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  1. The AMP-activated protein kinase is involved in the regulation of ketone body production by astrocytes.

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    Blázquez, C; Woods, A; de Ceballos, M L; Carling, D; Guzmán, M

    1999-10-01

    The possible role of the AMP-activated protein kinase (AMPK), a highly conserved stress-activated kinase, in the regulation of ketone body production by astrocytes was studied. AMPK activity in rat cortical astrocytes was three times higher than in rat cortical neurons. AMPK in astrocytes was shown to be functionally active. Thus, incubation of astrocytes with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMPK, stimulated both ketogenesis from palmitate and carnitine palmitoyltransferase I. This was concomitant to a decrease of intracellular malonyl-CoA levels and an inhibition of acetyl-CoA carboxylase/fatty acid synthesis and 3-hydroxy-3-methylglutaryl-CoA reductase/cholesterol synthesis. Moreover, in microdialysis experiments AICAR was shown to stimulate brain ketogenesis markedly. The effect of chemical hypoxia on AMPK and the ketogenic pathway was studied subsequently. Incubation of astrocytes with azide led to a remarkable drop of fatty acid beta-oxidation. However, activation of AMPK during hypoxia compensated the depression of beta-oxidation, thereby sustaining ketone body production. This effect seemed to rely on the cascade hypoxia --> increase of the AMP/ATP ratio --> AMPK stimulation --> acetyl-CoA carboxylase inhibition --> decrease of malonyl-CoA concentration --> carnitine palmitoyltransferase I deinhibition --> enhanced ketogenesis. Furthermore, incubation of neurons with azide blunted lactate oxidation, but not 3-hydroxybutyrate oxidation. Results show that (a) AMPK plays an active role in the regulation of ketone body production by astrocytes, and (b) ketone bodies produced by astrocytes during hypoxia might be a substrate for neuronal oxidative metabolism.

  2. The 5'-AMP-Activated Protein Kinase (AMPK Is Involved in the Augmentation of Antioxidant Defenses in Cryopreserved Chicken Sperm.

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    Thi Mong Diep Nguyen

    Full Text Available Semen cryopreservation is a unique tool for the management of animal genetic diversity. However, the freeze-thaw process causes biochemical and physical alterations which make difficult the restoration of sperm energy-dependent functions needed for fertilization. 5'-AMP activated protein kinase (AMPK is a key sensor and regulator of intracellular energy metabolism. Mitochondria functions are known to be severely affected during sperm cryopreservation with deleterious oxidative and peroxidative effects leading to cell integrity and functions damages. The aim of this study was thus to examine the role of AMPK on the peroxidation/antioxidant enzymes defense system in frozen-thawed sperm and its consequences on sperm functions. Chicken semen was diluted in media supplemented with or without AMPK activators (AICAR or Metformin [MET] or inhibitor (Compound C [CC] and then cryopreserved. AMPKα phosphorylation, antioxidant enzymes activities, mitochondrial potential, ATP, citrate, viability, acrosome reaction ability (AR and various motility parameters were negatively affected by the freeze-thaw process while reactive oxygen species (ROS production, lipid peroxidation (LPO and lactate concentration were dramatically increased. AICAR partially restored superoxide dismutase (SOD, Glutathione Peroxidase (GPx and Glutathione Reductase (GR, increased ATP, citrate, and lactate concentration and subsequently decreased the ROS and LPO (malondialdehyde in frozen-thawed semen. Motility parameters were increased (i.e., + 23% for motility, + 34% for rapid sperm as well as AR (+ 100%. MET had similar effects as AICAR except that catalase activity was restored and that ATP and mitochondrial potential were further decreased. CC showed effects opposite to AICAR on SOD, ROS, LPO and AR and motility parameters. Taken together, our results strongly suggest that, upon freeze-thaw process, AMPK stimulated intracellular anti-oxidative defense enzymes through ATP regulation

  3. Glucosensing by GnRH Neurons: Inhibition by Androgens and Involvement of AMP-Activated Protein Kinase

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    Roland, Alison V.

