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Sample records for thrombomodulin exerts cytoprotective

  1. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    International Nuclear Information System (INIS)

    Han, Jae Yun; Cho, Seung Sik; Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho; Park, Da Eon; Bang, Joon Seok; Jung, Young Suk; Ki, Sung Hwan

    2015-01-01

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  2. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jae Yun [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Cho, Seung Sik [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Park, Da Eon [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Bang, Joon Seok [Graduate School of Clinical Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Jung, Young Suk [College of Pharmacy, Pusan National University, Busan (Korea, Republic of); Ki, Sung Hwan, E-mail: shki@chosun.ac.kr [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of)

    2015-08-15

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  3. NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

    International Nuclear Information System (INIS)

    Chen, Zhi-Dong; Xu, Liang; Tang, Kan-Kai; Gong, Fang-Xiao; Liu, Jing-Quan; Ni, Yin; Jiang, Ling-Zhi; Hong, Jun; Han, Fang; Li, Qian; Yang, Xiang-Hong; Sun, Ren-Hua; Mo, Shi-Jing

    2016-01-01

    Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a NF

  4. NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhi-Dong [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Xu, Liang [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Tang, Kan-Kai [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Gong, Fang-Xiao; Liu, Jing-Quan; Ni, Yin; Jiang, Ling-Zhi; Hong, Jun; Han, Fang; Li, Qian; Yang, Xiang-Hong [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Sun, Ren-Hua, E-mail: jqin168@hotmail.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Mo, Shi-Jing, E-mail: msj860307@163.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China)

    2016-09-10

    Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a NF

  5. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia.

    Science.gov (United States)

    Turner, Rosanne J; Bloemenkamp, Kitty W M; Bruijn, Jan A; Baelde, Hans J

    2016-04-01

    Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are increased. We aimed to investigate placental thrombomodulin dysregulation and consequent downstream effects in the pathogenesis of preeclampsia. Placentas from 28 preeclampsia pregnancies, 30 uncomplicated pregnancies, and 21 pregnancies complicated by growth restriction as extra controls were included. Immunohistochemical staining of thrombomodulin, caspase-3, and fibrin was performed. Placental mRNA expression of thrombomodulin, inflammatory markers, matrix metalloproteinases 2 and 9, and soluble Flt-1 were measured with quantitative polymerase chain reaction. Thrombomodulin mRNA expression was determined in vascular endothelial growth factor-transfected trophoblast cell lines. Thrombomodulin protein and mRNA expression were decreased in preeclampsia as compared with both control groups (P=0.001). Thrombomodulin mRNA expression correlated with maternal body mass index (Ppreeclampsia. An increase in placental apoptotic cells was associated with preeclampsia (Ppreeclampsia, but not with fibrin deposits or inflammatory markers. Placental soluble Flt-1 expression correlated with decreased thrombomodulin expression. Vascular endothelial growth factor induced upregulation of thrombomodulin expression in trophoblast cells. Decreased thrombomodulin expression in preeclampsia may play a role in placental dysfunction in preeclampsia and is possibly caused by an angiogenic imbalance. Hypertension and obesity are associated with thrombomodulin downregulation. These results set the stage for further basic and clinical research on thrombomodulin in the pathogenesis of preeclampsia and other syndromes characterized by endothelial dysfunction. © 2016 American Heart Association, Inc.

  6. Thrombomodulin expression regulates tumorigenesis in bladder cancer

    International Nuclear Information System (INIS)

    Wu, Chun-Te; Chang, Ying-Hsu; Lin, Paul- Yang; Chen, Wen-Cheng; Chen, Miao-Fen

    2014-01-01

    The identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer. We studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness. The data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer. TM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer

  7. Cytoprotective function of sAppalpha in human keratinocytes.

    Science.gov (United States)

    Wehner, Sven; Siemes, Christina; Kirfel, Gregor; Herzog, Volker

    2004-12-01

    sAPPalpha, the soluble form of the beta-amyloid precursor protein, has been shown to act as a potent epidermal growth factor by stimulating keratinocyte proliferation and migration. In this report we provide evidence for a cytoprotective role of sAPPalpha. As a model we used HaCaT cells and normal human keratinocytes (NHK) cultured in the absence of fetal calf serum and bovine pituitary extract. Under these conditions keratinocytes began to undergo apoptosis at increasing rates after 96 h of culture. Surprisingly, keratinocytes were protected from apoptosis by the addition of 50 nM recombinant sAPPalpha. Subsequent experiments were performed to elucidate the regulatory basis of the cytoprotective role of sAPPalpha. We found that recombinant sAPPalpha facilitated the substrate adhesion of keratinocytes in the first 30 minutes after seeding. The basis for this adhesion-promoting function was shown by the ability of recombinant sAPPalpha to continuously coat the culture dish thereby promoting the ability to bind keratinocytes. A second mechanism explaining the cytoprotective role was found in the significant inhibition of apoptosis by recombinant sAPPalpha. In HaCaT cells moderate UV-B irradiation was sufficient to induce apoptosis. In contrast, induction of apoptosis in NHK required additionally the depletion of endogenous sAPPalpha suggesting that sAPPalpha mediates protection against UV-B irradiation. Staurosporine-induced apoptosis rates were significantly reduced by about 59% after addition of recombinant sAPPalpha. These results show that sAPPalpha exerts a pronounced cytoprotective effect and that this effect is mediated by facilitated cell adhesion and by the antiapoptotic function of sAPPalpha.

  8. Exerting Capacity.

    Science.gov (United States)

    Leger, J Michael; Phillips, Carolyn A

    2017-05-01

    Patient safety has been at the forefront of nursing research since the release of the Institute of Medicine's report estimating the number of preventable adverse events in hospital settings; yet no research to date has incorporated the perspectives of bedside nurses using classical grounded theory (CGT) methodology. This CGT study explored the perceptions of bedside registered nurses regarding patient safety in adult acute care hospitals. Data analysis used three techniques unique to CGT-the constant comparative method, coding, and memoing-to explore the values, realities, and beliefs of bedside nurses about patient safety. The analysis resulted in a substantive theory, Exerting Capacity, which explained how bedside nurses balance the demands of keeping their patients safe. Exerting Capacity has implications for health care organization leaders, nursing leaders, and bedside nurses; it also has indications for future research into the concept of patient safety.

  9. Quercetin Oxidation Paradoxically Enhances its Antioxidant and Cytoprotective Properties.

    Science.gov (United States)

    Fuentes, Jocelyn; Atala, Elías; Pastene, Edgar; Carrasco-Pozo, Catalina; Speisky, Hernán

    2017-12-20

    Quercetin oxidation is generally believed to ultimately result in the loss of its antioxidant properties. To test this assertion, quercetin oxidation was induced, and after each of its major metabolites was identified and isolated by HPLC-DAD-ESI-MS/MS, the antioxidant (dichlorodihydrofluorescein oxidation-inhibiting) and cytoprotective (LDH leakage-preventing) properties were evaluated in Hs68 and Caco2 cells exposed to indomethacin. Compared to quercetin, the whole mixture of metabolites (Q OX ) displayed a 20-fold greater potency. After resolution of Q OX into 12 major peaks, only one (peak 8), identified as 2,5,7,3',4'-pentahydroxy-3,4-flavandione or its 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone tautomer, could account for the antioxidant and cytoprotective effects afforded Q OX . Peak 8 exerted such effects at a 50 nM concentration, revealing a potency 200-fold higher than that of quercetin. The effects of peak 8 were seen regardless of whether it was added to the cells 40 min before or simultaneously with the oxygen-reactive species-generating agent, suggesting an intracellular ability to trigger early antioxidant responses. Thus, the present study is the first to reveal that in regard to the intracellular actions of quercetin, attention should be extended toward some of its oxidation products.

  10. Thrombomodulin and von Willebrand factor as markers of radiation-induced endothelial injury

    International Nuclear Information System (INIS)

    Zhou Quansheng; Zhao Yimin; Li Peixia; Bai Xia; Ruan Changgeng

    1992-02-01

    Cultured confluent human umbilical vein endothelial cells were irradiated in vitro by 60 Co-gamma ray at doses from 0 to 50 Gy. After irradiation Thrombomodulin in the supernatants of endothelial cell culture medium, on the surface of the cells and within the cells was measured at different times over six days. At twenty-four hours after irradiation, an increase in the release of Thrombomodulin and von Willebrand factor from irradiated endothelial cells and an increase in the number of molecules and the activity of Thrombomodulin on the surface of the cells were observed, which were radiation-dose dependent. The capacity of the cells to produce and release Thrombomodulin was decreased from two to six days after exposure to 60 Co-gamma ray. Our data indicate that radiation can injure endothelial cells and that Thrombomodulin may be as a marker of radiation-induced endothelial cell injury. The relationship between dysfunction of irradiated endothelial cells and the pathological mechanisms of acute radiation sickness are discussed

  11. CYTOPROTECTIVE AND NEUROTROPHIC THERAPY FOR CEREBRAL STROKE

    Directory of Open Access Journals (Sweden)

    M. Yu. Martynov

    2013-01-01

    Full Text Available The paper gives the data of Russian and foreign studies on the pathophysiological mechanisms of brain injury in ischemic and hemorrhagicstroke, the specific features of brain plasticity and its activation after cerebral stroke, and main directions for basic and differentiation therapy for acute cerebrovascular pathology. Particular emphasis is placed on the issues of cytoprotective and neurotrophic therapy for cerebral stroke. Analysis of the data available in the literature shows that cytoprotective and neurotrophic therapies are important components of combination treatment in patients with stroke and favorably affect the functional outcome of the disease.

  12. GASTRIC AND DUODENAL ANTIULCER AND CYTOPROTECTIVE ...

    African Journals Online (AJOL)

    Aqureous ethanolic extract of the aerial parts of Cissus quadrangularis L. variant II (Vitaceae) was found to possess antiulcer activities. It also has cytoprotective, mucin stimulation activities and selectively increased prostaglandin synthesis thereby decreasing the incidence of ulcer. Samples collected during the flowering ...

  13. The relation of thrombomodulin G33A and C1418T gene ...

    African Journals Online (AJOL)

    Background: Acute myocardial infarction (AMI) is one of the major causes of morbidity and mortality worldwide. There is an increased interest in the genetic risk factors in the pathogenesis of ischemic heart disease. Thrombomodulin (TM), a natural anticoagulant, may play a critical role in the pathogenesis of AMI. Aim of the ...

  14. The relation of thrombomodulin G33A and C1418T gene ...

    African Journals Online (AJOL)

    Wael Alkhiary

    2017-08-31

    Aug 31, 2017 ... Background: Acute myocardial infarction (AMI) is one of the major causes of morbidity and mortality worldwide. There is an increased interest in the genetic risk factors in the pathogenesis of ischemic heart disease. Thrombomodulin (TM), a natural anticoagulant, may play a critical role in the pathogenesis ...

  15. Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.

    Directory of Open Access Journals (Sweden)

    Mayumi Nakahara

    Full Text Available INTRODUCTION: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM. rTM has been approved for the treatment of disseminated intravascular coagulation (DIC in Japan, and is currently undergoing a phase III clinical trial in the United States. METHODS: Histone H3 levels in plasma of healthy volunteers and patients with sepsis and DIC were measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected intravenously with purified histones, and pathological examinations were performed. The protective effects of rTM against histone toxicity were analyzed both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors than in survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding. Platelet depletion protected mice from histone-induced death in the first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might be responsible for death during the early phase. Furthermore, rTM bound to extracellular histones, suppressed histone-induced platelet aggregation, thrombotic occlusion of pulmonary capillaries, and dilatation of the right ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS: Extracellular histones cause massive

  16. ABO Gene Polymorphism and Thrombomodulin ?33G>A Polymorphism Were Not Risk Factors for Myocardial Infarction in Javanese Men

    OpenAIRE

    Lukitasari, Mifetika; Sadewa, Ahmad Hamim; Rohman, Mohammad Saifur

    2017-01-01

    Genetic factors contribute to about a half of coronary artery diseases. During the last several decades, some studies suggested that non-O blood group and thrombomodulin polymorphism ?33G>A are the risk factors of coronary artery disease especially in Asia. There was no prior study in Indonesia regarding this issue. Hence, this study was designed to investigate the correlation of ABO polymorphism and thrombomodulin polymorphism ?33G>A with the incidence of acute myocardial infarction (AMI). A...

  17. [Low sensibility to the action of thrombomodulin in cirrhotic patients. Interest of thrombinography].

    Science.gov (United States)

    Sinegre, Thomas; Abergel, Armand; Sapin, Anne-Françoise; Lamblin, Géraldine; Marques-Verdier, Alain; Duron, Cédric; Lebreton, Aurélien

    2016-01-01

    Cirrhosis is associated with complex hemostatic modifications. Most coagulation factors, either procoagulants or anticoagulants, are reduced. Conventional coagulation tests (prothrombin time, activated partial thromboplastin time) don't allow to precisely identify the thrombotic risk as they are not sensible to coagulation inhibitors deficiencies. The aim of this study was to evaluate the coagulation in a population of cirrhotic patients using thrombinography. We analyzed the plasma samples from 30 cirrhotic patients (10 Child A, 10 Child B, Child C 10) compared to 10 healthy controls using thrombinography with and without thrombomodulin to sensiblise this test at the activated protein C pathway. The results of endogenous thrombin potential, the main parameter, expressed as a ratio (thrombinography with/without thrombomodulin) were significantly higher in cirrhotic patients (0.69 ± 0.16) than in controls (0.49 ± 0.10) which reflects a low sensibility to the action of thrombomodulin. This resistance increases with the severity of the disease assessed by the Child-Pugh score, demonstrating a potential hypercoagulable state. The results of the thrombinography challenge the dogma that cirrhotic patients are naturally "anticoagulated." These results highlight the potential interest of the thrombinography in the detection and monitoring of hypercoagulability in cirrhotic patient. Increasing hypercoagulability with the severity of the disease seems to be correlated with clinical observations since the occurrence of thrombosis is more common when cirrhosis is at an advanced stage.

  18. Radioadaptive Cytoprotective Pathways in the Mouse Retina

    Science.gov (United States)

    Zanello, Susana B.; Wotring, V.; Theriot, C.; Ploutz-Snyder, R.; Zhang, Y.; Wu, H.

    2010-01-01

    Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments.

  19. Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction

    Science.gov (United States)

    Roel, María; Rubiolo, Juan A.; Ternon, Eva; Thomas, Olivier P.; Vieytes, Mercedes R.; Botana, Luis M.

    2015-01-01

    The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities. PMID:26225985

  20. LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin

    Energy Technology Data Exchange (ETDEWEB)

    Kawamoto, Eiji [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Okamoto, Takayuki, E-mail: okamotot@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Takagi, Yoshimi [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Honda, Goichi [Medical Affairs Department, Asahi Kasei Pharma Corporation, 1-105 Kanda Jinbo-cho, Chiyoda-ku, Tokyo 101-8101 (Japan); Suzuki, Koji [Faculty of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3, Minamitamagaki-cho, Suzuka, Mie 513-8679 (Japan); Imai, Hiroshi [Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Shimaoka, Motomu, E-mail: shimaoka@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan)

    2016-05-13

    LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins regulate leukocyte trafficking in health and disease by binding primarily to IgSF ligand ICAM-1 and ICAM-2 on endothelial cells. Here we have shown that the anti-coagulant molecule thrombomodulin (TM), found on the surface of endothelial cells, functions as a potentially new ligand for leukocyte integrins. We generated a recombinant extracellular domain of human TM and Fc fusion protein (TM-domains 123-Fc), and showed that pheripheral blood mononuclear cells (PBMCs) bind to TM-domains 123-Fc dependent upon integrin activation. We then demonstrated that αL integrin-blocking mAb, αM integrin-blocking mAb, and β2 integrin-blocking mAb inhibited the binding of PBMCs to TM-domains 123-Fc. Furthermore, we show that the serine/threonine-rich domain (domain 3) of TM is required for the interaction with the LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins to occur on PBMCs. These results demonstrate that the LFA-1 and Mac-1 integrins on leukocytes bind to TM, thereby establishing the molecular and structural basis underlying LFA-1 and Mac-1 integrin interaction with TM on endothelial cells. In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells. - Highlights: • LFA-1 and Mac-1 integrins bind to the anti-coagulant molecule thrombomodulin. • The serine/threonine-rich domain of thrombomodulin is essential to interact with the LFA-1 and Mac-1 integrins on PBMCs. • Integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells.

  1. Thrombomodulin as a New Marker of Endothelial Dysfunction in Chronic Kidney Disease in Children

    Directory of Open Access Journals (Sweden)

    Dorota Drożdż

    2018-01-01

    Full Text Available Endothelial dysfunction (ED and oxidative stress are potential new pathomechanisms of cardiovascular diseases in patients with chronic kidney disease (CKD. The aim of the study was to assess the association between endothelial dysfunction, oxidative stress biomarkers, and cardiovascular risk factors in children with CKD. Serum oxidized LDL (oxLDL, protein carbonyl group, urea, creatinine, cystatin C, thrombomodulin, asymmetric dimethylarginine (ADMA, von Willebrand factor, brain natriuretic peptide (BNP, lipids, high sensitivity C-reactive protein, intercellular adhesion molecule-1 levels, and albuminuria were measured. Anthropometric, ambulatory blood pressure (BP measurements and echocardiography were performed. The studied group consisted of 59 patients aged 0.7–18.6 (mean 11.1 years with stages 1 to 5 CKD. Thrombomodulin strongly correlated with creatinine (R=0.666; p<0.001, cystatin C (R=0.738; p<0.001, BNP (R=0.406; p=0.001, ADMA (R=0.353; p=0.01, oxLDL (R=0.340; p=0.009, 24-hour systolic (R=0.345; p=0.011 and mean (R=0.315; p<0.05 BP values, and left ventricular mass index (LVMI, R=0.293; p=0.024 and negatively with estimated glomerular filtration rate (R=−0.716; p<0.001. In children with CKD, TM strongly depended on kidney function parameters, oxLDL levels, and 24-hour systolic and mean BP values. Thrombomodulin seems to be a valuable marker of ED in CKD patients, correlating with CKD stage as well as oxidative stress, BP values, and LVMI.

  2. Gastric cytoprotective activity of ilicic aldehyde: structure-activity relationships.

    Science.gov (United States)

    Donadel, Osvaldo J; Guerreiro, Eduardo; María, Alejandra O; Wendel, Graciela; Enriz, Ricardo D; Giordano, Oscar S; Tonn, Carlos E

    2005-08-01

    A series of sesquiterpene compounds possessing both eudesmane and eremophilane skeletons were tested as gastric cytoprotective agents on male Wistar rats. The presence of an alpha,beta-unsaturated aldehyde on the C-7 side chain together with a hydroxyl group at C-4 is the requirement for the observed antiulcerogenic activity. In an attempt to establish new molecular structural requirements for this gastric cytoprotective activity, a structure-activity study was performed.

  3. Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma

    NARCIS (Netherlands)

    Elisen, M. G.; von dem Borne, P. A.; Bouma, B. N.; Meijers, J. C.

    1998-01-01

    Protein C inhibitor (PCI), which was originally identified as an inhibitor of activated protein C, also efficiently inhibits coagulation factors such as factor Xa and thrombin. Recently it was found, using purified proteins, that the anticoagulant thrombin-thrombomodulin complex was also inhibited

  4. ABO Gene Polymorphism and Thrombomodulin -33G>A Polymorphism Were Not Risk Factors for Myocardial Infarction in Javanese Men.

    Science.gov (United States)

    Lukitasari, Mifetika; Sadewa, Ahmad Hamim; Rohman, Mohammad Saifur

    2017-01-01

    Genetic factors contribute to about a half of coronary artery diseases. During the last several decades, some studies suggested that non-O blood group and thrombomodulin polymorphism -33G>A are the risk factors of coronary artery disease especially in Asia. There was no prior study in Indonesia regarding this issue. Hence, this study was designed to investigate the correlation of ABO polymorphism and thrombomodulin polymorphism -33G>A with the incidence of acute myocardial infarction (AMI). A total of 192 subjects were enrolled in this case control study. AMI patients were diagnosed based on World Health Organization criteria. Healthy patients were subjects with AMI risk factor without any sign and symptoms of AMI. Patients with diabetes mellitus, cancer, and arrhythmia were excluded from this study. Genotyping for both polymorphisms was performed by PCR RFLP methods. The result of this study suggested that ABO polymorphism and thrombomodulin polymorphism -33G>A were not risk factors of AMI, p = 0.727 and p = 0.699, respectively. Furthermore, the analysis to identify the synergy of these polymorphisms failed to prove their correlation with AMI ( p = 0.118). Conclusively, this study showed that ABO polymorphism and thrombomodulin polymorphism -33G>A were not risk factors of AMI.

  5. Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism

    Czech Academy of Sciences Publication Activity Database

    Nocchi, L.; Tomasetti, M.; Amati, M.; Neužil, Jiří; Santarelli, L.; Saccucci, F.

    2011-01-01

    Roč. 286, č. 22 (2011), s. 19478-19488 ISSN 0021-9258 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Thrombomodulin gene promoter * malignant mesothelioma * poly(ADP-ribose) polymerase-1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.773, year: 2011

  6. Bioactive Flavonoids, Antioxidant Behaviour, and Cytoprotective Effects of Dried Grapefruit Peels (Citrus paradisi Macf.

    Directory of Open Access Journals (Sweden)

    Lucia Castro-Vazquez

    2016-01-01

    Full Text Available Grapefruit (Citrus paradisi Macf. is an important cultivar of the Citrus genus which contains a number of nutrients beneficial to human health. The objective of the present study was to evaluate changes in bioactive flavonoids, antioxidant behaviour, and in vitro cytoprotective effect of processed white and pink peels after oven-drying (45°C–60°C and freeze-drying treatments. Comparison with fresh grapefruit peels was also assessed. Significant increases in DPPH, FRAPS, and ABTS values were observed in dried grapefruit peel samples in comparison with fresh peels, indicating the suitability of the treatments for use as tools to greatly enhance the antioxidant potential of these natural byproducts. A total of thirteen flavonoids were quantified in grapefruit peel extracts by HPLC-MS/MS. It was found that naringin, followed by isonaringin, was the main flavonoid occurring in fresh, oven-dried, and freeze-dried grapefruit peels. In vivo assay revealed that fresh and oven-dried grapefruit peel extracts (45°C exerted a strong cytoprotective effect on SH-SY5Y neuroblastoma cell lines at concentrations ranging within 0.1–0.25 mg/mL. Our data suggest that grapefruit (Citrus paradisi Macf. peel has considerable potential as a source of natural bioactive flavonoids with outstanding antioxidant activity which can be used as agents in several therapeutic strategies.

  7. Mapping the specific cytoprotective interaction of humanin with the pro-apoptotic protein bid.

    Science.gov (United States)

    Choi, Jungyuen; Zhai, Dayong; Zhou, Xin; Satterthwait, Arnold; Reed, John C; Marassi, Francesca M

    2007-11-01

    Humanin is a short endogenous peptide, which can provide protection from cell death through its association with various receptors, including the pro-apoptotic Bcl-2 family proteins Bid, Bim, and Bax. By using NMR chemical shift mapping experiments, we demonstrate that the interaction between Humanin-derived peptides and Bid is specific, and we localize the binding site to a region on the surface of Bid, which includes residues from the conserved helical BH3 domain of the protein. The BH3 domain mediates the association of Bid with other Bcl-2 family members and is essential for the protein's cytotoxic activity. The data suggest that Humanin exerts its cytoprotective activity by engaging the Bid BH3 domain; this would hinder the association of Bid with other Bcl-2 family proteins, thereby mitigating its toxicity. The identification of a Humanin-specific binding site on the surface of Bid reinforces its importance as a direct modulator of programmed cell death, and suggests a strategy for the design of cytoprotective peptide inhibitors of Bid.

  8. Testicular cytoprotective activities of Curcuma longa in STZ-induced ...

    African Journals Online (AJOL)

    This study was aimed at investigating the cytoprotective activities of Curcuma longa (Turmeric) on the histological structure of the testes in diabetic male rats. Turmeric is commonly called the golden spice, is used as a spice in cooking and also has a long history of medicinal use, dating back nearly 4000 years to the Vedic ...

  9. Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation

    OpenAIRE

    Kim, Ji Eun; Yoo, Hyun Ju; Gu, Ja Yoon; Kim, Hyun Kyung

    2016-01-01

    The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assa...

  10. Chronic Exertional Compartment Syndrome

    Science.gov (United States)

    ... it's more common in athletes who participate in activities that involve repetitive impact, such as running. Chronic exertional compartment syndrome ... and female athletes under 30. Type of exercise. Repetitive impact activity — such as running or fast walking — increases your ...

  11. The Association of Serum Thrombomodulin with Endothelial Injuring Factors in Abdominal Aortic Aneurysm

    Directory of Open Access Journals (Sweden)

    Magdalena Budzyń

    2017-01-01

    Full Text Available Background. The aim of the present study was to evaluate the concentration of serum thrombomodulin (sTM in the AAA patients and to examine its correlation with various factors which may potentially participate in the endothelial injury. Materials and Methods. Forty-one patients with AAA were involved and divided into subgroups based on different criteria. Concentration of sTM was measured using enzyme-linked-immunosorbent assay (ELISA. The results were compared with those obtained in 30 healthy age- and sex-matched volunteers. Results. The higher concentration of sTM was observed in AAA patients compared with those in controls volunteers [2.37 (1.97–2.82 ng/mL versus 3.93 (2.43–9.20 ng/mL, P < 0.001]. An elevated sTM associated significantly with increased triglycerides (TAG [P = 0.022], cholesterol [P = 0.029], hsCRP [P = 0.031], and advanced glycation end products (AGEs [P = 0.033]. Conclusions. The elevation of serum sTM level suggests that endothelial damage occurs in AAA pathogenesis. The correlations observed indicate that lipids abnormalities, inflammation, and oxidative stress may be involved in this destructive process.

  12. Cytoprotective, antihyperglycemic and phytochemical properties of Cocos nucifera (L.) inflorescence.

    Science.gov (United States)

    Renjith, R S; Chikku, A M; Rajamohan, T

    2013-10-01

    To analyze the cytoprotective and antidiabetic activities as well as phytochemical composition of the immature inflorescence of Cocos nucifera belonging to the Arecaceae Family. The phytochemical screening of inflorescence was done to determine the major constituents present in Cocos nucifera inflorescence. The free radical scavenging potential of inflorescence extracts were evaluated using in vitro radical scavenging assay models. The phytochemical analyses on inflorescence showed the presence of phenolic compounds, flavonoids, resins and alkaloids. The macronutrient analyses, on the other hand, showed the presence of carbohydrate, proteins and fibers. Administration of the methanol extract of coconut inflorescence to the diabetic rats showed dose dependent reduction in hyperglycemia. The cytoprotective property of coconut inflorescence was evidenced from the acute toxicological evaluation. The levels of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly decreased in the diabetic rats treated with inflorescence when compared with the diabetic control rats. The results obtained from the present study apparently proved the non-toxic nature and the cytoprotective and antihyperglycemic properties of coconut inflorescence. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  13. Cytoprotective Mechanisms Mediated by Polyphenols from Chilean Native Berries against Free Radical-Induced Damage on AGS Cells

    Directory of Open Access Journals (Sweden)

    Felipe Ávila

    2017-01-01

    Full Text Available The prevalence of cytoprotective mechanisms induced by polyphenols such as activation of intracellular antioxidant responses (ICM and direct free radical scavenging was investigated in native Chilean species of strawberries, raspberries, and currants. Human gastric epithelial cells were co- and preincubated with polyphenolic-enriched extracts (PEEs from Chilean raspberries (Rubus geoides, strawberries (Fragaria chiloensis ssp. chiloensis f. chiloensis, and currants (Ribes magellanicum and challenged with peroxyl and hydroxyl radicals. Cellular protection was determined in terms of cell viability, glyoxalase I and glutathione s-transferases activities, and carboxymethyl lysine (CML and malondialdehyde levels. Our results indicate that cytoprotection induced by ICM was the prevalent mechanism for Rubus geoides and F. chiloensis. This agreed with increased levels of glyoxalase I and glutathione S-transferase activities in cells preincubated with PEEs. ORAC index indicated that F. chiloensis was the most efficient peroxyl radical scavenger. Moreover, ICM mediated by F. chiloensis was effective in protecting cells from CML accumulation in contrast to the protective effects induced by free radical scavenging. Our results indicate that although both polyphenol-mediated mechanisms can exert protective effects, ICM was the most prevalent in AGS cells. These results suggest a potential use of these native berries as functional food.

  14. Cytoprotective Mechanisms Mediated by Polyphenols from Chilean Native Berries against Free Radical-Induced Damage on AGS Cells.

    Science.gov (United States)

    Ávila, Felipe; Theoduloz, Cristina; López-Alarcón, Camilo; Dorta, Eva; Schmeda-Hirschmann, Guillermo

    2017-01-01

    The prevalence of cytoprotective mechanisms induced by polyphenols such as activation of intracellular antioxidant responses (ICM) and direct free radical scavenging was investigated in native Chilean species of strawberries, raspberries, and currants. Human gastric epithelial cells were co- and preincubated with polyphenolic-enriched extracts (PEEs) from Chilean raspberries ( Rubus geoides ), strawberries ( Fragaria chiloensis ssp. chiloensis f . chiloensis ), and currants ( Ribes magellanicum ) and challenged with peroxyl and hydroxyl radicals. Cellular protection was determined in terms of cell viability, glyoxalase I and glutathione s-transferases activities, and carboxymethyl lysine (CML) and malondialdehyde levels. Our results indicate that cytoprotection induced by ICM was the prevalent mechanism for Rubus geoides and F. chiloensis . This agreed with increased levels of glyoxalase I and glutathione S-transferase activities in cells preincubated with PEEs. ORAC index indicated that F. chiloensis was the most efficient peroxyl radical scavenger. Moreover, ICM mediated by F. chiloensis was effective in protecting cells from CML accumulation in contrast to the protective effects induced by free radical scavenging. Our results indicate that although both polyphenol-mediated mechanisms can exert protective effects, ICM was the most prevalent in AGS cells. These results suggest a potential use of these native berries as functional food.

  15. Synthesis of an endothelial cell mimicking surface containing thrombomodulin and endothelial protein C receptor

    Science.gov (United States)

    Kador, Karl Erich

    Synthetic materials for use in blood contacting applications have been studied for many years with limited success. One of the main areas of need for these materials is the design of synthetic vascular grafts for use in the hundreds of thousands of patients who have coronary artery bypass grafting, many without suitable veins for autologous grafts. The design of these grafts is constrained by two common modes of failure, the formation of intimal hyperplasia (IH) and thrombosis. IH formation has been previously linked to a mismatching of the mechanical properties of the graft and has been overcome by creating grafts using materials whose compliance mimics that of the native artery. Several techniques and surface modification have been designed to limit thrombosis on the surface of synthetic materials. One which has shown the greatest promise is the immobilization of Thrombomodulin (TM), a protein found on the endothelial cell membrane lining native blood vessels involved in the activation of the anticoagulant Protein C (PC). While TM immobilization has been shown to arrest thrombin formation and limit fibrous formations in in-vitro and in-vivo experiments, it has shown to be transport limiting under arterial flow. On the endothelial cell surface, TM is co-localized with Endothelial Protein C Receptor (EPCR), which increases PC transport onto the cell surface and increases PC activation via TM between 20-100 fold. This dissertation will describe the chemical modification of medical grade polyurethane (PU), whose compliance has been shown to match that of native arteries. This modification will enable the immobilization of two proteins on an enzymatically relevant scale estimated at less than 10 nm. This dissertation will further describe the immobilization of the proteins TM and EPCR, and analyze the ability of a surface co-immobilized with these proteins to activate the anticoagulant PC. Finally, it will compare the ability of this co-immobilized surface to delay

  16. Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

    International Nuclear Information System (INIS)

    Gonzalez-Rubio, Sandra; Linares, Clara I.; Bello, Rosario I.; Gonzalez, Raul; Ferrin, Gustavo; Hidalgo, Ana B.; Munoz-Gomariz, Elisa; Rodriguez, Blanca A.; Barrera, Pilar; Ranchal, Isidora; Duran-Prado, Mario; Aguilar-Melero, Patricia; De la Mata, Manuel; Muntane, Jordi

    2010-01-01

    The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca 2+ on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca 2+ pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca 2+ entrance was induced by A23187 in HepG2. Cell death, Ca 2+ mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca 2+ concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and L-NAME enhanced, GCDCA-induced cell death. The reduction of Ca 2+ entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca 2+ entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca 2+ concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca 2+ -dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.

  17. ABO Gene Polymorphism and Thrombomodulin −33G>A Polymorphism Were Not Risk Factors for Myocardial Infarction in Javanese Men

    Science.gov (United States)

    Lukitasari, Mifetika; Sadewa, Ahmad Hamim

    2017-01-01

    Genetic factors contribute to about a half of coronary artery diseases. During the last several decades, some studies suggested that non-O blood group and thrombomodulin polymorphism −33G>A are the risk factors of coronary artery disease especially in Asia. There was no prior study in Indonesia regarding this issue. Hence, this study was designed to investigate the correlation of ABO polymorphism and thrombomodulin polymorphism −33G>A with the incidence of acute myocardial infarction (AMI). A total of 192 subjects were enrolled in this case control study. AMI patients were diagnosed based on World Health Organization criteria. Healthy patients were subjects with AMI risk factor without any sign and symptoms of AMI. Patients with diabetes mellitus, cancer, and arrhythmia were excluded from this study. Genotyping for both polymorphisms was performed by PCR RFLP methods. The result of this study suggested that ABO polymorphism and thrombomodulin polymorphism −33G>A were not risk factors of AMI, p = 0.727 and p = 0.699, respectively. Furthermore, the analysis to identify the synergy of these polymorphisms failed to prove their correlation with AMI (p = 0.118). Conclusively, this study showed that ABO polymorphism and thrombomodulin polymorphism −33G>A were not risk factors of AMI. PMID:28811939

  18. ABO Gene Polymorphism and Thrombomodulin −33G>A Polymorphism Were Not Risk Factors for Myocardial Infarction in Javanese Men

    Directory of Open Access Journals (Sweden)

    Mifetika Lukitasari

    2017-01-01

    Full Text Available Genetic factors contribute to about a half of coronary artery diseases. During the last several decades, some studies suggested that non-O blood group and thrombomodulin polymorphism −33G>A are the risk factors of coronary artery disease especially in Asia. There was no prior study in Indonesia regarding this issue. Hence, this study was designed to investigate the correlation of ABO polymorphism and thrombomodulin polymorphism −33G>A with the incidence of acute myocardial infarction (AMI. A total of 192 subjects were enrolled in this case control study. AMI patients were diagnosed based on World Health Organization criteria. Healthy patients were subjects with AMI risk factor without any sign and symptoms of AMI. Patients with diabetes mellitus, cancer, and arrhythmia were excluded from this study. Genotyping for both polymorphisms was performed by PCR RFLP methods. The result of this study suggested that ABO polymorphism and thrombomodulin polymorphism −33G>A were not risk factors of AMI, p=0.727 and p=0.699, respectively. Furthermore, the analysis to identify the synergy of these polymorphisms failed to prove their correlation with AMI (p=0.118. Conclusively, this study showed that ABO polymorphism and thrombomodulin polymorphism −33G>A were not risk factors of AMI.

  19. Thrombomodulin Induces a Quiescent Phenotype and Inhibits Migration in Vascular Smooth Muscle Cells In Vitro.

    Science.gov (United States)

    Bass, Heather M; Beard, Richard S; Cha, Byeong J; Yuan, Sarah Y; Nelson, Peter R

    2016-01-01

    Loss of critical endothelial cell function and subsequent vascular smooth muscle cell (VSMC) migration is central to the pathology of injury-induced neointimal hyperplasia and recurrent stenosis. Thrombomodulin (TM), well known for its function as an endothelial surface anticoagulant, may have an unknown direct effect on VSMC physiology that would be lost after injury. Here, we examined a novel effect of TM on VSMC by testing the hypothesis that direct application of TM induces favorable changes to the morphology of VSMC and inhibits their migration. Primary human VSMC were harvested using the explant technique and used in early passage (1-4) for all experiments. Laser-scanning confocal fluorescent imaging was performed to assess the effect of soluble TM on VSMC morphology. In vitro, migration of VSMC was measured using: (1) a 4-hr modified Boyden chemotaxis assay and (2) a 24-hr electric cell-substrate impedance sensing injury migration assay. Migration experiments were conducted with VSMC exposed to increasing doses of soluble recombinant TM. Recombinant thrombin served as a positive control and serum-free media as a negative control for all experimentation. Data were analyzed using a Student's t-test or repeated measures analysis of variance where appropriate (α < 0.05). VSMC exposed to TM clearly demonstrated a quiescent morphology with organized stress fibers consistent with a quiescent, differentiated, contractile phenotype; whereas, thrombin stimulation led to an activated, dedifferentiated, synthetic phenotype. VSMC demonstrated a low, baseline level of migration in unstimulated serum-free conditions. Thrombin significantly stimulated VSMC migration as expected. TM, independent of thrombin, significantly inhibited baseline VSMC migration in a dose-response fashion. The maximal inhibition was observed at (5 μg/mL) with 70% reduction (56 ± 1.7 vs. 18 ± 3.5 cells/5 high-power fields, P = 0.0005). TM has a direct effect on VSMC resulting in a quiescent

  20. Treatment effects of recombinant human soluble thrombomodulin in patients with severe sepsis: a historical control study.

    Science.gov (United States)

    Yamakawa, Kazuma; Fujimi, Satoshi; Mohri, Tomoyoshi; Matsuda, Hiroki; Nakamori, Yasushi; Hirose, Tomoya; Tasaki, Osamu; Ogura, Hiroshi; Kuwagata, Yasuyuki; Hamasaki, Toshimitsu; Shimazu, Takeshi

    2011-01-01

    Cross-talk between the coagulation system and inflammatory reactions during sepsis causes organ damage followed by multiple organ dysfunction syndrome or even death. Therefore, anticoagulant therapies have been expected to be beneficial in the treatment of severe sepsis. Recombinant human soluble thrombomodulin (rhTM) binds to thrombin to inactivate coagulation, and the thrombin-rhTM complex activates protein C to produce activated protein C. The purpose of this study was to examine the efficacy of rhTM for treating patients with sepsis-induced disseminated intravascular coagulation (DIC). This study comprised 65 patients with sepsis-induced DIC who required ventilatory management. All patients fulfilled the criteria of severe sepsis and the International Society on Thrombosis and Haemostasis criteria for overt DIC. The initial 45 patients were treated without rhTM (control group), and the following 20 consecutive patients were treated with rhTM (0.06 mg/kg/day) for six days (rhTM group). The primary outcome measure was 28-day mortality. Stepwise multivariate Cox regression analysis was used to assess which independent variables were associated with mortality. Comparisons of Sequential Organ Failure Assessment (SOFA) score on sequential days between the two groups were analyzed by repeated measures analysis of variance. Cox regression analysis showed 28-day mortality to be significantly lower in the rhTM group than in the control group (adjusted hazard ratio, 0.303; 95% confidence interval, 0.106 to 0.871; P = 0.027). SOFA score in the rhTM group decreased significantly in comparison with that in the control group (P = 0.028). In the post hoc test, SOFA score decreased rapidly in the rhTM group compared with that in the control group on day 1 (P < 0.05). We found that rhTM administration may improve organ dysfunction in patients with sepsis-induced DIC. Further clinical investigations are necessary to evaluate the effect of rhTM on the pathophysiology of sepsis

  1. Flavonolignan 2,3-dehydroderivatives: Preparation, antiradical and cytoprotective activity.

    Science.gov (United States)

    Pyszková, Michaela; Biler, Michal; Biedermann, David; Valentová, Kateřina; Kuzma, Marek; Vrba, Jiří; Ulrichová, Jitka; Sokolová, Romana; Mojović, Miloš; Popović-Bijelić, Ana; Kubala, Martin; Trouillas, Patrick; Křen, Vladimír; Vacek, Jan

    2016-01-01

    The protective constituents of silymarin, an extract from Silybum marianum fruits, have been extensively studied in terms of their antioxidant and hepatoprotective activities. Here, we explore the electron-donor properties of the major silymarin flavonolignans. Silybin (SB), silychristin (SCH), silydianin (SD) and their respective 2,3-dehydroderivatives (DHSB, DHSCH and DHSD) were oxidized electrochemically and their antiradical/antioxidant properties were investigated. Namely, Folin-Ciocalteau reduction, DPPH and ABTS(+) radical scavenging, inhibition of microsomal lipid peroxidation and cytoprotective effects against tert-butyl hydroperoxide-induced damage to a human hepatocellular carcinoma HepG2 cell line were evaluated. Due to the presence of the highly reactive C3-OH group and the C-2,3 double bond (ring C) allowing electron delocalization across the whole structure in the 2,3-dehydroderivatives, these compounds are much more easily oxidized than the corresponding flavonolignans SB, SCH and SD. This finding was unequivocally confirmed not only by experimental approaches, but also by density functional theory (DFT) calculations. The hierarchy in terms of ability to undergo electrochemical oxidation (DHSCH~DHSD>DHSB>SCH/SD>SB) was consistent with their antiradical activities, mainly DPPH scavenging, as well as in vitro cytoprotection of HepG2 cells. The results are discussed in the context of the antioxidant vs. prooxidant activities of flavonolignans and molecular interactions in complex biological systems. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients With Sepsis and Suspected Disseminated Intravascular Coagulation

    NARCIS (Netherlands)

    Vincent, Jean-Louis; Ramesh, Mayakonda K.; Ernest, David; Larosa, Steven P.; Pachl, Jan; Aikawa, Naoki; Hoste, Eric; Levy, Howard; Hirman, Joe; Levi, Marcel; Daga, Mradul; Kutsogiannis, Demetrios J.; Crowther, Mark; Bernard, Gordon R.; Devriendt, Jacques; Puigserver, Joan Vidal; Blanzaco, Daniel U.; Esmon, Charles T.; Parrillo, Joseph E.; Guzzi, Louis; Henderson, Seton J.; Pothirat, Chaicharn; Mehta, Parthiv; Fareed, Jawed; Talwar, Deepak; Tsuruta, Kazuhisa; Gorelick, Kenneth J.; Osawa, Yutaka; Kaul, Inder

    2013-01-01

    Objectives: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Design: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial.

  3. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  4. Synthetic Growth Hormone-Releasing Peptides (GHRPs: A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects

    Directory of Open Access Journals (Sweden)

    Jorge Berlanga-Acosta

    2017-02-01

    Full Text Available Background: Growth hormone-releasing peptides (GHRPs constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. Methodology: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. Results and Conclusions: GHRPs bind to two different receptors (GHS-R1a and CD36, which redundantly or independently exert relevant biological effects. GHRPs’ binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of “drugable” peptides awaits for a definitive clinical niche.

  5. Antioxidation and Cytoprotection of Acteoside and Its Derivatives: Comparison and Mechanistic Chemistry

    Directory of Open Access Journals (Sweden)

    Xican Li

    2018-02-01

    Full Text Available The study tried to explore the role of sugar-residues and mechanisms of phenolic phenylpropanoid antioxidants. Acteoside, along with its apioside forsythoside B and rhamnoside poliumoside, were comparatively investigated using various antioxidant assays. In three electron-transfer (ET-based assays (FRAP, CUPRAC, PTIO•-scavenging at pH 4.5, the relative antioxidant levels roughly ruled as: acteoside >forsythoside B > poliumoside. Such order was also observed in H+-transfer-involved PTIO•-scavenging assay at pH 7.4, and in three multiple-pathway-involved radical-scavenging assays, i.e., ABTS+•-scavenging, DPPH•-scavenging, and •O2−-scavenging. In UV-vis spectra, each of them displayed a red-shift at 335→364 nm and two weak peaks (480 and 719 nm, when mixed with Fe2+; however, acteoside gave the weakest absorption. In Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC−ESI−Q−TOF−MS/MS analysis, no radical-adduct-formation (RAF peak was found. MTT assay revealed that poliumoside exhibited the highest viability of oxidative-stressed bone marrow-derived mesenchymal stem cells. In conclusion, acteoside, forsythoside B, and poliumoside may be involved in multiple-pathways to exert the antioxidant action, including ET, H+-transfer, or Fe2+-chelating, but not RAF. The ET and H+-transfer may be hindered by rhamnosyl and apiosyl moieties; however, the Fe2+-chelating potential can be enhanced by two sugar-residues (especially rhamnosyl moiety. The general effect of rhamnosyl and apiosyl moieties is to improve the antioxidant or cytoprotective effects.

  6. Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro.

    Science.gov (United States)

    Paunovic, V; Kosic, M; Djordjevic, S; Zugic, A; Djalinac, N; Gasic, U; Trajkovic, V; Harhaji-Trajkovic, J

    2016-09-30

    Marrubium vulgare is a European medicinal plant with numerous beneficial effects on human health. The aim of the study was to isolate the plant ethanolic extract (MVE) and to investigate its anti-melanoma and anti-glioma effects. MVE was prepared by the modified pharmacopoeial percolation method and characterized by UHPLC-LTQ OrbiTrap MS. MVE dose-dependently reduced viability of melanoma (B16) and glioma (U251) cells, but not peripheral blood mononuclear cells. It arrested cell cycle in S+G2/M phase, which was associated with the activation of MAP kinase p38 and up-regulation of antiproliferative genes p53, p21 and p27. MVE induced oxidative stress, while antioxidants abrogated its antitumor effect. Furthermore, MVE induced mitochondrial depolarization, activation of caspase-9 and -3, Parp cleavage, phosphatidylserine exposure and DNA fragmentation. The mitochondrial apoptotic pathway was associated with the up-regulation of proapoptotic genes Pten, Bak1, Apaf1, and Puma and down-regulation of antiapoptotic genes survivin and Xiap. MVE also stimulated the expression of autophagy-related genes Atg5, Atg7, Atg12, Beclin-1, Gabarab and Sqstm1, as well as LC3-I conversion to the autophagosome associated LC3-II, while autophagy inhibitors exacerbated its cytotoxicity. Finally, the most abundant phenolic components of MVE, ferulic, p-hydroxybenzoic, caffeic and chlorogenic acids, did not exert a profound effect on viability of tumor cells, suggesting that other components individually or in concert are the mediators of the extracts' cytotoxicity. By demonstrating the ability of MVE to inhibit proliferation, induce apoptosis and cytoprotective autophagy, our results suggest that MVE, alone or combined with autophagy inhibitors, could be a good candidate for anti-melanoma and anti-glioma therapy.

  7. Fructose 1,6-Bisphosphate: A Summary of Its Cytoprotective Mechanism.

    Science.gov (United States)

    Alva, Norma; Alva, Ronald; Carbonell, Teresa

    2016-01-01

    In clinical and experimental settings, a great deal of effort is being made to protect cells and tissues against harmful conditions and to facilitate metabolic recovery following these insults. Much of the recent attention has focused on the protective role of a natural form of sugar, fructose 1,6-bisphosphate (F16bP). F16bP is a high-energy glycolytic intermediate that has been shown to exert a protective action in different cell types and tissues (including the brain, kidney, intestine, liver and heart) against various harmful conditions. For example, there is much evidence that it prevents neuronal damage due to hypoxia and ischemia. Furthermore, the cytoprotective effects of F16bP have been documented in lesions caused by chemicals or cold storage, in a decrease in mortality during sepsis shock and even in the prevention of bone loss in experimental osteoporosis. Intriguingly, protection in such a variety of targets and animal models suggests that the mechanisms induced by F16bP are complex and involve different pathways. In this review we will discuss the most recent theories concerning the molecular model of action of F16bP inside cells. These include its incorporation as an energy substrate, the mechanism for the improvement of ATP availability, and for preservation of organelle membrane stability and functionality. In addition we will present new evidences regarding the capacity of F16bP to decrease oxidative stress by limiting free radical production and improving antioxidant systems, including the role of nitric oxide in the protective mechanism induced by F16bP. Finally we will review the proposed mechanisms for explaining its anti-inflammatory, immunomodulatory and neuroprotective properties.

  8. When exercise causes exertional rhabdomyolysis.

    Science.gov (United States)

    Furman, Janet

    2015-04-01

    Exertional rhabdomyolysis is a clinical condition caused by intense, repetitive exercise or a sudden increase in exercise in an untrained person, although rhabdomyolysis can occur in trained athletes. In many cases, the presentation of early, uncomplicated rhabdomyolysis is subtle, but serious complications such as renal failure, compartment syndrome, and dysrhythmias may arise if severe exertional rhabdomyolysis is undiagnosed or untreated. Management is further complicated by the lack of concrete management guidelines for treating rhabdomyolysis and returning patients to activity.

  9. Cytoprotective effect of imatinib mesylate in non-BCR-ABL-expressing cells along with autophagosome formation

    Energy Technology Data Exchange (ETDEWEB)

    Ohtomo, Tadashi [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan); Miyazawa, Keisuke, E-mail: miyazawa@tokyo-med.ac.jp [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan); Naito, Munekazu [Department of Anatomy, Tokyo Medical University, Tokyo (Japan); Moriya, Shota [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan); Kuroda, Masahiko [Department of Molecular Pathology, Tokyo Medical University, Tokyo (Japan); Itoh, Masahiro [Department of Anatomy, Tokyo Medical University, Tokyo (Japan); Tomoda, Akio [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan)

    2010-01-01

    Treatment with imatinib mesylate (IM) results in an increased viable cell number of non-BCR-ABL-expressing cell lines by inhibiting spontaneous apoptosis. Electron microscopy revealed an increase of autophagosomes in response to IM. IM attenuated the cytotoxic effect of cytosine arabinoside, as well as inhibiting cell death with serum-deprived culture. Cytoprotection with autophagosome formation by IM was observed in various leukemia and cancer cell lines as well as normal murine embryonic fibroblasts (MEFs). Complete inhibition of autophagy by knockdown of atg5 in the Tet-off atg5{sup -/-} MEF system attenuated the cytoprotective effect of IM, indicating that the effect is partially dependent on autophagy. However, cytoprotection by IM was not mediated through suppression of ROS production via mitophagy, ER stress via ribophagy, or proapoptotic function of ABL kinase. Although the target tyrosine kinase(s) of IM remains unclear, our data provide novel therapeutic possibilities of using IM for cytoprotection.

  10. Cytoprotective effects of Glycyrrhizae radix extract and its active component liquiritigenin against cadmium-induced toxicity (effects on bad translocation and cytochrome c-mediated PARP cleavage)

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    Kim, Sang Chan; Byun, Sung Hui; Yang, Chae Ha; Kim, Chul Young; Kim, Jin Woong; Kim, Sang Geon

    2004-01-01

    Glycyrrhizae radix has been popularly used as one of the oldest and most frequently employed botanicals in herbal medicine in Asian countries, and currently occupies an important place in food products. Cadmium (Cd) induces both apoptotic and non-apoptotic cell death, in which alterations in cellular sulfhydryls participate. In the present study, we determined the effects of G. radix extract (GRE) and its representative active components on cell death induced by Cd and explored the mechanistic basis of cytoprotective effects of G. radix. Incubation of H4IIE cells with GRE inhibited cell death induced by 10 μM Cd. Also, GRE effectively blocked Cd (1 μM)-induced cell death potentiated by buthionine sulfoximine (BSO) without restoration of cellular GSH. GRE prevented both apoptotic and non-apoptotic cell injury induced by Cd (10 μM) or Cd (0.3-1 μM) + BSO. Inhibition of Cd-induced cell injury by pretreatment of cells with GRE suggested that the cytoprotective effect result from alterations in the levels of the protein(s) responsible for cell viability. GRE inhibited mitochondrial Bad translocation by Cd or Cd+BSO, and caused restoration of mitochondrial Bcl xL and cytochrome c levels. Cd-induced poly(ADP-ribose)polymerase cleavage in control cells or in cells deprived of sulfhydryls was prevented by GRE treatment. Among the major components present in GRE, liquiritigenin, but not liquiritin, isoliquiritigenin or glycyrrhizin, exerted cytoprotective effect. These results demonstrated that GRE blocked Cd-induced cell death by inhibiting the apoptotic processes involving translocation of Bad into mitochondria, decreases in mitochondrial Bcl xL and cytochrome c, and poly(ADP-ribose)polymerase cleavage

  11. Cytoprotective effects of dietary flavonoids against cadmium-induced toxicity.

    Science.gov (United States)

    Li, Xia; Jiang, Xinwei; Sun, Jianxia; Zhu, Cuijuan; Li, Xiaoling; Tian, Lingmin; Liu, Liu; Bai, Weibin

    2017-06-01

    Cadmium (Cd) damages the liver, kidney, bones, reproductive system, and other organs. Flavonoids, such as anthocyanins and flavonols, which are commonly found in plant foods, have shown protective effects against Cd-induced damage. The cytoprotective effects of flavonoids against Cd-induced diseases are mainly attributable to three mechanisms. First, flavonoids clear reactive oxygen species, thereby reducing lipid peroxide production and improving the activity of antioxidation enzymes. Second, flavonoids chelate Cd, thus reducing the accumulation of Cd and altering the levels of other essential metal ions in vivo. Third, flavonoids reduce DNA damage and inhibit apoptosis. In addition, flavonoids were found to inhibit inflammation and fibrosis and improve glycometabolism and the secretion of reproductive hormones. We introduce the daily dosage and absorption rate of flavonoids and then focus on their bioactive effects against Cd-induced toxicity and reveal the underlying metabolic pathway, which provides a basis for further study of the nutritional prevention of Cd-induced injury. In particular, a better understanding is needed of the structure-activity relationship of flavonoids against Cd toxicity, which has not yet been reported. © 2017 New York Academy of Sciences.

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

    Science.gov (United States)

    Varshney, Ritu; Gupta, Sumeet; Roy, Partha

    2017-06-15

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

  13. The Vitamin E Analog Gamma-Tocotrienol (GT3 and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM

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    Rupak Pathak

    2016-11-01

    Full Text Available Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR and strongly induce endothelial thrombomodulin (TM; which is known to have anti-inflammatory; anti-coagulation; anti-oxidant; and radioprotective properties. However; high-dose toxicity limits the clinical use of statins. The vitamin E family member gamma-tocotrienol (GT3 also suppresses HMGCR activity and induces TM expression without causing significant adverse side effects; even at high concentrations. To investigate the synergistic effect of statins and GT3 on TM; a low dose of atorvastatin and GT3 was used to treat human primary endothelial cells. Protein-level TM expression was measured by flow cytometry. TM functional activity was determined by activated protein C (APC generation assay. Expression of Kruppel-like factor 2 (KLF2, one of the key transcription factors of TM, was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. TM expression increased in a dose-dependent manner after both atorvastatin and GT3 treatment. A combined treatment of a low-dose of atorvastatin and GT3 synergistically up-regulated TM expression and functional activity. Finally; atorvastatin and GT3 synergistically increased KLF2 expression. These findings suggest that combined treatment of statins with GT3 may provide significant health benefits in treating a number of pathophysiological conditions; including inflammatory and cardiovascular diseases.

  14. Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.

    Science.gov (United States)

    Kim, Ji Eun; Yoo, Hyun Ju; Gu, Ja Yoon; Kim, Hyun Kyung

    2016-01-01

    The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.

  15. Cytoprotective effect of seaweeds with high antioxidant activity from the Peniche coast (Portugal).

    Science.gov (United States)

    Pinteus, Susete; Silva, Joana; Alves, Celso; Horta, André; Fino, Nádia; Rodrigues, Ana Inês; Mendes, Susana; Pedrosa, Rui

    2017-03-01

    Screening of antioxidant potential of dichloromethane and methanolic extracts of twenty-seven seaweeds from the Peniche coast was performed by: total phenolic contents (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Seaweeds revealing the highest antioxidant activity were screened for cytoprotective potential in MCF-7 cells, including the mitochondrial membrane potential analysis and the caspase-9 activity. High correlation was found between TPC of seaweed extracts and their scavenging capacity on DPPH and peroxyl radicals. The highest antioxidant activity was displayed by the methanolic fraction of brown seaweeds belonging to Fucales, however Ulva compressa presented the highest cytoprotective effect by blunting the apoptosis process. These results suggest that high antioxidant activity may not be directly related with high cytoprotective potential. Thus, seaweeds reveal to be a promising source of compounds with potential against oxidative stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The Role of Mcl-1 in S. aureus-Induced Cytoprotection of Infected Macrophages

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    Joanna Koziel

    2013-01-01

    cytoprotection of infected cells leading to apoptosis. Increased MCL1 expression in infected cells was associated with enhanced NFκB activation and subsequent IL-6 secretion, since the inhibition of both NFκB and IL-6 signalling pathways abrogated Mcl-1 induction and cytoprotection. Finally, we confirmed our observation in vivo in murine model of septic arthritis showing the association between the severity of arthritis and Mcl-1 expression. Therefore, we propose that S. aureus is hijacking the Mcl-1-dependent inhibition of apoptosis to prevent the elimination of infected host cells, thus allowing the intracellular persistence of the pathogen, its dissemination by infected macrophages, and the progression of staphylococci diseases.

  17. A new method to determine tissue specific tissue factor thrombomodulin activities: endotoxin and particulate air pollution induced disbalance

    Directory of Open Access Journals (Sweden)

    Gerlofs-Nijland Miriam E

    2008-10-01

    Full Text Available Abstract Background Increase in tissue factor (TF and loss in thrombomodulin (TM antigen levels has been described in various inflammatory disorders. The functional consequences of such changes in antigen concentrations in the coagulation balance are, however, not known. This study was designed to assess the consequences of inflammation-driven organ specific functional properties of the procoagulant response. Methods Tissue specific procoagulant activity was assessed by adding tissue homogenate to normal human pool plasma and recording of the thrombin generation curve. The new technique was subsequently applied on two inflammation driven animal models: 1 mouse lipopolysaccharide (LPS induced endotoxemia and 2 spontaneously hypertensive rats exposed to environmental air pollution (particulate matter (PM. Results Addition of lung tissue from untreated animals to human plasma suppressed the endogenous thrombin potential (ETP (175 ± 61 vs. 1437 ± 112 nM.min for control. This inhibitory effect was due to TM, because a it was absent in protein C deficient plasma and b lungs from TMpro/pro mice allowed full thrombin generation (ETP: 1686 ± 209 nM.min. The inhibitory effect of TM was lost after LPS administration to mice, which induced TF activity in lungs of C57Bl/6 mice as well as increased the ETP (941 ± 523 vs. 194 ± 159 nM.min for control. Another pro-inflammatory stimulus, PM dose-dependently increased TF in the lungs of spontaneously hypertensive rats at 4 and 48 hours after PM exposure. The ETP increased up to 48 hours at the highest concentration of PM (1441 ± 289 nM.min vs. saline: 164 ± 64 nM.min, p Conclusion Inflammation associated procoagulant effects in tissues are dependent on variations in activity of the TF-TM balance. The application of these novel organ specific functional assays is a useful tool to monitor inflammation-driven shifts in the coagulation balance within animal or human tissues.

  18. ICAM-1–targeted thrombomodulin mitigates tissue factor–driven inflammatory thrombosis in a human endothelialized microfluidic model

    Science.gov (United States)

    Johnston, Ian H.; Villa, Carlos H.; Gollomp, Kandace; Esmon, Charles T.; Cines, Douglas B.; Poncz, Mortimer

    2017-01-01

    Diverse human illnesses are characterized by loss or inactivation of endothelial thrombomodulin (TM), predisposing to microvascular inflammation, activation of coagulation, and tissue ischemia. Single-chain antibody fragment (scFv)/TM) fusion proteins, previously protective against end-organ injury in murine models of inflammation, are attractive candidates to treat inflammatory thrombosis. However, animal models have inherent differences in TM and coagulation biology, are limited in their ability to resolve and control endothelial biology, and do not allow in-depth testing of “humanized” scFv/TM fusion proteins, which are necessary for translation to the clinical domain. To address these challenges, we developed a human whole-blood, microfluidic model of inflammatory, tissue factor (TF)–driven coagulation that features a multichannel format for head-to-head comparison of therapeutic approaches. In this model, fibrin deposition, leukocyte adhesion, and platelet adhesion and aggregation showed a dose-dependent response to tumor necrosis factor-α activation and could be quantified via real-time microscopy. We used this model to compare hTM/R6.5, a humanized, intracellular adhesion molecule 1 (ICAM-1)–targeted scFv/TM biotherapeutic, to untargeted antithrombotic agents, including soluble human TM (shTM), anti–TF antibodies, and hirudin. The targeted hTM/R6.5 more effectively inhibited TF-driven coagulation in a protein C (PC)–dependent manner and demonstrated synergy with supplemental PC. These results support the translational prospects of ICAM-targeted scFv/TM and illustrate the utility of the microfluidic system as a platform to study humanized therapeutics at the interface of endothelium and whole blood under flow. PMID:29296786

  19. Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.

    Directory of Open Access Journals (Sweden)

    Ji Eun Kim

    Full Text Available The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF and anticoagulant thrombomodulin (TM. Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.

  20. Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.

    Directory of Open Access Journals (Sweden)

    Josée Bouchard

    Full Text Available Endothelial dysfunction contributes to the development of acute kidney injury (AKI in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC and soluble thrombomodulin (sTM levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr and urine output criteria (AKI UO. We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78. The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89, which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02 and PC levels independently predicted mortality/non-renal recovery (p=0.04. In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI.

  1. Mycolactone-Dependent Depletion of Endothelial Cell Thrombomodulin Is Strongly Associated with Fibrin Deposition in Buruli Ulcer Lesions.

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    Joy Ogbechi

    2015-07-01

    Full Text Available A well-known histopathological feature of diseased skin in Buruli ulcer (BU is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM expression on the surface of human dermal microvascular endothelial cells (HDMVEC at doses as low as 2 ng/ml and as early as 8 hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this

  2. Does mental exertion alter maximal muscle activation?

    Directory of Open Access Journals (Sweden)

    Vianney eRozand

    2014-09-01

    Full Text Available Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 minutes each: i high mental exertion (incongruent Stroop task, ii moderate mental exertion (congruent Stroop task, iii low mental exertion (watching a movie. In each condition, mental exertion was combined with ten intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 minutes. Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors.

  3. Salivary Cytoprotective Proteins in Inflammation and Resolution during Experimental Gingivitis--A Pilot Study.

    Science.gov (United States)

    Aboodi, Guy M; Sima, Corneliu; Moffa, Eduardo B; Crosara, Karla T B; Xiao, Yizhi; Siqueira, Walter L; Glogauer, Michael

    2015-01-01

    The protective mechanisms that maintain periodontal homeostasis in gingivitis and prevent periodontal tissue destruction are poorly understood. The aim of this study was to identify changes in the salivary proteome during experimental gingivitis. We used oral neutrophil quantification and whole saliva (WS) proteomics to assess changes that occur in the inflammatory and resolution phases of gingivitis in healthy individuals. Oral neutrophils and WS samples were collected and clinical parameters measured on days 0, 7, 14, 21, 28, and 35. Increased oral neutrophil recruitment and salivary cytoprotective proteins increased progressively during inflammation and decreased in resolution. Oral neutrophil numbers in gingival inflammation and resolution correlated moderately with salivary β-globin, thioredoxin, and albumin and strongly with collagen alpha-1 and G-protein coupled receptor 98. Our results indicate that changes in salivary cytoprotective proteins in gingivitis are associated with a similar trend in oral neutrophil recruitment and clinical parameters. We found moderate to strong correlations between oral neutrophil numbers and levels of several salivary cytoprotective proteins both in the development of the inflammation and in the resolution of gingivitis. Our proteomics approach identified and relatively quantified specific cytoprotective proteins in this pilot study of experimental gingivitis; however, future and more comprehensive studies are needed to clearly identify and validate those protein biomarkers when gingivitis is active.

  4. Salivary Cytoprotective Proteins in Inflammation and Resolution during Experimental Gingivitis—A Pilot Study

    Science.gov (United States)

    Aboodi, Guy M.; Sima, Corneliu; Moffa, Eduardo B.; Crosara, Karla T. B.; Xiao, Yizhi; Siqueira, Walter L.; Glogauer, Michael

    2016-01-01

    Objective: The protective mechanisms that maintain periodontal homeostasis in gingivitis and prevent periodontal tissue destruction are poorly understood. The aim of this study was to identify changes in the salivary proteome during experimental gingivitis. Study design: We used oral neutrophil quantification and whole saliva (WS) proteomics to assess changes that occur in the inflammatory and resolution phases of gingivitis in healthy individuals. Oral neutrophils and WS samples were collected and clinical parameters measured on days 0, 7, 14, 21, 28, and 35. Results: Increased oral neutrophil recruitment and salivary cytoprotective proteins increased progressively during inflammation and decreased in resolution. Oral neutrophil numbers in gingival inflammation and resolution correlated moderately with salivary β-globin, thioredoxin, and albumin and strongly with collagen alpha-1 and G-protein coupled receptor 98. Conclusions: Our results indicate that changes in salivary cytoprotective proteins in gingivitis are associated with a similar trend in oral neutrophil recruitment and clinical parameters. Clinical relevance: We found moderate to strong correlations between oral neutrophil numbers and levels of several salivary cytoprotective proteins both in the development of the inflammation and in the resolution of gingivitis. Our proteomics approach identified and relatively quantified specific cytoprotective proteins in this pilot study of experimental gingivitis; however, future and more comprehensive studies are needed to clearly identify and validate those protein biomarkers when gingivitis is active. PMID:26779447

  5. Chemical Characterization and Cytoprotective Effect of the Hydroethanol Extract from Annona coriacea Mart. (Araticum)

    Science.gov (United States)

    Júnior, José G. A. S.; Coutinho, Henrique D. M.; Boris, Ticiana C. C.; Cristo, Janyketchuly S.; Pereira, Nara L. F.; Figueiredo, Fernando G.; Cunha, Francisco A. B.; Aquino, Pedro E. A.; Nascimento, Polyana A. C.; Mesquita, Francisco J. C.; Moreira, Paulo H. F.; Coutinho, Sáskia T. B.; Souza, Ivon T.; Teixeira, Gabriela C.; Ferreira, Najla M. N.; Farina, Eleonora O.; Torres, Cícero M. G.; Holanda, Vanderlan N.; Pereira, Vandbergue S.; Guedes, Maria I. F.

    2016-01-01

    Introduction: Annona coriacea Mart. (araticum) is a widely distributed tree in the cerrado. Its value is attributed principally to the consumption of its fruit which possesses a large nutritive potential. The objective was to identify the chemical profile and evaluate the antimicrobial and cytoprotective activity of the hydroethanol extract of A. coriacea Mart. (HEAC) leaves against the toxicity of mercury chloride. Materials and Methods: The characterization of components was carried out using high-performance liquid chromatography (HPLC). The minimum inhibitory concentration (MIC) was determined by microdilution method in broth with strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. For evaluation of the modulatory and cytoprotective activity of aminoglycoside antibiotics (gentamicin and amikacin) and mercury chloride (HgCl2), the substances were associated with the HEAC at subinhibitory concentrations (MIC/8). Results and Discussion: The HPLC analysis revealed the presence of flavonoids such as Luteolin (1.84%) and Quercetin (1.19%) in elevated concentrations. The HEAC presented an MIC ≥512 μg/mL and significant antagonistic action in aminoglycosides modulation, and it also showed cytoprotective activity to S. aureus (significance P < 0.0001) and E. coli (significance P < 0.05) bacteria against the mercury chloride heavy metal with significance, this action being attributed to the chelating properties of the flavonoids found in the chemical identification. Conclusions: The results acquired in this study show that the HEAC presents cytoprotective activity over the tested strains in vitro and can also present antagonistic effect when associated with aminoglycosides, reinforcing the necessity of taking caution when combining natural and pharmaceutical products. SUMMARY The hydroalcoholic extract of A. coriacea Mart. presents in vitro cytoprotective activity against the toxic effect of Hg. Abbreviations Used: HPLC-DAD: High

  6. Cytoprotective effect of recombinant human erythropoietin produced in transgenic tobacco plants.

    Directory of Open Access Journals (Sweden)

    Farooqahmed S Kittur

    Full Text Available Asialo-erythropoietin, a desialylated form of human erythropoietin (EPO lacking hematopoietic activity, is receiving increased attention because of its broader protective effects in preclinical models of tissue injury. However, attempts to translate its protective effects into clinical practice is hampered by unavailability of suitable expression system and its costly and limit production from expensive mammalian cell-made EPO (rhuEPO(M by enzymatic desialylation. In the current study, we took advantage of a plant-based expression system lacking sialylating capacity but possessing an ability to synthesize complex N-glycans to produce cytoprotective recombinant human asialo-rhuEPO. Transgenic tobacco plants expressing asialo-rhuEPO were generated by stably co-expressing human EPO and β1,4-galactosyltransferase (GalT genes under the control of double CaMV 35S and glyceraldehyde-3-phosphate gene (GapC promoters, respectively. Plant-produced asialo-rhuEPO (asialo-rhuEPO(P was purified by immunoaffinity chromatography. Detailed N-glycan analysis using NSI-FTMS and MS/MS revealed that asialo-rhuEPO(P bears paucimannosidic, high mannose-type and complex N-glycans. In vitro cytoprotection assays showed that the asialo-rhuEPO(P (20 U/ml provides 2-fold better cytoprotection (44% to neuronal-like mouse neuroblastoma cells from staurosporine-induced cell death than rhuEPO(M (21%. The cytoprotective effect of the asialo-rhuEPO(P was found to be mediated by receptor-initiated phosphorylation of Janus kinase 2 (JAK2 and suppression of caspase 3 activation. Altogether, these findings demonstrate that plants are a suitable host for producing cytoprotective rhuEPO derivative. In addition, the general advantages of plant-based expression system can be exploited to address the cost and scalability issues related to its production.

