize that dystrophin acts as a scaffolding protein organizing the K(ATP channel complex and the enzymes necessary for its correct functioning. Therefore, the lack of proper functioning of the cardio-protective K(ATP system in the mdx cardiomyocytes may be part of the mechanism contributing to development of cardiac disease in dystrophic patients.

  1. Factors influencing the potential for strong brand relationships with consumer product brands: An overview and research agenda

    DEFF Research Database (Denmark)

    Bech-Larsen, Tino; Bergkvist, Lars; Francis, Julie

    Based on the premise that consumer product brands are different with respect to their potential to form strong long-term relationships with consumers, this paper aims to identify factors that influence brands' potential for strong long-term relationships and to suggest how these can be empirically...... investigated. The paper reviews brand-centric and consumer-centric research and identifies twelve brand variables that may influence the relationship potential of consumer product brands. A research agenda is suggested and a number of issues that needs to be resolved before empirical research can be carried...... out are discussed. The paper concludes by speculating on possible outcomes in future empirical studies and it is suggested that multiple brand variables will have to be employed to evaluate the relationship potential of brands....

  2. Potential Risk Factors for the Onset of Complex Regional Pain Syndrome Type 1: A Systematic Literature Review

    Directory of Open Access Journals (Sweden)

    Tracey Pons

    2015-01-01

    Full Text Available Anaesthetists in the acute and chronic pain teams are often involved in treating Complex Regional Pain Syndromes. Current literature about the risk factors for the onset of Complex Regional Pain Syndrome Type 1 (CRPS 1 remains sparse. This syndrome has a low prevalence, a highly variable presentation, and no gold standard for diagnosis. In the research setting, the pathogenesis of the syndrome continues to be elusive. There is a growing body of literature that addresses efficacy of a wide range of interventions as well as the likely mechanisms that contribute to the onset of CRPS 1. The objective for this systematic search of the literature focuses on determining the potential risk factors for the onset of CRPS 1. Eligible articles were analysed, dated 1996 to April 2014, and potential risk factors for the onset of CRPS 1 were identified from 10 prospective and 6 retrospective studies. Potential risk factors for the onset of CRPS 1 were found to include being female, particularly postmenopausal female, ankle dislocation or intra-articular fracture, immobilisation, and a report of higher than usual levels of pain in the early phases of trauma. It is not possible to draw definite conclusions as this evidence is heterogeneous and of mixed quality, relevance, and weighting strength against bias and has not been confirmed across multiple trials or in homogenous studies.

  3. Determinants of Perceived Stress in Individuals with Obesity: Exploring the Relationship of Potentially Obesity-Related Factors and Perceived Stress.

    Science.gov (United States)

    Junne, Florian; Ziser, Katrin; Giel, Katrin Elisabeth; Schag, Kathrin; Skoda, Eva; Mack, Isabelle; Niess, Andreas; Zipfel, Stephan; Teufel, Martin

    2017-01-01

    Associations of specific types of stress with increased food intake and subsequent weight gain have been demonstrated in animal models as well as in experimental and epidemiological studies on humans. This study explores the research question of to what extent potentially obesity-related factors determine perceived stress in individuals with obesity. N = 547 individuals with obesity participated in a cross-sectional study assessing perceived stress as the outcome variable and potential determinants of stress related to obesity. Based on the available evidence, a five factorial model of 'obesity-related obesogenic stressors' was hypothesized, including the dimensions, 'drive for thinness', 'impulse regulation', 'ineffectiveness', 'social insecurity', and 'body dissatisfaction'. The model was tested using multiple linear regression analyses. The five factorial model of 'potentially obesity-related stressors' resulted in a total variance explanation of adjusted R² = 0.616 for males and adjusted R² = 0.595 for females for perceived stress. The relative variance contribution of the five included factors differed substantially for the two sexes. The findings of this cross-sectional study support the hypothesized, potentially obesity-related factors: 'drive for thinness', 'impulse regulation', 'ineffectiveness', 'social insecurity', and 'body dissatisfaction' as relevant determinants of perceived stress in individuals with obesity. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

  4. SPATIAL VARIETY AND DISTRIBUTION OF TRADITIONAL MARKETS IN SURAKARTA AS POTENTIAL FACTORS IN IMPROVING SPATIAL-BASED MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Istijabatul Aliyah

    2017-02-01

    Full Text Available Traditional markets function as trading place, socio-culture interaction, and recreation facility either in regional or urban scope. Distribution and variety of spatial condition influence traditional markets’ planning both physically and non-physically. Therefore, this research aimed to conduct a mapping of traditional markets’ spatial distribution and variety as potential factors to improve spatial-based management. Analysis methods including: (1 Mapping by employing Geographic Information System, (2 Category Based Analysis (CBA, and (3 Interactive Analysis were applied in Surakarta City as the research location. The result of this research signifies that spatial variety and distribution of traditional markets in Surakarta had similar pattern between one market to others; overlapping service function; specific commodity types in accordance with the market’s characteristics; diverse operating hours. Spatial variety and distribution could be potential factors to improve traditional market management as shopping service. This result was contrasted with Central Place Theory by Christaller and NÆss & Jensen’s research finding stating that distance became a key factor influencing accessibility to a number of activity facilities. Therefore, distance toward the service center is not considered as the main factor in traditional market management. The main factor in managing and controlling traditional markets’ development includes service function, commodity specification, and operating hour’s flexibility.

  5. The transcription factor EGR1 regulates metastatic potential of v-src transformed sarcoma cells

    Czech Academy of Sciences Publication Activity Database

    Čermák, Vladimír; Kosla, Jan; Plachý, Jiří; Trejbalová, Kateřina; Hejnar, Jiří; Dvořák, Michal

    2010-01-01

    Roč. 67, č. 20 (2010), s. 3557-3568 ISSN 1420-682X R&D Projects: GA AV ČR KAN200520801; GA MŠk(CZ) LC06061; GA ČR(CZ) GA204/07/1030 Institutional research plan: CEZ:AV0Z50520514 Keywords : smooth muscle cells * endothelial kinase * Rho kinase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.047, year: 2010

  6. Inflammation and cancer: macrophage migration inhibitory factor (MIF)--the potential missing link.

    LENUS (Irish Health Repository)

    Conroy, H

    2010-11-01

    Macrophage migration inhibitory factor (MIF) was the original cytokine, described almost 50 years ago and has since been revealed to be an important player in pro-inflammatory diseases. Recent work using MIF mouse models has revealed new roles for MIF. In this review, we present an increasing body of evidence implicating the key pro-inflammatory cytokine MIF in specific biological activities related directly to cancer growth or contributing towards a microenvironment favouring cancer progression.

  7. Hyperlipemia in a population of aged donkeys: description, prevalence, and potential risk factors.

    Science.gov (United States)

    Burden, F A; Du Toit, N; Hazell-Smith, E; Trawford, A F

    2011-01-01

    Hyperlipemia is a common disorder of the donkey, with mortality rates of up to 80% reported. Such a poor prognosis makes prevention of this disorder or amelioration in the early stages crucial. The objective of this study was to describe and determine the prevalence of hyperlipemia in a population of donkeys and to determine risk factors for development of the disease. A total of 449 cases were investigated from a population of 3829 donkeys; donkeys were resident at The Donkey Sanctuary, a charity providing refuge for unwanted donkeys in the UK. Animals were selected on the basis of presence of clinical disease. A retrospective case-control study design was used, and all donkeys presenting with hyperlipemia over a 4-year period were included. Each case was matched with 2 controls that had not suffered from hyperlipemia in the previous month. Multivariable analysis was carried out to determine risk factors. A total of 449 clinical cases of hyperlipemia were reported with an associated mortality rate of 48.5%. Concurrent disease was present in 72% of donkeys and was the greatest risk factor (OR = 76.98); others included cardboard bedding (OR = 3.86), movement (OR = 3.94), weight loss (OR = 6.4), dental disease (OR = 1.73), and concentrate feeding (OR = 1.87). This study shows that this population of donkeys in the UK often develops hyperlipemia, particularly in response to stress or primary illness, and provides useful insights in to health and management risk factors that may be addressed to decrease the risk of hyperlipemia both in the study population and in other similar donkey populations. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  8. Potentials and Influencing Factors of Dynamic Pricing in Business: Empirical Insights of European Experts

    OpenAIRE

    Christopher Reichstein; Ralf-Christian Härting; Martina Häußler

    2017-01-01

    With a continuously increasing speed of information exchange on the World Wide Web, retailers in the E-Commerce sector are faced with immense possibilities regarding different online purchase processes like dynamic price settings. By use of Dynamic Pricing, retailers are able to set short time price changes in order to optimize producer surplus. The empirical research illustrates the basics of Dynamic Pricing and identifies six influencing factors of Dynamic Pricing. The results of a structur...

  9. Structure factor of 36Ar and long range pair-potential properties

    International Nuclear Information System (INIS)

    Barocchi, F.; Chieux, P.; Fredrikze, H.; Magli, R.

    1992-01-01

    Recent diffraction data on low density Ar have been analyzed with the aim of determining the low k behaviour of the structure factor and from that the long range dipole-dipole interaction strength. The results are compared with the presently best known estimates of the van der Waals C 6 coefficient and with a previous analysis of neutron diffraction data on liquid Ar. (orig.)

  10. Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Tom J. Burdon

    2011-01-01

    Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

  11. Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Min-Gu Kang

    2014-01-01

    Full Text Available We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM. So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1 pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL group, the hazard ratio (HR for overall survival was higher for group with high PTH level (≥68.3 pg/mL (HR, 1.710. Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P=0.056. Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients.

  12. Grit: A Potential Protective Factor Against Substance Use and Other Risk Behaviors Among Latino Adolescents.

    Science.gov (United States)

    Guerrero, Lourdes R; Dudovitz, Rebecca; Chung, Paul J; Dosanjh, Kulwant K; Wong, Mitchell D

    2016-04-01

    Grit, defined as "working strenuously toward challenges, maintaining effort and interest over years despite failure, adversity, and plateaus in progress," is strongly associated with academic achievement and life success and may also be associated with health outcomes and behaviors. We examined predictors of grit, and the association between grit and health behaviors among at-risk Latino adolescents. We analyzed baseline survey data collected in 2013-2014 from a sample of 1270 9th graders in low-income neighborhoods of Los Angeles. We examined factors associated with grit and whether grit is associated with substance use and delinquent behaviors, controlling for adolescent and parent sociodemographic factors. In a sample of mostly Latino adolescents (89.5%), compared to those with low grit, those with high grit had significantly lower odds of alcohol use in the last 30 days (odds ratio 0.30, P authoritative parenting style, parental employment, and high self-efficacy scores. Grit may be an important candidate protective factor against substance use and other risk behaviors among Latino adolescents. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  13. Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

    Directory of Open Access Journals (Sweden)

    Masayoshi Hashimoto

    2016-10-01

    Full Text Available The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant’s resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable. Moreover, recessive resistance may be acquired by a deficiency in a negative regulator of plant defense responses, possibly due to the autoactivation of defense signaling. Eukaryotic translation initiation factor (eIF 4E and eIF4G and their isoforms are the most widely exploited recessive resistance genes in several crop species, and they are effective against a subset of viral species. However, the establishment of efficient, recessive resistance-type antiviral control strategies against a wider range of plant viral diseases requires genetic resources other than eIF4Es. In this review, we focus on recent advances related to antiviral recessive resistance genes evaluated in model plants and several crop species. We also address the roles of next-generation sequencing and genome editing technologies in improving plant genetic resources for recessive resistance-based antiviral breeding in various crop species.

  14. Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin.

    Science.gov (United States)

    Bisagno, Verónica; Cadet, Jean Lud

    2014-09-01

    Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

  15. The expanding universe of neurotrophic factors: therapeutic potential in aging and age-associated disorders.

    Science.gov (United States)

    Lanni, C; Stanga, S; Racchi, M; Govoni, S

    2010-01-01

    Multiple molecular, cellular, structural and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively by employing multiple mechanisms in order to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands. Otherwise, they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's diseases. An important role in this balancement is played by neurotrophic factors, which are central to many aspects of nervous system function since they regulate the development, maintenance and survival of neurons and neuron-supporting cells such as glia and oligodendrocytes. A vast amount of evidence indicates that alterations in levels of neurotrophic factors or their receptors can lead to neuronal death and contribute to aging as well as to the pathogenesis of diseases of abnormal trophic support (such as neurodegenerative diseases and depression) and diseases of abnormal excitability (such as epilepsy and central pain sensitization). Cellular and molecular mechanisms by which neurotrophic factors may influence cell survival and excitability are also critically examined to provide novel concepts and targets for the treatment of physiological changes bearing detrimental functional alterations and of different diseases affecting the central nervous system during aging.

  16. An examination of factors potentially influencing birth distributions in golden snub-nosed monkeys (Rhinopithecus roxellana

    Directory of Open Access Journals (Sweden)

    Zuofu Xiang

    2017-01-01

    Full Text Available Many species of primates are considered seasonal breeders, but the set of factors, such as food availability, day length and temperature, that influence the timing of reproductive events for both wild and captive individuals remains unclear. Here, we examine the role of factors in shaping breeding patterns in Rhinopithecus roxellana, a temperate colobine primate. We used circular statistics to describe and compare the patterns of reproductive seasonality among individuals in 13 captive groups and two free ranging but provisioned groups at various locations throughout China. Almost 90% of births occurred in March, April and May in adult females residing in both free ranging (n = 131 and captive groups (n = 407. Births occurred principally in 2–4 months prior to the peak of food availability, while conceptions occurred in 1–2 months after the peak of food availability in free ranging but provisioned groups. Day length (latitude had a significant effect on the timing of reproduction. However, females that experienced a wide variation of temperature between the lowest and highest monthly average temperature had a later conception date. These results support that day length and temperature might be factor influencing the timing of reproductive activity.

  17. A Global Assessment of Runoff Sensitivity to Changes in Precipitation, Potential Evaporation, and Other Factors

    OpenAIRE

    Berghuijs, Wouter; Larsen, Joshua; van Emmerik, Tim; Woods, Ross

    2017-01-01

    Precipitation (P) and potential evaporation (Ep) are commonly studied drivers of changing freshwater availability, as aridity (Ep/P) explains ∼90% of the spatial differences in mean runoff across the globe. However, it is unclear if changes in aridity over time are also the most important cause for temporal changes in mean runoff and how this degree of importance varies regionally. We show that previous global assessments that address these questions do not properly account for changes due to...

  18. Learner-to-teacher bullying as a potential factor influencing teachers' mental health

    OpenAIRE

    Woudstra, Marit Helen; Janse van Rensburg, Estie; Visser, Maretha; Jordaan, Joyce

    2018-01-01

    Learner-to-teacher bullying is a focus area that has not been widely researched. The current research, underpinned by the ecosystemic paradigm, examined the proportion of teachers who reported exposure to bullying by learners. The study was carried out by using the Learner-to-teacher Bullying Questionnaire developed for this research. Additionally, the potential effect that learner-to-teacher bullying may have on teachers' experience of mental health was investigated using the Hospital Anxiet...

  19. Drinking yerba mate infusion: a potential risk factor for invasive fungal diseases?

    Science.gov (United States)

    Vieira, N O; Peres, A; Aquino, V R; Pasqualotto, A C

    2010-12-01

    Yerba mate (Ilex paraguariensis) infusion is a very popular drink in South America. Although several studies have evaluated the potential for fungal contamination in foodstuff, very few investigations have been conducted with yerba mate samples. In order to evaluate for the presence of potentially pathogenic fungi, here we studied 8 brands of yerba mate commercially available in Southern Brazil. Fungal survival in adverse conditions such as gastric pH was determined by incubating samples at pH 1.5. Because hot water is generally used to prepare yerba mate infusion, the effect of several temperatures on fungal growth was also investigated. All but 1 yerba mate brand showed substantial fungal growth, in the range of <10–4900 colony-forming units per gram. Some of these fungi were able to survive extreme variations in pH and temperature. Because of the potential for yerba mate to carry pathogenic fungi, immunocompromised patients may be at risk of acquiring invasive fungal diseases by drinking yerba mate infusion.