    2011-01-01

    GnRH neurons integrate steroidal and metabolic cues to regulate fertility centrally. Central glucoprivation reduces LH secretion, which is governed by GnRH release, suggesting GnRH neuron activity is modulated by glucose availability. Here we tested whether GnRH neurons can sense changes in extracellular glucose, and whether glucosensing is altered by the steroids dihydrotestosterone (DHT) and/or estradiol (E). Extracellular recordings were made from GnRH neurons in brain slices from ovariectomized (OVX) mice ± DHT and/or E implants. Firing rate was reduced by a switch from 4.5 to 0.2 mm glucose in cells from OVX, OVX+E, and OVX+DHT+E mice, but not OVX+DHT mice. This suggests that androgens reduce the sensitivity of GnRH neurons to changes in extracellular glucose, but E mitigates this effect. Next we investigated potential mechanisms. In the presence of the ATP-sensitive potassium channel antagonist tolbutamide, glucosensing persisted. In contrast, glucosensing was attenuated in the presence of compound C, an antagonist of AMP-activated protein kinase (AMPK), suggesting a role for AMPK in glucosensing. The AMPK activator N1-(b-d-ribofuranosyl)-5-aminoimidazole-4-carboxamide (AICAR) mimicked the effect of low glucose and was less effective in cells from DHT-treated mice. The effect of DHT to diminish responses to low glucose and AICAR was abolished by blockade of fast synaptic transmission. Both AICAR and low glucose activated a current with a reversal potential near −50 mV, suggesting a nonspecific cation current. These studies indicate that glucosensing is one mechanism by which GnRH neurons sense fuel availability and point to a novel role for AMPK in the central regulation of fertility. PMID:21393446

  4. AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks.

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    Chun, Min Jeong; Kim, Sunshin; Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

    2016-08-16

    Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway.

  5. In Vitro Anti-Echinococcal and Metabolic Effects of Metformin Involve Activation of AMP-Activated Protein Kinase in Larval Stages of Echinococcus granulosus

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    Loos, Julia A.; Cumino, Andrea C.

    2015-01-01

    Metformin (Met) is a biguanide anti-hyperglycemic agent, which also exerts antiproliferative effects on cancer cells. This drug inhibits the complex I of the mitochondrial electron transport chain inducing a fall in the cell energy charge and leading 5'-AMP-activated protein kinase (AMPK) activation. AMPK is a highly conserved heterotrimeric complex that coordinates metabolic and growth pathways in order to maintain energy homeostasis and cell survival, mainly under nutritional stress conditions, in a Liver Kinase B1 (LKB1)-dependent manner. This work describes for the first time, the in vitro anti-echinococcal effect of Met on Echinococcus granulosus larval stages, as well as the molecular characterization of AMPK (Eg-AMPK) in this parasite of clinical importance. The drug exerted a dose-dependent effect on the viability of both larval stages. Based on this, we proceeded with the identification of the genes encoding for the different subunits of Eg-AMPK. We cloned one gene coding for the catalytic subunit (Eg-ampkɑ) and two genes coding for the regulatory subunits (Eg-ampkβ and Eg-ampkγ), all of them constitutively transcribed in E. granulosus protoscoleces and metacestodes. Their deduced amino acid sequences show all the conserved functional domains, including key amino acids involved in catalytic activity and protein-protein interactions. In protoscoleces, the drug induced the activation of AMPK (Eg-AMPKɑ-P176), possibly as a consequence of cellular energy charge depletion evidenced by assays with the fluorescent indicator JC-1. Met also led to carbohydrate starvation, it increased glucogenolysis and homolactic fermentation, and decreased transcription of intermediary metabolism genes. By in toto immunolocalization assays, we detected Eg-AMPKɑ-P176 expression, both in the nucleus and the cytoplasm of cells as in the larval tegument, the posterior bladder and the calcareous corpuscles of control and Met-treated protoscoleces. Interestingly, expression of Eg