  7. Role of Thrombin in Soluble Thrombomodulin-Induced Suppression of Peripheral HMGB1-Mediated Allodynia in Mice.

    Science.gov (United States)

    Tsujita, Ryuichi; Tsubota, Maho; Hayashi, Yusuke; Saeki, Haruka; Sekiguchi, Fumiko; Kawabata, Atsufumi

    2017-12-01

    High mobility group box 1 (HMGB1), a nuclear protein, once released into the extracellular space under pathological conditions, plays a pronociceptive role in redox-dependent distinct active forms, all-thiol HMGB1 (at-HMGB1) and disulfide HMGB1 (ds-HMGB1), that accelerate nociception through the receptor for advanced glycation endproducts (RAGE) and Toll-like receptor 4 (TLR4), respectively. Thrombomodulin (TM), an endothelial membrane protein, and soluble TM, known as TMα, promote thrombin-mediated activation of protein C and also sequester HMGB1, which might facilitate thrombin degradation of HMGB1. The present study aimed at clarifying the role of thrombin in TMα-induced suppression of peripheral HMGB1-dependent allodynia in mice. Thrombin-induced degradation of at-HMGB1 and ds-HMGB1 was accelerated by TMα in vitro. Intraplantar (i.pl.) injection of bovine thymus-derived HMGB1 in an unknown redox state, at-HMGB1, ds-HMGB1 or lipopolysaccharide (LPS), known to cause HMGB1 secretion, produced long-lasting mechanical allodynia in mice, as assessed by von Frey test. TMα, when preadministered i.pl., prevented the allodynia caused by bovine thymus-derived HMGB1, at-HMGB1, ds-HMGB1 or LPS, in a dose-dependent manner. The TMα-induced suppression of the allodynia following i.pl. at-HMGB1, ds-HMGB1 or LPS was abolished by systemic preadministration of argatroban, a thrombin-inhibiting agent, and accelerated by i.pl. co-administered thrombin. Our data clearly indicate that TMα is capable of promoting the thrombin-induced degradation of both at-HMGB1 and ds-HMGB1, and suppresses the allodynia caused by either HMGB1 in a thrombin-dependent manner. Considering the emerging role of HMGB1 in distinct pathological pain models, the present study suggests the therapeutic usefulness of TMα for treatment of intractable and/or persistent pain.

  8. I1 Imidazoline Receptor: Novel Potential Cytoprotective Target of TVP1022, the S-Enantiomer of Rasagiline

    Science.gov (United States)

    Frolov, Luba; Ovcharenko, Elena; Angel, Itzchak; Youdim, Moussa B. H.; Binah, Ofer

    2012-01-01

    TVP1022, the S-enantiomer of rasagiline (Azilect®) (N-propargyl-1R-aminoindan), exerts cyto/cardio-protective effects in a variety of experimental cardiac and neuronal models. Previous studies have demonstrated that the protective activity of TVP1022 and other propargyl derivatives involve the activation of p42/44 mitogen-activated protein kinase (MAPK) signaling pathway. In the current study, we further investigated the molecular mechanism of action and signaling pathways of TVP1022 which may account for the cyto/cardio-protective efficacy of the drug. Using specific receptor binding and enzyme assays, we demonstrated that the imidazoline 1 and 2 binding sites (I1 & I2) are potential targets for TVP1022 (IC50 = 9.5E-08 M and IC50 = 1.4E-07 M, respectively). Western blotting analysis showed that TVP1022 (1–20 µM) dose-dependently increased the immunoreactivity of phosphorylated p42 and p44 MAPK in rat pheochromocytoma PC12 cells and in neonatal rat ventricular myocytes (NRVM). This effect of TVP1022 was significantly attenuated by efaroxan, a selective I1 imidazoline receptor antagonist. In addition, the cytoprotective effect of TVP1022 demonstrated in NRVM against serum deprivation-induced toxicity was markedly inhibited by efaroxan, thus suggesting the importance of I1imidazoline receptor in mediating the cardioprotective activity of the drug. Our findings suggest that the I1imidazoline receptor represents a novel site of action for the cyto/cardio-protective efficacy of TVP1022. PMID:23166584

  9. I1 imidazoline receptor: novel potential cytoprotective target of TVP1022, the S-enantiomer of rasagiline.

    Directory of Open Access Journals (Sweden)

    Yaron D Barac

    Full Text Available TVP1022, the S-enantiomer of rasagiline (Azilect® (N-propargyl-1R-aminoindan, exerts cyto/cardio-protective effects in a variety of experimental cardiac and neuronal models. Previous studies have demonstrated that the protective activity of TVP1022 and other propargyl derivatives involve the activation of p42/44 mitogen-activated protein kinase (MAPK signaling pathway. In the current study, we further investigated the molecular mechanism of action and signaling pathways of TVP1022 which may account for the cyto/cardio-protective efficacy of the drug. Using specific receptor binding and enzyme assays, we demonstrated that the imidazoline 1 and 2 binding sites (I(1 & I(2 are potential targets for TVP1022 (IC(50 =9.5E-08 M and IC(50 =1.4E-07 M, respectively. Western blotting analysis showed that TVP1022 (1-20 µM dose-dependently increased the immunoreactivity of phosphorylated p42 and p44 MAPK in rat pheochromocytoma PC12 cells and in neonatal rat ventricular myocytes (NRVM. This effect of TVP1022 was significantly attenuated by efaroxan, a selective I(1 imidazoline receptor antagonist. In addition, the cytoprotective effect of TVP1022 demonstrated in NRVM against serum deprivation-induced toxicity was markedly inhibited by efaroxan, thus suggesting the importance of I(1imidazoline receptor in mediating the cardioprotective activity of the drug. Our findings suggest that the I(1imidazoline receptor represents a novel site of action for the cyto/cardio-protective efficacy of TVP1022.

  10. Antiradical and cytoprotective activities of several C-geranyl-substituted flavanones from Paulownia tomentosa fruit.

    Science.gov (United States)

    Zima, Ales; Hosek, Jan; Treml, Jakub; Muselík, Jan; Suchý, Pavel; Prazanová, Gabriela; Lopes, Ana; Zemlicka, Milan

    2010-08-31

    Antiradical and cytoprotective activities of several flavanones isolated from Paulownia tomentosa (Thunb.) Steud. (Scrophulariaceae) have been evaluated using different in vitro and in vivo methods. The capacity of flavanones to scavenge radicals was measured in vitro by means of DPPH and ABTS assays, the inhibition of hydroxyl radicals produced in Fenton reactions, FRAP, scavenging superoxide radicals using enzymatic and nonenzymatic assays and the inhibition of peroxynitrite-induced nitration of tyrosine. The in vivo testing involved measuring the cytoprotective effect of chosen flavanones against alloxan-induced diabetes in mice. The activity of tested compounds was expressed either as a Trolox® equivalent or was compared with rutin or morine as known antioxidant compounds. The highest activity in most tests was observed for diplacone and 3´-O-methyl-5´-hydroxydiplacone, and the structure vs. the antioxidant activity relationship of geranyl or prenyl-substituted flavonoids with different substitutions at the B and C ring was discussed.

  11. Phenolic Composition and Evaluation of Antioxidant and Cytoprotective Activity of Chiliadenus montanus

    OpenAIRE

    Tarek F. Eissa; Elena González-Burgos; M. Emilia Carretero; M. Pilar Gómez-Serranillos

    2013-01-01

    The antioxidant and cytoprotective activities of the hydroalcoholic extract of Chiliadenus montanus, widely used in Egyptian traditional medicine, were investigated. The antioxidant potential, determined using ORAC assay, revealed that Chiliadenus montanus extracts are active radical scavengers (ORAC value 1.720 µmol TE/mg sample). Total phenolic content, measured by Folin-Ciocalteau, was 107.4 mg galic acid/g sample. HPLC and HPLC-MS analysis allowed individual polyphenolic compounds to be i...

  12. Association of postmenopausal hormone replacement therapy with carotid atherosclerosis and soluble thrombomodulin: the vascular aging (EVA) study. Etude du Vieillissement Artériel.

    Science.gov (United States)

    Petit, Laure; van Oort, Floor V A; Le Gal, Grégoire; Mennen, Louise I; Alhenc-Gelas, Martine; Touboul, Pierre-Jean; Zureik, Mahmoud; Scarabin, Pierre-Yves

    2002-02-15

    Hormone replacement therapy (HRT) may reduce atherosclerosis among postmenopausal women, partly by reducing vascular endothelium damage. We have tested this hypothesis by evaluating the association of HRT with firstly, carotid intima media thickness (IMT) and plaques, and secondly, with endothelial cell damage, indicated by soluble thrombomodulin (sTM). Then, we tested the association between the two markers of atherosclerosis and the levels of sTM. Among 747 postmenopausal women included into the EVA study, we compared 154 HRT users (including 80% transdermal treatment) with 593 never users. Carotid IMT and plaques were measured with B-mode ultrasonography and sTM with ELISA. At least one plaque was detected among 13.6% of HRT users and 27.3% of never users. After adjustment for confounding factors, the odds ratio for the presence of plaque was 0.45 (95% confidence interval, 0.25-0.78, P=0.005) in HRT users in comparison with nonusers. HRT users had a slightly lower crude mean IMT than nonusers, but the difference was not significant. sTM was positively associated with mean IMT (P for trend=0.001) but not with plaques. Finally, estrogen users had a lower sTM level than nonusers (difference 0.14 ng/ml, P=0.03). As HRT was associated with sTM and plaques, but not with IMT, while sTM was only associated with IMT, our hypothesis was not confirmed. This suggests that the possible beneficial effects of HRT on atherosclerosis may not go through the endothelial cell damage assessed by plasma thrombomodulin.

  13. Dengue virus enhances thrombomodulin and ICAM-1 expression through the macrophage migration inhibitory factor induction of the MAPK and PI3K signaling pathways.

    Directory of Open Access Journals (Sweden)

    Trai-Ming Yeh

    Full Text Available Dengue virus (DV infections cause mild dengue fever (DF or severe life-threatening dengue hemorrhagic fever (DHF. The mechanisms that cause hemorrhage in DV infections remain poorly understood. Thrombomodulin (TM is a glycoprotein expressed on the surface of vascular endothelial cells that plays an important role in the thrombin-mediated activation of protein C. Prior studies have shown that the serum levels of soluble TM (sTM and macrophage migration inhibitory factor (MIF are significantly increased in DHF patients compared to levels in DF patients or normal controls. In this study, we investigated how MIF and sTM concentrations are enhanced in the plasma of DHF patients and the potential effect of MIF on coagulation through its influence on two factors: thrombomodulin (TM and intercellular adhesion molecule-1 (ICAM-1 in endothelial cells and monocytes. Recombinant human macrophage migration inhibitory factor (rMIF was used to treat monocytic THP-1 cells and endothelial HMEC-1 cells or primary HUVEC cells. The subsequent expression of TM and ICAM-1 was assessed by immunofluorescent staining and flow cytometry analysis. Additionally, the co-incubation of THP-1 cells with various cell signaling pathway inhibitors was used to determine the pathways through which MIF mediated its effect. The data provided evidence that severe DV infections induce MIF expression, which in turn stimulates monocytes or endothelial cells to express TM and ICAM-1 via the Erk, JNK MAPK and the PI3K signaling pathways, supporting the idea that MIF may play an important role as a regulator of coagulation.

  14. Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1.

    Science.gov (United States)

    Aayadi, Hoda; Mittal, Smriti P K; Deshpande, Anjali; Gore, Makarand; Ghaskadbi, Saroj S

    2017-11-01

    Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3β). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA. Expression of BTB and CNC homolog 1 (BACH-1), another regulator of HO-1, is also down-regulated by up-regulating microRNA 98 (miR-98), a negative regulator of BACH-1. Thus, geraniin up-regulates HO-1 expression both through activating its positive regulator Nrf-2 and by down-regulating its negative regulator BACH-1. Up-regulation of HO-1 also confers protection to HepG2 cells from tertiary butyl hydroperoxide (TBH) induced cytotoxicity. [BMB Reports 2017; 50(11): 560-565].

  15. Reflections on the Design of Exertion Games.

    Science.gov (United States)

    Mueller, Florian Floyd; Altimira, David; Khot, Rohit Ashot

    2015-02-01

    The design of exertion games (i.e., digital games that require physical effort from players) is a difficult intertwined challenge of combining digital games and physical effort. To aid designers in facing this challenge, we describe our experiences of designing exertion games. We outline personal reflections on our design processes and articulate analyses of players' experiences. These reflections and analyses serve to highlight the unique opportunities of combining digital games and physical effort. The insights we seek aim to enhance the understanding of exertion game design, contributing to the advancement of the field, and ultimately resulting in better games and associated player experiences.

  16. Design Strategies for Balancing Exertion Games

    DEFF Research Database (Denmark)

    Jensen, Mads Møller; Grønbæk, Kaj

    2016-01-01

    In sports, if players' physical and technical abilities are mismatched, the competition is often uninteresting for them. With the emergence of exertion games, this could be changing. Player balancing, known from video games, allows players with different skill levels to compete, however......, it is unclear how balancing mechanisms should be applied in exertion games, where physical and digital elements are fused. In this paper, we present an exertion game and three approaches for balancing it; a physical, an explicit-digital and an implicit-digital balancing approach. A user study that compares...... these three approaches is used to investigate the qualities and challenges within each approach and explore how the player experience is affected by them. Based on these findings, we suggest four design strategies for balancing exertion games, so that players will stay engaged in the game and contain...

  17. Gastric anti-ulcer and cytoprotective effect of selenium in rats

    Energy Technology Data Exchange (ETDEWEB)

    Parmar, N.S.; Tariq, M.; Ageel, A.M.

    1988-01-01

    Selenium, a trace element, in the form of sodium selenite has been studied for its ability to protect the gastric mucosa against the injuries caused by hypothermic restraint stress, aspirin, indomethacin, reserpine, dimaprit, and various other gastric mucosal-damaging (necrotizing) agents in rats. The results demonstrate that oral administration of sodium selenite produces a significant inhibition of the gastric mucosal damage induced by all the procedures used in this study. Selenium, in a nonantisecretory dose, produced a marked cytoprotective effect against all the necrotizing agents. The cytoprotective effect of selenium against the effects of 80% ethanol and 0.6 M HCl was significantly reversed by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis. These data indicate that sodium selenite inhibits the formation of these lesions by the mucosal generation of prostaglandins. The concentrations of nonprotein sulfhydryls (NP-SH) were significantly decreased in the gastric mucosa following the administration of necrotizing agents--80% ethanol and 0.6 M HCl. Treatment with sodium selenite, which significantly reduced the intensity of gastric lesions, did not replenish the reduced levels of gastric mucosal NP-SH, thus ruling out the mediation of its protective effect through sulfhydryls. The antisecretory effect of sodium selenite, which becomes evident only in the high dose of 20 mumol/kg, may be responsible for the inhibition of gastric lesions induced by aspirin, indomethacin, reserpine, and dimaprit. Our findings show that selenium possesses significant anti-ulcer and adaptive cytoprotective effects. However, further detailed studies are required to confirm these effects, to establish its mechanism(s) of action, and to determine its role in the prophylaxis and treatment of peptic ulcer disease.

  18. Cytoprotective effect of selective small-molecule caspase inhibitors against staurosporine-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Wu J

    2014-05-01

    Full Text Available Jianghong Wu, Yuren Wang, Shuguang Liang, Haiching Ma Reaction Biology Corp, Malvern, PA, USA Abstract: Caspases are currently known as the central executioners of the apoptotic pathways. Inhibition of apoptosis and promotion of normal cell survival by caspase inhibitors would be a tremendous benefit for reducing the side effects of cancer therapy and for control of neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. The objective of this study was to discover small-molecule caspase inhibitors with which to achieve cytoprotective effect. We completed the high-throughput screening of Bionet's 37,500-compound library (Key Organics Limited, Camelford, Cornwall, UK against caspase-1, -3, and -9 and successfully identified 43 initial hit compounds. The 43 hit compounds were further tested for cytoprotective activity against staurosporine-induced cell death in NIH3T3 cells. Nineteen compounds were found to have significant cytoprotective effects in cell viability assays. One of the compounds, RBC1023, was demonstrated to protect NIH3T3 cells from staurosporine-induced caspase-3 cleavage and activation. RBC1023 was also shown to protect against staurosporine-induced impairment of mitochondrial membrane potential. DNA microarray analysis demonstrated that staurosporine treatment induced broad global gene expression alterations, and RBC1023 co-treatment significantly restored these changes, especially of the genes that are related to cell growth and survival signaling such as Egr1, Cdc25c, cdkn3, Rhob, Nek2, and Taok1. Collectively, RBC1023 protects NIH3T3 cells against staurosporine-induced apoptosis via inhibiting caspase activity, restoring mitochondrial membrane potential, and possibly upregulating some cell survival-related gene expressions and pathways. Keywords: cell death, caspase inhibition, mitochondria, RBC1023

  19. Role of submandibular saliva and epidermal growth factor in gastric cytoprotection

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    without submandibular glands. Exogenous EGF and saliva with a high but still physiological concentration of EGF significantly reduced the median area in the stomach displaying ulcers and ulcerations, whereas saliva without EGF had no effect. Although EGF is a known inhibitor of gastric acid secretion......, the dose used in the present study had no effect on gastric acid secretion in chronic gastric fistula rats; removal of the submandibular glands also did not have any such effect. We conclude that exocrine secretion of submandibular EGF has a cytoprotective function in the stomach, an effect that may...

  20. Cytoprotective effect of tocopherols in hepatocytes cultured with polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Mikkelsen, L.; Hansen, Harald S.; Grunnet, N.

    1994-01-01

    When highly unsaturated fatty acids are added to cell cultures, it can become important to include antioxidants in the culture medium to prevent cytotoxic peroxidation. To find an optimal antioxidant for this purpose, the effect of 50 µM a-tocopherol, ¿-tocopherol, a-tocopheryl acetate, a...... of thiobarbituric acid reactive substances in the cultures was also measured. a-Tocopheryl acid succinate was found to be the most effective cytoprotective compound, followed by N,N'-diphenyl-1,4-phenylenediamine, a- tocopherol, ¿-tocopherol and a-tocopheryl acetate, and a-tocopheryl phosphate was without effect....

  1. Cytoprotective effects of essential oil of Pinus halepensis L. against aspirin-induced toxicity in IEC-6 cells.

    Science.gov (United States)

    Bouzenna, Hafsia; Hfaiedh, Najla; Bouaziz, Mouhamed; Giroux-Metges, Marie-Agnès; Elfeki, Abdelfattah; Talarmin, Hélène

    2017-12-01

    Essential oils from Pinus species have been reported to have various therapeutic properties. This study was undertaken to identify the chemical composition and cytoprotective effects of the essential oil of Pinus halepensis L. against aspirin-induced damage in cells in vitro. The cytoprotection of the oil against toxicity of aspirin on the small intestine epithelial cells IEC-6 was tested. The obtained results have shown that 35 different compounds were identified. Aspirin induced a decrease in cell viability, and exhibited significant damage to their morphology and an increase in superoxide dismutase (SOD) and catalase (CAT) activities. However, the co-treatment of aspirin with the essential oil of Pinus induced a significant increase in cell viability and a decrease in SOD and CAT activities. Overall, these finding suggest that the essential oil of Pinus halepensis L. has potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

  2. Assessment of Antioxidant and Cytoprotective Potential of Jatropha (Jatropha curcas) Grown in Southern Italy.

    Science.gov (United States)

    Papalia, Teresa; Barreca, Davide; Panuccio, Maria Rosaria

    2017-03-18

    Jatropha ( Jatropha curcas L.) is a plant native of Central and South America, but widely distributed in the wild or semi-cultivated areas in Africa, India, and South East Asia. Although studies are available in literature on the polyphenolic content and bioactivity of Jatropha curcas L., no information is currently available on plants grown in pedoclimatic and soil conditions different from the autochthon regions. The aim of the present work was to characterize the antioxidant system developed by the plant under a new growing condition and to evaluate the polyphenol amount in a methanolic extract of leaves. Along with these analyses we have also tested the antioxidant and cytoprotective activities on lymphocytes. RP-HPLC-DAD analysis of flavonoids revealed a chromatographic profile dominated by the presence of flavone C -glucosydes. Vitexin is the most abundant identified compound followed by vicenin-2, stellarin-2, rhoifolin, and traces of isovitexin and isorhoifolin. Methanolic extract had high scavenging activity in all antioxidant assays tested and cytoprotective activity on lymphocytes exposed to tertz-buthylhydroperoxide. The results highlighted a well-defined mechanism of adaptation of the plant and a significant content of secondary metabolites with antioxidant properties, which are of interest for their potential uses, especially as a rich source of biologically active products.

  3. Cytoprotective effect against mercury chloride and bioinsecticidal activity of Eugenia jambolana Lam.

    Directory of Open Access Journals (Sweden)

    Celestina E. Sobral-Souza

    2014-01-01

    Full Text Available The fruit fly Drosophila melanogaster is often utilized in genetic research, and in the last decades, it has become one of best organisms for studies of human diseases and toxicological research. Mercury chloride (HgCl2, the main representative of mercury compounds, is the target of numerous investigations, not only because of its intrinsic toxicity but also because it accounts for the toxicity of elemental mercury since the latter is converted to Hg+2 by oxidation. Eugenia jambolana Lam. Myrtaceae, known in Brazil as “jambolão”, is of great interest because of its medicinal applications, especially its leaves and fruits. The aim of this work was to characterize, by CG–MS, the chemical constituents of the essential oil of Eugenia jambolana and to evaluate its bioinsecticidal action in the Drosophila melanogaster model, as well as to determine the cytoprotective and chelating effect of the extract of E. jambolana. The results obtained here point to the potential of essential oils as a source in biological prospecting for bioinsecticides. Because of their biodegradability, essential oils can be important tools in the biological control of pests. The results demonstrated that the extract has an allelopathic effect on lettuce seeds and that its interaction with mercury chloride allows a greater growth of the radicle and plumule of Lactuta sativa seedlings, showing that this plant can provide an alternative solution to the problem of contamination by heavy metals, besides having cytoprotective potential and moderate chelating activity.

  4. Antiradical and Cytoprotective Activities of Several C-Geranyl-substituted Flavanones from Paulownia tomentosa Fruit

    Directory of Open Access Journals (Sweden)

    Ana Lopes

    2010-08-01

    Full Text Available Antiradical and cytoprotective activities of several flavanones isolated from Paulownia tomentosa (Thunb. Steud. (Scrophulariaceae have been evaluated using different in vitro and in vivo methods. The capacity of flavanones to scavenge radicals was measured in vitro by means of DPPH and ABTS assays, the inhibition of hydroxyl radicals produced in Fenton reactions, FRAP, scavenging superoxide radicals using enzymatic and nonenzymatic assays and the inhibition of peroxynitrite-induced nitration of tyrosine. The in vivo testing involved measuring the cytoprotective effect of chosen flavanones against alloxan-induced diabetes in mice. The activity of tested compounds was expressed either as a Trolox® equivalent or was compared with rutin or morine as known antioxidant compounds. The highest activity in most tests was observed for diplacone and 3´-O-methyl-5´-hydroxydiplacone, and the structure vs. the antioxidant activity relationship of geranyl or prenyl-substituted flavonoids with different substitutions at the B and C ring was discussed.

  5. Antioxidant, antibrowning, and cytoprotective activities of Ligustrum robustum (Rxob.) Blume extract.

    Science.gov (United States)

    Yu, Zhi-Long; Zeng, Wei-Cai

    2013-09-01

    The antioxidant, antibrowning, and cytoprotective activities of Ligustrum robustum (Rxob.) Blume extract (LRE) were investigated and the main antioxidant component was isolated and identified. With its high content of phenols and flavonoids, the LRE showed remarkable antioxidant capacity to scavenge free radicals in vitro and to inhibit oil oxidation in a peanut oil system. Moreover, LRE was observed to inhibit tyrosinase action and browning of fresh-cut apple slices effectively. Furthermore, the cytoprotective activity of LRE was evaluated in a human intestine model using Caco-2 cell lines. According to the activity-guided isolation and identification, by using column chromatography, high-performance liquid chromatography, time-of-flight mass spectrometry, and nuclear magnetic resonance analyses, ursolic acid was characterized as the main antioxidant component of LRE; it showed the strongest free radical-scavenging activity. The results suggested that L. robustum (Rxob.) Blume could be a new resource for preparing functional food and nutraceutical products for use in food and pharmacology industries. © 2013 Institute of Food Technologists®

  6. Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain

    Science.gov (United States)

    Horowitz, Netanel A.; Blevins, Elizabeth A.; Miller, Whitney M.; Perry, Ashley R.; Talmage, Kathryn E.; Mullins, Eric S.; Flick, Matthew J.; Queiroz, Karla C. S.; Shi, Kun; Spek, C. Arnold; Conway, Edward M.; Monia, Brett P.; Weiler, Hartmut; Degen, Jay L.

    2011-01-01

    Thrombomodulin (TM) is a predominantly endothelial transmembrane glycoprotein that modulates hemostatic function through a domain that controls thrombin-mediated proteolysis and an N-terminal lectin-like domain that controls inflammatory processes. To test the hypothesis that TM is a determinant of malignancy and dissect the importance of these functional domains in cancer biology, metastatic potential was evaluated in TMPro mice expressing a mutant form of TM with reduced thrombin affinity and TMLeD mice lacking the N-terminal lectin-like domain. Studies of TMPro mice revealed that TM is a powerful determinant of hematogenous metastasis. TMPro mice exhibited a strongly prometastatic phenotype relative to control mice that was found to result from increased survival of tumor cells newly localized to the lung rather than any alteration in tumor growth. The impact of the TMPro mutation on metastasis was dependent on both tumor cell-associated tissue factor and thrombin procoagulant function. In contrast, expression of a mutant form of TM lacking the lectin-like domain had no significant impact on metastasis. These studies directly demonstrate for the first time that TM-mediated regulation of tumor cell-driven procoagulant function strongly influences metastatic potential and suggest that endothelial cell-associated modulators of hemostasis may represent novel therapeutic targets in limiting tumor dissemination. PMID:21788337

  7. Pulmonary antioxidants exert differential protective effects against ...

    Indian Academy of Sciences (India)

    Unknown

    fractions than on the PM2⋅5–0⋅1 fractions, supporting the previous findings that respirable PM and urban samples contain fewer free radical sources than inhalable PM and industrial samples. [Greenwell L L, Moreno T and Richards R J 2003 Pulmonary antioxidants exert differential protective effects against urban and ...

  8. Pulmonary antioxidants exert differential protective effects against ...

    Indian Academy of Sciences (India)

    When repeated in the presence of a low molecular weight fraction of fresh pulmonary lavage fluid, as well as in artificial lung lining fluid (200 M urate, glutathione and ascorbate), the DNA damage was significantly reduced in all cases ( < 0.05). The antioxidants exerted a greater effect on the industrial samples than on ...

  9. Perceived exertion influences pacing among ultramarathon runners ...

    African Journals Online (AJOL)

    Objectives. This study investigated whether post-race mood changes among ultramarathon runners are associated with perceived exertion or the discrepancy between their actual and predicted performance times. Methods. Eight runners completed the Puffer ultramarathon, which is a challenging 73 km mountainous race ...

  10. Sevoflurane improves gaseous exchange and exerts protective ...

    African Journals Online (AJOL)

    Original Research Article. Sevoflurane improves gaseous exchange and exerts protective effects in lipopolysaccharide-induced lung injury in mice models .... field microscope [20]. Statistical analysis. All data are expressed as mean ± standard error of the mean (SEM). One-way ANOVA followed by Tukey's test were used ...

  11. Cytotoxic and cytoprotective activities of curcumin. Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes

    NARCIS (Netherlands)

    Donatus, I A; Sardjoko,; Vermeulen, N P

    1990-01-01

    The cytoprotective effect of curcumin, a natural constituent of Curcuma longa, on the cytotoxicity of paracetamol in rat hepatocytes was studied. Paracetamol was selected as a model-toxin, since it is known to be bioactivated by 3-methylcholanthrene inducible cytochromes P450 presumably to

  12. Yeast as a Tool to Study Signaling Pathways in Mitochondrial Stress Response and Cytoprotection

    Directory of Open Access Journals (Sweden)

    Maša Ždralević

    2012-01-01

    Full Text Available Cell homeostasis results from the balance between cell capability to adapt or succumb to environmental stress. Mitochondria, in addition to supplying cellular energy, are involved in a range of processes deciding about cellular life or death. The crucial role of mitochondria in cell death is well recognized. Mitochondrial dysfunction has been associated with the death process and the onset of numerous diseases. Yet, mitochondrial involvement in cellular adaptation to stress is still largely unexplored. Strong interest exists in pharmacological manipulation of mitochondrial metabolism and signaling. The yeast Saccharomyces cerevisiae has proven a valuable model organism in which several intracellular processes have been characterized in great detail, including the retrograde response to mitochondrial dysfunction and, more recently, programmed cell death. In this paper we review experimental evidences of mitochondrial involvement in cytoprotection and propose yeast as a model system to investigate the role of mitochondria in the cross-talk between prosurvival and prodeath pathways.

  13. Solventless extraction methods for immature fruits: Evaluation of their antioxidant and cytoprotective activities.

    Science.gov (United States)

    Heng, Ming Yuan; Katayama, Shigeru; Mitani, Takakazu; Ong, Eng Shi; Nakamura, Soichiro

    2017-04-15

    In this study, extraction of immature fruits using an environmentally friendly pressurized hot water extraction (PHWE) method was compared with the traditional reflux method. Extracts were tested for their polyphenol content using the Folin-Ciocalteu assay and for their antioxidant activity using the oxygen radical absorbance capacity (ORAC) assay. The highest amount of polyphenol was extracted from grape (stem) using PHWE at 100°C, or reflux extraction. This was followed by reflux extraction of grape (fruit). The results were similar for the ORAC assay. All samples extracted using PHWE at 100°C showed cytoprotective activity against H 2 O 2 -induced oxidative stress in Crandell-Reese feline kidney (CRFK) cells. This study demonstrated that beneficial compounds can be extracted from immature fruits without the use of organic solvents. The utilization of beneficial compounds present in immature fruits can also contribute to the reduction in agriculture waste generated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Cytoprotective effect of tocopherols in hepatocytes cultured with polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Mikkelsen, L.; Hansen, Harald S.; Grunnet, N.

    1994-01-01

    When highly unsaturated fatty acids are added to cell cultures, it can become important to include antioxidants in the culture medium to prevent cytotoxic peroxidation. To find an optimal antioxidant for this purpose, the effect of 50 µM a-tocopherol, ¿-tocopherol, a-tocopheryl acetate, a......- tocopheryl acid succinate, or a-tocopheryl phosphate, or of 1 µM N,N'- diphenyl-1,4-phenylenediamine, was investigated with respect to the agent's ability to prevent lactate dehydrogenase leakage in long-term rat hepatocyte cultures supplemented with 0.5 mM highly unsaturated fatty acids. Formation...... of thiobarbituric acid reactive substances in the cultures was also measured. a-Tocopheryl acid succinate was found to be the most effective cytoprotective compound, followed by N,N'-diphenyl-1,4-phenylenediamine, a- tocopherol, ¿-tocopherol and a-tocopheryl acetate, and a-tocopheryl phosphate was without effect....

  15. Health and Cellular Impacts of Air Pollutants: From Cytoprotection to Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Karine Andreau

    2012-01-01

    Full Text Available Air pollution as one of the ravages of our modern societies is primarily linked to urban centers, industrial activities, or road traffic. These atmospheric pollutants have been incriminated in deleterious health effects by numerous epidemiological and in vitro studies. Environmental air pollutants are a heterogeneous mixture of particles suspended into a liquid and gaseous phase which trigger the disruption of redox homeostasis—known under the term of cellular oxidative stress—in relation with the establishment of inflammation and cell death via necrosis, apoptosis, or autophagy. Activation or repression of the apoptotic process as an adaptative response to xenobiotics might lead to either acute or chronic toxicity. The purpose of this paper is to highlight the central role of oxidative stress induced by air pollutants and to focus on the subsequent cellular impacts ranging from cytoprotection to cytotoxicity by decreasing or stimulating apoptosis, respectively.

  16. An antioxidant nanozyme that uncovers the cytoprotective potential of vanadia nanowires

    Science.gov (United States)

    Vernekar, Amit A.; Sinha, Devanjan; Srivastava, Shubhi; Paramasivam, Prasath U.; D'Silva, Patrick; Mugesh, Govindasamy

    2014-11-01

    Nanomaterials with enzyme-like properties has attracted significant interest, although limited information is available on their biological activities in cells. Here we show that V2O5 nanowires (Vn) functionally mimic the antioxidant enzyme glutathione peroxidase by using cellular glutathione. Although bulk V2O5 is known to be toxic to the cells, the property is altered when converted into a nanomaterial form. The Vn nanozymes readily internalize into mammalian cells of multiple origin (kidney, neuronal, prostate, cervical) and exhibit robust enzyme-like activity by scavenging the reactive oxygen species when challenged against intrinsic and extrinsic oxidative stress. The Vn nanozymes fully restore the redox balance without perturbing the cellular antioxidant defense, thus providing an important cytoprotection for biomolecules against harmful oxidative damage. Based on our findings, we envision that biocompatible Vn nanowires can provide future therapeutic potential to prevent ageing, cardiac disorders and several neurological conditions, including Parkinson’s and Alzheimer’s disease.

  17. Role of submandibular saliva and epidermal growth factor in gastric cytoprotection

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    , the dose used in the present study had no effect on gastric acid secretion in chronic gastric fistula rats; removal of the submandibular glands also did not have any such effect. We conclude that exocrine secretion of submandibular EGF has a cytoprotective function in the stomach, an effect that may......The role of submandibular epidermal growth factor in protection of the gastric mucosa was investigated in rats. Removal of the submandibular glands and thereby submandibular epidermal growth factor (EGF) caused rats to develop gastric lesions (ulcerations and ulcers) after administration...... of the duodenal ulcerogen cysteamine. The median output of EGF in gastric juice was reduced from 45.6 pmol/12 h (total range 17.5-65.0) in unoperated controls to less than 0.06 pmol/12 h (total range less than 0.06-1.82) in rats given cysteamine after extirpation of the submandibular glands. The contents of EGF...

  18. Cytoprotective effects of fisetin against hypoxia-induced cell death in PC12 cells.

    Science.gov (United States)

    Chen, Pei-Yi; Ho, Yi-Ru; Wu, Ming-Jiuan; Huang, Shun-Ping; Chen, Po-Kong; Tai, Mi-Hsueh; Ho, Chi-Tang; Yen, Jui-Hung

    2015-01-01

    Fisetin (3,7,3',4'-tetrahydroxyflavone), a flavonol compound of flavonoids, exhibits a broad spectrum of biological activities including anti-oxidant, anti-inflammatory, anti-cancer and neuroprotective effects. The aim of this study is to investigate the cytoprotective effect of fisetin and the underlying molecular mechanism against hypoxia-induced cell death in PC12 cells. The results of this study showed that fisetin significantly restored the cell viability of PC12 cells under both cobalt chloride (CoCl₂)- and low oxygen-induced hypoxic conditions. Treatment with fisetin successfully reduced the CoCl₂-mediated reactive oxygen species (ROS) production, which was accompanied by an increase in the cell viability of PC12 cells. Furthermore, we found that treatment of PC12 cells with fisetin markedly upregulated hypoxia-inducible factor 1α (HIF-1α), its nuclear accumulation and the hypoxia-response element (HRE)-driven transcriptional activation. The fisetin-mediated cytoprotection during CoCl₂ exposure was significantly attenuated through the administration of HIF-1α siRNA. Moreover, we demonstrated that MAPK/ERK kinase 1/2 (MEK1/2), p38 MAPK and phosphatidylinositol 3-kinase (PI3 K) inhibitors significantly blocked the increase in cell survival that was induced by fisetin treatment under hypoxic conditions. Consistently, increased phosphorylation of ERK, p38 and Akt proteins was observed in PC12 cells treated with fisetin. However, the fisetin-induced HRE-driven transcription was not affected by inhibition of these kinase signaling pathways. Current results reveal for the first time that fisetin promotes cell survival and protects against hypoxia-induced cell death through ROS scavenging and the activation of HIF1α-, MAPK/ERK-, p38 MAPK- and PI3 K/Akt-dependent signaling pathways in PC12 cells.

  19. Antioxidant and cytoprotective properties of D-tagatose in cultured murine hepatocytes.

    Science.gov (United States)

    Paterna, J C; Boess, F; Stäubli, A; Boelsterli, U A

    1998-01-01

    D-Tagatose is a zero-energy producing ketohexose that is a powerful cytoprotective agent against chemically induced cell injury. To further explore the underlying mechanisms of cytoprotection, we investigated the effects of D-tagatose on both the generation of superoxide anion radicals and the consequences of oxidative stress driven by prooxidant compounds in intact cells. Primary cultures of hepatocytes derived from male C57BL/6 mice were exposed to the redox cycling drug nitrofurantoin (NFT). Lethal cell injury induced by 300 microM NFT was completely prevented by high concentrations (20 mM) of D-tagatose, whereas equimolar concentrations of glucose, mannitol, or xylose were ineffective. The extent of NFT-induced intracellular superoxide anion radical formation was not altered by D-tagatose, indicating that the ketohexose did not inhibit the reductive bioactivation of NFT. However, the NFT-induced decline of the intracellular GSH content was largely prevented by D-tagatose. The sugar also afforded complete protection against NFT toxicity in hepatocytes that had been chemically depleted of GSH. Furthermore, the ketohexose fully protected from increases in both membrane lipid peroxidation and protein carbonyl formation. In addition, D-tagatose completely prevented oxidative cell injury inflicted by toxic iron overload with ferric nitrilotriacetate (100 microM). In contrast, D-tagatose did not protect against lethal cell injury induced by tert-butyl hydroperoxide, a prooxidant which acts by hydroxyl radical-independent mechanisms and which is partitioned in the lipid bilayer. These results indicate that D-tagatose, which is a weak iron chelator, can antagonize the iron-dependent toxic consequences of intracellular oxidative stress in hepatocytes. The antioxidant properties of D-tagatose may result from sequestering the redox-active iron, thereby protecting more critical targets from the damaging potential of hydroxyl radical.

  20. Chaperone heat shock protein 90 mobilization and hydralazine cytoprotection against acrolein-induced carbonyl stress.

    Science.gov (United States)

    Burcham, Philip C; Raso, Albert; Kaminskas, Lisa M

    2012-11-01

    Toxic carbonyls such as acrolein participate in many degenerative diseases. Although the nucleophilic vasodilatory drug hydralazine readily traps such species under "test-tube" conditions, whether these reactions adequately explain its efficacy in animal models of carbonyl-mediated disease is uncertain. We have previously shown that hydralazine attacks carbonyl-adducted proteins in an "adduct-trapping" reaction that appears to take precedence over direct "carbonyl-sequestering" reactions, but how this reaction conferred cytoprotection was unclear. This study explored the possibility that by increasing the bulkiness of acrolein-adducted proteins, adduct-trapping might alter the redistribution of chaperones to damaged cytoskeletal proteins that are known targets for acrolein. Using A549 lung adenocarcinoma cells, the levels of chaperones heat shock protein (Hsp) 40, Hsp70, Hsp90, and Hsp110 were measured in intermediate filament extracts prepared after a 3-h exposure to acrolein. Exposure to acrolein alone modestly increased the levels of all four chaperones. Coexposure to hydralazine (10-100 μM) strongly suppressed cell ATP loss while producing strong adduct-trapping in intermediate filaments. Most strikingly, hydralazine selectively boosted the levels of cytoskeletal-associated Hsp90, including a high-mass species that was sensitive to the Hsp90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin. Biochemical fractionation of acrolein- and hydralazine-treated cells revealed that hydralazine likely promoted Hsp90 migration from cytosol into other subcellular compartments. A role for Hsp90 mobilization in cytoprotection was confirmed by the finding that brief heat shock treatment suppressed acute acrolein toxicity in A549 cells. Taken together, these findings suggest that by increasing the steric bulk of carbonyl-adducted proteins, adduct-trapping drugs trigger the intracellular mobilization of the key molecular chaperone Hsp90.

  1. Induction of cyto-protective autophagy by paramontroseite VO2 nanocrystals

    Science.gov (United States)

    Zhou, Wei; Miao, Yanyan; Zhang, Yunjiao; Liu, Liang; Lin, Jun; Yang, James Y.; Xie, Yi; Wen, Longping

    2013-04-01

    A variety of inorganic nanomaterials have been shown to induce autophagy, a cellular degradation process critical for the maintenance of cellular homeostasis. The overwhelming majority of autophagic responses elicited by nanomaterials were detrimental to cell fate and contributed to increased cell death. A widely held view is that the inorganic nanoparticles, when encapsulated and trapped by autophagosomes, may compromise the normal autophagic process due to the inability of the cells to degrade these materials and thus they manifest a detrimental effect on the well-being of a cell. Here we show that, contrary to this notion, nano-sized paramontroseite VO2 nanocrystals (P-VO2) induced cyto-protective, rather than death-promoting, autophagy in cultured HeLa cells. P-VO2 also caused up-regulation of heme oxygenase-1 (HO-1), a cellular protein with a demonstrated role in protecting cells against death under stress situations. The autophagy inhibitor 3-methyladenine significantly inhibited HO-1 up-regulation and increased the rate of cell death in cells treated with P-VO2, while the HO-1 inhibitor protoporphyrin IX zinc (II) (ZnPP) enhanced the occurrence of cell death in the P-VO2-treated cells while having no effect on the autophagic response induced by P-VO2. On the other hand, Y2O3 nanocrystals, a control nanomaterial, induced death-promoting autophagy without affecting the level of expression of HO-1, and the pro-death effect of the autophagy induced by Y2O3. Our results represent the first report on a novel nanomaterial-induced cyto-protective autophagy, probably through up-regulation of HO-1, and may point to new possibilities for exploiting nanomaterial-induced autophagy for therapeutic applications.

  2. Riluzole increases the amount of latent HSF1 for an amplified heat shock response and cytoprotection.

    Directory of Open Access Journals (Sweden)

    Jingxian Yang

    Full Text Available BACKGROUND: Induction of the heat shock response (HSR and increased expression of the heat shock proteins (HSPs provide mechanisms to ensure proper protein folding, trafficking, and disposition. The importance of HSPs is underscored by the understanding that protein mis-folding and aggregation contribute centrally to the pathogenesis of neurodegenerative diseases. METHODOLOGY/PRINCIPAL FINDINGS: We used a cell-based hsp70-luciferease reporter gene assay system to identify agents that modulate the HSR and show here that clinically relevant concentrations of the FDA-approved ALS drug riluzole significantly increased the heat shock induction of hsp70-luciferse reporter gene. Immuno-Western and -cytochemical analysis of HSF1 show that riluzole increased the amount of cytosolic HSF1 to afford a greater activation of HSF1 upon heat shock. The increased HSF1 contributed centrally to the cytoprotective activity of riluzole as hsf1 gene knockout negated the synergistic activity of riluzole and conditioning heat shock to confer cell survival under oxidative stress. Evidence of a post-transcriptional mechanism for the increase in HSF1 include: quantitation of mRNA(hsf1 by RT-PCR showed no effect of either heat shock or riluzole treatment; riluzole also increased the expression of HSF1 from a CMV-promoter; analysis of the turnover of HSF1 by pulse chase and immunoprecipitation show that riluzole slowed the decay of [(35S]labeled-HSF1. The effect of riluzole on HSF1 was qualitatively different from that of MG132 and chloroquine, inhibitors of the proteasome and lysosome, respectively, and appeared to involve the chaperone-mediated autophagy pathway as RNAi-mediated knockdown of CMA negated its effect. CONCLUSION/SIGNIFICANCE: We show that riluzole increased the amount of HSF1 to amplify the HSR for cytoprotection. Our study provides novel insight into the mechanism that regulates HSF1 turnover, and identifies the degradation of HSF1 as a target for

  3. Cytoprotective Effects of Pumpkin (Cucurbita Moschata) Fruit Extract against Oxidative Stress and Carbonyl Stress.

    Science.gov (United States)

    Shayesteh, Reyhaneh; Kamalinejad, Mohammad; Adiban, Hasan; Kardan, Azin; Keyhanfar, Fariborz; Eskandari, Mohammad Reza

    2017-10-01

    Background Diabetes mellitus is a chronic endocrine disorder that is associated with significant mortality and morbidity due to microvascular and macrovascular complications. Diabetes complications accompanied with oxidative stress and carbonyl stress in different organs of human body because of the increased generation of free radicals and impaired antioxidant defense systems. In the meantime, reactive oxygen species (ROS) and reactive carbonyl species (RCS) have key mediatory roles in the development and progression of diabetes complications. Therapeutic strategies have recently focused on preventing such diabetes-related abnormalities using different natural and chemical compounds. Pumpkin ( Cucurbita moschata ) is one of the most important vegetables in the world with a broad-range of pharmacological activities such as antihyperglycemic effect. Methods In the present study, the cytoprotective effects of aqueous extract of C. moschata fruit on hepatocyte cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonylation model) were investigated using freshly isolated rat hepatocytes. Results The extract of C. moschata (50 μg/ml) excellently prevented oxidative and carbonyl stress markers, including hepatocyte lysis, ROS production, lipid peroxidation, glutathione depletion, mitochondrial membrane potential collapse, lysosomal damage, and cellular proteolysis. In addition, protein carbonylation was prevented by C. moschata in glyoxal-induced carbonyl stress. Conclusion It can be concluded that C. moschata has cytoprotective effects in oxidative stress and carbonyl stress models and this valuable vegetable can be considered as a suitable herbal product for the prevention of toxic subsequent of oxidative stress and carbonyl stress seen in chronic hyperglycemia. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Cytoprotective response induced by electromagnetic stimulation on SH-SY5Y human neuroblastoma cell line.

    Science.gov (United States)

    Osera, Cecilia; Fassina, Lorenzo; Amadio, Marialaura; Venturini, Letizia; Buoso, Erica; Magenes, Giovanni; Govoni, Stefano; Ricevuti, Giovanni; Pascale, Alessia

    2011-10-01

    It is well known that physiological functions and pathological conditions of cells and tissues can be influenced not only by chemical molecules, but also by physical stimuli such as electromagnetic waves. In particular, epidemiological studies suggest possible associations between exposure to electromagnetic fields and an increased risk of tumors and neurodegenerative disorders, such as Alzheimer's disease. However, depending on the dose and on the length of treatment, the electromagnetic stimuli can be harmful or induce a cytoprotective cellular response, suggesting a possible application in medical therapy. In this study, under a tissue engineering viewpoint, we investigated the effects of an electromagnetic wave (magnetic field intensity, 2 mT; frequency, 75 Hz) on a neuronal cellular model characterized by the overexpression of the amyloid precursor protein (APP). After a prolonged electromagnetic treatment, lower mitochondrial activity and proliferation rate, resulting in a higher cellular quiescence, were observed. Focusing on the stress and oxidative pathways, we detected an overall increase of two fundamental proteins, the chaperone heat shock protein HSP70 and the free radical scavenger superoxide dismutase-1 enzyme (SOD-1). Interestingly, we found that the electromagnetic stimulation promotes the nonamyloidogenic processing of APP through an increased expression of the α-secretase ADAM10 and an enhanced release of the soluble neurotrophic factor sAPPα (a product of the ADAM10-mediated cleavage of APP). In conclusion, these findings suggest that the electromagnetic stimulus, if properly administered in terms of dose and timing, is able to induce a cytoprotective response in the cell. Moreover, these results suggest a possible use of this particular physical stimulation to improve the functional capability of the cells to face noxae. © Mary Ann Liebert, Inc.

  5. Cytoprotective effect of glutaraldehyde erythropoietin on HEK293 kidney cells after silver nanoparticle exposure

    Directory of Open Access Journals (Sweden)

    Sooklert K

    2016-02-01

    Full Text Available Kanidta Sooklert,1,2 Supreecha Chattong,3 Krissanapong Manotham,3 Chawikan Boonwong,1 I-yanut Klaharn,1 Depicha Jindatip,4 Amornpun Sereemaspun1,4 1Nanobiomedicine Laboratory, Department of Anatomy, Faculty of Medicine, 2Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, 3Renal Unit, Department of Medicine, Lerdsin General Hospital, 4Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandAbstract: The toxic effects from exposure to silver nanoparticles (AgNPs, which are broadly present in many consumer products, have long raised concerns. Many studies have focused on the mechanisms of nanosilver, which cause toxicity in human cells, but little is known about prevention of this type of injury. This study investigated the in vitro effects of glutaraldehyde erythropoietin (GEPO, a cytoprotective compound derived from erythropoietin, in terms of cell protection against AgNP-induced injury. HEK293 cells were pretreated with or without GEPO before administration of AgNPs. The protective effects of GEPO in this cell line were assessed by the percentage of viable cells, alterations of cell morphology, and the proliferative capability of the cells. In addition, we assessed the role of GEPO in lowering cellular oxidative stress and regulating expression of the anti-apoptotic protein Bcl2. The results showed rescue effects on the percentage of viable and proliferative cells among GEPO pretreated cells. Pretreatment with GEPO maintained the normal cell shape and ultrastructural morphology. Moreover, GEPO reduced the generation of reactive oxygen species in cells and activated expression of Bcl2, which are the major mechanisms in protection against cellular toxicity induced by AgNPs. In conclusion, our study showed that the cytotoxic effects from exposure to AgNPs can be prevented by GEPO. Keywords: glutaraldehyde erythropoietin, silver nanoparticles, cytoprotection

  6. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon.

    Science.gov (United States)

    Ward, Joseph B J; Lajczak, Natalia K; Kelly, Orlaith B; O'Dwyer, Aoife M; Giddam, Ashwini K; Ní Gabhann, Joan; Franco, Placido; Tambuwala, Murtaza M; Jefferies, Caroline A; Keely, Simon; Roda, Aldo; Keely, Stephen J

    2017-06-01

    Ward JB, Lajczak NK, Kelly OB, O'Dwyer AM, Giddam AK, Ní Gabhann J, Franco P, Tambuwala MM, Jefferies CA, Keely S, Roda A, Keely SJ. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol 312: G550-G558, 2017. First published March 30, 2017; doi:10.1152/ajpgi.00256.2016.-Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. We aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions. The anti-inflammatory efficacy of UDCA, a nonmetabolizable analog, 6α-methyl-UDCA (6-MUDCA), and its primary colonic metabolite lithocholic acid (LCA) was assessed in the murine dextran sodium sulfate (DSS) model of mucosal injury. The effects of bile acids on cytokine (TNF-α, IL-6, Il-1β, and IFN-γ) release from cultured colonic epithelial cells and mouse colonic tissue in vivo were investigated. Luminal bile acids were measured by gas chromatography-mass spectrometry. UDCA attenuated release of proinflammatory cytokines from colonic epithelial cells in vitro and was protective against the development of colonic inflammation in vivo. In contrast, although 6-MUDCA mimicked the effects of UDCA on epithelial cytokine release in vitro, it was ineffective in preventing inflammation in the DSS model. In UDCA-treated mice, LCA became the most common colonic bile acid. Finally, LCA treatment more potently inhibited epithelial cytokine release and protected against DSS-induced mucosal inflammation than did UDCA. These studies identify a new role for the primary metabolite of UDCA, LCA, in preventing colonic

  7. Human soluble thrombomodulin-induced blockade of peripheral HMGB1-dependent allodynia in mice requires both the lectin-like and EGF-like domains.

    Science.gov (United States)

    Hayashi, Yusuke; Tsujita, Ryuichi; Tsubota, Maho; Saeki, Haruka; Sekiguchi, Fumiko; Honda, Goichi; Kawabata, Atsufumi

    2018-01-01

    Thrombomodulin (TM), an endothelial protein with anti-coagulant activity, is composed of 5 domains, D1-D5. Recombinant human soluble TM (TMα) consisting of D1-D3, which is generated in CHO cells, suppresses inflammatory and nociceptive signals by inactivating high mobility group box 1 (HMGB1), one of damage-associated molecular patterns. TMα sequesters HMGB1 with the lectin-like D1 and promotes its degradation by thrombin binding to the EGF-like D2. We prepared TM's D123, D1 and D2 by the protein expression system of yeast, and evaluated their effects on HMGB1 degradation in vitro and on the allodynia caused by HMGB1 in distinct redox forms in mice in vivo. TMα and TM's D123, but not D1, promoted the thrombin-dependent degradation of all-thiol (at-HMGB1) and disulfide HMGB1 (ds-HMGB1), an effect mimicked by TM's D2, though to a lesser extent. Intraplantar administration of TMα and TM's D123, but not D1, D2 or D1 plus D2, strongly prevented the mechanical allodynia caused by intraplantar at-HMGB1, ds-HMGB1 or lipopolysaccharide in mice. Our data suggest that, apart from the role of D3, TMα and TM's D123 require both lectin-like D1 capable of sequestering HMGB1 and EGF-like D2 responsible for thrombin-dependent degradation of HMGB1, in abolishing the allodynia caused by exogenous or endogenous HMGB1. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The roles of selected arginine and lysine residues of TAFI (Pro-CPU) in its activation to TAFIa by the thrombin-thrombomodulin complex.

    Science.gov (United States)

    Wu, Chengliang; Kim, Paul Y; Manuel, Reg; Seto, Marian; Whitlow, Marc; Nagashima, Mariko; Morser, John; Gils, Ann; Declerck, Paul; Nesheim, Michael E

    2009-03-13

    Thrombomodulin (TM) increases the catalytic efficiency of thrombin (IIa)-mediated activation of thrombin-activable fibrinolysis inhibitor (TAFI) 1250-fold. Negatively charged residues of the C-loop of TM-EGF-like domain 3 are required for TAFI activation. Molecular models suggested several positively charged residues of TAFI with which the C-loop residues could interact. Seven TAFI mutants were constructed to determine if these residues are required for efficient TAFI activation. TAFI wild-type or mutants were activated in the presence or absence of TM and the kinetic parameters of TAFI activation were determined. When the three consecutive lysine residues in the activation peptide of TAFI were substituted with alanine (K42/43/44A), the catalytic efficiencies for TAFI activation with TM decreased 8-fold. When other positively charged surface residues of TAFI (Lys-133, Lys-211, Lys-212, Arg-220, Lys-240, or Arg-275) were mutated to alanine, the catalytic efficiencies for TAFI activation with TM decreased by 1.7-2.7-fold. All decreases were highly statistically significant. In the absence of TM, catalytic efficiencies ranged from 2.8-fold lower to 1.24-fold higher than wild-type. None of these, except the 2.8-fold lower value, was statistically significant. The average half-life of the TAFIa mutants was 8.1+/-0.6 min, and that of wild type was 8.4+/-0.3 min at 37 degrees C. Our data show that these residues are important in the activation of TAFI by IIa, especially in the presence of TM. Whether the mutated residues promote a TAFI-TM or TAFI-IIa interaction remains to be determined. In addition, these residues do not influence spontaneous inactivation of TAFIa.

  9. Therapeutic potential of recombinant thrombomodulin for lung injury after pneumonectomy via inhibition of high-mobility group box 1 in mice.

    Science.gov (United States)

    Takahashi, Yusuke; Matsutani, Noriyuki; Dejima, Hitoshi; Nakayama, Takashi; Okamura, Ryo; Uehara, Hirofumi; Kawamura, Masafumi

    2016-11-01

    Surgical acute respiratory distress syndrome (ARDS) is an extremely critical condition which may occur after major lung resection. Despite advances in minimally invasive surgical procedures and progress in the therapeutic management of this disease, prognosis remains poor. In this study, we investigated the contribution of high-mobility group box 1 (HMGB1) in a surgical ARDS model and evaluated the possible therapeutic effect of recombinant thrombomodulin (rTM) for the treatment of surgical ARDS. C57BL/6J mice underwent left pneumonectomy. rTM was injected at 12 hours before surgery, followed by 12 hours for 3 days after surgery. Lipopolysaccharide (LPS) was administered at 2 hours after surgery. We conducted a histologic analysis and measured HMGB1, IL-6, IL-1β, and TNF-α in bronchoalveolar lavage fluid on day 3 after pneumonectomy. Data were compared between the treatment groups. On histologic analysis, left pneumonectomy followed by LPS administration induced both severe inflammatory cellular infiltration and alveolar wall congestion with hemorrhage. rTM administration rescued these histologic changes. The level of HMGB1, IL-6, IL-1β, and TNF-α in bronchoalveolar lavage fluid was significantly increased by LPS administration after pneumonectomy and significantly decreased by rTM administration with LPS and pneumonectomy (p < 0.001). Also, LPS alone showed no statistical differences in HMGB1 or proinflammatory cytokine level compared with pneumonectomy (PNX) group. In addition, the survival outcome was also improved by rTM administration. LPS administration after left pneumonectomy could induce the severe lung injury. PNX and LPS have similar contribution to this model and may play a synergistic role in this process. rTM may have the potential therapeutic effect for surgical ARDS via suppression of HMGB1 and the secretion of proinflammatory cytokines induced by the administration of LPS after left pneumonectomy.

  10. Association DENV1 and DENV2 infection with high serum levels of soluble thrombomodulin and VEGF in patients with dengue fever and dengue hemorrhagic fever.

    Science.gov (United States)

    Del Moral-Hernández, Oscar; Martínez-Hernández, Norma E; Mosso-Pani, Manuel A; Hernández-Sotelo, Daniel; Illades-Aguiar, Berenice; Flores-Alfaro, Eugenia; Antonio-Vejar, Verónica; Leyva-Vázquez, Marco Antonio

    2014-01-01

    INFECTION BY DENGUE VIRUS (DENV) CAN BE ASYMPTOMATIC OR MANIFEST IN TWO CLINICALLY DIFFERENTIATED FORMS: dengue fever (DF) and denguehemorrhagic fever (DHF). The principal pathophysiological characteristic of DHF is the increase in vascular permeability and the loss of plasma caused by the malfunction of the vascular endothelium that induces the release of chemical mediators. However, so far there is nothing that allows for the identification the patients that are at risk of developing the more severe form of the illness. The objective of this study was to investigate the relationship between the serum levels of soluble thrombomodulin (sTM) and VEGF with the severity of dengue and the viral serotype. 231 serum samples were analyzed, 70 DF, 80 DHF and 81 control group, all were residents of Guerrero state in Mexico. The infection by dengue virus as well and the levels of sTM and VEGF were determined using the ELISA sandwich, while the serotype was determined by real time RT-PCR. Our results show that the concentrations of sTM correlate with the degree of severity of the disease given that they are significantly higher (p<0.001) in the DHF group (median = 10.2 ng/mL) than in the DF group (median = 7.2 ng/mL), and these in turn higher than those of the control group (median = 3.3 ng/mL). The concentration of sTM was significantly higher (p=0.0002) in the patients infected with DENV2. For the VEGF, the highest levels were found in DF (median = 291.3 pg/mL) and did not correlate with the severity of the disease. In conclusion, our results indicate that sTM is a good marker for the severity of the infection by DENV, better than VEGF, and with higher sensibility and specificity.

  11. Thrombomodulin-dependent effect of factor V Leiden mutation on the cross-linking of α2-plasmin inhibitor to fibrin and its consequences on fibrinolysis.

    Science.gov (United States)

    Koncz, Zsuzsa; Bagoly, Zsuzsa; Haramura, Gizella; Mezei, Zoltán A; Muszbek, László

    2012-09-01

    It has been shown that thrombomodulin (TM) considerably delays factor XIII (FXIII) activation and this effect is abrogated by Factor V Leiden (FV(Leiden)) mutation. The aim of the study was to explore the effect of TM on the cross-linking of α(2)-plasmin inhibitor (α(2)-PI) to fibrin in plasma samples of different FV genotypes and how this effect is related to the impaired fibrinolysis of FV(Leiden) carriers. In the plasma samples of fifteen individuals with different FV genotypes and in FV deficient plasma supplemented with wild type FV or FV(Leiden) coagulation was initiated by recombinant human tissue factor and phospholipids with or without recombinant human TM (rhTM). In the recovered clots the extent of α(2)-PI-fibrin cross-linking was evaluated by Western blotting and quantitative densitometry. The effect of rhTM on tissue plasminogen activator (tPA) induced clot lysis was measured by turbidimetric method. rhTM significantly delayed the formation of α(2)-PI-fibrin α-chain heterodimers/oligomers in plasma samples containing wild type FV. This effect of rhTM was impaired in the presence of FV(Leiden). rhTM delayed tPA-induced clot lysis and this effect of rhTM was more pronounced in plasma containing FV(Leiden). When TAFIa was inhibited by potato carboxypeptidase inhibitor, rhTM accelerated clot lysis in the presence of wild type FV, which is explained by the delayed α(2)-PI-fibrin cross-linking. This effect of rhTM did not prevail in the presence of FV(Leiden). FV(Leiden) abrogates the delaying effect of rhTM on α(2)-PI-fibrin cross-linking, which contributes to the impaired fibrinolysis observed in FV(Leiden) carriers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Pig-to-baboon heterotopic heart transplantation--exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade-based regimens.

    Science.gov (United States)

    Iwase, Hayato; Ekser, Burcin; Satyananda, Vikas; Bhama, Jay; Hara, Hidetaka; Ezzelarab, Mohamed; Klein, Edwin; Wagner, Robert; Long, Cassandra; Thacker, Jnanesh; Li, Jiang; Zhou, Hao; Jiang, Maolin; Nagaraju, Santosh; Zhou, Huidong; Veroux, Massimiliano; Bajona, Pietro; Wijkstrom, Martin; Wang, Yi; Phelps, Carol; Klymiuk, Nikolai; Wolf, Eckhard; Ayares, David; Cooper, David K C

    2015-01-01

    Three costimulation blockade-based regimens have been explored after transplantation of hearts from pigs of varying genetic backgrounds to determine whether CTLA4-Ig (abatacept) or anti-CD40mAb+CTLA4-Ig (belatacept) can successfully replace anti-CD154mAb. All pigs were on an α1,3-galactosyltransferase gene-knockout/CD46 transgenic (GTKO.CD46) background. Hearts transplanted into Group A baboons (n=4) expressed additional CD55, and those into Group B (n=3) expressed human thrombomodulin (TBM). Immunosuppression included anti-thymocyte globulin with anti-CD154mAb (Regimen 1: n=2) or abatacept (Regimen 2: n=2) or anti-CD40mAb+belatacept (Regimen 3: n=2). Regimens 1 and 2 included induction anti-CD20mAb and continuous heparin. One further baboon in Group B (B16311) received a modified Regimen 1. Baboons were followed by clinical/laboratory monitoring of immune/coagulation parameters. At biopsy, graft failure, or euthanasia, the graft was examined by microscopy. Group A baboons survived 15 to 33 days, whereas Group B survived 52, 99, and 130 days, respectively. Thrombocytopenia and reduction in fibrinogen occurred within 21 days in Group A, suggesting thrombotic microangiopathy (TM), confirmed by histopathology. In Group B, with follow-up for >4 m, areas of myofiber degeneration and scarring were seen in two hearts at necropsy. A T-cell response was documented only in baboons receiving Regimen 2. The combination of anti-CD40mAb+belatacept proved effective in preventing a T-cell response. The expression of TBM prevented thrombocytopenia and may possibly delay the development of TM and/or consumptive coagulopathy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Does heavy physical exertion trigger myocardial infarction?

    DEFF Research Database (Denmark)

    Hallqvist, J; Möller, J; Ahlbom, A

    2000-01-01

    To study possible triggering of first events of acute myocardial infarction by heavy physical exertion, the authors conducted a case-crossover analysis (1993-1994) within a population-based case-referent study in Stockholm County, Sweden (the Stockholm Heart Epidemiology Program). Interviews were...... million person-hours, and the attributable proportion was 5.7 percent. The risk was modified by physical fitness, with an increased risk being seen among sedentary subjects as in earlier studies, but the data also suggested a U-shaped association. In addition, the trigger effect was modified...

  14. Synthesis of a Series of Caffeic Acid Phenethyl Amide (CAPA) Fluorinated Derivatives: Comparison of Cytoprotective Effects to Caffeic Acid Phenethyl Ester (CAPE)

    Science.gov (United States)

    2010-06-11

    Synthesis of a series of caffeic acid phenethyl amide (CAPA) fluorinated derivatives: Comparison of cytoprotective effects to caffeic acid phenethyl...to induce genes with the downstream effect of counter- acting oxidative stress.5,6 Caffeic acid phenethyl ester (CAPE), a plant polyphenolic con... synthesis and investigation of catechol ring-fluorinated derivatives of CAPE with regard to cytoprotective ability against oxidative stress in vitro.14

  15. A novel strategy to activate cytoprotective genes in the injured brain

    International Nuclear Information System (INIS)

    Zhao, Jing; Redell, John B.; Moore, Anthony N.; Dash, Pramod K.

    2011-01-01

    Highlights: → A strategy to increase cytoprotective gene expression in injured tissue is outlined. → A peptide containing a DEETGE motif can increase Nrf2 responsive genes in vivo. → Gene expression in injured brains requires a calpain cleavage site. → This peptide decreases BBB compromise when infused pre- or post-brain injury. → Cleavage sites for disease-specific proteases could be used to treat that condition. -- Abstract: The transcription factor nuclear factor E2-related factor 2 (Nrf2) regulates the expression of multiple cytoprotective genes that have been shown to offer protection in response to a number of insults. The present study describes a novel strategy to increase expression of Nrf2-responsive genes in brain injured mice. Under normal conditions, the adapter protein Kelch-like ECH-associated protein 1 (Keap1) binds to Nrf2 and promotes its proteosomal degradation in the cytoplasm. The amino acid sequence DEETGE, located at amino acid 77-82 of Nrf2, is critical for Nrf2-Keap1 interaction, and synthetic peptides containing this sequence can be used to disrupt the complex in vitro. We observed that intracerebroventricular (i.c.v.) infusion of a peptide containing the DEETGE sequence along with the cell transduction domain of the HIV-TAT protein (TAT-DEETGE) into brain-injured mice did not increase the mRNA levels for Nrf2-driven genes. However, when a calpain cleavage sequence was introduced between the TAT sequence and the DEETGE sequence, the new peptide (TAT-CAL-DEETGE) increased the mRNA levels of these genes. Increased gene expression was not observed when the TAT-CAL-DEETGE peptide was injected into uninjured animals. Furthermore, injection of TAT-CAL-DEETGE peptides before or after brain injury reduced blood-brain barrier compromise, a prominent secondary pathology that negatively influences outcome. The present strategy to increase Nrf2-responsive gene expression can be adapted to treat other insults or diseases based on their

  16. Novel PI3K/Akt inhibitors screened by the cytoprotective function of human immunodeficiency virus type 1 Tat.

    Directory of Open Access Journals (Sweden)

    Yuri Kim

    Full Text Available The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors.

  17. Novel PI3K/Akt Inhibitors Screened by the Cytoprotective Function of Human Immunodeficiency Virus Type 1 Tat

    Science.gov (United States)

    Kim, Dong-Hyun; Kim, Baek

    2011-01-01

    The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors. PMID:21765914

  18. Traction Forces exerted by crawling cells

    Science.gov (United States)

    Alonso-Latorre, Baldomero; Del Alamo, Juan C.; Rodriguez-Rodriguez, Javier; Aliseda, Alberto; Meili, Rudolph; Firtel, Richard; Lasheras, Juan C.

    2006-11-01

    We measure the forces exerted by Dictyostelium discoideum cells crawling over a deformable substrate from the displacements of fluorescent beads embedded in it. A particle tracking technique similar to PIV is used to obtain the displacements. From them, forces are computed by solving the elasto-static equation in a finite thickness slab. We will show that the finite thickness of the substrate and the distance of the beads to its surface affect substantially the results, although previous traction cytometry techniques neglected them. The measured forces are correlated to the different stages of the crawling cycle for various cell strains. It has been observed that a large fraction of the forces measured on the substrate are originated by the cell's internal tension through all the stages of motion, including the protrusion of pseudopods. This result suggests that the viscous drag exerted by the fluid in which the cells are immersed is very small compared to the forces applied by the cytoskeleton on the substrate.

  19. Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins

    International Nuclear Information System (INIS)

    Nakaso, Kazuhiro; Nakamura, Chiharu; Sato, Hiromi; Imamura, Keiko; Takeshima, Takao; Nakashima, Kenji

    2006-01-01

    Neuroprotection has received considerable attention as a strategy for the treatment of Parkinson's disease (PD). Deprenyl (Selegiline) is a promising candidate for neuroprotection; however, its cytoprotective mechanism has not been fully clarified. Here, we report a novel cytoprotective mechanism of deprenyl involving PI3K and Nrf2-mediated induction of oxidative stress-related proteins. Deprenyl increased the expression of HO-1, PrxI, TrxI, TrxRxI, γGCS, and p62/A170 in SH-SY5Y cells. Deprenyl also induced the nuclear accumulation of Nrf2 and increased the binding activity of Nrf2 to the enhancer region of human genomic HO-1. The Nrf2-mediated induction of antioxidative molecules was controlled by PI3K. Indeed, furthermore, neurotrophin receptor TrkB was identified as an upstream signal for PI3K-Nrf2 activation by deprenyl. These results suggest that the cytoprotective effect of deprenyl is, in part, dependent on Nrf2-mediated induction of antioxidative proteins, suggesting that activation of the PI3K-Nrf2 system may be a useful therapeutic strategy for PD

  20. Virtual exertions: evoking the sense of exerting forces in virtual reality using gestures and muscle activity.

    Science.gov (United States)

    Chen, Karen B; Ponto, Kevin; Tredinnick, Ross D; Radwin, Robert G

    2015-06-01

    This study was a proof of concept for virtual exertions, a novel method that involves the use of body tracking and electromyography for grasping and moving projections of objects in virtual reality (VR). The user views objects in his or her hands during rehearsed co-contractions of the same agonist-antagonist muscles normally used for the desired activities to suggest exerting forces. Unlike physical objects, virtual objects are images and lack mass. There is currently no practical physically demanding way to interact with virtual objects to simulate strenuous activities. Eleven participants grasped and lifted similar physical and virtual objects of various weights in an immersive 3-D Cave Automatic Virtual Environment. Muscle activity, localized muscle fatigue, ratings of perceived exertions, and NASA Task Load Index were measured. Additionally, the relationship between levels of immersion (2-D vs. 3-D) was studied. Although the overall magnitude of biceps activity and workload were greater in VR, muscle activity trends and fatigue patterns for varying weights within VR and physical conditions were the same. Perceived exertions for varying weights were not significantly different between VR and physical conditions. Perceived exertion levels and muscle activity patterns corresponded to the assigned virtual loads, which supported the hypothesis that the method evoked the perception of physical exertions and showed that the method was promising. Ultimately this approach may offer opportunities for research and training individuals to perform strenuous activities under potentially safer conditions that mimic situations while seeing their own body and hands relative to the scene. © 2014, Human Factors and Ergonomics Society.