  20. Factors influencing academic library users' intention to use mobile systems:A comparison of current users and potential adopters

    Institute of Scientific and Technical Information of China (English)

    Haijuan YANG; Sisi GUI

    2014-01-01

    Purpose:The study intends to examine the factors influencing the behavioral intention to use academic libraries' mobile systems from the perspective of current users and potential adopters,respectively.Design/methodology/approach:Our study investigates the mobile library system's acceptance by using a context-specific extension of the theory of reasoned action (TRA) and the technology acceptance model (TAM),which includes such factors as mobile self-efficacy,personal innovativeness and perceived playfulness.Structural equation modeling was used to test the validity of the proposed model based on the empirical data which was collected from 210 questionnaire survey participants.Findings:The result shows that 1) for both current users and potential adopters,attitude toward use and subjective norm both have a significant and positive impact on behavioral intention to use;2) perceived usefulness and perceived ease of use are significantly correlated to potential adopters' attitude toward use whereas perceived usefulness and perceived playfulness are significantly related to current users' attitude toward use;3) as for the comparison between the two groups of users,personal innovativeness not only affects perceived usefulness of both current users and potential adopters,but also affects potential adopters' perceived playfulness positively.Mobile self-efficacy has a significant effect on perceived ease of use for both types of users.Research limitations:Although the sample size met the basic statistics requirements for the social research,the participants were mainly college students,and other mobile system users like faculty members and researchers were not investigated.In addition,some influencing factors,such as information quality,system quality and service quality were not considered in the research model.Practical implications:This study reveals main factors which influence both current users and potential adopters' intention to use the mobile system

  1. Factors influencing academic library users’ intention to use mobile systems: A comparison of current users and potential adopters

    Institute of Scientific and Technical Information of China (English)

    Haijuan; YANG; Sisi; GUI

    2014-01-01

    Purpose: The study intends to examine the factors influencing the behavioral intention to use academic libraries’ mobile systems from the perspective of current users and potential adopters, respectively. Design/methodology/approach: Our study investigates the mobile library system’s acceptance by using a context-specific extension of the theory of reasoned action(TRA) and the technology acceptance model(TAM), which includes such factors as mobile self-efficacy, personal innovativeness and perceived playfulness. Structural equation modeling was used to test the validity of the proposed model based on the empirical data which was collected from 210 questionnaire survey participants.Findings: The result shows that 1) for both current users and potential adopters, attitude toward use and subjective norm both have a significant and positive impact on behavioral intention to use; 2) perceived usefulness and perceived ease of use are significantly correlated to potential adopters’ attitude toward use whereas perceived usefulness and perceived playfulness are significantly related to current users’ attitude toward use; 3) as for the comparison between the two groups of users, personal innovativeness not only affects perceived usefulness of both current users and potential adopters, but also affects potential adopters’ perceived playfulness positively. Mobile self-efficacy has a significant effect on perceived ease of use for both types of users.Research limitations: Although the sample size met the basic statistics requirements for the social research, the participants were mainly college students, and other mobile system users like faculty members and researchers were not investigated. In addition, some influencing factors, such as information quality, system quality and service quality were not considered in the research model.Practical implications: This study reveals main factors which influence both current users and potential adopters’ intention to use

  2. Potential role of a new PEGylated recombinant factor VIII for hemophilia A

    Directory of Open Access Journals (Sweden)

    Wynn TT

    2016-06-01

    Full Text Available Tung Thanh Wynn,1 Burak Gumuscu,2,3 1Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Florida, Gainesville, FL, 2Pediatric Hematology-Oncology, Bon Secours Health System, St. Mary’s Hospital, Richmond, VA, 3Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Virginia, Charlottesville, VA, USA Abstract: Hemophilia A, a deficiency in the activity of coagulation factor (F VIII, is an X-linked bleeding disorder with an approximate incidence of one in 5,000 male infants. Bleeding-related complications often result in greater severity of disease, poor quality of life, surgical interventions for severe joint destruction, and shortened life span. With the availability of plasma-derived and recombinant FVIII products, the benefits of primary prophylaxis were demonstrated and is now the standard of care for patients with severe factor deficiencies. Current hemophilia research is focusing on the creation of new factor replacement therapies with longer half-lives; accessing alternative mechanisms to achieve desired hemostasis and enhance bypassing ­activity; and limiting the immunogenicity of the protein. PEGylation involves the covalent attachment of polyethylene glycol (PEG to a protein, peptide, or a small molecule drug. PEG effectively increases the molecular weight and size of the protein by creating a hydrophilic cloud around the molecule. This molecular change may reduce susceptibility of the molecule to proteolytic activity and degradation. It is also believed that PEGylation changes the surface charge of the protein that ultimately interferes with some receptor-mediated clearance processes. The half-life of PEGylated factor is more prolonged when compared to non-PEGylated full-length recombinant FVIII. The dawn of a new era in the care of hemophilia patients is upon us with the release of recombinant FVIII products with extended half-lives, and products with even more extended half

  3. Hypoxia-Inducible Factor-1α: A Potential Factor for the Enhancement of Osseointegration between Dental Implants and Tissue-Engineered Bone

    Directory of Open Access Journals (Sweden)

    Duohong Zou

    2011-07-01

    Full Text Available Introduction: Tissue-engineered bones are widely utilized to protect healthy tissue, reduce pain, and increase the success rate of dental implants. one of the most challenging obstacles lies in obtaining effective os-seointegration between dental implants and tissue-engineered structures. Deficiencies in vascularization, osteogenic factors, oxygen, and other nutrients inside the tissue-engineered bone during the early stages following implantation all inhibit effective osseointe-gration. Oxygen is required for aerobic metabolism in bone and blood vessel tissues, but oxygen levels inside tissue-engineered bone are not suf-ficient for cell proliferation. HIF-1α is a pivotal regulator of hypoxic and ischemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and osteogenesis.The hypothesis: Hypoxia-Inducible Factor-1α seems a potential factor for the enhancement of osseointegration between dental implants and tissue-engineered bone.Evaluation of the hypothesis: Enhancement of HIF-1α protein expression is recognized as the most promising approach for angiogenesis, because it can induce multiple angiogenic targets in a coordinated manner. Therefore, it will be a novel potential therapeutic methods targeting HIF-1α expression to enhance osseointegration be-tween dental implants and tissue-engineered bone.

  4. Form factors and charge radii in a quantum chromodynamics-inspired potential model using variationally improved perturbation theory

    International Nuclear Information System (INIS)

    Hazarika, Bhaskar Jyoti; Choudhury, D.K.

    2015-01-01

    We use variationally improved perturbation theory (VIPT) for calculating the elastic form factors and charge radii of D, D s , B, B s and B c mesons in a quantum chromodynamics (QCD)-inspired potential model. For that, we use linear-cum-Coulombic potential and opt the Coulombic part first as parent and then the linear part as parent. The results show that charge radii and form factors are quite small for the Coulombic parent compared to the linear parent. Also, the analysis leads to a lower as well as upper bounds on the four-momentum transfer Q 2 , hinting at a workable range of Q 2 within this approach, which may be useful in future experimental analyses. Comparison of both the options shows that the linear parent is the better option. (author)

  5. CYP1B1 expression, a potential risk factor for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

    2001-05-31

    CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

  6. Predictive Factors of Potential Malignant Transformation in Recurrent Calcifying Cystic Odontogenic Tumor: Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sepideh Mokhtari

    2013-01-01

    Full Text Available Calcifying cystic odontogenic tumor (CCOT demonstrates considerable diversity in histopathology and clinical behavior. Ghost cell odontogenic carcinoma (GCOC is the rare malignant counterpart of CCOT and it frequently arises from malignant transformation of a recurrent CCOT. In this paper, we present a case of CCOT and discuss its distinct histopathologic features in recurrence. Then, we will have a review on clinical, histopathological, and immunohistochemical aspects of GCOC in the literature. Predictive factors of malignant transformation in a benign CCOT will also be discussed.

  7. Remote Preconditioning as a Novel "Conditioning" Approach to Repair the Broken Heart: Potential Mechanisms and Clinical Applications

    Czech Academy of Sciences Publication Activity Database

    Ravingerová, T.; Farkasová, V.; Griecsová, L.; Čarnická, S.; Murariková, M.; Barlaka, E.; Kolář, František; Barteková, M.; Lonek, L.; Slezák, J.; Lazou, A.

    2016-01-01

    Roč. 65, Suppl.1 (2016), S55-S64 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : ischemia/reperfusion * remote preconditioning * innate cardioprotection Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.461, year: 2016

  8. KEY DEVELOPMENT FACTORS OF THE TRANSIT AND TRANSPORT POTENTIAL OF KAZAKHSTAN

    Directory of Open Access Journals (Sweden)

    Seidulla ABDULLAYEV

    2016-06-01

    Full Text Available Nowadays, the Republic of Kazakhstan is dynamically forming up its transit policy, improving its directions and the development of new vectors. This article looks into the development of the transit and transport potential of the Republic of Kazakhstan. It presents the main conclusions on the development of a feasibility study for the construction of a logistics terminal in the seaport of Lianyungang (China as one of the directions of building transit policy, improving its direction and the formation of new vectors. The urgency of building a logistics terminal is conditioned by the necessity for national interests and further expansion of political and economic advantages of Kazakhstan.

  9. Determinants of Perceived Stress in Individuals with Obesity: Exploring the Relationship of Potentially Obesity-Related Factors and Perceived Stress

    OpenAIRE

    Florian Junne; Katrin Ziser; Katrin Elisabeth Giel; Kathrin Schag; Eva Skoda; Isabelle Mack; Andreas Niess; Stephan Zipfel; Martin Teufel

    2017-01-01

    Objective: Associations of specific types of stress with increased food intake and subsequent weight gain have been demonstrated in animal models as well as in experimental and epidemiological studies on humans. This study explores the research question of to what extent potentially obesity-related factors determine perceived stress in individuals with obesity. Methods: N = 547 individuals with obesity participated in a cross-sectional study assessing perceived stress as the outcome variable ...

  10. Revascularization and cardioprotective drug treatment in myocardial infarction patients: how do they impact on patients' survival when delivered as usual care

    Directory of Open Access Journals (Sweden)

    Courteau Josiane

    2006-05-01

    Full Text Available Abstract Background Randomized clinical trials showed the benefit of pharmacological and revascularization treatments in secondary prevention of myocardial infarction (MI, in selected population with highly controlled interventions. The objective of this study is to measure these treatments' impact on the cardiovascular (CV mortality rate among patients receiving usual care in the province of Quebec. Methods The study population consisted of a "naturalistic" cohort of all patients ≥ 65 years old living in the Quebec province, who survived a MI (ICD-9: 410 in 1998. The studied dependant variable was time to death from a CV disease. Independent variables were revascularization procedure and cardioprotective drugs. Death from a non CV disease was also studied for comparison. Revascularization procedure was defined as percutaneous transluminal coronary angioplasty (PTCA or coronary artery bypass graft (CABG. The exposure to cardioprotective drugs was defined as the number of cardioprotective drug classes (Acetylsalicylic Acid (ASA, Beta-Blockers, Angiotensin-Converting Enzyme (ACE Inhibitors, Statins claimed within the index period (first 30 days after the index hospitalization. Age, gender and a comorbidity index were used as covariates. Kaplan-Meier survival curves, Cox proportional hazard models, logistic regressions and regression trees were used. Results The study population totaled 5596 patients (3206 men; 2390 women. We observed 1128 deaths (20% within two years following index hospitalization, of them 603 from CV disease. The CV survival rate at two years is much greater for patients with revascularization, regardless of pharmacological treatments. For patients without revascularization, the CV survival rate increases with the number of cardioprotective drug classes claimed. Finally, Cox proportional hazard models, regression tree and logistic regression analyses all revealed that the absence of revascularization and, to a lower extent

  11. Identification of host factors potentially involved in RTM-mediated resistance during potyvirus long distance movement.

    Science.gov (United States)

    Sofer, Luc; Cabanillas, Daniel Garcia; Gayral, Mathieu; Téplier, Rachèle; Pouzoulet, Jérôme; Ducousso, Marie; Dufin, Laurène; Bréhélin, Claire; Ziegler-Graff, Véronique; Brault, Véronique; Revers, Frédéric

    2017-07-01

    The long distance movement of potyviruses is a poorly understood step of the viral cycle. Only factors inhibiting this process, referred to as "Restricted TEV Movement" (RTM), have been identified in Arabidopsis thaliana. On the virus side, the potyvirus coat protein (CP) displays determinants required for long-distance movement and for RTM-based resistance breaking. However, the potyvirus CP was previously shown not to interact with the RTM proteins. We undertook the identification of Arabidopsis factors which directly interact with either the RTM proteins or the CP of lettuce mosaic virus (LMV). An Arabidopsis cDNA library generated from companion cells was screened with LMV CP and RTM proteins using the yeast two-hybrid system. Fourteen interacting proteins were identified. Two of them were shown to interact with CP and the RTM proteins suggesting that a multiprotein complex could be formed between the RTM proteins and virions or viral ribonucleoprotein complexes. Co-localization experiments in Nicotiana benthamiana showed that most of the viral and cellular protein pairs co-localized at the periphery of chloroplasts which suggests a putative role for plastids in this process.

  12. Sequence Analysis of Hypothetical Proteins from 26695 to Identify Potential Virulence Factors

    Directory of Open Access Journals (Sweden)

    Ahmad Abu Turab Naqvi

    2016-09-01

    Full Text Available Helicobacter pylori is a Gram-negative bacteria that is responsible for gastritis in human. Its spiral flagellated body helps in locomotion and colonization in the host environment. It is capable of living in the highly acidic environment of the stomach with the help of acid adaptive genes. The genome of H. pylori 26695 strain contains 1,555 coding genes that encode 1,445 proteins. Out of these, 340 proteins are characterized as hypothetical proteins (HP. This study involves extensive analysis of the HPs using an established pipeline which comprises various bioinformatics tools and databases to find out probable functions of the HPs and identification of virulence factors. After extensive analysis of all the 340 HPs, we found that 104 HPs are showing characteristic similarities with the proteins with known functions. Thus, on the basis of such similarities, we assigned probable functions to 104 HPs with high confidence and precision. All the predicted HPs contain representative members of diverse functional classes of proteins such as enzymes, transporters, binding proteins, regulatory proteins, proteins involved in cellular processes and other proteins with miscellaneous functions. Therefore, we classified 104 HPs into aforementioned functional groups. During the virulence factors analysis of the HPs, we found 11 HPs are showing significant virulence. The identification of virulence proteins with the help their predicted functions may pave the way for drug target estimation and development of effective drug to counter the activity of that protein.

  13. Proteomic analysis of polyribosomes identifies splicing factors as potential regulators of translation during mitosis.

    Science.gov (United States)

    Aviner, Ranen; Hofmann, Sarah; Elman, Tamar; Shenoy, Anjana; Geiger, Tamar; Elkon, Ran; Ehrlich, Marcelo; Elroy-Stein, Orna

    2017-06-02

    Precise regulation of mRNA translation is critical for proper cell division, but little is known about the factors that mediate it. To identify mRNA-binding proteins that regulate translation during mitosis, we analyzed the composition of polysomes from interphase and mitotic cells using unbiased quantitative mass-spectrometry (LC-MS/MS). We found that mitotic polysomes are enriched with a subset of proteins involved in RNA processing, including alternative splicing and RNA export. To demonstrate that these may indeed be regulators of translation, we focused on heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a test case and confirmed that it is recruited to elongating ribosomes during mitosis. Then, using a combination of pulsed SILAC, metabolic labeling and ribosome profiling, we showed that knockdown of hnRNP C affects both global and transcript-specific translation rates and found that hnRNP C is specifically important for translation of mRNAs that encode ribosomal proteins and translation factors. Taken together, our results demonstrate how proteomic analysis of polysomes can provide insight into translation regulation under various cellular conditions of interest and suggest that hnRNP C facilitates production of translation machinery components during mitosis to provide daughter cells with the ability to efficiently synthesize proteins as they enter G1 phase. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Tissue factor expression in rheumatoid synovium: a potential role in pannus invasion of rheumatoid arthritis.

    Science.gov (United States)

    Chen, Lujun; Lu, Yahua; Chu, Yang; Xie, Jun; Ding, Wen'ge; Wang, Fengming

    2013-09-01

    Angiogenesis, as well as pannus formation within the joint, plays an important role in the erosion of articular cartilage and bone in the pathological process of rheumatoid arthritis (RA). Tissue factor (TF), an essential initiator of the extrinsic pathway of blood coagulation, is also involved in the angiogenesis and the pannus formation of RA progression. In the present study, we used immunofluorescence and confocal scanning methods to characterize TF immunolocalization in RA synovium. We showed that positive staining of TF could be immunolocalized in synoviocytes, CD19(+) B cells and CD68(+) macrophages, whereas weak or negative staining of tissue factor could be found in CD34(+) endothelial cells of neo-vessels, CD3(+) T cells and CD14(+) monocytes in RA synovium tissues. Our study demonstrates a detailed local expression of TF in the rheumatoid synovium, and supports the notion that TF, expressed not only by the synoviocytes themselves, but also the infiltrating CD19(+) B cells and CD68(+) macrophages, is involved in the pannus invasion in the progression of rheumatoid arthritis. Copyright © 2013 Elsevier GmbH. All rights reserved.

  15. Conjugated linoleic acid as a potential protective factor in prevention of breast cancer 

    Directory of Open Access Journals (Sweden)

    Agnieszka Białek

    2013-01-01

    Full Text Available Cancers are the second leading cause of deaths in Poland, among both women and men. Breast cancer is the malignancy most frequently diagnosed in women. In 2008 mammary cancer was diagnosed in up to 14 500 patients. It is also the second most common cause of cancer deaths among women in our country. Although the etiology of most cases of this disease is not known, risk factors include a variety of nutritional factors. The amount of fat consumed in the diet and the quantity and quality of fatty acids are especially crucial. Among fatty acids to which great importance in modification of cancer risk is attributed are conjugated linoleic acid. Conjugated linoleic acids (CLA are a group of positional and geometric isomers of linoleic acid, with a conjugated double bond system in the carbon chain. The main natural source of them is milk and dairy products and meat of different species of ruminants, in which cis-9, trans-11 octadecadienoic acid (rumenic acid occurs in the largest quantities, constituting over 90�0of the total pool of CLA. Another important isomer is trans-10, cis-12 octadecadienoic acid, which occurs with rumenic acid in dietary supplements, usually in the ratio 1:1. Surveys conducted show their possible health promoting effects in obesity, atherosclerosis, cardiovascular diseases, osteoporosis, diabetes, insulin resistance, inflammation, and various types of cancer, especially breast cancer. 

  16. Spatial and temporal evolution of climatic factors and its impacts on potential evapotranspiration in Loess Plateau of Northern Shaanxi, China.

    Science.gov (United States)

    Li, C; Wu, P T; Li, X L; Zhou, T W; Sun, S K; Wang, Y B; Luan, X B; Yu, X

    2017-07-01

    Agriculture is very sensitive to climate change, and correct forecasting of climate change is a great help to accurate allocation of irrigation water. The use of irrigation water is influenced by crop water demand and precipitation. Potential evapotranspiration (ET 0 ) is a measure of the ability of the atmosphere to remove water from the surface through the processes of evaporation and transpiration, assuming no control on water supply. It plays an important role in assessing crop water requirements, regional dry-wet conditions, and other factors of water resource management. This study analyzed the spatial and temporal evolution processes and characteristics of major meteorological parameters at 10 stations in the Loess Plateau of northern Shaanxi (LPNS). By using the Mann-Kendall trend test with trend-free pre-whitening and the ArcGIS platform, the potential evapotranspiration of each station was quantified by using the Penman-Monteith equation, and the effects of climatic factors on potential evapotranspiration were assessed by analyzing the contribution rate and sensitivity of the climatic factors. The results showed that the climate in LPNS has become warmer and drier. In terms of the sensitivity of ET 0 to the variation of each climatic factor in LPNS, relative humidity (0.65) had the highest sensitivity, followed by daily maximum temperature, wind speed, sunshine hours, and daily minimum temperature (-0.05). In terms of the contribution rate of each factor to ET 0 , daily maximum temperature (5.16%) had the highest value, followed by daily minimum temperature, sunshine hours, relative humidity, and wind speed (1.14%). This study provides a reference for the management of agricultural water resources and for countermeasures to climate change. According to the climate change and the characteristics of the study area, farmers in the region should increase irrigation to guarantee crop water demand. Copyright © 2017. Published by Elsevier B.V.

  17. Factors promoting or potentially impeding school success: disparities and state variations for children with special health care needs.

    Science.gov (United States)

    Bethell, Christina; Forrest, Christopher B; Stumbo, Scott; Gombojav, Narangerel; Carle, Adam; Irwin, Charles E

    2012-04-01

    School success predicts many pathways for health and well-being across the life span. Factors promoting or potentially impeding school success are critical to understand for all children and for children with special health care needs (CSHCN), whose life course trajectories are already impacted by their chronic health problems. The 2007 National Survey of Children's Health was used (1) to estimate national and state prevalence and within and across states disparities in factors promoting school success (engagement, participation, safety) or potentially impeding success (missing school, grade repetition, school identified problems) for all children and CSHCN and (2) to evaluate associations with CSHCN service need complexity and presence of emotional, behavioral or developmental problems (EBD) as well as with school case management policies in states. Among school age children, 60 % experienced all three factors promoting school success (49.3-73.8 % across states), dropping to 51.3 % for CSHCN (39.4-64.7 % across states) and to 36.2 % for the 40 % of all CSHCN who have both more complex service needs and EBD. CSHCN were more likely to experience factors potentially impeding school success. After accounting for child factors, CSHCN living in states requiring case management in schools for children with disabilities were less likely to experience grade repetition (OR 0.65). Within-state disparities between non-CSHCN and CSHCN varied across states. Threats to school success for US children are pervasive and are especially pronounced for CSHCN with more complex needs and EBD. Findings support broad, non-condition specific efforts to promote school success for CSHCN and consideration of state school policies, such as case management.

  18. Potentially modifiable lifestyle factors, cognitive reserve, and cognitive function in later life: A cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Linda Clare

    2017-03-01

    Full Text Available Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people.We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales cohort collected in 2011-2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors-cognitive and social activity, physical activity, diet, alcohol consumption, and smoking-and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%-23% of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%-27% of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve.Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition, and maintenance of cognitive health

  19. Potential risk factors associated with contact dermatitis, lameness, negative emotional state, and fear of humans in broiler chicken flocks.

    Science.gov (United States)

    Bassler, A W; Arnould, C; Butterworth, A; Colin, L; De Jong, I C; Ferrante, V; Ferrari, P; Haslam, S; Wemelsfelder, F; Blokhuis, H J

    2013-11-01

    The objectives of this study were to 1) identify determinants of poor welfare in commercial broiler chicken flocks by studying the associations between selected resource-based measures (RBM, potential risk factors), such as litter quality and dark period, and animal-based welfare indicators (ABM), such as foot pad dermatitis and lameness, and 2) establish the breadth of effect of a risk factor by determining the range of animal welfare indicators associated with each of the risk factors (i.e., the number of ABM related to a specific RBM). Eighty-nine broiler flocks were inspected in 4 European countries (France, Italy, the United Kingdom, and the Netherlands) in a cross-sectional study. The ABM were contact dermatitis (measured using scores of foot-pad dermatitis and hock burn, respectively), lameness (measured as gait score), fear of humans (measured by the avoidance distance test and the touch test), and negative emotional state (measured using qualitative behavior assessment, QBA). In a first step, risk factors were identified by building a multiple linear regression model for each ABM. Litter quality was identified as a risk factor for contact dermatitis. Length of dark period at 3 wk old (DARK3) was a risk factor for the touch test result. DARK3 and flock age were risk factors for lameness, and the number of different stockmen and DARK3 were risk factors for QBA results. Next, the ABM were grouped according to risk factor and counted. Then, in a second step, associations between the ABM were investigated using common factor analysis. The breadth of a risk factor's effect was judged by combining the number (count) of ABM related to this factor and the strength of association between these ABM. Flock age and DARK3 appeared to affect several weakly correlated ABM, thus indicating a broad range of effects. Our findings suggest that manipulation of the predominant risk factors identified in this study (DARK3, litter quality, and slaughter age) could generate

  20. Mothers of children with externalizing behavior problems: cognitive risk factors for abuse potential and discipline style and practices.

    Science.gov (United States)

    McElroy, Erika M; Rodriguez, Christina M

    2008-08-01

    Utilizing the conceptual framework of the Social Information Processing (SIP) model (Milner, 1993, 2000), associations between cognitive risk factors and child physical abuse risk and maladaptive discipline style and practices were examined in an at-risk population. Seventy-three mothers of 5-12-year-old children, who were identified by their therapist as having an externalizing behavior problem, responded to self-report measures pertaining to cognitive risk factors (empathic perspective taking, frustration tolerance, developmental expectations, parenting locus of control), abuse risk, and discipline style and practices. The Child Behavior Checklist (CBCL) provided a confirmation of the child's externalizing behaviors independent of the therapist's assessment. The results of this study suggest several cognitive risk factors significantly predict risk of parental aggression toward children. A parent's ability to empathize and take the perspective of their child, parental locus of control, and parental level of frustration tolerance were significant predictors of abuse potential (accounting for 63% of the variance) and inappropriate discipline practices (accounting for 55% of the variance). Findings of the present study provide support for processes theorized in the SIP model. Specifically, results underscore the potential role of parents' frustration tolerance, developmental expectations, locus of control, and empathy as predictive of abuse potential and disciplinary style in an at-risk sample.

  1. Prevalence of Hookworm infection and Strongyloidiasis in Cats and Potential Risk Factor of Human Diseases

    Science.gov (United States)

    Sedionoto, Blego; Anamnart, Witthaya

    2018-02-01

    Hookworm infection and Stronyloidiasis are public health problem in the worldwide which both of them could infective in human by penetrated on skin and they have potential risk from Gastrointestinal zoonotic helminths of pets, including cats. We investigated the prevalence soil transmitted helminths infection in human and cats used modified Formal-Ether Concentration and agar plate culture. Fecal samples of 23 cats and human from Naitung and Subua Villages (area study 1), and fecal samples of 15 cats and 17 humans from Thasala Beach villages (area study 2) were collected. Result of study in area study 1 showed prevalence of infection in human was not hookworm and strongyloidiasis but 10% humans have infected Ascaris and Tricuris, and in cats have infected by hookworm 75.2% and S. strercoralis 8.5%, toxocara 13%, spirometra 13% and overall prevalence 82.5%. In area study 2 showed in human has infected by Trichuris 100% and S. stercoralis 29.4% and in cats have infected by hookworm 100% and S. strercoralis 40%, toxocora 20%, and spirometra 20%. Helminth infection found in both humans in two areas study are S. strercoralis. Hookworms were the most common helminth in cats but did not connection with infection in human, while S. strercoralis was helminth infection in cats which has potential zoonotic disease to human.

  2. A Multi-Factor Analysis of Sustainable Agricultural Residue Removal Potential

    Energy Technology Data Exchange (ETDEWEB)

    Jared Abodeely; David Muth; Paul Adler; Eleanor Campbell; Kenneth Mark Bryden

    2012-10-01

    Agricultural residues have significant potential as a near term source of cellulosic biomass for bioenergy production, but sustainable removal of agricultural residues requires consideration of the critical roles that residues play in the agronomic system. Previous work has developed an integrated model to evaluate sustainable agricultural residue removal potential considering soil erosion, soil organic carbon, greenhouse gas emission, and long-term yield impacts of residue removal practices. The integrated model couples the environmental process models WEPS, RUSLE2, SCI, and DAYCENT. This study uses the integrated model to investigate the impact of interval removal practices in Boone County, Iowa, US. Residue removal of 4.5 Mg/ha was performed annually, bi-annually, and tri-annually and were compared to no residue removal. The study is performed at the soil type scale using a national soil survey database assuming a continuous corn rotation with reduced tillage. Results are aggregated across soil types to provide county level estimates of soil organic carbon changes and individual soil type soil organic matter content if interval residue removal were implemented. Results show interval residue removal is possible while improving soil organic matter. Implementation of interval removal practices provide greater increases in soil organic matter while still providing substantial residue for bioenergy production.

  3. New Factors of Conflict Potential of Modern Ethno-Political Processes in the South of Russia

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    Usmanov Rafik Khammatovich

    2015-12-01

    Full Text Available On the basis of recent studies of modern ethno-political processes the author shows the new threats and challenges of uncontrolled migration flows from the Middle East and North Africa. These processes have created a serious threat not only to EU countries but also in other continents. The author analyzes and forecasts the growing conflict potential in the Caspian region, which is particularly applied to Southern Russia. On the basis of a comparative analysis of the old and the modern conflicts, the author makes conclusion about the continuity of data due to the lack of development of negative processes of democratic processes and the low level of tolerance in the regions of the North Caucasus, which is a breeding ground for Islamic radicalism. The only constructive solution to this problem in the present period is the socio-economic stabilization of the society and the revival of the principles of tolerance since the Soviet period, taking into account regional peculiarities of the peoples living in these territories. As a result, it is necessary to provide recommendations and suggestions of scientists, economists and social scientists to expand intellectual scientific potential with a degree of respect for the principles of tolerance. In conclusion it is noted that today for Russia there cannot be a future without policy capable of ensuring harmony in inter-ethnic and religious relations, the cooperation of all constituent peoples.

  4. Contributing factors to potential turnover in a sample of South African management-level employees

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    Rudolph Muteswa

    2011-12-01

    Full Text Available Purpose: The overall purpose of this study was to explore the extent to which a number of key organisational variables influence the potential decision to leave the organisation in a sample of managerial-level employees. Organisational variables focused on included: career path strategies, management style, intrinsic and extrinsic rewards, team dynamics, training and development opportunities, and work / life balance. Methodology: An exploratory and descriptive research design was adopted. A questionnaire was developed by the researchers based on the related literature. 106 MBA students based in KwaZulu-Natal participated in the study. Findings: The three aspects of internal organisational functioning found to have a significant influence on the participant's potential turnover considerations were: management / leadership style, career path strategies and rewards. Value of the research: According to the Department of Labour (2008:5 there is need for an additional 22 600 managers in various professions in South Africa. As a result of the skills shortages, South African organisations find themselves competing with international organisations for managerial-level employees, resulting in a 'war for talent'. This research is of significant value to organisations as it provides information relevant to the design and support of talent management and retention strategies in South African organisations.

  5. Invasion-Related Factors as Potential Diagnostic and Therapeutic Targets in Oral Squamous Cell Carcinoma—A Review

    Science.gov (United States)

    Siriwardena, Samadarani B. S. M.; Tsunematsu, Takaaki; Qi, Guangying; Ishimaru, Naozumi; Kudo, Yasusei

    2018-01-01

    It is well recognized that the presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). In solid epithelial cancer, the first step during the process of metastasis is the invasion of cancer cells into the underlying stroma, breaching the basement membrane (BM)—the natural barrier between epithelium and the underlying extracellular matrix (ECM). The ability to invade and metastasize is a key hallmark of cancer progression, and the most complicated and least understood. These topics continue to be very active fields of cancer research. A number of processes, factors, and signaling pathways are involved in regulating invasion and metastasis. However, appropriate clinical trials for anti-cancer drugs targeting the invasion of OSCC are incomplete. In this review, we summarize the recent progress on invasion-related factors and emerging molecular determinants which can be used as potential for diagnostic and therapeutic targets in OSCC. PMID:29758011

  6. Profiling antibody responses to infections by Chlamydia abortus enables identification of potential virulence factors and candidates for serodiagnosis.