  1. Cytoprotective effects of atmospheric-pressure plasmas against hypoxia-induced neuronal injuries

    Science.gov (United States)

    Yan, Xu; Meng, Zhaozhong; Ouyang, Jiting; Qiao, Yajun; Li, Jiaxin; Jia, Mei; Yuan, Fang; (Ken Ostrikov, Kostya

    2018-02-01

    Atmospheric pressure plasma jet (APPJ) has recently been the focus of cytoprotective research due to the physiological roles of ROS and RNS. In the current study, we investigated the effect of APPJ treatment on the hypoxia (1% oxygen) induced cell injuries. SH-SY5Y cells were treated by APPJ for different duration and incubated in normoxic condition (20% oxygen) for 5 h followed by 24 h hypoxia treatment. Cell viability was evaluated by lactate dehydrogenase (LDH) release and further monitored using the electric cell-substrate impedance sensing (ECIS) system after APPJ treatment. Results showed that APPJ could reduce cell injuries after 24 h hypoxia, which was consistent with the ECIS results. Furthermore, extracellular NO and H2O2 production was significantly increased with the APPJ treatment. It was also interesting to find that APPJ treatment reduced SH-SY5Y cells proliferation in the hypoxic microenvironment during the first 20 h of hypoxia. Although more work was still need to clarify whether the cell viability maintenance was related to the cell proliferation during hypoxia, our results provide the first evidence of real-time cell viability changes after APPJ treatment under both normoxic and hypoxic conditions, which could provide evidence for the neuroprotective applications of APPJ.

  2. Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation.

    Science.gov (United States)

    Kang, Kyoung Ah; Lee, Kyoung Hwa; Chae, Sungwook; Zhang, Rui; Jung, Myung Sun; Ham, Young Min; Baik, Jong Seok; Lee, Nam Ho; Hyun, Jin Won

    2006-02-15

    We investigated the cytoprotective effect of phloroglucinol, which was isolated from Ecklonia cava (brown alga), against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Phloroglucinol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H(2)O(2)), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, phloroglucinol reduced H(2)O(2) induced apoptotic cells formation in V79-4 cells. In addition, phloroglucinol inhibited cell damage induced by serum starvation and radiation through scavenging ROS. Phloroglucinol increased the catalase activity and its protein expression. In addition, catalase inhibitor abolished the protective effect of phloroglucinol from H(2)O(2) induced cell damage. Furthermore, phloroglucinol increased phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that phloroglucinol protects V79-4 cells against oxidative damage by enhancing the cellular catalase activity and modulating ERK signal pathway. (c) 2005 Wiley-Liss, Inc.

  3. Interaction of Cytotoxic and Cytoprotective Bile Acids with Model Membranes: Influence of the Membrane Composition.

    Science.gov (United States)

    Esteves, M; Ferreira, M J; Kozica, A; Fernandes, A C; Gonçalves da Silva, A; Saramago, B

    2015-08-18

    To understand the role of bile acids (BAs) in cell function, many authors have investigated their effect on biomembrane models which are less complex systems, but there are still many open questions. The present study aims to contribute for the deepening of the knowledge of the interaction between BAs and model membranes, in particular, focusing on the effect of BA mixtures. The cytotoxic deoxycholic acid (DCA), the cytoprotective ursodeoxycholic acid (UDCA), and the equimolar mixture (DCA + UDCA) were investigated. Monolayers and liposomes were taken as model membranes with two lipid compositions: an equimolar mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM), and cholesterol (Chol)) traditionally associated with the formation of lipid rafts and an equimolar POPC/SM binary mixture. The obtained results showed that DCA causes the fluidization of monolayers and bilayers, leading to the eventual rupture of POPC/SM liposomes at high concentration. UDCA may provide a stabilization of POPC/SM membranes but has a negligible effect on the Chol-containing liposomes. In the case of equimolar mixture DCA/UDCA, the interactions depend not only on the lipid composition but also on the design of the experiment. The BA mixture has a greater impact on the monolayers than do pure BAs, suggesting a cooperative DCA-UDCA interaction that enhances the penetration of UDCA in both POPC/SM and POPC/SM/Chol monolayers. For the bilayers, the presence of UDCA in the mixture decreases the disturbing effect of DCA.

  4. An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

    Science.gov (United States)

    Bath, Sundeep

    2015-01-01

    Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment. PMID:26180596

  5. Cytoprotective effect of cytoflavinum in the treatment of thermal injuries of various severity levels

    Directory of Open Access Journals (Sweden)

    Alexey J. Bozhedomov

    2012-12-01

    Full Text Available The research aimed to conduct studying of cytoprotective effect of cytoflavinum in thermal traumas of various severity levels. Material and methods – 169 patients were included into the research with thermal burns and with a favorable outcome and the severity of a thermal injury from 30 to 170 points according Frank index. 28 patients received cytoflavinum in a complex therapy in a standard dosage. Results – During the cytoflavinum usage in patients with the severity of a thermal injury more than 60 points by Frank there had been fixed: the decrease of a systemic inflammatory response syndrome (SIRS, reduction of stab neutrophils content, slower decrease of erythrocytes, smaller activation of thrombopoiesis, decrease of concentration of the vascular endothelial growth factor. In the group of patients with thermal injuries less than 60 points who had been receiving cytoflavinum there had not positive effects been fixed. Conclusion – Cytoflavinum is the most effective when the severity of a thermal trauma is more than 60 points by Frank.

  6. VDAC-Targeted Drugs Affecting Cytoprotection and Mitochondrial Physiology in Cerebrovascular and Cardiovascular Diseases.

    Science.gov (United States)

    Karachitos, Andonis; Jordan, Joaquin; Kmita, Hanna

    2017-01-01

    Cerebrovascular and cardiovascular diseases are caused by impairment of the brain and/or heart circulation. Insufficient blood flow results in decreased oxygen delivery (ischemia), which affects mitochondrial functioning and consequently leads to insufficient ATP production. The predominant mitochondrial outer membrane protein, the voltage dependent anion selective channel (VDAC), is considered to be crucial for mitochondrial functioning. In human mitochondria, as in other vertebrates, three isoforms of VDAC (VDAC1-VDAC3) are present, and they likely play different roles. In this review, we summarize the available data concerning VDAC involvement in cardiovascular and cerebrovascular diseases with regard to VDAC isoforms and discuss the use of possible VDAC-related intervention targets as well as known VDAC-interacting and cytoprotection- conferring molecules in the treatment of cerebrovascular and cardiovascular diseases. The suitable references on disorders defined as cerebrovascular and cardiovascular diseases as well as VDAC contribution to these conditions were searched using PubMed and ClinicalTrials.gov databases. The review is based on the 138 carefully selected articles. Mitochondrial dysfunction triggered by changes in VDAC properties undoubtedly contributes to cell death and related diseases, including cerebrovascular and cardiovascular diseases. Thus, beside diagnostic application, modulation of VDAC activity, including its isoforms, is thus of great importance for the development of efficient therapeutic interventions. Moreover, identification of VDAC-interacting molecules that protect against mitochondrial dysfunction and cell death seems to be of great importance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Humanin, a cytoprotective peptide, is expressed in carotid atherosclerotic [corrected] plaques in humans.

    Science.gov (United States)

    Zacharias, David G; Kim, Sung Gyun; Massat, Alfonso Eirin; Bachar, Adi R; Oh, Yun K; Herrmann, Joerg; Rodriguez-Porcel, Martin; Cohen, Pinchas; Lerman, Lilach O; Lerman, Amir

    2012-01-01

    The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN) is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques. Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13% of plaque area, p<0.0001). These data were further confirmed by immunoblot (density of HN/β-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01). TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46% of nuclei, p<0.01). Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization), smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9. The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque.

  8. Mechanisms of exertional fatigue in muscle glycogenoses

    DEFF Research Database (Denmark)

    Vissing, John; Haller, Ronald G

    2012-01-01

    Exertional fatigue early in exercise is a clinical hallmark of muscle glycogenoses, which is often coupled with painful muscle contractures and episodes of myoglobinuria. A fundamental biochemical problem in these conditions is the impaired generation of ATP to fuel muscle contractions, which...... relates directly to the metabolic defect, but also to substrate-limited energy deficiency, as exemplified by the "second wind" phenomenon in McArdle disease. A number of secondary events may also play a role in inducing premature fatigue in glycogenoses, including (1) absent or blunted muscle acidosis......, which may be important for maintaining muscle membrane excitability by decreasing chloride permeability, (2) loss of the osmotic effect related to lactate accumulation, which may account for absence of the normal increase in water content of exercised muscle, and thus promote higher than normal...

  9. Does heavy physical exertion trigger myocardial infarction?

    DEFF Research Database (Denmark)

    Hallqvist, J; Möller, J; Ahlbom, A

    2000-01-01

    million person-hours, and the attributable proportion was 5.7 percent. The risk was modified by physical fitness, with an increased risk being seen among sedentary subjects as in earlier studies, but the data also suggested a U-shaped association. In addition, the trigger effect was modified...... carried out with 699 myocardial infarction patients after onset of the disease. These cases represented 47 percent of all cases in the study base, and 70 percent of all nonfatal cases. The relative risk from vigorous exertion was 6.1 (95% confidence interval: 4.2, 9.0). The rate difference was 1.5 per...... by socioeconomic status. Premonitory symptoms were common, and this implies risks of reverse causation bias and misclassification of case exposure information that require methodological consideration. Different techniques (the use of the usual-frequency type of control information, a pair-matched analysis...

  10. Traction forces exerted by epithelial cell sheets

    International Nuclear Information System (INIS)

    Saez, A; Anon, E; Ghibaudo, M; Di Meglio, J-M; Hersen, P; Ladoux, B; Du Roure, O; Silberzan, P; Buguin, A

    2010-01-01

    Whereas the adhesion and migration of individual cells have been well described in terms of physical forces, the mechanics of multicellular assemblies is still poorly understood. Here, we study the behavior of epithelial cells cultured on microfabricated substrates designed to measure cell-to-substrate interactions. These substrates are covered by a dense array of flexible micropillars whose deflection enables us to measure traction forces. They are obtained by lithography and soft replica molding. The pillar deflection is measured by video microscopy and images are analyzed with home-made multiple particle tracking software. First, we have characterized the temporal and spatial distributions of traction forces of cellular assemblies of various sizes. The mechanical force balance within epithelial cell sheets shows that the forces exerted by neighboring cells strongly depend on their relative position in the monolayer: the largest deformations are always localized at the edge of the islands of cells in the active areas of cell protrusions. The average traction stress rapidly decreases from its maximum value at the edge but remains much larger than the inherent noise due to the force resolution of our pillar tracking software, indicating an important mechanical activity inside epithelial cell islands. Moreover, these traction forces vary linearly with the rigidity of the substrate over about two decades, suggesting that cells exert a given amount of deformation rather than a force. Finally, we engineer micropatterned substrates supporting pillars with anisotropic stiffness. On such substrates cellular growth is aligned with respect to the stiffest direction in correlation with the magnitude of the applied traction forces.

  11. Understanding the Mismatch Between Coaches' and Players' Perceptions of Exertion

    NARCIS (Netherlands)

    Brink, Michel S.; Kersten, Anna W.; Frencken, Wouter G. P.

    A mismatch between the training exertion intended by a coach and the exertion perceived by players is well established in sports. However, it is unknown whether coaches can accurately observe exertion of individual players during training. Furthermore, the discrepancy in coaches' and players'

  12. Enzyme-treated asparagus extract promotes expression of heat shock protein and exerts antistress effects.

    Science.gov (United States)

    Ito, Tomohiro; Maeda, Takahiro; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Sato, Atsuya

    2014-03-01

    A novel enzyme-treated asparagus extract (ETAS) has been developed as a functional material produced from asparagus stem. Studies were conducted to determine the effect of ETAS on heat shock protein 70 (HSP70) expression and alleviation of stress. HeLa cells were treated with ETAS, and HSP70 mRNA and protein levels were measured using a reverse transcription-polymerase chain reaction (RT-PCR) assay and an enzyme-linked immunosorbent assay (ELISA), respectively. ETAS showed significant increases in HSP70 mRNA at more than 0.125 mg/mL and the protein at more than 1.0 mg/mL. The antistress effect was evaluated in a murine sleep-deprivation model. A sleep-deprivation stress load resulted in elevation of blood corticosterone and lipid peroxide concentrations, while supplementation with ETAS at 200 and 1000 mg/kg body weight was associated with significantly reduced levels of both stress markers, which were in the normal range. The HSP70 protein expression level in mice subjected to sleep-deprivation stress and supplemented with ETAS was significantly enhanced in stomach, liver, and kidney, compared to ETAS-untreated mice. A preliminary and small-sized human study was conducted among healthy volunteers consuming up to 150 mg/d of ETAS daily for 7 d. The mRNA expression of HSP70 in peripheral leukocytes was significantly elevated at intakes of 100 or 150 mg/d, compared to their baseline levels. Since HSP70 is known to be a stress-related protein and its induction leads to cytoprotection, the present results suggest that ETAS might exert antistress effects under stressful conditions, resulting from enhancement of HSP70 expression. © 2014 Institute of Food Technologists®

  13. Cytoprotection mediated antiulcer effect of aqueous fruit pulp extract of Cucumis sativus

    Directory of Open Access Journals (Sweden)

    Swapnil Sharma

    2012-05-01

    Full Text Available Objective: The study was aimed to evaluate the gastroprotective potential of Cucumis Sativus fruit pulp aqueous extract (CSE in gastric ulcerated rats. Methods: Cytoprotective potential was evaluated via oral administration of CSE at the doses of 250, 500 &1000 mg/kg three times in a day, for 5 days before the induction of ulcers in indomethacin and pyloric ligation induced ulcer model. Further, its effects were studied on various parameters volume of gastric juice, pH, free and total acidity, protein concentration, acid output in gastric juice, lipid peroxide (LPO, and activities of enzymic antioxidants-super oxide dismutase (SOD and catalase (CAT in gastric mucosa. The levels of hexose, hexosamine, sialic acid, fucose in gastric mucosa and gastric juice were also examined. The extent of healing was also determined with post administration of CSE at the same doses & dosage schedule in acetic acid induced model. Results: In indomethacin and pyloric ligation model, the pretreatment with CSE and ranitidine significantly reduced the lesion index, in comparison with control treated group (P< 0.05. The percentages of protection of ulcers were 25.8, 65.7, 80.6 & 93.8 for the treated groups of CSE and ranitidine whereas in pyloric ligation it was 31.26, 55.18, 93.26 & 95.51 respectively. In pyloric ligation model, CSE resulted in significant increase in pH, enzymic antioxidants i.e. SOD & CAT, with a significant decrease in volume of gastric juice, free and total acidity, protein & carbohydrate concentration and LPO levels. In acetic acid inducer model, treatment with Cucumis sativus (CSE caused significant reduction in lesion index in when compared to control treated group, providing evidence for ulcer healing capacity of it. The presence of the flavonoids and polyphenols may be responsible for the gastroprotective effect of CSE. Conclusions: The aqueous fruit pulp extract of Cucumis sativus (CSE has a gastroprotective property.

  14. An Odyssey of cytoprotective bisbenzimidazole as therapeutic agent for human well being

    International Nuclear Information System (INIS)

    Tandon, Vibha

    2014-01-01

    Radiotherapy is utilized by 80% patients as a part of their treatment to most prevalent disease like cancer. Ionizing radiation causes radiolysis of water, generation of ROS and has deleterious effect penetrating the living tissues resulting in the-transfer of radiation energy to the biological materials. Radioprotectors protect the normal cells from the unwanted radiation damage. Since the beginning of the nuclear era, despite extensive research on the development of radioprotectors from natural and synthetic compounds, success has been limited. The only clinically acceptable radioprotector, amifostine, has inherent dose-limiting toxicities and has therefore stimulated extensive search for nontoxic, effective, and alternative radioprotectors. We have developed a cytoprotective radioprotector DMA, having a bisbenzimidazole nucleus. Relative quantitation of gene expression of the identified proteins and their interacting partners led to the identification of NFkB inducing kinase (NIK) as one of the plausible target. Subsequently, over expression and knock down of NIK suggested that DMA affects NFkB inducing kinase mediated phosphorylation of IKKα and IKKβ both alone and in the presence of ionizing radiation. We observed 51% radioprotection in untreated cells that attenuated to 17% in siRNA NIK treated U87 cells at 24h. Further studies concluded that the Coactivation of AKT/NFkB triggered by DMA, is a reason behind protection against ionizing radiation-induced apoptosis of normal cells, and this was consistent with the alteration of DNA-PKcs. Pharmacokinetic (PK) evaluations and bioavailability measurements proved superior in vivo efficacy, higher AUCs, greater residence time of DMA. (author)

  15. Humanin, a cytoprotective peptide, is expressed in carotid atherosclerotic [corrected] plaques in humans.

    Directory of Open Access Journals (Sweden)

    David G Zacharias

    Full Text Available The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques.Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13% of plaque area, p<0.0001. These data were further confirmed by immunoblot (density of HN/β-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01. TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46% of nuclei, p<0.01. Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization, smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9.The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque.

  16. Humanin, a Cytoprotective Peptide, Is Expressed in Carotid Artherosclerotic Plaques in Humans

    Science.gov (United States)

    Zacharias, David G.; Kim, Sung Gyun; Massat, Alfonso Eirin; Bachar, Adi R.; Oh, Yun K.; Herrmann, Joerg; Rodriguez-Porcel, Martin; Cohen, Pinchas; Lerman, Lilach O.; Lerman, Amir

    2012-01-01

    Objective The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN) is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques. Methods and Results Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13% of plaque area, p<0.0001). These data were further confirmed by immunoblot (density of HN/β-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01). TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46% of nuclei, p<0.01). Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization), smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9. Conclusions The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque. PMID:22328926

  17. Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthium L. ethanolic extracts

    Directory of Open Access Journals (Sweden)

    Craciunescu Oana

    2012-09-01

    Full Text Available Abstract Background Arnica montana L. and Artemisia absinthium L. (Asteraceae are medicinal plants native to temperate regions of Europe, including Romania, traditionally used for treatment of skin wounds, bruises and contusions. In the present study, A. montana and A. absinthium ethanolic extracts were evaluated for their chemical composition, antioxidant activity and protective effect against H2O2-induced oxidative stress in a mouse fibroblast-like NCTC cell line. Results A. absinthium extract showed a higher antioxidant capacity than A. montana extract as Trolox equivalent antioxidant capacity, Oxygen radical absorbance capacity and 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging activity, in correlation with its flavonoids and phenolic acids content. Both plant extracts had significant effects on the growth of NCTC cells in the range of 10–100 mg/L A. montana and 10–500 mg/L A. absinthium. They also protected fibroblast cells against hydrogen peroxide-induced oxidative damage, at the same doses. The best protection was observed in cell pre-treatment with 10 mg/L A. montana and 10–300 mg/L A. absinthium, respectively, as determined by Neutral red and lactate dehydrogenase assays. In addition, cell pre-treatment with plant extracts, at these concentrations, prevented morphological changes induced by hydrogen peroxide. Flow-cytometry analysis showed that pre-treatment with A. montana and A. absinthium extracts restored the proportion of cells in each phase of the cell cycle. Conclusions A. montana and A. absinthium extracts, rich in flavonoids and phenolic acids, showed a good antioxidant activity and cytoprotective effect against oxidative damage in fibroblast-like cells. These results provide scientific support for the traditional use of A. montana and A. absinthium in treatment of skin disorders.

  18. Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1

    DEFF Research Database (Denmark)

    Huelsenbeck, Stefanie C; Roggenkamp, Dennis; May, Martin

    2013-01-01

    B expression, based on the inactivation of Rho/Ras proteins. In this study, we report on a long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. The observations of this study highlight a new pathway involving Rac1...... without any signs of cell death. In conclusion, the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivating Rho/Ras proteins but also by the Rac1-activating toxin CNF1....

  19. Factors associated with high physical exertion during manual lifting

    DEFF Research Database (Denmark)

    Andersen, Lars L.; Sundstrup, Emil; Brandt, Mikkel

    2018-01-01

    BACKGROUND: High physical exertion during work is a risk factor for back pain and long-term sickness absence. OBJECTIVE: To investigate which factors are associated with physical exertion during manual lifting. METHODS: From 14 workplaces across Denmark, 200 blue-collar workers reported perceived...... physical exertion (Borg-CR10) during manual lifting from floor to table height of 5, 10, 20 and 30 kg at the beginning and end of the working day. The workers also responded to a questionnaire and went through testing of isometric back muscle strength. Associations were modelled using logistic regression...... pain intensity (OR 2.80 [95% CI 1.43-5.48] for high) were associated with high perceived physical exertion. Age, smoking, Body Mass Index (BMI), and time of the day were not associated with physical exertion. CONCLUSIONS: Gender, load, back muscle strength and back pain influence physical exertion...

  20. Myogenic differentiation induces taurine transporter in association with taurine-mediated cytoprotection in skeletal muscles

    Science.gov (United States)

    Uozumi, Yoriko; Ito, Takashi; Hoshino, Yuki; Mohri, Tomomi; Maeda, Makiko; Takahashi, Kyoko; Fujio, Yasushi; Azuma, Junichi

    2005-01-01

    Skeletal muscle homoeostasis is maintained by a variety of cytoprotective mechanisms. Since ablation of the TauT (taurine transporter) gene results in susceptibility to exercise-induced muscle weakness in vivo, it has been suggested that TauT is essential for skeletal muscle function. However, the regulatory mechanisms of TauT expression remain to be elucidated. In the present study, we demonstrated that TauT was up-regulated during myogenesis in C2C12 cells. Treatment with bFGF (basic fibroblast growth factor), which inhibited muscle differentiation, abrogated myogenic induction of TauT. The promoter activities of TauT were up-regulated during muscle differentiation in C2C12 cells. Database analyses identified an MEF2 (myocyte enhancer binding factor 2) consensus sequence at −844 in the rat TauT gene. Truncation of the promoter region containing the MEF2 site significantly reduced the promoter activity, demonstrating the functional importance of the MEF2 site. Electrophoretic mobility-shift assays confirmed that MEF2 bound to the MEF2 consensus sequence and that DNA–protein complex levels were increased during differentiation. Promoter analyses using mutated promoter-reporter plasmids demonstrated that this site was functional. Importantly, transfection with a MyoD expression vector markedly enhanced TauT promoter activity in the (non-myogenic) 10T1/2 cells. Moreover, co-transfection with an MEF2 expression vector augmented MyoD-induced TauT promoter activity, suggesting that MEF2 is required for full activation of TauT expression. Finally, we examined the effects of taurine on myotube atrophy to clarify the biological significance of the up-regulation of TauT, and demonstrated that taurine attenuated muscle atrophy induced by dexamethasone. TauT expression is regulated under the control of the myogenic programme, and we propose that this is the mechanism for taurine-mediated resistance to muscle atrophy. PMID:16318624

  1. The cytoprotective role of taurine in exercise-induced muscle injury.

    Science.gov (United States)

    Dawson, R; Biasetti, M; Messina, S; Dominy, J

    2002-06-01

    exercise in the liver and both taurine and beta-alanine blocked this effect. There was no effect of either exercise or the diets on MPO activity in the lung or spleen. Running performance as assessed by a subjective rating scale was improved by taurine supplementation and there was a significant loss in body weight in the beta-alanine-treated rats 24 hours after exercise. In summary, taurine supplementation or taurine depletion had measurable cytoprotective actions to attenuate exercise-induced injury.

  2. Antioxidant and cytoprotective effects of an ethanol extract of Acalypha wilkesiana var. macafeana from Malaysia.

    Science.gov (United States)

    Din, Wardah M; Chu, Jessica; Clarke, Garry; Jin, Khoo T; Bradshaw, Tracey D; Fry, Jeff R; Wiart, Christophe

    2013-03-01

    In the annals of biomedical theory perhaps no single class of natural product has enjoyed more ingenious speculation than antioxidants formally aimed at counteracting oxidative insults which are involved in the pathophysiology of Alzheimer's and Parkinson's disease, cancer, amyotrophic lateral sclerosis, skin ageing and wound healing. In pursuing our study of Malaysian traditional medicines with antioxidant properties, we became interested in Acalypha wilkesiana var. macafeana hort., used traditionally to heal wounds. To examine whether Acalypha wilkesiana var. macafeana hort. could suppress oxidation an ethanol extract was tested by conventional chemical in vitro assays i.e., ferric reducing antioxidant potential assay (FRAP), DPPH scavenging assay and beta-carotene bleaching (BCB) assay. To explore whether Acalypha wilkesiana var. macafeana hort. protected cells against oxidative injuries, we exposed human hepatocellular liver carcinoma (HepG2) cells to tert-butylhydroperoxide (t-BHP). In all the aforementioned experiments, the ethanol extracts elicited potent antioxidant and cytoprotective activities. To gain a better understanding of the phytochemical nature of the antioxidant principle involved, five fractions (F1-F5) obtained from the ethanol extract were tested using FRAP, DPPH and BCB assays. Our results provided evidence that F5 was the most active fraction with antioxidant potentials equal to 2.090 +/- 0.307 microg/mL, 0.532 +/- 0.041 microg/mL, 0.032 +/- 0.025 microg/mL in FRAP, DPPH and BCB assay, respectively. Interestingly, F5 protected HepG2 against t-BHP oxidative insults. To further define the chemical identity of the antioxidant principle, we first performed a series of phytochemical tests, followed by liquid-chromatography and mass spectrometry (LC/MS) profiling which showed that the major compound contained in F5 was geraniin. To the best of our knowledge, this is the first report showing that the wound healing property of Acalypha wilkesiana

  3. Understanding the Mismatch Between Coaches' and Players' Perceptions of Exertion.

    Science.gov (United States)

    Brink, Michel S; Kersten, Anna W; Frencken, Wouter G P

    2017-04-01

    A mismatch between the training exertion intended by a coach and the exertion perceived by players is well established in sports. However, it is unknown whether coaches can accurately observe exertion of individual players during training. Furthermore, the discrepancy in coaches' and players' perceptions has not been explained. To determine the relation between intended and observed training exertion by the coach and perceived training exertion by the players and establish whether on-field training characteristics, intermittent endurance capacity, and maturity status explain the mismatch. During 2 mesocycles of 4 wk (in November and March), rating of intended exertion (RIE), rating of observed exertion (ROE), and rating of perceived exertion (RPE) were monitored in 31 elite young soccer players. External and internal training loads were objectively quantified with accelerometers (PlayerLoad) and heart-rate monitors (TRIMPmod). Results of an interval shuttle-run test (ISRT) and age at peak height velocity (APHV) were determined for all players. RIE, ROE, and RPE were monitored in 977 training sessions. The correlations between RIE and RPE (r = .58; P base their intended and observed exertion on what they expect players will do and what they actually did on the field. When doing this, they consider the intermittent endurance capacity of individual players.

  4. Cytoprotection, proliferation and epidermal differentiation of adipose tissue-derived stem cells on emu oil based electrospun nanofibrous mat.

    Science.gov (United States)

    Pilehvar-Soltanahmadi, Younes; Nouri, Mohammad; Martino, Mikaël M; Fattahi, Amir; Alizadeh, Effat; Darabi, Masoud; Rahmati-Yamchi, Mohammad; Zarghami, Nosratollah

    2017-08-15

    Electrospun nanofibrous scaffolds containing natural substances with wound healing properties such as Emu oil (EO) may have a great potential for increasing the efficiency of stem cell-based skin bioengineering. For this purpose, EO blended PCL/PEG electrospun nanofibrous mats were successfully fabricated and characterized using FE-SEM, FTIR and Universal Testing Machine. The efficiency of the scaffolds in supporting the adherence, cytoprotection, proliferation and differentiation of adipose tissue-derived stem cells (ADSCs) to keratinocyte was evaluated. GC/MS and HPLC were used to determine the composition of pure EO, which revealed to be mainly fatty acids and carotenoids. FE-SEM and cell proliferation assays showed that adhesion and proliferation of ADSCs on EO-PCL/PEG nanofibers was significantly higher than on PCL/PEG nanofibers. Additionally, EO-PCL/PEG nanofibers with free radical scavenging properties conferred a cytoprotective effect against cell-damaging free radicals, while the ability to support cell adhesion and growth was maintained or even improved. Immunostaining of ADSCs on EO-PCL/PEG nanofibers confirmed the change in morphology of ADSCs from spindle to polygonal shape suggesting their differentiation toward an epidermal linage. Moreover, the expression levels of the keratin 10, filaggrin, and involucrin that are involved in epidermal differentiation were upregulated in a stage-specific manner. This preliminary study shows that EO-PCL/PEG nanofibers could be a good candidate for the fabrication of wound dressings and skin bioengineered substitutes with ADSCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

    Science.gov (United States)

    Said, T; Dutot, M; Martin, C; Beaudeux, J-L; Boucher, C; Enee, E; Baudouin, C; Warnet, J-M; Rat, P

    2007-03-01

    The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

  6. Unique inhibition of bile salt-induced apoptosis by lecithins and cytoprotective bile salts in immortalized mouse cholangiocytes.

    Science.gov (United States)

    Komichi, Daisuke; Tazuma, Susumu; Nishioka, Tomoji; Hyogo, Hideyuki; Une, Mizuho; Chayama, Kazuaki

    2003-12-01

    Bile duct epithelium is physiologically exposed to high concentrations of bile salts, suggesting the presence of a cytoprotective mechanism(s). The aim of this study was to clarify whether bile salts cause bile duct cell damage and to elucidate the mechanism(s) providing protection against such an action of bile salts. Immortalized mouse cholangiocytes were incubated with taurocholate, taurochenodeoxycholate, glycochenodeoxycholate (GCDC), taurodeoxycholate, and tauroursodeoxycholate (TUDC), followed by flow-cytometric analysis and caspase activity assay to evaluate the induction of apoptosis. GCDC time-dependently induced caspase 3 (3.4-fold)- and caspase 9 (1.4-fold)-mediated apoptosis of cholangiocytes, but this was inhibited by lecithins and TUDC. Further, expression of cholangiocyte bile salt transporters (apical sodium-dependent bile salt transporter [Asbt] and multidrug resistance protein 3 [Mrp3]) was examined by RT-PCR and western blotting, and cholangiocyte bile salt uptake was determined using radiolabeled bile salts. Expression of cholangiocyte Asbt and Mrp3 was increased by bile salts, whereas lecithins interestingly reduced bile salt uptake to inhibit cholangiocyte apoptosis. In conclusion, bile salts themselves cause cholangiocyte apoptosis when absorbed by and retained inside the cell, but this is inhibited by washing out cytotoxic bile salts according to Mrp3, a rescue exporting molecule. Biliary lecithin is seemingly another cytoprotective player against cytotoxic bile salts, reducing their uptake, and this is associated with a reduced expression of Mrp3.

  7. Traditional Herbal Medicine, Rikkunshito, Induces HSP60 and Enhances Cytoprotection of Small Intestinal Mucosal Cells as a Nontoxic Chaperone Inducer

    Directory of Open Access Journals (Sweden)

    Kumiko Tamaki

    2012-01-01

    Full Text Available Increasing incidence of small intestinal ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs has become a topic with recent advances of endoscopic technology. However, the pathogenesis and therapy are not fully understood. The aim of this study is to examine the effect of Rikkunshito (TJ-43, a traditional herbal medicine, on expression of HSP60 and cytoprotective ability in small intestinal cell line (IEC-6. Effect of TJ-43 on HSP60 expression in IEC-6 cells was evaluated by immunoblot analysis. The effect of TJ-43 on cytoprotective abilities of IEC-6 cells against hydrogen peroxide or indomethacin was studied by MTT assay, LDH-release assay, caspase-8 activity, and TUNEL. HSP60 was significantly induced by TJ-43. Cell necrosis and apoptosis were significantly suppressed in IEC-6 cells pretreated by TJ-43 with overexpression of HSP60. Our results suggested that HSP60 induced by TJ-43 might play an important role in protecting small intestinal epithelial cells from apoptosis and necrosis in vitro.

  8. Cytoprotective effect of the enzyme-mediated polygallic acid on fibroblast cells under exposure of UV-irradiation.

    Science.gov (United States)

    Sánchez-Sánchez, Roberto; Romero-Montero, Alejandra; Montiel, Carmina; Melgarejo-Ramírez, Yaaziel; Sánchez-Ortega, Carmina; Lugo-Martínez, Haydée; Cabello-Arista, Beatriz; García-Arrazola, Roeb; Velasquillo, Cristina; Gimeno, Miquel

    2017-07-01

    The poly(gallic acid), produced by laccase-mediated oxidation of gallic acid in aqueous media (pH5.5) to attain a novel material with well-defined molecular structure and high water solubility (500mg/mL at 25°C), has been investigated to understand its potential biological activities. In this regard, a biomedical approach based on cytoprotective effect on human fibroblast cells exposed to UV-irradiation in the presence of the polymer has been demonstrated. The results also shows that 200μg/mL of poly(gallic acid) inhibits the growth and migration of dermal fibroblasts and cancer cell lines without affecting cell viability. Poly(gallic acid) pretreatment with 10μg/mL protects dermal fibroblasts from UV induced cell death and additionally, the cytoprotective effect reduce ROS presence in the cells. This property can be correlated with the antioxidant power (IC 50 of 23.5μg/mL) of this novel material, which was ascertained by electronic paramagnetic resonance spectroscopy and spectrophotometrically. Additionally, the antimicrobial activity of this material was corroborated with the inhibition of Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 29212) strains (MIC=400mg/mL) common bacteria found in hospitals. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 20 CFR 404.1567 - Physical exertion requirements.

    Science.gov (United States)

    2010-04-01

    ... activities. If someone can do light work, we determine that he or she can also do sedentary work, unless... Physical exertion requirements. To determine the physical exertion requirements of work in the national... making disability determinations under this subpart, we use the following definitions: (a) Sedentary work...

  10. 20 CFR 416.967 - Physical exertion requirements.

    Science.gov (United States)

    2010-04-01

    ... activities. If someone can do light work, we determine that he or she can also do sedentary work, unless... Physical exertion requirements. To determine the physical exertion requirments of work in the national... making disability determinations under this subpart, we use the following definitions: (a) Sedentary work...

  11. Exertional Rhabdomyolysis: What Is It and Why Should We Care?

    Science.gov (United States)

    Thomas, David Q.; Carlson, Kelli A.; Marzano, Amy; Garrahy, Deborah

    2012-01-01

    Exertional rhabdomyolysis gained increased attention recently when 13 football players from the University of Iowa developed this condition after an especially demanding practice session and were hospitalized. Exertional rhabdomyolysis may lead to severe kidney stress, kidney failure, and even sudden death. Anyone who does physical exercise at a…

  12. Role of the p-Coumaroyl Moiety in the Antioxidant and Cytoprotective Effects of Flavonoid Glycosides: Comparison of Astragalin and Tiliroside

    Directory of Open Access Journals (Sweden)

    Xican Li

    2017-07-01

    Full Text Available The aim of this study was to explore the role of p-coumaroyl in the antioxidant and cytoprotective effects of flavonoid glycosides. The antioxidant effects of astragalin and tiliroside were compared using ferric ion reducing antioxidant power, DPPH• scavenging, ABTS•+ scavenging, •O2– scavenging, and Fe2+-chelating assays. The results of these assays revealed that astragalin and tiliroside both exhibited dose-dependent activities; however, tiliroside exhibited lower IC50 values than astragalin. In the Fe2+-chelating assay, tiliroside gave a larger shoulder-peak at 510 nm than astragalin, and was also found to be darker in color. Both of these compounds were subsequently evaluated in a Fenton-induced mesenchymal stem cell (MSC damaged assay, where tiliroside performed more effectively as a cytoprotective agent than astragalin. Tiliroside bearing a 6′′-O-p-coumaroyl moiety exhibits higher antioxidant and cytoprotective effects than astragalin. The 6′′-O-p-coumaroyl moiety of tiliroside not only enhances the possibility of electron-transfer and hydrogen-atom-transfer-based multi-pathways, but also enhances the likelihood of Fe-chelating. The p-coumaroylation of the 6"-OH position could therefore be regarded as a potential approach for improving the antioxidant and cytoprotective effects of flavonoid glycosides in MSC implantation therapy.

  13. The cytoprotective peptide humanin is induced and neutralizes Bax after pro-apoptotic stress in the rat testis.

    Science.gov (United States)

    Jia, Y; Lue, Y-H; Swerdloff, R; Lee, K-W; Cobb, L J; Cohen, P; Wang, C

    2013-07-01

    We have previously demonstrated that the mitochondria-derived cytoprotective peptide humanin (HN), when administered intratesticularly to rats, rescues germ cells from apoptosis secondary to testicular stress of hormonal deprivation induced by gonadotropin-releasing hormone antagonist (GnRH-A). To decipher the cellular mechanisms of HN action in the amelioration of GnRH-A-induced germ cell apoptosis, adult male rats received the following treatments for 5 days: (i) daily intratesticular (IT) injections with saline (control); (ii) a single subcutaneous injection of GnRH-A on Day 1 and daily IT injection of saline; (iii) daily IT injection of synthetic HN; and (iv) GnRH-A injection on Day 1 and daily IT injection of HN (GnRH-A+HN). HN alone had no effect on germ cell apoptosis. GnRH-A increased germ cell apoptosis and BAX in the testicular mitochondrial fractions. Synthetic HN decreased germ cell apoptosis induced by GnRH-A and BAX in the mitochondria. We deduced that the cytoprotective action of synthetic HN on GnRH-A-induced germ cell apoptosis was mediated by attenuating p38 mitogen-activated protein kinase activity and increasing STAT3 phosphorylation. The effect of synthetic HN on the expression of endogenous rat HN in the testis was studied using rat HN specific antibody. GnRH-A treatment increased, but concomitant treatment with synthetic HN reduced endogenous rat HN expression in both cytosolic and mitochondrial fractions in testis. Co-immunoprecipitation experiments demonstrated that the increased rat HN was physically associated with BAX in the cytosolic testicular fractions after GnRH-A treatment. Double-immunofluorescence staining confirmed the co-localization of BAX and rat HN in the cytoplasm of Leydig cells and spermatocytes after GnRH-A treatment. We conclude that the cytoprotective effect of exogenously administered synthetic HN is mediated by interactions of endogenous rat HN with BAX in the cytoplasm preventing the entry of BAX to the mitochondria

  14. Prior Acute Mental Exertion in Exercise and Sport

    Science.gov (United States)

    Silva-Júnior, Fernando Lopes e; Emanuel, Patrick; Sousa, Jordan; Silva, Matheus; Teixeira, Silmar; Pires, Flávio Oliveira; Machado, Sérgio; Arias-Carrion, Oscar

    2016-01-01

    Introduction: Mental exertion is a psychophysiological state caused by sustained and prolonged cognitive activity. The understanding of the possible effects of acute mental exertion on physical performance, and their physiological and psychological responses are of great importance for the performance of different occupations, such as military, construction workers, athletes (professional or recreational) or simply practicing regular exercise, since these occupations often combine physical and mental tasks while performing their activities. However, the effects of implementation of a cognitive task on responses to aerobic exercise and sports are poorly understood. Our narrative review aims to provide information on the current research related to the effects of prior acute mental fatigue on physical performance and their physiological and psychological responses associated with exercise and sports. Methods: The literature search was conducted using the databases PubMed, ISI Web of Knowledge and PsycInfo using the following terms and their combinations: “mental exertion”, “mental fatigue”, “mental fatigue and performance”, “mental exertion and sports” “mental exertion and exercise”. Results: We concluded that prior acute mental exertion affects effectively the physiological and psychophysiological responses during the cognitive task, and performance in exercise. Conclusion: Additional studies involving prior acute mental exertion, exercise/sports and physical performance still need to be carried out in order to analyze the physiological, psychophysiological and neurophysiological responses subsequently to acute mental exertion in order to identify cardiovascular factors, psychological, neuropsychological associates. PMID:27867415

  15. Effect of acetylation on antioxidant and cytoprotective activity of polysaccharides isolated from pumpkin (Cucurbita pepo, lady godiva).

    Science.gov (United States)

    Song, Yi; Yang, Yang; Zhang, Yuyu; Duan, Liusheng; Zhou, Chunli; Ni, Yuanying; Liao, Xiaojun; Li, Quanhong; Hu, Xiaosong

    2013-10-15

    Acetylation of pumpkin (Cucurbita pepo, lady godiva variety) polysaccharide using acetic anhydride with pyridines as catalyst under different conditions was conducted to obtain different degrees of acetylation on a laboratory scale. Furthermore, antioxidant activities and cytoprotective effects of pumpkin polysaccharide and its acetylated derivatives were investigated employing various established in vitro systems. Results showed that addition of pyridine as catalyst could increase the degree of substitution, whereas volume of acetic anhydride had little effect. The acetylated polysaccharides in DPPH scavenging radical activity assay, superoxide anion radical activity assay and reducing power assay exhibited higher antioxidant activity than that of unmodified polysaccharide. H2O2-induced oxidative damages on rat thymic lymphocyte were also prevented by pumpkin polysaccharide and its acetylated derivatives and the derivatives presented higher protective effects. On the whole, acetylated polysaccharide showed relevant antioxidant activity both in vitro and in a cell system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Irradiation Effect on the antioxidant properties, anti-microbial and cytoprotective of the bark of Punica granatum

    International Nuclear Information System (INIS)

    Sanaa, Chahnez

    2013-01-01

    The bark of pomegranate has been used for some years to treat various health problems . Several studies have focused on specifying these problems, including antibacterial , antioxidant and cytoprotective . The use of pomegranate rind powder is an effective treatment against gastric ulcer and intestines and to strengthen the wall of the gastrointestinal tract. In this work, we studied the effects of gamma irradiation on the type antibacterial, anti-ulcer and bark grenade. This study was conducted on powdered pomegranate bark irradiated by applying decreasing radiation doses from 25kGy to 1.25KGy. All of our results shows that irradiation with a low degree improves the effectiveness of pomegranate bark for the treatment of gastric ulcer , however high degree irradiation enhances the antibacterial activity of bark pomegranate against Staphylococcus aureus.

  17. Chemical constituents from Phyllanthus emblica and the cytoprotective effects on H2O2-induced PC12 cell injuries.

    Science.gov (United States)

    Zhang, Yao; Zhao, Lijuan; Guo, Xiaojiang; Li, Chao; Li, Haizhen; Lou, Hongxiang; Ren, Dongmei

    2016-09-01

    Two new compounds (1-2), including a bisabolane-type sesquiterpenoid (1), one new diphenyl ether derivative (2), together with 23 known compounds (3-25), were isolated from the fruits of Phyllanthus emblica. Their structures were elucidated by detailed spectroscopic analysis. All the isolated compounds were screened for the DPPH scavenging effects and cytoprotective effects against H2O2 induced PC12 cells injury. Compounds 12-15 showed significant DPPH scavenging effects with the IC50 values in the range of 3.25-4.18 μM. Among these potential antioxidants, compound 14 improved the survival of PC12 cells after H2O2 exposure without showing any cytotoxicity at the tested concentrations.

  18. Antioxidative and cytoprotective effects of andrographolide against CCl4-induced hepatotoxicity in HepG2 cells.

    Science.gov (United States)

    Krithika, R; Verma, R J; Shrivastav, P S

    2013-05-01

    This article describes antioxidative and cytoprotective property of andrographolide, a major active component of the plant Andrographis paniculata (A. paniculata). High yields (2.7%) of andrographolide was isolated from the aerial parts of this plant via silica column chromatography. The purity of the compound was determined by high-performance thin-layer chromatography (HPTLC) and reversed phase high-performance liquid chromatography (HPLC) analysis. The structure was elucidated using techniques such as UV-visible spectrophotometry, elemental analysis, Fourier transform infrared (FT-IR), (1)H nuclear magnetic resonance ((1)H NMR), (13)C nuclear magnetic resonance ((13)C NMR) and mass spectral analysis and the data obtained were comparable with reported results. It was observed that andrographolide exhibited significant antioxidative property (IC50 = 3.2 µg/ml) by its ability to scavenge a stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) as compared to known antioxidants like ascorbic acid, butylated hydroxy toluene (BHT) and the plant extract. The cytoprotective role of andrographolide against carbon tetrachloride (CCl4) toxicity in human hepatoma HepG2 cell line was assessed using trypan blue exclusion test, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, by estimation of various leakage enzymes and by measuring the glutathione levels. The recovery obtained for andrographolide treatment in the presence of CCl4 was two-fold compared to A. paniculata extract for all other related biochemical parameters investigated. The results of the study indicate that andrographolide is a potent inhibitor of CCl4-mediated lipid peroxidation.

  19. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    NARCIS (Netherlands)

    Scalco, R.S.; Snoeck, M.; Quinlivan, R.; Treves, S.; Laforet, P.; Jungbluth, H.; Voermans, N.C.

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild

  20. Musical agency reduces perceived exertion during strenuous physical performance.

    Science.gov (United States)

    Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

    2013-10-29

    Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting.

  1. Do placebo expectations influence perceived exertion during physical exercise?

    Directory of Open Access Journals (Sweden)

    Hendrik Mothes

    Full Text Available This study investigates the role of placebo expectations in individuals' perception of exertion during acute physical exercise. Building upon findings from placebo and marketing research, we examined how perceived exertion is affected by expectations regarding a the effects of exercise and b the effects of the exercise product worn during the exercise. We also investigated whether these effects are moderated by physical self-concept. Seventy-eight participants conducted a moderate 30 min cycling exercise on an ergometer, with perceived exertion (RPE measured every 5 minutes. Beforehand, each participant was randomly assigned to 1 of 4 conditions and watched a corresponding film clip presenting "scientific evidence" that the exercise would or would not result in health benefits and that the exercise product they were wearing (compression garment would additionally enhance exercise benefits or would only be worn for control purposes. Participants' physical self-concept was assessed via questionnaire. Results partially demonstrated that participants with more positive expectations experienced reduced perceived exertion during the exercise. Furthermore, our results indicate a moderator effect of physical self-concept: Individuals with a high physical self-concept benefited (in terms of reduced perceived exertion levels in particular from an induction of generally positive expectations. In contrast, individuals with a low physical self-concept benefited when positive expectations were related to the exercise product they were wearing. In sum, these results suggest that placebo expectations may be a further, previously neglected class of psychological factors that influence the perception of exertion.

  2. Musical agency reduces perceived exertion during strenuous physical performance

    Science.gov (United States)

    Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

    2013-01-01

    Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting. PMID:24127588

  3. Successful Administration of Recombinant Human Soluble Thrombomodulin α (Recomodulin for Disseminated Intravascular Coagulation during Induction Chemotherapy in an Elderly Patient with Acute Monoblastic Leukemia Involving the t(9;11(p22;q23 MLL/AF9 Translocation

    Directory of Open Access Journals (Sweden)

    Kazutaka Takagi

    2011-01-01

    Full Text Available Patients with acute myelogenous leukemia complicate with disseminated intravascular coagulation (DIC, not only at the time of the initially leukemia diagnosis, but also during induction chemotherapy. In Japan, recently, a recombinant human soluble thrombomodulin alpha (Recomodulin has been introduced as a new type of anti-DIC agent for clinical use in patients with hematological cancer or infectious disease. We describe a 67-year-old female case in which 25,600 units of Recomodulin for 6 days were successfully administered for both initially complicating and therapy-induced DIC without any troubles of bleeding in an acute monoblastic leukemia (AML-M5a patient with the MLL gene translocation. Furthermore, the levels of DIC biomarkers recovered rapidly after the Recomodulin treatment. Our case suggests that DIC control using Recomodulin is one of the crucial support-therapies during remission induction chemotherapy in patients with acute leukemia of which type tends to complicate extramedullary or extranodal infiltration having potential to onset DIC.

  4. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    Science.gov (United States)

    Scalco, Renata S; Snoeck, Marc; Quinlivan, Ros; Treves, Susan; Laforét, Pascal; Jungbluth, Heinz; Voermans, Nicol C

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild cases may remain unnoticed or undiagnosed. Exertional rhabdomyolysis is well described among athletes and military personnel, but may occur in anybody exposed to unaccustomed exercise. In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed. PMID:27900193

  5. Cytoprotective and Antioxidant Effects of an Edible Herb, Enhydra fluctuans Lour. (Asteraceae, against Experimentally Induced Lead Acetate Intoxication.

    Directory of Open Access Journals (Sweden)

    Tarun K Dua

    Full Text Available Enhydra fluctuans Lour. (Asteraceae, an edible aquatic herb, is traditionally employed against toxic effects of heavy metals in India. The present study was planned to discover the protective effect of edible extract of E. fluctuans (AEEF against Pb toxicity.The cytoprotective role of AEEF was determined on murine hepatocytes employing MTT assay and Hoechst staining. The effects on lipid peroxidation, protein carbonylation, endogenous redox systems and the transcription levels of apoptotic proteins were studied after incubating the hepatocytes with AEEF (400 μg/ml + Pb-acetate (6.8 μM. The defensive role of AEEF (100 mg/kg against Pb-acetate (5 mg/kg intoxication was measured in mice by in vivo assays. Biochemical, haematological and histological parameters, intracellular Pb burden and redox status were measured.AEEF exhibited a concentration dependent cytoprotective effect against Pb-induced cytotoxicity in vitro. Pb-acetate incubation significantly (p < 0.01 altered the extents of ROS production ↑, protein carbonylation ↑, lipid peroxidation ↑, endogenous antioxidant enzymes ↓ and GSH ↓ in vitro. Besides, Pb-acetate significantly (p < 0.01 induced apoptosis in the hepatocytes apparent from the altered expressions of apoptotic proteins viz. Apaf-1 ↑, Bad ↑, Bcl-2 ↓, Cyt C ↑, cleaved caspases↑, Bid ↑ and Fas ↑. However, AEEF (400 μg/ml could significantly (p < 0.05-0.01 attenuate the Pb-acetate mediated toxic manifestation in vitro. In in vivo assay, Pb-acetate (5 mg/kg treated mice exhibited significantly (p < 0.01 high intracellular Pb content. A high Pb-burden within the tissues caused significant (p < 0.05-0.01 patho-physiological alterations viz. ROS production ↑, protein carbonylation↑, lipid peroxidation ↑, DNA fragmentation ↑, ATP formation ↑, mitochondrial co-enzymes Q ↓, endogenous antioxidant enzymes ↓ and GSH ↓ within the selected tissues. The haematological and serum biochemical parameters

  6. Mechanochemistry Induced Using Force Exerted by a Functionalized Microscope Tip

    DEFF Research Database (Denmark)

    Zhang, Yajie; Wang, Yongfeng; Lü, Jing-Tao

    2017-01-01

    Atomic-scale mechanochemistry is realized from force exerted by a C60 -functionalized scanning tunneling microscope tip. Two conformers of tin phthalocyanine can be prepared on coinage-metal surfaces. A transition between these conformers is induced on Cu(111) and Ag(100). Density-functional calc......Atomic-scale mechanochemistry is realized from force exerted by a C60 -functionalized scanning tunneling microscope tip. Two conformers of tin phthalocyanine can be prepared on coinage-metal surfaces. A transition between these conformers is induced on Cu(111) and Ag(100). Density...

  7. 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on keratinocytes against reactive oxygen species by insect virus-derived protein microcrystals

    International Nuclear Information System (INIS)

    Shimabukuro, Junji; Yamaoka, Ayako; Murata, Ken-ichi; Kotani, Eiji; Hirano, Tomoko; Nakajima, Yumiko; Matsumoto, Goichi; Mori, Hajime

    2014-01-01

    Stable protein microcrystals called polyhedra are produced by certain insect viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7 polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture and melanin was also typically observed in the lower layer. The 3D cell culture model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis due to effective melanogenesis, proliferation and differentiation of keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when keratinocytes were treated with menadione, which is a generator of reactive oxygen species. The cytoprotective effect was activated by the inositol triphosphate kinase–Akt pathway leading to upregulation of the antioxidant enzymes superoxide dismutase and peroxiredoxin 6. - Highlights: • 3D cultures using FGF-2 and FGF-7 microcrystals as a human skin model • Cytoprotection of keratinocytes against ROS by FGF-7 microcrystals • Overexpression of SOD and Prdx6 in keratinocytes by FGF-7 microcrystals

  8. 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on keratinocytes against reactive oxygen species by insect virus-derived protein microcrystals

    Energy Technology Data Exchange (ETDEWEB)

    Shimabukuro, Junji; Yamaoka, Ayako; Murata, Ken-ichi [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Kotani, Eiji [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan); Hirano, Tomoko [Venture Laboratory, Kyoto Institute of Technology, Kyoto (Japan); Nakajima, Yumiko [Functional Genomics Group, COMB, Tropical Biosphere Research Center, University of the Ryukyus, Okinawa (Japan); Matsumoto, Goichi [Division of Oral Surgery, Yokohama Clinical Education Center of Kanagawa Dental University, Yokohama (Japan); Mori, Hajime, E-mail: hmori@kit.ac.jp [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan)

    2014-09-01

    Stable protein microcrystals called polyhedra are produced by certain insect viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7 polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture and melanin was also typically observed in the lower layer. The 3D cell culture model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis due to effective melanogenesis, proliferation and differentiation of keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when keratinocytes were treated with menadione, which is a generator of reactive oxygen species. The cytoprotective effect was activated by the inositol triphosphate kinase–Akt pathway leading to upregulation of the antioxidant enzymes superoxide dismutase and peroxiredoxin 6. - Highlights: • 3D cultures using FGF-2 and FGF-7 microcrystals as a human skin model • Cytoprotection of keratinocytes against ROS by FGF-7 microcrystals • Overexpression of SOD and Prdx6 in keratinocytes by FGF-7 microcrystals.

  9. Chronic exertional compartment syndrome in the forearm of a rower

    African Journals Online (AJOL)

    2 2014. CASE STUDY. This case report describes chronic exertional compartment syndrome in the forearm of a professional rower. We consider this to be a rare anatomical location for this type of syndrome. Morever, not much is known about its clinical presentation and the subsequent optimal medical management thereof ...

  10. Exertional abdominal pain as a symptom of secondary pulmonary ...

    African Journals Online (AJOL)

    2011-04-21

    Apr 21, 2011 ... symptoms appear, such as orthopnea, hemoptysis, and peripheral edema. This is the first ... characteristics of a 55-year-old woman with mitral stenosis and severe pulmonary hypertension, whose first symptom was exertional .... mitral stenosis: Its postoperative management with a diet of medium-chain.

  11. Exertional Heat Illness among Secondary School Athletes: Statewide Policy Implications

    Science.gov (United States)

    Rodgers, Jill; Slota, Peggy; Zamboni, Beth

    2018-01-01

    Exertional heat illness (EHI) is a leading cause of preventable death among student athletes. While causes and preventative measures for EHI are known, school districts may not be implementing evidence-based practices. This descriptive, exploratory study explored school policies, resources, and practices of coaches in a mid-Atlantic state in the…

  12. 20 CFR 404.1569a - Exertional and nonexertional limitations.

    Science.gov (United States)

    2010-04-01

    ... some physical feature(s) of certain work settings, e.g., you cannot tolerate dust or fumes; or (vi) You... as pain, only affect your ability to perform the nonexertional aspects of work-related activities... of jobs by various exertional levels (sedentary, light, medium, heavy, and very heavy) in terms of...

  13. 20 CFR 220.135 - Exertional and nonexertional limitations.

    Science.gov (United States)

    2010-04-01

    ... hearing; (v) Difficulty tolerating some physical feature(s) of certain work settings, e.g., the claimant... nonexertional aspects of work-related activities, the rules in appendix 2 do not direct factual conclusions of... of jobs by various exertional levels (sedentary, light, medium, heavy, and very heavy) in terms of...

  14. Visual control in basketball shooting under exertion conditions.

    Science.gov (United States)

    Zwierko, Teresa; Popowczak, Marek; Woźniak, Jarosław; Rokita, Andrzej

    2017-07-25

    This study examined the effect of physical exertion on gaze behavior during basketball shooting in both stationary and dynamic conditions. Thirteen skilled basketball players performed two-point shooting during a 60 second fatigue protocol. Before and after a jump shot test, players performed two free throws. Eye movements were registered using an SMI Mobile EyeTracker. The frequency of all fixation points (number) and fixation duration during the motor phases of shooting were determined using frame-by- frame analysis. The type of basketball shot differentiated gaze control: (1) fixations were longer and more frequent during free throws as compared to jump shots, (2) shooting accuracy was positively influenced by less frequent and longer fixations, (3) physical exertion resulted in significantly more frequent fixations during free throws, and (4) exertion conditions resulted in a high variation in the patterns of total fixation times during jump shots. The findings suggest that physical exertion may reduce oculomotor efficiency during aiming at a distant target. Moreover, stationary and dynamic shots require different gaze behavior strategies.

  15. Exertional abdominal pain as a symptom of secondary pulmonary ...

    African Journals Online (AJOL)

    We report a rare presentation of mitral stenosis (MS). MS is a common valvular disease, the first manifestation of which is usually easy fatigability and exertional dyspnea. As the disease progresses in severity, other signs and symptoms appear, such as orthopnea, hemoptysis, and peripheral edema. This is the first report of ...

  16. 20 CFR 416.969a - Exertional and nonexertional limitations.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Exertional and nonexertional limitations. 416.969a Section 416.969a Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME... the strength demands for sitting, standing, walking, lifting, carrying, pushing, and pulling. Sections...

  17. 20 CFR 220.132 - Physical exertion requirements.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Physical exertion requirements. 220.132 Section 220.132 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT... of walking and standing is often necessary in carrying out job duties. Jobs are sedentary if walking...

  18. Improvement of anti-tumor activity of photodynamic therapy through inhibition of cytoprotective mechanism in tumor cells

    Science.gov (United States)

    Nowis, Dominika; Szokalska, Angelika; Makowski, Marcin; Winiarska, Magdalena; Golab, Jakub

    2009-06-01

    Photodynamic therapy (PDT) leads to oxidative damage of cellular macromolecules, including numerous proteins that undergo multiple modifications such as fragmentation, cross-linking and carbonylation that result in protein unfolding and aggregation. Several mechanisms are involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Identification of these cytoprotective mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. By using various molecular biology approaches, including microarray-based technologies we have identified genes that are up-regulated following PDT. Subsequent experiments revealed that some of these gene products can become targets for the combined therapeutic regimens encompassing PDT and selective small-molecule inhibitors. These include superoxide dismutase (SOD-2), cyclooxygenase 2 (COX-2), heme oxygenase 1 (HO-1), and proteins engaged in signaling endoplasmatic reticulum (ER) stress and unfolded protein response (UPR). Since a major mechanism for elimination of carbonylated proteins is their degradation by proteasomes, we hypothesized that a combination of PDT with proteasome inhibitors might lead to accumulation of carbonylated proteins in ER, aggravated ER stress and potentiated cytotoxicity towards tumor cells. Indeed, we observed that incubation of tumor cells with three different proteasome inhibitors, including bortezomib, MG132 and PSI gave increased accumulation of carbonylated and ubiquitinated proteins in PDT-treated cells. Proteasome inhibitors effectively sensitized tumor cells to PDT-mediated cytotoxicity and augmented antitumor effects of PDT in vivo.

  19. The Effect of Covalently-Attached ATRP-Synthesized Polymers on Membrane Stability and Cytoprotection in Human Erythrocytes.

    Science.gov (United States)

    Clafshenkel, William P; Murata, Hironobu; Andersen, Jill; Creeger, Yehuda; Koepsel, Richard R; Russell, Alan J

    2016-01-01

    Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atom-transfer radical polymerization (ATRP), may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of free-radical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidyl)suberate (BS3). A free radical scavenging polymer, NHS-pDMAA-TEMPO˙, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system.

  20. Isolating a cytoprotective compound from Ganoderma tsugae: effects on induction of Nrf-2-related genes in endothelial cells.

    Science.gov (United States)

    Wei, Yu-Shan; Wung, Being-Sun; Lin, Yuan-Chun; Hsieh, Chia-Wen

    2009-08-01

    Ganoderma tsugae is a medicinal fungus with several biological activities. It has long been used as a folk remedy for the promotion of health and longevity in China and other oriental countries. Here, a bioactive fraction of G. tsugae was progressively purified to be enriched in the activity of cytoprotective enzymes. The highest bioactivity was detected in the 20% EtOH-precipitated fraction, which was prepared from submerged fermentation filtrate of G. tsugae. Following further purification by gel filtration chromatography and acetone extraction, the most bioactive fraction, F5-2, was identified as a peptidoglycan-like compound. Extracts of G. tsugae (F5-2) induced heme oxygenase-1 (HO-1) and thioredoxin reductase-1 (TrxR1) expression in endothelial cells by increasing NF-E2-related factor-2 (Nrf2) nuclear translocation. Pretreatment with F5-2 increased intracellular glutathione (GSH) and protected against H(2)O(2), suggesting that induction of these antioxidant enzymes is important in protection against oxidative stress. Hence the bioactive peptidoglycan-like compound from G. tsugae might protect endothelial cells.

  1. In vitro antioxidant and cytoprotective properties of Maillard reaction products from phloridzin-amino acid model systems.

    Science.gov (United States)

    Han, Linna; Li, Feng; Yu, Qijian; Li, Dapeng

    2018-01-01

    The aim of this study was to investigate in vitro antioxidant activities and cytoprotective effect of Maillard reaction products (MRPs) from phloridzin (Pz)-amino acid model systems. Their structures were also characterised by Fourier transform-infrared spectroscopy (FTIR). MRPs were prepared from the Pz-methionine (Met), Pz-lysine (Lys), Pz-isoleucine (Ile), Pz-histidine (His) or Pz-glutamic acid (Glu) model system. The Pz-Lys MRPs, rich in antioxidant potency, were subjected to ultrafiltration to yield four MRPs fractions with different molecular weights (Mw). The fraction with Mw 30-50 kDa had significantly (P Maillard reaction. The results obtained in this study may provide some basis for the purported health-promoting effects of MRPs and their potential application as antioxidant agents in food industry. Also, it is important for our understanding of the variation of bioactive substances in food during thermal processing. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  2. The Effect of Covalently-Attached ATRP-Synthesized Polymers on Membrane Stability and Cytoprotection in Human Erythrocytes.

    Directory of Open Access Journals (Sweden)

    William P Clafshenkel

    Full Text Available Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atom-transfer radical polymerization (ATRP, may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of free-radical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidylsuberate (BS3. A free radical scavenging polymer, NHS-pDMAA-TEMPO˙, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system.

  3. Measurement and Relation between Received and Exerted Violence against Partner

    Directory of Open Access Journals (Sweden)

    José Moral de la Rubia

    2014-07-01

    Full Text Available A female victimization model is often assumed in the study of couple violence, even in general population. In Mexico, a questionnaire of couple violence has been developed. This instrument evaluates suffered and exerted violence. The aims of this paper were to contrast the factor structure of this questionnaire, calculate its internal consistency, describe its distributions, compare means of violence between both sexes and between persons who live or not with their partners, and study the relationship between received and exerted violence. A non-experimental research with a trans-sectional design was performed. The questionnaire was applied to a non probability sample of 223 women and 177 men with heterosexual couples from general population. Confirmatory factor analysis and structural equation modeling were used for data analysis. The factor structure of received violence scale was one-dimensional, and the one of exerted violence scale was two-dimensional. Both sexes reported to exert violence with the same frequency, but men complained to receive violence with more frequency than women. Persons who live with their partners reported to receive more violence and to exert more non-psychological violence than persons who do not live with their partners. The correlations between received and exercised violence were moderate. A recursive model of violent reaction showed a fit to data from good to adequate, and had good properties of invariance between both sexes, and between persons who live or not with their partners. It is concluded that the questionnaire has good properties of factor structure and internal consistency, and data refute a model of female victimization.

  4. A comparison of a maximum exertion and a model-based, sub-maximum exertion method for normalizing trunk EMG

    NARCIS (Netherlands)

    Cholewicki, J.; van Dieen, J.H.; Lee, A.

    2011-01-01

    The problem with normalizing EMG data from patients with painful symptoms (e.g., low back pain) is that such patients may be unwilling or unable to perform maximum exertions. Furthermore, the normalization to a reference signal, obtained from a maximal or sub-maximal task, tends to mask differences

  5. Pressure exerted by a vesicle on a surface

    International Nuclear Information System (INIS)

    Owczarek, A L; Prellberg, T

    2014-01-01

    Several recent works have considered the pressure exerted on a wall by a model polymer. We extend this consideration to vesicles attached to a wall, and hence include osmotic pressure. We do this by considering a two-dimensional directed model, namely that of area-weighted Dyck paths. Not surprisingly, the pressure exerted by the vesicle on the wall depends on the osmotic pressure inside, especially its sign. Here, we discuss the scaling of this pressure in the different regimes, paying particular attention to the crossover between positive and negative osmotic pressure. In our directed model, there exists an underlying Airy function scaling form, from which we extract the dependence of the bulk pressure on small osmotic pressures. (paper)

  6. Differentiated Ratings of Perceived Exertion during Physical Exercise

    Science.gov (United States)

    1982-01-01

    MEDICINE AND SCIENCE IN SPORTS AND EXERCISE VOl 14, No 5. Pp 397-405. 1982 -1982 Differentiated ratings of perceived exertion during physical...Subjects are asked to indicate a Aeciied e pblicfim1mw.196 y - . ; MEDICINE AND SCIENCE IN SPORTS AND EXERCISE local muscular rating pertaining to...suggests that the interrela-11 1 1 Jl MEDICINE AND SCIENCE IN SPORTS AND

  7. Optimal diet of horses with chronic exertional myopathies.

    Science.gov (United States)

    McKenzie, Erica C; Firshman, Anna M

    2009-04-01

    Chronic exertional rhabdomyolysis represents a syndrome of recurrent exercise-associated muscle damage in horses that arises from a variety of etiologies. Major advances have been made in the understanding of the pathophysiology of this disease, and causative genetic defects have been recently identified for two conditions-polysaccharide storage myopathy of quarter horses, paints, warm bloods, and draft breeds. Dietary management in combination with a regular exercise regimen comprises the most effective means for control of clinical signs.

  8. Measurement and Relation between Received and Exerted Violence against Partner

    OpenAIRE

    Moral de la Rubia, José; López Rosales, Fuensanta

    2014-01-01

    A female victimization model is often assumed in the study of couple violence, even in general population. In Mexico, a questionnaire of couple violence has been developed. This instrument evaluates suffered and exerted violence. The aims of this paper were to contrast the factor structure of this questionnaire, calculate its internal consistency, describe its distributions, compare means of violence between both sexes and between persons who live or not with their partners, and study the rel...

  9. Cable Robot Performance Evaluation by Wrench Exertion Capability

    Directory of Open Access Journals (Sweden)

    Giovanni Boschetti

    2018-03-01

    Full Text Available Although cable driven robots are a type of parallel manipulators, the evaluation of their performances cannot be carried out using the performance indices already developed for parallel robots with rigid links. This is an obvious consequence of the peculiar features of flexible cables—a cable can only exert a tensile and limited force in the direction of the cable itself. A comprehensive performance evaluation can certainly be attained by computing the maximum force (or torque that can be exerted by the cables on the moving platform along a specific (or any direction within the whole workspace. This is the idea behind the index—called the Wrench Exertion Capability (WEC—which can be employed to evaluate the performance of any cable robot topology and is characterized by an efficient and simple formulation based on linear programming. By significantly improving a preliminary computation method for the WEC, this paper proposes an ultimate formulation suitable for any cable robot topology. Several numerical investigations on planar and spatial cable robots are presented to give evidence of the WEC usefulness, comparisons with popular performance indices are also provided.

  10. Exercise, physical activity, and exertion over the business cycle.

    Science.gov (United States)

    Colman, Gregory; Dave, Dhaval

    2013-09-01

    Shifts in time and income constraints over economic expansions and contractions would be expected to affect individuals' behaviors. We explore the impact of the business cycle on individuals' exercise, time use, and total physical exertion, utilizing information on 112,000 individual records from the 2003-2010 American Time Use Surveys. In doing so, we test a key causal link that has been hypothesized in the relation between unemployment and health, but not heretofore assessed. Using more precise measures of exercise (and other activities) than previous studies, we find that as work-time decreases during a recession, recreational exercise, TV-watching, sleeping, childcare, and housework increase. This, however, does not compensate for the decrease in work-related exertion due to job-loss, and total physical exertion declines. These effects are strongest among low-educated men, which is validating given that employment in the Great Recession has declined most within manufacturing, mining, and construction. We also find evidence of intra-household spillover effects, wherein individuals respond to shifts in spousal employment conditional on their own labor supply. The decrease in total physical activity during recessions is especially problematic for vulnerable populations concentrated in boom-and-bust industries, and may have longer-term effects on obesity and related health outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Mechanisms, measurement and management of exertional dyspnoea in asthma

    Directory of Open Access Journals (Sweden)

    Jason Weatherald

    2017-06-01

    Full Text Available Asthma is a heterogeneous condition, with dyspnoea during exercise affecting individuals to a variable degree. This narrative review explores the mechanisms and measurement of exertional dyspnoea in asthma and summarises the available evidence for the efficacy of various interventions on exertional dyspnoea. Studies on the mechanisms of dyspnoea in asthma have largely utilised direct bronchoprovocation challenges, rather than exercise, which may invoke different physiological mechanisms. Thus, the description of dyspnoea during methacholine challenge can differ from what is experienced during daily activities, including exercise. Dyspnoea perception during exercise is influenced by many interacting variables, such as asthma severity and phenotype, bronchoconstriction, dynamic hyperinflation, respiratory drive and psychological factors. In addition to the intensity of dyspnoea, the qualitative description of dyspnoea may give important clues as to the underlying mechanism and may be an important endpoint for future interventional studies. There is currently little evidence demonstrating whether pharmacological or non-pharmacological interventions specifically improve exertional dyspnoea, which is an important area for future research.

  12. SerpinB2 (PAI-2 Modulates Proteostasis via Binding Misfolded Proteins and Promotion of Cytoprotective Inclusion Formation.

    Directory of Open Access Journals (Sweden)

    Jodi A Lee

    Full Text Available SerpinB2 (PAI-2, a member of the clade B family of serine protease inhibitors, is one of the most upregulated proteins following cellular stress. Originally described as an inhibitor of urokinase plasminogen activator, its predominant cytoplasmic localisation suggests an intracellular function. SerpinB2 has been reported to display cytoprotective properties in neurons and to interact with intracellular proteins including components of the ubiquitin-proteasome system (UPS. In the current study we explored the potential role of SerpinB2 as a modulator of proteotoxic stress. Initially, we transiently transfected wild-type SerpinB2 and SerpinB2-/- murine embryonic fibroblasts (MEFs with Huntingtin exon1-polyglutamine (fused C-terminally to mCherry. Inclusion body formation as result of Huntingtin aggregation was evident in the SerpinB2 expressing cells but significantly impaired in the SerpinB2-/- cells, the latter concomitant with loss in cell viability. Importantly, recovery of the wild-type phenotype and cell viability was rescued by retroviral transduction of SerpinB2 expression. SerpinB2 modestly attenuated Huntingtin and amyloid beta fibril formation in vitro and was able to bind preferentially to misfolded proteins. Given the modest chaperone-like activity of SerpinB2 we tested the ability of SerpinB2 to modulate UPS and autophagy activity using a GFP reporter system and autophagy reporter, respectively. Activity of the UPS was reduced and autophagy was dysregulated in SerpinB2-/- compared to wild-type MEFs. Moreover, we observed a non-covalent interaction between ubiquitin and SerpinB2 in cells using GFP-pulldown assays and bimolecular fluorescence complementation. We conclude that SerpinB2 plays an important role in proteostasis as its loss leads to a proteotoxic phenotype associated with an inability to compartmentalize aggregating proteins and a reduced capacity of the UPS.