    Science.gov (United States)

    Forsbach-Birk, Vera; Foddis, Corinna; Simnacher, Ulrike; Wilkat, Max; Longbottom, David; Walder, Gernot; Benesch, Christiane; Ganter, Martin; Sachse, Konrad; Essig, Andreas

    2013-01-01

    Enzootic abortion of ewes (EAE) due to infection with the obligate intracellular pathogen Chlamydia (C.) abortus is an important zoonosis leading to considerable economic loss to agriculture worldwide. The pathogen can be transmitted to humans and may lead to serious infection in pregnant women. Knowledge about epidemiology, clinical course and transmission to humans is hampered by the lack of reliable diagnostic tools. Immunoreactive proteins, which are expressed in infected animals and humans, may serve as novel candidates for diagnostic marker proteins and represent putative virulence factors. In order to broaden the spectrum of immunogenic C. abortus proteins we applied 2D immunoblot analysis and screening of an expression library using human and animal sera. We have identified 48 immunoreactive proteins representing potential diagnostic markers and also putative virulence factors, such as CAB080 (homologue of the "macrophage infectivity potentiator", MIP), CAB167 (homologue of the "translocated actin recruitment protein", TARP), CAB712 (homologue of the "chlamydial protease-like activity factor", CPAF), CAB776 (homologue of the "Polymorphic membrane protein D", PmpD), and the "hypothetical proteins" CAB063, CAB408 and CAB821, which are predicted to be type III secreted. We selected two putative virulence factors for further characterization, i.e. CAB080 (cMIP) and CAB063, and studied their expression profiles at transcript and protein levels. Analysis of the subcellular localization of both proteins throughout the developmental cycle revealed CAB063 being the first C. abortus protein shown to be translocated to the host cell nucleus.

  7. Profiling antibody responses to infections by Chlamydia abortus enables identification of potential virulence factors and candidates for serodiagnosis.

    Directory of Open Access Journals (Sweden)

    Vera Forsbach-Birk

    Full Text Available Enzootic abortion of ewes (EAE due to infection with the obligate intracellular pathogen Chlamydia (C. abortus is an important zoonosis leading to considerable economic loss to agriculture worldwide. The pathogen can be transmitted to humans and may lead to serious infection in pregnant women. Knowledge about epidemiology, clinical course and transmission to humans is hampered by the lack of reliable diagnostic tools. Immunoreactive proteins, which are expressed in infected animals and humans, may serve as novel candidates for diagnostic marker proteins and represent putative virulence factors. In order to broaden the spectrum of immunogenic C. abortus proteins we applied 2D immunoblot analysis and screening of an expression library using human and animal sera. We have identified 48 immunoreactive proteins representing potential diagnostic markers and also putative virulence factors, such as CAB080 (homologue of the "macrophage infectivity potentiator", MIP, CAB167 (homologue of the "translocated actin recruitment protein", TARP, CAB712 (homologue of the "chlamydial protease-like activity factor", CPAF, CAB776 (homologue of the "Polymorphic membrane protein D", PmpD, and the "hypothetical proteins" CAB063, CAB408 and CAB821, which are predicted to be type III secreted. We selected two putative virulence factors for further characterization, i.e. CAB080 (cMIP and CAB063, and studied their expression profiles at transcript and protein levels. Analysis of the subcellular localization of both proteins throughout the developmental cycle revealed CAB063 being the first C. abortus protein shown to be translocated to the host cell nucleus.

  8. Potential risk factors associated with risk for drop-out and relapse during and following withdrawal of opioid prescription medication.

    Science.gov (United States)

    Heiwe, Susanne; Lönnquist, Ingeborg; Källmén, Håkan

    2011-10-01

    Withdrawal of opioid medication in patients with chronic pain has a drop-out and relapse problem. To evaluate if depressive symptoms, anxiety and pain intensity are potential risk factors for drop-out or relapse during the withdrawal process. Further, to assess internal consistency of scales for assessment of these potential risk factors. Twenty-nine patients were included. After 2 years 28 of these were followed-up. Those with depressive symptoms at baseline had a significant risk for drop-out from the withdrawal program (odds ratio 1.37) and relapse into use of opioids at follow-up (odds ratio 1.44). Drop-outs rated depressive symptoms significantly higher before detoxification. Those who relapsed rated significantly higher for pain intensity, depressive symptoms and abstinence prior to withdrawal. All scales had high reliability. To avoid drop-out and relapse clinical practice need to screen for depressive symptoms, pain intensity, and abstinence. This article presents significant reliability of scales useful within dependency centers. They can be used to identify these risk factors for drop-out and relapse, respectively, when initiating the withdrawal process. Taking these risk factors into consideration could improve the outcome of the withdrawal process by preventing drop-out and relapse. Copyright © 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  9. Genome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factors.

    Science.gov (United States)

    Eichenberger, Ramon M; Ramakrishnan, Chandra; Russo, Giancarlo; Deplazes, Peter; Hehl, Adrian B

    2017-06-13

    Infections of dogs with virulent strains of Babesia canis are characterized by rapid onset and high mortality, comparable to complicated human malaria. As in other apicomplexan parasites, most Babesia virulence factors responsible for survival and pathogenicity are secreted to the host cell surface and beyond where they remodel and biochemically modify the infected cell interacting with host proteins in a very specific manner. Here, we investigated factors secreted by B. canis during acute infections in dogs and report on in silico predictions and experimental analysis of the parasite's exportome. As a backdrop, we generated a fully annotated B. canis genome sequence of a virulent Hungarian field isolate (strain BcH-CHIPZ) underpinned by extensive genome-wide RNA-seq analysis. We find evidence for conserved factors in apicomplexan hemoparasites involved in immune-evasion (e.g. VESA-protein family), proteins secreted across the iRBC membrane into the host bloodstream (e.g. SA- and Bc28 protein families), potential moonlighting proteins (e.g. profilin and histones), and uncharacterized antigens present during acute crisis in dogs. The combined data provides a first predicted and partially validated set of potential virulence factors exported during fatal infections, which can be exploited for urgently needed innovative intervention strategies aimed at facilitating diagnosis and management of canine babesiosis.

  10. Factors Associated with Potential Food-Drug Interaction in Hospitalized Patients: A Cross-Sectional Study in Northeast Iran

    Directory of Open Access Journals (Sweden)

    Mostafa Abdollahi

    2018-04-01

    Full Text Available Background: The minimization of adverse food-drug interactions will improve patient care by optimizing the therapeutic effects and maintaining proper nutritional status. Aim: The aim of the present study was to find the main factors that may place the hospitalized patients at risk of potential food-drug interactions. Method: This cross-sectional, descriptive study was conducted on 400 inpatients admitted to the Department of Internal Medicine of a teaching hospital in Mashhad, Northeast Iran, within 20 March 2013 to 20 April 2013. The potential food-drug interactions were evaluated for 19 commonly prescribed medications. The main factors (e.g., age, gender, education level, number of medications, and duration of the disease that may place the patients at risk of potential food-drug interactions were analyzed for each patient. Results: Out of the 19 commonly prescribed medications, 17 drugs (89% were not properly used with respect to meal. Furthermore, 14 commonly prescribed drugs were found to have a high frequency (≥50% of potential food-drug interactions. Most of the patients (n=359, 89.8% consumed their medicines at inappropriate time with respect to meals. The results of a multiple logistic regression after adjustment for confounders revealed that the age [β=0.005, CI: 0.0-0.01; P=033], number of medications [β=0.1, CI: 0.083-0.117; P

  11. TDRP deficiency contributes to low sperm motility and is a potential risk factor for male infertility.

    Science.gov (United States)

    Mao, Shanhua; Wu, Fei; Cao, Xinyi; He, Min; Liu, Naijia; Wu, Huihui; Yang, Zhihong; Ding, Qiang; Wang, Xuanchun

    2016-01-01

    TDRP (Testis Development-Related Protein), a nuclear factor, might play an important role in spermatogenesis. However, the molecular mechanisms of TDRP underlying these fundamental processes remain elusive. In this study, a Tdrp-deficient mouse model was generated. Fertility tests and semen analysis were performed. Tdrp-deficient mice were not significantly different from wild-type littermates in development of testes, genitourinary tract, or sperm count. Morphologically, spermatozoa of the Tdrp-deficient mice was not significantly different from the wild type. Several sperm motility indexes, i.e. the average path velocity (VAP), the straight line velocity (VSL) and the curvilinear velocity (VCL) were significantly decreased in Tdrp-deficient mice (psperm also increased significantly in the mutant mice (psperm motility, but Tdrp deficiency alone was not sufficient to cause male infertility in mice. Additionally, TDRP1 might participate in spermatogenes is through interaction with PRM2.

  12. [Sexual harassment among students - prevalence, developmental factors and potential ways of intervention].

    Science.gov (United States)

    Allroggen, M; Rau, T; Fegert, J M

    2014-01-01

    Sexual harassment among adolescents has long been neglected in Germany though it is frequent and leads to significant strain for the victims. In international studies, the prevalence of sexual harassment ranges from 10 to 80 % among students. For the development of sexual harassment individual as well as school based factors play a role. Different pathways lead to this problematic behaviour. The effect of new media in the development of sexual harassment cannot be estimated so far. Frequent consequences of sexual harassment in addition to school associated difficulties are unspecific somatic complaints. General practitioners and pediatricians are frequently consulted tn the first place. Recommendations for consultation and interventions are presented. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Vitamin D deficiency: A potential risk factor for Clostridium difficile infection

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    Youssef D

    2012-10-01

    Full Text Available Dima Youssef,1 William B Grant,2 Alan N Peiris3,41Department of Internal Medicine, Division of Infectious Diseases, 2Sunlight, Nutrition and Health Research Center, San Francisco, CA USA; 3Department of Medicine, Mountain Home VAMC, 4Department of Medicine, East Tennessee State University, Johnson City, Tennessee, USAIn the July 3, 2012 issue of the journal of Risk Management and Healthcare Policy, Martinez et al present a nice review on Clostridium difficile (C. difficile infections.1 The different manifestations of this challenging disease along with the high cost and burden on the health care system were discussed. While the authors did an admirable job in discussing traditional risk factors, they do not mention vitamin D deficiency.View original paper by Martinez and colleagues.

  14. IL-1β a potential factor for discriminating between thyroid carcinoma and atrophic thyroiditis.

    Science.gov (United States)

    Kammoun-Krichen, Maha; Bougacha-Elleuch, Noura; Mnif, Mouna; Bougacha, Fadia; Charffedine, Ilhem; Rebuffat, Sandra; Rebai, Ahmed; Glasson, Emilie; Abid, Mohamed; Ayadi, Fatma; Péraldi-Roux, Sylvie; Ayadi, Hammadi

    2012-01-01

    Interactions between cytokines and others soluble factors (hormones, antibodies...) can play an important role in the development of thyroid pathogenesis. The purpose of the present study was to examine the possible correlation between serum cytokine concentrations, thyroid hormones (FT4 and TSH) and auto-antibodies (Tg and TPO), and their usefulness in discriminating between different thyroid conditions. In this study, we investigated serum from 115 patients affected with a variety of thyroid conditions (44 Graves' disease, 17 Hashimoto's thyroiditis, 11 atrophic thyroiditis, 28 thyroid nodular goitre and 15 papillary thyroid cancer), and 30 controls. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Thyroid hormones and auto-antibodies were measured using ELISA. Our study showed that IL-1β serum concentrations allow the discrimination between atrophic thyroiditis and papillary thyroid cancer groups (p = 0.027).

  15. The Impact of Obesity in the Workplace: a Review of Contributing Factors, Consequences and Potential Solutions.

    Science.gov (United States)

    Shrestha, Nipun; Pedisic, Zeljko; Neil-Sztramko, Sarah; Kukkonen-Harjula, Katriina T; Hermans, Veerle

    2016-09-01

    This narrative review summarized findings from previous reviews and the most recently published studies, regarding the following: (1) the association between two occupational risk factors-shift work and sedentary work-and obesity, (2) the effects of obesity on workplace productivity and (3) the effectiveness of workplace interventions aimed at preventing or reducing obesity. Despite some inconsistencies in findings, there is convincing evidence that shift work increases the risk of obesity, while most studies did not show a significant association between sedentary work and obesity. Overweight and obesity were found to be associated with absenteeism, disability pension and overall work impairment, whilst evidence of their relationship with presenteeism, unemployment and early retirement was not consistent. Due to the vast heterogeneity in the types of workplace-based interventions to prevent or treat obesity, no sound conclusions can as yet be drawn about their overall effectiveness and best practice recommendations for their implementation.

  16. Tobacco Smoke Exposure Impairs Brain Insulin/IGF Signaling: Potential Co-Factor Role in Neurodegeneration.

    Science.gov (United States)

    Deochand, Chetram; Tong, Ming; Agarwal, Amit R; Cadenas, Enrique; de la Monte, Suzanne M

    2016-01-01

    Human studies suggest tobacco smoking is a risk factor for cognitive impairment and neurodegeneration, including Alzheimer's disease (AD). However, experimental data linking tobacco smoke exposures to underlying mediators of neurodegeneration, including impairments in brain insulin and insulin-like growth factor (IGF) signaling in AD are lacking. This study tests the hypothesis that cigarette smoke (CS) exposures can impair brain insulin/IGF signaling and alter expression of AD-associated proteins. Adult male A/J mice were exposed to air for 8 weeks (A8), CS for 4 or 8 weeks (CS4, CS8), or CS8 followed by 2 weeks recovery (CS8+R). Gene expression was measured by qRT-PCR analysis and proteins were measured by multiplex bead-based or direct binding duplex ELISAs. CS exposure effects on insulin/IGF and insulin receptor substrate (IRS) proteins and phosphorylated proteins were striking compared with the mRNA. The main consequences of CS4 or CS8 exposures were to significantly reduce insulin R, IGF-1R, IRS-1, and tyrosine phosphorylated insulin R and IGF-1R proteins. Paradoxically, these effects were even greater in the CS8+R group. In addition, relative levels of S312-IRS-1, which inhibits downstream signaling, were increased in the CS4, CS8, and CS8+R groups. Correspondingly, CS and CS8+R exposures inhibited expression of proteins and phosphoproteins required for signaling through Akt, PRAS40, and/or p70S6K, increased AβPP-Aβ, and reduced ASPH protein, which is a target of insulin/IGF-1 signaling. Secondhand CS exposures caused molecular and biochemical abnormalities in brain that overlap with the findings in AD, and many of these effects were sustained or worsened despite short-term CS withdrawal.

  17. In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

    International Nuclear Information System (INIS)

    Barbon, Silvia; Stocco, Elena; Negro, Alessandro; Dalzoppo, Daniele; Borgio, Luca; Rajendran, Senthilkumar; Grandi, Francesca; Porzionato, Andrea; Macchi, Veronica; De Caro, Raffaele

    2016-01-01

    In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in the future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was

  18. An Epidemiologic Investigation of Potential Risk Factors for Nodding Syndrome in Kitgum District, Uganda.

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    Jennifer L Foltz

    Full Text Available Nodding Syndrome (NS, an unexplained illness characterized by spells of head bobbing, has been reported in Sudan and Tanzania, perhaps as early as 1962. Hypothesized causes include sorghum consumption, measles, and onchocerciasis infection. In 2009, a couple thousand cases were reportedly in Northern Uganda.In December 2009, we identified cases in Kitgum District. The case definition included persons who were previously developmentally normal who had nodding. Cases, further defined as 5- to 15-years-old with an additional neurological deficit, were matched to village controls to assess risk factors and test biological specimens. Logistic regression models were used to evaluate associations.Surveillance identified 224 cases; most (95% were 5-15-years-old (range = 2-27. Cases were reported in Uganda since 1997. The overall prevalence was 12 cases per 1,000 (range by parish = 0·6-46. The case-control investigation (n = 49 case/village control pairs showed no association between NS and previously reported measles; sorghum was consumed by most subjects. Positive onchocerciasis serology [age-adjusted odds ratio (AOR1 = 14·4 (2·7, 78·3], exposure to munitions [AOR1 = 13·9 (1·4, 135·3], and consumption of crushed roots [AOR1 = 5·4 (1·3, 22·1] were more likely in cases. Vitamin B6 deficiency was present in the majority of cases (84% and controls (75%.NS appears to be increasing in Uganda since 2000 with 2009 parish prevalence as high as 46 cases per 1,000 5- to 15-year old children. Our results found no supporting evidence for many proposed NS risk factors, revealed association with onchocerciasis, which for the first time was examined with serologic testing, and raised nutritional deficiencies and toxic exposures as possible etiologies.