  13. Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK

    Directory of Open Access Journals (Sweden)

    Arnau Panisello-Roselló

    2018-01-01

    Full Text Available Institute Goeorges Lopez 1 (IGL-1 and Histidine-Tryptophan-Ketoglutarate (HTK preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 °C in IGL-1 or HTK preservation solutions. After organ recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in mechanistic target of rapamycin (mTOR signaling activation, liver autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7 and apoptotic markers (caspase 3, caspase 9 and TUNEL. These determinations were correlated with the prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT, histology and mitochondrial damage (glutamate dehydrogenase (GLDH and confocal microscopy findings. Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis, including inflammatory cytokines such as HMGB1. Together, our results revealed that IGL-1 preservation solution better protected fatty liver grafts against cold ischemia damage than HTK solution. IGL-1 protection was associated with a reduced liver damage, higher induced autophagy and decreased apoptosis. All these effects would contribute to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures.

  14. Oxidative stress modulates heme synthesis and induces peroxiredoxin-2 as a novel cytoprotective response in β-thalassemic erythropoiesis.

    Science.gov (United States)

    De Franceschi, Lucia; Bertoldi, Mariarita; De Falco, Luigia; Santos Franco, Sara; Ronzoni, Luisa; Turrini, Franco; Colancecco, Alessandra; Camaschella, Clara; Cappellini, Maria Domenica; Iolascon, Achille

    2011-11-01

    β-thalassemic syndromes are inherited red cell disorders characterized by severe ineffective erythropoiesis and increased levels of reactive oxygen species whose contribution to β-thalassemic anemia is only partially understood. We studied erythroid precursors from normal and β-thalassemic peripheral CD34(+) cells in two-phase liquid culture by proteomic, reverse transcriptase polymerase chain reaction and immunoblot analyses. We measured intracellular reactive oxygen species, heme levels and the activity of δ-aminolevulinate-synthase-2. We exposed normal cells and K562 cells with silenced peroxiredoxin-2 to H(2)O(2) and generated a recombinant peroxiredoxin-2 for kinetic measurements in the presence of H(2)O(2) or hemin. In β-thalassemia the increased production of reactive oxygen species was associated with down-regulation of heme oxygenase-1 and biliverdin reductase and up-regulation of peroxiredoxin-2. In agreement with these observations in β-thalassemic cells we found decreased heme levels related to significantly reduced activity of the first enzyme of the heme pathway, δ-aminolevulinate synthase-2 without differences in its expression. We demonstrated that the activity of recombinant δ-aminolevulinate synthase-2 is inhibited by both reactive oxygen species and hemin as a protective mechanism in β-thalassemic cells. We then addressed the question of the protective role of peroxiredoxin-2 in erythropoiesis by exposing normal cells to oxidative stress and silencing peroxiredoxin-2 in human erythroleukemia K562 cells. We found that peroxiredoxin-2 expression is up-regulated in response to oxidative stress and required for K562 cells to survive oxidative stress. We then showed that peroxiredoxin-2 binds heme in erythroid precursors with high affinity, suggesting a possible multifunctional cytoprotective role of peroxiredoxin-2 in β-thalassemia. In β-thalassemic erythroid cells the reduction of δ-aminolevulinate synthase-2 activity and the increased

  15. Topical application of the synthetic triterpenoid RTA 408 activates Nrf2 and induces cytoprotective genes in rat skin.

    Science.gov (United States)

    Reisman, Scott A; Lee, Chun-Yue I; Meyer, Colin J; Proksch, Joel W; Ward, Keith W

    2014-07-01

    RTA 408 is a member of the synthetic oleanane triterpenoid class of compounds known to potently activate the cytoprotective transcription factor Nrf2. Because skin is constantly exposed to external oxidative stress, such as that from ultraviolet radiation, from chemical exposure, during improper wound healing, and throughout the course of cancer radiation therapy, it may benefit from activation of Nrf2. This study was conducted to evaluate the transdermal penetration properties and Nrf2 activation potential of RTA 408 in normal rat skin. RTA 408 (0.1, 1.0, or 3.0%) was applied topically to the shaved skin of male Sprague-Dawley rats twice daily for 4 days and once on Day 5. Topical application of RTA 408 resulted in transdermal penetration, with low but dose-dependent plasma exposure with AUC(0-24 h) values of 3.6, 26.0, and 41.1 h ng/mL for the 0.1, 1.0, and 3.0% doses, respectively. Further, topical application of RTA 408 resulted in increased translocation of Nrf2 to the nucleus, dose-dependent mRNA induction of Nrf2 target genes (e.g. Nqo1, Srxn1, Gclc, and Gclm), and induction of the protein expression of the prototypical Nrf2 target gene Nqo1 and increased total glutathione (GSH) in normal rat skin. Immunohistochemistry demonstrated that increased staining for Nqo1 and total GSH of structures in both the epidermis and dermis was consistent with the full transdermal penetration of RTA 408. Finally, topically administered RTA 408 was well tolerated with no adverse in-life observations and normal skin histology. Thus, the data support the further development of RTA 408 for the potential treatment of skin diseases.

  16. Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress

    Science.gov (United States)

    Bachar, Adi R.; Scheffer, Lea; Schroeder, Andreas S.; Nakamura, Hiromi K.; Cobb, Laura J.; Oh, Yun K.; Lerman, Lilach O.; Pagano, Richard E.; Cohen, Pinchas; Lerman, Amir

    2010-01-01

    Aims Humanin (HN) is a 24-amino acid peptide that has been shown to have an anti-apoptotic function against neuronal cell death caused by Alzheimer's disease. Increased oxidative stress, one of the major factors contributing to this cell death, also plays an important role in the inflammatory process of atherosclerosis. The current study was designed to test the hypothesis that HN is expressed in the human vascular wall and may protect against oxidative stress. Methods and results HN expression in the vascular wall was detected by immunostaining in the endothelial cell layer of human internal mammary arteries (n = 5), atherosclerotic coronary arteries (n = 17), and sections of the greater saphenous vein (n = 3). HN mRNA was expressed in the human aortic endothelial cells (HAECs). Cytoprotective effects of HN against oxidative stress were tested in vitro in HAECs. Pre-treatment with 0.1 µM HN reduced oxidized LDL (Ox-LDL)-induced (i) formation of reactive oxygen species by 50%, (ii) apoptosis by ∼50% as determined by TUNEL staining, and (iii) formation of ceramide, a lipid second messenger involved in the apoptosis signalling cascade, by ∼20%. Conclusion The current study demonstrates for the first time the expression of HN in the endothelial cell layer of human blood vessels. Exogenous addition of HN to endothelial cell cultures was shown to be effective against Ox-LDL-induced apoptosis. These findings suggest that HN may play a role and may have a protective effect in early atherosclerosis in humans. PMID:20562421

  17. SerpinB2 (PAI-2) Modulates Proteostasis via Binding Misfolded Proteins and Promotion of Cytoprotective Inclusion Formation

    Science.gov (United States)

    Farrawell, Natalie; Shearer, Robert F.; Constantinescu, Patrick; Hatters, Danny M.; Schroder, Wayne A.; Suhrbier, Andreas; Wilson, Mark R.; Saunders, Darren N.; Ranson, Marie

    2015-01-01

    SerpinB2 (PAI-2), a member of the clade B family of serine protease inhibitors, is one of the most upregulated proteins following cellular stress. Originally described as an inhibitor of urokinase plasminogen activator, its predominant cytoplasmic localisation suggests an intracellular function. SerpinB2 has been reported to display cytoprotective properties in neurons and to interact with intracellular proteins including components of the ubiquitin-proteasome system (UPS). In the current study we explored the potential role of SerpinB2 as a modulator of proteotoxic stress. Initially, we transiently transfected wild-type SerpinB2 and SerpinB2-/- murine embryonic fibroblasts (MEFs) with Huntingtin exon1-polyglutamine (fused C-terminally to mCherry). Inclusion body formation as result of Huntingtin aggregation was evident in the SerpinB2 expressing cells but significantly impaired in the SerpinB2-/- cells, the latter concomitant with loss in cell viability. Importantly, recovery of the wild-type phenotype and cell viability was rescued by retroviral transduction of SerpinB2 expression. SerpinB2 modestly attenuated Huntingtin and amyloid beta fibril formation in vitro and was able to bind preferentially to misfolded proteins. Given the modest chaperone-like activity of SerpinB2 we tested the ability of SerpinB2 to modulate UPS and autophagy activity using a GFP reporter system and autophagy reporter, respectively. Activity of the UPS was reduced and autophagy was dysregulated in SerpinB2-/- compared to wild-type MEFs. Moreover, we observed a non-covalent interaction between ubiquitin and SerpinB2 in cells using GFP-pulldown assays and bimolecular fluorescence complementation. We conclude that SerpinB2 plays an important role in proteostasis as its loss leads to a proteotoxic phenotype associated with an inability to compartmentalize aggregating proteins and a reduced capacity of the UPS. PMID:26083412

  18. Endoplasmic Reticulum Stress-Induced Autophagy Provides Cytoprotection from Chemical Hypoxia and Oxidant Injury and Ameliorates Renal Ischemia-Reperfusion Injury.

    Directory of Open Access Journals (Sweden)

    Bhavya B Chandrika

    Full Text Available We examined whether endoplasmic reticulum (ER stress-induced autophagy provides cytoprotection from renal tubular epithelial cell injury due to oxidants and chemical hypoxia in vitro, as well as from ischemia-reperfusion (IR injury in vivo. We demonstrate that the ER stress inducer tunicamycin triggers an unfolded protein response, upregulates ER chaperone Grp78, and activates the autophagy pathway in renal tubular epithelial cells in culture. Inhibition of ER stress-induced autophagy accelerated caspase-3 activation and cell death suggesting a pro-survival role of ER stress-induced autophagy. Compared to wild-type cells, autophagy-deficient MEFs subjected to ER stress had enhanced caspase-3 activation and cell death, a finding that further supports the cytoprotective role of ER stress-induced autophagy. Induction of autophagy by ER stress markedly afforded cytoprotection from oxidants H2O2 and tert-Butyl hydroperoxide and from chemical hypoxia induced by antimycin A. In contrast, inhibition of ER stress-induced autophagy or autophagy-deficient cells markedly enhanced cell death in response to oxidant injury and chemical hypoxia. In mouse kidney, similarly to renal epithelial cells in culture, tunicamycin triggered ER stress, markedly upregulated Grp78, and activated autophagy without impairing the autophagic flux. In addition, ER stress-induced autophagy markedly ameliorated renal IR injury as evident from significant improvement in renal function and histology. Inhibition of autophagy by chloroquine markedly increased renal IR injury. These studies highlight beneficial impact of ER stress-induced autophagy in renal ischemia-reperfusion injury both in vitro and in vivo.

  19. Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

    Energy Technology Data Exchange (ETDEWEB)

    Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil); Borsato, Débora Maria [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Almeida, Martinha Antunes [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Barboza, Fernanda Malaquias [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zawadzki, Sônia Faria [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Kanunfre, Carla Cristine [Postgraduate Program in Biomedical Science, Department of General Biology, State University of Ponta Grossa (Brazil); Farago, Paulo Vitor, E-mail: pvfarago@gmail.com [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zanin, Sandra Maria Warumby [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil)

    2016-07-01

    This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3 μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. - Highlights: • Ferulic acid-loaded Eudragit® L100 microparticles with high drug-loading were obtained. • Spray-dried Eudragit® L100 microparticles containing ferulic acid showed improved in vitro cytoprotective effect. • Ferulic acid spray-dried microparticles had potential as in vitro anti-inflammatory and immunomodulatory. • In vivo studies demonstrated an enhanced antiplatelet effect for ferulic acid-loaded Eudragit® L100 microparticles.

  20. NEBIVOLOL IN TREATMENT OF STABLE EXERTIONAL ANGINA PECTORIS

    Directory of Open Access Journals (Sweden)

    Y. V. Gavrilov

    2015-12-01

    Full Text Available Aim. To evaluate antianginal and antiischemic efficiency of nebivolol in patients with stable angina pectoris.Material and methods. 100 patients with ischemic heart disease showing stable exertional angina pectoris and having no contraindications to beta-blockers were studied. After 5-7 days of control period 50 randomly selected patients began to take nebivolol in initial dose of 5mg once daily and 50 patients started to take metoprolol in initial dose of 50 mg twice daily. Duration of treatment was 8 weeks. Efficiency of treatment was assessed according to the results of control treadmill assessment and control daily ECG monitoring.Results. 56-day therapy with nebivolol at a dose of 7,5 mg per day results in increase in duration of treadmill test before angina or ST depression (p<0.05. Antianginal and antiischemic effect of nebivolol 7.5 mg once daily is rather similar with that of metoprolol in average daily dose of 175 mg. Nebivolol compared to metoprolol significantly (p<0.05 more effectively reduces the number of silent myocardial ischemia.Conclusion. Nebivolol is an efficient antianginal and antiischemic drug for patients with stable exertional angina pectoris.

  1. Infrared imaging of the anterior deltoid during overhead static exertions.

    Science.gov (United States)

    Bertmaring, Ian; Babski-Reeves, Kari; Nussbaum, Maury A

    2008-10-01

    Infrared imaging has been used to detect the presence of neuromuscular disorders of the cervical spine and upper extremities. Despite diagnostic uses, evaluative or prognostic uses of thermography are limited. The objective of this study was to quantify surface temperature changes over the anterior deltoid and evaluate efficacy of thermography as an assessment tool. Surface temperature, discomfort ratings and endurance time were quantified during overhead static exertions until exhaustion at two work loads (15 and 30% maximum voluntary contraction) and shoulder angles (90 degrees and 115 degrees ). Ten participants free of confounding conditions participated in the study. The 90 degrees shoulder angle and 30% exertion level resulted in significantly faster thermal image rates of change, shorter endurance times and faster perceived discomfort increases. Thermography readings were more sensitive to changes in shoulder posture than load changes. This study provides preliminary evidence that thermography may be a useful exposure assessment tool. There is a need for new evaluation tools to quantify risk factor exposure for injury. Thermography was sensitive to changes in task loadings, illustrating its potential use for risk assessment. Specifically, changes in observed blood flow patterns during task performance are likely to conform to known physiological responses to injury.

  2. NEBIVOLOL IN TREATMENT OF STABLE EXERTIONAL ANGINA PECTORIS

    Directory of Open Access Journals (Sweden)

    Y. V. Gavrilov

    2007-01-01

    Full Text Available Aim. To evaluate antianginal and antiischemic efficiency of nebivolol in patients with stable angina pectoris.Material and methods. 100 patients with ischemic heart disease showing stable exertional angina pectoris and having no contraindications to beta-blockers were studied. After 5-7 days of control period 50 randomly selected patients began to take nebivolol in initial dose of 5mg once daily and 50 patients started to take metoprolol in initial dose of 50 mg twice daily. Duration of treatment was 8 weeks. Efficiency of treatment was assessed according to the results of control treadmill assessment and control daily ECG monitoring.Results. 56-day therapy with nebivolol at a dose of 7,5 mg per day results in increase in duration of treadmill test before angina or ST depression (p<0.05. Antianginal and antiischemic effect of nebivolol 7.5 mg once daily is rather similar with that of metoprolol in average daily dose of 175 mg. Nebivolol compared to metoprolol significantly (p<0.05 more effectively reduces the number of silent myocardial ischemia.Conclusion. Nebivolol is an efficient antianginal and antiischemic drug for patients with stable exertional angina pectoris.

  3. Chronic Exertional Compartment Syndrome in a High School Soccer Player

    Directory of Open Access Journals (Sweden)

    James J. Bresnahan

    2015-01-01

    Full Text Available Chronic exertional compartment syndrome (CECS is a relatively rare condition that affects young adult athletes and often causes them to present to the emergency department. If left untreated, those who continue to compete at high levels may experience debilitating leg pain. Physicians may have difficulty differentiating CECS from other syndromes of the lower leg such as medial tibial stress syndrome, stress fractures, and popliteal artery entrapment. The gold standard for diagnosing CECS is intramuscular compartment pressure monitoring before and/or after 10 minutes of exercise. Some patients may choose to stop participation in sports in order to relieve their pain, which otherwise does not respond well to nonoperative treatments. In patients who wish to continue to participate in sports and live an active life, fasciotomy provides relief in 80% or more. The typical athlete can return to training in about 8 weeks. This is a case of a high school soccer player who stopped competing due to chronic exertional compartment syndrome. She had a fascial hernia, resting intramuscular pressure of 30 mmHg, and postexercise intramuscular pressure of 99 mmHg. Following fasciotomy she experienced considerable life improvement and is once again training and playing soccer without symptoms.

  4. Chronic Exertional Compartment Syndrome in a High School Soccer Player.

    Science.gov (United States)

    Bresnahan, James J; Hennrikus, William L

    2015-01-01

    Chronic exertional compartment syndrome (CECS) is a relatively rare condition that affects young adult athletes and often causes them to present to the emergency department. If left untreated, those who continue to compete at high levels may experience debilitating leg pain. Physicians may have difficulty differentiating CECS from other syndromes of the lower leg such as medial tibial stress syndrome, stress fractures, and popliteal artery entrapment. The gold standard for diagnosing CECS is intramuscular compartment pressure monitoring before and/or after 10 minutes of exercise. Some patients may choose to stop participation in sports in order to relieve their pain, which otherwise does not respond well to nonoperative treatments. In patients who wish to continue to participate in sports and live an active life, fasciotomy provides relief in 80% or more. The typical athlete can return to training in about 8 weeks. This is a case of a high school soccer player who stopped competing due to chronic exertional compartment syndrome. She had a fascial hernia, resting intramuscular pressure of 30 mmHg, and postexercise intramuscular pressure of 99 mmHg. Following fasciotomy she experienced considerable life improvement and is once again training and playing soccer without symptoms.

  5. National Athletic Trainers' Association Position Statement: Exertional Heat Illnesses

    Science.gov (United States)

    Casa, Douglas J.; DeMartini, Julie K.; Bergeron, Michael F.; Csillan, Dave; Eichner, E. Randy; Lopez, Rebecca M.; Ferrara, Michael S.; Miller, Kevin C.; O'Connor, Francis; Sawka, Michael N.; Yeargin, Susan W.

    2015-01-01

    Objective  To present best-practice recommendations for the prevention, recognition, and treatment of exertional heat illnesses (EHIs) and to describe the relevant physiology of thermoregulation. Background  Certified athletic trainers recognize and treat athletes with EHIs, often in high-risk environments. Although the proper recognition and successful treatment strategies are well documented, EHIs continue to plague athletes, and exertional heat stroke remains one of the leading causes of sudden death during sport. The recommendations presented in this document provide athletic trainers and allied health providers with an integrated scientific and clinically applicable approach to the prevention, recognition, treatment of, and return-to-activity guidelines for EHIs. These recommendations are given so that proper recognition and treatment can be accomplished in order to maximize the safety and performance of athletes. Recommendations  Athletic trainers and other allied health care professionals should use these recommendations to establish onsite emergency action plans for their venues and athletes. The primary goal of athlete safety is addressed through the appropriate prevention strategies, proper recognition tactics, and effective treatment plans for EHIs. Athletic trainers and other allied health care professionals must be properly educated and prepared to respond in an expedient manner to alleviate symptoms and minimize the morbidity and mortality associated with these illnesses. PMID:26381473

  6. Leg 201Tl-SPECT in chronic exertional compartment syndrome

    International Nuclear Information System (INIS)

    Elkadri, N.; Slim, I.; Blondet, C.; Choquet, Ph.; Constantinesco, A.; Lecocq, J.

    2004-01-01

    Leg 201 Tl-SPECT in chronic exertional compartment syndrome Background: The chronic exertional compartment syndrome is one of the most frequent origins regarding leg pain due to sport training. The diagnosis can be established by invasive compartment pressure measurement. The aim of this study is to evaluate the role that could have 201 Tl-SPECT for patients with suspicion of compartment syndrome. Patients and methods: 51 leg 201 Tl-SPECT exams were performed (exercise - and rest without reinjection) in 49 patients; 28 had compartment syndrome confirmed by pressure measurement. About 100 MBq of 201 Tl were injected during exercise, when pain appeared or at least after 25 minutes exercise. We studied mean percentages of level uptake for each compartment, referred to the maximal uptake of both legs. Results: 47 compartments were concerned by compartment syndrome and 361 compartments were not. Scintigraphic patterns in compartments are reversible ischaemia (45%), uptake stability (36%) or reverse redistribution (19%); these patterns are not linked to compartment syndrome. However, there is a significant difference of rest 201 Tl level uptake between compartments with and without compartment syndrome and a significant correlation between muscular pressure measurement and rest level uptake. Conclusion: 201 Tl-SPECT shows that only ischaemia does not explain compartment syndrome. Moreover, it allows to predict pressure variation during exercise but it does not offer any interest in order to select patients for muscular invasive pressure measurement. (author)

  7. Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon.

    Science.gov (United States)

    Del Coso, Juan; Valero, Marjorie; Salinero, Juan José; Lara, Beatriz; Gallo-Salazar, César; Areces, Francisco

    2017-01-01

    Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A). Using Williams and Folland's model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise.

  8. Cytoprotection by omega-3 fatty acids as a therapeutic drug vehicle when combined with nephrotoxic drugs in an intravenous emulsion: Effects on intraglomerular mesangial cells

    Directory of Open Access Journals (Sweden)

    Gabriel Alejandro Bonaterra

    2014-01-01

    Full Text Available During therapeutic interventions, blood concentrations of intravenously applied drugs are higher, and their onset of pharmacological action is faster than with other routes of drug administration. However, acute drug therapy often produces nephrotoxic side effects, as commonly seen after treatment with Ketorolac or Gentamicin leading to questions about their use, especially for patients at risk for acute renal failure. Omega-6(n-6 and omega-3(n-3 polyunsaturated fatty acids (PUFA affect eicosanoid metabolism, which plays a role in the regulation of inflammation. Eicosanoids derived from n-6 FA have proinflammatory and immunoactive functions, whereas eicosanoids derived from n-3 PUFA have anti-inflammatory and cytoprotective properties. We hypothesized that providing such injectable drugs with nephrotoxic potential in combination with n3-PUFAs from the outset, might afford rapid cytoprotection of renal cells, given the recent evidence that intravenously administered n3-PUFAs are rapidly incorporated into cell membranes. We used intraglomerular mesangial cells (MES13 that are sensitive to treatment with Ketorolac or Gentamicin instead of proximal tubular cells which do not respond to Ketorolac. We found a significant inhibition of Ketorolac (0.25, 0.5, 1 mM or Gentamicin (2.5, 5 mM induced cytotoxicity after pretreatment of MES13 cells with 0.01% of 20%w/v LipOmega-3 Emulsion 9/1, containing 90:10 wt/wt mixture of fish oil derived triglycerides to medium chain triglycerides.

  9. Cellular Metabolomics Revealed the Cytoprotection of Amentoflavone, a Natural Compound, in Lipopolysaccharide-Induced Injury of Human Umbilical Vein Endothelial Cells

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    Weifeng Yao

    2016-09-01

    Full Text Available Amentoflavone is one of the important bioactive flavonoids in the ethylacetate extract of “Cebaiye”, which is a blood cooling and hematostatic herb in traditional Chinese medicine. The previous work in our group has demonstrated that the ethylacetate extract of Cebaiye has a notable antagonistic effect on the injury induced by lipopolysaccharide (LPS to human umbilical vein endothelial cells (HUVECs. The present investigation was designed to assess the effects and possible mechanism of cytoprotection of amentoflavone via metabolomics. Ultra-performance liquid chromatography/quadrupole time of flight-mass spectrometry (UPLC/QTOF-MS coupled with multivariate data analysis was used to characterize the variations in the metabolites of HUVECs in response to exposure to LPS and amentoflavone treatment. Seven putative metabolites (glycine, argininosuccinic acid, putrescine, ornithine, spermidine, 5-oxoproline and dihydrouracil were discovered in cells incubated with LPS and/or amentoflavone. Functional pathway analysis uncovered that the changes of these metabolites related to various significant metabolic pathways (glutathione metabolism, arginine and proline metabolism, β-alanine metabolism and glycine, serine and threonine metabolism, which may explain the potential cytoprotection function of amentoflavone. These findings also demonstrate that cellular metabolomics through UPLC/QTOF-MS is a powerful tool for detecting variations in a range of intracellular compounds upon toxin and/or drug exposure.

  10. Hsp27 binding to the 3′UTR of bim mRNA prevents neuronal death during oxidative stress–induced injury: a novel cytoprotective mechanism

    Science.gov (United States)

    Dávila, David; Jiménez-Mateos, Eva M.; Mooney, Claire M.; Velasco, Guillermo; Henshall, David C.; Prehn, Jochen H. M.

    2014-01-01

    Neurons face a changeable microenvironment and therefore need mechanisms that allow rapid switch on/off of their cytoprotective and apoptosis-inducing signaling pathways. Cellular mechanisms that control apoptosis activation include the regulation of pro/antiapoptotic mRNAs through their 3′-untranslated region (UTR). This region holds binding elements for RNA-binding proteins, which can control mRNA translation. Here we demonstrate that heat shock protein 27 (Hsp27) prevents oxidative stress–induced cell death in cerebellar granule neurons by specific regulation of the mRNA for the proapoptotic BH3-only protein, Bim. Hsp27 depletion induced by oxidative stress using hydrogen peroxide (H2O2) correlated with bim gene activation and subsequent neuronal death, whereas enhanced Hsp27 expression prevented these. This effect could not be explained by proteasomal degradation of Bim or bim promoter inhibition; however, it was associated with a specific increase in the levels of bim mRNA and with its binding to Hsp27. Finally, we determined that enhanced Hsp27 expression in neurons exposed to H2O2 or glutamate prevented the translation of a reporter plasmid where bim-3′UTR mRNA sequence was cloned downstream of a luciferase gene. These results suggest that repression of bim mRNA translation through binding to the 3′UTR constitutes a novel cytoprotective mechanism of Hsp27 during stress in neurons. PMID:25187648

  11. Cytotoxicity and Hsp 70 induction in Hep G2 cells in response to zearalenone and cytoprotection by sub-lethal heat shock

    International Nuclear Information System (INIS)

    Hassen, Wafa; Golli, Emna El; Baudrimont, Isabelle; Mobio, A. Theophile; Ladjimi, M. Moncef; Creppy, E. Edmond; Bacha, Hassen

    2005-01-01

    Zearalenone (ZEN) is a mycotoxin with several adverse effects in laboratory and domestic animals. The mechanism of ZEN toxicity that involves mainly binding to oestrogen receptors and inhibition of macromolecules synthesis is not fully understood. Using human hepatocytes Hep G2 cells as a model, the aim of this work was (i) to investigate the ability of ZEN to induce heat shock proteins Hsp 70 and (ii) to find out the mechanisms of ZEN cytotoxicity by examining cell proliferation and protein synthesis. Our study demonstrated that ZEN induces Hsp 70 expression in a time and dose-dependant manner; this induction occurs at non-cytotoxic concentrations, it could be therefore considered as a biomarker of toxicity. A cytoprotective effect of Hsp 70 was elicited when Hep G2 cells were exposed to Sub-Lethal heat shock prior to ZEN treatment and evidenced by a reduced ZEN cytolethality. This cytoprotection suggests that Hsp 70 may constitute an important cellular defence mechanism. Finally, our data show that ZEN is cytotoxic in Hep G2 cells by inhibiting cell proliferation and total protein synthesis and pointed out oxidative damage as possible pathway involved in ZEN toxicity; however, other investigations are needed to further confirm Zen induced oxidative stress

  12. Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon.

    Directory of Open Access Journals (Sweden)

    Juan Del Coso

    Full Text Available Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs to explain inter-individual variability of serum creatine kinase (CK concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A.Using Williams and Folland's model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK <400 U·L-1 vs. marathoners with a high CK response (n = 31; serum CK ≥400 U·L-1.At the end of the race, low CK responders had lower serum CK (290±65 vs. 733±405 U·L-1; P<0.01 and myoglobin concentrations (443±328 vs. 1009±971 ng·mL-1, P<0.01 than high CK responders. Although the groups were similar in age, anthropometric characteristics, running experience and training habits, total genotype score was higher in low CK responders than in high CK responders (5.2±1.4 vs. 4.4±1.7 point, P = 0.02.Marathoners with a lower CK response after the race had a more favorable polygenic profile than runners with high serum CK concentrations. This might suggest a significant role of genetic polymorphisms in the levels of exertional muscle damage and rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise.

  13. Cardiopulmonary exercise testing in the assessment of exertional dyspnea

    Directory of Open Access Journals (Sweden)

    Debapriya Datta

    2015-01-01

    Full Text Available Dyspnea on exertion is a commonly encountered problem in clinical practice. It is usually investigated by resting tests such as pulmonary function tests and echocardiogram, which may at times can be non-diagnostic. Cardiopulmonary exercise testing (CPET measures physiologic parameters during exercise which can enable accurate identification of the cause of dyspnea. Though CPET has been around for decades and provides valuable and pertinent physiologic information on the integrated cardiopulmonary responses to exercise, it remains underutilized. The objective of this review is to provide a comprehensible overview of the underlying principles of exercise physiology, indications and contraindications of CPET, methodology and interpretative strategies involved and thereby increase the understanding of the insights that can be gained from the use of CPET.

  14. Physical exertion and working efficiency of reforestation workers.

    Science.gov (United States)

    Hodges, Alastair Nh; Kennedy, Michael D

    2011-06-28

    The purpose of this study was to quantify the physical exertion during tree planting work and to examine the relationships between exertion, task efficiency, and productivity. Heart rate (HR) was monitored on 34 tree planters while they worked. HR data was collected for a complete working day on 19 subjects and for shorter periods of time on 15 subjects. Video of work tasks was recorded on 22 subjects (video was recorded on 7 of the subjects for whom HR was monitored through a full working day) and analyzed for working pace and proportion of time spent on each task. HR during a full day (9.0 ± 1.2 hours) of tree planting work was 115.2 ± 8.8 beats.min-1, and working HR was 128.2 ± 15.6 beats.min-1 for 82.5 ± 6.8% of the work day. Mean work pace was 452 ± 174 trees.h-1, and the proportion of time spent planting each tree was 53 ± 8% of the working time. Significant (P < 0.05) positive correlations were found between work pace and experience level, and between work pace and working HR, and a significant (P < 0.05) negative correlation was found between experience level and HR for a given work pace. No significant relationships were found between experience level or work pace and the proportion of time spent planting each tree. Tree planters work at approximately 65% of age-predicted HRmax, and maintain HR at approximately 59% of HRmax throughout the entire working day. Productivity in these workers appears to be related to effort rather than to experience or task efficiency per se.

  15. The use of subjective rating of exertion in Ergonomics.

    Science.gov (United States)

    Capodaglio, P

    2002-01-01

    In Ergonomics, the use of psychophysical methods for subjectively evaluating work tasks and determining acceptable loads has become more common. Daily activities at the work site are studied not only with physiological methods but also with perceptual estimation and production methods. The psychophysical methods are of special interest in field studies of short-term work tasks for which valid physiological measurements are difficult to obtain. The perceived exertion, difficulty and fatigue that a person experiences in a certain work situation is an important sign of a real or objective load. Measurement of the physical load with physiological parameters is not sufficient since it does not take into consideration the particular difficulty of the performance or the capacity of the individual. It is often difficult from technical and biomechanical analyses to understand the seriousness of a difficulty that a person experiences. Physiological determinations give important information, but they may be insufficient due to the technical problems in obtaining relevant but simple measurements for short-term activities or activities involving special movement patterns. Perceptual estimations using Borg's scales give important information because the severity of a task's difficulty depends on the individual doing the work. Observation is the most simple and used means to assess job demands. Other evaluations integrating observation are the followings: indirect estimation of energy expenditure based on prediction equations or direct measurement of oxygen consumption; measurements of forces, angles and biomechanical parameters; measurements of physiological and neurophysiological parameters during tasks. It is recommended that determinations of performances of occupational activities assess rating of perceived exertion and integrate these measurements of intensity levels with those of activity's type, duration and frequency. A better estimate of the degree of physical activity

  16. Traction Stresses Exerted by Adherent Cells: From Angiogenesis to Metastasis

    Science.gov (United States)

    Reinhart-King, Cynthia

    2010-03-01

    Cells exert traction stresses against their substrate that mediate their ability to sense the mechanical properties of their microenvironment. These same forces mediate cell adhesion, migration and the formation of stable cell-cell contacts during tissue formation. In this talk, I will present our data on the traction stresses generated by endothelial cells and metastatic breast cancer cells focused on understanding the processes of angiogenesis and metastasis, respectively. In the context of capillary formation, our data indicate that the mechanics of the substrate play a critical role in establishing endothelial cell-cell contacts. On more compliant substrates, endothelial cell shape and traction stresses polarize and promote the formation of stable cell-cell contacts. On stiffer substrates, traction stresses are less polarized and cell connectivity is disrupted. These data indicate that the mechanical properties of the microenvironment may drive cell connectivity and the formation of stable cell-cell contacts through the reorientation of traction stresses. In our studies of metastatic cell migration, we have found that traction stresses increase with increasing metastatic potential. We investigated three lines of varying metastatic potential (MCF10A, MCF7 and MDAMB231). MDAMB231, which are the most invasive, exert the most significant forces as measured by Traction Force Microscopy. These data present the possibility that cellular traction stress generation aids in the ability of metastatic cells to migrate through the matrix-dense tumor microenvironment. Such measurements are integral to link the mechanical and chemical microenvironment with the resulting response of the cell in health and disease.

  17. Association between work engagement and perceived exertion among healthcare workers

    Directory of Open Access Journals (Sweden)

    Rodrigo Luiz Carregaro

    Full Text Available INTRODUCTION: Complaints and musculoskeletal discomforts are common manifestations of individuals affected by work-related disorders (WRMD, and the influence of individual and/or psychosocial risk factors may play a significant role in WRMD development. OBJECTIVE: To evaluate and to compare work engagement (WE and ratings of perceived exertion (RPE and to assess the association between indexes of WE and RPE among healthcare workers. MATERIALS AND METHODS: Seventeen female subjects (36 ± 11 years, 1.58 ± 0.06 m and 59 ± 9 kg participated, all officially employed on a nonprofit agency. The Nordic Questionnaire was used to evaluate musculoskeletal complaints and the Borg Scale used to evaluate the RPE. The Utrecht Work Engagement Scale quantified WE (vigor, dedication and absorption domains. Participants were divided into two groups, according to their sectors: healthcare clinics and institution for the elderly. The independent student t test was used to verify differences between groups and the chi-square test to verify associations between variables. RESULTS: All subjects reported musculoskeletal complaints, mainly in the low back (58%. RPE did not differ between groups, while in the vigor, it was found a significant statistically difference (p = 0.035. An association between RPE and vigor and RPE and dedication was establish (p = 0.02 and p = 0.036, respectively. CONCLUSION: The association between WE and RPE suggests that workers with lower indexes of vigor and dedication may perceive greater physical demand, which can be imposed by work demands.

  18. Is muscle energy production disturbed in exertional heat stroke?

    Science.gov (United States)

    Sagui, Emmanuel; Abriat, Amandine; Kozak-Ribbens, Geneviève; Foutrier-Morello, Catherine; Bernard, Monique; Canini, Frédéric; Brosset, Christian; Bendahan, David

    2014-03-01

    Exertional heat stroke (EHS) is a life-threatening disease that shares some clinical similarities with malignant hyperthermia (MH). By use of (31)Phosphorus magnetic resonance spectroscopy (MRS), EHS patients with MH susceptibility and MH patients shared common metabolic abnormalities. The aim of this study was to determine whether subjects who suffered from an EHS episode had disturbed muscle energetics. This retrospective study was performed within the French database of military subjects that were explored from 2004 to 2010 after they suffered an EHS. All subjects had both in vitro contracture test to determine their MH susceptibility and (31)Phosphorus MRS at 4.7 Tesla to assess muscle energetics by means of MRS score, a composite score corresponding to the sum of metabolic abnormalities recorded during a standardized rest-exercise-recovery protocol. 437 subjects were investigated and 32.5% of them exhibited abnormal MRS score. MRS score did not segregate subjects on demographic, clinical, or biological grounds. No clear correlation could be done between MH status and MRS score. These results did not confirm the potential relationship between calcium homeostasis and muscle energetics previously reported. However, muscle energy production was disturbed in a significant number of EHS subjects. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  19. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-07-01

    Full Text Available Astaxanthin (ATX is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and peroxisome proliferator-activated receptor gamma (PPARγ. Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  20. Ratings of perceived exertion during aerobic exercise in multiple sclerosis.

    Science.gov (United States)

    Morrison, Elizabeth H; Cooper, Dan M; White, Lesley J; Larson, Jennifer; Leu, Szu-Yun; Zaldivar, Frank; Ng, Alexander V

    2008-08-01

    To compare ratings of perceived exertion (RPEs) during aerobic exercise in people with multiple sclerosis (MS) and control participants. Prospective experimental study. An exercise testing laboratory. Sedentary adults (n=12) with mild MS (Expanded Disability Status Scale score exercise test on a cycle ergometer with breath-by-breath gas measurements and continuous heart rate monitoring. After completing the Modified Fatigue Impact Scale, participants rated their effort sense every 30 seconds during exercise using the modified Borg 10-point scale. The 2 study groups showed similar baseline characteristics except for higher fatigue scores in the MS group. There were no significant differences for any fitness measure, including oxygen cost slope (in VO(2) x min(-1) x W(-1)), VO(2), or work rate during exercise. Neither heart rate nor RPE--measured at 25%, 50%, 75%, and 100% of VO(2)peak--differed between groups. Despite greater reported fatigue levels, participants with MS showed similar RPE and physiologic responses to submaximal and maximal exercise compared with controls. In MS, the Borg 10-point scale may help improve evidence-based exercise prescriptions, which otherwise may be limited by fatigue, motor impairment, heat sensitivity, or autonomic dysfunction.

  1. Matrix Metalloproteinase 9 Exerts Antiviral Activity against Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Abdoulaye J Dabo

    Full Text Available Increased lung levels of matrix metalloproteinase 9 (MMP9 are frequently observed during respiratory syncytial virus (RSV infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells. Using knockout mice the effect of the loss of Mmp9 expression was examined during RSV infection to demonstrate MMP9's role in viral clearance and disease progression. Seven days following RSV infection, Mmp9-/- mice displayed substantial weight loss, increased RSV-induced airway hyperresponsiveness (AHR and reduced clearance of RSV from the lungs compared to wild type mice. Although total bronchoalveolar lavage fluid (BALF cell counts were similar in both groups, neutrophil recruitment to the lungs during RSV infection was significantly reduced in Mmp9-/- mice. Reduced neutrophil recruitment coincided with diminished RANTES, IL-1β, SCF, G-CSF expression and p38 phosphorylation. Induction of p38 signaling was required for RANTES and G-CSF expression during RSV infection in airway epithelial cells. Therefore, MMP9 in RSV lung infection significantly enhances neutrophil recruitment, cytokine production and viral clearance while reducing AHR.

  2. Petiveria alliacea exerts mnemonic and learning effects on rats.

    Science.gov (United States)

    Silva, Mallone Lopes; Luz, Diandra Araújo; Paixão, Thiago Portal da; Silva, João Paulo Bastos; Belém-Filho, Ivaldo Jesus Almeida; Fernandes, Luanna Melo Pereira; Gonçalves, Ana Cristina Baetas; Fontes-Júnior, Enéas Andrade; de Andrade, Marciene Ataíde; Maia, Cristiane Socorro Ferraz

    2015-07-01

    Petiveria alliacea L. (Phytolaccaceae) is a perennial shrub native to the Amazon region and other tropical areas such as Central America and the Caribbean. Popularly known as mucuracaá, P. alliacea is used in the folk medicine for a broad variety of therapeutic purpose and also in religious ceremonies by slaves as a sedative, which highlights its properties on the Central Nervous System (CNS). The present study evaluated the effects of the P. alliacea leaves hydroalcoholic extract (PaLHE) on the cognition, including learning and memory. Three-month-old male and female Wistar rats (n=8-10/group) were administered with 900mg/kg of PaLHE. The behavioral assays included Step-down Inhibitory avoidance (IA) and Morris Water Maze (MWM) tests. Consistent with our previous reports, P. alliacea improved long-term memory. It also exerted previously unreported effects on short-term and spatial memory improvement, and increased learning in the tasks. The P. alliacea extract elicited mnemonic effects and improved the learning process in both IA and MWM tests. Our results highlight the importance of further studies in order to identify the active substances of the PaLHE and investigate the pharmacological mechanisms that underlies the reported effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Synthetic oligorotaxanes exert high forces when folding under mechanical load

    Science.gov (United States)

    Sluysmans, Damien; Hubert, Sandrine; Bruns, Carson J.; Zhu, Zhixue; Stoddart, J. Fraser; Duwez, Anne-Sophie

    2018-01-01

    Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3-5. Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6-8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

  4. Effect of radiation exerted to creep rate of resin

    Energy Technology Data Exchange (ETDEWEB)

    Hirade, Tetsuya; Hama, Yoshimasa (Waseda Univ., Tokyo (Japan)); Udagawa, Akira; Takeda, Nobuo; Seguchi, Tadao

    1990-12-01

    One of the high performance composite materials which became to be manufactured by the progress of working techniques and the improvement of material performance is fiber-reinforced plastics (FRP). Carbon fiber-reinforced plastics (CFRP) are used as space and aircraft material, and glass fiber-reinforced plastics (GFRP) are expected as the structural material for superconducting magnets in nuclear fusion. In these materials, the use for long term must be considered, and the creep characteristics, of resin should be taken as one of the design factors. Therefore, the effect that radiation exerted to the stress relaxation of epoxy resin was measured, and its mechanism was investigated. The sample was bisphenol F system epoxy. The measurements of DSC, dynamic viscoelasticity and stress relaxation were carried out. The stress relaxation in bisphenol F system epoxy resin occurred down to 10 % of the initial stress only at 3 MGy. This is the dose far lower than the life in the radiation resistance of this resin. It is considered that the stress relaxation of the resin was caused by the change in molecular structure instead of the cut of molecular chain, as energy was given to the microscopic region by the interaction with radiation. (K.I.).

  5. Cytoprotection of human endothelial cells against oxidative stress by 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im): application of systems biology to understand the mechanism of action.

    Science.gov (United States)

    Wang, Xinyu; Bynum, James A; Stavchansky, Solomon; Bowman, Phillip D

    2014-07-05

    Cellular damage from oxidative stress, in particular following ischemic injury, occurs during heart attack, stroke, or traumatic injury, and is potentially reducible with appropriate drug treatment. We previously reported that caffeic acid phenethyl ester (CAPE), a plant-derived polyphenolic compound, protected human umbilical vein endothelial cells (HUVEC) from menadione-induced oxidative stress and that this cytoprotective effect was correlated with the capacity to induce heme oxygenase-1 (HMOX1) and its protein product, a phase II cytoprotective enzyme. To further improve this cytoprotective effect, we studied a synthetic triterpenoid, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), which is known as a potent phase II enzyme inducer with antitumor and anti-inflammatory activities, and compared it to CAPE. CDDO-Im at 200nM provided more protection to HUVEC against oxidative stress than 20μM CAPE. We explored the mechanism of CDDO-Im cytoprotection with gene expression profiling and pathway analysis and compared to that of CAPE. In addition to potent up-regulation of HMOX1, heat shock proteins (HSP) were also found to be highly induced by CDDO-Im in HUVEC. Pathway analysis results showed that transcription factor Nrf2-mediated oxidative stress response was among the top canonical pathways commonly activated by both CDDO-Im and CAPE. Compared to CAPE, CDDO-Im up-regulated more HSP and some of them to a much higher extent. In addition, CDDO-Im treatment affected Nrf2 pathway more significantly. These findings may provide an explanation why CDDO-Im is a more potent cytoprotectant than CAPE against oxidative stress in HUVEC. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Joydeb Kumar [College of Pharmacy, Keimyung University, Daegu 704-701 (Korea, Republic of); Liu, Lijia; Shin, Jun-Wan [Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of); Surh, Young-Joon, E-mail: surh@plaza.snu.ac.kr [Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul 110-799 (Korea, Republic of)

    2013-09-06

    Highlights: •Thymoquinone inhibits phorbol ester-induced COX-2 expression in mouse skin. •Thymoquinone attenuates phosphorylation of IκBα and DNA binding of NF-κB in mouse skin. •Thymoquinone inhibits phosphorylation of p38 MAP kinase, JNK and Akt in mouse skin. •Thymoquinone induces the expression of cytoprotective proteins in mouse skin. -- Abstract: Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin.

  7. Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo

    International Nuclear Information System (INIS)

    Kundu, Joydeb Kumar; Liu, Lijia; Shin, Jun-Wan; Surh, Young-Joon

    2013-01-01

    Highlights: •Thymoquinone inhibits phorbol ester-induced COX-2 expression in mouse skin. •Thymoquinone attenuates phosphorylation of IκBα and DNA binding of NF-κB in mouse skin. •Thymoquinone inhibits phosphorylation of p38 MAP kinase, JNK and Akt in mouse skin. •Thymoquinone induces the expression of cytoprotective proteins in mouse skin. -- Abstract: Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin

  8. Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy

    Science.gov (United States)

    He, Jun; Yu, Jing-Jie; Xu, Qing; Wang, Lin; Zheng, Jenny Z; Liu, Ling-Zhi; Jiang, Bing-Hua

    2015-01-01

    Cisplatin is commonly used in ovarian cancer treatment by inducing apoptosis in cancer cells as a result of lethal DNA damage. However, the intrinsic and acquired resistance to cisplatin in cancer cells remains a big challenge for improving overall survival. The cyto-protective functions of autophagy in cancer cells have been suggested as a potential mechanism for chemoresistance. Here, we reported MIR152 as a new autophagy-regulating miRNA that plays a role in cisplatin-resistance. We showed that MIR152 expression was dramatically downregulated in the cisplatin-resistant cell lines A2780/CP70, SKOV3/DDP compared with their respective parental cells, and in ovarian cancer tissues associated with cisplatin-resistance. Overexpression of MIR152 sensitized cisplatin-resistant ovarian cancer cells by reducing cisplatin-induced autophagy, enhancing cisplatin-induced apoptosis and inhibition of cell proliferation. A mouse subcutaneous xenograft tumor model using A2780/CP70 cells with overexpressing MIR152 was established and displayed decreased tumor growth in response to cisplatin. We also identified that ATG14 is a functional target of MIR152 in regulating autophagy inhibition. Furthermore, we found that EGR1 (early growth response 1) regulated the MIR152 gene at the transcriptional level. Ectopic expression of EGR1 enhanced efficacy of chemotherapy in A2780/CP70 cells. More importantly, these findings were relevant to clinical cases. Both EGR1 and MIR152 expression levels were significantly lower in ovarian cancer tissues with high levels of ERCC1 (excision repair cross-complementation group 1), a marker for cisplatin-resistance. Collectively, these data provide insights into novel mechanisms for acquired cisplatin-resistance. Activation of EGR1 and MIR152 may be a useful therapeutic strategy to overcome cisplatin-resistance by preventing cyto-protective autophagy in ovarian cancer. PMID:25650716

  9. Hsp27 binding to the 3'UTR of bim mRNA prevents neuronal death during oxidative stress-induced injury: a novel cytoprotective mechanism.

    Science.gov (United States)

    Dávila, David; Jiménez-Mateos, Eva M; Mooney, Claire M; Velasco, Guillermo; Henshall, David C; Prehn, Jochen H M

    2014-11-01

    Neurons face a changeable microenvironment and therefore need mechanisms that allow rapid switch on/off of their cytoprotective and apoptosis-inducing signaling pathways. Cellular mechanisms that control apoptosis activation include the regulation of pro/antiapoptotic mRNAs through their 3'-untranslated region (UTR). This region holds binding elements for RNA-binding proteins, which can control mRNA translation. Here we demonstrate that heat shock protein 27 (Hsp27) prevents oxidative stress-induced cell death in cerebellar granule neurons by specific regulation of the mRNA for the proapoptotic BH3-only protein, Bim. Hsp27 depletion induced by oxidative stress using hydrogen peroxide (H2O2) correlated with bim gene activation and subsequent neuronal death, whereas enhanced Hsp27 expression prevented these. This effect could not be explained by proteasomal degradation of Bim or bim promoter inhibition; however, it was associated with a specific increase in the levels of bim mRNA and with its binding to Hsp27. Finally, we determined that enhanced Hsp27 expression in neurons exposed to H2O2 or glutamate prevented the translation of a reporter plasmid where bim-3'UTR mRNA sequence was cloned downstream of a luciferase gene. These results suggest that repression of bim mRNA translation through binding to the 3'UTR constitutes a novel cytoprotective mechanism of Hsp27 during stress in neurons. © 2014 Dávila et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  10. Rotenone exerts developmental neurotoxicity in a human brain spheroid model.

    Science.gov (United States)

    Pamies, David; Block, Katharina; Lau, Pierre; Gribaldo, Laura; Pardo, Carlos A; Barreras, Paula; Smirnova, Lena; Wiersma, Daphne; Zhao, Liang; Harris, Georgina; Hartung, Thomas; Hogberg, Helena T

    2018-02-08

    Growing concern suggests that some chemicals exert (developmental) neurotoxicity (DNT and NT) and are linked to the increase in incidence of autism, attention deficit and hyperactivity disorders. The high cost of routine tests for DNT and NT assessment make it difficult to test the high numbers of existing chemicals. Thus, more cost effective neurodevelopmental models are needed. The use of induced pluripotent stem cells (iPSC) in combination with the emerging human 3D tissue culture platforms, present a novel tool to predict and study human toxicity. By combining these technologies, we generated multicellular brain spheroids (BrainSpheres) from human iPSC. The model has previously shown to be reproducible and recapitulates several neurodevelopmental features. Our results indicate, rotenone's toxic potency varies depending on the differentiation status of the cells, showing higher reactive oxygen species (ROS) and higher mitochondrial dysfunction during early than later differentiation stages. Immuno-fluorescence morphology analysis after rotenone exposure indicated dopaminergic-neuron selective toxicity at non-cytotoxic concentrations (1 μM), while astrocytes and other neuronal cell types were affected at (general) cytotoxic concentrations (25 μM). Omics analysis showed changes in key pathways necessary for brain development, indicating rotenone as a developmental neurotoxicant and show a possible link between previously shown effects on neurite outgrowth and presently observed effects on Ca2+ reabsorption, synaptogenesis and PPAR pathway disruption. In conclusion, our BrainSpheres model has shown to be a reproducible and novel tool to study neurotoxicity and developmental neurotoxicity. Results presented here support the idea that rotenone can potentially be a developmental neurotoxicant. Copyright © 2018. Published by Elsevier Inc.

  11. Relationship between perceived exertion during exercise and subsequent recovery measurements

    Directory of Open Access Journals (Sweden)

    TN Mann

    2016-12-01

    Full Text Available The return towards resting homeostasis in the post-exercise period has the potential to represent the internal training load of the preceding exercise bout. However, the relative potential of metabolic and autonomic recovery measurements in this role has not previously been established. Therefore the aim of this study was to investigate which of 4 recovery measurements was most closely associated with Borg’s Rating of Perceived Exertion (RPE, a measurement widely acknowledged as an integrated measurement of the homeostatic stress of an exercise bout. A heterogeneous group of trained and untrained participants (n = 36 completed a bout of exercise on the treadmill (3 km at 70% of maximal oxygen uptake followed by 1 hour of controlled recovery. Expired respiratory gases and heart rate (HR were measured throughout the exercise and recovery phases of the trial with recovery measurements used to calculate the magnitude of excess post-exercise oxygen consumption (EPOCMAG, the time constant of the EPOC curve (EPOCτ, 1 min heart rate recovery (HRR60s and the time constant of the HR recovery curve (HRRτ for each participant. RPE taken in the last minute of exercise was significantly associated with HRR60s (r=-0.69, EPOCτ (r=0.52 and HRRτ (r=0.43 but not with EPOCMAG. This finding suggests that, of the 4 recovery measurements under investigation, HRR60s shows modest potential to represent inter-individual variation in the homeostatic stress of a standardized exercise bout, in a group with a range of fitness levels.

  12. Relationship between perceived exertion during exercise and subsequent recovery measurements.

    Science.gov (United States)

    Mann, T N; Lamberts, R P; Nummela, A; Lambert, M I

    2017-03-01

    The return towards resting homeostasis in the post-exercise period has the potential to represent the internal training load of the preceding exercise bout. However, the relative potential of metabolic and autonomic recovery measurements in this role has not previously been established. Therefore the aim of this study was to investigate which of 4 recovery measurements was most closely associated with Borg's Rating of Perceived Exertion (RPE), a measurement widely acknowledged as an integrated measurement of the homeostatic stress of an exercise bout. A heterogeneous group of trained and untrained participants (n = 36) completed a bout of exercise on the treadmill (3 km at 70% of maximal oxygen uptake) followed by 1 hour of controlled recovery. Expired respiratory gases and heart rate (HR) were measured throughout the exercise and recovery phases of the trial with recovery measurements used to calculate the magnitude of excess post-exercise oxygen consumption (EPOC MAG ), the time constant of the EPOC curve (EPOCτ), 1 min heart rate recovery (HRR 60s ) and the time constant of the HR recovery curve (HRRτ) for each participant. RPE taken in the last minute of exercise was significantly associated with HRR 60s (r=-0.69), EPOCτ (r=0.52) and HRRτ (r=0.43) but not with EPOC MAG . This finding suggests that, of the 4 recovery measurements under investigation, HRR 60s shows modest potential to represent inter-individual variation in the homeostatic stress of a standardized exercise bout, in a group with a range of fitness levels.

  13. Humanin Exerts Neuroprotection During Cardiac Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Kumfu, Sirinart; Charununtakorn, Savitree T; Jaiwongkam, Thidarat; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-01-01

     Cardiac ischemia-reperfusion (I/R) injury has been shown to impair brain function. Humanin analogue (HNG) given prior to cardiac ischemia has been shown to attenuate both heart and brain mitochondrial dysfunction caused by cardiac I/R injury. In a clinical setting, patients received medical treatment for acute myocardial infarction either during or after the onset of myocardial ischemia; thus, in this study, we tested the hypothesis that the administration of HNG during cardiac I/R injury has therapeutic potential for brain protection. Thirty-six male Wistar rats were divided into two groups: a cardiac I/R group (n = 30), and a sham group (n = 6). The I/R rats were then divided into five subgroups to receive: 1) vehicle; 2) HNG (84 μg/kg); 3) HNG (168 μg/kg); 4) HNG (252 μg/kg) intravenously administered during the cardiac-ischemia; and 5) HNG at 252 μg/kg given at the onset of reperfusion. At the end of treatment, brains were removed for determination of blood-brain barrier (BBB) breakdown, oxidative stress, brain mitochondrial function, brain mitochondrial dynamics, p-tau, amyloid-β (Aβ) and apoptosis. HNG at a dose of 168 and 252 μg/kg administered during ischemia, and 252 μg/kg given at the onset of reperfusion effectively attenuated the brain mitochondrial dysfunction, tau hyperphosphorylation and Aβ accumulation, and apoptosis, without reducing BBB breakdown, brain oxidative stress, or mitochondrial dynamic, caused by cardiac I/R injury. In conclusion, humanin exerted neuroprotection during induced cardiac I/R injury via improvement in brain mitochondrial function, and the reduction of Alzheimer's disease pathology and apoptosis.

  14. Outcomes of exertional rhabdomyolysis following high-intensity resistance training.

    Science.gov (United States)

    Huynh, A; Leong, K; Jones, N; Crump, N; Russell, D; Anderson, M; Steinfort, D; Johnson, D F

    2016-05-01

    High-intensity resistance training (HIRT) programmes are increasingly popular amongst personal trainers and those attending gymnasiums. We report the experience of exertional rhabdomyolysis (ER) at two tertiary hospitals in Melbourne, Australia. To compare the clinical outcomes of ER with other causes of rhabdomyolysis. Retrospective cross-sectional study of patients presenting with a serum creatine kinase (CK) of greater than 25 000 units/L from 1 September 2013 to 31 August 2014 at two tertiary referral hospitals in Melbourne, Australia. Records were examined to identify care measures implemented during hospital stay, clinical outcomes during admission and on subsequent follow up. Thirty four cases of rhabdomyolysis with a CK of greater than 25 000 units/L (normal range: 20-180 units/L) were identified during the 12-month study period. Twelve of the 34 cases (35%) had ER with 10 of 12 related to HIRT. No acute kidney injury, intensive care admission or death were seen among those with ER. All cases were managed conservatively, with 11 admitted and 9 receiving intravenous fluids only. In contrast, patients with rhabdomyolysis from other causes experienced significantly higher rates of intensive care admission (64%, P = 0.0002), acute kidney injury (82%, P = 0.0001) and death (27%, P = 0.069). ER resulting from HIRT appears to have a benign course compared with rhabdomyolysis of other aetiologies in patients with a serum CK greater than 25 000 units/L. Conservative management of ER appears to be adequate, although this requires confirmation in future prospective studies. © 2016 Royal Australasian College of Physicians.

  15. Effects of music and video on perceived exertion during high-intensity exercise

    Directory of Open Access Journals (Sweden)

    Enoch C. Chow

    2017-03-01

    Conclusion: Music and video in combination may result in lower perceived exertion during high-intensity exercise when compared to music or video in isolation. Future research will be necessary to test if reductions in perceived exertion in response to dissociative attentional stimuli have implications for exercise adherence.

  16. Impaired Player-Coach Perceptions of Exertion and Recovery During Match Congestion

    NARCIS (Netherlands)

    Doeven, Steven H.; Brink, Michel S.; Frencken, Wouter G. P.; Lemmink, Koen A. P. M.

    2017-01-01

    During intensified phases of competition, attunement of exertion and recovery is crucial to maintain performance. Although a mismatch between coach' and players' perceptions of training load is demonstrated, it is unknown if these discrepancies also exist for match exertion and recovery. PURPOSE:

  17. Stiffness and thickness of fascia do not explain chronic exertional compartment syndrome

    DEFF Research Database (Denmark)

    Dahl, Morten; Hansen, Philip; Stål, Per

    2011-01-01

    Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown.......Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown....

  18. Fatigue induced by physical and mental exertion increases perception of effort and impairs subsequent endurance performance

    Directory of Open Access Journals (Sweden)

    Benjamin Pageaux

    2016-11-01

    Full Text Available Endurance performance involves the prolonged maintenance of constant or self-regulated power/velocity or torque/force. While the impact of numerous determinants of endurance performance has been previously reviewed, the impact of fatigue on subsequent endurance performance still needs to be documented. This review aims to present the impact of fatigue induced by physical or mental exertion on subsequent endurance performance. For the purpose of this review, endurance performance refers to performance during whole-body or single-joint endurance exercise soliciting mainly the aerobic energy system. First, the impact of physical and mental exertion on force production capacity is presented, with specific emphasize on the fact that solely physical exertion and not mental exertion induces a decrease in force production capacity of the working muscles. Then, the negative impact of fatigue induced by physical exertion and mental exertion on subsequent endurance performance is highlighted based on experimental data. Perception of effort being identified as the variable altered by both prior physical exertion and mental exertion, future studies should investigate the underlying mechanisms increasing perception of effort overtime and in presence of fatigue during endurance exercise. Perception of effort should be considered not only as marker of exercise intensity, but also as a factor limiting endurance performance. Therefore, using a psychophysiological approach to explain the regulation of endurance performance would allow a better understanding of the interaction between physiological and psychological phenomena known to impact endurance performance.

  19. Seaweed extracts and unsaturated fatty acid constituents from the green alga Ulva lactuca as activators of the cytoprotective Nrf2–ARE pathway

    Science.gov (United States)

    Wang, Rui; Paul, Valerie J.; Luesch, Hendrik

    2013-01-01

    Increased amounts of reactive oxygen species (ROS) have been implicated in many pathological conditions, including cancer. The major machinery that the cell employs to neutralize excess ROS is through the activation of the antioxidant-response element (ARE) that controls the activation of many phase II detoxification enzymes. The transcription factor that recognizes the ARE, Nrf2, can be activated by a variety of small molecules, most of which contain an α,β-unsaturated carbonyl system. In the pursuit of chemopreventive agents from marine organisms, we built, fractionated, and screened a library of 30 field-collected eukaryotic algae from Florida. An edible green alga, Ulva lactuca, yielded multiple active fractions by ARE–luciferase reporter assay. We isolated three monounsaturated fatty acid (MUFA) derivatives as active components, including a new keto-type C18 fatty acid (1), the corresponding shorter chain C16 acid (2), and an amide derivative (3) of the C18 acid. Their chemical structures were elucidated by NMR and mass spectrometry. All three contain the conjugated enone motif between C7 and C9, which is thought to be responsible for the ARE activity. Subsequent biological studies focused on 1, the most active and abundant ARE activator isolated. C18 acid 1 induced the expression of ARE-regulated cytoprotective genes, including NAD(P)H:quinone oxidoreductase 1, heme oxygenase 1, thioredoxin reductase 1, both subunits of the glutamate–cysteine ligase (catalytic subunit and modifier subunit), and the cystine/glutamate exchange transporter, in IMR-32 human neuroblastoma cells. Its cellular activity requires the presence of Nrf2 and PI3K function, based on RNA interference and pharmacological inhibitor studies, respectively. Treatment with 1 led only to Nrf2 activation, and not the increase in production of NRF2 mRNA. To test its ARE activity and cytoprotective potential in vivo, we treated mice with a single dose of a U. lactuca fraction that was enriched

  20. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    International Nuclear Information System (INIS)

    Li, Kuiqing; Chen, Xu; Liu, Cheng; Gu, Peng; Li, Zhuohang; Wu, Shaoxu; Xu, Kewei; Lin, Tianxin; Huang, Jian

    2015-01-01

    Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway

  1. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Kuiqing; Chen, Xu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Liu, Cheng [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Gu, Peng; Li, Zhuohang; Wu, Shaoxu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Xu, Kewei [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Lin, Tianxin, E-mail: tianxinl@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Huang, Jian, E-mail: urolhj@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China)

    2015-05-01

    Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway.

  2. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress.

    Science.gov (United States)

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki; Izumi, Yasuhiko; Park, Si-Bum; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2016-04-01

    Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. Copyright © 2016. Published by Elsevier Inc.

  3. Mechanisms of CDDO-imidazolide-mediated cytoprotection against acrolein-induced neurocytotoxicity in SH-SY5Y cells and primary human astrocytes.

    Science.gov (United States)

    Speen, Adam; Jones, Colton; Patel, Ruby; Shah, Halley; Nallasamy, Palanisamy; Brooke, Elizabeth A S; Zhu, Hong; Li, Y Robert; Jia, Zhenquan

    2015-10-01

    Acrolein is a ubiquitous unsaturated aldehyde has been implicated in the pathogenesis of various neurological disorders. However, limited study has been conducted into potential therapeutic protection and underlying mechanism against acrolein-induced cytotoxicity via upregulation of cellular aldehyde-detoxification defenses. In this study we have utilized RA-differentiated human SH-SY5Y cells and primary human astrocytes to investigate the induction of glutathione (GSH) by the synthetic triterpenoid 2-cyano-3,12-dixooleana-1,9-dien-28-imidazolide (CDDO-Im) and the protective effects CDDO-Im-mediated antioxidant defenses on acrolein toxicity. Acrolein exposure to RA-differentiated SH-SY5Y cells resulted in a significant time dependent depletion of cellular GSH preceding a reduction in cell viability and LDH release. Further, we demonstrated the predominance of cellular GSH in protection against acrolein-induced cytotoxicity. Buthionine sulfoximine (BSO) at 25μM dramatically depleted GSH and significantly potentiated acrolein-induced cytotoxicity. Pretreatment of the cells with 100nM CDDO-Im afforded a dramatic protection against acrolein-induced cytotoxicity. Pretreatment of BSO and CDDO was found to prevent the CDDO-Im-mediated GSH induction and partially reversed the cytoprotective effects of CDDO-Im against acrolein cytotoxicity. Overall, this study represents for the first time the CDDO-Im mediated upregulation of GSH is a predominant mechanism against acrolein-induced neurotoxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema.

    Science.gov (United States)

    Tan, Li Hui; Bahmed, Karim; Lin, Chih-Ru; Marchetti, Nathaniel; Bolla, Sudhir; Criner, Gerard J; Kelsen, Steven; Madesh, Muniswamy; Kosmider, Beata

    2018-02-23

    Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary surfactants and proliferate to restore the epithelium after damage. We isolated ATII cells from control non-smokers, smokers and patients with emphysema to determine the role of NFE2 (nuclear factor, erythroid-derived 2). NFE2 is a heterodimer composed of two subunits, a 45 kDa (p45 NFE2) and 18 kDa (p18 NFE2) polypeptides. Low expression of p45 NFE2 in patients with emphysema correlated with a high ECM degradation. Moreover, we found that NFE2 knockdown increased cell death induced by cigarette smoke extract. We also studied the cross talk between p45 NFE2 and DJ-1. DJ-1 protein is a redox-sensitive chaperone that protects cells from oxidative stress. We detected that cigarette smoke significantly increased p45 NFE2 levels in DJ-1 KO mice compared to wild-type mice. Our results indicate that p45 NFE2 expression is induced by exposure to cigarette smoke, has a cytoprotective activity against cell injury, and its downregulation in human primary ATII cells may contribute to emphysema pathogenesis.

  5. Motivational incentives lead to a strong increase in lateral prefrontal activity after self-control exertion.

    Science.gov (United States)

    Luethi, Matthias S; Friese, Malte; Binder, Julia; Boesiger, Peter; Luechinger, Roger; Rasch, Björn

    2016-10-01

    Self-control is key to success in life. Initial acts of self-control temporarily impair subsequent self-control performance. Why such self-control failures occur is unclear, with prominent models postulating a loss of a limited resource vs a loss of motivation, respectively. Here, we used functional magnetic resonance imaging to identify the neural correlates of motivation-induced benefits on self-control. Participants initially exerted or did not exert self-control. In a subsequent Stroop task, participants performed worse after exerting self-control, but not if they were motivated to perform well by monetary incentives. On the neural level, having exerted self-control resulted in decreased activation in the left inferior frontal gyrus. Increasing motivation resulted in a particularly strong activation of this area specifically after exerting self-control. Thus, after self-control exertion participants showed more prefrontal neural activity without improving performance beyond baseline level. These findings suggest that impaired performance after self-control exertion may not exclusively be due to a loss of motivation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  6. Synchrony and exertion during dance independently raise pain threshold and encourage social bonding.

    Science.gov (United States)

    Tarr, Bronwyn; Launay, Jacques; Cohen, Emma; Dunbar, Robin

    2015-10-01

    Group dancing is a ubiquitous human activity that involves exertive synchronized movement to music. It is hypothesized to play a role in social bonding, potentially via the release of endorphins, which are analgesic and reward-inducing, and have been implicated in primate social bonding. We used a 2 × 2 experimental design to examine effects of exertion and synchrony on bonding. Both demonstrated significant independent positive effects on pain threshold (a proxy for endorphin activation) and in-group bonding. This suggests that dance which involves both exertive and synchronized movement may be an effective group bonding activity. © 2015 The Authors.

  7. Posterior Tibial Arterial System Deficiency Mimicking Chronic Exertional Compartment Syndrome: A Case Report.

    Science.gov (United States)

    Lavery, Kyle P; Parcells, Bertrand W; Hosea, Timothy

    2016-01-01

    A 15-year-old female competitive high school basketball player presented as an outpatient with a 3-month history of bilateral exertional calf pain. Patient history and compartment pressure measurements were consistent with the diagnosis of chronic exertional compartment syndrome, and the patient underwent bilateral fasciotomies. Postoperatively, her symptoms recurred and she was found to have a deficient posterior tibial arterial system bilaterally, as confirmed on advanced imaging. We advocate the careful consideration of vascular etiologies in athletes who present with exertional leg pain.

  8. An investigation of perceived exertion via whole body exertion and direct muscle force indicators during the determination of the maximum acceptable weight of lift.

    Science.gov (United States)

    Davis, K G; Jorgensen, M J; Marras, W S

    2000-02-01

    The objective of this study was to identify the perceived exertion mechanisms (direct muscle force and whole body exertion) associated with the decision to change the weight of lift during the determination of the maximum acceptable weight of lift (MAWL). Fifteen males lifted a box of unknown weight at a rate of 4.3 lifts/min, and adjusted the weight until their MAWL was reached. Variables such as the predicted muscle forces and heart rate were measured during the lifting exertion, as well as the predicted spinal loading in three dimensions using an EMG-assisted biomechanical model. Multiple logistic regression techniques were used to identify variables that were associated with the decision to change the weights up and down prior to a subsequent lift. Results indicated that the force in the left erector spinae, right internal oblique, and left latissimus dorsi muscles as well as heart rate were associated with decreases in the weight prior to the next lift. It appears that a combination of local factors (muscle force) and whole body exertion factors (heart rate) provide the feedback for the perceived exertion when decreasing the weight. The up-change model indicated that the forces of the right erector spinae, left internal oblique, and the right latissimus dorsi muscles were associated with the decision to increase the weight prior to the next lift. Thus, local factors provide feedback during the decision to increase the weight when starting from light weights. Collectively, these findings indicate that psychophysically determined weight limits may be more sensitive to muscular strain rather than spinal loading.

  9. Stiffness and thickness of fascia do not explain chronic exertional compartment syndrome

    DEFF Research Database (Denmark)

    Dahl, Morten; Hansen, Philip; Stål, Per

    2011-01-01

    Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown....

  10. EXERT Yourself and Help in the Search for an Alzheimer's Cure

    Science.gov (United States)

    ... Yourself and Help in the Search for an Alzheimer’s Cure Can exercise slow or prevent cognitive decline in older people who are at increased risk for Alzheimer’s disease? The EXERT Study: Building Memories Through Exercise ...