  19. Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.

    Science.gov (United States)

    Nguyen, Quan Dong; De Falco, Sandro; Behar-Cohen, Francine; Lam, Wai-Ching; Li, Xuri; Reichhart, Nadine; Ricci, Federico; Pluim, Jennifer; Li, William W

    2018-02-01

    The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.

  20. In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Barbon, Silvia, E-mail: silvia.barbon@yahoo.it [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling (TES) ONLUS, Via De Sanctis 10, Caselle di Selvazzano Dentro, 35030 Padua (Italy); Stocco, Elena, E-mail: elena.stocco@gmail.com [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling (TES) ONLUS, Via De Sanctis 10, Caselle di Selvazzano Dentro, 35030 Padua (Italy); Negro, Alessandro, E-mail: alessandro.negro@unipd.it [Department of Biomedical Sciences, University of Padova, Via Colombo 3, 35121 Padua (Italy); Dalzoppo, Daniele, E-mail: daniele.dalzoppo@unipd.it [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Borgio, Luca, E-mail: borgio.luca@gmail.com [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Rajendran, Senthilkumar, E-mail: senthilstem@gmail.com [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Grandi, Francesca, E-mail: francesca.grandi7825@gmail.com [Department of Women' s and Children' s Health, Pediatric Surgery, University of Padua, Via Giustiniani 3, 35121 Padua (Italy); Porzionato, Andrea, E-mail: andrea.porzionato@unipd.it [Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Via Gabelli 65, 35121 Padua (Italy); Macchi, Veronica, E-mail: veronica.macchi@unipd.it [Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Via Gabelli 65, 35121 Padua (Italy); De Caro, Raffaele, E-mail: raffaele.decaro@unipd.it [Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Via Gabelli 65, 35121 Padua (Italy); and others

    2016-10-15

    In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in the future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was

  1. The potential roles of hepatocyte growth factor (HGF-MET pathway inhibitors in cancer treatment

    Directory of Open Access Journals (Sweden)

    Parikh RA

    2014-06-01

    Full Text Available Rahul A Parikh,1 Peng Wang,2 Jan H Beumer,3 Edward Chu,1 Leonard J Appleman11Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; 2Division of Medical Oncology, University of Kentucky College of Medicine, Markey Cancer Center, Lexington, KY, USA; 3University of Pittsburgh School of Pharmacy, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USAAbstract: MET is located on chromosome 7q31 and is a proto-oncogene that encodes for hepatocyte growth factor (HGF receptor, a member of the receptor tyrosine kinase (RTK family. HGF, also known as scatter factor (SF, is the only known ligand for MET. MET is a master regulator of cell growth and division (mitogenesis, mobility (motogenesis, and differentiation (morphogenesis; it plays an important role in normal development and tissue regeneration. The HGF-MET axis is frequently dysregulated in cancer by MET gene amplification, translocation, and mutation, or by MET or HGF protein overexpression. MET dysregulation is associated with an increased propensity for metastatic disease and poor overall prognosis across multiple tumor types. Targeting the dysregulated HGF-MET pathway is an area of active research; a number of monoclonal antibodies to HGF and MET, as well as small molecule inhibitors of MET, are under development. This review summarizes the key biological features of the HGF-MET axis, its dysregulation in cancer, and the therapeutic agents targeting the HGF-MET axis, which are in development.Keywords: MET inhibitor, HGF inhibitor, cancer

  2. Study of different factors which can explain the radon exhalation potential of soils

    International Nuclear Information System (INIS)

    Demongeot, St.

    1997-01-01

    Radon is a natural radioactive gas belonging to the Uranium-238 chain, which is present in the earth crust and produced by the disintegration of radium-226. It is considered as the major source of radiological exposure of man to natural radiation because it can accumulate in indoor atmosphere. So, this health risk must be take into account.The aim of this study is to find some tools in order to identify high radon level area. The first part of this study has consisted in measurement of radon emission from different not sufficient for the estimation of the radon exhalation potential in a given area. In the second part of this work, we have studied the variations of in situ radon concentration as a function of different geological and pedologic parameters of the site. With the results obtained, we have determined the data which have to be considered, and the methodology to be applied for the determination of the radon exhalation of a given area. Furthermore, by the mean of numerical simulations (TRACH Model), it was possible to know the scale of radon flux variation in a given point versus the hydric state of the ground and thus the permeability: these parameters are not easy to measure because of their variabilities with time. The methodology ESPERAS (EStimation du Potential d'Exhalation en Radon des Sols) developed during this work was applied first, at a local scale and then to greater area. The values estimated by this way are in a good agreement with the results of measurements. So, we can determine the areas which are affected by high radon levels. (author)

  3. Recombinant Human Acidic Fibroblast Growth Factor (aFGF) Expressed in Nicotiana benthamiana Potentially Inhibits Skin Photoaging.

    Science.gov (United States)

    Ha, Jang-Ho; Kim, Ha-Neul; Moon, Ki-Beom; Jeon, Jae-Heung; Jung, Dai-Hyun; Kim, Su-Jung; Mason, Hugh S; Shin, Seo-Yeon; Kim, Hyun-Soon; Park, Kyung-Mok

    2017-07-01

    Responding to the need for recombinant acidic fibroblast growth factor in the pharmaceutical and cosmetic industries, we established a scalable expression system for recombinant human aFGF using transient and a DNA replicon vector expression in Nicotiana benthamiana . Recombinant human-acidic fibroblast growth factor was recovered following Agrobacterium infiltration of N. benthamiana . The optimal time point at which to harvest recombinant human acidic fibroblast growth factor expressing leaves was found to be 4 days post-infiltration, before necrosis was evident. Commassie-stained SDS-PAGE gels of His-tag column eluates, concentrated using a 10 000 molecular weight cut-off column, showed an intense band at the expected molecular weight for recombinant human acidic fibroblast growth factor. An immunoblot confirmed that this band was recombinant human acidic fibroblast growth factor. Up to 10 µg recombinant human-acidic fibroblast growth factor/g of fresh leaves were achieved by a simple affinity purification protocol using protein extract from the leaves of agroinfiltrated N. benthamiana . The purified recombinant human acidic fibroblast growth factor improved the survival rate of UVB-irradiated HaCaT and CCD-986sk cells approximately 89 and 81 %, respectively. N. benthamiana -derived recombinant human acidic fibroblast growth factor showed similar effects on skin cell proliferation and UVB protection compared to those of Escherichia coli -derived recombinant human acidic fibroblast growth factor. Additionally, N. benthamiana- derived recombinant human acidic fibroblast growth factor increased type 1 procollagen synthesis up to 30 % as well as reduced UVB-induced intracellular reactive oxygen species generation in fibroblast (CCD-986sk) cells.UVB is a well-known factor that causes various types of skin damage and premature aging. Therefore, the present study demonstrated that N. benthamiana -derived recombinant human acidic fibroblast growth factor

  4. Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

    1998-06-01

    In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.

  5. Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

    Science.gov (United States)

    Park, Paula E; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Schulteis, Gery; Koob, George F

    2013-09-01

    Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

  6. Dialkoxyquinazolines: Screening Epidermal Growth Factor ReceptorTyrosine Kinase Inhibitors for Potential Tumor Imaging Probes

    Energy Technology Data Exchange (ETDEWEB)

    VanBrocklin, Henry F.; Lim, John K.; Coffing, Stephanie L.; Hom,Darren L.; Negash, Kitaw; Ono, Michele Y.; Hanrahan, Stephen M.; Taylor,Scott E.; Vanderpoel, Jennifer L.; Slavik, Sarah M.; Morris, Andrew B.; Riese II, David J.

    2005-09-01

    The epidermal growth factor receptor (EGFR), a long-standingdrug development target, is also a desirable target for imaging. Sixteendialkoxyquinazoline analogs, suitable for labeling with positron-emittingisotopes, have been synthesized and evaluated in a battery of in vitroassays to ascertain their chemical and biological properties. Thesecharacteristics provided the basis for the adoption of a selection schemato identify lead molecules for labeling and in vivo evaluation. A newEGFR tyrosine kinase radiometric binding assay revealed that all of thecompounds possessed suitable affinity (IC50 = 0.4 - 51 nM) for the EGFRtyrosine kinase. All of the analogs inhibited ligand-induced EGFRtyrosine phosphorylation (IC50 = 0.8 - 20 nM). The HPLC-estimatedoctanol/water partition coefficients ranged from 2.0-5.5. Four compounds,4-(2'-fluoroanilino)- and 4-(3'-fluoroanilino)-6,7-diethoxyquinazoline aswell as 4-(3'-chloroanilino)- and4-(3'-bromoanilino)-6,7-dimethoxyquinazoline, possess the bestcombination of characteristics that warrant radioisotope labeling andfurther evaluation in tumor-bearing mice.

  7. Effect of potential factors in manufacturing process on mechanical properties of F82H

    Energy Technology Data Exchange (ETDEWEB)

    Sakasegawa, Hideo, E-mail: sakasegawa.hideo@jaea.go.jp [Japan Atomic Energy Agency, Rokkasho, Aomori 039-3212 (Japan); Tanigawa, Hiroyasu [Japan Atomic Energy Agency, Rokkasho, Aomori 039-3212 (Japan); Tanigawa, Hisashi; Hirose, Takanori [Japan Atomic Energy Agency, Naka, Ibaraki 311-0193 (Japan)

    2014-10-15

    Highlights: • Effects of hot forging and cooling method on mechanical properties were studied. • Differences, inhomogeneity, and anisotropy in tensile and Charpy impact properties were observed for plates with a lower hot forging level. • No significant difference was observed in tensile and Charpy impact properties between air cooled and water quenched samples. - Abstract: A DEMO reactor requires over 3500 tons of reduced activation ferritic/martensitic steel. To prepare such a large quantity of the material with appropriate mechanical properties, it is important to study the effect of various factors in the manufacturing process for mass production. In our work, we focused on the effects of hot forging and the cooling method after normalizing, which have not been previously studied. Plates with three different thicknesses were fabricated from slabs with two different hot forging reduction ratios, and the tensile and Charpy impact properties were evaluated for each of these plates. The plates made using a lower hot forging reduction ratio had different tensile properties, and inhomogeneity and anisotropy were observed in the Charpy impact test results. These results indicate that the hot forging operation to which the ingot is initially subjected must be sufficiently high to ensure that the appropriate mechanical properties are achieved. To test the effect of the cooling method, plates cooled in air and those quenched in water after normalizing were prepared, and tensile and Charpy impact tests were performed on these plates. No significant differences were observed indicating that air cooling is sufficient to obtain the appropriate mechanical properties.

  8. Overview of Macrophage Migration Inhibitory Factor (MIF as a Potential Biomarker Relevant to Adiposity

    Directory of Open Access Journals (Sweden)

    Jun Nishihira

    2012-07-01

    Full Text Available The cytokine “macrophage migration inhibitory factor (MIF” is generally recognized as a proinflammatory cytokine, and MIF is involved in broad range of acute and chronic inflammatory states. With regard to glucose metabolism and insulin secretion, MIF is produced by pancreatic β cells and acts as a positive regulator of insulin secretion. In contrast, it is evident that MIF expressed in adipose tissues causes insulin resistance. Concerning MIF gene analysis, we found four alleles: 5-, 6-, 7-and 8-CATT at position −794 of MIF gene in a Japanese population. Genotypes without the 5-CATT allele were more common in the obese subjects than in the lean or overweight groups. It is conceivable that promoter polymorphism in the MIF gene is profoundly linked with obesity relevant to lifestyle diseases, such as diabetes. Obesity has become a serious social issue due to the inappropriate nutritional balance, and the consumption of functional foods (including functional foods to reduce fat mass is expected to overcome this issue. In this context, MIF would be a reliable quantitative biomarker to evaluate the effects of functional foods on adiposity.

  9. Cancer surgeons' distress and well-being, II: modifiable factors and the potential for organizational interventions.

    Science.gov (United States)

    Guest, Rebecca S; Baser, Ray; Li, Yuelin; Scardino, Peter T; Brown, Arthur E; Kissane, David W

    2011-05-01

    We showed in a companion paper that the prevalence of burnout among surgical oncologists at a comprehensive cancer center was 42% and psychiatric morbidity 27%, and high quality of life (QOL) was absent for 54% of surgeons. Here we examine modifiable workplace factors and other stressors associated with burnout, psychiatric morbidity, and low QOL, together with interest in interventions to reduce distress and improve wellness. Study-specific questions important for morale, QOL, and stressors associated with burnout were included in an anonymous Internet-based survey distributed to the surgical faculty at Memorial Sloan-Kettering Cancer Center. Among the 72 surgeons who responded (response rate of 73%), surgeons identified high stress from medical lawsuits, pressure to succeed in research, financial worries, negative attitudes to gender, and ability to cope with patients' suffering and death. Workplace features requiring greatest change were the reimbursement system, administrative support, and schedule. Work-life balance and relationship issues with spouse or partner caused high stress. Strongest correlations with distress were a desire to change communication with patients and the tension between the time devoted to work versus time available to be with family. Surgeons' preferences for interventions favored a fitness program, nutrition consultation, and increased socialization with colleagues, with less interest in interventions conventionally used to address psychological distress. Several opportunities to intervene at the organizational level permit efforts to reduce burnout and improve QOL.

  10. Potential virulence factors of bacteria associated with tail fan necrosis in the spiny lobster, Jasus edwardsii.

    Science.gov (United States)

    Zha, H; Jeffs, A; Dong, Y; Lewis, G

    2018-05-01

    Tail fan necrosis (TFN) is a common condition found in commercially exploited spiny lobsters that greatly diminishes their commercial value. Bacteria possessing proteolytic, chitinolytic and lipolytic capabilities were associated with TFN in spiny lobsters, Jasus edwardsii. In this study, 69 bacterial isolates exhibiting all the three enzymatic capabilities from the haemolymph and tail fans of J. edwardsii with and without TFN were further characterized and compared, including morphology, biofilm formation, antimicrobial activity, antimicrobial resistance, and production of siderophores, melanin and ammonia. The genomic patterns of the most common Vibrio crassostreae isolates were also compared between TFN-affected and unaffected lobsters. Biofilm formation was stronger in bacterial isolates from both haemolymph and tail fans of TFN-affected lobsters compared to those from the unaffected lobsters, while melanin production and siderophore production were stronger in the isolates from tail fans of lobsters with TFN. By contrast, the other characteristics of isolates were similar in lobsters with and without TFN. The Vib. crassostreae isolates from the affected lobsters had similar genomic patterns. Overall, the results indicate that in addition to proteolytic, chitinolytic and lipolytic activities, the bacteria associated with TFN commonly have enhanced activity of important virulence factors, including biofilm formation, melanin production and siderophore production. © 2018 John Wiley & Sons Ltd.

  11. Traits associated with internet addiction in young adults: Potential risk factors

    Directory of Open Access Journals (Sweden)

    Michael Lyvers

    2016-06-01

    Full Text Available The present study sought to determine whether certain personality traits associated with problematic substance use may also characterize young adults who report problematic internet use. An index of internet addiction as well as measures of traits previously linked to problematic substance use were administered to a sample of 86 young adults aged 18–30 years. Measures included the Internet Addiction Test (IAT, Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ, Depression Anxiety and Stress Scales (DASS-21, Toronto Alexithymia Scale (TAS-20, and the Fear of Intimacy Scale (FIS. Results indicated that IAT scores were significantly positively correlated with TAS-20, DASS-21, SPSRQ and FIS scores, as predicted. When age, gender and negative mood were controlled in a hierarchical regression, sensitivity to punishment (SP, sensitivity to reward (SR and FIS significantly contributed to variance in IAT in the final model. SP partially mediated the relationship between TAS-20 and IAT, whereas no such mediation was indicated for SR or FIS. Present findings suggest that alexithymia and reward sensitivity may be important risk factors for internet addiction as for problematic substance use, whereas sensitivity to punishment may account for at least part of the association between alexithymia and problematic use of the internet.