  11. Exertional heat stroke management strategies in United States high school football.

    Science.gov (United States)

    Kerr, Zachary Y; Marshall, Stephen W; Comstock, R Dawn; Casa, Douglas J

    2014-01-01

    The 5-year period of 2005-2009 saw more exertional heat stroke-related deaths in organized sports than any other 5-year period in the past 35 years. The risk of exertional heat stroke appears highest in football, particularly during the preseason. To estimate the incidence of exertional heat stroke events and assess the utilization of exertional heat stroke management strategies during the 2011 preseason in United States high school football programs. Cross-sectional study; Level of evidence, 3. A self-administered online questionnaire addressing the incidence of exertional heat stroke events and utilization of exertional heat stroke management strategies (eg, removing athlete's football equipment, calling Emergency Medical Services [EMS]) was completed in May to June 2012 by 1142 (18.0%) athletic trainers providing care to high school football athletes during the 2011 preseason. Among all respondents, 20.3% reported treating at least 1 exertional heat stroke event. An average of 0.50 ± 1.37 preseason exertional heat stroke events were treated per program. Athletic trainers responding to exertional heat stroke reported using an average of 6.6 ± 1.8 management strategies. The most common management strategies were low-level therapeutic interventions such as removing the athlete's football equipment (98.2%) and clothing (77.8%) and moving the athlete to a shaded area (91.6%). Few athletic trainers reported active management strategies such as calling EMS (29.3%) or using a rectal thermometer to check core body temperature (0.9%). Athletic trainers in states with mandated preseason heat acclimatization guidelines reported a higher utilization of management strategies such as cooling the athlete through air conditioning (90.1% vs 65.0%, respectively; P < .001), immersion in ice water (63.0% vs 45.4%, respectively; P = .01), or fans (54.3% vs 42.0%, respectively; P = .06) and monitoring the athlete's temperature (60.5% vs 46.2%, respectively; P = .04). Preseason

  12. Physical exercise at the workplace reduces perceived physical exertion during healthcare work: cluster randomized controlled trial.

    Science.gov (United States)

    Jakobsen, Markus Due; Sundstrup, Emil; Brandt, Mikkel; Jay, Kenneth; Aagaard, Per; Andersen, Lars L

    2015-11-01

    High physical exertion during work is a risk factor for musculoskeletal pain and long-term sickness absence. Physical exertion (RPE) reflects the balance between physical work demands and physical capacity of the individual. Thus, increasing the physical capacity through physical exercise may decrease physical exertion during work. This study investigates the effect of workplace-based versus home-based physical exercise on physical exertion during work (WRPE) among healthcare workers. 200 female healthcare workers (age: 42.0, body mass index: 24.1, average pain intensity: 3.1 on a scale of 0 to 10, average WRPE: 3.6 on a scale of 0 to 10) from 18 departments at three participating hospitals. Participants were randomly allocated at the cluster level to 10 weeks of: (1) workplace physical exercise (WORK) performed in groups during working hours for 5×10 minutes per week and up to five group-based coaching sessions on motivation for regular physical exercise, or (2) home-based physical exercise (HOME) performed during leisure time for 5×10 minutes per week. Physical exertion was assessed at baseline and at 10-week follow-up. 2.2 (SD: 1.1) and 1.0 (SD: 1.2) training sessions were performed per week in WORK and HOME, respectively. Physical exertion was reduced more in WORK than HOME (p<0.01). Between-group differences in physical exertion at follow-up (WORK vs. HOME) was -0.5 points (95% CI -0.8 to -0.2). Within-group effect size (Cohen's d) in WORK and HOME was 0.43 and 0.13, respectively. Physical exercise performed at the workplace appears more effective than home-based exercise in reducing physical exertion during daily work tasks in healthcare workers. © 2015 the Nordic Societies of Public Health.

  13. High self-perceived exercise exertion before bedtime is associated with greater objectively assessed sleep efficiency.

    Science.gov (United States)

    Brand, Serge; Kalak, Nadeem; Gerber, Markus; Kirov, Roumen; Pühse, Uwe; Holsboer-Trachsler, Edith

    2014-09-01

    To assess the association between self-perceived exercise exertion before bedtime and objectively measured sleep. Fifty-two regularly exercising young adults (mean age, 19.70 years; 54% females) underwent sleep electroencephalographic recordings 1.5 h after completing moderate to vigorous exercise in the evening. Before sleeping, participants answered questions regarding degree of exertion of the exercise undertaken. Greater self-perceived exertion before bedtime was associated with higher objectively assessed sleep efficiency (r = 0.69, P sleep efficiency (R2 = 0.48). Moreover, high self-perceived exercise exertion was associated with more deep sleep, shortened sleep onset time, fewer awakenings after sleep onset, and shorter wake duration after sleep onset. Multiple linear regression analysis showed that objective sleep efficiency was predicted by increased exercise exertion, shortened sleep onset time, increased deep sleep, and decreased light sleep. Against expectations and general recommendations for sleep hygiene, high self-perceived exercise exertion before bedtime was associated with better sleep patterns in a sample of healthy young adults. Further studies should also focus on elderly adults and adults suffering from insomnia. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2012-2016.

    Science.gov (United States)

    2017-03-01

    Among active component service members in 2016, there were 525 incident diagnoses of rhabdomyolysis likely due to physical exertion and/or heat stress ("exertional rhabdomyolysis"). The crude incidence rate in 2016 was 40.7 cases per 100,000 person-years. Annual rates of incident diagnoses of exertional rhabdomyolysis increased 46.2% between 2013 and 2016, with the greatest percentage change occurring between 2014 and 2015. In 2016, relative to their respective counterparts, the highest incidence rates of exertional rhabdomyolysis affected service members who were male; younger than 20 years of age; and black, non-Hispanic. During the surveillance period, annual incidence rates were highest among service members of the Marine Corps, intermediate among those in the Army, and lowest among those in the Air Force and Navy. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or the Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain or swelling, limited range of motion, or the excretion of dark urine (possibly due to myoglobinuria) after strenuous physical activity, particularly in hot, humid weather.

  15. Seaweed extracts and unsaturated fatty acid constituents from the green alga Ulva lactuca as activators of the cytoprotective Nrf2-ARE pathway.

    Science.gov (United States)

    Wang, Rui; Paul, Valerie J; Luesch, Hendrik

    2013-04-01

    Increased amounts of reactive oxygen species (ROS) have been implicated in many pathological conditions, including cancer. The major machinery that the cell employs to neutralize excess ROS is through the activation of the antioxidant-response element (ARE) that controls the activation of many phase II detoxification enzymes. The transcription factor that recognizes the ARE, Nrf2, can be activated by a variety of small molecules, most of which contain an α,β-unsaturated carbonyl system. In the pursuit of chemopreventive agents from marine organisms, we built, fractionated, and screened a library of 30 field-collected eukaryotic algae from Florida. An edible green alga, Ulva lactuca, yielded multiple active fractions by ARE-luciferase reporter assay. We isolated three monounsaturated fatty acid (MUFA) derivatives as active components, including a new keto-type C18 fatty acid (1), the corresponding shorter chain C16 acid (2), and an amide derivative (3) of the C18 acid. Their chemical structures were elucidated by NMR and mass spectrometry. All three contain the conjugated enone motif between C7 and C9, which is thought to be responsible for the ARE activity. Subsequent biological studies focused on 1, the most active and abundant ARE activator isolated. C18 acid 1 induced the expression of ARE-regulated cytoprotective genes, including NAD(P)H:quinone oxidoreductase 1, heme oxygenase 1, thioredoxin reductase 1, both subunits of the glutamate-cysteine ligase (catalytic subunit and modifier subunit), and the cystine/glutamate exchange transporter, in IMR-32 human neuroblastoma cells. Its cellular activity requires the presence of Nrf2 and PI3K function, based on RNA interference and pharmacological inhibitor studies, respectively. Treatment with 1 led only to Nrf2 activation, and not the increase in production of NRF2 mRNA. To test its ARE activity and cytoprotective potential in vivo, we treated mice with a single dose of a U. lactuca fraction that was enriched with

  16. Src subfamily kinases regulate nuclear export and degradation of transcription factor Nrf2 to switch off Nrf2-mediated antioxidant activation of cytoprotective gene expression.

    Science.gov (United States)

    Niture, Suryakant K; Jain, Abhinav K; Shelton, Phillip M; Jaiswal, Anil K

    2011-08-19

    Nrf2 (NF-E2-related factor 2) is a nuclear transcription factor that in response to chemical and radiation stress regulates coordinated induction of a battery of cytoprotective gene expressions leading to cellular protection. In this study, we investigated the role of Src kinases in the regulation of Nrf2 and downstream signaling. siRNA-mediated inhibition of Fyn, Src, Yes, and Fgr, but not Lyn, in mouse hepatoma Hepa-1 cells, led to nuclear accumulation of Nrf2 and up-regulation of Nrf2 downstream gene expression. Mouse embryonic fibroblasts with combined deficiency of Fyn/Src/Yes/Fgr supported results from siRNA. In addition, steady-state overexpression of Fyn, Src, and Yes phosphorylated Nrf2Tyr568 that triggered nuclear export and degradation of Nrf2 and down-regulation of Nrf2 downstream gene expression. Exposure of cells to antioxidant, oxidant, or UV radiation increased nuclear import of Fyn, Src, and Yes kinases, which phosphorylated Nrf2Tyr568 resulting in nuclear export and degradation of Nrf2. Further analysis revealed that stress-activated GSK3β acted upstream to the Src kinases and phosphorylated the Src kinases, leading to their nuclear localization and Nrf2 phosphorylation. The overexpression of Src kinases in Hepa-1 cells led to decreased Nrf2, increased apoptosis, and decreased cell survival. Mouse embryonic fibroblasts deficient in Src kinases showed nuclear accumulation of Nrf2, induction of Nrf2 and downstream gene expression, reduced apoptosis, and increased cell survival. The studies together demonstrate that Src kinases play a critical role in nuclear export and degradation of Nrf2, thereby providing a negative feedback mechanism to switch off Nrf2 activation and restore normal cellular homeostasis.

  17. Cytoprotective effects of 12-oxo phytodienoic acid, a plant-derived oxylipin jasmonate, on oxidative stress-induced toxicity in human neuroblastoma SH-SY5Y cells.

    Science.gov (United States)

    Taki-Nakano, Nozomi; Ohzeki, Hiromitsu; Kotera, Jun; Ohta, Hiroyuki

    2014-12-01

    Jasmonates are plant lipid-derived oxylipins that act as key signaling compounds when plants are under oxidative stress, but little is known about their functions in mammalian cells. Here we investigated whether jasmonates could protect human neuroblastoma SH-SY5Y cells against oxidative stress-induced toxicity. The cells were pretreated with individual jasmonates for 24h and exposed to hydrogen peroxide (H2O2) for 24h. Before the resulting cytotoxicity, intracellular reactive oxygen species (ROS) levels, and mitochondrial membrane potential were measured. We also measured intracellular glutathione (GSH) levels and investigated changes in the signaling cascade mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) in cells treated with 12-oxo phytodienoic acid (OPDA). Among the jasmonates, only OPDA suppressed H2O2-induced cytotoxicity. OPDA pretreatment also inhibited the H2O2-induced ROS increase and mitochondrial membrane potential decrease. In addition, OPDA induced the nuclear translocation of Nrf2 and increased intracellular GSH level and the expression of the Nrf2-regulated phase II antioxidant enzymes heme oxygenase-1, NADPH quinone oxidoreductase 1, and glutathione reductase. Finally, the cytoprotective effects of OPDA were reduced by siRNA-induced knockdown of Nrf2. These results demonstrated that among jasmonates, only OPDA suppressed oxidative stress-induced death of human neuroblastoma cells, which occurred via activation of the Nrf2 pathway. Plant-derived oxylipin OPDA may have the potential to provide protection against oxidative stress-related diseases. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Elevation of serum N-terminal pro-brain natriuretic peptide after exercise is an index of myocardial damage or a cytoprotective reflection?

    Science.gov (United States)

    Faviou, E; Zachari, A; Nounopoulos, C; Agrafiotis, E; Vourli, G; Dionyssiou-Asteriou, A

    2008-03-01

    Recent investigations have suggested the occurrence of transient cardiac dysfunction and reversible myocardial injury in healthy individuals after heavy exercise. Our purpose was to examine if the release of N-terminal pro-brain natriuretic peptide (NT-proBNP) after intense exercise in obviously healthy participants may have cytoprotective and growth-regulating effects or may result from myocardial dysfunction/damage with changes in cTnT as a marker for myocardial cell necrosis during exercise. In 43 highly-trained male athletes exercising as well as 2 days later, 21 age-matched male patients classified as stage-B according to ACC/AHA guidelines and 35 healthy age-matched males, we evaluated NT-proBNP and 3rd generation's cTnT by electrochemiluminescence immunoassay. All participants underwent a detailed cardiac protocol including echocardiography and electrocardiogram (ECG). In athletes, cTnT consistently remained exercising as well as after 2 days. NTproBNP immediately after exercising was 58.27+/-19.48 ng/L, without reaching pathological levels, decreasing 2 days later to 22.93+/-10.22 ng/L. Our patients maintained high levels of NTproBNP, as much as a six-fold increase with reference to the levels of our study's control group and with cTnT exercising. NT-proBNP as a biological marker can reliably discriminate pathological from physiological cardiac hypertrophy. A normal plasma concentration of NT-proBNP in consecutive routine check-up, before and after exercise, could minimize the possibility of cardiac dysfunction, whereas persistent elevated plasma concentrations warrant further cardiological evaluation.

  19. Hydrogen Sulfide Releasing 2-Mercaptoacrylic Acid-Based Derivative Possesses Cytoprotective Activity in a Small Intestine of Rats with Medication-Induced Enteropathy

    Directory of Open Access Journals (Sweden)

    Yulia Sklyarova

    2017-10-01

    Full Text Available Small intestinal injury is known to be one of the most commonly appearing pathologies, resulting in the use of medications such as: nonsteroidal anti-inflammatory drugs (NSAIDs, antitumor drugs and angiotensin-converting enzyme (ACE inhibitors. The principal objective of this study is to evaluate the action of a novel mercaptoacrylic acid derivative able to release H2S on parameters of NO-synthase system and oxidative stress. Inducing enteropathy, three types of medications were used: indomethacin, an NSAID (35 mg/kg; methotrexate, an antitumor drug (10 mg/kg; and enalapril, an ACE inhibitor (2 mg/kg/day. 2-[(4-chlorophenyl-carbamoyl-methyl]-3-(3,5-di-tert-butyl-4-hydroxyphenyl-acrylic acid (2C3DHTA was introduced based on the background of medication-induced enteropathy (10 mg/kg/day. The survey showed that malondialdehyde (MDA concentration, myeloperoxidase (MPO activity, superoxide dismutase (SOD, catalase, and NO-synthases (NOS were determined in the small intestinal mucosa. The increase in inducible NO-synthase (iNOS activity was due to indomethacin and methotrexate administration. Constitutive NO-synthase (cNOS activity was decreased by an ACE-inhibitor. The cytoprotective effect was demonstrated by 2C3DHTA, which returned iNOS activity to its control level and increased cNOS activity. The enterotoxic action of studied medication was accompanied by the development of oxidative stress manifested, activity of MPO was increased. MPO activity and manifestations of oxidative stress were decreased by 2C3DHTA. Effects of 2C3DHTA can be explained by the action of H2S, released from this compound in the gastrointestinal (GI system.

  20. Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Kazuaki Kajimoto

    2014-01-01

    Full Text Available The fatty acid binding protein 4 (FABP4, one of the most abundant proteins in adipocytes, has been reported to have a proinflammatory function in macrophages. However, the physiological role of FABP4, which is constitutively expressed in adipocytes, has not been fully elucidated. Previously, we demonstrated that FABP4 was involved in the regulation of interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF production in 3T3-L1 adipocytes. In this study, we examined the effects of FABP4 silencing on the oxidative and endoplasmic reticulum (ER stress in 3T3-L1 adipocytes. We found that the cellular reactive oxygen species (ROS and 8-nitro-cyclic GMP levels were significantly elevated in the differentiated 3T3-L1 adipocytes transfected with a small interfering RNA (siRNA against Fabp4, although the intracellular levels or enzyme activities of antioxidants including reduced glutathione (GSH, superoxide dismutase (SOD and glutathione S-transferase A4 (GSTA4 were not altered. An in vitro evaluation using the recombinant protein revealed that FABP4 itself functions as a scavenger protein against hydrogen peroxide (H2O2. FABP4-knockdown resulted in a significant lowering of cell viability of 3T3-L1 adipocytes against H2O2 treatment. Moreover, four kinds of markers related to the ER stress response including the endoplasmic reticulum to nucleus signaling 1 (Ern1, the signal sequence receptor α (Ssr1, the ORM1-like 3 (Ormdl3, and the spliced X-box binding protein 1 (Xbp1s, were all elevated as the result of the knockdown of FABP4. Consequently, FABP4 might have a new role as an antioxidant protein against H2O2 and contribute to cytoprotection against oxidative and ER stress in adipocytes.

  1. Prohibitin confers cytoprotection against ISO-induced hypertrophy in H9c2 cells via attenuation of oxidative stress and modulation of Akt/Gsk-3β signaling.

    Science.gov (United States)

    Chowdhury, Debabrata; Kumar, Dinesh; Bhadra, Utpal; Devi, Tangutur Anjana; Bhadra, Manika Pal

    2017-01-01

    Numerous hypertrophic stimuli, including β-adrenergic agonists such as isoproterenol (ISO), result in generation of reactive oxygen species (ROS) and alteration in the mitochondrial membrane potential (Δψ) leading to oxidative stress. This process is well associated with phosphorylation of thymoma viral proto-oncogene Akt (Ser473) and glycogen synthase kinase-3β (Gsk-3β) (Ser9), with resultant inactivation of Gsk-3β. In the present study, we found that the protective defensive role of prohibitin (PHB) against ISO-induced hypertrophic response in rat H9c2 cells is via attenuation of oxidative stress-dependent signaling pathways. The intracellular levels of mitochondrial membrane potential along with cellular ROS levels and mitochondrial superoxide generation were determined. In order to understand the regulation of Akt/Gsk-3β signaling pathway, we carried out immmunoblotting for key proteins of the pathway such as PTEN, PI3K, phosphorylated, and unphosphorylated forms of Akt, Gsk-3β, and immunofluorescence experiments of p-Gsk-3β. Enforced expression of PHB in ISO-treated H9c2 cells suppressed cellular ROS production with mitochondrial superoxide generation and enhanced the mitochondrial membrane potential resulting in suppression of oxidative stress which likely offered potent cellular protection, led to the availability of more healthy cells, and also, significant constitutive activation of Gsk-3β via inactivation of Akt was observed. Knockdown of PHB expression using PHB siRNA in control H9c2 cells reversed these effects. Overall, our results demonstrate that PHB confers cytoprotection against oxidative stress in ISO-induced hypertrophy and this process is associated with modulation of Akt/Gsk-3β signaling mechanisms as evident from our PHB overexpression and knockdown experiments.

  2. MicroRNA-148a-3p enhances cisplatin cytotoxicity in gastric cancer through mitochondrial fission induction and cyto-protective autophagy suppression.

    Science.gov (United States)

    Li, Bowen; Wang, Weizhi; Li, Zheng; Chen, Zheng; Zhi, Xiaofei; Xu, Jianghao; Li, Qing; Wang, Lu; Huang, Xiaoxu; Wang, Linjun; Wei, Song; Sun, Guangli; Zhang, Xuan; He, Zhongyuan; Zhang, Lu; Zhang, Diancai; Xu, Hao; El-Rifai, Wael; Xu, Zekuan

    2017-12-01

    Cisplatin (CDDP) resistance is a major clinical problem associated with poor prognosis in gastric cancer (GC) patients. In this study, we performed integrated analysis of TCGA data from microRNAs (miRNAs) expression matrix of GC patients who received CDDP-based chemotherapy with GEO dataset which contains differential miRNAs expression profiles in CDDP-resistant and -sensitive cell lines. We identified miR-148a-3p downregulation as a key step involved in CDDP resistance. Using a cohort consisting 105 GC patients who received CDDP-based therapy, we found that miR-148a-3p downregulation was associated with a decrease in patients' disease-free survival (DFS, P = 0.0077). A series of experiment data demonstrated that: 1) miR-148a-3p was downregulated in CDDP-resistant GC cell lines; 2) miR-148a-3p reconstitution sensitized CDDP-resistant cells to CDDP treatment through promoting mitochondrial fission and decreasing AKAP1 expression level; 3) AKAP1 played a novel role in CDDP resistance by inhibiting P53-mediated DRP1 dephosphorylation; 4) miR-148a-3p reconstitution in CDDP-resistant cells inhibits the cyto-protective autophagy by suppressing RAB12 expression and mTOR1 activation. Taken together, our study demonstrates that miR-148a-3p could be a promising prognostic marker or therapeutic candidate for overcoming CDDP resistance in GC. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Amifostine (WR-2721, a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

    Directory of Open Access Journals (Sweden)

    De Souza C.A.

    2000-01-01

    Full Text Available Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY (7 g/m2, used to mobilize peripheral blood progenitor cells (PBPC and to reduce tumor burden. We enrolled 29 patients, 22 (75.9% affected by aggressive and 7 (24.1% by indolent non-Hodgkin's lymphoma (NHL, who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04. None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively. Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

  4. Enhancement of High-Density Lipoprotein Cholesterol Functions by Encapsulation of Policosanol Exerts Anti-Senescence and Tissue Regeneration Effects Via Improvement of Anti-Glycation, Anti-Apoptosis, and Cholesteryl Ester Transfer Inhibition.

    Science.gov (United States)

    Lim, So-Mang; Yoo, Jeong-Ah; Lee, Eun-Young; Cho, Kyung-Hyun

    2016-02-01

    Consumption of policosanol (PCO), a refined mixture of sugar cane wax alcohols, can elevate serum levels of high-density lipoprotein cholesterol (HDL-C), although the molecular mechanism is still unknown. To investigate the mechanism of action responsible for the anti-senescence effects of PCO on lipoprotein metabolism and HDL functionality, we synthesized reconstituted HDL (rHDL) containing PCO. Encapsulation of PCO by rHDL (PCO-rHDL) enhanced anti-oxidant activity against cupric ion-mediated low-density lipoprotein (LDL) oxidation. PCO-rHDL (final concentration, 9 μM PCO) showed more potent anti-oxidant activity than vitamin C treatment (final concentration, 100 μM). PCO-rHDL inhibited fructose-mediated glycation, which is a major pathological mechanism of diabetic complications, in a dose-dependent manner. PCO also showed cytoprotective effects in monocytes and macrophages with less triggering of apoptotic processes and reactive oxygen species (ROS) production in the presence of hydrogen peroxide (H2O2). PCO-rHDL strongly inhibited uptake of acetylated LDL into macrophages, which is an initial atherosclerotic process. Surprisingly, PCO-rHDL inhibited human serum cholesteryl ester transfer protein (CETP) activity by up to 47% (final concentration, 10 μM PCO). Subcutaneous injection of PCO-rHDL dose-dependently enhanced tissue regeneration activity by 2.4-fold and 3.6-fold compared to that of the phosphate-buffered saline (PBS) control. In conclusion, PCO in HDL showed potent anti-oxidant, anti-glycation, and CETP inhibitory activities along with tissue regenerative activity, especially upon incorporation into HDL. These results suggest that PCO can enhance functionality of HDL in serum to exert anti-senescence and longevity effects.

  5. Cognitive control exertion leads to reductions in peak power output and [Formula: see text] as well as increased perceived exertion on a graded exercise test to exhaustion.

    Science.gov (United States)

    Zering, Jennifer C; Brown, Denver M Y; Graham, Jeffrey D; Bray, Steven R

    2017-09-01

    We investigated effects of a brief (10.5 min) cognitively demanding task on graded exercise test performance. Untrained, university students (N = 15) completed two graded exercise tests in counterbalanced, randomised order. One test was preceded by restful viewing of a documentary video (control); the other by a stop-signal task. Cardiorespiratory functions and perceived exertion were monitored during exercise. Peak power output (W) was lower following the stop-signal task (M = 240.03, SD = 53.37) compared to control (M = 246.03, SD = 52.60), P = 0.002, η P 2  = 0.493, as was [Formula: see text] (P = 0.042, Cohen's d = 0.55). Perceived exertion was significantly higher at 50% (d = 0.77) and 75% (d = 0.83) of iso-time following the cognitive task (Ps ≤ 0.01). Results are consistent with research showing negative carryover effects of cognitively demanding tasks on whole-body endurance performance. Results also support the psychobiological model of exercise as performance of the cognitive task did not affect perceived exertion when exercise task demands were lower, but lead to greater perceived exertion and earlier withdrawal of effort at higher levels of exercise task demand. Findings have implications for understanding psychological determinants of exercise performance and conditions that may lead to underestimation of [Formula: see text].

  6. Rating of perceived exertion and acute mountain sickness during a high-altitude trek.

    Science.gov (United States)

    Mellor, Adrian J; Woods, David R; O'Hara, John; Howley, Mark; Watchorn, James; Boos, Christopher

    2014-12-01

    There is a widely held belief that strenuous exercise should be avoided on arrival at high altitude (HA) and during acclimatization. Data from chamber studies are contradictory and the studies are usually of short duration, therefore differing from the "real world." We studied 48 trekkers during a 10-d ascent to 16,827 ft (5129 m) in the Cordillera Real area of Bolivia. Borg Rating of Perceived Exertion (RPE) scores were recorded for the hardest perceived exertion during the day after ascents to 12,576, 14,600, and 16,827 ft (3833, 4450, and 5129 m). Heart rate, Spo2, and Lake Louise Score (LLS) were recorded simultaneously. Statistical testing was performed using SPSS 21 software. A P-value of ≤ 0.05 was deemed significant. Acute mountain sickness (AMS) rates were higher after trekking days with higher levels of perceived exertion. The LLS was higher in those with a Borg RPE score ≥ 15 both following exercise (mean LLS 2.6 vs. 1.7) and at rest the following day (mean LLS 2.7 vs. 1.7). Heart rate was higher in those with high Borg RPE scores (80 vs. 87) and oxygen saturations lower at rest (86 vs. 83) the following morning. This data lends weight to the advice of moderate exertion during a trek to HA and suggests that reducing perceived exertion may reduce AMS.

  7. Perceived exertion at work in women with fibromyalgia: explanatory factors and comparison with healthy women.

    Science.gov (United States)

    Palstam, Annie; Larsson, Anette; Bjersing, Jan; Löfgren, Monika; Ernberg, Malin; Bileviciute-Ljungar, Indre; Ghafouri, Bijar; Sjörs, Anna; Larsson, Britt; Gerdle, Björn; Kosek, Eva; Mannerkorpi, Kaisa

    2014-09-01

    To investigate perceived exertion at work in women with fibromyalgia. A controlled cross-sectional multi-centre study. Seventy-three women with fibromyalgia and 73 healthy women matched by occupation and physical workload were compared in terms of perceived exertion at work (0-14), muscle strength, 6-min walk test, symptoms rated by Fibromyalgia Impact Questionnaire (FIQ), work status (25-100%), fear avoidance work beliefs (0-42), physical activity at work (7-21) and physical workload (1-5). Spearman's correlation coefficient and linear regression analysis were conducted. Perceived exertion at work was significantly higher in the fibromyalgia group than in the reference group (p = 0.002), while physical activity at work did not differ between the groups. Physical capacity was lower and symptom severity higher in fibromyalgia compared with references (p work showed moderate correlation with physical activity at work, physical workload and fear avoidance work beliefs (rs = 0.53-0.65, p work and fear avoidance work beliefs explained 50% of the perceived exertion at work. Women with fibromyalgia perceive an elevated exertion at work, which is associated with physical work-related factors and factors related to fear and anxiety.

  8. Effect of Complex Working Conditions on Nurses Who Exert Coercive Measures in Forensic Psychiatric Care.

    Science.gov (United States)

    Gustafsson, Niclas; Salzmann-Erikson, Martin

    2016-09-01

    Nurses who exert coercive measures on patients within psychiatric care are emotionally affected. However, research on their working conditions and environment is limited. The purpose of the current study was to describe nurses' experiences and thoughts concerning the exertion of coercive measures in forensic psychiatric care. The investigation was a qualitative interview study using unstructured interviews; data were analyzed with inductive content analysis. Results described participants' thoughts and experiences of coercive measures from four main categories: (a) acting against the patients' will, (b) reasoning about ethical justifications, (c) feelings of compassion, and (d) the need for debriefing. The current study illuminates the working conditions of nurses who exert coercive measures in clinical practice with patients who have a long-term relationship with severe symptomatology. The findings are important to further discuss how nurses and leaders can promote a healthier working environment. [Journal of Psychosocial Nursing and Mental Health Services, 54(9), 37-43.]. Copyright 2016, SLACK Incorporated.

  9. Diagnosis and Treatment of Chronic Exertional Compartment Syndrome - a Proposition for an Algorithm

    DEFF Research Database (Denmark)

    Larsen, Peter Birk; Jensen, Steffen Skov

    Title: Diagnosis and treatment of chronic exertional compartment syndrome - a proposition for an algorithm based on case series of patients treated at Sports Medicine Division, Department of Orthopaedic Surgery, Viborg Regional Hospital, Denmark Background: Chronic exertional compartment syndrome...... (CECS) is a well recognized but often under diagnosed cause of chronic exertional lower extremity pain, most often encountered in young physically active individuals. Aim of Study: The aim of this preliminary study is to present an algorithm for diagnosis and treatment of CECS. We hypothesize...... in conjunction with a thorough medical history formed the basis for the diagnosis. Results: 11 patients were offered surgical treatment consisting of EASF of the affected compartment (10 bilateral and 1 unilateral, 8 affected in specific compartments and 3 affected in all compartments. Only 1 patient required...

  10. Exertional Tolerance Assessments After Mild Traumatic Brain Injury: A Systematic Review.

    Science.gov (United States)

    Quatman-Yates, Catherine; Bailes, Anna; Constand, Sara; Sroka, Mary Claire; Nissen, Katharine; Kurowski, Brad; Hugentobler, Jason

    2018-05-01

    To review the literature to identify and summarize strategies for evaluating responses to physical exertion after mild traumatic brain injury (mTBI) for clinical and research purposes. PubMed and EBSCOhost through December 31, 2016. Two independent reviewers selected studies based on the following criteria: (1) inclusion of participants with mTBI/concussion, (2) use of a measurement of physiological or psychosomatic response to exertion, (3) a repeatable description of the exertion protocol was provided, (4) a sample of at least 10 participants with a mean age between 8 and 65 years, and (5) the article was in English. The search process yielded 2685 articles, of which 14 studies met the eligibility requirements. A quality assessment using a checklist was conducted for each study by 2 independent study team members and verified by a third team member. Data were extracted by one team member and verified by a second team member. A qualitative synthesis of the studies revealed that most protocols used a treadmill or cycle ergometer as the exercise modality. Protocol methods varied across studies including differences in initial intensity determination, progression parameters, and exertion duration. Common outcome measures were self-reported symptoms, heart rate, and blood pressure. The strongest evidence indicates that exertional assessments can provide important insight about mTBI recovery and should be administered using symptoms as a guide. Additional studies are needed to verify optimal modes and protocols for post-mTBI exertional assessments. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  11. [Exercise laryngoscopy: a new method for the differential diagnosis of dyspnea on exertion].

    Science.gov (United States)

    Tervonen, Hanna; Iljukov, Sergei; Niskanen, Minna-Liisa; Vilkman, Erkki; Sovijärvi, Anssi; Aaltonen, Leena-Maija

    2011-01-01

    Exertional dyspnea originating from the laryngeal level can be established with certainty only if the paradoxical vocal cord adduction is observed during dyspnea. We have developed a novel diagnostic method, exercise laryngoscopy, which involves observation of the larynx with a flexible endoscope applied via the nose during a bicycle ergometry test. It has been our aim to improve the differential diagnosis of dyspnea on exertion and thus also reduce unnecessary antiasthmatic medication. Exercise laryngoscopy allows examination in the out-patient clinics because the method is well tolerated.

  12. Exertional Heat Stroke and American Football: What the Team Physician Needs to Know.

    Science.gov (United States)

    Sylvester, Jillian E; Belval, Luke N; Casa, Douglas J; O'Connor, Francis G

    Football is recognized as a leading contributor to sports injury secondary to the contact collision nature of the endeavor. While direct deaths from head and spine injury remain a significant contributor to the number of catastrophic injuries, indirect deaths (systemic failure) predominate. Exertional heat stroke has emerged as one of the leading indirect causes of death in high school and collegiate football. This review details for the team physician the unique challenge of exercising in the heat to the football player, and the prevention, diagnosis, management, and return-to-play issues pertinent to exertional heat illnesses.

  13. Chronic exertional compartment syndrome in a collegiate soccer player: a case report and literature review.

    Science.gov (United States)

    Farr, Derek; Selesnick, Harlan

    2008-07-01

    Chronic exertional compartment syndrome is a relatively rare condition among running athletes. In those who engage in repetitive activity, it can cause severe, debilitating leg pain. The diagnosis can be made with a thorough workup that includes history and physical examination, radiologic studies (x-rays, magnetic resonance imaging, bone scan), and compartment pressure monitoring. Most patients do not respond well to nonoperative intervention. Fasciotomy provides satisfactory relief of symptoms and helps patients return to their sports. We present the case of a high-level collegiate soccer player with chronic exertional compartment syndrome.

  14. 3′-epi-12β-hydroxyfroside, a new cardenolide, induces cytoprotective autophagy via blocking the Hsp90/Akt/mTOR axis in lung cancer cells

    Science.gov (United States)

    Sun, Yan; Huang, Yong-Hao; Huang, Feng-Ying; Mei, Wen-Li; Liu, Quan; Wang, Cai-Chun; Lin, Ying-Ying; Huang, Canhua; Li, Yue-Nan; Dai, Hao-Fu; Tan, Guang-Hong

    2018-01-01

    Rationale: Cardenolides have potential as anticancer drugs. 3′-epi-12β-hydroxyfroside (HyFS) is a new cardenolide structure isolated by our research group, but its molecular mechanisms remain poorly understood. This study investigates the relationship between its antitumor activities and autophagy in lung cancer cells. Methods: Cell growth and proliferation were detected by MTT, lactate dehydrogenase (LDH) release, 5-ethynyl-20-deoxyuridine (EDU) and colony formation assays. Cell apoptosis was detected by flow cytometry. Autophagic and signal proteins were detected by Western blotting. Markers of autophagy and autophagy flux were also detected by immunofluorescence, transmission electron microscopy and acridine orange staining. Real time RT-PCR was used to analyze the gene expression of Hsp90. Hsp90 ubiquitination was detected by coimmunoprecipitation. The antitumore activities of HyFS were observed in nude mice. Results: HyFS treatment inhibited cell proliferation and induced autophagy in A549 and H460 lung cancer cells, but stronger inhibition of cell proliferation and induction of cell apoptosis were shown when HyFS-mediated autophagy was blocked. The Hsp90/Akt/mTOR axis was found to be involved in the activation of HyFS-mediated autophagy. Evidence of direct interaction between Hsp90 and Akt was observed. HyFS treatment resulted in decreased levels of heat shock protein 90 (Hsp90) and phosphorylated Akt, overexpression of Hsp90 increased activation of autophagy, and inhibition of Hsp90 expression decreased autophagy. In addition, ubiquitin-mediated degradation of Hsp90 and subsequent dephosphorylation of its client protein Akt were also found in HyFS-treated lung cancer cells. Moreover, combination treatment with HyFS and chloroquine showed remarkably increased tumor inhibition in both A549- and H460-bearing mice. Conclusion: Our results demonstrate that HyFS induced cytoprotective autophagy through ubiquitin-mediated degradation of Hsp90, which further

  15. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby

  16. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; van Brunschot, C.; Schipper, P.; Korte-Bouws, G.; van Luijtelaar, G.; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac (R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and

  17. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac(R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and

  18. [Characteristics of non-exertional heat-related illness in Japan].

    Science.gov (United States)

    Miyake, Yasufumi

    2012-06-01

    This report shows characteristics of non-exertional heat-related illness in Japan. The findings are similar to those of previous reports in heatwaves of Europe and The United States. Eldery people with pre-existing diseases, homeless, living alone, poverty are independent risk factors of heatstoke and are strongly associated with severity and mortality.

  19. Forces exerted during exercises by patients with adolescent idiopathic scoliosis wearing fiberglass braces

    OpenAIRE

    Romano Michele; Carabalona Roberta; Petrilli Silvia; Sibilla Paolo; Negrini Stefano

    2006-01-01

    Abstract Objective To quantify and compare the forces exerted by scoliosis patients in fiberglass braces during exercises usually prescribed in departments where casts are made. The exercises are intended to increase corrective forces, activate muscles, stimulate ventilation and help the patient psychologically. Setting Outpatient care. Patients 17 consecutive adolescent patients wearing fiberglass brace for idiopathic scoliosis. Interventions Exercises (kyphotization, rotation, "escape from ...

  20. Baseline Intraocular Pressure Is Associated with Subjective Sensitivity to Physical Exertion in Young Males

    Science.gov (United States)

    Vera, Jesús; Jiménez, Raimundo; García, José Antonio; Perales, José Cesar; Cárdenas, David

    2018-01-01

    Purpose: The purposes of this study were to (a) investigate the effect of physical effort (cycling for 60 min at 60 ± 5% of individually computed reserve heart-rate capacity), combined with 2 different levels of cognitive demand (2-back, oddball), on intraocular pressure (IOP) and subjective judgments of perceived exertion (ratings of perceived…

  1. Citrus-derived flavonoid naringenin exerts uterotrophic effects in female mice at human relevant doses

    DEFF Research Database (Denmark)

    Breinholt, Vibeke Miller; Svendsen, Gitte Winkel; Dragsted, Lars Ove

    2004-01-01

    ingestion of 400-760 ml of orange juice (Erlund et al. 2001). This could be taken to suggests that ingestion of orange juice and other citrus fruits and juices may give rise to sufficiently high tissue levels of naringenin in man to exert a biological effect....

  2. Prevalence and potential determinants of exertional dyspnea after acute pulmonary embolism.

    NARCIS (Netherlands)

    Klok, F.A.; Kralingen, K.W. van; Dijk, A.P.J. van; Heyning, F.H.; Vliegen, H.W.; Huisman, M.V.

    2010-01-01

    BACKGROUND: The exact prevalence and etiology of exertional dyspnea in the clinical course of acute pulmonary embolism (PE) have not yet been established. METHODS: A large cohort of consecutive patients diagnosed with acute PE was subjected to a dyspnea questionnaire and invited for cardiopulmonary

  3. Hydrocortisone Infusion Exerts Dose- and Sex-Dependent Effects on Attention to Emotional Stimuli

    Science.gov (United States)

    Breitberg, Alaina; Drevets, Wayne C.; Wood, Suzanne E.; Mah, Linda; Schulkin, Jay; Sahakian, Barbara J.; Erickson, Kristine

    2013-01-01

    Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to…

  4. Exertion of forces by children performing a free-style jump

    NARCIS (Netherlands)

    Moes, C.C.M.; Visser, R.J.

    1998-01-01

    This research project focuses on the force characteristics and force/time relationships of loads exerted by jumping children. The current study is an experimental research into children jumping on both hard and soft substrates. The hard substrate is obtained by using a force plate. For the soft

  5. Superiority of the dominant and nondominant hands in static strength and controlled force exertion.

    Science.gov (United States)

    Noguchi, Takanori; Demura, Shinichi; Aoki, Hiroki

    2009-10-01

    The dominant hand can be defined in such a way that Oldfield's Handedness Inventory may not identify the superior hand, i.e., the hand with more strength and/or more force control. The dominant and nondominant hands were compared for two different grip force-exertion tests. 50 healthy young men (M age = 21.1 yr.) performed two tests with each hand: a maximal grip strength test and a controlled force-exertion test with dynamic demand. In the latter test, the participants matched their submaximal grip force to the changing demand values with real-time feedback. The total sum of the differences between the demand value and grip force value for 25 sec. was used as an evaluation parameter for the test (unit: %). Mean maximal grip force values in the right and left hands were 439.9 N (SD = 59.1) and 405.6 N (SD = 59.3), respectively. Mean controlled force-exertion test values in the right and left hands were 610.3% (SD = 150.2) and 722.6% (SD = 147.8), respectively. In both tests, the dominant hand was significantly stronger and controlled dynamic force better. The relationship between the two hands was very high. Based on this study's criteria, the dominant hand was stronger in 34% (n = 17) of participants during the maximal grip strength test and more controlled in 54% (n = 27) of participants during the controlled force-exertion test. Thus, the dynamic force control test showed that for significantly more people the dominant hand is stronger and controls force better. Controlled force exertion may be a better test for identifying the superior hand.

  6. Effects of acclimation on water and electrolitic disbalance in soldiers during exertional heat stress

    Directory of Open Access Journals (Sweden)

    Radaković Sonja S.

    2007-01-01

    Full Text Available Background/Aim. Exertional heat stress is a common problem in military services. The aim of this study was to examine changes in body water and serum concentrations of some electrolites in soldiers during exertional heat stress (EHST, as well as effects of 10-day passive or active acclimation in a climatic chamber. Methods. Forty male soldiers with high aerobic capacity, performed EHST either in cool (20 ºC, 16 ºC WBGT-wet bulb globe temperature, or hot (40 ºC, 25 ºC WBGT environment, unacclimatized, or after 10 days of passive or active acclimation. The subjects were allowed to drink tap water ad libitum during EHST. Mean skin (Tsk and tympanic (Tty temperatures and heart rates (HR measured physiological strain, while sweat rate (SwR, and serum concentrations of sodium, potassium and osmolality measured changes in water and electrolyte status. Blood samples were collected before and immediately after the EHST. Results. Exertional heat stress in hot conditions induced physiological heat stress (increase in Tty, HR, and SwR, with significant decrease in serum sodium concentration (140.6±1.52 before vs 138.5±1.0 mmol/l after EHST, p < 0.01 and osmolality (280.7±3.8 vs 277.5±2.6 mOsm/kg, p < 0.05 in the unacclimatized group. The acclimated soldiers suffered no such effects of exertional heat stress, despite almost the same degree of heat strain, measured by Tty, HR and SwR. Conclusion. In the trained soldiers, 10-day passive or active acclimation in a climatic chamber can prevent disturbances in water and electrolytic balance, i.e. decrease in serum sodium concentrations and osmolality induced by exertional heat stress.

  7. Exertional Rhabdomyolysis in a 21-Year-Old Healthy Woman: A Case Report.

    Science.gov (United States)

    McKay, Brianna D; Yeo, Noelle M; Jenkins, Nathaniel D M; Miramonti, Amelia A; Cramer, Joel T

    2017-05-01

    McKay, BD, Yeo, NM, Jenkins, NDM, Miramonti, AA, and Cramer, JT. Exertional rhabdomyolysis in a 21-year-old healthy woman: a case report. J Strength Cond Res 31(5): 1403-1410, 2017-The optimal resistance training program to elicit muscle hypertrophy has been recently debated and researched. Although 3 sets of 10 repetitions at 70-80% of the 1 repetition maximum (1RM) are widely recommended, recent studies have shown that low-load (∼30% 1RM) high-repetition (3 sets of 30-40 repetitions) resistance training can elicit similar muscular hypertrophy. Incidentally, this type of resistance training has gained popularity. In the process of testing this hypothesis in a research study in our laboratory, a subject was diagnosed with exertional rhabdomyolysis after completing a resistance training session that involved 3 sets to failure at 30% 1RM. Reviewed were the events leading up to and throughout the diagnosis of exertional rhabdomyolysis in a healthy recreationally-trained 21-year-old woman who was enrolled in a study that compared the acute effects of high-load low-repetition vs. low-load high-repetition resistance training. The subject completed a total of 143 repetitions of the bilateral dumbbell biceps curl exercise. Three days after exercise, she reported excessive muscle soreness and swelling and sought medical attention. She was briefly hospitalized and then discharged with instructions to take acetaminophen for soreness, drink plenty of water, rest, and monitor her creatine kinase (CK) concentrations. Changes in the subject's CK concentrations, ultrasound-determined muscle thickness, and echo intensity monitored over a 14-day period are reported. This case illustrates the potential risk of developing exertional rhabdomyolysis after a low-load high-repetition resistance training session in healthy, young, recreationally-trained women. The fact that exertional rhabdomyolysis is a possible outcome may warrant caution when prescribing this type of resistance

  8. Modeling trajectories of perceived leg exertion during maximal cycle ergometer exercise in children and adolescents.

    Science.gov (United States)

    Huebner, Marianne; Zhang, Zhen; Therneau, Terry; McGrath, Patrick; Pianosi, Paolo

    2014-01-09

    Borg developed scales for rating pain and perceived exertion in adults that have also been used in pediatric populations. Models describing functional relationships between perceived exertion and work capacity have not been studied in children. We compared different models and their fits to individual trajectories and assessed the variability in these trajectories. Ratings of perceived exertion (RPE) were collected from 79 children. Progressive cycle ergonometric testing was performed to maximal work capacity with test duration ranging from 6- 12 minutes. Ratings were obtained during each 1-minute increment. Work was normalized to individual maximal work capacity (Wmax). A delay was defined as the fraction of Wmax at which point an increase in ratings of leg fatigue occurred. Such a delay term allows the characterization of trajectories for children whose ratings were initially constant with increasing work. Two models were considered, a delay model and a power model that is commonly used to analyze Borg ratings. Individual model fit was assessed with root mean squared error (RMSE). Functional clustering algorithms were used to identify patterns. Leg tiredness developed quickly for some children while for others there was a delay before an in- creased ratings of leg exertion occurred with increasing work. Models for individual trajectories with the smallest RMSE included a delay and a quadratic term (quadratic-delay model), or a power function and a delay term (power-delay model) compared to a simple power function. The median delay was 40% Wmax (interquartile range (IQR): 26-49%) in a quadratic-delay model, while the median exponent was 1.03 (IQR: 0.83-1.78) in a power-delay model. Nine clusters were identified showing linear or quadratic patterns with or without a delay. Cluster membership did not depend on age, gender or diagnosis. Children and adolescents vary widely in their capacity to rate their perceptions and exhibit different functional relationships

  9. Epidemiology of Exertional Rhabdomyolysis Susceptibility in Standardbred Horses Reveals Associated Risk Factors and Underlying Enhanced Performance

    Science.gov (United States)

    Isgren, Cajsa M.; Upjohn, Melissa M.; Fernandez-Fuente, Marta; Massey, Claire; Pollott, Geoff; Verheyen, Kristien L. P.; Piercy, Richard J.

    2010-01-01

    Background Exertional rhabdomyolysis syndrome is recognised in many athletic horse breeds and in recent years specific forms of the syndrome have been identified. However, although Standardbred horses are used worldwide for racing, there is a paucity of information about the epidemiological and performance-related aspects of the syndrome in this breed. The objectives of this study therefore were to determine the incidence, risk factors and performance effects of exertional rhabdomyolysis syndrome in Standardbred trotters and to compare the epidemiology and genetics of the syndrome with that in other breeds. Methodology/Principal Findings A questionnaire-based case-control study (with analysis of online race records) was conducted following identification of horses that were determined susceptible to exertional rhabdomyolysis (based on serum biochemistry) from a total of 683 horses in 22 yards. Thirty six exertional rhabdomyolysis-susceptible horses were subsequently genotyped for the skeletal muscle glycogen synthase (GYS1) mutation responsible for type 1 polysaccharide storage myopathy. A total of 44 susceptible horses was reported, resulting in an annual incidence of 6.4 (95% CI 4.6–8.2%) per 100 horses. Female horses were at significantly greater risk than males (odds ratio 7.1; 95% CI 2.1–23.4; p = 0.001) and nervous horses were at a greater risk than horses with calm or average temperaments (odds ratio 7.9; 95% CI 2.3–27.0; p = 0.001). Rhabdomyolysis-susceptible cases performed better from standstill starts (p = 0.04) than controls and had a higher percentage of wins (p = 0.006). All exertional rhabdomyolysis-susceptible horses tested were negative for the R309H GYS1 mutation. Conclusions/Significance Exertional rhabdomyolysis syndrome in Standardbred horses has a similar incidence and risk factors to the syndrome in Thoroughbred horses. If the disorder has a genetic basis in Standardbreds, improved performance in susceptible animals may

  10. Epidemiology of exertional rhabdomyolysis susceptibility in standardbred horses reveals associated risk factors and underlying enhanced performance.

    Directory of Open Access Journals (Sweden)

    Cajsa M Isgren

    Full Text Available BACKGROUND: Exertional rhabdomyolysis syndrome is recognised in many athletic horse breeds and in recent years specific forms of the syndrome have been identified. However, although Standardbred horses are used worldwide for racing, there is a paucity of information about the epidemiological and performance-related aspects of the syndrome in this breed. The objectives of this study therefore were to determine the incidence, risk factors and performance effects of exertional rhabdomyolysis syndrome in Standardbred trotters and to compare the epidemiology and genetics of the syndrome with that in other breeds. METHODOLOGY/PRINCIPAL FINDINGS: A questionnaire-based case-control study (with analysis of online race records was conducted following identification of horses that were determined susceptible to exertional rhabdomyolysis (based on serum biochemistry from a total of 683 horses in 22 yards. Thirty six exertional rhabdomyolysis-susceptible horses were subsequently genotyped for the skeletal muscle glycogen synthase (GYS1 mutation responsible for type 1 polysaccharide storage myopathy. A total of 44 susceptible horses was reported, resulting in an annual incidence of 6.4 (95% CI 4.6-8.2% per 100 horses. Female horses were at significantly greater risk than males (odds ratio 7.1; 95% CI 2.1-23.4; p = 0.001 and nervous horses were at a greater risk than horses with calm or average temperaments (odds ratio 7.9; 95% CI 2.3-27.0; p = 0.001. Rhabdomyolysis-susceptible cases performed better from standstill starts (p = 0.04 than controls and had a higher percentage of wins (p = 0.006. All exertional rhabdomyolysis-susceptible horses tested were negative for the R309H GYS1 mutation. CONCLUSIONS/SIGNIFICANCE: Exertional rhabdomyolysis syndrome in Standardbred horses has a similar incidence and risk factors to the syndrome in Thoroughbred horses. If the disorder has a genetic basis in Standardbreds, improved performance in susceptible animals may be

  11. A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model

    Directory of Open Access Journals (Sweden)

    Haule Emmanuel E

    2012-10-01

    Full Text Available Abstract Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich. Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae, Maytenus senegalensis (Lam. Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922, Salmonella typhi (NCTC 8385, Vibrio cholerae (clinical isolate, and Klebsiella pneumoniae (clinical isolate using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole

  12. A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model

    Science.gov (United States)

    2012-01-01

    Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich.) Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae), Maytenus senegalensis (Lam.) Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.)Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholerae (clinical isolate), and Klebsiella pneumoniae (clinical isolate) using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole. Both the individual

  13. Virtual Exertions: a user interface combining visual information, kinesthetics and biofeedback for virtual object manipulation.

    Science.gov (United States)

    Ponto, Kevin; Kimmel, Ryan; Kohlmann, Joe; Bartholomew, Aaron; Radwin, Robert G

    2012-01-01

    Virtual Reality environments have the ability to present users with rich visual representations of simulated environments. However, means to interact with these types of illusions are generally unnatural in the sense that they do not match the methods humans use to grasp and move objects in the physical world. We demonstrate a system that enables users to interact with virtual objects with natural body movements by combining visual information, kinesthetics and biofeedback from electromyograms (EMG). Our method allows virtual objects to be grasped, moved and dropped through muscle exertion classification based on physical world masses. We show that users can consistently reproduce these calibrated exertions, allowing them to interface with objects in a novel way.

  14. Incidental Finding of Inferior Vena Cava Atresia Presenting with Deep Venous Thrombosis following Physical Exertion

    Directory of Open Access Journals (Sweden)

    Shalini Koppisetty

    2015-01-01

    Full Text Available Inferior vena cava atresia (IVCA is a rare but well described vascular anomaly. It is a rare risk factor for deep venous thrombosis (DVT, found in approximately 5% of cases of unprovoked lower extremity (LE DVT in patients <30 years of age. Affected population is in the early thirties, predominantly male, often with a history of major physical exertion and presents with extensive or bilateral DVTs. Patients with IVC anomalies usually develop compensatory circulation through the collateral veins with enlarged azygous/hemizygous veins. Despite the compensatory circulation, the venous drainage of the lower limbs is often insufficient leading to venous stasis and thrombosis. We describe a case of extensive and bilateral deep venous thrombosis following physical exertion in a thirty-six-year-old male patient with incidental finding of IVCA on imaging.

  15. Angina and exertional myocardial ischemia in diabetic and nondiabetic patients: assessment by exercise thallium scintigraphy

    International Nuclear Information System (INIS)

    Nesto, R.W.; Phillips, R.T.; Kett, K.G.; Hill, T.; Perper, E.; Young, E.; Leland, O.S. Jr.

    1988-01-01

    Patients with diabetes mellitus and coronary artery disease are thought to have painless myocardial ischemia more often than patients without diabetes. We studied 50 consecutive patients with diabetes and 50 consecutive patients without diabetes, all with ischemia, on exercise thallium scintigraphy to show the reliability of angina as a marker for exertional ischemia. The two groups had similar clinical characteristics, treadmill test results, and extent of infarction and ischemia, but only 7 patients with diabetes compared with 17 patients without diabetes had angina during exertional ischemia. In diabetic patients the extent of retinopathy, nephropathy, or peripheral neuropathy was similar in patients with and without angina. Angina is an unreliable index of myocardial ischemia in diabetic patients with coronary artery disease. Given the increased cardiac morbidity and mortality in such patients, periodic objective assessments of the extent of ischemia are warranted

  16. [Relationship between efficacy exertion of diuretic traditional Chinese medicines and aquaporin].

    Science.gov (United States)

    Wang, Peng-cheng; Zhao, Shan; Wang, Qiu-hong; Kuang, Hai-xue

    2015-06-01

    In recent years, the discovery and studies on aquaporin have made us have a more in-depth understanding about the physiological and pathological processes of water metabolism. Over years, however, there has been no quantitative study on the target sites of diuretic traditional Chinese medicines at the molecular level. In that case, aquaporin was found to been a new target molecule to explain the efficacy exertion of diuretic traditional Chinese medicines. By studying aquaporin, researchers can understand the implicit meaning of the diuretic effect of traditional Chinese medicines and conduct quantitative studies on the diuretic effect. So far, many scholars have conducted a series of studies in the traditional Chinese medicine field by using the findings on aquaporin and made certain advances. This article provides a summary about the efficacy exertion of diuretic traditional Chinese medicines through target molecule aquaporin.

  17. Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory

    OpenAIRE

    Lapish, C.C.; Balaguer-Ballester, Emili; Seamans, J.K.; Phillips, A.G.; Durstewitz, D.

    2015-01-01

    Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of app...

  18. Cylindrical spirals of myofilamentous origin associated with exertional cramps and rhabdomyolysis.

    Science.gov (United States)

    Wolfe, G I; Burns, D K; Krampitz, D; Barohn, R J

    1997-12-01

    We describe the presence of cylindrical spirals on muscle biopsy from a 31-year-old man who developed rhabodomyolysis following a long run. He had a prior history of exertional cramps and myoglobinuria. His maternal grandfather had similar symptoms. Transmission electron micrographs demonstrated continuity between the lamellae of the cylindrical spirals and native myofilaments. Whether these unusual structures confer a derangement in myofilament function is uncertain.

  19. Within-year Exertional Heat Illness Incidence in U.S. Army Soldiers, 2008-2012

    Science.gov (United States)

    2015-06-01

    ranging from relatively minor heat cramps and heat exhaustion to more severe illnesses, including potentially-fatal exertional heat stroke. The...the within-season proportion to 78.7%. Next, we used week 17 as the start of the season but retained the original week 39 end-of-season breakpoint...calculated the within-season proportion, using the original 1 May and 30 September definition of the heat season (weeks 18 and 39). This approach

  20. Fgf8-Related Secondary Organizers Exert Different Polarizing Planar Instructions along the Mouse Anterior Neural Tube

    OpenAIRE

    Crespo-Enriquez, Ivan; Partanen, Juha; Martinez, Salvador; Echevarria, Diego

    2012-01-01

    Early brain patterning depends on proper arrangement of positional information. This information is given by gradients of secreted signaling molecules (morphogens) detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical...

  1. Physical exercise at the workplace reduces perceived physical exertion during healthcare work

    DEFF Research Database (Denmark)

    Jakobsen, Markus Due; Sundstrup, Emil; Brandt, Mikkel

    2015-01-01

    exercise may decrease physical exertion during work. This study investigates the effect of workplace-based versus home-based physical exercise on physical exertion during work (WRPE) among healthcare workers. METHODS: 200 female healthcare workers (age: 42.0, body mass index: 24.1, average pain intensity......: 3.1 on a scale of 0 to 10, average WRPE: 3.6 on a scale of 0 to 10) from 18 departments at three participating hospitals. Participants were randomly allocated at the cluster level to 10 weeks of: (1) workplace physical exercise (WORK) performed in groups during working hours for 5×10 minutes per...... week and up to five group-based coaching sessions on motivation for regular physical exercise, or (2) home-based physical exercise (HOME) performed during leisure time for 5×10 minutes per week. Physical exertion was assessed at baseline and at 10-week follow-up. RESULTS: 2.2 (SD: 1.1) and 1.0 (SD: 1...

  2. Frequent Exertion and Frequent Standing at Work, by Industry and Occupation Group - United States, 2015.

    Science.gov (United States)

    Shockey, Taylor M; Luckhaupt, Sara E; Groenewold, Matthew R; Lu, Ming-Lun

    2018-01-12

    Repeated exposure to occupational ergonomic hazards, such as frequent exertion (repetitive bending or twisting) and frequent standing, can lead to injuries, most commonly musculoskeletal disorders (1). Work-related musculoskeletal disorders have been estimated to cost the United States approximately $2.6 billion in annual direct and indirect costs (2). A recent literature review provided evidence that prolonged standing at work also leads to adverse health outcomes, such as back pain, physical fatigue, and muscle pain (3). To determine which industry and occupation groups currently have the highest prevalence rates of frequent exertion at work and frequent standing at work, CDC analyzed data from the 2015 National Health Interview Survey (NHIS) Occupational Health Supplement (OHS) regarding currently employed adults in the United States. By industry, the highest prevalence of both frequent exertion and frequent standing at work was among those in the agriculture, forestry, fishing, and hunting industry group (70.9%); by occupation, the highest prevalence was among those in the construction and extraction occupation group (76.9%). Large differences among industry and occupation groups were found with regard to these ergonomic hazards, suggesting a need for targeted interventions designed to reduce workplace exposure.

  3. Exertional Myopathy in a Juvenile Green Sea Turtle (Chelonia mydas Entangled in a Large Mesh Gillnet

    Directory of Open Access Journals (Sweden)

    Brianne E. Phillips

    2015-01-01

    Full Text Available A juvenile female green sea turtle (Chelonia mydas was found entangled in a large mesh gillnet in Pamlico Sound, NC, and was weak upon presentation for treatment. Blood gas analysis revealed severe metabolic acidosis and hyperlactatemia. Plasma biochemistry analysis showed elevated aspartate aminotransferase and creatine kinase, marked hypercalcemia, hyperphosphatemia, and hyperkalemia. Death occurred within 24 hours of presentation despite treatment with intravenous and subcutaneous fluids and sodium bicarbonate. Necropsy revealed multifocal to diffuse pallor of the superficial and deep pectoral muscles. Mild, multifocal, and acute myofiber necrosis was identified by histopathological examination. While histological changes in the examined muscle were modest, the acid-base, mineral, and electrolyte abnormalities were sufficiently severe to contribute to this animal’s mortality. Exertional myopathy in reptiles has not been well characterized. Sea turtle mortality resulting from forced submergence has been attributed to blood gas derangements and seawater aspiration; however, exertional myopathy may also be an important contributing factor. If possible, sea turtles subjected to incidental capture and entanglement that exhibit weakness or dull mentation should be clinically evaluated prior to release to minimize the risk of delayed mortality. Treatment with appropriate fluid therapy and supportive care may mitigate the effects of exertional myopathy in some cases.

  4. Chronic exertional compartment syndrome of the forearm in motocross racers: findings on MRI

    International Nuclear Information System (INIS)

    Gielen, Jan Louis; Peersman, Benjamin; Dyck, Pieter van; Vanhoenacker, Filip; Peersman, Geert; Roelant, Ella; Roeykens, Johan

    2009-01-01

    The purpose of this prospective study was to demonstrate the findings of MRI in motocross racers with chronic exertional compartment syndrome (CECS) of the forearm. Racers with proven CECS and without CECS and male individuals not involved in strenuous activities with the forearm were included. Signal intensity (SI) and signal-to-noise ratio (SNR) obtained before and after exercise were compared (D-SNR). Magnetic resonance imaging after exercise showed an increase in SI and SNR in the muscles on T2-WI. The SI increase was obvious in the flexor digitorum superficialis (FDS) and profundus (FDP) in all CECS patients. In addition, a minor SI and SNR increase in the extensor carpi radialis longus (ECRL) was noted. In the non-symptomatic group of motocross racers, there was only a minor increase in SI and the SNR, which was similar in the FDP and ECRL muscles. In the untrained individuals a remarkable increase in the SI and SNR of the FDS/FDP-ECRL was noted. This increased SI and SNR was not present in the majority of non-symptomatic racers. Post-exertional MRI produces significant findings in CECS of the forearm. The motocross racers without post-exertional oedema in the FDP/FDS had no CECS. (orig.)

  5. Chronic exertional compartment syndrome of the forearm in motocross racers: findings on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Gielen, Jan Louis [Antwerp University Hospital, Department of Radiology, Antwerp (Belgium); Antwerp University Hospital, Multidisciplinary Department of Sports Medicine, Antwerp (Belgium); Peersman, Benjamin; Dyck, Pieter van; Vanhoenacker, Filip [Antwerp University Hospital, Department of Radiology, Antwerp (Belgium); Peersman, Geert [ZNA, Department of Orthopaedic Surgery, Antwerp (Belgium); Roelant, Ella [Antwerp University Hospital, Department of Scientific Coordination, Antwerp (Belgium); Roeykens, Johan [Antwerp University Hospital, Multidisciplinary Department of Sports Medicine, Antwerp (Belgium)

    2009-12-15

    The purpose of this prospective study was to demonstrate the findings of MRI in motocross racers with chronic exertional compartment syndrome (CECS) of the forearm. Racers with proven CECS and without CECS and male individuals not involved in strenuous activities with the forearm were included. Signal intensity (SI) and signal-to-noise ratio (SNR) obtained before and after exercise were compared (D-SNR). Magnetic resonance imaging after exercise showed an increase in SI and SNR in the muscles on T2-WI. The SI increase was obvious in the flexor digitorum superficialis (FDS) and profundus (FDP) in all CECS patients. In addition, a minor SI and SNR increase in the extensor carpi radialis longus (ECRL) was noted. In the non-symptomatic group of motocross racers, there was only a minor increase in SI and the SNR, which was similar in the FDP and ECRL muscles. In the untrained individuals a remarkable increase in the SI and SNR of the FDS/FDP-ECRL was noted. This increased SI and SNR was not present in the majority of non-symptomatic racers. Post-exertional MRI produces significant findings in CECS of the forearm. The motocross racers without post-exertional oedema in the FDP/FDS had no CECS. (orig.)

  6. Caffeine and theanine exert opposite effects on attention under emotional arousal.

    Science.gov (United States)

    Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Taylor, Holly A; Kanarek, Robin B

    2017-01-01

    Tea is perceived as more relaxing than coffee, even though both contain caffeine. L-theanine in tea may account for the difference. Consumed together, caffeine and theanine exert similar cognitive effects to that of caffeine alone, but exert opposite effects on arousal, in that caffeine accentuates and theanine mitigates physiological and felt stress responses. We evaluated whether caffeine and theanine influenced cognition under emotional arousal. Using a double-blind, repeated-measures design, 36 participants received 4 treatments (200 mg caffeine + 0 mg theanine, 0 mg caffeine + 200 mg theanine, 200 mg caffeine + 200 mg theanine, 0 mg caffeine + 0 mg theanine) on separate days. Emotional arousal was induced by highly arousing negative film clips and pictures. Mood, salivary cortisol, and visual attention were evaluated. Caffeine accentuated global processing of visual attention on the hierarchical shape task (p Caffeine reduced flanker conflict difference scores on the Attention Network Test (p caffeine and theanine exert opposite effects on certain attentional processes, but when consumed together, they counteract the effects of each other.

  7. Whole-Exome Molecular Autopsy After Exertion-Related Sudden Unexplained Death in the Young.

    Science.gov (United States)

    Anderson, Jason H; Tester, David J; Will, Melissa L; Ackerman, Michael J

    2016-06-01

    Targeted postmortem genetic testing of the 4 major channelopathy-susceptibility genes (KCNQ1, KCNH2, SCN5A, and RYR2) have yielded putative pathogenic mutations in ≤30% of autopsy-negative sudden unexplained death in the young (SUDY) cases with highest yields derived from the subset of exertion-related SUDY. Here, we evaluate the role of whole-exome sequencing in exertion-related SUDY cases. From 1998 to 2010, 32 cases of exertion-related SUDY were referred by Medical Examiners for a cardiac channel molecular autopsy. A mutational analysis of the major long-QT syndrome-susceptibility genes (KCNQ1, KCNH2, and SCN5A) and catecholaminergic polymorphic ventricular tachycardia-susceptibility gene (RYR2) identified a putative pathogenic mutation in 11 cases. Whole-exome sequencing was performed on the remaining 21 targeted gene-negative SUDY cases. After whole-exome sequencing, a gene-specific surveillance of all genes (N=100) implicated in sudden death was performed to identify putative pathogenic mutation(s). Three of these 21 decedents had a clinically actionable, pathogenic mutation (CALM2-F90L, CALM2-N98S, and PKP2-N634fs). Of the 18 remaining cases, 7 hosted at least 1 variant of unknown significance with a minor allele frequency autopsy-negative SUDY cases. © 2016 American Heart Association, Inc.

  8. [Preliminary study on the best-exerted force chance in the female menstrual cycle].

    Science.gov (United States)

    Yang, Xi; Dai, Hongwei; Wang, Bin; Huang, Lan

    2014-06-01

    To investigate the exerted force in different phases of the female menstrual cycle, as well as the changes in estrogen (E2), osteocalcin (OCN), receptor activator of nuclear factor-kappa B ligand (RANKL), and osteoprotegerin (OPG) levels in the gingival crevicular fluid (GCF) during orthodontic tooth movement, to provide a theoretical basis for the selection of the best opportunity for efficient tooth movement. Twelve women (aged 18 years to 28 years) with extracted first premolars had been selected. Six women in the group were randomly selected as the menstrual period group, whereas the remaining six were assigned to the ovulation period group. Right canines were retracted with 1.5 N NiTi close coil spring. GCF samples were collected prior to the force exertion experiments at 0 (T0), 15 (T1), 30 (T2), and 45 d (T3). The levels of E2, OCN, OPG and RANKL in GCF were measured by chemiluminescence and enzymelinked immunosorbent assay. The E2 and OCN levels were significantly higher in the ovulation period group than in the menstrual period group (P 0.05). Finally, no significant difference was found in RANKL/OPG ratio between the two groups (P > 0.05). Exerted force on teeth during the menstrual period may promote rapid tooth movement.

  9. Comparison of Fourier and wavelet analysis for fatigue assessment during repetitive dynamic exertion.

    Science.gov (United States)

    Chowdhury, Suman Kanti; Nimbarte, Ashish D

    2015-04-01

    The comparative ability of the Fourier transform (FFT) and discrete wavelet transform (DWT) algorithms in assessing muscle fatigue during sub-maximal repetitive dynamic exertion was investigated in this study. Surface electromyography data recorded from the upper trapezius muscle during forty minutes of repetitive upper extremity exertion performed by 10 male participants were used in the analysis. Multi-model regression analysis was performed to study the trend in the power values of the different frequency bands estimated using the FFT and DWT algorithms. Less variability and higher statistical significance was observed for the power value trend computed using the DWT algorithm compared to the FFT algorithm. The regression models provided a better fit for the power values estimated under more fatigued condition compared to the less fatigued condition. The lower frequency bands of 23-46 Hz and 46-93 Hz exhibited the expected and consistent power trend independent of the algorithm (DWT or FFT) used. For the exertions tested in this study, a cubic or curvilinear model explained the fatigue development process with a higher precision than the linear models. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. The Influence of a Bout of Exertion on Novice Barefoot Running Dynamics

    Directory of Open Access Journals (Sweden)

    Rami Hashish, Sachithra D. Samarawickrame, Lucinda Baker, George J. Salem

    2016-06-01

    Full Text Available Barefoot, forefoot strike (FFS running has recently risen in popularity. Relative to shod, rear-foot strike (RFS running, employing a FFS is associated with heightened triceps surae muscle activation and ankle mechanical demand. Novice to this pattern, it is plausible that habitually shod RFS runners exhibit fatigue to the triceps surae when acutely transitioning to barefoot running, thereby limiting their ability to attenuate impact. Therefore, the purpose was to determine how habitually shod RFS runners respond to an exertion bout of barefoot running, operationally defined as a barefoot run 20% of mean daily running distance. Twenty-one RFS runners performed novice barefoot running, before and after exertion. Ankle peak torque, triceps surae EMG median frequency, foot-strike patterns, joint energy absorption, and loading rates were evaluated. Of the 21 runners, 6 maintained a RFS, 10 adopted a mid-foot strike (MFS, and 5 adopted a FFS during novice barefoot running. In-response to exertion, MFS and FFS runners demonstrated reductions in peak torque, median frequency, and ankle energy absorption, and an increase in loading rate. RFS runners demonstrated reductions in peak torque and loading rate. These results indicate that a short bout of running may elicit fatigue to novice barefoot runners, limiting their ability to attenuate impact.

  11. Computer mouse position as a determinant of posture, muscular load and perceived exertion.

    Science.gov (United States)

    Karlqvist, L K; Bernmark, E; Ekenvall, L; Hagberg, M; Isaksson, A; Rostö, T

    1998-02-01

    This study concerned the influence of 6 positions of the computer mouse on the work table on posture, muscular load, and perceived exertion during text editing. An optoelectronic 3-dimensional motion analysis system was used to register the postures of 10 men and 10 women using video display units. Muscular load was also registered (with electromyography), as was perceived exertion (with rating scales). A neutral posture with a relaxed and supported arm showed the least perceived exertion, and the electromyographic results showed low activity in both trapezius muscles in this position. Short operators (all women) showed a numerically higher activity in the 4 examined muscles than the tall operators (all men, except 1). This finding could be related to lower muscle force among women and to anthropometric differences, which also influence biomechanic load moments. Narrow-shouldered operators (8 women and 1 man) and short operators worked with larger outward rotation and abduction of the shoulder in a position of the mouse lateral to the keyboard than the broad-shouldered (7 men and 2 women) and tall operators did. Arm support markedly reduced muscle load in the neck-shoulder region among the operators. The operators using video display units in this study preferred to use the mouse on a table in a close to relaxed, neutral posture of the arm in combination with arm support. Short and narrow-shouldered operators worked in more strenuous postures of the arm when the mouse was located lateral to the keyboard.

  12. An Exploration of Exertion in Mixed Reality Systems via the ``Table Tennis for Three'' Game

    Science.gov (United States)

    Mueller, Florian ‘Floyd'; Gibbs, Martin R.; Vetere, Frank

    Humans experience their physical and social environment through their bodies and their associated movement actions. However, most mixed reality systems approach the integration of the real with a virtual world from a computational perspective, often neglecting the body’s capabilities by offering only limited interaction possibilities with a few augmented tangible objects. We propose a view on mixed reality systems that focuses on the human body and its movements, because we believe such an approach has the potential to support novel interaction experiences, as explored by a prototypal gaming system that was inspired by exertion actions exhibited in table tennis. “Table Tennis for Three” enables augmented bodily experiences while offering new opportunities for interaction, such as supporting three players simultaneously across geographical distances. This case study offers an exploration of the role of the human body and its associated movement actions in mixed reality systems, aiming to contribute toward an understanding of the use of exertion in such systems. Such an understanding can support leveraging the many benefits of exertion through mixed reality systems and therefore guide future advances in this research field.

  13. Defining the Focus of Attention: Effects of Attention on Perceived Exertion and Fatigue.

    Directory of Open Access Journals (Sweden)

    Keith eLohse

    2011-11-01

    Full Text Available This manuscript presents two experiments designed to explore the effects of attention on perceived exertion and time to failure in a fatiguing athletic task. There were two major motivating factors for these experiments. First, there are few studies evaluating attentional focus effects in endurance tasks and, second, there is a lack of integration between studies of attentional focus as external/internal (e.g., Wulf, 2007 compared to associative/dissociative (e.g., Stevenson & Biddle, 1998. In Experiment 1, we used a fatiguing wall-sit posture (essentially a complex, isometric task to compare two different types of external attention with an internal focus on the position of the legs. An external focus (regardless of type increased the time taken to failure and reduced perceived exertion. In Experiment 2, we manipulated subjects’ expectancy of fatigue to test the interaction of attention and expectancy (both top-down factors in this highly fatiguing task. Previous theories of attention during endurance tasks have suggested that as fatigue/pain increase, bottom-up factors begin to dominate subjects’ attention. While this may be true, Experiment 2 showed that even in a highly fatiguing task, attentional strategies and expectancies affected the time to failure and perceived exertion.

  14. Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis.

    Science.gov (United States)

    Valberg, S J; McKenzie, E C; Eyrich, L V; Shivers, J; Barnes, N E; Finno, C J

    2016-09-01

    Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). Prospective and retrospective histopathological description. Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann-Whitney U and Fisher's exact tests. Centrally located myonuclei in mature myofibres were found in significantly more (Prhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a strong resemblance to a myofibrillar myopathy. While many of these horses were previously diagnosed with type 2 polysaccharide storage myopathy, pools of glycogen forming within disrupted myofibrils appeared to give the false appearance of a glycogen storage disorder. © 2015 EVJ Ltd.

  15. Team Size and Stretching-Exercise Effects on Simulated Chest Compression Performance and Exertion

    Directory of Open Access Journals (Sweden)

    Jessica C. Schoen

    2017-09-01

    Full Text Available Introduction: Investigators conducted a prospective experimental study to evaluate the effect of team size and recovery exercises on individual providers’ compression quality and exertion. Investigators hypothesized that 1 larger teams would perform higher quality compressions with less exertion per provider when compared to smaller teams; and 2 brief stretching and breathing exercises during rest periods would sustain compressor performance and mitigate fatigue. Methods: In Phase I, a volunteer cohort of pre-clinical medical students performed four minutes of continuous compressions on a Resusci-Anne manikin to gauge the spectrum of compressor performance in the subject population. Compression rate, depth, and chest recoil were measured. In Phase II, the highest-performing Phase I subjects were placed into 2-, 3-, and/or 4-compressor teams; 2-compressor teams were assigned either to control group (no recovery exercises or intervention group (recovery exercises during rest. All Phase II teams participated in 20-minute simulations with compressor rotation every two minutes. Investigators recorded compression quality and real-time heart rate data, and calculated caloric expenditure from contact heart rate monitor measurements using validated physiologic formulas. Results: Phase I subjects delivered compressions that were 24.9% (IQR1–3: [0.5%–74.1%] correct with a median rate of 112.0 (IQR1–3: [103.5–124.9] compressions per minute and depth of 47.2 (IQR1–3: [35.7–55.2] mm. In their first rotations, all Phase II subjects delivered compressions of similar quality and correctness (p=0.09. Bivariate analyses of 2-, 3-, and 4-compressor teams’ subject compression characteristics by subsequent rotation did not identify significant differences within or across teams. On multivariate analyses, only subjects in 2-compressor teams exhibited significantly lower compression rates (control subjects; p<0.01, diminished chest release (intervention

  16. Update: Exertional rhabdomyolysis, active component, U.S. Army, Navy, Air Force, and Marine Corps, 2011-2015.

    Science.gov (United States)

    Armed Forces Health Surveillance Branch

    2016-03-01

    Among active component members of the U.S. Army, Navy, Air Force, and Marine Corps in 2015, there were 456 incident episodes of rhabdomyolysis likely due to physical exertion or heat stress ("exertional rhabdomyolysis"). Annual rates of incident diagnoses of exertional rhabdomyolysis increased 17% between 2014 and 2015. In 2015, the highest incidence rates occurred in service members who were male; younger than 20 years of age; black, non-Hispanic; members of the Marine Corps and Army; recruit trainees; and in combat-specific occupations. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain and swelling, limited range of motion, or the excretion of dark urine (e.g., myoglobinuria) after strenuous physical activity, particularly in hot, humid weather.

  17. [Effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in COPD].

    Science.gov (United States)

    Ozgur, Eylem Sercan; Atis, Sibel; Kanik, Arzu

    2008-01-01

    There is increasing evidence that dynamic hyperinflation (DH) have negative effects on exercise performance and quality of life in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in patients with COPD. 72 clinically stable patients with moderate to severe COPD and 30 healthy age-matched control subjects were included in this study. Pulmonary function tests including lung volumes and maximal respiratory muscle forces, arterial blood gas analyses, evaluation of exertional dyspnea with the Borg scale, and The Saint George Respiratory Questionnaire (SGRQ, Turkish version) were performed at rest and after a 6-min walk test. We measured the change in inspiratory capacity (AlphaIC) after exercise to reflect DH. 80% of patients with COPD significantly decreased IC after exercise (DH). AlphaIC were -0.27 +/- 0.26 L in COPD and 0.8 +/- 0.17 L in controls (p= 0.001). A stepwise multiple regression analysis showed that to be a patient with COPD, Basal Dyspnea Index (BDI) and AlphaIC were the best predictors of 6 MWD (r(2)= 0.53, p< 0.001). FEV1 added an additinal 9% to the variance in 6 MWD. Exertional dyspnea (AlphaBorg) correlated with AlphaIC (r= -0.44, p= 0.0001) and BDI (r= 0.34, p= 0.02). AlphaIC significantly correlated with symptom (r= -0.36, p= 0.008), activity (r= -0.31, p= 0.03) and total scores (r= -0.30, p= 0.04) of SGRQ. Dynamic hyperinflation can often occur during exersice in patients with COPD. Extent of dynamic hyperinflation could able to explain exercise capacity limitation, exercise dyspnea, and poor quality of life in patients with COPD.

  18. Humanin exerts cardioprotection against cardiac ischemia/reperfusion injury through attenuation of mitochondrial dysfunction.

    Science.gov (United States)

    Thummasorn, Savitree; Apaijai, Nattayaporn; Kerdphoo, Sasiwan; Shinlapawittayatorn, Krekwit; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-12-01

    Myocardial reperfusion via the re-canalization of occluded coronary arteries is gold standard for the treatment of acute myocardial infarction. However, reperfusion itself can cause myocardial damage due to increased reactive oxygen species (ROS) production, a process known as ischemia/reperfusion (I/R) injury. Cardiac mitochondria are the major organelle of ROS production in the heart. Cardiac mitochondrial dysfunction caused by an increased ROS production can increase cardiac arrhythmia incidence, myocardial infarct size, and cardiac dysfunction. Thus, preservation of cardiac mitochondrial function is a promising pharmacological approach to reduce cardiac I/R injury. Humanin (HN), a newly discovered 24-amino acid polypeptide, has been shown to exert antioxidative stress and antiapoptotic effects. Although the cardioprotective effects of HN against I/R injury has been reported, the effect of HN on cardiac mitochondrial function has not yet been investigated. Thus, we tested the hypothesis that HN exerts its cardioprotective effects against I/R injury through the attenuation of cardiac mitochondrial dysfunction. I/R protocol was carried out using a 30-minutes occlusion of a left anterior descending coronary artery followed by a 120-minutes of reperfusion. The plasma HN level, infarct size, arrhythmia incidence, left ventricular function, and cardiac mitochondrial function were determined. Endogenous HN level before I/R injury showed no difference between groups, but was markedly decreased after I/R injury. HN analogue pretreatment decreased arrhythmia incidence and infarct size, improved cardiac mitochondrial function, and attenuated cardiac dysfunction. Humanin analogue pretreatment exerted cardioprotective effects against I/R injury through the attenuation of cardiac mitochondrial dysfunction. © 2016 John Wiley & Sons Ltd.

  19. Delayed Onset Muscle Soreness and Perceived Exertion After Blood Flow Restriction Exercise.

    Science.gov (United States)

    Brandner, Christopher R; Warmington, Stuart A

    2017-11-01

    Brandner, CR, and Warmington, SA. Delayed onset muscle soreness and perceived exertion after blood flow restriction exercise. J Strength Cond Res 31(11): 3101-3108, 2017-The purpose of this study was to determine the perceptual responses to resistance exercise with heavy loads (80% 1 repetition maximum [1RM]), light loads (20% 1RM), or light loads in combination with blood flow restriction (BFR). Despite the use of light loads, it has been suggested that the adoption of BFR resistance exercise may be limited because of increases in delayed onset muscle soreness (DOMS) and perceived exertion. Seventeen healthy untrained males participated in this balanced, randomized cross-over study. After 4 sets of elbow-flexion exercise, participants reported ratings of perceived exertion (RPE), with DOMS also recorded for 7 days after each trial. Delayed onset muscle soreness was significantly greater for low-pressure continuous BFR (until 48 hours postexercise) and high-pressure intermittent BFR (until 72 hours postexercise) than for traditional heavy-load resistance exercise and light-load resistance exercise. In addition, RPE was higher for heavy-load resistance exercise and high-pressure intermittent BFR than for low-pressure continuous BFR, with all trials greater than light-load resistance exercise. For practitioners working with untrained participants, this study provides evidence to suggest that to minimize the perception of effort and postexercise muscle soreness associated with BFR resistance exercise, continuous low-pressure application may be more preferential than intermittent high-pressure application. Importantly, these perceptual responses are relatively short-lived (∼2 days) and have previously been shown to subside after a few exercise sessions. Combined with smaller initial training volumes (set × repetitions), this may limit RPE and DOMS to strengthen uptake and adherence and assist in program progression for muscle hypertrophy and gains in strength.

  20. Systemic exertion intolerance disease/chronic fatigue syndrome is common in sleep centre patients with hypersomnolence: A retrospective pilot study.

    Science.gov (United States)

    Maness, Caroline; Saini, Prabhjyot; Bliwise, Donald L; Olvera, Victoria; Rye, David B; Trotti, Lynn M

    2018-04-06

    Symptoms of the central disorders of hypersomnolence extend beyond excessive daytime sleepiness to include non-restorative sleep, fatigue and cognitive dysfunction. They share much in common with myalgic encephalomyelitis/chronic fatigue syndrome, recently renamed systemic exertion intolerance disease, whose additional features include post-exertional malaise and orthostatic intolerance. We sought to determine the frequency and correlates of systemic exertion intolerance disease in a hypersomnolent population. One-hundred and eighty-seven hypersomnolent patients completed questionnaires regarding sleepiness and fatigue; questionnaires and clinical records were used to assess for systemic exertion intolerance disease. Sleep studies, hypocretin and cataplexy were additionally used to assign diagnoses of hypersomnolence disorders or sleep apnea. Included diagnoses were idiopathic hypersomnia (n = 63), narcolepsy type 2 (n = 25), persistent sleepiness after obstructive sleep apnea treatment (n = 25), short habitual sleep duration (n = 41), and sleepiness with normal sleep study (n = 33). Twenty-one percent met systemic exertion intolerance disease criteria, and the frequency of systemic exertion intolerance disease was not different across sleep diagnoses (p = .37). Patients with systemic exertion intolerance disease were no different from those without this diagnosis by gender, age, Epworth Sleepiness Scale, depressive symptoms, or sleep study parameters. The whole cohort reported substantial fatigue on questionnaires, but the systemic exertion intolerance disease group exhibited more profound fatigue and was less likely to respond to traditional wake-promoting agents (88.6% versus 67.7%, p = .01). Systemic exertion intolerance disease appears to be a common co-morbidity in patients with hypersomnolence, which is not specific to hypersomnolence subtype but may portend a poorer prognosis for treatment response. © 2018 European Sleep Research Society.

  1. The endoplasmic reticulum exerts control over organelle streaming during cell expansion.

    Science.gov (United States)

    Stefano, Giovanni; Renna, Luciana; Brandizzi, Federica

    2014-03-01

    Cytoplasmic streaming is crucial for cell homeostasis and expansion but the precise driving forces are largely unknown. In plants, partial loss of cytoplasmic streaming due to chemical and genetic ablation of myosins supports the existence of yet-unknown motors for organelle movement. Here we tested a role of the endoplasmic reticulum (ER) as propelling force for cytoplasmic streaming during cell expansion. Through quantitative live-cell analyses in wild-type Arabidopsis thaliana cells and mutants with compromised ER structure and streaming, we demonstrate that cytoplasmic streaming undergoes profound changes during cell expansion and that it depends on motor forces co-exerted by the ER and the cytoskeleton.

  2. An exertional heat illness triage tool for a jungle training environment.

    Science.gov (United States)

    Smith, Mike; Withnall, R; Boulter, M

    2017-09-06

    This article introduces a practical triage tool designed to assist commanders, jungle training instructors (JTIs) and medical personnel to identify Defence Personnel (DP) with suspected exertional heat illness (EHI). The challenges of managing suspected EHI in a jungle training environment and the potential advantages to stratifying the urgency of evacuation are discussed. This tool has been designed to be an adjunct to the existing MOD mandated heat illness recognition and first aid training. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    DEFF Research Database (Denmark)

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H

    2015-01-01

    BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... and promotes functional recovery after stroke. However, the core actions of endogenous IFN-β signaling in stroke are unclear. METHODS: To address this question, we used two clinically relevant models of focal cerebral ischemia, transient and permanent middle cerebral artery occlusion, and two genetically...

  4. Histamine exerts multiple effects on expression of genes associated with epidermal barrier function.

    Science.gov (United States)

    Gutowska-Owsiak, D; Salimi, M; Selvakumar, T A; Wang, X; Taylor, S; Ogg, G S

    2014-01-01

    The role of epidermal barrier genes in the pathogenesis of atopic skin inflammation has recently been highlighted. Cytokines that are abundant in the skin during inflammation have been shown to exert various effects on the expression of barrier genes, although the role of histamine in this area of skin biology is not yet fully understood. To assess the effect of stimulation with histamine on keratinocytes by analysis of the pathways involved in epidermal barrier integrity. We performed a gene expression analysis of histamine-stimulated keratinocytes. Functional changes were tested using the dye penetration assay. Differential changes in filaggrin and the filaggrin-processing enzyme bleomycin hydrolase (BLMH) were validated at the protein level, and expression was also assessed in filaggrin knock-down keratinocytes. Histamine altered expression of multiple barrier genes. Expression of filaggrin was downregulated, as was that of other markers, thus suggesting the presence of delayed/aberrant keratinocyte differentiation. Expression of genes involved in cellular adhesiveness and genes of protease expression was dysregulated, but expression of protease inhibitors was increased. BLMH was upregulated in keratinocytes subjected to histamine and filaggrin knockdown. Histamine exerts a dual effect on epidermal barrier genes; it suppresses keratinocyte differentiation and dysregulates genes of cellular adhesiveness, although it induces genes contributing to stratum corneum function. Upregulation of BLMH and protease inhibitors could support maintenance of the permeability barrier by enhanced generation of moisturizing compounds and suppressed desquamation. In contrast, in the case of stratum corneum damage, histamine could enhance transcutaneous sensitization.

  5. Influence of fatigue, stress, muscle soreness and sleep on perceived exertion during submaximal effort.

    Science.gov (United States)

    Haddad, Monoem; Chaouachi, Anis; Wong, Del P; Castagna, Carlo; Hambli, Mourad; Hue, Olivier; Chamari, Karim

    2013-07-02

    The aim of this study was to assess the effects of the Hooper's Index variations (i.e., self-ratings of fatigue, stress, delayed onset muscle soreness (DOMS), and sleep) on rating of perceived exertion during a 10 min submaximal exercise training session (RPE-10 min) and then check the stability and the internal consistency of RPE-10 min. Seventeen junior soccer players took part in this study. The individual Hooper's indices taken before each training session were correlated with RPE-10 min during a constant intensity and duration effort (10 min) using Pearson product moment correlation. Intraclass correlation (ICC) was used to assess the internal consistency of the RPE-10 min. All individual correlations between RPE-10 min and quality of sleep and quantity of fatigue, stress, and DOMS were non-significant (p>0.05). No significant correlations were resulted between RPE-10 min and Hooper's Index in all athletes. The ICC of RPE-10 min was 0.77 thus demonstrating internal consistency. The results of the present study demonstrated the objectivity and utility of RPE as a psychological tool for monitoring training during traditional soccer training. Therefore, the results of the present study suggest that fatigue, stress, DOMS and sleep are not major contributors of perceived exertion during traditional soccer training without excessive training loads. It seems that psychobiological factors other than fatigue, stress, DOMS and sleep may have mediated the 10 min exercise perceptual intensity. © 2013.

  6. Cognition and performance: anxiety, mood and perceived exertion among Ironman triathletes.

    Science.gov (United States)

    Parry, David; Chinnasamy, Camilla; Papadopoulou, Eleni; Noakes, Timothy; Micklewright, Dominic

    2011-11-01

    The authors examined the changing patterns of mood before and after an Ironman triathlon, and the relationships between expected performance outcomes, perception of effort and pacing. Twelve participants in the 2008 Ironman Austria triathlon competition were studied before, during and after the event. Each participant completed measures of mood, anxiety and perceived exertion, while pacing was calculated from official race timings at various points on the course. Positive correlations were found between distance covered and rating of perceived exertion (RPE) during each of the individual disciplines, and also between RPE and the percentage of overall race time completed (r=0.826, panxiety was higher before the race compared with baseline measures. RPE followed a linear progression of RPE during each discipline followed by a re-setting of the perception of effort at the start of the next discipline. The increase in RPE for the entire event followed a linear increase. The linear decline in run pace is consistent with a recent model in which expected RPE is used to modulate pacing. Anxiety and mood responses of participants in this study indicate that the emotional response of athletes before and after ultra-endurance exercise is closely aligned with their conscious thoughts.

  7. The effects of hand force variation on shoulder muscle activation during submaximal exertions.

    Science.gov (United States)

    Meszaros, Kimberly A; Vidt, Meghan E; Dickerson, Clark R

    2018-03-01

    Upper limb injuries are highly prevalent in the workplace and new tools are needed to proactively design workstations to reduce injury risk. The objective was to characterize spatial, load and direction dependency of muscle activity for hand exertions in the upper limb workspace. Electromyographic signals were collected from 14 upper limb muscles during exertions for all combinations of 4 submaximal hand forces (20/30/50/60 N) in 6 cardinal (up/down/left/right/forward/backward) directions at 5 hand locations. Linear muscle activity increases accompanied increased hand forces. Total muscle activity increases between 20 and 60 N hand forces ranged by direction from 92% (downward) to 189% (right). Prediction equations for all muscles depended on hand force, and linear, quadratic and interaction permutations of hand location. Muscle activity associated with manual tasks is load, direction and spatially dependent. Equations developed to describe these complex relationships can be used to better design future and evaluate current occupational activities.

  8. Post-match Perceived Exertion, Feeling and Wellness in Professional Soccer Players.

    Science.gov (United States)

    Fessi, Mohamed Saifeddin; Moalla, Wassim

    2018-01-18

    The aim of this study was to assess post-match perceived exertion, feeling and wellness according to the match outcome (winning, drawing or losing) in professional soccer players. Twelve outfield players were followed during 52 official matches where the outcomes (win, draw or lose) were noted. Following each match players completed both a 10-point scale rating of perceived exertion (RPE) and an 11-point scale rating of perceived feeling. Rating of perceived sleep quality, stress, fatigue and muscle soreness were collected separately on a 7-point scale the day following each match. Player RPE was higher by a very largely magnitude following a loss compared to a draw or a win and higher by a small magnitude after a draw compared to a win. Players felt more pleasure after a win compared to a draw or loss and more displeasure after a loss compared to draw. The players reported a largely and moderately better-perceived sleep quality, less stress and fatigue following a win compared to draw or a loss, and a moderately bad-perceived sleep quality, higher stress and fatigue following a draw compared to a loss. In contrast, only a trivial-small change was observed in perceived muscle soreness between all outcomes. Matches outcomes moderately to largely affect RPE, perceived feeling, sleep quality, stress and fatigue whereas perceived muscle soreness remains high regardless of the match outcome. However, winning a match decreases the strain and improves both pleasure and wellness in professional soccer players.

  9. Validity of the CALER and OMNI-bike ratings of perceived exertion.

    Science.gov (United States)

    Barkley, Jacob E; Roemmich, James N

    2008-04-01

    To test the validity of the Cart and Load Effort Rating (CALER) and OMNI bike RPE scales. Children (16 boys aged 9.5 +/- 0.7 and 16 girls aged 9.4 +/- 0.8) performed a progressive exercise test on a cycle ergometer to exhaustion. Random effects models and correlation analysis were used to determine the association of the undifferentiated perceived exertion from the CALER and OMNI bike scales with heart rate and V O2 for concurrent validity and the association of the CALER scale with the validated OMNI bike scale for construct validity. Tests of proportions were performed to compare the proportion of maximal RPE scale (CALER, OMNI bike) with the proportion of maximal heart rate achieved during the final stage of the exercise test. Concurrent validity of the CALER and OMNI bike scales was established, as increases in scores of both scales were associated with (P bike scale (r = 0.93). The proportion of maximal CALER (75 +/- 20%) and OMNI bike (74 +/- 19%) scales were less (P bike RPE scales was established for a progressively increasing exercise paradigm. However, the proportion of maximal perceived exertion scores from both scales was lower than the proportion of predicted maximal heart rate achieved during the final stage of the exercise test.

  10. Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

    Science.gov (United States)

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Betty, Sarabia-Alcocer; Monica, Velázquez-Sarabia Betty

    2014-01-01

    Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases (P = 0.05) the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001–100 nM); however, this phenomenon was significantly inhibited (P = 0.06) by indomethacin and PINANE-TXA2  (P = 0.05) at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation. PMID:24839599

  11. Estimation of the flow resistances exerted in coronary arteries using a vessel length-based method.

    Science.gov (United States)

    Lee, Kyung Eun; Kwon, Soon-Sung; Ji, Yoon Cheol; Shin, Eun-Seok; Choi, Jin-Ho; Kim, Sung Joon; Shim, Eun Bo

    2016-08-01

    Flow resistances exerted in the coronary arteries are the key parameters for the image-based computer simulation of coronary hemodynamics. The resistances depend on the anatomical characteristics of the coronary system. A simple and reliable estimation of the resistances is a compulsory procedure to compute the fractional flow reserve (FFR) of stenosed coronary arteries, an important clinical index of coronary artery disease. The cardiac muscle volume reconstructed from computed tomography (CT) images has been used to assess the resistance of the feeding coronary artery (muscle volume-based method). In this study, we estimate the flow resistances exerted in coronary arteries by using a novel method. Based on a physiological observation that longer coronary arteries have more daughter branches feeding a larger mass of cardiac muscle, the method measures the vessel lengths from coronary angiogram or CT images (vessel length-based method) and predicts the coronary flow resistances. The underlying equations are derived from the physiological relation among flow rate, resistance, and vessel length. To validate the present estimation method, we calculate the coronary flow division over coronary major arteries for 50 patients using the vessel length-based method as well as the muscle volume-based one. These results are compared with the direct measurements in a clinical study. Further proving the usefulness of the present method, we compute the coronary FFR from the images of optical coherence tomography.

  12. Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Systemic Exertion Intolerance Disease: Three Distinct Clinical Entities

    Directory of Open Access Journals (Sweden)

    Frank N.M. Twisk

    2018-04-01

    Full Text Available Many researchers consider chronic fatigue syndrome (CFS to be a synonym of Myalgic Encephalomyelitis (ME. However, the case criteria of ME and CFS define two distinct clinical entities. Although some patients will meet both case criteria, other patients can meet the diagnosis of ME and not fulfil the case criteria for CFS, while the diagnosis of CFS is largely insufficient to be qualified as a ME patient. ME is a neuromuscular disease with distinctive muscular symptoms, including prolonged muscle weakness after exertion, and neurological signs implicating cerebral dysfunction, including cognitive impairment and sensory symptoms. The only mandatory symptom of CFS is chronic fatigue. Chronic fatigue must be accompanied by at least four out of eight nonspecific symptoms: substantial impairment in short-term memory or concentration, a sore throat, tender lymph nodes, muscle pain, multijoint pain, a new type of headaches, unrefreshing sleep, and postexertional “malaise” lasting more than 24 h. So, regardless whether the name ME is appropriate or not, ME is not synonymous to CFS. That is not a matter of opinion, but a matter of definition. Due to the definitions of ME and CFS, “ME/CFS” does not exist and cannot be replaced by a new clinical entity (SEID: Systemic Exertion Intolerance Disease, as recently suggested.

  13. Febuxostat exerts dose-dependent renoprotection in rats with cisplatin-induced acute renal injury.

    Science.gov (United States)

    Fahmi, Alaa N A; Shehatou, George S G; Shebl, Abdelhadi M; Salem, Hatem A

    2016-08-01

    .0001 versus control group), 114.50 ± 78.63 (P < 0.05 versus CIS group), and 60.91 ± 14.30 (P < 0.001 versus CIS group) mg/dl, respectively). Histological analysis of renal tissues also demonstrated that febuxostat offered a dose-dependent renoprotection. The present study suggests that antioxidant, anti-inflammatory, and cytoprotective mechanisms potentially mediate the renoprotective effects of febuxostat in CIS-administered rats, presenting febuxostat as a promising combinatorial strategy for cancer patients undergoing CIS chemotherapy.

  14. A Fuzzy Logic-Based Personalized Method to Classify Perceived Exertion in Workplaces Using a Wearable Heart Rate Sensor

    Directory of Open Access Journals (Sweden)

    Pablo Pancardo

    2018-01-01

    Full Text Available Knowing the perceived exertion of workers during their physical activities facilitates the decision-making of supervisors regarding the worker allocation in the appropriate job, actions to prevent accidents, and reassignment of tasks, among others. However, although wearable heart rate sensors represent an effective way to capture perceived exertion, ergonomic methods are generic and they do not consider the diffuse nature of the ranges that classify the efforts. Personalized monitoring is needed to enable a real and efficient classification of perceived individual efforts. In this paper, we propose a heart rate-based personalized method to assess perceived exertion; our method uses fuzzy logic as an option to manage imprecision and uncertainty in involved variables. We applied some experiments to cleaning staff and obtained results that highlight the importance of a custom method to classify perceived exertion of people doing physical work.

  15. The effect of wearing jeans on maximum static lifting strength for men and women at various exertion heights.

    Science.gov (United States)

    Chen, Yi-Lang; Li, Chia-Ying; Wang, Chao-Hsuan; Hu, Shiun

    2018-03-13

    This study collected maximum static lifting strength (MSLS) data from 13 males and 13 females at an exertion height of 10-100 cm above the floor (in 10-cm increments) in wearing athletic shorts and wearing jeans conditions. Knee angles were also examined when participants performed the MSLS tasks. Results showed that gender, pant type and exertion height significantly affected participants' MSLS and corresponding knee angle. The effect of wearing jeans primarily occurred at 10-40 cm; meanwhile, male participants tended to stoop while exerting force. This substantially decreased their MSLS (55 N). For female participants in this exertion height range, no significant difference was found in knee angles; accordingly, wearing jeans only slightly affected their MSLS. In summary, wearing jeans had a noticeable effect on the MSLS of male participants, who should be particularly careful when performing lifting tasks at a height of less than 50 cm above the floor.

  16. A Fuzzy Logic-Based Personalized Method to Classify Perceived Exertion in Workplaces Using a Wearable Heart Rate Sensor

    OpenAIRE

    Pancardo, Pablo; Hernández-Nolasco, J. A.; Acosta-Escalante, Francisco

    2018-01-01

    Knowing the perceived exertion of workers during their physical activities facilitates the decision-making of supervisors regarding the worker allocation in the appropriate job, actions to prevent accidents, and reassignment of tasks, among others. However, although wearable heart rate sensors represent an effective way to capture perceived exertion, ergonomic methods are generic and they do not consider the diffuse nature of the ranges that classify the efforts. Personalized monitoring is ne...

  17. Exertional Heat Illness in American Football Players: When Is the Risk Greatest?

    Science.gov (United States)

    Cooper, Earl R; Ferrara, Michael S; Casa, Douglas J; Powell, John W; Broglio, Steven P; Resch, Jacob E; Courson, Ronald W

    2016-08-01

    Knowledge about the specific environmental and practice risks to participants in American intercollegiate football during preseason practices is limited. Identifying risks may mitigate occurrences of exertional heat illness (EHI). To evaluate the associations among preseason practice day, session number, and wet bulb globe temperature (WBGT) and the incidence of EHI. Descriptive epidemiology study. Sixty colleges and universities representing 5 geographic regions of the United States. National Collegiate Athletic Association football players. Data related to preseason practice day, session number, and WBGT. We measured WBGT every 15 minutes during the practice sessions and used the mean WBGT from each session in the analysis. We recorded the incidence of EHIs and calculated the athlete-exposures (AEs). A total of 553 EHI cases and 365 810 AEs were reported for an overall EHI rate of 1.52/1000 AEs (95% confidence interval [CI] = 1.42, 1.68). Approximately 74% (n = 407) of the reported EHI cases were exertional heat cramps (incidence rate = 1.14/1000 AEs; 95% CI = 1.03, 1.25), and about 26% (n = 146) were a combination of exertional heat syncope and heat exhaustion (incidence rate = 0.40/1000 AEs; 95% CI = 0.35, 0.48). The highest rate of EHI occurred during the first 14 days of the preseason period, and the greatest risk was during the first 7 days. The risk of EHI increased substantially when the WBGT was 82.0°F (27.8°C) or greater. We found an increased rate of EHI during the first 14 days of practice, especially during the first 7 days. When the WBGT was greater than 82.0°F (27.8°C), the rate of EHI increased. Sports medicine personnel should take all necessary preventive measures to reduce the EHI risk during the first 14 days of practice and when the environmental conditions are greater than 82.0°F (27.8°C) WBGT.

  18. Association between the Rating Perceived Exertion, Heart Rate and Blood Lactate in Successive Judo Fights (Randori)

    Science.gov (United States)

    Branco, Braulio H.M.; Massuça, Luis M.; Andreato, Leonardo V.; Marinho, Bruno F.; Miarka, Bianca; Monteiro, Luis; Franchini, Emerson

    2013-01-01

    Purpose This study aims to investigate the association between the rating of perceived exertion (RPE), heart rate (HR) and the blood lactate concentration ([La]) in successive judo fight simulations (randori). Methods Ten athletes participated in the study (age: 25.6±2.1 years; stature: 1.75±0.07 m; body mass: 75.6±14.9kg; %BF: 11.5±7.8%; practice: 14.5±6.2 years) and completed 4 judo fight simulations (T1 to T4) with duration of 5 min separated by 5 min passive recovery periods. Before each randori, [La] and HR were collected, and after each randori, the same measures and the RPE (CR-10 scale) were collected. Results Significant correlations were observed between: (1) CR-10 and HR (T2: r =0.70; T3: r =0.64; both, Pjudo fight simulations (Pjudo, should be done with caution. PMID:23802054

  19. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    Science.gov (United States)

    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

  20. Influence of plane bed on the force exerted on a cylinder oscillating in still water

    Energy Technology Data Exchange (ETDEWEB)

    Naeeni, S.T.O. [Tehran Univ., Dept. of Civil Engineering, Tehran (Iran); Narayanan, R. [Universiti Teknologi Malaysia, Faculty of Civil Engineering, Johor Bahru (Malaysia)

    2005-12-01

    The wall pressure field on a cylinder oscillating over a plane bed in still water is reported in this paper. Two gaps between the cylinder and the bed were considered. Pressures on the periphery of the cylinder were measured by a transducer and were found to be essentially repeatable from one cycle to the next. The forces determined from the pressure profiles compare well with those measured directly by a force transducer except significantly at Keulegan-Carpenter number of 15.0. The importance of the plane bed when it is stationary or moving with the cylinder is examined. The significance of the roughness of the bed with respect to the oscillatory forces exerted on the cylinder is also assessed. (Author)

  1. A three-year follow-up of 195 reported occupational over-exertion injuries.

    Science.gov (United States)

    Kemmlert, K; Orelius-Dallner, M; Kilbom, A; Gamberale, F

    1993-03-01

    Three years after reporting occupational over-exertion injuries, 181 persons took part in a follow-up study by questionnaire. The objective was to study these persons with respect to their current status of health, well-being and functional capacity and when possible compare collected data to reference data from the "normal population". The studied group reported more physical and psychological symptoms than the reference groups. More than 50% reported difficulties in activities of daily living. Long sick-leaves in the year following the reported injury were associated with remaining pain and low rate of employment. Three years after the injury, 109 persons were in employment. Almost one third of these had changed occupations and now had more varied tasks than at the time of the report. Those whose work loads had been reduced after the injury, did not report less musculoskeletal disorders than others. However, access to social support was positively related with health and psychological well-being.

  2. Fgf8-related secondary organizers exert different polarizing planar instructions along the mouse anterior neural tube.

    Directory of Open Access Journals (Sweden)

    Ivan Crespo-Enriquez

    Full Text Available Early brain patterning depends on proper arrangement of positional information. This information is given by gradients of secreted signaling molecules (morphogens detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical location of the secondary organizers: the isthmic organizer (IsO and the anterior neural ridge (anr but not on zona limitans intrathalamica (zli. Our results suggest that Sprouty2, a negative modulator of RAS/ERK pathway, is important for regulating Fgf8 morphogenetic signal activity by controlling Fgf8-induced signaling pathways and positional information during early brain development.

  3. Optical force exerted on a Rayleigh particle by a vector arbitrary-order Bessel beam

    International Nuclear Information System (INIS)

    Yang, Ruiping; Li, Renxian

    2016-01-01

    An analytical description of optical force on a Rayleigh particle by a vector Bessel beam is investigated. Linearly, radially, azimuthally, and circularly polarized Bessel beams are considered. The radial, azimuthal, and axial forces by a vector Bessel beam are numerically simulated. The effect of polarization, order of beams, and half-cone angle to the optical force are mainly discussed. For Bessel beams of larger half-cone angle, the non-paraxiality of beams plays an important role in optical forces. Numerical calculations show that optical forces, especially azimuthal forces, are very sensitive to the polarization of beams. - Highlights: • Optical force exerted on a Rayleigh particle by a vector Bessel beam is analytically derived. • Radial, azimuthal, and axial forces are numerically analyzed. • The effect of polarization, order of beam, and non-paraxiality is analyzed.

  4. Exertional myopathy in a grizzly bear (Ursus arctos) captured by leghold snare.

    Science.gov (United States)

    Cattet, Marc; Stenhouse, Gordon; Bollinger, Trent

    2008-10-01

    We diagnosed exertional myopathy (EM) in a grizzly bear (Ursus arctos) that died approximately 10 days after capture by leghold snare in west-central Alberta, Canada, in June 2003. The diagnosis was based on history, post-capture movement data, gross necropsy, histopathology, and serum enzyme levels. We were unable to determine whether EM was the primary cause of death because autolysis precluded accurate evaluation of all tissues. Nevertheless, comparison of serum aspartate aminotransferase and creatine kinase concentrations and survival between the affected bear and other grizzly bears captured by leghold snare in the same research project suggests EM also occurred in other bears, but that it is not generally a cause of mortality. We propose, however, occurrence of nonfatal EM in grizzly bears after capture by leghold snare has potential implications for use of this capture method, including negative effects on wildlife welfare and research data.

  5. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

    Directory of Open Access Journals (Sweden)

    Judith R Homberg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI Prozac® (fluoxetine is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg at postnatal day (PND 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (norfluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (norfluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential

  6. Auxin and physical constraint exerted by the perianth promote androgynophore bending in Passiflora mucronata L. (Passifloraceae).

    Science.gov (United States)

    Rocha, D I; Monte Bello, C C; Sobol, S; Samach, A; Dornelas, M C

    2015-05-01

    The androgynophore column, a distinctive floral feature in passion flowers, is strongly crooked or bent in many Passiflora species pollinated by bats. This is a floral feature that facilitates the adaptation to bat pollination. Crooking or bending of plant organs are generally caused by environmental stimulus (e.g. mechanical barriers) and might involve the differential distribution of auxin. Our aim was to study the role of the perianth organs and the effect of auxin in bending of the androgynophore of the bat-pollinated species Passiflora mucronata. Morpho-anatomical characterisation of the androgynophore, including measurements of curvature angles and cell sizes both at the dorsal (convex) and ventral (concave) sides of the androgynophore, was performed on control flowers, flowers from which perianth organs were partially removed and flowers treated either with auxin (2,4-dichlorophenoxyacetic acid; 2,4-D) or with an inhibitor of auxin polar transport (naphthylphthalamic acid; NPA). Asymmetric growth of the androgynophore column, leading to bending, occurs at a late stage of flower development. Removing the physical constraint exerted by perianth organs or treatment with NPA significantly reduced androgynophore bending. Additionally, the androgynophores of plants treated with 2,4-D were more curved when compared to controls. There was a larger cellular expansion at the dorsal side of the androgynophores of plants treated with 2,4-D and in both sides of the androgynophores of plants treated with NPA. This study suggests that the physical constraint exerted by perianth and auxin redistribution promotes androgynophore bending in P. mucronata and might be related to the evolution of chiropterophily in the genus Passiflora. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

  7. American football and fatal exertional heat stroke: a case study of Korey Stringer

    Science.gov (United States)

    Grundstein, Andrew; Knox, John A.; Vanos, Jennifer; Cooper, Earl R.; Casa, Douglas J.

    2017-08-01

    On August 1, 2001, Korey Stringer, a Pro Bowl offensive tackle for the Minnesota Vikings, became the first and to date the only professional American football player to die from exertional heat stroke (EHS). The death helped raise awareness of the dangers of exertional heat illnesses in athletes and prompted the development of heat safety policies at the professional, collegiate, and interscholastic levels. Despite the public awareness of this death, no published study has examined in detail the circumstances surrounding Stringer's fatal EHS. Using the well-documented details of the case, our study shows that Stringer's fatal EHS was the result of a combination of physiological limitations, organizational and treatment failings, and extreme environmental conditions. The COMfort FormulA (COMFA) energy budget model was used to assess the relative importance of several extrinsic factors on Stringer's EHS, including weather conditions, clothing insulation, and activity levels. We found that Stringer's high-intensity training in relation to the oppressive environmental conditions was the most prominent factor in producing dangerous, uncompensable heat stress conditions and that the full football uniform played a smaller role in influencing Stringer's energy budget. The extreme energy budget levels that led to the fatal EHS would have been avoided according to our modeling through a combination of reduced intensity and lower clothing insulation. Finally, a long delay in providing medical treatment made the EHS fatal. These results highlight the importance of modern heat safety guidelines that provide controls on extrinsic factors, such as the adjustment of duration and intensity of training along with protective equipment modifications based on environmental conditions and the presence of an emergency action plan focused on rapid recognition and immediate on-site aggressive cooling of EHS cases.

  8. Social variables exert selective pressures in the evolution and form of primate mimetic musculature.

    Science.gov (United States)

    Burrows, Anne M; Li, Ly; Waller, Bridget M; Micheletta, Jerome

    2016-04-01

    Mammals use their faces in social interactions more so than any other vertebrates. Primates are an extreme among most mammals in their complex, direct, lifelong social interactions and their frequent use of facial displays is a means of proximate visual communication with conspecifics. The available repertoire of facial displays is primarily controlled by mimetic musculature, the muscles that move the face. The form of these muscles is, in turn, limited by and influenced by phylogenetic inertia but here we use examples, both morphological and physiological, to illustrate the influence that social variables may exert on the evolution and form of mimetic musculature among primates. Ecomorphology is concerned with the adaptive responses of morphology to various ecological variables such as diet, foliage density, predation pressures, and time of day activity. We present evidence that social variables also exert selective pressures on morphology, specifically using mimetic muscles among primates as an example. Social variables include group size, dominance 'style', and mating systems. We present two case studies to illustrate the potential influence of social behavior on adaptive morphology of mimetic musculature in primates: (1) gross morphology of the mimetic muscles around the external ear in closely related species of macaque (Macaca mulatta and Macaca nigra) characterized by varying dominance styles and (2) comparative physiology of the orbicularis oris muscle among select ape species. This muscle is used in both facial displays/expressions and in vocalizations/human speech. We present qualitative observations of myosin fiber-type distribution in this muscle of siamang (Symphalangus syndactylus), chimpanzee (Pan troglodytes), and human to demonstrate the potential influence of visual and auditory communication on muscle physiology. In sum, ecomorphologists should be aware of social selective pressures as well as ecological ones, and that observed morphology might

  9. Camphene, a Plant Derived Monoterpene, Exerts Its Hypolipidemic Action by Affecting SREBP-1 and MTP Expression.

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    Ioanna Vallianou

    Full Text Available The control of hyperlipidemia plays a central role in cardiovascular disease. Previously, we have shown that camphene, a constituent of mastic gum oil, lowers cholesterol and triglycerides (TG in the plasma of hyperlipidemic rats without affecting HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. In the present study, we examine the mechanism by which camphene exerts its hypolipidemic action. We evaluated the effect of camphene on the de novo synthesis of cholesterol and TG from [14C]-acetate in HepG2 cells, along with the statin mevinolin. Camphene inhibited the biosynthesis of cholesterol in a concentration-dependent manner, and a maximal inhibition of 39% was observed at 100 μM while mevinolin nearly abolished cholesterol biosynthesis. Moreover, treatment with camphene reduced TG by 34% and increased apolipoprotein AI expression. In contrast, mevinolin increased TG by 26% and had a modest effect on apolipoprotein AI expression. To evaluate the mode of action of camphene, we examined its effects on the expression of SREBP-1, which affects TG biosynthesis and SREBP-2, which mostly affects sterol synthesis. Interestingly, camphene increased the nuclear translocation of the mature form of SREBP-1 while mevinolin was found to increase the amount of the mature form of SREBP-2. The effect of camphene is most likely regulated through SREBP-1 by affecting MTP levels in response to a decrease in the intracellular cholesterol. We propose that camphene upregulates SREBP-1 expression and MTP inhibition is likely to be a probable mechanism whereby camphene exerts its hypolipidemic effect.

  10. ASSESSMENT OF SUBJECTIVE PERCEIVED EXERTION AT THE ANAEROBIC THRESHOLD WITH THE BORG CR-10 SCALE

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    Antonio R. Zamunér

    Full Text Available The purpose of this study was to evaluate the anaerobic threshold (AT with a graphic visual method for estimating the intensity of ventilatory and metabolic exertion and to determine the ratings of perceived exertion (RPE on the Borg CR-10 scale during a continuous ramp type exercise test (CT-R. Forty healthy, physically active and sedentary young women (age 23.1 ± 3.52 years were divided into two groups according to their fitness level: active group (AG and sedentary group (SG and were submitted to a CT-R on a cycloergometer with 20 to 25 W/min increments. Shortly before the end of each one-minute period, the subjects were asked to rate dyspnea (RPE-D and leg fatigue (RPE-L on the Borg CR-10 scale. After the AT was determined with the graphic visual method, the score that the volunteers gave on the Borg CR10 scale was verified. Data were analyzed using the Mann-Whitney and Spearman correlation tests with the significance level set at 5%. The mean ratings of RPE-L and RPE-D at the AT level were not significantly different between groups (p > 0.05. Significant correlations were found between VO2, heart rate (HR, power output and RPE for both groups. The muscular and respiratory RPE, according to the Borg CR-10 scale, were correlated with the AT, suggesting that scores close to 5, which correspond to a "strong" perception, may be used as parameters for quantifying aerobic exercise intensity for active and sedentary individuals. The similar perception of exercise intensity, which corresponded to the AT of different individuals, makes it possible to prescribe exercise at an intensity equivalent to the AT by means of the RPE.

  11. The Cytoprotective Effects of E-α-(4-Methoxyphenyl-2',3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC--A Novel and Non-Cytotoxic HO-1 Inducer.

    Directory of Open Access Journals (Sweden)

    Kai B Kaufmann

    Full Text Available Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1, is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2',3,4,4'-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2'-hydroxychalcone, calythropsin and 2'-hydroxy-3,4,4'-trimethoxychalcone prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl-2',3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264

  12. Structures, physicochemical and cytoprotective properties of new oxidovanadium(IV) complexes -[VO(mIDA)(dmbipy)]·1.5H2O and [VO(IDA)(dmbipy)]·2H2O

    Science.gov (United States)

    Drzeżdżon, Joanna; Jacewicz, Dagmara; Wyrzykowski, Dariusz; Inkielewicz-Stępniak, Iwona; Sikorski, Artur; Tesmar, Aleksandra; Chmurzyński, Lech

    2017-09-01

    New oxidovanadium(IV) complexes with a modification of the ligand in the VO2+ coordination sphere were synthesized. [VO(mIDA)(dmbipy)]•1.5H2O and [VO(IDA)(dmbipy)]•2H2O were obtained as dark green crystals and grey-green powder, respectively (mIDA = N-methyliminodiacetic anion, IDA = iminodiacetic anion, dmbipy = 4,4‧-dimethoxy-2,2‧-dipyridyl). The crystal structure of [VO(mIDA)(dmbipy)]·1.5H2O has been determined by the X-ray diffraction method. The studies of structure of [VO(mIDA)(dmbipy)]•1.5H2O have shown that this compound occurs in the crystal as two rotational conformers. Furthermore, the stability constants of [VO(mIDA)(dmbipy)]•1.5H2O and [VO(IDA)(dmbipy)]•2H2O complexes in aqueous solutions were studied by using the potentiometric titration method and, consequently, determined using the Hyperquad2008 program. Moreover, the title complexes were investigated as antioxidant substances. The impact of the structure modification in the VO2+ complexes on the radical scavenging activity has been studied. The ability to scavenge the superoxide radical by two complexes - [VO(mIDA)(dmbipy)]·1.5H2O and [VO(IDA)(dmbipy)]·2H2O was studied by cyclic voltammetry (CV) and nitrobluetetrazolium (NBT) methods. The title complexes were also examined by the spectrophotometric method as scavengers of neutral organic radical - 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and radical cation - 2,2'-azinobis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS•+). Furthermore, the biological properties of two oxidovanadium(IV) complexes were investigated in relation to its cytoprotective properties by the MTT and LDH tests based on the hippocampal HT22 neuronal cell line during the oxidative damage induced by hydrogen peroxide. Finally, the results presented in this paper have shown that the both new oxidovanadium(IV) complexes with the 4,4‧-dimethoxy-2,2‧-dipyridyl ligand can be treated as the cytoprotective substances.

  13. The Cytoprotective Effects of E-α-(4-Methoxyphenyl)-2’,3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC)—A Novel and Non-Cytotoxic HO-1 Inducer

    Science.gov (United States)

    Kaufmann, Kai B.; Al-Rifai, Nafisah; Ulbrich, Felix; Schallner, Nils; Rücker, Hannelore; Enzinger, Monika; Petkes, Hermina; Pitzl, Sebastian

    2015-01-01

    Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1), is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2’,3,4,4’-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS) production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2’-hydroxychalcone, calythropsin and 2’-hydroxy-3,4,4’-trimethoxychalcone) prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl)-2’,3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC) demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264

  14. Three-minute constant rate step test for detecting exertional dyspnea relief after bronchodilation in COPD

    Directory of Open Access Journals (Sweden)

    Borel B

    2016-11-01

    Full Text Available Benoit Borel,1,2 Courtney A Wilkinson-Maitland,3 Alan Hamilton,4 Jean Bourbeau,5 Hélène Perrault,6 Dennis Jensen,3,5,7 François Maltais2 1Laboratoire HAVAE, Université de Limoges, Limoges, France; 2Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, 3Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, McGill University, Montréal, QC, 4Boehringer Ingelheim (Canada Limited, Burlington, ON, 5Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Center, Montreal, QC, 6Faculty of Health Sciences, University of Ottawa, Ottawa, ON, 7Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada Background: The aim of this study was to evaluate the responsiveness of the 3-minute constant rate step test (3-MST to detect the relief of exertional dyspnea (respiratory discomfort after acute bronchodilation in COPD patients. Patients and methods: A total of 40 patients with moderate-to-severe COPD (mean forced expiratory volume in 1 second: 45.7 (±14.7, % predicted performed four 3-MSTs at randomly assigned stepping rates of 14, 16, 20 and 24 steps/min after inhalation of nebulized ipratropium bromide (500 µg/salbutamol (2.5 mg and saline placebo, which were randomized to order. Patients rated their intensity of perceived dyspnea at the end of each 3-MST using Borg 0–10 category ratio scale. Results: A total of 37 (92.5%, 36 (90%, 34 (85% and 27 (67.5% patients completed all 3 minutes of exercise at 14, 16, 20 and 24 steps/min under both treatment conditions, respectively. Compared with placebo, ipratropium bromide/salbutamol significantly decreased dyspnea at the end of the third minute of exercise at 14 steps/min (by 0.6±1.0 Borg 0–10 scale units, P<0.01 and 16 steps/min (by 0.7±1.3 Borg 0–10 scale

  15. Ultrasound-Guided Fasciotomy for Chronic Exertional Compartment Syndrome: A Cadaveric Investigation.

    Science.gov (United States)

    Lueders, Daniel R; Sellon, Jacob L; Smith, Jay; Finnoff, Jonathan T

    2017-07-01

    Chronic exertional compartment syndrome (CECS) is a common cause of exertional leg pain. It is commonly treated with a surgical fasciotomy, which has a surgical complication rate of up to 16% and takes approximately 6-12 weeks to return to preprocedure activity levels. Therefore, the development of a less invasive, effective outpatient intervention to treat CECS is desirable. To describe and validate an ultrasound-guided (USG) fasciotomy technique for the anterior and lateral compartments of the lower limb in an unembalmed cadaveric model. Prospective, cadaveric laboratory investigation. Academic institution procedural skills laboratory. Ten unembalmed cadaveric knee-ankle-foot specimens from 1 female (2 specimens) and 7 male donors aged 62-91 years (mean 78.6 years) with body mass indices of 18.9-35.3 kg/m 2 (mean 27.1 kg/m 2 ). Two experienced operators each performed USG anterior and lateral compartment fasciotomies on 5 unembalmed cadaveric legs. A third physician subsequently dissected the legs to assess the continuity of the fasciotomies and to identify any neurovascular damage related to the procedures. Fasciotomy length (in centimeters) and classification by completeness (achieved target length or did not achieve target length) and continuity (continuous or discontinuous) based on predetermined criteria. Muscles, retinaculae, and neurovascular structures were assessed for damage. No neurovascular injuries occurred in any of the 20 USG fasciotomies. The average fasciotomy length was 22.5 cm. All 20 of the fasciotomies achieved the target length. A continuous cephalocaudal fasciotomy was accomplished in 13 of 20 fasciotomies. When a fasciotomy was not continuous, the average length and number of intact fascial bands was 1.52 cm and 2.3, respectively. USG fasciotomy of the anterior and lateral leg compartments can be safely performed in a cadaveric model and can achieve a fasciotomy length comparable to surgical fasciotomy. Most procedures successfully

  16. Prevalence of exertional rhabdomyolysis in endurance horses in the Pacific Northwestern United States.

    Science.gov (United States)

    Wilberger, M S; McKenzie, E C; Payton, M E; Rigas, J D; Valberg, S J

    2015-03-01

    Exertional rhabdomyolysis (ER) is a reported syndrome in competing endurance horses; however, the prevalence and cause of ER in this population have not been defined. To determine the prevalence of ER in a sample of endurance racing horses and investigate factors, including relevant genetic defects, contributing to the occurrence of rhabdomyolysis in this group. Prospective clinical study. Riders of 101 horses participating in one of four 50-mile (80.5 km) distance races completed a comprehensive questionnaire regarding the medical history, management and performance of their horse. Serum creatine kinase activity (CK) was measured before and 4 h after completion of exercise. Hair samples were analysed by PCR for the R309H mutation in the glycogen synthase gene (GYS1) responsible for type 1 polysaccharide storage myopathy (PSSM) and the C7360G mutation in the ryanodine receptor 1 (RYR1) gene causing malignant hyperthermia (MH). Samples were obtained from 68 Arabians, 20 half-Arabians and 13 horses of other breeds. Serum CK was above the resting reference interval (145-633 u/l) in 38 horses after racing (median 883 u/l, range 658-3739) but was compatible with values previously reported in apparently healthy endurance horses. Pathological ER was suspected to occur in 4 horses with serum CK activities exceeding 10,000 u/l 4 h after racing (median 84,825 u/l; range 10,846-381,790) including 3 Arabians and one half-Arabian horse. GYS1 and RYR1 mutations were not present in hair samples from any horses. Exertional rhabdomyolysis occurred at a prevalence of 4.0% in a sample of horses participating in 50 mile distance events and all affected horses were Arabian or half-Arabian. The cause of ER in the endurance horse population remains unknown; however, ER in competing Arabian endurance horses is unlikely to be due to type 1 PSSM or MH. © 2014 EVJ Ltd.

  17. Investigation of a cuboidal permanent magnet’s force exerted on a robotic capsule

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    Yang W

    2014-08-01

    Full Text Available Wan’an Yang,1 Chengbing Tang,2 Fengqing Qin1 1School of Computer and Information Engineering, Yibin University, Yibin, 2CNPC Chuanqing Geophysical Prospecting Company Research Center Computer Department, Chengdu, Sichuan, People’s Republic of China Abstract: To control and drive a robotic capsule accurately from outside a patient’s body, we present a schema in which the capsule enclosing the imaging device, circuits, batteries, etc is looped by a permanent magnet ring that acts as an actuator. A cuboidal permanent magnet situated outside the patient's body attracts or pushes the magnet ring from different directions to make the capsule move or rotate. A mathematic model of attractive or repulsive force that the cuboidal magnet exerts on the magnet ring is presented for accurate calculation of force. The experiments showed that the measuring force was in agreement with the theoretical one, and the relations between the dimensions of the cuboidal magnet and force are useful to produce a cuboidal magnet with optimal shape to get appropriate force. Keywords: control and drive, robotic capsule, permanent magnet ring, optimal dimension, force model

  18. Acute effects of exercise and active video games on adults' reaction time and perceived exertion.

    Science.gov (United States)

    Guzmán, José F; López-García, Jesús

    2016-11-01

    The purpose of the present study was to examine the acute effects of resting, aerobic exercise practised alone, and aerobic exercise with active video games (AVG), on complex reaction time (CRT) and the post-exercise acute rate of perceived exertion (RPE) in young healthy adults. The experimental group was composed of 92 healthy young adults, 78 males and 13 females (age M = 21.9 ± 2.7 years) who completed two sessions, A and B. In session A, participants rode 30 min on an ergometer, while in session B they exercised for 30 min on an ergometer while playing an AVG on a Wii. The control group was composed of 30 young adults, 26 males and 4 females (age M = 21.4 ± 2.9 years) who rested for 30 min. In each session, a CRT task was performed before and after exercising or resting, and post-exercise global RPE was noted. Repeated measures general linear model (GLM) and Wilcoxon tests were performed. (1) Both aerobic exercise alone and aerobic exercise combined with AVG improved CRT, while resting did not; (2) aerobic exercise combined with AVG did not improve CRT more than aerobic exercise only; and (3) RPE was lower after aerobic exercise combined with AVG compared with aerobic exercise only. In young adults, exercise produces acute benefits on CRT, and practising exercise with AVG helps to decrease RPE.

  19. Apico-basal forces exerted by apoptotic cells drive epithelium folding.

    Science.gov (United States)

    Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

    2015-02-12

    Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

  20. Thymus cell population exerting a regulatory function in the immune response of mice of polyvinyl pyrrolidone

    International Nuclear Information System (INIS)

    Rotter, V.; Trainin, N.

    1974-01-01

    An increased response to PVP was observed after adult mouse thymectomy and was partially reversed either by thymus implantation or by a single injection of thymic cells. In addition, an injection of thymic cells was found to reduce the response to PVP in normal recipients. An enhanced response to PVP was measured in B mice compared to that of normals. In such mice reduction of the response to PVP was observed when repeated doses of thymus cells were administered. Lower doses of HC resistant thymus cells strongly inhibited the response to PVP. The cells involved in the thymus regulatory function appear to be radiosensitive, since it was shown that radiation by itself resulted in an increased response to PVP. This inhibitory function of the thymus seems to disappear relatively early in progression of life, as seen by an increased response to PVP in elder mice. These results indicate that a T cell population exerts a regulatory function in the immunological response to PVP that was previously considered to be thymus independent

  1. Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects in Olfactory Bulbectomized Mice.

    Science.gov (United States)

    Matsui, Nobuaki; Akae, Haruka; Hirashima, Nana; Kido, Yuki; Tanabe, Satoshi; Koseki, Mayumi; Fukuyama, Yoshiyasu; Akagi, Masaaki

    2016-11-01

    Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain-derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein after 3 h. The present data indicate that magnolol exerts antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Acute Effect on Arterial Stiffness after Performing Resistance Exercise by Using the Valsalva Manoeuvre during Exertion

    Directory of Open Access Journals (Sweden)

    Wai Yip Vincent Mak

    2015-01-01

    Full Text Available Background. Performing resistance exercise could lead to an increase in arterial stiffness. Objective. We investigate the acute effect on arterial stiffness by performing Valsalva manoeuvre during resistance exercise. Materials and Methods. Eighteen healthy young men were assigned to perform bicep curls by using two breathing techniques (exhalation and Valsalva manoeuvre during muscle contraction on two separate study days. Carotid pulsed wave velocity (cPWV was measured as an indicator to reflect the body central arterial stiffness using a high-resolution ultrasound system, and its value was monitored repeatedly at three predefined time intervals: before resistance exercise, immediately after exercise, and 15 minutes after exercise. Results. At the 0th minute after resistance exercise was performed using the Valsalva manoeuvre during exertion, a significant increase in cPWV (4.91 m/s ± 0.52 compared with the baseline value (4.67 m/s ± 0.32, P=0.008 was observed, and then it nearly returned to its baseline value at the 15th minute after exercise (4.66 m/s ± 0.44, P=0.010. These findings persisted after adjusting for age, body mass index, and systolic blood pressure. Conclusion. Our result suggests short duration of resistance exercise may provoke a transient increase in central arterial stiffness in healthy young men.

  3. Rating of perceived exertion during cycling is associated with subsequent running economy in triathletes.

    Science.gov (United States)

    Bonacci, Jason; Vleck, Veronica; Saunders, Philo U; Blanch, Peter; Vicenzino, Bill

    2013-01-01

    To determine which commonly measured variables of cycling intensity are related to subsequent running economy in triathletes. Cross-sectional laboratory study. Running economy was compared between a control run (no preceding cycle) and a run performed after a 45 min high-intensity cycle in eighteen triathletes. Power output, heart rate, rating of perceived exertion (RPE) and blood lactate concentration were monitored throughout the cycle. The relationship between measures of cycle intensity and the change in running economy was evaluated using Pearson's product moment correlation. Changes in running economy were also interpreted using the smallest worthwhile change (>2.4%) and grouped accordingly (i.e. impaired, no change, or improved running economy). Triathletes' RPE at the end of the cycling bout was significantly associated with the change in running economy after cycling (r=0.57, p=0.01). Average RPE of the cycle bout and RPE at the end of the cycling bout were significantly different between groups, with higher RPE scores being related to impairments in running economy (p=0.04 and p=0.02 respectively). RPE during cycling is associated with subsequent running economy in triathletes. RPE is a simple, cost-effective measure that triathletes and their coaches can use in competition and training to control cycling intensity without the need for specialist equipment such as crank systems or blood analysers. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  4. Effective range of reproductive interference exerted by an alien dandelion, Taraxacum officinale, on a native congener.

    Science.gov (United States)

    Takakura, Koh-Ichi; Matsumoto, Takashi; Nishida, Takayoshi; Nishida, Sachiko

    2011-03-01

    Reproductive interference (RI), defined as the fitness cost of interspecific sexual interactions, such as interspecific pollen transfer (IPT) in plants, is ecologically important. Theoretically, RI could result in competitive exclusion, as it operates in a frequency-dependent manner. Additionally, IPT may have a greater range than resource competition, although information about the range of IPT is lacking. In the present study, we measured the range of IPT exerted by Taraxacum officinale (an alien species) on a native dandelion, T. japonicum. We used two approaches. In one, we analyzed the RI effect on a native seed set at three spatial scales. In the second, we tracked IPT from alien to native flower heads using fluorescent pigments as markers. We estimated that pollination distances were in the order of several meters. These distances exceeded the mean distance from each native plant to the nearest alien. As hypothesized, the effect of RI reached farther than neighboring individuals. These data indicate the spatial range from which alien dandelions should be removed to allow the conservation of natives.

  5. Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes

    Science.gov (United States)

    Block, Linda; Jörneberg, Per; Björklund, Ulrika; Westerlund, Anna; Biber, Björn; Hansson, Elisabeth

    2013-01-01

    Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated Na+ channels when used for neuro-axial blockades. Much lower concentrations of bupivacaine than in normal clinical use, bupivacaine exerts an influence on the Ca2+ signaling and interleukin-1β (IL-1β) secretion in inflammation-reactive astrocytes when used at ultralow concentrations, bupivacaine interacts with the opioid-, 5-hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the μ-opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. With respect to the glutamate-receptor system, bupivacaine, in combination with an ultralow concentration of the μ-opioid receptor antagonist naloxone and μ-opioid receptor agonists, restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. Ultralow concentrations of bupivacaine attenuated the inflammation-induced upregulation of IL-1β secretion. The results indicate that bupivacaine interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting Ca2+ signaling and IL-1β release in inflammation-reactive astrocytes. These results suggest that bupivacaine may be used at ultralow concentrations as an anti-inflammatory drug, either alone or in combination with opioid agonists and ultralow concentrations of an opioid antagonist. PMID:24083665

  6. Interleukin-1 exerts distinct actions on different cell types of the brain in vitro

    Directory of Open Access Journals (Sweden)

    Ying An

    2011-01-01

    Full Text Available Ying An, Qun Chen, Ning QuanDepartment of Oral Biology, Ohio State University, Columbus, OH, USAAbstract: Interleukin-1 (IL-1 is a critical neuroinflammatory mediator in the central nervous system (CNS. In this study, we investigated the effect of IL-1 on inducing inflammation-related gene expression in three astrocyte, two microglial, and one brain endothelial cell line. Interleukin-1 beta (IL-1β is found to be produced by the two microglial cell lines constitutively, but these cells do not respond to IL-1β stimulation. The three astrocyte cell lines responded to IL-1ß stimulation by expressing MCP-1, CXCL-1, and VCAM-1, but different subtypes of astrocytes exhibited different expression profiles after IL-1β stimulation. The brain endothelial cells showed strongest response to IL-1β by producing MCP-1, CXCL-1, VCAM-1, ICAM-1, IL-6, and COX-2 mRNA. The induction of endothelial COX-2 mRNA is shown to be mediated by p38 MAPK pathway, whereas the induction of other genes is mediated by the NF-κB pathway. These results demonstrate that IL-1 exerts distinct cell type-specific action in CNS cells and suggest that IL-1-mediated neuroinflammation is the result of the summation of multiple responses from different cell types in the CNS to IL-1.Keywords: astrocyte, microglia, endothelial cells, signal transduction pathways, gene expression 

  7. The prozone effect exerted by the complement-binding anti-Lea on anti-D.

    Science.gov (United States)

    Joshi, Sanmukh R; Parekh, Kamlesh H

    2017-01-01

    Prozone phenomenon is seen with very high-titer antibodies in an immune serum. The prozone effect on anti-D by a low-titer anti-Le a was investigated associated with neonatal jaundice. Standard methods were used in investigations. The child was born at full-term developed mild jaundice. With weak direct antiglobulin test+, her indirect serum bilirubin was progressed to 27.5 mg/dL in 48 h. Anti-D and anti-Le a were detected in the mother. Both these antibodies were detected in the child's serum though the eluate from red blood cells (RBCs) contained only anti-D. Mother's anti-D was masked by anti-Le a if the RBCs possessed both the antigens together. Anti-D was revealed only with D-positive RBCs lacking Le a or if the serum was modified by mixing with Le a+ saliva or was heated at 56°C or fortified with citrate solution. An anti-D showed prozone effect exerted by the complement-fixing anti-Le a in the test.

  8. Exertional dyspnoea in interstitial lung diseases: the clinical utility of cardiopulmonary exercise testing

    Directory of Open Access Journals (Sweden)

    Matteo Bonini

    2017-02-01

    Full Text Available Interstitial lung diseases (ILDs represent a heterogeneous group of pathologies characterised by alveolar and interstitial damage, pulmonary inflammation (usually associated with fibrosis, decreased lung function and impaired gas exchange, which can be attributed to either a known or an unknown aetiology. Dyspnoea is one of the most common and disabling symptoms in patients with ILD, significantly impacting quality of life. The mechanisms causing dyspnoea are complex and not yet fully understood. However, it is recognised that dyspnoea occurs when there is an imbalance between the central respiratory efferent drive and the response of the respiratory musculature. The respiratory derangement observed in ILD patients at rest is even more evident during exercise. Pathophysiological mechanisms responsible for exertional dyspnoea and reduced exercise tolerance include altered respiratory mechanics, impaired gas exchange, cardiovascular abnormalities and peripheral muscle dysfunction. This review describes the respiratory physiology of ILD, both at rest and during exercise, and aims to provide comprehensive and updated evidence on the clinical utility of the cardiopulmonary exercise test in the assessment and management of these pathological entities. In addition, the role of exercise training and pulmonary rehabilitation programmes in the ILD population is addressed.

  9. Validity of Borg Ratings of Perceived Exertion During Active Video Game Play.

    Science.gov (United States)

    Pollock, Brandon S; Barkley, Jacob E; Potenzini, Nick; Desalvo, Renee M; Buser, Stacey L; Otterstetter, Ronald; Juvancic-Heltzel, Judith A

    During physically interactive video game play (e.g., Nintendo Wii), users are exposed to potential distracters (e.g., video, music), which may decrease their ratings of perceived exertion (RPE) throughout game play. The purpose of this investigation was to determine the association between RPE scores and heart rate while playing the Nintendo Wii. Healthy adults (N = 13, 53.5 ± 5.4 years old) participated in two exercise sessions using the Nintendo Wii Fit Plus. During each session participants played a five-minute warm-up game (Basic Run), two separate Wii Fit Plus games (Yoga, Strength Training, Aerobics or Balance Training) for fifteen minutes each, and then a five-minute cool down game (Basic Run). Borg RPE and heart rate were assessed during the final 30 seconds of the warm up and cool down, as well during the final 30 seconds of play for each Wii Fit Plus game. Correlation analysis combining data from both exercise sessions indicated a moderate positive relationship between heart rate and RPE (r = 0.32). Mixed-effects model regression analyses demonstrated that RPE scores were significantly associated with heart rate ( p positively associated with heart rate in adults during exercise sessions using the Wii Fit Plus. However, this relationship was lower than observed in past research assessing RPE validity during different modes of exercise (e.g. walking, running) without distracters.

  10. Selection mosaic exerted by specialist and generalist herbivores on chemical and physical defense of Datura stramonium.

    Science.gov (United States)

    Castillo, Guillermo; Cruz, Laura L; Tapia-López, Rosalinda; Olmedo-Vicente, Erika; Olmedo-Vicente, Eika; Carmona, Diego; Anaya-Lang, Ana Luisa; Fornoni, Juan; Andraca-Gómez, Guadalupe; Valverde, Pedro L; Núñez-Farfán, Juan

    2014-01-01

    Selection exerted by herbivores is a major force driving the evolution of plant defensive characters such as leaf trichomes or secondary metabolites. However, plant defense expression is highly variable among populations and identifying the sources of this variation remains a major challenge. Plant populations are often distributed across broad geographic ranges and are exposed to different herbivore communities, ranging from generalists (that feed on diverse plant species) to specialists (that feed on a restricted group of plants). We studied eight populations of the plant Datura stramonium usually eaten by specialist or generalist herbivores, in order to examine whether the pattern of phenotypic selection on secondary compounds (atropine and scopolamine) and a physical defense (trichome density) can explain geographic variation in these traits. Following co-evolutionary theory, we evaluated whether a more derived alkaloid (scopolamine) confers higher fitness benefits than its precursor (atropine), and whether this effect differs between specialist and generalist herbivores. Our results showed consistent directional selection in almost all populations and herbivores to reduce the concentration of atropine. The most derived alkaloid (scopolamine) was favored in only one of the populations, which is dominated by a generalist herbivore. In general, the patterns of selection support the existence of a selection mosaic and accounts for the positive correlation observed between atropine concentration and plant damage by herbivores recorded in previous studies.