  12. High-density lipoprotein is a potential growth factor for adrenocortical cells

    International Nuclear Information System (INIS)

    Murao, Koji; Imachi, Hitomi; Cao, Wenming; Yu, Xiao; Li, Junhua; Yoshida, Kazuya; Ahmed, Rania A.M.; Matsumoto, Kensuke; Nishiuchi, Takamasa; Wong, Norman C.W.; Ishida, Toshihiko

    2006-01-01

    The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [ 3 H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor

  13. Identification of anthranilamide derivatives as potential factor Xa inhibitors: drug design, synthesis and biological evaluation.

    Science.gov (United States)

    Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin

    2015-05-05

    The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Dialkoxyquinazolines: Screening Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Potential Tumor Imaging Probes

    International Nuclear Information System (INIS)

    VanBrocklin, Henry F.; Lim, John K.; Coffing, Stephanie L.; Hom, Darren L.; Negash, Kitaw; Ono, Michele Y.; Hanrahan, Stephen M.; Taylor, Scott E.; Vanderpoel, Jennifer L.; Slavik, Sarah M.; Morris, Andrew B.; Riese II, David J.

    2005-01-01

    The epidermal growth factor receptor (EGFR), a long-standing drug development target, is also a desirable target for imaging. Sixteen dialkoxyquinazoline analogs, suitable for labeling with positron-emitting isotopes, have been synthesized and evaluated in a battery of in vitro assays to ascertain their chemical and biological properties. These characteristics provided the basis for the adoption of a selection schema to identify lead molecules for labeling and in vivo evaluation. A newEGFR tyrosine kinase radiometric binding assay revealed that all of the compounds possessed suitable affinity (IC50 = 0.4 - 51 nM) for the EGFR tyrosine kinase. All of the analogs inhibited ligand-induced EGFR tyrosine phosphorylation (IC50 = 0.8 - 20 nM). The HPLC-estimated octanol/water partition coefficients ranged from 2.0-5.5. Four compounds,4-(2'-fluoroanilino)- and 4-(3'-fluoroanilino)-6,7-diethoxyquinazoline as well as 4-(3'-chloroanilino)- and4-(3'-bromoanilino)-6,7-dimethoxyquinazoline, possess the best combination of characteristics that warrant radioisotope labeling and further evaluation in tumor-bearing mice

  15. Complement Factor H as a potential atherogenic marker in chronic Chagas disease.

    Science.gov (United States)

    Lidani, Kárita Cláudia Freitas; Sandri, Thaisa Lucas; Andrade, Fabiana Antunes; Bavia, Lorena; Nisihara, Renato; Reason, Iara J Messias

    2018-05-19

    We aimed to investigate the association between plasma levels of complement Factor H (FH) with cardiac involvement, inflammatory and cardiometabolic parameters in patients with chronic Chagas disease (CD). FH plasmatic levels were determined in 80 chronic CD patients. Glycemic index, lipidogram (high-density lipoprotein cholesterol HDL-C, low-density lipoprotein cholesterol LDL-C, triglycerides and total cholesterol), and Ultrasensitive C-Reactive Protein (uCRP) values were obtained from medical records. Height, weight, body mass index (BMI) blood pressure and left ventricular ejection fraction (LVEF) were obtained from echocardiography exams. Comparisons between chronic CD clinical forms were performed using Mann-Whitney test and correlation Spearman test. FH levels were correlated positively with triglycerides (p=0.001, r=0.39), LDL-C (p=0.009, r=0.3), cholesterol (p=0.02, r=0.28), uCRP (p=0.029, r=0.31) and BMI (p=0.008, r=0.34); and negatively with HDL-C (p=0.03, r=-0.25) levels. Dyslipidemic patients showed higher FH levels compared to normolipidemic, although no difference for FH levels were observed between chronic CD clinical forms. Alternative pathway of complement may be a link between immune response and metabolic disorders, with important immunoregulatory role in chronic CD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Ric-8A, a Gα protein guanine nucleotide exchange factor potentiates taste receptor signaling

    Directory of Open Access Journals (Sweden)

    Claire J Fenech

    2009-10-01

    Full Text Available Taste receptors for sweet, bitter and umami tastants are G-protein coupled receptors (GPCRs. While much effort has been devoted to understanding G-protein-receptor interactions and identifying the components of the signalling cascade downstream of these receptors, at the level of the G-protein the modulation of receptor signal transduction remains relatively unexplored. In this regard a taste-specific regulator of G-protein signaling (RGS, RGS21, has recently been identified. To study whether guanine nucleotide exchange factors (GEFs are involved in the transduction of the signal downstream of the taste GPCRs we investigated the expression of Ric-8A and Ric-8B in mouse taste cells and their interaction with G-protein subunits found in taste buds. Mammalian Ric-8 proteins were initially identified as potent GEFs for a range of Gα subunits and Ric-8B has recently been shown to amplify olfactory signal transduction. We find that both Ric-8A and Ric-8B are expressed in a large portion of taste bud cells and that most of these cells contain IP3R-3 a marker for sweet, umami and bitter taste receptor cells. Ric-8A interacts with Gα-gustducin and Gαi2 through which it amplifies the signal transduction of hTas2R16, a receptor for bitter compounds. Overall, these findings are consistent with a role for Ric-8 in mammalian taste signal transduction.

  17. Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2.

    Directory of Open Access Journals (Sweden)

    Kunihiko Hatanaka

    Full Text Available The fibroblast growth factor (FGF system plays a critical role in the maintenance of vascular integrity via enhancing the stability of VE-cadherin at adherens junctions. However, the precise molecular mechanism is not well understood. In the present study, we aimed to investigate the detailed mechanism of FGF regulation of VE-cadherin function that leads to endothelial junction stabilization.In vitro studies demonstrated that the loss of FGF signaling disrupts the VE-cadherin-catenin complex at adherens junctions by increasing tyrosine phosphorylation levels of VE-cadherin. Among protein tyrosine phosphatases (PTPs known to be involved in the maintenance of the VE-cadherin complex, suppression of FGF signaling reduces SHP2 expression levels and SHP2/VE-cadherin interaction due to accelerated SHP2 protein degradation. Increased endothelial permeability caused by FGF signaling inhibition was rescued by SHP2 overexpression, indicating the critical role of SHP2 in the maintenance of endothelial junction integrity.These results identify FGF-dependent maintenance of SHP2 as an important new mechanism controlling the extent of VE-cadherin tyrosine phosphorylation, thereby regulating its presence in adherens junctions and endothelial permeability.

  18. POTENTIAL FOR COOPERATION WITHIN BRICS AND THE CULTURAL-CIVILIZATIONAL FACTOR

    Directory of Open Access Journals (Sweden)

    S. I. Lunev

    2014-01-01

    Full Text Available The concept of development of relations in the format of RIC, BRIC and BRICS, the scale and the scope of cooperation, the direction of activity are still relatively vague. However, there are significant prerequisites for a substantial rapprochement of states, and the main of them is the rejection of the establishment of a unipolar world. The BRICS could become for its participants a key factor both for strengthening positions in the world economic system, and for realization of concrete projects. The economic relations in the triangle Russia — China — India should be mentioned especially as the implementation of such projects is facilitated by the neighborhood of the countries in Eurasia. It is also very important to develop comprehensively cultural subsystem, first of all, the cooperation in the educational sphere (the strong increase in Chinese and Indian student enrollments to Russian universities, and medicine and natural science should be priority directions; the strengthening of the ties in the sphere of higher education and science. Cultural activities should also be dramatically expanded. The BRICS countries are not interested in a radical breaking of international political and economic relations, but are obliged to contribute to sharp strengthening of their positions in the world system.

  19. Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Makoto Akashi

    2017-06-01

    Full Text Available Hypercholesterolemia is a well-known risk factor for a wide range of diseases in developed countries. Here, we report that mice lacking functional LDLR (low density lipoprotein receptor, an animal model of human familial hypercholesterolemia, show circadian abnormalities. In free running behavioral experiments in constant darkness, these mice showed a prolonged active phase and distinctly bimodal rhythms. Even when the circadian rhythms were entrained by light and dark cycles, these mice showed a significant attenuation of behavioral onset intensity at the start of the dark period. Further, we hypothesized that the combination of hypercholesterolemia and circadian abnormalities may affect cardiovascular disease progression. To examine this possibility, we generated LDLR-deficient mice with impaired circadian rhythms by simultaneously introducing a mutation into Period2, a core clock gene, and found that these mice showed a significant enlargement of artery plaque area with an increase in inflammatory cytokine IL-6 levels. These results suggest that circadian dysfunction may be associated with the development or progression of cardiovascular diseases.

  20. Mortality of centrarchid fishes in the Potomac drainage: survey results and overview of potential contributing factors.

    Science.gov (United States)

    Blazer, V S; Iwanowicz, L R; Starliper, C E; Iwanowicz, D D; Barbash, P; Hedrick, J D; Reeser, S J; Mullican, J E; Zaugg, S D; Burkhardt, M R; Kelble, J

    2010-09-01

    Skin lesions and spring mortality events of smallmouth bass Micropterus dolomieu and selected other species were first noted in the South Branch of the Potomac River in 2002. Since that year morbidity and mortality have also been observed in the Shenandoah and Monocacy rivers. Despite much research, no single pathogen, parasite, or chemical cause for the lesions and mortality has been identified. Numerous parasites, most commonly trematode metacercariae and myxozoans; the bacterial pathogens Aeromonas hydrophila, Aeromonas salmonicida, and Flavobacterium columnare; and largemouth bass virus have all been observed. None have been consistently isolated or observed at all sites, however, nor has any consistent microscopic pathology of the lesions been observed. A variety of histological changes associated with exposure to environmental contaminants or stressors, including intersex (testicular oocytes), high numbers of macrophage aggregates, oxidative damage, gill lesions, and epidermal papillomas, were observed. The findings indicate that selected sensitive species may be stressed by multiple factors and constantly close to the threshold between a sustainable (healthy) and nonsustainable (unhealthy) condition. Fish health is often used as an indicator of aquatic ecosystem health, and these findings raise concerns about environmental degradation within the Potomac River drainage. Unfortunately, while much information has been gained from the studies conducted to date, due to the multiple state jurisdictions involved, competing interests, and other issues, there has been no coordinated approach to identifying and mitigating the stressors. This synthesis emphasizes the need for multiyear, interdisciplinary, integrative research to identify the underlying stressors and possible management actions to enhance ecosystem health.

  1. Vocal fold nodules in school age children: attention deficit hyperactivity disorder as a potential risk factor.

    Science.gov (United States)

    D'Alatri, Lucia; Petrelli, Livia; Calò, Lea; Picciotti, Pasqualina Maria; Marchese, Maria Raffaella; Bussu, Francesco

    2015-05-01

    To evaluate the presence of symptoms of inattention and hyperactivity/impulsivity in a population of school age children affected by vocal fold nodules. Parents and teachers of 18 children with vocal fold nodules (10 males, eight females; aged between 6 and 12 years) and 20 matched controls without dysphonia and/or vocal fold diseases (11 males, nine females; aged between 6 and 12 years) completed Attention-Deficit/Hyperactivity Disorder (ADHD) rating scale for parents (SDAG [Scala per i Disturbi di Attenzione/Iperattività per Genitori]) and teachers (SDAI [Scala per i Disturbi di Attenzione/Iperattività per Insegnanti) rating scales containing in two subscales items that specifically evaluate the symptoms of ADHD according to the DSM-IV. All children were subjected to videolaryngoscopy. The group with vocal fold nodules scored significantly higher than the controls; the difference between the two groups was statistically significant for both the subscales of both questionnaires (SDAG and SDAI) (P ADHD was formulated. ADHD is a possible risk factor for the development of vocal fold nodules in childhood. SDAG and SDAI rating scales may supplement the diagnostic assessment of children with vocal fold nodules. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  2. Potentially modifiable lifestyle factors, cognitive reserve, and cognitive function in later life: A cross-sectional study

    Science.gov (United States)

    Wu, Yu-Tzu

    2017-01-01

    Background Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people. Methods and findings We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales) cohort collected in 2011–2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors—cognitive and social activity, physical activity, diet, alcohol consumption, and smoking—and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%–23%) of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%–27%) of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve. Conclusions Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition

  3. Modeling the potential risk factors of bovine viral diarrhea prevalence in Egypt using univariable and multivariable logistic regression analyses

    Directory of Open Access Journals (Sweden)

    Abdelfattah M. Selim

    2018-03-01

    Full Text Available Aim: The present cross-sectional study was conducted to determine the seroprevalence and potential risk factors associated with Bovine viral diarrhea virus (BVDV disease in cattle and buffaloes in Egypt, to model the potential risk factors associated with the disease using logistic regression (LR models, and to fit the best predictive model for the current data. Materials and Methods: A total of 740 blood samples were collected within November 2012-March 2013 from animals aged between 6 months and 3 years. The potential risk factors studied were species, age, sex, and herd location. All serum samples were examined with indirect ELIZA test for antibody detection. Data were analyzed with different statistical approaches such as Chi-square test, odds ratios (OR, univariable, and multivariable LR models. Results: Results revealed a non-significant association between being seropositive with BVDV and all risk factors, except for species of animal. Seroprevalence percentages were 40% and 23% for cattle and buffaloes, respectively. OR for all categories were close to one with the highest OR for cattle relative to buffaloes, which was 2.237. Likelihood ratio tests showed a significant drop of the -2LL from univariable LR to multivariable LR models. Conclusion: There was an evidence of high seroprevalence of BVDV among cattle as compared with buffaloes with the possibility of infection in different age groups of animals. In addition, multivariable LR model was proved to provide more information for association and prediction purposes relative to univariable LR models and Chi-square tests if we have more than one predictor.

  4. Increasing the industrial potential of a region as a factor of improving the region’s competitiveness

    Directory of Open Access Journals (Sweden)

    Lidiya Viktorovna Shamray

    2015-09-01

    Full Text Available Objective to determine the factors of increasing the region competitiveness by defining the industrial potential of its enterprises. Methods in the research the systemic structural functional situational economic analysis was widely used as well as modelling of the economic entities functioning. The main modeling method used in this work is the model of breakeven point widely known and tested in many enterprises. The dependence proposed by the author is of analytical character. Results the article considers different approaches to the definition of competitiveness the effect of the factors is described. The industrial potential of the enterprises is presented as one of the factors of regional competitiveness. The difference is described between the competitive advantage in commercial and production activities. The author suggests a methodology allowing to evaluate the competitiveness of industrial enterprises through the performance of production capacity the possibility of making managerial decisions based on the results of its application the results of the model testing are present. The possibility of applying the model at the regional level is shown. Scientific novelty the article presents the authorrsquos method allowing to calculate the potential growth of the enterprises competitiveness using the output capacities as the difference between the maximum and actual values of capacity. Practical significance the use of models in the practice of the company allows to evaluate the enterprise competitiveness identifying the marginal productivity of the equipment. Once it has been reached the questions arise how long the company will remain competitive in achieving 100 capacity utilization selection of areas of extensive growth due to the fact that the limits of intensive growth have been achieved. Testing of the model was carried out at the Volgograd baking enterprises it showed a high accuracy of the calculation the deviation of calculated

  5. Genome-Wide Analysis to Identify HLA Factors Potentially Associated With Severe Dengue

    Directory of Open Access Journals (Sweden)

    Sudheer Gupta

    2018-04-01

    Full Text Available The pathogenesis of dengue hemorrhagic fever (DHF, following dengue virus (DENV infection, is a complex and poorly understood phenomenon. In view of the clinical need of identifying patients with higher likelihood of developing this severe outcome, we undertook a comparative genome-wide association analysis of epitope variants from sequences available in the ViPR database that have been reported to be differentially related to dengue fever and DHF. Having enumerated the incriminated epitope variants, we determined the corresponding HLA alleles in the context of which DENV infection could potentially precipitate DHF. Our analysis considered the development of DHF in three different perspectives: (a as a consequence of primary DENV infection, (b following secondary DENV infection with a heterologous serotype, (c as a result of DENV infection following infection with related flaviviruses like Zika virus, Japanese Encephalitis virus, West Nile virus, etc. Subject to experimental validation, these viral and host markers would be valuable in triaging DENV-infected patients for closer supervision owing to the relatively higher risk of poor prognostic outcome and also for the judicious allocation of scarce institutional resources during large outbreaks.