  11. The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity

    Directory of Open Access Journals (Sweden)

    Emmanuel Ampofo

    2015-11-01

    Full Text Available Background: The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Methods: Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte aggregates (PLA formation were analyzed by flow cytometry. Mouse dorsal skinfold chambers were used to determine in vivo the effect of fascaplysin on photochemically induced thrombus formation and tail-vein bleeding time. Results: Pre-treatment of platelets with fascaplysin reduced the activation of glycoprotein (GPIIb/IIIa after protease-activated receptor-1-activating peptide (PAR-1-AP, adenosine diphosphate (ADP and phorbol-12-myristate-13-acetate (PMA stimulation, but did not markedly affect the expression of P-selectin. This was associated with a decreased platelet aggregation. Fascaplysin also decreased PLA formation after PMA but not PAR-1-AP and ADP stimulation. This may be explained by an increased expression of CD11b on leukocytes in PAR-1-AP- and ADP-treated whole blood. In the dorsal skinfold chamber model of photochemically induced thrombus formation, fascaplysin-treated mice revealed a significantly extended complete vessel occlusion time when compared to controls. Furthermore, fascaplysin increased the tail-vein bleeding time. Conclusion: Fascaplysin exerts anti-thrombotic activity, which represents a novel mode of action in the pleiotropic activity spectrum of this compound.

  12. The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity.

    Science.gov (United States)

    Ampofo, Emmanuel; Später, Thomas; Müller, Isabelle; Eichler, Hermann; Menger, Michael D; Laschke, Matthias W

    2015-11-09

    The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte aggregates (PLA) formation were analyzed by flow cytometry. Mouse dorsal skinfold chambers were used to determine in vivo the effect of fascaplysin on photochemically induced thrombus formation and tail-vein bleeding time. Pre-treatment of platelets with fascaplysin reduced the activation of glycoprotein (GP)IIb/IIIa after protease-activated receptor-1-activating peptide (PAR-1-AP), adenosine diphosphate (ADP) and phorbol-12-myristate-13-acetate (PMA) stimulation, but did not markedly affect the expression of P-selectin. This was associated with a decreased platelet aggregation. Fascaplysin also decreased PLA formation after PMA but not PAR-1-AP and ADP stimulation. This may be explained by an increased expression of CD11b on leukocytes in PAR-1-AP- and ADP-treated whole blood. In the dorsal skinfold chamber model of photochemically induced thrombus formation, fascaplysin-treated mice revealed a significantly extended complete vessel occlusion time when compared to controls. Furthermore, fascaplysin increased the tail-vein bleeding time. Fascaplysin exerts anti-thrombotic activity, which represents a novel mode of action in the pleiotropic activity spectrum of this compound.

  13. Exertional Dyspnoea in Chronic Respiratory Diseases: From Physiology to Clinical Application.

    Science.gov (United States)

    Dubé, Bruno-Pierre; Vermeulen, François; Laveneziana, Pierantonio

    2017-02-01

    Dyspnoea is a complex, highly personalized and multidimensional sensory experience, and its underlying cause and mechanisms are still being investigated. Exertional dyspnoea is one of the most frequently encountered symptoms of patients with cardiopulmonary diseases, and is a common reason for seeking medical help. As the symptom usually progresses with the underlying disease, it can lead to an avoidance of physical activity, peripheral muscle deconditioning and decreased quality of life. Dyspnoea is closely associated with quality of life, exercise (in)tolerance and prognosis in various conditions, including chronic obstructive pulmonary disease, heart failure, interstitial lung disease and pulmonary hypertension, and is therefore an important therapeutic target. Effective management and treatment of dyspnoea is an important challenge for caregivers, and therapeutic options that attempt to reverse its underlying cause have been only partially successful This "review" will attempt to shed light on the physiological mechanisms underlying dyspnoea during exercise and to translate/apply them to a broad clinical spectrum of cardio-respiratory disorders. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Aerobic exercise training without weight loss reduces dyspnea on exertion in obese women

    Science.gov (United States)

    Bernhardt, Vipa; Stickford, Jonathon L.; Bhammar, Dharini M.; Babb, Tony G.

    2015-01-01

    Dyspnea on exertion (DOE) is a common symptom in obesity. We investigated whether aerobic exercise training without weight loss could reduce DOE. Twenty-two otherwise healthy obese women participated in a 12-week supervised aerobic exercise training program, exercising 30 min/day at 70–80% heart rate reserve, 4 days/week. Subjects were grouped based on their Ratings of Perceived Breathlessness (RPB) during constant load 60W cycling: +DOE (n = 12, RPB ≥ 4, 37 ± 7 years, 34 ± 4kg/m2) and −DOE (n = 10, RPB ≤ 2, 32 ± 6 years, 33 ± 3kg/m2). No significant differences between the groups in body composition, pulmonary function, or cardiorespiratory fitness were observed pre-training. Post-training, peak was improved significantly in both groups (+DOE: 12 ± 7, −DOE: 14 ± 8%). RPB was significantly decreased in the + DOE (4.7 ± 1.0–2.5 ± 1.0) and remained low in the −DOE group (1.2 ± 0.6–1.3 ± 1.0) (interaction p Aerobic exercise training improved cardiorespiratory fitness and DOE and thus appears to be an effective treatment for DOE in obese women. PMID:26593640

  15. Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro

    Directory of Open Access Journals (Sweden)

    Shen X

    2017-02-01

    Full Text Available Xin Shen,1,* Nan Zhou,1,* Le Mi,1 Zishuo Hu,2 Libin Wang,1 Xueying Liu,1 Shengyong Zhang1 1Department of Medicinal Chemistry, School of Pharmacy, 2Student Brigade, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Abstract: The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph. In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6 myotubes. Daily oral treatment with Ph for 4 weeks significantly (P<0.05 reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD–POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of T2D rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes. Keywords: phloretin, diabetes, insulin sensitivity, blood glucose consumption, skeletal muscle

  16. Local strain exerted on Nb3Sn filaments in an ITER strand

    International Nuclear Information System (INIS)

    Osamura, Kozo; Machiya, Shutaro; Harjo, Stefanus; Nakamoto, Tatsushi; Cheggour, Najib; Nijhuis, Arend

    2015-01-01

    As part of an international project to benchmark facilities for measuring the strain dependence of critical current in International Thermonuclear Experimental Reactor (ITER) Nb 3 Sn strands, direct measurement of local strain exerted on Nb 3 Sn filaments was attempted at cryogenic temperature by means of a pulsed neutron technique. The lattice axial strain increased linearly with a slope close to unity against applied strain, while the thermal axial strain was −0.22% at 8.5 K. As a result, the force-free strain was evaluated to be 0.22–0.23%. This key parameter should provide an accurate estimate of the peak location of critical current versus applied strain. The lattice transverse strain decreased linearly as a function of applied strain with a slope of 0.33–0.34. The lattice strains of the Nb and Cu components were also measured and their behavior was analyzed by computing diffraction elastic moduli based on micromechanics theories. The stress–strain curve calculated according to the rule of mixtures described quite well the macroscopic curve measured for the present ITER Nb 3 Sn strand. (paper)

  17. Melittin exerts an antitumor effect on non‑small cell lung cancer cells.

    Science.gov (United States)

    Zhang, Su-Fang; Chen, Zhe

    2017-09-01

    Lung cancer accounts for a significant percentage of all cancer‑associated mortalities in men and women, with non‑small cell lung cancer being the most frequently occurring type of lung cancer. Melittin is the principal active component of apitoxin (bee venom) that has been reported to exert anti‑chronic inflammatory and anti‑cancer effects. In the present study, the antitumor effect of melittin was evaluated using in vivo and in vitro analyses. The results demonstrated that melittin significantly inhibited the epidermal growth factor‑induced invasion and migration of non‑small cell lung cancer cells. Subcutaneous injection of melittin at doses of 1 and 10 mg/kg significantly suppressed non‑small cell lung cancer tumor growth by 27 and 61%, respectively. In addition, melittin significantly inhibited the secretion of vascular endothelial growth factor (VEGF) in non‑small cell lung cancer cells. Furthermore, melittin decreased the protein expression of VEGF and hypoxia‑inducible factor 1‑α. Therefore, the antitumor activity of melittin may be associated with the anti‑angiogenic actions of inhibiting the VEGF and hypoxia‑inducible factor signaling pathways.

  18. Selection mosaic exerted by specialist and generalist herbivores on chemical and physical defense of Datura stramonium.

    Directory of Open Access Journals (Sweden)

    Guillermo Castillo

    Full Text Available Selection exerted by herbivores is a major force driving the evolution of plant defensive characters such as leaf trichomes or secondary metabolites. However, plant defense expression is highly variable among populations and identifying the sources of this variation remains a major challenge. Plant populations are often distributed across broad geographic ranges and are exposed to different herbivore communities, ranging from generalists (that feed on diverse plant species to specialists (that feed on a restricted group of plants. We studied eight populations of the plant Datura stramonium usually eaten by specialist or generalist herbivores, in order to examine whether the pattern of phenotypic selection on secondary compounds (atropine and scopolamine and a physical defense (trichome density can explain geographic variation in these traits. Following co-evolutionary theory, we evaluated whether a more derived alkaloid (scopolamine confers higher fitness benefits than its precursor (atropine, and whether this effect differs between specialist and generalist herbivores. Our results showed consistent directional selection in almost all populations and herbivores to reduce the concentration of atropine. The most derived alkaloid (scopolamine was favored in only one of the populations, which is dominated by a generalist herbivore. In general, the patterns of selection support the existence of a selection mosaic and accounts for the positive correlation observed between atropine concentration and plant damage by herbivores recorded in previous studies.

  19. Biological effects of compressive forces exerted on particulate bone grafts during socket preservation: animal study.

    Science.gov (United States)

    Delgado-Ruiz, Rafael; Romanos, Georgios E; Alexandre Gerhke, Sergio; Gomez-Moreno, Gerardo; Maté-Sánchez de Val, José Eduardo; Calvo-Guirado, José Luis

    2016-08-02

    To compare different compressive forces exerted on a particulate graft material during socket preservation and their effects on bone regeneration. Six male dogs were used. The second, third, and fourth premolars, and the first molar were extracted bilaterally at the lower jaws. A particulate synthetic biphasic grafting material (60% HA and 40% β-tricalcium phosphate) was used. Three different standardized compressive forces were applied randomly during the socket preservation. The sample was divided into four experimental groups Test A (10 g), Test B (50 g), Test C (200 g), and Control (empty sockets). Collagen membranes were placed, and primary closure was obtained. Two months after the surgery the animals were sacrificed, and histomorphometric analysis of non-decalcified samples was performed at the coronal, middle, and apical thirds. Grafted sockets resulted in higher bony contour (3 ± 0.43 mm 2 ; P  0.05). Within the limitations of this experimental animal study, it might be concluded that grafted sockets compressed with 200 g force will have higher bony contours; higher compressive forces facilitate the penetration of the particulate graft material into the apical area of the socket and results in more bone formation at the coronal, middle, and apical thirds. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Exertional muscle injury: evaluation of concentric versus eccentric actions with serial MR imaging.

    Science.gov (United States)

    Shellock, F G; Fukunaga, T; Mink, J H; Edgerton, V R

    1991-06-01

    Eccentric muscular actions involve the forced lengthening or stretching of muscles and tend to produce exertional injuries. This study used magnetic resonance (MR) imaging to serially evaluate muscles in five healthy, untrained subjects who performed exhaustive biceps exercise by doing isolated eccentric and concentric actions with a dumbbell. Symptoms were assessed, and T2-weighted images of the arms were obtained before exercise and 1, 3, 5, 10, 25, 40, 50, 60, and 80 days after exercise. Statistically significant increases in T2 relaxation times indicative of muscle injury occurred on each day of MR imaging evaluation in muscles performing eccentric actions, peaking on day 3 in two subjects; day 5, two subjects; and day 10, one subject. The pattern and extent of the abnormalities on MR images were variable. Pain, soreness, and joint stiffness were present on days 1, 3, and 5 in muscles that performed eccentric actions. MR imaging showed subclinical abnormalities that lasted as long as 75 days after the disappearance of symptoms (two subjects). Muscles that performed concentric actions had no changes in T2 relaxation times and were asymptomatic throughout the study.

  1. Effect of Music Tempo on Attentional Focus and Perceived Exertion during Self-selected Paced Walking.

    Science.gov (United States)

    Silva, Aldo Coelho; Dos Santos Ferreira, Sandro; Alves, Ragami Chaves; Follador, Lucio; DA Silva, Sergio Gregorio

    2016-01-01

    This study investigated the influence of music on the rating of perceived exertion (RPE) and attentional focus during walking at a self-selected pace. Fifteen overweight and obese women volunteered to participate in the study. They underwent four sessions: the first for incremental maximal test and anthropometric measurement followed by three experimental sessions. After the first session, they were exposed to three 30-minute walking sessions at a self-selected pace in a counterbalanced order: fast-tempo music (FT), medium-tempo music (MT) and no-music control (NM). Borg's RPE Scale and an Attentional Focus Questionnaire were used to measure the perceptual response and attentional focus, respectively. Results showed that the RPE was higher in the no-music control than in the medium-tempo music (12.05 ± 0.6 vs. 10.5 ± 0.5). Furthermore, dissociative attentional focus was greater for both conditions with music in comparison with the no-music control (NM= 39.0 ± 4.1; MT= 48.4 ± 4.1 and FT= 47.9 ± 4.5). The results indicated that the use of music during walking can modulate attentional focus, increasing dissociative thought, and medium-tempo music can reduce the RPE.

  2. Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

    Directory of Open Access Journals (Sweden)

    Keisuke Ishizawa

    Full Text Available Diabetic nephropathy (DN is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice, NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

  3. Rating of Perceived Exertion and Physiological Responses in Water-Based Exercise

    Directory of Open Access Journals (Sweden)

    Santana Pinto Stephanie

    2015-12-01

    Full Text Available The aim of the present study was to relate the overall rating of perceived exertion (RPE-overall with cardiorespiratory and neuromuscular variables during stationary running with the elbow flexion/extension performed with water-floating equipment. The sample consisted of eleven women that performed the water-based exercise at submaximal cadences. The heart rate, oxygen uptake, ventilation, and electromyographic signal (EMG from biceps brachii (%EMG BB, triceps brachii (%EMG TB, biceps femoris (%EMG BF and rectus femoris (%EMG RF muscles were measured during the exercise, and the overall RPE was measured immediately following its completion. The Pearson product-moment linear correlation was used to investigate associations between the variables analyzed in the present study. Significant relationships were observed between the RPE-overall and all the cardiorespiratory variables, with the r values ranging from 0.60 to 0.70 (p<0.05. In addition, the RPE-overall showed a significant (p<0.05 relationship with %EMG BB (r=0.55 and %EMG BF (r=0.50. These results suggest an association between the RPE-overall with all cardiorespiratory and two neuromuscular variables during the execution of a water-based aerobic exercise using water-floating equipment.

  4. Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry.

    Science.gov (United States)

    Holnthoner, Wolfgang; Bonstingl, Cornelia; Hromada, Carina; Muehleder, Severin; Zipperle, Johannes; Stojkovic, Stefan; Redl, Heinz; Wojta, Johann; Schöchl, Herbert; Grillari, Johannes; Weilner, Sylvia; Schlimp, Christoph J

    2017-06-16

    Endothelial cells (ECs) are major modulators of hemostasis by expressing and releasing pro- and anticoagulant mediators into the circulation. Previous studies showed that cultured ECs release procoagulant mediators into cell culture supernatants as evidenced by the reduction of viscoelastic clotting time. This effect was reversed with an anti-tissue factor antibody. Here, we aimed to investigate whether tissue factor (TF) was released by endothelial-derived extracellular vesicles (EVs) and which portion of the released vesicles displays the most prominent procoagulant properties. After stimulation of ECs with tumor-necrosis factor-α (TNF-α) the supernatants of EC cultures were subjected to differential centrifugation steps to collect larger and smaller EVs which were then characterised by nanoparticle tracking analysis (NTA) and flow cytometry. Mixed with fresh human blood and analysed by thromboelastometry EVs exerted a significant procoagulant stimulus, which could be partly reversed by addition of an anti-TF antibody. Moreover, TF activity was confirmed in the centrifuged fractions. In summary, our results provide evidence of the procoagulant potential of smaller and larger endothelial-derived EV fractions detected by thromboelastometry. The observed effect is most likely due to the release of TF-bearing EVs of different dimensions, which are released upon TNF-α stimulation of endothelial cell cultures.

  5. YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers.

    Science.gov (United States)

    Stein, Claudia; Bardet, Anaïs Flore; Roma, Guglielmo; Bergling, Sebastian; Clay, Ieuan; Ruchti, Alexandra; Agarinis, Claudia; Schmelzle, Tobias; Bouwmeester, Tewis; Schübeler, Dirk; Bauer, Andreas

    2015-08-01

    YAP1 is a major effector of the Hippo pathway and a well-established oncogene. Elevated YAP1 activity due to mutations in Hippo pathway components or YAP1 amplification is observed in several types of human cancers. Here we investigated its genomic binding landscape in YAP1-activated cancer cells, as well as in non-transformed cells. We demonstrate that TEAD transcription factors mediate YAP1 chromatin-binding genome-wide, further explaining their dominant role as primary mediators of YAP1-transcriptional activity. Moreover, we show that YAP1 largely exerts its transcriptional control via distal enhancers that are marked by H3K27 acetylation and that YAP1 is necessary for this chromatin mark at bound enhancers and the activity of the associated genes. This work establishes YAP1-mediated transcriptional regulation at distal enhancers and provides an expanded set of target genes resulting in a fundamental source to study YAP1 function in a normal and cancer setting.

  6. YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers.

    Directory of Open Access Journals (Sweden)

    Claudia Stein

    2015-08-01

    Full Text Available YAP1 is a major effector of the Hippo pathway and a well-established oncogene. Elevated YAP1 activity due to mutations in Hippo pathway components or YAP1 amplification is observed in several types of human cancers. Here we investigated its genomic binding landscape in YAP1-activated cancer cells, as well as in non-transformed cells. We demonstrate that TEAD transcription factors mediate YAP1 chromatin-binding genome-wide, further explaining their dominant role as primary mediators of YAP1-transcriptional activity. Moreover, we show that YAP1 largely exerts its transcriptional control via distal enhancers that are marked by H3K27 acetylation and that YAP1 is necessary for this chromatin mark at bound enhancers and the activity of the associated genes. This work establishes YAP1-mediated transcriptional regulation at distal enhancers and provides an expanded set of target genes resulting in a fundamental source to study YAP1 function in a normal and cancer setting.

  7. Revised model for the radiation force exerted by standing surface acoustic waves on a rigid cylinder

    Science.gov (United States)

    Liang, Shen; Chaohui, Wang

    2018-03-01

    In this paper, a model for the radiation force exerted by standing surface acoustic waves (SSAWs) on a rigid cylinder in inviscid fluids is extended to account for the dependence on the Rayleigh angle. The conventional model for the radiation force used in the SSAW-based applications is developed in plane standing waves, which fails to predict the movement of the cylinder in the SSAW. Our revised model reveals that, in the direction normal to the piezoelectric substrate on which the SSAW is generated, acoustic radiation force can be large enough to drive the cylinder even in the long-wavelength limit. Furthermore, the force in this direction can not only push the cylinder away, but also pull it back toward the substrate. In the direction parallel to the substrate, the equilibrium positions for particles can be actively tuned by changing Rayleigh angle. As an example considered in the paper, with the reduction of Rayleigh angle the equilibrium positions for steel cylinders in water change from pressure nodes to pressure antinodes. The model can thus be used in the design of SSAWs for particle manipulations.

  8. Victorianizing Guangxu: Arresting Flows, Minting Coins, and Exerting Authority in Early Twentieth-Century Kham

    Directory of Open Access Journals (Sweden)

    Scott Relyea

    2016-06-01

    Full Text Available In the late Qing and early Republican eras, eastern Tibet (Kham was a borderland on the cusp of political and economic change. Straddling Sichuan Province and central Tibet, it was coveted by both Chengdu and Lhasa. Informed by an absolutist conception of territorial sovereignty, Sichuan officials sought to exert exclusive authority in Kham by severing its inhabitants from regional and local influence. The resulting efforts to arrest the flow of rupees from British India and the flow of cultural identity entwined with Buddhism from Lhasa were grounded in two misperceptions: that Khampa opposition to Chinese rule was external, fostered solely by local monasteries as conduits of Lhasa’s spiritual authority, and that Sichuan could arrest such influence, the absence of which would legitimize both exclusive authority in Kham and regional assertions of sovereignty. The intersection of these misperceptions with the significance of Buddhism in Khampa identity determined the success of Sichuan’s policies and the focus of this article, the minting and circulation of the first and only Qing coin emblazoned with an image of the emperor. It was a flawed axiom of state and nation builders throughout the world that severing local cultural or spiritual influence was possible—or even necessary—to effect a borderland’s incorporation.

  9. Sam68 exerts separable effects on cell cycle progression and apoptosis

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    Resnick Ross J

    2004-01-01

    Full Text Available Abstract Background The RNA-binding protein Sam68 has been implicated in a number of cellular processes, including transcription, RNA splicing and export, translation, signal transduction, cell cycle progression and replication of the human immunodeficiency virus and poliovirus. However, the precise impact it has on essential cellular functions remains largely obscure. Results In this report we show that conditional overexpression of Sam68 in fibroblasts results in both cell cycle arrest and apoptosis. Arrest in G1 phase of the cell cycle is associated with decreased levels of cyclins D1 and E RNA and protein, resulting in dramatically reduced Rb phosphorylation. Interestingly, cell cycle arrest does not require the specific RNA binding ability of Sam68. In marked contrast, induction of apoptosis by Sam68 absolutely requires a fully-functional RNA binding domain. Moreover, the anti-cancer agent trichostatin A potentiates Sam68-driven apoptosis. Conclusions For the first time we have shown that Sam68, an RNA binding protein with multiple apparent functions, exerts functionally separable effects on cell proliferation and survival, dependent on its ability to bind specifically to RNA. These findings shed new light on the ability of signal transducing RNA binding proteins to influence essential cell function. Moreover, the ability of a class of anti-cancer therapeutics to modulate its ability to promote apoptosis suggests that Sam68 status may impact some cancer treatments.

  10. Perceived exertion during muscle fatigue as reflected in movement-related cortical potentials: an event-related potential study.

    Science.gov (United States)

    Guo, Feng; Sun, Yong-Jun; Zhang, Ri-Hui

    2017-02-08

    The aim of this study was to explore the mechanism on perceived exertion during muscle fatigue. A total of 15 individuals in the fatigue group and 13 individuals in the nonfatigue group were recruited into this study, performing 200 intermittent handgrip contractions with 30% maximal voluntary contraction. The force, surface electromyography (sEMG), movement-related cortical potentials (MRCPs), and rating perception of effort (RPE) were combined to evaluate the perceived exertion during muscle fatigue. The maximal handgrip force significantly decreased (Pfatigue. The RPE scores reported by the individuals and the motor potential amplitude of MRCPs in the fatigue group significantly increased (Pfatigue but could also reflect the peripheral local muscle fatigue.

  11. Ratings of Perceived Exertion, Heart Rate, and Power Output in Predicting Maximal Oxygen Uptake During Submaximal Cycle Ergometry.

    Science.gov (United States)

    Wilmore, Jack H.; And Others

    1986-01-01

    Sixty-two subjects completed a four-stage submaximal cycle ergometer test to determine if estimates of maximal oxygen uptake could be improved by using ratings of perceived exertion singly or in combination with easily obtainable physiological measures. These procedures could be used to estimate the aerobic power of patients and athletes. (MT)

  12. Chemical and pharmacological evaluation of the effectiveness of enalapril maleate in exertional angina pectoris in elderly and senile patients

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    I. M. Belay

    2013-06-01

    Full Text Available The long-term administration of enalapril maleate in complex therapy of exertional angina pectoris in elderly persons showed antiischemic, antiarrhythmic effects of angiotensin converting enzyme inhibitors. Using chemical-pharmacological analysis the administration of enalapril against the background of basic therapy in patients with ischemic heart disease was grounded.

  13. Should Cooling Vests Be Used to Treat Exertional Heatstroke? A Critically Appraised Topic.

    Science.gov (United States)

    Keen, Megan L; Miller, Kevin C

    2017-05-01

    Clinical Scenario: Exercise performed in hot and humid environments increases core body temperature (T C ). If T C exceeds 40.5°C for prolonged periods of time, exertional heat stroke (EHS) may occur. EHS is a leading cause of sudden death in athletes. Mortality and morbidity increase the longer the patient's T C remains above 40.5°C; thus, it is imperative to initiate cooling as quickly as possible. Acceptable cooling rates in EHS situations are 0.08-0.15°C/min, while ideal cooling rates are above 0.16°C/min. Cooling vests are popular alternatives for cooling hyperthermic adults. Most vests cover the anterior and posterior torso and have varying numbers of pouches for phase-change materials (eg, gel packs); some vests only use circulating water to cool. While cooling vests offer several advantages (eg, portability), studies demonstrating their effectiveness at rapidly reducing T C in EHS scenarios are limited. Are T C cooling rates acceptable (ie, >0.08°C/min) when hyperthermic humans are treated with cooling vests postexercise? No significant differences in T C cooling rates occurred between cooling vests and no cooling vests. Cooling rates across all studies were ≤0.053°C/min. Clinical Bottom Line: Cooling vests do not provide acceptable cooling rates of hyperthermic humans postexercise and should not be used to treat EHS. Instead, EHS patients should be treated with cold-water immersion within 30 min of collapse to avoid central nervous system dysfunction and organ failure. Strength of Recommendation: Strong evidence (eg, level 2 studies with PEDro scores ≥5) suggests that cooling vests do not reduce T C quickly and thus should not be used in EHS scenarios.

  14. Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory.

    Science.gov (United States)

    Lapish, Christopher C; Balaguer-Ballester, Emili; Seamans, Jeremy K; Phillips, Anthony G; Durstewitz, Daniel

    2015-07-15

    Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of appropriate statistical methods required to assess attractor-like behavior in vivo. The present study used a combination of advanced multivariate statistical, time series analysis, and machine learning methods to assess dynamic changes in network activity from multiple single-unit recordings from the medial prefrontal cortex (mPFC) of rats while the animals performed a foraging task guided by working memory after pretreatment with different doses of d-amphetamine (AMPH), which increases monoamine efflux in the mPFC. A dose-dependent, bidirectional effect of AMPH on neural dynamics in the mPFC was observed. Specifically, a 1.0 mg/kg dose of AMPH accentuated separation between task-epoch-specific population states and convergence toward these states. In contrast, a 3.3 mg/kg dose diminished separation and convergence toward task-epoch-specific population states, which was paralleled by deficits in cognitive performance. These results support the computationally derived hypothesis that moderate increases in monoamine efflux would enhance attractor stability, whereas high frontal monoamine levels would severely diminish it. Furthermore, they are consistent with the proposed inverted U-shaped and concentration-dependent modulation of cortical efficiency by monoamines. Copyright © 2015 the authors 0270-6474/15/3510172-16$15.00/0.

  15. Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model.

    Science.gov (United States)

    Khan, Archie A; Shekh-Ahmad, Tawfeeq; Khalil, Ayatakin; Walker, Matthew C; Ali, Afia B

    2018-03-25

    A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy. In an attempt to understand the mechanisms by which CBD exerts its anti-seizure effects, we investigated the effects of CBD at synaptic connections, and the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin -expressing (PV) and adapting, cholecystokinin-expressing (CCK) interneurons. We also investigated whether in vivo treatment with CBD altered the fate of CCK and PV interneurons using immunohistochemistry. Electrophysiological intracellular whole-cell recordings combined with neuroanatomy were performed in acute brain slices of rat temporal lobe epilepsy (in vivo kainic acid-induced) and in vitro (Mg 2+ -free-induced) epileptic seizure models. For immunohistochemistry experiments, CBD was administered in vivo (100 mg kg -1 ) at zero time and 90 minutes post status epilepticus (SE) induced with kainic acid. Bath-application of CBD (10 μM), dampened excitability at unitary synapses between pyramidal cells, but enhanced inhibitory synaptic potentials elicited by fast spiking and adapting interneurons at postsynaptic pyramidal cells. Furthermore, CBD restored impaired membrane excitability of PV, CCK, and pyramidal cells in a cell type-specific manner. These neuroprotective effects of CBD were corroborated by immunohistochemistry experiments that revealed a significant reduction of atrophy and death of PV- and CCK-expressing interneurons after CBD treatment. In conclusion, our data suggest CBD restores excitability and morphological impairment in epileptic models to pre-epilepsy control levels through multiple mechanisms to restore normal network function. This article is protected by copyright. All rights reserved.

  16. Implementing exertional heat illness prevention strategies in US high school football.

    Science.gov (United States)

    Kerr, Zachary Y; Marshall, Stephen W; Comstock, R Dawn; Casa, Douglas J

    2014-01-01

    Approximately 6500 high school football athletes are treated annually for exertional heat illness (EHI). In 2009, the National Athletic Trainers Association (NATA)-led Inter-Association Task Force (NATA-IATF) released preseason heat acclimatization guidelines to help athletes become accustomed to environmental factors contributing to EHI. This study examines compliance with NATA-IATF guidelines and related EHI prevention strategies. The study used a cross-sectional survey completed by 1142 certified athletic trainers (AT), which captured compliance with 17 NATA-IATF guidelines and EHI prevention strategies in high school football during the 2011 preseason. On average, AT reported football programs complying with 10.4 NATA-IATF guidelines (SD = 3.2); 29 AT (2.5%) reported compliance with all 17. Guidelines with the lowest compliance were as follows: "Single-practice days consisted of practice no more than three hours in length" (39.7%); and "During days 3-5 of acclimatization, only helmets and shoulder pads should be worn" (39.0%). An average of 7.6 EHI prevention strategies (SD = 2.5) were used. Common EHI prevention strategies were as follows: having ice bags/cooler available (98.5%) and having a policy with written instructions for initiating emergency medical service response (87.8%). Programs in states with mandated guidelines had higher levels of compliance with guidelines and greater prevalence of EHI prevention strategies. A low proportion of surveyed high school football programs fully complied with all 17 NATA-IATF guidelines. However, many EHI prevention strategies were voluntarily implemented. State-level mandated EHI prevention guidelines may increase compliance with recognized best practices recommendations. Ongoing longitudinal monitoring of compliance is also recommended.

  17. Evaluation of perceived and self-reported manual forces exerted in occupational materials handling.

    Science.gov (United States)

    Wiktorin, C; Selin, K; Ekenvall, L; Kilbom, A; Alfredsson, L

    1996-08-01

    The main objective of the study was to evaluate the ability of workers to reproduce simulated manual work forces correctly and to quantify these forces in Newtons (N) by means of self-reports. Fourteen male and 14 female workers participated in the study. Three experiments were carried out. In the first experiment, the ability to reproduce the magnitudes of simulated manual forces occurring in daily work and to estimate these forces in Newtons was tested. A specially designed force-measuring device was used for this purpose. In the second experiment, the subjects estimated the weights of five boxes ranging from 1 to 30 kg. In the third experiment, the subjects were asked to produce five predetermined push and pull forces ranging in magnitude from 10 to 300 N on to the handle of the force-measuring device. The ability to reproduce the magnitudes of manual forces when simulating four familiar work tasks was good (the intraclass correlation coefficients ranged from 0.75 to 0.95). The ability to quantify these forces in Newtons was not as good (the product moment correlation coefficients ranged from 0.21 to 0.69). When the subjects estimated the weights of boxes they underestimated the weights. When they produced predetermined push and pull forces they exerted higher forces than expected when low force levels were requested and lower forces when high force levels were requested. However, the forces were correctly ranked. In summary, simulation of the manual push/pull forces used in familiar work tasks seemed to offer sufficient reproducibility to be worth testing for validity. Self-reports, used without previous training or without known 'reference forces', seemed to be very rough when the aim was to estimate in kg or Newtons. However, the fact that individuals could rank the forces correctly opens a potential for refinement of self-reports as a method for quantifying manual forces in objective terms, e.g. kg or Newtons.

  18. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Song Zhang

    Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

  19. Contralateral risk factors associated with exertional medial tibial pain in women.

    Science.gov (United States)

    Verrelst, Ruth; De Clercq, Dirk; Willems, Tine Marieke; Roosen, Philip; Witrouw, Erik

    2014-08-01

    This study aimed to prospectively analyze the role of factors on the contralateral side of the kinetic chain in the development of exertional medial tibial pain (EMTP). Eighty-one female physical education students were tested at the beginning of their first academic year. Within the testing protocol, contralateral isokinetic hip muscle strength and full-body kinematic parameters during a single-leg drop jump were evaluated. Online questionnaires were administered weekly, and personal interviews were conducted every 3 months to assess injury follow-up. EMTP was diagnosed by an experienced medical doctor. Cox regression analysis was used to identify the potential risk factors for the development of EMTP. After exclusion of subjects with diagnosed bilateral EMTP, 11 subjects were included in the EMTP group. Fifty-three subjects did not develop any lower extremity overuse injury and were included in the control group. The leg not at risk within subjects who developed EMTP was compared with an uninjured leg of those in the control group. Increased transverse plane motion for the contralateral lower leg segment during landing phase was found to be a significant predictor (P = 0.012) for EMTP. Analysis of the isokinetic data did not reveal altered hip muscle strength parameters for the leg not at risk within the EMTP group. Impaired dynamic joint stability or accessory movements were found in the transverse plane of the contralateral lower leg segment of EMTP subjects. This contralateral instability might have contributed to altered movement patterns within the kinetic chain function of EMTP subjects. No contralateral hip muscle strength parameters were found to predict EMTP in this study.

  20. Risk factors associated with exertional medial tibial pain: a 12 month prospective clinical study.

    Science.gov (United States)

    Burne, S G; Khan, K M; Boudville, P B; Mallet, R J; Newman, P M; Steinman, L J; Thornton, E

    2004-08-01

    To investigate in a military setting the potential role of intrinsic biomechanical and anthropometric risk factors for, and the incidence of, exertional medial tibial pain (EMTP). A prospective clinical outcome study in a cohort of 122 men and 36 women at the Australian Defence Force Academy. Each cadet underwent measurements of seven intrinsic variables: hip range of motion, leg length discrepancy, lean calf girth, maximum ankle dorsiflexion range, foot type, rear foot alignment, and tibial alignment. Test-retest reliability was undertaken on each variable. A physician recorded any cadet presenting with diagnostic criteria of EMTP. Records were analysed at 12 months for EMTP presentation and for military fitness test results. 23 cadets (12 men, 11 women) met the criteria for EMTP after 12 months, with a cross gender (F/M) odds ratio of 3.1. In men, both internal and external range of hip motion was greater in those with EMTP: left internal (12 degrees, p = 0.000), right internal (8 degrees, p = 0.014), left external (8 degrees, p = 0.042), right external (9 degrees, p = 0.026). Lean calf girth was lower by 4.2% for the right leg (p = 0.040) but by only 2.9% for the left leg (p = 0.141). No intrinsic risk factor was associated with EMTP in women. EMTP was the major cause for non-completion of the run component of the ADFA fitness test in both men and women. Greater internal and external hip range of motion and lower lean calf girth were associated with EMTP in male military cadets. Women had high rates of injury, although no intrinsic factor was identified. Reasons for this sex difference need to be identified.

  1. Fluoxetine and aripiprazole treatment following prenatal immune activation exert longstanding effects on rat locomotor response.

    Science.gov (United States)

    Richtand, Neil M; Ahlbrand, Rebecca; Horn, Paul; Tambyraja, Rabindra; Grainger, Molly; Bronson, Stefanie L; McNamara, Robert K

    2012-05-15

    Studies characterizing treatment interventions in a naturalistic setting suggest that antidepressant and antipsychotic medications may be equally effective in improving clinical outcome in individuals at high risk for first-episode psychosis. Of interest, both beneficial as well as potentially adverse effects have been observed following fluoxetine treatment in a mouse prenatal immune activation model of relevance to psychosis prevention. We sought to extend those findings by examining the effects of fluoxetine, as well as the antipsychotic medication aripiprazole, in a rat prenatal immune activation model. Pregnant Sprague-Dawley rats were injected with poly I:C or saline on gestational day 14. Offspring of poly I:C and saline-treated dams received fluoxetine (10.0 mg/kg/d), aripiprazole (0.66 mg/kg/d), or vehicle from postnatal days 35 to 70. Locomotor responses to novelty, saline injection, and amphetamine (1 and 5 mg/kg) were determined at three months, i.e., 21 days following drug discontinuation. Both fluoxetine and aripiprazole had beneficial effects on behavioral response to amphetamine (1 mg/kg) at 3 months, ameliorating the impact of prenatal immune activation on offspring of poly I:C-treated dams. Significantly, both drugs also exerted effects in offspring of control (saline-treated) dams on locomotor response to injection. Fluoxetine and aripiprazole pretreatment of poly I:C offspring from postnatal days 35 to 70 stabilized response to amphetamine exposure persisting through 3 months of age, similar to earlier findings in mice that fluoxetine treatment following prenatal immune activation prevented altered locomotor response to amphetamine. The current data also confirm earlier findings of potential adverse behavioral effects in offspring of control dams following treatment with fluoxetine and antipsychotic medications, highlighting the potential for both therapeutic as well as safety concerns with exposure to preventive pharmacological treatments over

  2. A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition.

    Science.gov (United States)

    Kobayashi, Yoshiki; Wada, Hiroo; Rossios, Christos; Takagi, Dai; Higaki, Manabu; Mikura, Shin'ichiro; Goto, Hajime; Barnes, Peter J; Ito, Kazuhiro

    2013-04-01

    Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease, such as chronic obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro and in vivo. However the anti-inflammatory efficacies of current macrolides are relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior anti-inflammatory effects to macrolides in current clinical use. The effects of solithromycin (SOL) on lipopolysaccharide-induced TNFα (tumor necrosis factor α) and/or CXCL8 (C-X-C motif chemokine ligand 8; interleukin-8) release, phorbol 12-myristate 13-acetate-induced MMP9 (matrix metalloproteinase 9) activity and NF-κB (nuclear factor-κB) activity under conditions of oxidative stress have been evaluated and compared with the effects of erythromycin, clarithromycin, azithromycin, and telithromycin in macrophage-like PMA-differentiated U937 cells and peripheral blood mononuclear cells (PBMC) obtained from COPD patients. We also examined effect of SOL on cigarette smoke-induced airway inflammation in mice. SOL exerted superior inhibitory effects on TNFα/CXCL8 production and MMP9 activity in monocytic U937 cells. In addition, SOL suppressed TNFα release and MMP9 activity in PBMC from COPD patients at 10 µM, which is 10 times more potent than the other macrolides tested. Activated NF-κB by oxidative stress was completely reversed by SOL. SOL also inhibited cigarette smoke-induced neutrophilia and pro-MMP9 production in vivo, although erythromycin did not inhibit them. Thus, SOL showed better anti-inflammatory profiles compared with macrolides currently used in the clinic and may be a promising anti-inflammatory and antimicrobial macrolide for the treatment of COPD in future.

  3. Reliability and Validity of Ratings of Perceived Exertion in Persons With Multiple Sclerosis.

    Science.gov (United States)

    Cleland, Brice T; Ingraham, Benjamin A; Pitluck, Molly C; Woo, Douglas; Ng, Alexander V

    2016-06-01

    To test the reliability and validity of using the Borg rating of perceived exertion (RPE) scale (ratings 6-20) in persons with multiple sclerosis (PwMS). Nonrandomized repeated measures. Research laboratory. Volunteer sample (N=27) comprised of 16 PwMS (10 women) and 11 age-matched persons without multiple sclerosis (MS) (6 women). Clinical measures included symptomatic fatigue, depression, and MS functional capacity. A submaximal cycling test was performed to estimate maximal capacity. Participants then pedaled for 2 minutes at 50% and 60% of predicted maximal oxygen consumption per unit time (V˙o2), and physiological measures and RPE were obtained (week 1: response protocol). One week later, participants replicated the prescribed V˙o2 using the RPE range from week 1 (week 2: reproduction protocol). V˙o2, heart rate, and respiratory quotient were measured continuously; RPE and workload were measured every minute; and blood lactate and mean arterial pressure were measured after exercise. RPE, workload, V˙o2, and heart rate from week 1 to week 2. PwMS had greater fatigue (Pexercise, RPE, workload, V˙o2, and heart rate were similar between groups. Both groups had an intraclass correlation coefficient >.86 for RPE, workload, and V˙o2. The intraclass correlation coefficient was comparatively lower for heart rate for both groups (MS group: .72, non-MS group: .83). RPE was highly correlated with V˙o2 (r=.691, Pexercise prescription in mildly to moderately impaired PwMS during cycling exercise. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  4. Timing Effect on Training-Session Rating of Perceived Exertion in Top-Class Soccer Referees.

    Science.gov (United States)

    Castagna, Carlo; Bizzini, Mario; Póvoas, Susana Cristina Araújo; D'Ottavio, Stefano

    2017-10-01

    To examine the effect of recall timing on training-session rating of perceived exertion (sRPE) in a population of athletes well familiarized with the method and procedures during a 5-d training microcycle. Fifty-one top-class field referees (FRs) (age 38.4 ± 3.3 y, height 181 ± 5.6 cm, body mass 76.8 ± 6.8 kg, body-mass index 23.4 ± 1.7 kg/m 2 , body fat 20.4% ± 3.6%, international refereeing experience 5 ± 3.5 y) from 43 national football associations worldwide, preselected by the FIFA refereeing department for officiating during the FIFA World Cup 2014 Brazil, volunteered for this study. The FRs were randomly allocated into 3 assessment groups (n = 17 each), defined according to the timing of the sRPE, ie, immediately at the end of or 30 min or 7 h after the training sessions' end. The CR10 Borg scale was used to rate the training sessions (n = 5). All FRs again rated each training session of the 5-d training microcycle on the next morning (~20 h after) for confirmation (absolute and relative reliability). No significant timing effect was found between or within groups. Relative reliability ranged from large to very large with trivial within- and between-groups differences. This study showed no effect of recall timing on postexercise RPE when well-familiarized athletes are submitted to training during a weekly microcycle. Posttraining RPE was reported to be a reliable subjective measure; however, specific timing is advisable to reduce difference in RPE values.

  5. Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats.

    Science.gov (United States)

    Silveira, Mason M; Adams, Wendy K; Morena, Maria; Hill, Matthew N; Winstanley, Catharine A

    2017-03-01

    Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ 9 -Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana. We tested the hypothesis that THC impairs a relevant cognitive function for long-term success, namely willingness to exert cognitive effort for greater rewards, and that CBD could attenuate such decision-making impairments. Male Long-Evans rats ( n = 29) performing the rat cognitive effort task (rCET) received acute THC and CBD, independently and concurrently, in addition to other cannabinoids. Rats chose between 2 options differing in reward magnitude, but also in the cognitive effort (attentional load) required to obtain them. We found that THC decreased choice of hard trials without impairing the animals' ability to accurately complete them. Strikingly, this impairment was correlated with CB1 receptor density in the medial prefrontal cortex - an area previously implicated in effortful decision-making. In contrast, CBD did not affect choice. Coadministration of 1:1 CBD:THC matching that in nabiximols modestly attenuated the deleterious effects of THC in "slacker" rats. Only male rats were investigated, and the THC/CBD coadministration experiment was carried out in a subset of individuals. These findings confirm that THC, but not CBD, selectively impairs decision-making involving cognitive effort costs. However, coadministration of CBD only partially ameliorates such THC-induced dysfunction.

  6. Sex differences in the intensity and qualitative dimensions of exertional dyspnea in physically active young adults

    Science.gov (United States)

    Cory, Julia M.; Schaeffer, Michele R.; Wilkie, Sabrina S.; Ramsook, Andrew H.; Puyat, Joseph H.; Arbour, Brandon; Basran, Robbi; Lam, Michael; Les, Christian; MacDonald, Benjamin; Jensen, Dennis

    2015-01-01

    Understanding sex differences in the qualitative dimensions of exertional dyspnea may provide insight into why women are more affected by this symptom than men. This study explored the evolution of the qualitative dimensions of dyspnea in 70 healthy, young, physically active adults (35 M and 35 F). Participants rated the intensity of their breathing discomfort (Borg 0-10 scale) and selected phrases that best described their breathing from a standardized list (work/effort, unsatisfied inspiration, and unsatisfied expiration) throughout each stage of a symptom-limited incremental-cycle exercise test. Following exercise, participants selected phrases that described their breathing at maximal exercise from a list of 15 standardized phrases. Intensity of breathing discomfort was significantly higher in women for a given ventilation, but differences disappeared when ventilation was expressed as a percentage of maximum voluntary ventilation. The dominant qualitative descriptor in both sexes throughout exercise was increased work/effort of breathing. At peak exercise, women were significantly more likely to select the following phrases: “my breathing feels shallow,” “I cannot get enough air in,” “I cannot take a deep breath in,” and “my breath does not go in all the way.” Women adopted a more rapid and shallow breathing pattern and had significantly higher end-inspiratory lung volumes relative to total lung capacity throughout exercise relative to men. These findings suggest that men and women do not differ in their perceived quality of dyspnea during submaximal exercise, but subjective differences appear at maximal exercise and may be related, at least in part, to underlying sex differences in breathing patterns and operating lung volumes during exercise. PMID:26338458

  7. The effects of superset configuration on kinetic, kinematic, and perceived exertion in the barbell bench press.

    Science.gov (United States)

    Weakley, Jonathon Js; Till, Kevin; Read, Dale B; Phibbs, Padraic J; Roe, Gregory; Darrall-Jones, Joshua; Jones, Ben L

    2017-08-04

    Training that is efficient and effective is of great importance to an athlete. One method of improving efficiency is by incorporating supersets into resistance training routines. However, the structuring of supersets is still unexplored. Therefore, the purpose of this study was to assess the effects of agonist-antagonist (A-A), alternate peripheral (A-P), and similar biomechanical (SB) superset configurations on rate of perceived exertion (RPE), kinetic and kinematic changes during the bench press. 10 subjects performed resistance training protocols in a randomized-crossover design, with magnitude-based inferences assessing changes/differences within and between protocols. Changes in RPE were very likely and almost certainly greater in the A-P and SB protocols when compared with the A-A, while all superset protocols had very likely to almost certain reductions in mean velocity and power from baseline. Reductions in mean velocity and power were almost certainly greater in the SB protocol, with differences between the A-A and A-P protocols being unclear. Decreases in peak force were likely and almost certain in the A-A and SB protocols respectively, with changes in A-P being unclear. Differences between these protocols showed likely greater decreases in SB peak forces when compared to A-A, with all other superset comparisons being unclear. This study demonstrates the importance of exercise selection when incorporating supersets into a training routine. It is suggested that the practitioner uses A-A supersets when aiming to improve training efficiency and minimize reductions in kinetic and kinematic output of the agonist musculature while completing the barbell bench press.

  8. Effect of wearing clothes on oxygen uptake and ratings of perceived exertion while swimming.

    Science.gov (United States)

    Choi, S W; Kurokawa, T; Ebisu, Y; Kikkawa, K; Shiokawa, M; Yamasaki, M

    2000-07-01

    For a comparative study between swimming in swimwear (control-sw) and swimming in clothes (clothes-sw), oxygen uptake (VO2) and ratings of perceived exertion (RPE) were measured. The subjects were six male members of a university swimming team. Three swimming strokes--the breaststroke, the front crawl stroke and the elementary backstroke--were applied. With regards to clothes-sw, swimmers wore T-shirts, sportswear (shirt and pants) over swimwear and running shoes. In both cases of control-sw and clothes-sw, the VO2 was increased exponentially with increased swimming speed. The VO2 of the subjects during the clothed tests did not exceed 1.4 times of that in the case of control-sw at swimming speeds below 0.3 m/s. As swimming speeds increased, VO2 difference in both cases increased. Consequently, VO2 in the clothed tests was equal to 1.5-1.6 times and 1.5-1.8 times of that in the swimwear tests at speeds of 0.5 and 0.7 m/s, respectively. At speeds below 0.6 m/s in clothes-sw, the breaststroke showed lower VO2 than the front crawl stroke, and the elementary backstroke showed higher VO2 than the other two swimming strokes. RPE increased linearly with %peak VO2. In addition, any RPE differences among the three swimming strokes were not shown in the control-sw tests. At an exercise intensity above 60 %peak VO2, clothed swimmers showed slightly higher RPE in the front crawl stroke compared to that in the two other swimming strokes.

  9. Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats

    Directory of Open Access Journals (Sweden)

    Hui-Qin Li

    2016-01-01

    Full Text Available Spontaneous intracerebral hemorrhage (ICH is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20 exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa’s scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH (P<0.05. In conclusion, the present results suggested that electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway.

  10. Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats.

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    Full Text Available The present study was conducted over a course of 104 weeks to estimate the carcinogenicity of ethanol-extracted Brazilian green propolis (EEP. Groups of 50 male and 50 female Wistar Hannover rats, 6-week-old at commencement were exposed to EEP at doses of 0, 0.5 or 2.5% in the diet. Survival rates of 0.5% and 2.5% EEP-treated male and female rats, respectively, were significantly higher than those of respective control groups. Overall histopathological evaluation of neoplasms in rat tissues after 2 years showed no significant increase of tumors or preneoplastic lesions in any organ of animals administered EEP. Significantly lower incidences of pituitary tumors in 0.5% EEP male and 2.5% EEP female groups, malignant lymphoma/leukemia in both 2.5% EEP-treated males and females and total thyroid tumors in 0.5% EEP male group were found. Administration of EEP caused significant decreases of lymphoid hyperplasia of the thymus and lymph nodes in 2.5% EEP-treated rats, tubular cell hyperplasia of kidneys in all EEP groups, and cortical hyperplasia of adrenals in EEP-treated females. In the blood, significant reduction of neutrophils in all EEP-treated males and band neutrophils in 2.5% EEP-treated females was found indicating lower levels of inflammation. Total cholesterol and triglicerides levels were significantly lower in the blood of 2.5% EEP-treated female rats. In conclusion, under the conditions of the 2-year feeding experiment, EEP was not carcinogenic, did not induce significant histopathological changes in any organ, and further exerted anti-inflammatory and antitumorigenic effects resulting in increase of survival of Wistar Hannover rats.

  11. Malignant hyperthermia susceptibility in patients with exertional rhabdomyolysis: a retrospective cohort study and updated systematic review.

    Science.gov (United States)

    Kraeva, Natalia; Sapa, Alexander; Dowling, James J; Riazi, Sheila

    2017-07-01

    Two potentially fatal syndromes, malignant hyperthermia (MH), an adverse reaction to general anesthesia, and exertional rhabdomyolysis (ER) share some clinical features, including hyperthermia, muscle rigidity, tachycardia, and elevated serum creatine kinase. Some patients with ER have experienced an MH event and/or have been diagnosed as MH susceptible (MHS). In order to assess the relationship between ER and MH further, we conducted a retrospective cohort study summarizing clinical and genetic information on Canadian patients with ER who were diagnosed as MHS. In addition, a systematic literature review was performed to compile further evidence on MH susceptibility and RYR1 and CACNA1S variants associated with rhabdomyolysis. Demographic, clinical, and genetic information was collected on Canadian MHS patients who presented with rhabdomyolysis. In addition, we performed a systematic review of the literature published during 1995-2016 on genetic screening of the RYR1 and CACNA1S genes in patients with ER. Retrospective data on Canadian MHS patients with ER showed that ten out of 17 patients carried RYR1 or CACNA1S variants that were either known MH-causative mutations or potentially pathogenic variants. The systematic review revealed 39 different rare RYR1 variants, including 13 MH-causative/associated mutations and five rare potentially deleterious CACNA1S variants in 78% of patients with ER. Findings from the Canadian patient cohort and the systematic review all signal a potential association between MH susceptibility and ER. The presence of MH-causative mutations and putative deleterious RYR1 variants in ER patients without a history of adverse anesthetic reactions suggests their possible increased risk for MH.

  12. The Secondary School Football Coach's Relationship With the Athletic Trainer and Perspectives on Exertional Heat Stroke

    Science.gov (United States)

    Adams, William M.; Mazerolle, Stephanie M.; Casa, Douglas J.; Huggins, Robert A.; Burton, Laura

    2014-01-01

    Context: Prior researchers have examined the first-aid knowledge and decision making among high school coaches, but little is known about their perceived knowledge of exertional heat stroke (EHS) or their relationships with an athletic trainer (AT). Objective: To examine secondary school football coaches' perceived knowledge of EHS and their professional relationship with an AT. Design: Qualitative study. Setting: Web-based management system. Patients or Other Participants: Thirty-eight secondary school head football coaches (37 men, 1 woman) participated in this study. Their average age was 47 ± 10 years old, and they had 12 ± 9 years' experience as a head football coach. Data Collection and Analysis: Participants responded to a series of online questions that were focused on their perceived knowledge of EHS and professional relationships with ATs. Data credibility was established through multiple-analyst triangulation and peer review. We analyzed the data by borrowing from the principles of a general inductive approach. Results: Two dominant themes emerged from the data: perceived self-confidence of the secondary school coach and the influence of the AT. The first theme highlighted the perceived confidence, due to basic emergency care training, of the coach regarding management of an emergency situation, despite a lack of knowledge. The second theme illustrated the secondary school coach's positive professional relationships with ATs regarding patient care and emergency procedures. Of the coaches who participated, 89% (34 out of 38) indicated positive interactions with their ATs. Conclusions: These secondary school coaches were unaware of the potential causes of EHS or the symptoms associated with EHS, and they had higher perceived levels of self-confidence in management abilities than indicated by their perceived knowledge level. The secondary school football coaches valued and understood the role of the AT regarding patient and emergency care. PMID:24933433

  13. Triterpenoids and Polysaccharide Fractions of Ganoderma tsugae Exert Different Effects on Antiallergic Activities

    Directory of Open Access Journals (Sweden)

    Miaw-Ling Chen

    2015-01-01

    Full Text Available This study was to investigate antiallergic effects of triterpenoids (Gt-TRE and polysaccharide (Gt-PS extracts from Ganoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL- 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4+ T cells cultures also confirmed that Gt-TRE (5~50 µg/mL significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL and significantly suppressed IFNγ secretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264.7 cells and transfected EL4 cells. IL-4 secreted by this transfected EL-4 cells was also significantly decreased by Gt-TRE but not by Gt-PS, suggesting that these two fractions may exert different effects on NF-κB related cytokines expression. These data suggested that triterpenoids fraction of Ganoderma tsugae might be the main constituents to alleviate allergic asthma.

  14. Physical Activity and Exertional Desaturation Are Associated with Mortality in Idiopathic Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Baruch Vainshelboim

    2016-08-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic lung disease that manifests in hypoxemia, inactivity, and poor prognosis. This study aimed to assess the prognostic role of physical activity (PA and exertional desaturation (ED with mortality in IPF. At baseline, 34 IPF patients (68 (50–81 years were interviewed using the International Physical Activity Questionnaire (IPAQ, and SpO2 was assessed pre to post 6-min walking test (∆SpO2. Patients were prospectively followed up for 40 months. Receiver operating characteristics curve analysis determined cut-off points associated with mortality, and Cox proportional hazard ratio (HR were conducted. Thresholds for increased mortality risk in IPF patients were determined as IPAQ ≤ 417 metabolic equivalent task (METS-min/week, p = 0.004 (HR; 9.7, CI 95% (1.3–71.9, p = 0.027, and ∆SpO2 ≥ 10%, p = 0.002, (HR; 23.3, CI 95% (1.5–365, p = 0.025. This study demonstrated a significant association of PA and ED with mortality in IPF patients. The findings emphasize the clinical importance of PA and ED assessments to aid in IPF risk stratification, prognosis prediction, and in providing early appropriate treatments, such as pulmonary rehabilitation, PA consultation, oxygen supplementation, and lung transplantation referral. These results underscore that even low levels of PA corresponding to 100–105 min/week were associated with a reduced mortality risk and better survival in IPF.

  15. Influence exerted by helicobacter pylori on regulatory t-cells differentiation

    Directory of Open Access Journals (Sweden)

    А.V. Matveichev

    2017-03-01

    Full Text Available Estimating risks of infections induced by gram-negative Helicobacter pylori, is a vital problem for healthcare due to wide spread of the agent and wide range of induced pathologies which include malignant neoplasms in gastrointestinal tract. The agent is prone to long-term chronic persistence despite its "fragility" and its being greatly demanding to culturing conditions. The persistence issue is of special interest here as it is related to data on Helicobacter pylori capability to change immune response in infected people inducing suppressive regulatory immune reactions which are more favorable for the agent, both in stomach and in a whole body. Our research goal was to estimate Helicobacter pylori capability to induce differentiation of regulatory CD4+CD25+FoxP3+ human T-cells as basic mediators of immune response regulation under direct contact between bacteria and T-cells without any participation of most professional antigen-presenting cells. Our research objects were clinical isolates of Helicobacter pylori and T-lymphocytes samples taken from people who didn't have Helicobacter pylori-infection in their case history; isolates and samples were jointly cultivated in vitro. We applied cytofluorometry to estimate changes in regulatory T-cells content. We detected that if T-lymphocytes and Helicobacter pylori were jointly cultivated during 18 hours in ratios from 1:10 to 1:50, regulatory T-cells content in cultures increased 2.12 times on average. This effects doesn't require any dendritic cells in a culture and obviously affects T-lymphocytes which are originally committed to regulatory T-cells in their development. Also, in our opinion, influence exerted on regulatory T-cells differentiation is a specific feature of Helicobacter pylori.

  16. Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis.

    Science.gov (United States)

    McKenzie, E C; Eyrich, L V; Payton, M E; Valberg, S J

    2016-10-01

    A previous report suggests a substantial incidence of exertional rhabdomyolysis (ER) in Arabian horses performing endurance racing. This study compared formalin histopathology and clinical and metabolic responses to a standardised field exercise test (SET) between Arabians with and without ER. Arabian horses with (n = 10; age 15.4 ± 5.6 years) and without (n = 9; 12.9 ± 6.1 years) prior ER were stall-rested for 24-48 h, after which paired ER and control horses were fitted with a telemetric ECG and performed a 47 min submaximal SET. Plasma glucose, lactate, electrolyte and total protein concentrations and packed cell volume were measured before and immediately after exercise. Blood and percutaneous gluteal muscle samples were also obtained before and 3 h after exercise for measurement of plasma creatine kinase (CK) activity and muscle glycogen concentration, respectively. Histopathologic analysis of formalin-fixed pre-exercise muscle sections was performed. Data were analyzed by ANOVA and non-parametric tests (P horses displayed clinical signs of ER during exercise, and plasma CK increased similarly in ER and control Arabians. Muscle glycogen, heart rate, and remaining plasma variables did not differ between horses with ER and control horses. Horses with ER had more internalised nuclei in mature myofibers, more aggregates of cytoplasmic glycogen and desmin, and higher myopathic scores than control horses. Although many horses with ER had histopathologic evidence of chronic myopathy, muscle glycogen concentrations and metabolic exercise responses were normal. Results did not support a consistent metabolic myopathy or a glycogen storage disorder in Arabians with ER. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Notochordal-cell derived extracellular vesicles exert regenerative effects on canine and human nucleus pulposus cells.

    Science.gov (United States)

    Bach, Frances; Libregts, Sten; Creemers, Laura; Meij, Björn; Ito, Keita; Wauben, Marca; Tryfonidou, Marianna

    2017-10-24

    During intervertebral disc ageing, chondrocyte-like cells (CLCs) replace notochordal cells (NCs). NCs have been shown to induce regenerative effects in CLCs. Since vesicles released by NCs may be responsible for these effects, we characterized NC-derived extracellular vesicles (EVs) and determined their effect on CLCs. EVs were purified from porcine NC-conditioned medium (NCCM) through size exclusion chromatography, ultracentrifugation or density gradient centrifugation. Additionally, the EVs were quantitatively analyzed by high-resolution flow cytometry. The effect of NCCM-derived EVs was studied on canine and human CLC micro-aggregates in vitro and compared with NCCM-derived proteins and unfractionated NCCM. Porcine NCCM contained a considerable amount of EVs. NCCM-derived EVs induced GAG deposition in canine CLCs to a comparable level as NCCM-derived proteins and unfractionated NCCM, and increased the DNA and glycosaminoglycan (GAG) content of human micro-aggregates, although to a lesser extent than unfractionated NCCM. The biological EV effects were not considerably influenced by ultracentrifugation compared with size exclusion-based purification. Upon ultracentrifugation, interfering GAGs, but not collagens, were lost. Nonetheless, collagen type I or II supplemented to CLCs in a concentration as present in NCCM induced no anabolic effects. Porcine NCCM-derived EVs exerted anabolic effects comparable to NCCM-derived proteins, while unfractionated NCCM was more potent in human CLCs. GAGs and collagens appeared not to mediate the regenerative EV effects. Thus, NC-derived EVs have regenerative potential, and their effects may be influenced by the proteins present in NCCM. The optimal combination of NC-secreted factors needs to be determined to fully exploit the regenerative potential of NC-based technology.

  18. Annonacin Exerts Antitumor Activity through Induction of Apoptosis and Extracellular Signal-regulated Kinase Inhibition.

    Science.gov (United States)

    Yap, Chee Voon; Subramaniam, Kavita S; Khor, Sik Wey; Chung, Ivy

    2017-01-01

    Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Annonacin, a natural pure compound extracted from the seeds of Annona muricata , is a potential alternative therapeutic agent to treat EC. To study the antitumor activity of annonacin and its mechanism of action in EC cells (ECCs). Viability of ECCs treated with annonacin for 72 h was determined using methyl thiazolyl tetrazolium assay. The induction of cell cycle arrest and apoptotic cell death was evaluated using propidium iodide and annexin V-PE/7-AAD assay, respectively. DNA strand breaks were visualized using transferase dUTP nick end labeling assay, and the effects of annonacin on survival signaling were determined using western blotting. Annonacin exhibited antiproliferative effects on EC cell lines (ECC-1 and HEC-1A) and primary cells (EC6-ept and EC14-ept) with EC 50 values ranging from 4.62 to 4.92 μg/ml. EC cells were shown arrested at G2/M phase after treated with 4 μg/ml of annonacin for 72 h. This led to a significant increase in apoptotic cell death (65.7%) in these cells when compared to vehicle-treated cells ( P cancer cells. Annonacin exerted antiproliferation effects on both endometrial cancer cell lines and primary cells via induction of apoptosis and inhibition of extracellular signal-regulated kinase. Our data represented that annonacin could be an alternative therapeutic treatment to combat endometrial cancer. Abbreviations Used: 7-AAD: 7-Amino-Actinomycin, ATP: Adenosine diphosphate, BSA: Bovine serum albumin, DNA: Deoxyribonucleic acid, EC: Endometrial cancer, ECC-1: Endometrial cancer cell-1, EC50: Half maximal effective concentration, Ept: Epithelial, FBS: Fetal bovine serum, HEC-1A: Human endometrial carcinoma-1A, MTT: Methyl thiazolyl tetrazolium, NaCl: Sodium chloride, NADH: Nicotinamide adenine dinucleotide, RPMI 1640: Roswell Park Memorial Institute Medium, SDS: Sodium dodecyl sulfate.

  19. Vegetation exerts a greater control on litter decomposition than climate warming in peatlands.

    Science.gov (United States)

    Ward, Susan E; Orwin, Kate H; Ostle, Nicholas J; Briones, J I; Thomson, Bruce C; Griffiths, Robert I; Oakley, Simon; Quirk, Helen; Bardget, Richard D

    2015-01-01

    Historically, slow decomposition rates have resulted in the accumulation of large amounts of carbon in northern peatlands. Both climate warming and vegetation change can alter rates of decomposition, and hence affect rates of atmospheric CO2 exchange, with consequences for climate change feedbacks. Although warming and vegetation change are happening concurrently, little is known about their relative and interactive effects on decomposition processes. To test the effects of warming and vegetation change on decomposition rates, we placed litter of three dominant species (Calluna vulgaris, Eriophorum vaginatum, Hypnum jutlandicum) into a peatland field experiment that combined warming.with plant functional group removals, and measured mass loss over two years. To identify potential mechanisms behind effects, we also measured nutrient cycling and soil biota. We found that plant functional group removals exerted a stronger control over short-term litter decomposition than did approximately 1 degrees C warming, and that the plant removal effect depended on litter species identity. Specifically, rates of litter decomposition were faster when shrubs were removed from the plant community, and these effects were strongest for graminoid and bryophyte litter. Plant functional group removals also had strong effects on soil biota and nutrient cycling associated with decomposition, whereby shrub removal had cascading effects on soil fungal community composition, increased enchytraeid abundance, and increased rates of N mineralization. Our findings demonstrate that, in addition to litter quality, changes in vegetation composition play a significant role in regulating short-term litter decomposition and belowground communities in peatland, and that these impacts can be greater than moderate warming effects. Our findings, albeit from a relatively short-term study, highlight the need to consider both vegetation change and its impacts below ground alongside climatic effects when

  20. Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

    KAUST Repository

    Arsenescu, Violeta

    2011-04-11

    Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

  1. Comparison of kettlebell swings and treadmill running at equivalent rating of perceived exertion values.

    Science.gov (United States)

    Hulsey, Caleb R; Soto, David T; Koch, Alexander J; Mayhew, Jerry L

    2012-05-01

    The purpose of this study was to compare metabolic demand of a kettlebell (KB) swing routine with treadmill (TM) running at equivalent rating of perceived exertion (RPE). Thirteen subjects (11 male, 2 female, age = 21.4 ± 2.1 years, weight = 73.0 ± 9.2 kg) completed a 10-minute KB swing routine consisting of 35-second swing intervals followed by 25-second rest intervals. Men used a 16-kg KB, and women used an 8-kg KB. After 48 hours of rest, the subjects completed a 10-minute TM run at equivalent RPEs as measured during the swing workout. Metabolic data were monitored each minute during each exercise using an automated cart, with the final 7 minutes used for analysis. The RPE and heart rate (HR) recorded at minutes 5, 7, 9, and 10 increased by 2-3 and 7-9%, respectively, for each exercise, producing a significantly increasing pattern but no significant difference between exercises. Average HR and RPE were not significantly different between KB and TM and averaged 90 and 89%, respectively, of age-predicted HRmax. Oxygen consumption, METS, pulmonary ventilation, and calorie expenditure were significantly higher for TM (25-39%) than for KB. Respiratory exchange ratio (TM = 0.94 ± 0.04, KB = 0.95 ± 0.05) and respiratory rate (TM = 38 ± 7, KB = 36 ± 4 b·min) were not significantly different between the exercises at any time point. During TM and KB exercises matched for RPE, the subjects are likely to have higher oxygen consumption, work at a higher MET level, and burn more kilocalories per minute during TM running than during KB swings. However, according to the American College of Sports Medicine standards, this KB drill could provide sufficient exercise stress to produce gains in aerobic capacity.

  2. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya, E-mail: jyli@mail.shcnc.ac.cn; Nan, Fa-Jun, E-mail: fjnan@mail.shcnc.ac.cn; Li, Jia, E-mail: jli@mail.shcnc.ac.cn

    2013-12-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome.

  3. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    International Nuclear Information System (INIS)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya; Nan, Fa-Jun; Li, Jia

    2013-01-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome

  4. Analysis of the cytoprotective effect of amifostine on the irradiated inner ear of guinea pigs: an experimental study Análise do efeito citoprotetor da amifostina na orelha interna irradiada de cobaias: estudo experimental

    Directory of Open Access Journals (Sweden)

    Ricardo Miranda Lessa

    2009-10-01

    Full Text Available Radiation can cause damage to the inner ear, from a simple hearing loss all the way to profound deafness. Amifostine is a cytoprotective substance extensively used during radio-chemotherapy for malignant tumors. AIM: the objective of the present investigation was to establish the antioxidant and radioprotective effects of amifostine on the organ of Corti of albino guinea pigs irradiated in the head and neck region. MATERIALS AND METHODS: An experimental study conducted on four groups of guinea pigs were used; One group received only amifostine, one group was submitted to a single dose of 350 cGy and the other two were similarly irradiated but received amifostine doses of 100 or 200 mg/kg. All animals were slaughtered 30 days after the experiment, their bullae were removed and the damaged outer hair cells were counted. RESULT: The extent of injury was lower in the outer hair cells of the two groups treated with amifostine compared to the group that was only irradiated. There was no difference between the group treated with 100 and 200 mg/kg of amifostine. The group that received only amifostine had no cochlear damage. CONCLUSION: Amifostine is an effective cytoprotective substance in the Organ of Corti of irradiated guinea pigs.A radiação pode causar lesão na orelha interna podendo provocar surdez sensório-neural e inclusive levar à anacusia. A amifostina é uma substância citoprotetora seletiva de tecidos sadios, amplamente utilizada durante a radio e quimioterapia de tumores malignos. OBJETIVO: O objetivo deste estudo experimental foi verificar se existe efeito antioxidante e radioprotetor da amifostina no órgão de Corti de cobaias albinas irradiadas em região de cabeça e pescoço. MATERIAL E MÉTODO: O estudo realizado envolveu quatro grupos de animais: um grupo foi submetido à irradiação em dose única de 350cGy. Dois grupos receberam a mesma dose de radiação, porém receberam doses de 100 e 200mg/kg de amifostina, 30 minutos

  5. Next Generation Sequencing of RYR1 and CACNA1S in Malignant Hyperthermia and Exertional Heat Illness

    Science.gov (United States)

    Fiszer, Dorota; Shaw, Marie-Anne; Fisher, Nickla A.; Carr, Ian M.; Gupta, Pawan K.; Watkins, Elizabeth J.; de Sa, Daniel Roiz; Kim, Jerry H.; Hopkins, Philip M.

    2015-01-01

    Background Variants in RYR1 are associated with the majority of cases of malignant hyperthermia (MH), a form of heat illness pharmacogenetically triggered by general anesthetics, and they have also been associated with exertional heat illness. CACNA1S has also been implicated in MH. We applied a targeted next generation sequencing approach to identify variants in RYR1 and CACNA1S in a cohort of unrelated patients diagnosed with MH susceptibility. We also provide the first comprehensive report of sequencing of these two genes in a cohort of survivors of exertional heat illness. Methods DNA extracted from blood was genotyped using a “long” polymerase chain reaction technique, with sequencing on the Illumina GAII® or MiSeq® platforms (Illumina Inc., San Diego, CA). Variants were assessed for pathogenicity using bioinformatic approaches. For further follow up DNA from additional family members and up to 211 MH normal and 556 MH susceptible unrelated individuals was tested. Results In 29 MH patients we identified three pathogenic and four novel RYR1 variants, with a further five RYR1 variants previously reported in association with MH. Three novel RYR1 variants were found in the exertional heat illness cohort (n = 28) along with two more previously reported in association with MH. Two other variants were reported previously associated with centronuclear myopathy. We found one and three rare variants of unknown significance in CACNA1S in the MH and exertional heat illness cohorts respectively. Conclusion Targeted next generation sequencing proved efficient at identifying diagnostically useful and potentially implicated variants in RYR1 and CACNA1S in MH and exertional heat illness. PMID:25658027

  6. Mechanism of Action of Nigella sativa on Human Colon Cancer Cells: the Suppression of AP-1 and NF-κB Transcription Factors and the Induction of Cytoprotective Genes.