  6. Benefits of Nut Consumption on Insulin Resistance and Cardiovascular Risk Factors: Multiple Potential Mechanisms of Actions

    Directory of Open Access Journals (Sweden)

    Yoona Kim

    2017-11-01

    Full Text Available Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM and related cardiovascular disease (CVD. The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies. The favourable effects of nuts could be explained by the unique nutrient composition and bioactive compounds in nuts. Unsaturated fatty acids (monounsaturated fatty acids and polyunsaturated fatty acids present in nuts may play a role in glucose control and appetite suppression. Fiber and polyphenols in nuts may also have an anti-diabetic effect by altering gut microbiota. Nuts lower serum cholesterol by reduced cholesterol absorption, inhibition of HMG-CoA reductase and increased bile acid production by stimulation of 7-α hydroxylase. Arginine and magnesium improve inflammation, oxidative stress, endothelial function and blood pressure. In conclusion, nuts contain compounds that favourably influence glucose homeostasis, weight control and vascular health. Further investigations are required to identify the most important mechanisms by which nuts decrease the risk of T2DM and CVD.

  7. Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study

    Science.gov (United States)

    Abbasi, Ali; Deetman, Petronella E.; Corpeleijn, Eva; Gansevoort, Ron T.; Gans, Rijk O.B.; Hillege, Hans L.; van der Harst, Pim; Stolk, Ronald P.; Navis, Gerjan; Alizadeh, Behrooz Z.; Bakker, Stephan J.L.

    2014-01-01

    Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6%). We used rs6742078 located in UDP-glucuronosyltransferase (UGT1A1) locus as instrumental variable (IV) to study a potential causal effect of serum total bilirubin on T2D risk. T2D developed in a total of 210 (6.2%) participants during a median follow-up of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; Pbilirubin levels, we observed a 25% (OR 0.75 [95%CI, 0.62-0.92]; P=0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal ORIVestimation per 1-SD increase in log-transformed bilirubin 0.58 [95%CI, 0.39-0.84]; P=0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman chi-square test Pfor difference =0.19). These novel results provide evidence that elevated bilirubin is causally associated with risk of T2D and support its role as a protective determinant. PMID:25368098

  8. Factors determining the potential for onward transmission of variant Creutzfeldt–Jakob disease via surgical instruments

    Science.gov (United States)

    Garske, Tini; Ward, Hester J.T; Clarke, Paul; Will, Robert G; Ghani, Azra C

    2006-01-01

    While the number of variant Creutzfeldt–Jakob disease (vCJD) cases continues to decline, concern has been raised that transmission could occur directly from one person to another through routes including the transfer of blood and shared use of surgical instruments. Here we firstly present data on the surgical procedures undertaken on vCJD patients prior to onset of clinical symptoms, which supports the hypothesis that cases via this route are possible. We then apply a mathematical framework to assess the potential for self-sustaining epidemics via surgical procedures. Data from hospital episode statistics on the rates of high- and medium-risk procedures in the UK were used to estimate model parameters, and sensitivity to other unknown parameters about surgically transmitted vCJD was assessed. Our results demonstrate that a key uncertainty determining the scale of an epidemic and whether it is self-sustaining is the number of times a single instrument is re-used, alongside the infectivity of contaminated instruments and the effectiveness of cleaning. A survey into the frequency of re-use of surgical instruments would help reduce these uncertainties. PMID:17015298

  9. Gastrointestinal obstruction caused by solidification and coagulation of enteral nutrition: pathogenetic mechanisms and potential risk factors

    Directory of Open Access Journals (Sweden)

    Leonello G

    2018-04-01

    Full Text Available Grazia Leonello,1 Antonio Giacomo Rizzo,1 Viviane Di Dio,2 Antonio Soriano,3 Claudia Previti,3 Grazia Giulia Pantè,3 Claudio Mastrojeni,1 Sebastiano Pantè1 1Department of Human Pathology of Adults and Evolutive Era “Gaetano Barresi”, University of Messina, Messina, Italy; 2Health Research Institute Bonino Pulejo, Piemonte Hospital, Messina, Italy; 3Department of Medical and Surgery Science, University of Messina, Messina, Italy Abstract: Enteral nutrition (EN is preferred in order to provide nutrition and reduce catabolism in critically ill patients. Recent studies suggest that the use of EN is successful and complications are rare. However, an underestimated mechanical complication of tube feedings seen in critically ill patients is the coagulation and solidification of the EN causing gastrointestinal obstruction. This report describes two clinical cases (1.23% of all cases seen at our clinic of obstruction and perforation of the small bowel secondary to the solidification of EN. The understanding and early recognition of this potential complication are essential for the prevention and successful treatment of this condition. Keywords: enteral nutrition, gastrointestinal contents, intestinal obstruction, small-bowel bezoar

  10. Periodontitis as a potential risk factor for chronic obstructive pulmonary disease: A retrospective study

    Directory of Open Access Journals (Sweden)

    Deo Vikas

    2009-01-01

    Full Text Available Aims and Objectives : A relationship between poor periodontal health and respiratory disease has been suggested by a number of recent studies. The present study was undertaken to evaluate potential association between respiratory diseases and periodontal health status and to co-relate the severity of periodontal disease with that of chronic obstructive pulmonary disease (COPD. Materials and Methods : 150 patients of COPD (test group and 50 Patients without COPD (control group were recruited for the study. Information regarding patient′s demographic and socioeconomic status and lifestyle (history of smoking were considered in the study. Patients with COPD were grouped into mild, moderate and severe category on the basis of Spirometry. Periodontal health was assessed by measuring probing pocket depth, Clinical Attachment Loss (CAL and Oral Hygiene Index (OHI. Results : The results showed that the subjects with COPD had significantly more mean CAL and a higher mean OHI than those without COPD. The risk for COPD appeared to be significantly elevated when attachment loss was found to be severe. A trend was noted in that lung function appeared to diminish as the amount of attachment loss increased. Conclusion : On the basis of the observed results of the study it can be concluded that the risk for COPD appeared to be significantly elevated when attachment loss was found to be severe. It is conceivable that oral interventions that improve oral health status may prove to lower the severity of lung infection in susceptible populations.

  11. Improving cluster-based methods for investigating potential for insect pest species establishment: region-specific risk factors

    Directory of Open Access Journals (Sweden)

    Michael J. Watts

    2011-09-01

    Full Text Available Existing cluster-based methods for investigating insect species assemblages or profiles of a region to indicate the risk of new insect pest invasion have a major limitation in that they assign the same species risk factors to each region in a cluster. Clearly regions assigned to the same cluster have different degrees of similarity with respect to their species profile or assemblage. This study addresses this concern by applying weighting factors to the cluster elements used to calculate regional risk factors, thereby producing region-specific risk factors. Using a database of the global distribution of crop insect pest species, we found that we were able to produce highly differentiated region-specific risk factors for insect pests. We did this by weighting cluster elements by their Euclidean distance from the target region. Using this approach meant that risk weightings were derived that were more realistic, as they were specific to the pest profile or species assemblage of each region. This weighting method provides an improved tool for estimating the potential invasion risk posed by exotic species given that they have an opportunity to establish in a target region.

  12. Provincial carbon intensity abatement potential estimation in China: A PSO–GA-optimized multi-factor environmental learning curve method

    International Nuclear Information System (INIS)

    Yu, Shiwei; Zhang, Junjie; Zheng, Shuhong; Sun, Han

    2015-01-01

    This study aims to estimate carbon intensity abatement potential in China at the regional level by proposing a particle swarm optimization–genetic algorithm (PSO–GA) multivariate environmental learning curve estimation method. The model uses two independent variables, namely, per capita gross domestic product (GDP) and the proportion of the tertiary industry in GDP, to construct carbon intensity learning curves (CILCs), i.e., CO 2 emissions per unit of GDP, of 30 provinces in China. Instead of the traditional ordinary least squares (OLS) method, a PSO–GA intelligent optimization algorithm is used to optimize the coefficients of a learning curve. The carbon intensity abatement potentials of the 30 Chinese provinces are estimated via PSO–GA under the business-as-usual scenario. The estimation reveals the following results. (1) For most provinces, the abatement potentials from improving a unit of the proportion of the tertiary industry in GDP are higher than the potentials from raising a unit of per capita GDP. (2) The average potential of the 30 provinces in 2020 will be 37.6% based on the emission's level of 2005. The potentials of Jiangsu, Tianjin, Shandong, Beijing, and Heilongjiang are over 60%. Ningxia is the only province without intensity abatement potential. (3) The total carbon intensity in China weighted by the GDP shares of the 30 provinces will decline by 39.4% in 2020 compared with that in 2005. This intensity cannot achieve the 40%–45% carbon intensity reduction target set by the Chinese government. Additional mitigation policies should be developed to uncover the potentials of Ningxia and Inner Mongolia. In addition, the simulation accuracy of the CILCs optimized by PSO–GA is higher than that of the CILCs optimized by the traditional OLS method. - Highlights: • A PSO–GA-optimized multi-factor environmental learning curve method is proposed. • The carbon intensity abatement potentials of the 30 Chinese provinces are estimated by

  13. CYP gene family variants as potential protective factors in drug addiction in Han Chinese.

    Science.gov (United States)

    Zhang, Hongxing; Yang, Qi; Zheng, Wenkai; Ouyang, Yongri; Yang, Min; Wang, Fengjiao; Jin, Tianbo; Zhang, Ji; Wang, Zhenyuan

    2016-08-01

    There is growing evidence that genetic factors also contribute to drug addiction. The human cytochrome P450 has shown special interest because of pharmacokinetic variation in different individuals and populations, which is largely determined by the relevant genes. The present study aimed to investigate the polymorphism of the CYP/addicts relationship. We genotyped 13 tag single-nucleotide polymorphisms (tSNPs) from three genes, including 692 cases and 700 controls. Sequenom MassARRAY RS1000 (Sequenom, Inc., San Diego, CA, USA) was used for SNP genotyping. Statistical analysis of the association between tSNPs and drug addiction was performed using the chi-squared test and SNP Stats software (http://bioinfo.iconcologia.net). The T/T genotype of rs2242480 in CYP3A4 was associated with decreased risk in the recessive model (p = 0.0002). Allele frequency at rs3743484 in CYP1A2 showed significant differences between addicts and controls (p = 0.046; odds ratio = 0.80; 95% confidence interval = 0.65-1.00). In genetic model analyses, the minor C allele of rs3743484 in CYP1A2 was associated with a reduced risk of drug addiction based on analysis using codominant and additive models (p = 0.027 dominant model; p =0.038 additive model). Our findings show that at allelic and genotypic level polymorphisms in CYP3A4 and CYP1A2 are significantly associated with a reduced risk of drug addiction in X'ian Han Chinese individuals. However, this result needs to be confirmed in additional studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Chiung-Mei Chen

    Full Text Available Mutations in the F-box only protein 7 gene (FBXO7, the substrate-specifying subunit of SCF E3 ubiquitin ligase complex, cause Parkinson's disease (PD-15 (PARK15. To identify new variants, we sequenced FBXO7 cDNA in 80 Taiwanese early onset PD patients (age at onset ≤ 50 and only two known variants, Y52C (c.155A>G and M115I (c.345G>A, were found. To assess the association of Y52C and M115I with the risk of PD, we conducted a case-control study in a cohort of PD and ethnically matched controls. There was a nominal difference in the Y52C G allele frequency between PD and controls (p = 0.045. After combining data from China [1], significant difference in the Y52C G allele frequency between PD and controls (p = 0.012 and significant association of G allele with decreased PD risk (p = 0.017 can be demonstrated. Upon expressing EGFP-tagged Cys52 FBXO7 in cells, a significantly reduced rate of FBXO7 protein decay was observed when compared with cells expressing Tyr52 FBXO7. In silico modeling of Cys52 exhibited a more stable feature than Tyr52. In cells expressing Cys52 FBXO7, the level of TNF receptor-associated factor 2 (TRAF2 was significantly reduced. Moreover, Cys52 FBXO7 showed stronger interaction with TRAF2 and promoted TRAF2 ubiquitination, which may be responsible for the reduced TRAF2 expression in Cys52 cells. After induced differentiation, SH-SY5Y cells expressing Cys52 FBXO7 displayed increased neuronal outgrowth. We therefore hypothesize that Cys52 variant of FBXO7 may contribute to reduced PD susceptibility in Chinese.

  15. Potential Angiogenic Role of Platelet-Activating Factor in Human Breast Cancer

    Science.gov (United States)

    Montrucchio, Giuseppe; Sapino, Anna; Bussolati, Benedetta; Ghisolfi, Gianpiero; Rizea-Savu, Simona; Silvestro, Luigi; Lupia, Enrico; Camussi, Giovanni

    1998-01-01

    This study investigated the presence of platelet-activating factor (PAF) in the lipid extracts of 18 primary breast carcinomas and 20 control breast tissues. The amount of PAF detected in breast carcinomas was significantly higher than in controls. The mass spectrometric analysis of PAF-bioactive lipid extract from breast carcinomas showed the presence of several molecular species of PAF, including C16-alkylPAF, C18-lysophosphatidylcholine (LPC), C16-LPC, lyso-PAF, and C16-acylPAF. The amount of bioactive PAF extracted from breast specimens significantly correlated with tumor vascularization revealed by the number of CD34- and CD31-positive cells. As C16-alkylPAF was previously shown to induce angiogenesis in vivo, we evaluated whether the thin layer chromatography-purified lipid extracts of breast specimens elicited neoangiogenesis in a murine model of subcutaneous Matrigel injection. The lipid extracts from specimens of breast carcinoma containing high levels of PAF bioactivity, but not from breast carcinomas containing low levels of PAF bioactivity or from normal breast tissue, induced a significant angiogenic response. This angiogenic response was significantly inhibited by the PAF receptor antagonist WEB 2170. T47D and MCF7 breast cancer cell lines, but not an immortalized nontumor breast cell line (MCF10), released PAF in the culture medium. A significant in vivo neoangiogenic response, inhibited by WEB 2170, was elicited by T47D and MCF7 but not by MCF10 culture medium. These results indicate that an increased concentration of PAF is present in tumors with high microvessel density and that PAF may account for the neoangiogenic activity induced in mice by the lipid extracts obtained from breast cancer. A contribution of PAF in the neovascularization of human breast cancer is suggested. PMID:9811351

  16. Identification of transcription factors potential related to brown planthopper resistance in rice via microarray expression profiling

    Directory of Open Access Journals (Sweden)

    Wang Yubing

    2012-12-01

    Full Text Available Abstract Background Brown planthopper (BPH, Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties. Results We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT. We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1. We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC of more than 2.0 (P10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT. Conclusions We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants protect themselves by reducing their metabolic level to inhibit feeding by BPH and prevent damage from water and nutrient loss. We have selected 21 TF genes related to BPH resistance for further analyses to understand the molecular responses to BPH feeding in rice.