    Science.gov (United States)

    Elkady, Ayman I; Hussein, Rania A; El-Assouli, Sufian M

    2015-01-01

    Colorectal cancer is one of the leading causes of death in the world. The aim of this study was to investigate the growth-suppression potentiality of a crude saponin extract (CSENS) prepared from medicinal herb, Nigella sativa, on human colon cancer cells, HCT116. HCT116 cells were subjected to increasing doses of CSENS for 24, 48 and 72 h, and then harvested and assayed for cell viability by WST-1. Flow cytometry analyses, cell death detection ELISA, fluorescent stains (Hoechst 33342 and acridine orange/ethidium bromide), DNA laddering and comet assays were carried out to confirm the apoptogenic effects of CSENS. Luciferase reporter gene assays, quantitative reverse transcription-polymerase chain reaction and Western blot analyses were performed to assess the impact of CAERS and CFEZO on the expression levels of key regulatory proteins in HCT116 cells. The results demonstrated that CSENS inhibited proliferation and induced apoptosis. Apoptosis was confirmed by flow cytometry analyses, while CSENS-treated cells exhibited morphological hallmarks of apoptosis including cell shrinkage, irregularity in cellular shape, cellular detachment and chromatin condensation. Biochemical signs of apoptosis, such as DNA degradation, were observed by comet assay and gel electrophoresis. The pro-apoptotic effect of CSENS was caspase-3-independent and associated with increase of the Bax/Bcl-2 ratio. CSENS treatment down-regulated transcriptional and DNA-binding activities of NF-κB and AP-1 proteins, associated with down-regulation of their target oncogenes, c-Myc, cyclin D1 and survivin. On the other hand, CSENS up-regulated transcriptional and DNA-binding activities of Nrf2 and expression of cytoprotective genes. In addition, CSENS modulated the expression levels of ERK1/2 MAPK, p53 and p21. These findings suggest that CSENS may be a valuable agent for treatment of colon cancer.

  7. Measuring exertion during caregiving of children and young adults with cerebral palsy who require assistance for mobility and self-care.

    Science.gov (United States)

    Andrews, Marcella; Bolt, Daniel M; Braun, Michael; Benedict, Ruth E

    2013-08-01

    Our purpose was to compare objective and subjective measures of energy exertion during caregiving tasks. Participants were primary caregivers (N = 19) of children and young adults (aged 3 -22 years) with cerebral palsy (CP) who require assistance for mobility and self-care (67% classified in level V on the Gross Motor Function Classification System). Measures of exertion were collected during two caregiving tasks: (1) transfers and (2) dressing. Objective measures included volume of oxygen (V02), heart rate (HR), and the subjective measure was a rating of perceived exertion (Borg RPE). Controlling for baseline status, perceived exertion correlated with VO2 (0.43, p measures of exertion appear to capture the strain of caregiving. Understanding a caregiver's perception of exertion can guide therapists in assessing the need for equipment, pharmacological, or respite interventions.

  8. Is there a link between exertional heat stroke and susceptibility to malignant hyperthermia?

    Directory of Open Access Journals (Sweden)

    Emmanuel Sagui

    Full Text Available The identification of a predisposition toward malignant hyperthermia (MH as a risk factor for exertional heat stroke (EHS remains a matter of debate. Such a predisposition indicates a causal role for MH susceptibility (MHS after EHS in certain national recommendations and has led to the use of an in vitro contracture test (IVCT to identify the MHS trait in selected or unselected EHS patients. The aim of this study was to determine whether the MHS trait is associated with EHS.EHS subjects in the French Armed Forces were routinely examined for MHS after experiencing an EHS episode. This retrospective study compared the features of IVCT-diagnosed MHS (iMHS EHS subjects with those of MH-normal EHS patients and MH patients during the 2004-2010 period. MHS status was assessed using the European protocol.During the study period, 466 subjects (median age 25 years; 31 women underwent MHS status investigation following an EHS episode. None of the subjects reported previous MH events. An IVCT was performed in 454 cases and was diagnostic of MHS in 45.6% of the study population, of MH susceptibility to halothane in 18.5%, of MH susceptibility to caffeine in 9.9%, and of MH susceptibility to halothane and caffeine in 17.2%. There were no differences in the clinical features, biological features or outcomes of iMHS EHS subjects compared with those of MH-normal or caffeine or halothane MHS subjects without known prior EHS episode. The recurrence rate was 12.7% and was not associated with MH status or any clinical or biological features. iMHS EHS patients exhibited a significantly less informative IVCT response than MH patients.The unexpected high prevalence of the MHS trait after EHS suggested a latent disturbance of calcium homeostasis that accounted for the positive IVCT results. This study did not determine whether EHS patients have an increased risk of MH, and it could not determine whether MH susceptibility is a risk factor for EHS.

  9. Preliminary investigation of cardiopulmonary function in stroke patients with stable heart failure and exertional dyspnea

    Science.gov (United States)

    Liaw, Mei-Yun; Wang, Lin-Yi; Pong, Ya-Ping; Tsai, Yu-Chin; Huang, Yu-Chi; Yang, Tsung-Hsun; Lin, Meng-Chih

    2016-01-01

    Abstract The aim of this study was to investigate the relationships between pulmonary function, respiratory muscle strength, perceived dyspnea, degree of fatigue, and activity of daily living with motor function and neurological status in stroke patients with stable congestive heart failure (CHF). This was a cohort study in a tertiary care medical center. Stroke patients with CHF and exertional dyspnea (New York Heart Association class I–III) were recruited. The baseline characteristics included duration of disease, Brunnstrom stage, spirometry, resting heart rate, resting oxyhemoglobin saturation (SpO2), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), Borg scale, fatigue scale, and Barthel index. A total of 47 stroke patients (24 males, 23 females, mean age 65.9 ± 11.5 years) were included. The average Brunnstrom stages of affected limbs were 3.6 ± 1.3 over the proximal parts and 3.5 ± 1.4 over the distal parts of upper limbs, and 3.9 ± 0.9 over lower limbs. The average forced vital capacity (FVC) was 2.0 ± 0.8 L, with a predicted FVC% of 67.9 ± 18.8%, forced expiratory volume in the first second (FEV1) of 1.6 ± 0.7 L, predicted FEV1% of 70.6 ± 20.1%, FEV1/FVC of 84.2 ± 10.5%, and maximum mid-expiratory flow of 65.4 ± 29.5%. The average MIP and MEP were −52.9 ± 33.3 cmH2O and 60.8 ± 29.0 cmH2O, respectively. The Borg scale was 1.5 ± 0.8. MIP was negatively associated with the average Brunnstrom stage of the proximal (r = −0.318, P lower extremities (r = −0.288, P lower extremities (r = −0.311, P limbs. FVC was more strongly associated with MIP and MEP than predicted FVC%. FEV1/FVC may be used as a reference for the pulmonary dysfunction. PMID:27749577

  10. Characterization of fluid forces exerted on a cylinder array oscillating laterally in axial flow

    International Nuclear Information System (INIS)

    Divaret, Lise

    2014-01-01

    This thesis presents an experimental and a numerical study of the fluid forces exerted on a cylinder or a cylinder array oscillating laterally in an axial flow. The parameters of the system are the amplitude, the oscillation frequency, the confinement and the length to diameter ratio of the cylinder. The objective is to determine the fluid damping created by the axial flow, i.e. the dissipative force. The industrial application of this thesis is the determination of the fluid damping of the fuel assemblies in the core of a nuclear power plant during an earthquake. The study focuses on the configurations where the oscillation velocity is small compared to the axial flow velocity. In a first part, we study the case of a cylinder with no confinement oscillating in axial flow. Two methods are used: a dynamical and a quasi-static approach. In dynamics, the damping rate is measured during free oscillations of the cylinder. In the quasi-static approach, the damping coefficient is calculated from the normal force measured on a yawed cylinder. The range of the small ratios between the oscillation and the axial flow velocities corresponds to a range of low yaw angle where the cylinder is in near-axial flow in statics. The case of a yawed cylinder has been studied both experimentally with experiments in a wind tunnel and numerically with CFD calculations. The analyses of the fluid forces shows that for yaw angles smaller than 5 degrees, a linear lift with the yaw angle creates the damping. The origin of the lift force is discussed from pressure and velocity measurements. The results of the quasi-static approach are compared to the results of the dynamical experiments. In a second part, an experimental study is performed on a rigid cylinder array made up of 40 cylinders oscillating in an axial flow. The normal force and the displacement of the cylinder array are measured simultaneously. The added mass and damping coefficient are calculated and their variation with the

  11. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hals, Ingrid K., E-mail: ingrid.hals@ntnu.no [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ogata, Hirotaka; Pettersen, Elin [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ma, Zuheng; Bjoerklund, Anneli [Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden); Skorpen, Frank [Department of Laboratory Medicine, NTNU, Trondheim (Norway); Egeberg, Kjartan Wollo [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Grill, Valdemar [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden)

    2012-06-29

    positive findings. A fourfold induction of UCP-2 was required to exert minor metabolic effects. These findings question an impact of moderately elevated UCP-2 levels in beta cells as seen in diabetes.

  12. Exertional-induced bronchoconstriction: Comparison between cardiopulmonary exercise test and methacholine challenging test

    Directory of Open Access Journals (Sweden)

    Mostafa Ghanei

    2015-01-01

    Full Text Available Introduction: Exertional-induced bronchoconstriction is a condition in which the physical activity causes constriction of airways in patients with airway hyper- responsiveness. In this study, we tried to study and evaluate any relationship between the findings of cardiopulmonary exercise testing (CPET and the response to methacholine challenge test (MCT in patients with dyspnea after activity. Materials and Methods: Thirty patients with complaints of dyspnea following activity referred to "Lung Clinic" of Baqiyatallah Hospital but not suffering from asthma were entered into the study. The subjects were excluded from the study if: Suffering from any other pulmonary diseases, smoking more than 1 cigarette a week in the last year, having a history of smoking more than 10 packets of cigarettes/year, having respiratory infection in the past 4 weeks, having abnormal chest X-ray or electrocardiogram, and cannot discontinue the use of medicines interfering with bronchial provocation. Baseline spirometry was performed for all the patients, and the values of forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC, and FEV/FVC were recorded. The MCT and then the CPET were performed on all patients. Results: The mean VO 2 (volume oxygen in patients with positive methacholine test (20.45 mL/kg/min was significantly lower than patients with negative MCT (28.69 mL/kg/min (P = 0.000. Respiratory rates per minute (RR and minute ventilation in the group with positive MCT (38.85 and 1.636 L were significantly lower than the group with negative methacholine test (46.78 and 2.114 L (P < 0.05. Also, the O 2 pulse rate in the group with negative methacholine test (116.27 mL/beat was significantly higher than the group with positive methacholine test (84.26 mL/beat (P < 0.001. Conclusion: Pulmonary response to exercise in patients with positive methacholine test is insufficient. The dead space ventilation in these patients has increased. Also, dynamic

  13. Low Prevalence of Periodontitis in Acromegaly: Growth Hormone May Exert a Protective Effect

    Directory of Open Access Journals (Sweden)

    Hülya Serinsöz

    2015-06-01

    Full Text Available Purpose: To evaluate bone mineral density (BMD measurements and the presence of periodontitis in patients with acromegaly, as well as to inquire the impact of interfering factors. Material and Method: Forty-seven acromegalic patients with any accompanying condition known to affect calcium-bone metabolism and 60 age-matched healthy controls were included. Age, gender, duration and activity of acromegaly, past-present therapy options, pituitary hormone profiles, replacement therapies, and the results of periodontal analysis were recorded. Results: Eighteen patients were male (38.3%, 29 were female (61.7%. The mean age of the patients was 46.6±11.5 years, twenty-five (53.1% had active, 22 (46.8% had inactive acromegaly. The latter were older and had longer disease duration (p=0.04, p=0.003, respectively. Serum calcium and phosphorus levels, 24-hour urinary calcium excretion and BMD at the lumbar spine and femur neck insignificantly associated with disease activity (p>0.05. Osteoporosis was detected in 6 patients (12.76%. Periodontitis and advanced periodontitis were more common in control group (66.7% vs. 44.7%, (43.3% vs. 12.8% (p=0.022, p=0.0001, respectively. There was no difference in chronic periodontitis and severity between active and inactive groups (48% vs. 40.9%; p=0.279. No difference was noted in other study parameters, as well. Repeated measures analysis of variance demonstrated statistically insignificant distribution between GH change in time and periodontitis subgroups. Discussion: We demonstrated that acromegaly exerted no clear negative impact on vertebral BMD in the absence of overt hypogonadism. Regardless of disease activity, acromegaly cases exhibited lower rates of periodontitis with less severity which remained unchanged in the presence of accompanying metabolic disorders known to have negative impact on periodontal tissue. Chronic exposure to excess GH may have a protective role against periodontitis. Turk Jem 2015; 19: 42-48

  14. Soluble epoxide hydrolase inhibition exerts beneficial anti-remodeling actions post-myocardial infarction.

    Science.gov (United States)

    Kompa, Andrew R; Wang, Bing H; Xu, Guoying; Zhang, Yuan; Ho, Pei-Yu; Eisennagel, Stephen; Thalji, Reema K; Marino, Joseph P; Kelly, Darren J; Behm, David J; Krum, Henry

    2013-07-15

    A contributory role for soluble epoxide hydrolase (sEH) in cardiac remodeling post-myocardial infarction (MI) has been suggested; however effects of sEH inhibition following MI have not been evaluated. In this study, we examined in vivo post-MI anti-remodeling effects of a novel sEH inhibitor (GSK2188931B) in the rat, and evaluated its direct in vitro effects on hypertrophy, fibrosis and inflammation. Post-MI administered GSK2188931B (80 mg/kg/d in chow) for 5 weeks improved left ventricular (LV) ejection fraction compared to vehicle-treated (Veh) rats (P<0.01; Sham 65 ± 2%, MI+Veh 30 ± 2%, MI+GSK 43 ± 2%) without affecting systolic blood pressure. Percentage area of LV tissue sections stained positive for picrosirius red (PS) and collagen I (CI) were elevated in LV non-infarct zone (P<0.05; NIZ; PS: Sham 1.46 ± 0.13%, MI+Veh 2.14 ± 0.22%, MI+GSK 1.28 ± 0.14%; CI: Sham 2.57 ± 0.17%, MI+Veh 5.06 ± 0.58%, MI+GSK 2.97 ± 0.34%) and peri-infarct zone (P<0.001; PIZ; PS: Sham 1.46 ± 0.13%, MI+Veh 9.06 ± 0.48%, MI+GSK 6.31 ± 0.63%; CI: Sham 2.57±0.17%, MI+Veh 10.51 ± 0.64%, MI+GSK 7.77 ± 0.57%); GSK2188931B attenuated this increase (P<0.05). GSK2188931B reduced macrophage infiltration into the PIZ (P<0.05). GSK2188931B reduced AngII- and TNFα-stimulated myocyte hypertrophy, AngII- and TGFβ-stimulated cardiac fibroblast collagen synthesis, including markers of gene expression ANP, β-MHC, CTGF and CI (P<0.05). GSK2188931B reduced TNFα gene expression in lipopolysaccharide (LPS)-stimulated monocytes (P<0.05). sEH inhibition exerts beneficial effects on cardiac function and ventricular remodeling post-MI, and direct effects on fibrosis and hypertrophy in cardiac cells. These findings suggest that sEH is an important contributor to the pathological remodeling following MI, and may be a useful target for therapeutic blockade in this setting. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Epigenetic memory of oxidative stress: does nephrilin exert its protective effects via Rac1?

    Directory of Open Access Journals (Sweden)

    Mascarenhas DD

    2017-07-01

    Full Text Available Desmond D Mascarenhas,1,2 David N Herndon,3 Istvan Arany4 1Mayflower Organization for Research & Education, Sunnyvale, CA, 2Transporin, Inc., Sunnyvale, CA, 3Department of Surgery, The University of Texas Medical Branch, and Shriners Hospitals for Children, Galveston, TX, 4Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS, USA Aim: Nephrilin peptide, a designed inhibitor of Rictor complex (mTORC2, exerts pleiotropic protective effects in metabolic, xenobiotic and traumatic stress models. Stress can generate enduring epigenetic changes in gene function. In this work we examine the possibility that nephrilin treatment protects against acute and enduring global changes in oxidative metabolism, with a focus on the Rictor-complex-mediated activation of Rac1, a subunit of NADPH oxidase (Nox via PKCs, Prex1 and p66shc. Methods: Given the wide range of animal models in which nephrilin peptide has previously demonstrated effectiveness in vivo, we chose three different experimental systems for this investigation: dermal fibroblasts, renal proximal tubule epithelial cells (PTECs, and kidney tissue and urine from an animal model of burn trauma in which nephrilin was previously shown to prevent loss of kidney function. Results: (1 Nephrilin protects dermal fibroblasts from loss of viability and collagen synthesis after ultraviolet A (UV-A or H2O2 insult. (2 Nephrilin reduces reactive oxygen species (ROS formation by H2O2–treated (PTECs with or without nicotine pretreatment. Using RNA arrays and pathway analysis we demonstrate that nicotine and H2O2-treated PTECs specifically induced Rac1 gene networks in these cells. (3 Using kidney tissue and urine from the burn trauma model we demonstrate significant elevations of [a] 8-aminoprostane in urine; [b] kidney tissue histone modification and DNA methylation; and [c] post-transcriptional phosphorylation events consistent with Rac1 activation in

  16. Polypyridylruthenium(II complexes exert anti-schistosome activity and inhibit parasite acetylcholinesterases.

    Directory of Open Access Journals (Sweden)

    Madhu K Sundaraneedi

    2017-12-01

    Full Text Available Schistosomiasis affects over 200 million people and there are concerns whether the current chemotherapeutic control strategy (periodic mass drug administration with praziquantel (PZQ-the only licenced anti-schistosome compound is sustainable, necessitating the development of new drugs.We investigated the anti-schistosome efficacy of polypyridylruthenium(II complexes and showed they were active against all intra-mammalian stages of S. mansoni. Two compounds, Rubb12-tri and Rubb7-tnl, which were among the most potent in their ability to kill schistosomula and adult worms and inhibit egg hatching in vitro, were assessed for their efficacy in a mouse model of schistosomiasis using 5 consecutive daily i.v. doses of 2 mg/kg (Rubb12-tri and 10 mg/kg (Rubb7-tnl. Mice treated with Rubb12-tri showed an average 42% reduction (P = 0.009, over two independent trials, in adult worm burden. Liver egg burdens were not significantly decreased in either drug-treated group but ova from both of these groups showed significant decreases in hatching ability (Rubb12-tri-68%, Rubb7-tnl-56% and were significantly morphologically altered (Rubb12-tri-62% abnormal, Rubb7-tnl-35% abnormal. We hypothesize that the drugs exerted their activity, at least partially, through inhibition of both neuronal and tegumental acetylcholinesterases (AChEs, as worms treated in vitro showed significant decreases in activity of these enzymes. Further, treated parasites exhibited a significantly decreased ability to uptake glucose, significantly depleted glycogen stores and withered tubercules (a site of glycogen storage, implying drug-mediated interference in this nutrient acquisition pathway.Our data provide compelling evidence that ruthenium complexes are effective against all intra-mammalian stages of schistosomes, including schistosomula (refractory to PZQ and eggs (agents of disease transmissibility. Further, the results of this study suggest that schistosome AChE is a target of

  17. Exertional Heat Illnesses and Environmental Conditions During High School Football Practices.

    Science.gov (United States)

    Tripp, Brady L; Eberman, Lindsey E; Smith, Michael Seth

    2015-10-01

    Guidelines for preventing exertional heat illnesses (EHIs) during extreme heat stress should be specific to regional environments, age, and sport and should be based on evidence of reducing the risk. Each year in the United States, over 1 million high school football players practice in the August heat; however, no published data describe the incidence of EHIs in these athletes. To describe the environmental conditions and incidence of EHIs during high school football practices over a 3-month period. Descriptive epidemiology study. For a 3-month period (August-October), athletic trainers at 12 high schools in North Central Florida recorded the practice time and length, environmental conditions (wet-bulb globe temperature), and incidences of EHIs in varsity football athletes. Athletes suffered 57 total EHIs during 29,759 athlete-exposures (AEs) for the 3-month data collection period (rate = 1.92/1000 AEs). August accounted for the majority of all EHIs, with 82.5% (47/57) and the highest rate (4.35/1000 AEs). Of total heat illnesses, heat cramps accounted for 70.2% (40/57), heat exhaustion 22.8% (13/57), and heat syncope 7.0% (4/57). The odds ratio indicated that athletes in August practices that lasted longer than the recommended 3 hours were 9.84 times more likely to suffer a heat illness than those in practices lasting ≤3 hours. The highest rate of EHIs was during August. Practices in August that exceeded the recommended 3 hours were associated with a greater risk of heat illnesses. The overall rate of EHIs was lower for the high school football athletes observed in the study compared with that reported for collegiate football athletes in the region. The low rates of EHIs recorded suggest that the prevention guidelines employed by sports medicine teams are appropriate for the region and population. Team physicians and athletic trainers should employ evidence-based, region- and population-specific EHI prevention guidelines. Sports medicine teams, coaches, and

  18. Subject-specific increases in serum S-100B distinguish sports-related concussion from sports-related exertion.

    Directory of Open Access Journals (Sweden)

    Karin Kiechle

    Full Text Available The on-field diagnosis of sports-related concussion (SRC is complicated by the lack of an accurate and objective marker of brain injury.To compare subject-specific changes in the astroglial protein, S100B, before and after SRC among collegiate and semi-professional contact sport athletes, and compare these changes to differences in S100B before and after non-contact exertion.Longitudinal cohort study.From 2009-2011, we performed a prospective study of athletes from Munich, Germany, and Rochester, New York, USA. Serum S100B was measured in all SRC athletes at pre-season baseline, within 3 hours of injury, and at days 2, 3 and 7 post-SRC. Among a subset of athletes, S100B was measured after non-contact exertion but before injury. All samples were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels.Forty-six athletes (30 Munich, 16 Rochester underwent baseline testing. Thirty underwent additional post-exertion S100B testing. Twenty-two athletes (16 Rochester, 6 Munich sustained a SRC, and 17 had S100B testing within 3 hours post-injury. The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline (0.099±0.008 µg/L vs. 0.058±0.006 µg/L, p = 0.0002. Mean post-exertion S100B was not significantly different than the preseason baseline. S100B levels at post-injury days 2, 3 and 7 were significantly lower than the 3-hour level, and not different than baseline. Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC (AUC 0.772 and 0.904, respectively. A 3-hour post-concussion S100B >0.122 µg/L and a proportional S100B increase of >45.9% over baseline were both 96.7% specific for SRC.Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion, and may be a useful adjunct to the diagnosis of SRC.

  19. Locomotor activity, enjoyment and perceived exertion from 7v7 football for patients with Parkinson’s disease

    DEFF Research Database (Denmark)

    Møller, Trine Kjeldgaard Tang; Madsen, Mads; Frederiksen, Jakob

    Background: The level of daily physical activity decrease with disease severity in patients with Parkinson’s disease. Furthermore, inactivity is associated with greater disabilities in daily life and secondary complications. Participation in recreational football, organized as small-sided games......, on a regularly basis show benefits in the health profile and physical capacity in untrained adult men, and improves both cardiovascular and metabolic fitness. Purpose: The purpose of this study is to describe locomotor activities, enjoyment and perceived exertion during football training for men with Parkinson...... on a 40x40 m artificial turf football pitch with 1.5x3 m goals. After each activity perceived exertion for lower limbs and total body individually was rated on a visual analogue scale (0-10). After the whole session the participants filled out a PACES questionnaire to rate enjoyment of the session. Height...

  20. Effects of 12 months aerobic exercise intervention on work ability, need for recovery, productivity and rating of exertion among cleaners

    DEFF Research Database (Denmark)

    Lidegaard, Mark; Søgaard, Karen; Krustrup, Peter

    2018-01-01

    PURPOSE: This study assessed the effects of a worksite aerobic exercise intervention among cleaners on: work ability, need for recovery, productivity, and rating of exertion. METHODS: In a monocentric randomised controlled trial in Denmark, 116, of 250 invited, cleaners were cluster-randomised (w......PURPOSE: This study assessed the effects of a worksite aerobic exercise intervention among cleaners on: work ability, need for recovery, productivity, and rating of exertion. METHODS: In a monocentric randomised controlled trial in Denmark, 116, of 250 invited, cleaners were cluster......-reported data on outcomes and sociodemographic information were collected at baseline, and at 4 and 12 month follow-up. All outcomes were analysed in a linear repeated-measures 2 × 2 mixed-model by an intention-to-treat analysis approach. RESULTS: Drop-out was 26 and 33% at 4 and 12 months, respectively...

  1. [A rare cause of exertional dry cough: agenesis of the left pulmonary artery associated with pulmonary hypoplasia].

    Science.gov (United States)

    Laaraje, Azzeddine; El Hafidi, Naima; Mahraoui, Chafik

    2017-01-01

    Agenesis of the left pulmonary artery associated with hypoplasia of the ipsilateral lung is a rare congenital malformation in children; it can be discovered fortuitously or because of the presence of recurrent respiratory infections. Diagnosis is based on thoracic angioscanner. Treatment is essentially conservative. We report the case of a 6-year old child with agenesis of the left pulmonary artery associated with hypoplasia of the ipsilateral lung detected because of exertional dry cough.

  2. Coulombian Model for 3D Analytical Calculation of the Torque Exerted on Cuboidal Permanent Magnets with Arbitrarly Oriented Polarizations

    OpenAIRE

    Allag , Hicham; Yonnet , Jean-Paul; Latreche , Mohamed E. H.; Bouchekara , Houssem

    2011-01-01

    International audience; The paper proposes improved analytical expressions of the torque on cuboidal permanent magnets. Expressions are valid for any relative magnet position and for any polarization direction. The analytical calculation is made by replacing polarizations by distributions of magnetic charges on the magnet poles (Coulombian approach). The torque exerted on the second magnet is calculated by Lorentz force formulas for any arbitrary position. The three components of the torque a...

  3. Improved arterial flow-mediated dilation after exertion involves hydrogen peroxide in overweight and obese adults following aerobic exercise training.

    Science.gov (United States)

    Robinson, Austin T; Franklin, Nina C; Norkeviciute, Edita; Bian, Jing Tan; Babana, James C; Szczurek, Mary R; Phillips, Shane A

    2016-07-01

    Acute strenuous physical exertion impairs arterial function in sedentary adults. We investigated the effects of 8 weeks of regular aerobic exercise training on acute physical exertion-induced arterial dysfunction in sedentary, overweight, and obese adults. Twenty-five overweight and obese adults (BMI 30.5 ± 7.2 years) were assigned to 8 weeks of aerobic training or to a control group. Brachial artery flow-mediated dilation (FMD) was assessed before and after acute leg press exercise at weeks 0 and 8. Gluteal adipose biopsies were performed at rest and post acute leg press to measure microvessel FMD with and without nitric oxide synthase inhibition via L-nitroarginine methyl ester or hydrogen peroxide (H2O2) scavenging with Catalase. Microvessel nitric oxide and H2O2 production were assessed via fluorescence microscopy. Brachial artery dilation was reduced post acute leg press at week 0 in the aerobic exercise and control groups, but was preserved in the aerobic-exercise group post acute leg press at week 8 (P aerobic exercise group but impaired in the control group at week 8 (P aerobic exercise group was more sensitive to H2O2 scavenging than inhibition of nitric oxide, and post acute leg press microvessel H2O2 production was increased compared with at rest (P Aerobic exercise prevents acute exertion-induced arterial dysfunction in overweight and obese adults via a phenotypic switch from nitric oxide-mediated dilation at rest to a predominately H2O2-mediated dilation after acute physical exertion.

  4. Effect of traditional resistance and power training using rated perceived exertion for enhancement of muscle strength, power, and functional performance

    OpenAIRE

    Tiggemann, Carlos Leandro; Dias, Caroline Pieta; Radaelli, Regis; Massa, J?ssica Cassales; Bortoluzzi, Rafael; Schoenell, Maira Cristina Wolf; Noll, Matias; Alberton, Cristine Lima; Kruel, Luiz Fernando Martins

    2016-01-01

    The present study compared the effects of 12?weeks of traditional resistance training and power training using rated perceived exertion (RPE) to determine training intensity on improvements in strength, muscle power, and ability to perform functional task in older women. Thirty healthy elderly women (60?75?years) were randomly assigned to traditional resistance training group (TRT; n?=?15) or power training group (PT; n?=?15). Participants trained twice a week for 12?weeks using six exercises...

  5. The relationship between biomechanical-anthropometrical parameters and the force exerted on the head when heading free kicks in soccer.

    Science.gov (United States)

    Teymouri, Meghdad; Sadeghi, Heydar; Nabaei, Amir; Kasaeian, Amir

    2012-01-01

    Soccer is a contact sport in which the players are frequently faced with the risk of injury. It has been shown that the force exerted on the head during heading can be as much as 500-1200 Newton (N). The main objective of this study was to determine whether there was any relationship between the force exerted on the head and several biomechanical and anthropometrical parameters related to heading free kicks. A total of 16 semi-professional soccer players with at least 5 years experience participated in this study. The mean age, height, and weight of the study participants were 21.36 ± 5.67, 178 ± 5.99 cm, and 70.55 ± 8.55 kg, respectively. To measure the force exerted on the heads of the players, a pressure gauge was installed on their foreheads. Each participant was asked to defend the ball using the heading technique three times. A camera with a sampling frequency of 150 frames per second was used to record the moment of impact between the ball and head during each heading event. For each participant and replicate, the ball and head velocity (m/s) as well as the angular body changes (degrees) were calculated using MATLAB and AutoCAD softwares, respectively. Descriptive statistics, including means and standard deviations were used to describe the data. Pearson correlation coefficient (alpha = 0.05) was used to examine potential relationships between the variables of interest. Significant correlations existed between the force exerted on the head during heading, participant age, body mass, body fat percentage, and head perimeter (P < 0.05). The study revealed the significance of anthropometric variables related to heading, such as age and head perimeter. Therefore, it was concluded that these variables should be considered when teaching and practicing the heading technique with players of different ages and anthropometric sizes.

  6. Arginine, N-carbamylglutamate, and glutamine exert protective effects against oxidative stress in rat intestine

    Directory of Open Access Journals (Sweden)

    Liang Xiao

    2016-09-01

    .05. Collectively, this study suggested that dietary supplementation with 1% GLN, 0.1% NCG, and 1% ARG was effective in enhancing the antioxidant status and maintaining the morphological structure of rat jejunum under oxidative stress; of these supplements, 1% GLN exerted the greatest effects on mitigating oxidative stress.

  7. Antitumor activity of miR-34a in peritoneal mesothelioma relies on c-MET and AXL inhibition: persistent activation of ERK and AKT signaling as a possible cytoprotective mechanism

    Directory of Open Access Journals (Sweden)

    Rihan El Bezawy

    2017-01-01

    -invasive activity. Conclusions Our preclinical data showing impressive inhibitory effects induced by miR-34a on DMPM cell proliferation, invasion, and growth in immunodeficient mice strongly suggest the potential clinical utility of a miR-34a-replacement therapy for the treatment of such a still incurable disease. On the other hand, we provide the first evidence of a potential cytoprotective/resistance mechanism that may arise towards miRNA-based therapies through the persistent activation of RTK downstream signaling.

  8. The effect of home-based inspiratory muscle training on exercise capacity, exertional dyspnea and pulmonary function in COPD patients.

    Science.gov (United States)

    Bavarsad, Maryam Bakhshandeh; Shariati, Abdolali; Eidani, Esmaeil; Latifi, Mahmud

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is currently the fourth cause of mortality worldwide. Patients with COPD experience periods of dyspnea, fatigue, and disability, which impact on their life. The objective of this study was to investigate the effect of short-term inspiratory muscle training on exercise capacity, exertional dyspnea, and pulmonary lung function. A randomized, controlled trial was performed. Thirty patients (27 males, 3 females) with mild to very severe COPD were randomly assigned to a training group (group T) or to a control group (group C). Patients in group T received training for 8 weeks (15 min/day for 6 days/week) with flow-volumetric inspiratory exerciser named (Respivol). Each patient was assessed before and after 8 weeks of training for the following clinical parameters: exercise capacity by 6-min walking test (6MWT), exertional dyspnea by Borg scale, and pulmonary lung function by spirometry. Patients used training together with medical treatment. The data were analyzed using paired t-test and independent t-test. Results showed statistically significant increase in 6MWT at the end of the training from 445.6 ± 22.99 to 491.06 ± 17.67 meters? (P training group but not in the control group. The values for exercise capacity and dyspnea improved after 8 weeks in group T in comparison with group C (P = 0.001 and P = 0.0001, respectively). No changes were observed in any measure of pulmonary function in both groups. Short-term inspiratory muscle training has beneficial effects on exercise capacity and exertional dyspnea in COPD patients.

  9. HER Specific TKIs Exert Their Antineoplastic Effects on Breast Cancer Cell Lines through the Involvement of STAT5 and JNK.

    Directory of Open Access Journals (Sweden)

    Daphne Gschwantler-Kaulich

    Full Text Available HER-targeted tyrosine kinase inhibitors (TKIs have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood.Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP-1 and immunolabeling for active caspase 3, respectively.All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively.We have shown that HER-TKIs exert a HER2 expression-dependent anti-cancer effect in breast cancer cell lines. This involves blockade of JNK and STAT5A/B signaling, which have been found to be required for in vitro growth of these cell lines.

  10. Ratings of perceived thigh and back exertion in forest workers during repetitive lifting using squat and stoop techniques.

    Science.gov (United States)

    Hagen, K B; Harms-Ringdahl, K

    1994-11-15

    Local thigh and low back perceived exertion (RPE), sagittal peak load moments, and leg and trunk muscular activity during repetitive submaximal lifting, with squat and stoop technique, were investigated. This study analyzed changes in kinetic variables caused by changes in body movements during the lifting bouts, and the contribution of the biomechanical and physiologic variables to the variability in the local RPE responses. Despite instructions that emphasize the "correct" lifting technique as the squat technique, the stoop technique is reported as more commonly used in practice. Few studies have investigated the effect of lifting technique on differentiated perceptual responses in repetitive lifting. Ten experienced forest workers performed submaximal repetitive lifting bouts until steady-state VO2 was reached, using five different weight and frequency combinations with both squat and stoop techniques. Borg's scale was used for RPE measurements. Muscular activity in lumbar, hip, knee extensors, and knee flexors was recorded with surface electrodes. Kinematic data was obtained from electronic liquid-level sensors, and vertical ground reaction forces from a two-dimensional force plate. Low back RPE was higher for stoop than for squat, whereas the opposite was true for thigh RPE. The total accountable variance (R2) for the biomechanical and physiologic variables to the RPE responses ranged from 0.25 (low back RPE in squat lifting) to 0.61-0.76 for the other assessments. During the time course in squat lifting at the highest frequency, the knee load moment decreased and the vertical ground reaction forces increased. The study indicates that "movement strategies" to reduce the demand on the knee-extensor muscles were used during the squat lifting bouts at the highest frequencies, which combined with the relatively high assessed thigh exertions, leads to the hypothesis that quadriceps muscle exertion is the "weak link" for the squat technique. The study also indicates

  11. Evaluation of Interhandle Distance During Pushing and Pulling of a Four-Caster Cart for Upper Limb Exertion.

    Science.gov (United States)

    Ohnishi, Akihiro; Takanokura, Masato; Sugama, Atsushi

    2016-09-01

    This study examined the relationship between interhandle distances and upper limb exertion during simply pushing and pulling of a cart with four swivel wheels, defined by a roll box pallet (RBP) in a Japanese industrial standard. Six healthy young male participants were asked to push and pull an RBP at a distance of 5.2 m under six conditions corresponding to different interhandle distances (40 cm, 60 cm, and 80 cm) and weights (130 kg and 250 kg). The upper limb exertion was studied by shoulder abduction and flexion, and elbow flexion, as well as surface electromyogram (EMG) in shoulder extensor, and elbow flexor and extensor. Participants were required to provide subjective evaluations on operability after each trial. Subjective operability indicated that a narrower interhandle distance had a better operability for pushing. Interhandle distance was also related to upper limb exertion especially for pushing. A narrow interhandle distance caused smaller shoulder adduction but larger elbow flexion. The normalized EMG data revealed that muscular activity became smaller with a narrow interhandle distance in shoulder extensor. During the pulling task, elbow flexion was smaller at a narrow interhandle distance, although subjective operability and normalized EMG were not significantly varied. A wider interhandle distance, such as 80 cm, was not suitable in the forwardbackward movement of the RBP. Therefore, this study concluded that an interhandle distance of 40 cm would be suitable for pushing and pulling an RBP to protect the workers' hands against the risk of injury by installing inner handles.

  12. High-dose Humanin analogue applied during ischemia exerts cardioprotection against ischemia/reperfusion injury by reducing mitochondrial dysfunction.

    Science.gov (United States)

    Thummasorn, Savitree; Shinlapawittayatorn, Krekwit; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2017-10-01

    Although the gold standard treatment for acute myocardial infarction is reperfusion therapy, reperfusion itself can cause myocardial damage via induction of cardiac mitochondrial dysfunction. This can lead to increased myocardial infarct size, arrhythmias, and left ventricular (LV) dysfunction. Recently, a newly discovered peptide, Humanin, has been shown to exert several beneficial effects including antioxidative and antiapoptosis effects. We recently reported that a Humanin analogue (HNG, 84 μg/kg) given prior to cardiac ischemia exerted cardioprotection against I/R injury, but failed to do so when it was given after ischemia was induced. However, in a clinical setting, patients can only be treated after the onset of ischemia. In this study, we investigated the potential benefit of various doses of HNG therapy (84, 168, 252 μg/kg) against myocardial I/R injury when applied during ischemia on cardiac arrhythmia, myocardial infarct size, cardiac mitochondrial function, and LV function. Myocardial I/R injury was induced in rats by 30-minute left anterior descending coronary artery occlusion, followed by 120-minute of reperfusion. HNG at the different doses were given intravenously at 15 minutes after ischemic onset and also at the onset of reperfusion. HNG (252 μg/kg) applied during the ischemic period not only increased HN levels in the damaged myocardium, but also significantly decreased cardiac arrhythmia, myocardial infarct size, cardiac mitochondrial dysfunction, and left ventricular dysfunction. These benefits were mediated through the attenuation of cardiac mitochondrial dysfunction. High-dose HN applied during ischemia in rats could exert cardioprotection against I/R injury-induced mitochondrial dysfunction. © 2017 John Wiley & Sons Ltd.

  13. Tungsten carbide cobalt nanoparticles exert hypoxia-like effects on the gene expression level in human keratinocytes.

    Science.gov (United States)

    Busch, Wibke; Kühnel, Dana; Schirmer, Kristin; Scholz, Stefan

    2010-01-27

    Tungsten carbide (WC) and tungsten carbide cobalt (WC-Co) nanoparticles are of occupational health relevance because of the increasing usage in hard metal industries. Earlier studies showed an enhanced toxic potential for WC-Co compared to WC or cobalt ions alone. Therefore, we investigated the impact of these particles, compared to cobalt ions applied as CoCl(2), on the global gene expression level in human keratinocytes (HaCaT) in vitro. WC nanoparticles exerted very little effects on the transcriptomic level after 3 hours and 3 days of exposure. In contrast, WC-Co nanoparticles caused significant transcriptional changes that were similar to those provoked by CoCl(2). However, CoCl(2) exerted even more pronounced changes in the transcription patterns. Gene set enrichment analyses revealed that the differentially expressed genes were related to hypoxia response, carbohydrate metabolism, endocrine pathways, and targets of several transcription factors. The role of the transcription factor HIF1 (hypoxia inducible factor 1) is particularly highlighted and aspects of downstream events as well as the role of other transcription factors related to cobalt toxicity are considered. This study provides extensive data useful for the understanding of nanoparticle and cobalt toxicity. It shows that WC nanoparticles caused low transcriptional responses while WC-Co nanoparticles are able to exert responses similar to that of free cobalt ions, particularly the induction of hypoxia-like effects via interactions with HIF1alpha in human keratinocytes. However, the enhanced toxicity of WC-Co particles compared to CoCl(2) could not be explained by differences in gene transcription.

  14. Tungsten carbide cobalt nanoparticles exert hypoxia-like effects on the gene expression level in human keratinocytes

    Science.gov (United States)

    2010-01-01

    Background Tungsten carbide (WC) and tungsten carbide cobalt (WC-Co) nanoparticles are of occupational health relevance because of the increasing usage in hard metal industries. Earlier studies showed an enhanced toxic potential for WC-Co compared to WC or cobalt ions alone. Therefore, we investigated the impact of these particles, compared to cobalt ions applied as CoCl2, on the global gene expression level in human keratinocytes (HaCaT) in vitro. Results WC nanoparticles exerted very little effects on the transcriptomic level after 3 hours and 3 days of exposure. In contrast, WC-Co nanoparticles caused significant transcriptional changes that were similar to those provoked by CoCl2. However, CoCl2 exerted even more pronounced changes in the transcription patterns. Gene set enrichment analyses revealed that the differentially expressed genes were related to hypoxia response, carbohydrate metabolism, endocrine pathways, and targets of several transcription factors. The role of the transcription factor HIF1 (hypoxia inducible factor 1) is particularly highlighted and aspects of downstream events as well as the role of other transcription factors related to cobalt toxicity are considered. Conclusions This study provides extensive data useful for the understanding of nanoparticle and cobalt toxicity. It shows that WC nanoparticles caused low transcriptional responses while WC-Co nanoparticles are able to exert responses similar to that of free cobalt ions, particularly the induction of hypoxia-like effects via interactions with HIF1α in human keratinocytes. However, the enhanced toxicity of WC-Co particles compared to CoCl2 could not be explained by differences in gene transcription. PMID:20105288

  15. Risk of cardiac disease and observations on lack of potential predictors by clinical history among children presenting for cardiac evaluation of mid-exertional syncope.

    Science.gov (United States)

    Miyake, Christina Y; Motonaga, Kara S; Fischer-Colbrie, Megan E; Chen, Liyuan; Hanisch, Debra G; Balise, Raymond R; Kim, Jeffrey J; Dubin, Anne M

    2016-06-01

    This study aimed to evaluate the incidence of cardiac disorders among children with mid-exertional syncope evaluated by a paediatric cardiologist, determine how often a diagnosis was not established, and define potential predictors to differentiate cardiac from non-cardiac causes. Study design We carried out a single-centre, retrospective review of children who presented for cardiac evaluation due to a history of exertional syncope between 1999 and 2012. Inclusion criteria included the following: (1) age ⩽18 years; (2) mid-exertional syncope; (3) electrocardiogram, echocardiogram and an exercise stress test, electrophysiology study, or tilt test, with exception of long QT, which did not require additional testing; and (4) evaluation by a paediatric cardiologist. Mid-exertional syncope was defined as loss of consciousness in the midst of active physical activity. Patients with peri-exertional syncope immediately surrounding but not during active physical exertion were excluded. A total of 60 patients met the criteria for mid-exertional syncope; 32 (53%) were diagnosed with cardiac syncope and 28 with non-cardiac syncope. A majority of cardiac patients were diagnosed with an electrical myopathy, the most common being Long QT syndrome. In nearly half of the patients, a diagnosis could not be established or syncope was felt to be vasovagal in nature. Neither the type of exertional activity nor the symptoms or lack of symptoms occurring before, immediately preceding, and after the syncopal event differentiated those with or without a cardiac diagnosis. Children with mid-exertional syncope are at risk for cardiac disease and warrant evaluation. Reported symptoms may not differentiate benign causes from life-threatening disease.

  16. The quaternary lidocaine derivative, QX-314, exerts biphasic effects on transient receptor potential vanilloid subtype 1 channels in vitro

    DEFF Research Database (Denmark)

    Rivera-Acevedo, Ricardo E; Pless, Stephan Alexander; Ahern, Christopher A

    2011-01-01

    BACKGROUND: Transient receptor potential vanilloid subfamily member 1 (TRPV1) channels are important integrators of noxious stimuli with pronounced expression in nociceptive neurons. The experimental local anesthetic, QX-314, a quaternary (i.e., permanently charged) lidocaine derivative, recently...... concentrations (less than 1 mM), QX-314 potently inhibited capsaicin-evoked TRPV1 currents with an IC₅₀ of 8.0 ± 0.6 μM. CONCLUSIONS: The results of this study show that the quaternary lidocaine derivative QX-314 exerts biphasic effects on TRPV1 channels, inhibiting capsaicin-evoked TRPV1 currents at lower...

  17. Ratings of Perceived Exertion During Acute Resistance Exercise Performed at Imposed and Self-Selected Loads in Recreationally Trained Women.

    Science.gov (United States)

    Cotter, Joshua A; Garver, Matthew J; Dinyer, Taylor K; Fairman, Ciaran M; Focht, Brian C

    2017-08-01

    Cotter, JA, Garver, MJ, Dinyer, TK, Fairman, CM, and Focht, BC. Ratings of perceived exertion during acute resistance exercise performed at imposed and self-selected loads in recreationally trained women. J Strength Cond Res 31(8): 2313-2318, 2017-Resistance exercise (RE) is commonly used to elicit skeletal muscle adaptation. Relative intensity of a training load links closely with the outcomes of regular RE. This study examined the rating of perceived exertion (RPE) responses to acute bouts of RE using imposed (40% and 70% of 1 repetition maximum [1RM]) and self-selected (SS) loads in recreationally trained women. Twenty physically active women (23.15 ± 2.92 years), who reported regular RE training of at least 3 weekly sessions for the past year, volunteered to participate. During the initial visit, participants completed 1RM testing on 4 exercises in the following order: leg extension, chest press, leg curl, and lat pull-down. On subsequent visits, the same exercises were completed at the SS or imposed loads. The RPE was assessed after the completion of each set of exercises during the 3 RE conditions using the Borg-15 category scale. Self-selected loads corresponded to an average of approximately 57%1RM (±7.62). Overall, RPE increased with load (40%1RM = 11.26 [±1.95]; SS 57%1RM = 13.94 [±1.58]; and, 70%1RM = 15.52 [±2.05]). Reflecting the linear pattern found between load and perceived effort, the present data provide evidence that RPE levels less than 15 likely equate to loads which are not consistent with contemporary American College of Sports Medicine (ACSM) guidelines for enhancing musculoskeletal health which includes strength and hypertrophy. Women desiring increases in strength and lean mass likely need to train at an exertion level at or surpassing a rating of 15 on the Borg-15 category. This article examined the modification of training load on perceived exertion, but other variables, such as the number of repetitions completed, may also be

  18. A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats

    DEFF Research Database (Denmark)

    Andreassen, Kim V; Feigh, Michael; Hjuler, Sara T

    2014-01-01

    -induced obese (DIO) and Zucker diabetic fatty (ZDF) rats. In vitro, KBP-042 demonstrated superior binding affinity and activation of amylin and calcitonin receptors, and ex vivo, KBP-042 exerted inhibitory action on stimulated insulin and glucagon release from isolated islets. In vivo, KBP-042 induced...... a superior and pronounced reduction in food intake in conjunction with a sustained pair-fed corrected weight loss in DIO rats. Concomitantly, KBP-042 improved glucose homeostasis and reduced hyperinsulinemia and hyperleptinemia in conjunction with enhanced insulin sensitivity. In ZDF rats, KBP-042 induced...

  19. Effect of interval training intensity on fat oxidation, blood lactate and the rate of perceived exertion in obese men

    OpenAIRE

    Alkahtani, Shaea A; King, Neil A; Hills, Andrew P; Byrne, Nuala M

    2013-01-01

    Purpose The objectives of this study were to examine the effect of 4-week moderate- and high-intensity interval training (MIIT and HIIT) on fat oxidation and the responses of blood lactate (BLa) and rating of perceived exertion (RPE). Methods Ten overweight/obese men (age?=?29 ?3.7?years, BMI?=?30.7 ?3.4?kg/m2) participated in a cross-over study of 4-week MIIT and HIIT training. The MIIT training sessions consisted of 5-min cycling stages at mechanical workloads 20% above and 20% below 45%VO2...

  20. Effect of inspiratory muscle training (IMT) on aerobic capacity, respiratory muscle strength and rate of perceived exertion in paraplegics.

    Science.gov (United States)

    Soumyashree, Sonali; Kaur, Jaskirat

    2018-04-18

    The purpose is to study the effect of inspiratory muscle training on aerobic capacity, respiratory muscle strength and rate of perceived exertion in paraplegics. Randomized controlled trial. Rehabilitation department in Indian Spinal Injuries Centre, New Delhi. A sample of 30 paraplegics (T1-T12) were randomly allocated into two groups: inspiratory muscle training (IMT) group and control group. The IMT group received inspiratory muscle training for 15 minutes 5 times a week for 4 weeks whereas the control group was given breathing exercises. Maximal inspiratory pressure(MIP), maximal expiratory pressure (MEP), modified Borg's scale (MBS), 12 minute wheelchair aerobic test (12MWAT), multistage fitness test (MSFT), and 6 minutes push test (6MPT). Out of 30 participants, 27 completed the study. The results show that after four weeks of IMT training, there were significant improvements in mean change scores of IMT group as compared to control group. Participants in IMT group performed better on 12MWAT (P = 0.001), MSFT (P = 0.001) and 6MPT (P = 0.001). Improvements in MIP scores (P = 0.001), MEP scores (P = 0.001) and MBS scores (P = 0.004) were also seen in IMT group. Both groups showed significant improvements, however inspiratory muscle training was seen to be more effective than deep breathing exercises for improving aerobic capacity, respiratory muscle strength and rate of perceived exertion in paraplegics.

  1. Chicory, a typical vegetable in Mediterranean diet, exerts a therapeutic role in established atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Lin, Weiqun; Liu, Chaoqun; Yang, Hai; Wang, Wenting; Ling, Wenhua; Wang, Dongliang

    2015-09-01

    Since protocatechuic acid exerts an atheroprotective role, we investigated how chicory (Cichorium intybus L. var. foliosum, Belgian endive) rich in protocatechuic acid, a typical vegetable in Mediterranean diet, affects preestablished atherosclerosis progression. Apolipoprotein E-deficient mice fed AIN diets containing 0.5% freeze-dried chicory for 10 weeks displayed a reduction in lesion size with a concomitant improvement in lesion stability indicated by fewer macrophages and more collagen content. Chicory consumption suppressed aortic cholesterol accumulation and intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 expression, whereas it increased aortic ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) expression. Furthermore, chicory consumption improved peritoneal macrophage phenotype with less cellular cholesterol associated with an enhancement of cholesterol efflux capacity through upregulation of ABCA1 and ABCG1, less cellular oxidative stress associated with an inhibition of nicotinamide adenine dinucleotide phosphate oxidase activity, and weaker inflammatory responses associated with an inhibition of nuclear factor-κB activation. Interestingly, ABCA1 and ABCG1 silencing tended to completely block beneficial effects of chicory in peritoneal macrophages. Chicory exerts an atheroprotective role in mice possibly by regulating lesional macrophage content and phenotype, suggesting that chicory is one underrated contributor to Mediterranean Diet-induced atheroprotection. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Assessment of Whole Body and Local Muscle Fatigue Using Electromyography and a Perceived Exertion Scale for Squat Lifting.

    Science.gov (United States)

    Ahmad, Imran; Kim, Jung-Yong

    2018-04-18

    This research study aims at addressing the paradigm of whole body fatigue and local muscle fatigue detection for squat lifting. For this purpose, a comparison was made between perceived exertion with the heart rate and normalized mean power frequency (NMPF) of eight major muscles. The sample consisted of 25 healthy males (age: 30 ± 2.2 years). Borg’s CR-10 scale was used for perceived exertion for two segments of the body (lower and upper) and the whole body. The lower extremity of the body was observed to be dominant compared to the upper and whole body in perceived response. First mode of principal component analysis (PCA) was obtained through the covariance matrix for the eight muscles for 25 subjects for NMPF of eight muscles. The diagonal entries in the covariance matrix were observed for each muscle. The muscle with the highest absolute magnitude was observed across all the 25 subjects. The medial deltoid and the rectus femoris muscles were observed to have the highest frequency for each PCA across 25 subjects. The rectus femoris, having the highest counts in all subjects, validated that the lower extremity dominates the sense of whole body fatigue during squat lifting. The findings revealed that it is significant to take into account the relation between perceived and measured effort that can help prevent musculoskeletal disorders in repetitive occupational tasks.

  3. Mesenchymal stromal cell secreted sphingosine 1-phosphate (S1P exerts a stimulatory effect on skeletal myoblast proliferation.

    Directory of Open Access Journals (Sweden)

    Chiara Sassoli

    Full Text Available Bone-marrow-derived mesenchymal stromal cells (MSCs have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P, a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK, blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration.

  4. Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

    Science.gov (United States)

    Tani, Alessia; Anderloni, Giulia; Pierucci, Federica; Matteini, Francesca; Chellini, Flaminia; Zecchi Orlandini, Sandra; Meacci, Elisabetta

    2014-01-01

    Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P), a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK), blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF) involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration. PMID:25264785

  5. Analysis of radiation pressure force exerted on a biological cell induced by high-order Bessel beams using Debye series

    International Nuclear Information System (INIS)

    Li, Renxian; Ren, Kuan Fang; Han, Xiang'e; Wu, Zhensen; Guo, Lixin; Gong, Shuxi

    2013-01-01

    Debye series expansion (DSE) is employed to the analysis of radiation pressure force (RPF) exerted on biological cells induced by high-order Bessel beams (BB). The beam shape coefficients (BSCs) for high-order Bessel beams are calculated using analytical expressions obtained by the integral localized approximation (ILA). Different types of cells, including a real Chinese Hamster Ovary (CHO) cell and a lymphocyte which are respectively modeled by a coated and five-layered sphere, are considered. The RPF induced by high-order Bessel beams is compared with that by Gaussian beams and zeroth-order Bessel beams, and the effect of different scattering processes on RPF is studied. Numerical calculations show that high-order Bessel beams with zero central intensity can also transversely trap particle in the beam center, and some scattering processes can provide longitudinal pulling force. -- Highlights: ► BSCs for high-order Bessel beam (HOBB) is derived using ILA. ► DSE is employed to study the RPF induced by HOBB exerted on multilayered cells. ► RPF is decided by radius relative to the interval of peaks in intensity profile. ► HOBB can also transversely trap high-index particle in the vicinity of beam axis. ► RPF for some scattering processes can longitudinally pull particles back

  6. The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines.

    Science.gov (United States)

    Sandra, Niro; Ester, Pereira; Marie-Agnès, Pélissier; Robert, Morfin; Olivier, Hennebert

    2012-04-01

    7β-Hydroxy-epiandrosterone (7β-OH-EpiA), an endogenous androgenic derivative of dehydroepiandrosterone, has previously been shown to exert anti-inflammatory action in vitro and in vivo via a shift from prostaglandin E2 (PGE2) to 15-deoxy-Δ(12,14)-PGJ2 production. This modulation in prostaglandin production was obtained with low concentrations of 7β-OH-EpiA (1-100nM) and suggested that it might act through a specific receptor. Inflammation and prostaglandin synthesis is important in the development and survival of estrogen-dependent mammary cancers. Estrogen induced PGE2 production and cell proliferation via its binding to estrogen receptors (ERs) in these tumors. Our objective was to test the effects of 7β-OH-EpiA on the proliferation (by counting with trypan blue exclusion), cell cycle and cell apoptosis (by flow cytometry) of breast cancer cell lines MCF-7 (ERα+, ERβ+, G-protein coupled receptor 30: GPR30+) and MDA-MB-231 (ERα-, ERβ+, GPR30+) and to identify a potential target of this steroid in these cell lineages (by transactivations) and in the nuclear ER-negative SKBr3 cells (GPR30+) (by proliferation assays). 7β-OH-EpiA exerted anti-estrogenic effects in MCF-7 and MDA-MB-231 cells associated with cell proliferation inhibition and cell cycle arrest. Moreover, transactivation and proliferation with ER agonists assays indicated that 7β-OH-EpiA interacted with ERβ. Data from proliferation assays on the MCF-7, MDA-MB-231 and SKBr3 cell lines suggested that 7β-OH-EpiA may also act through the membrane GPR30 receptor. These results support that this androgenic steroid acts as an anti-estrogenic compound. Moreover, this is the first evidence that low doses of androgenic steroid exert antiproliferative effects in these mammary cancer cells. Further investigations are needed to improve understanding of the observed actions of endogenous 7β-OH-EpiA. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Acute caffeine ingestion enhances strength performance and reduces perceived exertion and muscle pain perception during resistance exercise.

    Science.gov (United States)

    Duncan, Michael J; Stanley, Michelle; Parkhouse, Natalie; Cook, Kathryn; Smith, Mike

    2013-01-01

    The efficacy of caffeine ingestion in enhancing aerobic performance is well established. However, despite suggestions that caffeine may enhance resistance exercise performance, research is equivocal on the effect of acute caffeine ingestion on resistance exercise performance. It has also been suggested that dampened perception of perceived exertion and pain perception might be an explanation for any possible enhancement of resistance exercise performance due to caffeine ingestion. Therefore, the aim of this study was to examine the acute effect of caffeine ingestion on repetitions to failure, rating of perceived exertion (RPE) and muscle pain perception during resistance exercise to failure. Eleven resistance trained individuals (9 males, 2 females, mean age±SD=26.4±6.4 years), took part in this double-blind, randomised cross-over experimental study whereby they ingested a caffeinated (5 mg kg(-1)) or placebo solution 60 minutes before completing a bout of resistance exercise. Experimental conditions were separated by at least 48 hours. Resistance exercise sessions consisted of bench press, deadlift, prone row and back squat exercise to failure at an intensity of 60% 1 repetition maximum. Results indicated that participants completed significantly greater repetitions to failure, irrespective of exercise, in the presence of caffeine (p=0.0001). Mean±S.D of repetitions to failure was 19.6±3.7 and 18.5±4.1 in caffeine and placebo conditions, respectively. There were no differences in peak heart rate or peak blood lactate values across conditions (both p >0.05). RPE was significantly lower in the caffeine compared to the placebo condition (p=0.03) and was significantly higher during lower body exercises compared to upper body exercises irrespective of substance ingested (p=0.0001). For muscle pain perception, a significant condition by exercise interaction (p=0.027) revealed that muscle pain perception was lower in the caffeine condition, irrespective of exercise

  8. Blood lactate, heart rate and rating of perceived exertion responses of elite surf lifesavers to high-performance competition.

    Science.gov (United States)

    Sinclair, Wade H; Kerr, Rebecca M; Spinks, Warwick L; Leicht, Anthony S

    2009-01-01

    A paucity of empirical research exists into surf lifesaving competition from which coaches and athletes may formulate training and recovery strategies. Seventeen (male=9; female=8) high-performance surf lifesavers (21.2+/-3.9 years) contested multiple rounds of team and individual events at a 2-day surf lifesaving competition. Individual events consisted of the multi-discipline ironman (IRON), paddle board (BOARD) and surf swim (SWIM). Blood lactate (BLa), rating of perceived exertion (RPE) and heart rate (HR) were determined following heats, semi-finals and final. IRON HR and RPE following semi-finals (153.0+/-21.6beatsmin(-1) and 14.4+/-1.5) and final (171.0+/-9.1beatsmin(-1) and 19.1+/-0.2) were greater than heats (141.8+/-17.2beatsmin(-1) and 12.0+/-1.9; psurf lifesavers employ race strategies with all-out maximal exercise limited to semi-finals and finals.

  9. Quantifying session ratings of perceived exertion for field-based speed training methods in team sport athletes.

    Science.gov (United States)

    Lockie, Robert G; Murphy, Aron J; Scott, Brendan R; Janse de Jonge, Xanne A K

    2012-10-01

    Session ratings of perceived exertion (session RPE) are commonly used to assess global training intensity for team sports. However, there is little research quantifying the intensity of field-based training protocols for speed development. The study's aim was to determine the session RPE of popular training protocols (free sprint [FST], resisted sprint [RST], and plyometrics [PT]) designed to improve sprint acceleration over 10 m in team sport athletes. Twenty-seven men (age = 23.3 ± 4.7 years; mass = 84.5 ± 8.9 kg; height = 1.83 ± 0.07 m) were divided into 3 groups according to 10-m velocity. Training consisted of an incremental program featuring two 1-hour sessions per week for 6 weeks. Subjects recorded session RPE 30 minutes post training using the Borg category-ratio 10 scale. Repeated measures analysis of variance found significant (p sports conditioning program.

  10. Effects of ladder parameters on asymmetric patterns of force exertion during below-knee amputees climbing ladders.

    Science.gov (United States)

    Li, Weidong; Li, Shiqi; Fu, Yan; Chen, Jacon

    2017-03-01

    Different from walking, ladder climbing requires four-limb coordination and more energy exertion for below-knee amputees (BKAs). We hypothesized that functional deficiency of a disabled limb shall be compensated by the other three intact limbs, showing an asymmetry pattern among limbs. Hand and foot forces of six below-knee amputees and six able-bodied people were collected. Hand, foot and hand/foot sum force variances between groups (non-BKA, intact side and prosthetic side) were carefully examined. Our hypothesis was validated that there is asymmetry between prosthetic and intact side. Results further showed that the ipsilateral hand of the prosthetic leg is stronger than the hand on the intact side, compensating weakness of the prosthetic leg. Effects of ladder rung separations and ladder slant on asymmetric force distribution of BKAs were evaluated, indicating that rung separation has a more significant interactive effect on hand/foot force of BKAs than ladder slant.

  11. Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?

    International Nuclear Information System (INIS)

    Tjomsland, Vegard; Larsson, Marie; Sandström, Per; Spångeus, Anna; Messmer, Davorka; Emilsson, Johan; Falkmer, Ursula; Falkmer, Sture; Magnusson, Karl-Eric; Borch, Kurt

    2010-01-01

    Dendritic cells (DCs) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system. Ductal pancreatic adenocarcinoma (PDAC), the most common pancreatic cancer, is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence. We examined the systemic influence ductal pancreatic adenocarcinoma (PDAC) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors, chronic pancreatitis, and age-matched controls. All groups examined, including PDAC, had decreased levels of myeloid DCs (MDC) and plasmacytoid DCs (PDC) and enhanced apoptosis in these cells as compared to controls. We found elevated levels of PGE2 and CXCL8 in subjects with PDAC, and chronic pancreatitis. Levels of these inflammatory factors were in part restored in PDAC after tumor resection, whereas the levels of DCs were impaired in the majority of these patients ~12 weeks after tumor removal. Our results prove that solid pancreatic tumors, including PDAC, systemically affect blood DCs. The impairments do not seem to be tumor-specific, since similar results were obtained in subjects with chronic pancreatitis. Furthermore, we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival. Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs. Furthermore, the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and survival

  12. Sodium Butyrate Upregulates miR-203 Expression to Exert Anti-Proliferation Effect on Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruirui Han

    2016-10-01

    Full Text Available Background: As the end product of the bacterial fermentation of dietary fiber in the colonic lumen, sodium butyrate (NaBt has been reported to exert antitumor effects on colorectal cancer (CRC. In addition to functioning as a histone deacetylase (HDAC inhibitor, NaBt also regulates the expression of microRNAs (miRNAs to inhibit CRC cell proliferation. Yet, the mechanisms involved are not completely understood. Here we investigate whether NaBt regulates miR-203 to inhibit CRC growth and explore the promising target gene of miR-203 in CRC cells. Methods: We conducted qRT-PCR and Western blotting assays to evaluate the effects of NaBt on the expression of miR-203 and NEDD9 in HT-29 and Caco-2 cell lines. The promising target gene of miR-203 was predicted by miRNA target prediction and dual luciferase reporter assay. CRC Cell proliferation, colony formation, cell apoptosis and cell invasion assays were performed to explore the effect of NaBt, miR-203 and NEDD9 on HT-29 and Caco-2 cell lines. Results: The results showed that NaBt increased the expression of miR-203 to induce CRC cell apoptosis as well as inhibit cell proliferation, colony formation and cell invasion. Moreover, we determined that the NEDD9 was a target gene of miR-203. NEDD9 partially overcame the inhibitory effects of miR-203 on CRC cell colony formation and invasion. Conclusions: NaBt could induce CRC cell apoptosis, inhibit CRC cell proliferation, colony formation and invasion through miR-203/NEDD9 cascade. The present study may enrich the mechanisms underlying the process that NaBt exerts anti-tumor effects on CRC cells.

  13. Exertional muscle pain in familial Mediterranean fever patients evaluated by MRI and 31P magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Kushnir, T.; Eshed, I.; Heled, Y.; Livneh, A.; Langevitz, P.; Ben Zvi, I.; Konen, E.; Lidar, M.

    2013-01-01

    Aim: To evaluate the effect of physical activity on the structural, morphological, and metabolic characteristics of the gastrocnemius muscle in familial Mediterranean fever (FMF) patients, utilizing quantitative 31 P magnetic resonance spectroscopy (MRS), in order to elucidate the mechanism of their exertional leg pain. Materials and methods: Eleven FMF patients suffering from exertional leg pain (eight male, three female; mean age 33 years) and six healthy individuals (three male, three female; mean age 39 years) constituted the control group. All of the participants underwent magnetic resonance imaging (MRI) and non-selective 31 P MRS (3 T) of the leg muscles before and after graded exercise on a treadmill. Phosphocreatine (PCr):inorganic phosphate (Pi), PCr:adenosine triphosphate (ATP) ratios and the intracellular pH of the leg muscles were measured using 31 P MRS. Results: For both groups, normal muscle mass with no signal alterations was observed on the MRI images after exercise. The normal range of pre- and post- exercise MRS muscle parameters was observed in both groups. However, the intracellular pH post-exercise, was significantly higher (less acidic) in the FMF group compared to the control group [pH (FMF) = 7.03 ± 0.02; pH (control) 7.00 ± 0.02; p < 0.0006]. Conclusions: The finding of a less prominent, post-exercise acidification of the gastrocnemius muscle in this FMF patient group suggests a forme fruste of glycogenosis. This preliminary observation should be further investigated in a future, larger-scale study

  14. Extracts from Lentinula edodes (Shiitake) Edible Mushrooms Enriched with Vitamin D Exert an Anti-Inflammatory Hepatoprotective Effect.

    Science.gov (United States)

    Drori, Ariel; Shabat, Yehudit; Ben Ya'acov, Ami; Danay, Ofer; Levanon, Dan; Zolotarov, Lidya; Ilan, Yaron

    2016-04-01

    Vitamin D has been known for its anti-inflammatory properties. Extracts derived from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory effect. These extracts contain high levels of ergosterol, which converts into ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D]. To determine the anti-inflammatory effect of overexpression of vitamin D in edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze-dried, followed by measurement of vitamin D2 contents, in their dry weight. C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom extract prior and during concanavalin A-immune-mediated liver injury. Exposure to ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms. Following feeding of vitamin D-enriched mushroom extracts to mice with immune-mediated hepatitis, a significant decrease in liver damage was noted. This was shown by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels, a decrease in proportion of mice with severe liver injury, and by improvement in liver histology. These effects were associated with a decrease in serum interferon gamma levels. A synergistic effect was noted between the anti-inflammatory effect of the mushroom extracts and that of vitamin D. Oral administration of vitamin D-enriched L. edodes edible mushroom exerts a synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data support its potential use as safe immunomodulatory adjuvant for the treatment of HCV and nonalcoholic steatohepatitis.

  15. Antagonistic activity exerted in vitro and in vivo by Lactobacillus casei (strain GG) against Salmonella typhimurium C5 infection.

    Science.gov (United States)

    Hudault, S; Liévin, V; Bernet-Camard, M F; Servin, A L

    1997-02-01

    The aim of this study was to compare the antagonistic properties of Lactobacillus casei GG exerted in vitro against Salmonella typhimurium C5 in a cellular model, cultured enterocyte-like Caco-2 cells, to those exerted in vivo in an animal model, C3H/He/Oujco mice. Our results show that a 1-h contact between the invading strain C5 and either the culture or the supernatant of L. casei GG impeded the invasion by the Salmonella strain in Caco-2 cells, without modifying the viability of the strain. After neutralization at pH 7, no inhibition of the invasion by C5 was observed. The antagonistic activity of L. casei GG was examined in C3H/He/Oujco mice orally infected with C5 as follows: (i) L. casei GG was given daily to conventional animals as a probiotic, and (ii) it was given once to germ-free animals in order to study the effect of the population of L. casei GG established in the different segments of the gut. In vivo experiments show that after a single challenge with C5, this strain survives and persists at a higher level in the feces of the untreated conventional mice than in those of the treated group. In L. casei GG germ-free mice, establishment of L. casei GG in the gut significantly delayed the occurrence of 100% mortality of the animals (15 days after C5 challenge versus 9 days in germ-free mice [P L. casei GG population level in the gut dramatically decreased in these animals.

  16. The Influence of Playing Position and Contextual Factors on Soccer Players’ Match Differential Ratings of Perceived Exertion: A Preliminary Investigation

    Directory of Open Access Journals (Sweden)

    Steve Barrett

    2018-02-01

    Full Text Available (1 Background: Differential RPE (dRPE separates scores for breathlessness (RPE-B, leg muscle exertion (RPE-L and technical/cognitive exertion (RPE-T. Limited information for dRPE is available in soccer match play, yet these measurements may help inform practitioners training and recovery strategies. This preliminary study investigated the effects of playing position and contextual factors on elite soccer players’ dRPE. (2 Methods: Thirty-two male English Premier League players recorded dRPE scores 15–30 min post-match for RPE-B, RPE-L, and RPE-T. Data were analysed using linear mixed models, with magnitude-based inferences subsequently applied. (3 Results: Overall, the mean ± SD for the dRPE were 63 ± 23 arbitrary units (au (RPE-B, 67 ± 22 au (RPE-L, and 60 ± 24 au (RPE-T. Full Backs reported substantially higher RPE-B, RPE-L and RPE-T when compared to all other positions. Substantially higher RPE-T scores were reported for matches played against Top teams compared to Bottom (10 au; 90% Confidence Interval 5 to 15 au and Middle (10 au; 4 to 15 au ranked teams. The effects of match result and location on dRPE were not substantial. (4 Conclusions: Positional differences were observed following soccer match play for RPE-B, RPE-L and RPE-T. Full backs had substantially higher dRPE then any other position, with all players reporting increased RPE-T when playing teams at the Top of the league. These findings can he