  17. The Potential Risk Factors Relevant to Lateral Epicondylitis by Wrist Coupling Posture.

    Directory of Open Access Journals (Sweden)

    Su-Ya Lee

    Full Text Available The use of awkward wrist postures and unskilled techniques might induce lateral epicondylitis. This study thus investigated the effects of wrist deviation combined with extension and movement velocity on the dynamic performances of the wrist muscles during the coupling posture via a custom-made bi-planar isokinetic dynamometer. Thirty subjects were recruited to perform the isokinetic testing. We measured the muscle strengths and activities for the wrist extensors and flexors during concentric and eccentric contractions at three movement velocities, 30°s-1, 90°s-1, and 180°s-1, combined with three wrist postures, neutral position (NP, radial deviation (RD, and ulnar deviation (UD. The root mean square (RMS of the electromyographic signal in the extensor digitorum communis (EDC, normalized peak torque of extensors, and ratio of normalized peak torque between wrist extensors and flexors, were all greater in the NP than RD and UD in both contractions. The ratio of RMS between EDC and flexor digitorum superficialis (FDS had a significantly greater value in RD than UD during the concentric contraction. The EDC showed significantly higher activity at the fast velocity in both contractions. Nevertheless, a significantly higher RMS of the electromyographic signal between EDC and FDS and the ratio of strength between wrist extensors and flexors were found at slow velocity in both contractions. The wrist deviation combined with extension and movement velocity of the wrist joint should thus be considered as influential factors which might alter the dynamic performances, and may result in further injury of the elbow joint.

  18. Analytical insight into degradation processes of aminopolyphosphonates as potential factors that induce cyanobacterial blooms.

    Science.gov (United States)

    Drzyzga, Damian; Lipok, Jacek

    2017-11-01

    Aminopolyphosphonates (AAPs) are commonly used industrial complexones of metal ions, which upon the action of biotic and abiotic factors undergo a breakdown and release their substructures. Despite the low toxicity of AAPs towards vertebrates, products of their transformations, especially those that contain phosphorus and nitrogen, can affect algal communities. To verify whether such chemical entities are present in water ecosystems, much effort has been made in developing fast, inexpensive, and reliable methods for analyzing phosphonates. However, unfortunately, the methods described thus far require time-consuming sample pretreatment and offer relatively high values of the limit of detection (LOD). The aim of this study was to develop an analytical approach to study the environmental fate of AAPs. Four phosphonic acids, N,N-bis(phosphonomethyl)glycine (GBMP), aminotris(methylenephosphonic) acid (ATMP), hexamethylenediamine-N,N,N',N'-tetrakis(methylphosphonic) acid (HDTMP), and diethylenetriamine penta(methylenephosphonic) acid (DTPMP) were selected and examined in a water matrix. In addition, the susceptibility of these compounds to biotransformations was tested in colonies of five freshwater cyanobacteria-microorganisms responsible for the so-called blooms in the water. Our efforts to track the AAP decomposition were based on derivatization of N-alkyl moieties with p-toluenesulfonyl chloride (tosylation) followed by chromatographic (HPLC-UV) separation of derivatives. This approach allowed us to determine seven products of the breakdown of popular phosphonate chelators, in nanomolar concentrations and in one step. It should be noted that the LOD of four of those products, aminemethylphosphonic acid (AMPA), N-phosphomethyl glycine (NPMG), N-(methyl)aminemethanephosphonic acid (MAMPA), and N-(methyl) glycine (SAR), was set below the concentration of 50 nM. Among those substances, N-(methylamino)methanephosphonic acid (MAMPA) was identified for the first time as

  19. Polypharmacy and potentially inappropriate medication use as the precipitating factor in readmissions to the hospital

    Directory of Open Access Journals (Sweden)

    Vishal Sehgal

    2013-01-01

    Full Text Available Background and Aim: Readmission to the hospital within 30 days of discharge from the hospital is a common occurrence. Congestive heart failure is the most common cause of readmissions in the hospital. We hypothesized that irrespective of the admission diagnosis polypharmacy and potentially inappropriate use of medications (PIM leads to readmissions within 30 days of discharge from the hospital. Materials and Methods: A retrospective study was carried out by reviewing the hospital records of 414 patients who were readmitted to the hospital within 30 days of discharge from the hospital between January 2008 and December 2009. The data was stratified to see which patients were on polypharmacy and/or on PIM. Polypharmacy was defined as use of more than 5 medications. PIM was defined as per the modified Beers criteria. Day 0 was defined as the day of discharge and day1 was defined as the day-after Admission to the hospital. Statistical analysis was carried out using a two-way analysis of variance (ANOVA on the data to see if polypharmacy and/or PIM was related to readmission within 30 days of discharge irrespective of admission diagnosis. Results: Polypharmacy was related to hospital readmission at day 1 and day 0, however inappropriate drug use was found to be not related at any day. Polypharmacy and PIM combined had a positive correlation to readmission only on days 1 and 0 and it was statistically significant. The use of minimal and appropriate use of drugs was statistically significant compared to polypharmacy and PIM use. Conclusions: Polypharmacy and PIM are under recognized cause of readmissions to the hospital.

  20. Analysis of the influence of external factors on efficiency of use of resource potential and economic growth of the region

    Directory of Open Access Journals (Sweden)

    M. P. Vasiliev

    2017-01-01

    Full Text Available In the article are described and analyzed the influence of factors of external and internal environments on maintaining the planned economic growth, efficient use of the resource potential of the regional economic complex. Are provided methods of analysis and comprehensive measures to maintain the planned pace of economic growth of the region, expansion of competitive advantages. Enlargement and generalization determine the impact of economic environmental factors, in accordance with the duration of optimization and changes in the business cycle, provide a high level of confidence in the estimates of the impact of the macro environment on the process of achieving economic success, efficient use of the resource potential of the regional economic complex. Analysis of the internal conditions of region is carried out by management on the basis of establishing the optimal values of the distribution of the resource potential for high-priority, economically viable, and socially important areas of efficient use of logistical, labor, information, and natural resources, analysis of the current or having a tendency to the formation of informal communities in the sectoral components of economic activities, industrial complexes and social services. The possibilities of the availability and abilities of the region to influence the structural components in achieving the economic and financial goals of the activity are considered, including ensuring sustainable dynamics in increasing the efficiency of regional production, providing competitive advantages in the use of consumed resources. The factors proposed for consideration, different management of the regional economy, contribute to the creation of both formal and informal organizational and economic communities, taking into account the interests of all its participants. In addition, mechanisms and tools are proposed that facilitate the creation of favorable conditions for participants in informal clusters

  1. Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

    Science.gov (United States)

    Huynh, David N; Bessi, Valérie L; Ménard, Liliane; Piquereau, Jérôme; Proulx, Caroline; Febbraio, Maria; Lubell, William D; Carpentier, André C; Burelle, Yan; Ong, Huy; Marleau, Sylvie

    2018-02-01

    CD36 is a multiligand receptor involved in lipid metabolism. We investigated the mechanisms underlying the cardioprotective effect of CP-3(iv), an azapeptide belonging to a new class of selective CD36 ligands. The role of CP-3(iv) in mediating cardioprotection was investigated because CD36 signaling leads to activation of peroxisome proliferator-activated receptor-γ, a transcriptional regulator of adiponectin. CP-3(iv) pretreatment reduced infarct size by 54% and preserved hemodynamics in C57BL/6 mice subjected to 30 min coronary ligation and reperfusion but had no effect in CD36-deficient mice. The effects of CP-3(iv) were associated with an increase in circulating adiponectin levels, epididymal fat adiponectin gene expression, and adiponectin transcriptional regulators ( Pparg, Cebpb, Sirt1) after 6 h of reperfusion. Reduced myocardial oxidative stress and apoptosis were observed along with an increase in expression of myocardial adiponectin target proteins, including cyclooxygenase-2, phospho-AMPK, and phospho-Akt. Moreover, CP-3(iv) increased myocardial performance in isolated hearts, whereas blockade of adiponectin with an anti-adiponectin antibody abrogated it. CP-3(iv) exerts cardioprotection against myocardial ischemia and reperfusion (MI/R) injury and dysfunction, at least in part, by increasing circulating and myocardial adiponectin levels. Hence, both paracrine and endocrine effects of adiponectin may contribute to reduced reactive oxygen species generation and apoptosis after MI/R, in a CD36-dependent manner.-Huynh, D. N., Bessi, V. L., Ménard, L., Piquereau, J., Proulx, C., Febbraio, M., Lubell, W. D., Carpentier, A. C., Burelle, Y., Ong, H., Marleau, S. Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

  2. Endogenous EGF as a potential renotrophic factor in ischemia-induced acute renal failure.

    Science.gov (United States)

    Schaudies, R P; Nonclercq, D; Nelson, L; Toubeau, G; Zanen, J; Heuson-Stiennon, J A; Laurent, G

    1993-09-01

    The time course for the increases in soluble renal epidermal growth factor (EGF) after ischemia has been established. These elevated levels of EGF have been compared with the degree of tissue injury as well as the extent of cell proliferation in the recovering tissue. Levels of soluble immunoreactive EGF (irEGF) in control animals were 9.74 +/- 1.1 ng/g wet wt (n = 4-8 for all values) and rose to 83.9 +/- 30 ng/g within 12 h after injury. Soluble irEGF content peaked at 88.8 +/- 15 ng/g at 24 h postinjury and returned to control values by 72 h. We previously reported that trypsin digestion of crude renal membranes (CRM) generates rat EGF that is indistinguishable from that isolated from the submandibular gland. Initial levels of trypsin-releasable membrane-associated irEGF were 439 +/- 26 ng/g. These levels fell to 46.6 +/- 9.6 ng/g at 48 h after injury. The total renal EGF demonstrated an 80% decline 48 h after injury but returned to 50% of the initial values after 72 h representing significant new synthesis of EGF-containing proteins between 48 and 72 h postinjury. Immunohistochemical staining of kidney paraffin sections for EGF immunoreactivity demonstrated staining intensities that paralleled the amount of irEGF in the trypsin-digested CRM fraction, suggesting that the membrane-associated irEGF is the predominant form detected by this technique. Regenerative hyperplasia subsequent to tubular insult was monitored by immunostaining nuclei of S phase cells after pulse labeling with the thymidine analogue 5-bromo-2'-deoxyuridine. Cell proliferation was particularly prominent in the outer stripe of outer medulla of kidneys exposed to ischemia and reached a maximum (19-fold higher than the baseline value) 48 h after reperfusion. Renal cell turnover returned to control values by day 7. The observation that the peak in soluble EGF levels (24 h) precedes the peak in tubular regeneration (48 h) by 24 h is consistent with the hypothesis that EGF is one of the mitogenic

  3. Potential targets of transforming growth factor-beta1 during inhibition of oocyte maturation in zebrafish

    Directory of Open Access Journals (Sweden)

    Clelland Eric

    2005-09-01

    Full Text Available Abstract Background TGF-beta is a multifunctional growth factor involved in regulating a variety of cellular activities. Unlike mammals, the function of TGF-beta in the reproduction of lower vertebrates, such as fish, is not clear. Recently, we showed that TGF-beta1 inhibits gonadotropin- and 17alpha, 20beta-dihydroxyprogesterone (DHP-induced maturation in zebrafish. The aim of the present study was to investigate the mechanisms underlying this action. Method To determine if the effect of TGF-beta1 on oocyte maturation involves transcription and/or translation, ovarian follicles were pre-treated with actinomycin D, a blocker of transcription, and cyclohexamide, an inhibitor of translation, and incubated with hCG or DHP, either alone or in combination with TGF-beta1 and oocyte maturation scored. To determine the effect of TGF-beta1 on mRNA levels of several key effectors of oocyte maturation, three sets of experiments were performed. First, follicles were treated with control medium or TGF-beta1 for 2, 6, 12, and 24 h. Second, follicles were treated with different concentrations of TGF-beta1 (0 to 10 ng/ml for 18 h. Third, follicles were incubated with hCG in the absence or presence of TGF-beta1 for 18 h. At the end of each experiment, total RNA was extracted and reverse transcribed. PCR using primers specific for 20beta-hydroxysteroid dehydrogenase (20beta-HSD which is involved in DHP production, follicle stimulating hormone receptor (FSHR, luteinizing hormone receptor (LHR, the two forms of membrane progestin receptor: mPR-alpha and mPR-beta, as well as GAPDH (control, were performed. Results Treatment with actinomycin D, a blocker of transcription, reduced the inhibitory effect of TGF-beta1 on DHP-induced oocyte maturation, indicating that the inhibitory action of TGF-beta1 is in part due to regulation of gene transcription. Treatment with TGF-beta1 caused a dose and time-dependent decrease in mRNA levels of 20beta-HSD, LHR and mPR-beta in

  4. Identification of transcription factors potential related to brown planthopper resistance in rice via microarray expression profiling.

    Science.gov (United States)

    Wang, Yubing; Guo, Huimin; Li, Haichao; Zhang, Hao; Miao, Xuexia

    2012-12-10

    Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF) are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties. We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT). We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1). We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC) of more than 2.0 (Pgenes related to BPH-induced resistance, most of them were readily induced in TN1 than in RHT by BPH feeding, for instance, 154 TF genes were up-regulated in TN1, but only 31 TF genes were up-regulated in RHT at 24 hours after BPH infestation; 2-4 times more TF genes were induced in TN1 than in RHT by BPH. At an FC threshold of >10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT. We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants

  5. Evaluation of myocardial preconditioning and adenosine effects in cardioprotection in rat hearts with ischemia-reperfusion injury using 99MTc-glucarate imaging

    International Nuclear Information System (INIS)

    Liu Zhonglin; Barrett, H.H.; Koon Yan Pak

    2004-01-01

    Significant tolerance to myocardial ischemia-reperfusion injury, as assessed by biochemical assay and noninvasive infarct-avid imaging, was induced with an IPC protocol in the rat model. The cardioprotection of IPC could be simulated by adenosine receptor A1 agonist CCPA, or blocked by antagonist SPT. Thus, adenosine mediates protection by ischemic preconditioning in this specific rat heart model. 99mTc-glucarate imaging is not only useful in detecting early ischemia-reperfusion injury, but also invaluable in evaluating the effects of cardioprotective treatments. uantitative anal ses on dynamic images with 99m Tc-glucarate would make it possible to identify myocardial ischemia-reperfusion injury more accurate, and provide a unique tool for evaluation of cardioprotection. The FASTSPECT imaging with the ischenuc-reperfused rat heart model provides a solution-specific approach with high-resolution and fast dynamic acquisition for kinetic studies of new myocardial imaging agents as the evidence of its major role in the present study. (authors)

  6. [Research on carbon reduction potential of electric vehicles for low-carbon transportation and its influencing factors].

    Science.gov (United States)

    Shi, Xiao-Qing; Li, Xiao-Nuo; Yang, Jian-Xin

    2013-01-01

    Transportation is the key industry of urban energy consumption and carbon emissions. The transformation of conventional gasoline vehicles to new energy vehicles is an important initiative to realize the goal of developing low-carbon city through energy saving and emissions reduction, while electric vehicles (EV) will play an important role in this transition due to their advantage in energy saving and lower carbon emissions. After reviewing the existing researches on energy saving and emissions reduction of electric vehicles, this paper analyzed the factors affecting carbon emissions reduction. Combining with electric vehicles promotion program in Beijing, the paper analyzed carbon emissions and reduction potential of electric vehicles in six scenarios using the optimized energy consumption related carbon emissions model from the perspective of fuel life cycle. The scenarios included power energy structure, fuel type (energy consumption per 100 km), car type (CO2 emission factor of fuel), urban traffic conditions (speed), coal-power technologies and battery type (weight, energy efficiency). The results showed that the optimized model was able to estimate carbon emissions caused by fuel consumption more reasonably; electric vehicles had an obvious restrictive carbon reduction potential with the fluctuation of 57%-81.2% in the analysis of six influencing factors, while power energy structure and coal-power technologies play decisive roles in life-cycle carbon emissions of electric vehicles with the reduction potential of 78.1% and 81.2%, respectively. Finally, some optimized measures were proposed to reduce transport energy consumption and carbon emissions during electric vehicles promotion including improving energy structure and coal technology, popularizing energy saving technologies and electric vehicles, accelerating the battery R&D and so on. The research provides scientific basis and methods for the policy development for the transition of new energy vehicles

  7. Potential impact of single-risk-factor versus total risk management for the prevention of cardiovascular events in Seychelles.

    Science.gov (United States)

    Ndindjock, Roger; Gedeon, Jude; Mendis, Shanthi; Paccaud, Fred; Bovet, Pascal

    2011-04-01

    To assess the prevalence of cardiovascular (CV) risk factors in Seychelles, a middle-income African country, and compare the cost-effectiveness of single-risk-factor management (treating