  6. AMP-activated protein kinase and type 2 diabetes.

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    Musi, Nicolas

    2006-01-01

    AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge, being activated in situations of high-energy phosphate depletion. Upon activation, AMPK functions to restore cellular ATP by modifying diverse metabolic pathways. AMPK is activated robustly by skeletal muscle contraction and myocardial ischemia, and may be involved in the stimulation of glucose transport and fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid oxidation and in decreased production of glucose, cholesterol, and triglycerides. Recent studies have shown that AMPK is the cellular mediator for many of the metabolic effects of drugs such as metformin and thiazolidinediones, as well as the insulin sensitizing adipocytokines leptin and adiponectin. These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.

  7. Road accidents involving bicycles: configurations and injuries.

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    Orsi, Chiara; Montomoli, Cristina; Otte, Dietmar; Morandi, Anna

    2017-12-01

    This study analyzed the most common types of accident involving bicycles and compared the frequency of injuries. The data source was the database of German In-Depth Accident Study (GIDAS). Cases consist of bicycles and their riders involved in accidents between 2000 and 2010. In most collisions, the bicycle impacted with a car. The percentage of injured bicyclists was higher in collisions with a heavy vehicle and decreased when the bicycle impacted with lighter vehicles. A high percentage of injured bicyclists in single accidents was observed; the most severe injury was more frequently to head and extremities. Accidents involving a car and a bicycle with the right of way in a bicycle path represented about 20% of involved and injured bicyclists. The ten most frequent configurations represented about 60% of involved and injured bicyclists. These results contribute to understand the dangerous scenarios for bicyclists and to suggest preventive actions.

  8. AMP-activated kinase mediates adipose stem cell-stimulated neuritogenesis of PC12 cells.

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    Tan, B; Luan, Z; Wei, X; He, Y; Wei, G; Johnstone, B H; Farlow, M; Du, Y

    2011-05-05

    Adipose tissue stroma contains a population of mesenchymal stem cells, which support repair of damaged tissues through the protective effects of secreted trophic factors. Neurotrophic factors, including nerve growth factor (NGF) have been identified in media collected from cultured adipose-derived stem cells (ASC). We previously demonstrated that administration of cell-free ASC conditioned medium (ASC-CM) at 24 h after injury reduced lesion volume and promoted functional recovery in a rat model of neonatal brain hypoxic-ischemic (HI) injury. The timing of administration well after the peak in neural cell apoptosis in the affected region suggests that regeneration of lost neurons is promoted by factors in ASC-CM. In this study, we determined which of the factors in ASC-CM could induce neurogenesis by testing the ability of the mixture, either whole or after inactivating specific components, to stimulate neurite outgrowth in vitro using the neurogenic cell line PC12. Neuritogenesis in PC12 cells treated with ASC-CM was observed at a level comparable to that observed with purified recombinant NGF. It was observed that NGF in ASC-CM was mainly responsible for inducing PC12 cell neuritogenesis. Interestingly, both ASC-CM and NGF induced PC12 cell neuritogenesis through activation of the AMP-activated kinase (AMPK) pathway which is the central protein involved in controlling many critical functions in response to changes in the cellular energy status. Pharmacological and genetic inhibition of AMPK activity greatly reduced neuritogenesis in PC12 cells. These results suggest that, in addition to possessing neuroprotective properties, ASC-CM mediates repair of damaged tissues through inducing neuronal differentiation via NGF-induced AMPK activation. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema.

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    Cheng, Xiao-Yu; Li, Yang-Yang; Huang, Cheng; Li, Jun; Yao, Hong-Wei

    2017-04-04

    Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM). Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C. AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence. Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells. Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice. This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement. Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs. In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema.

  10. Inhibition of cAMP-activated intestinal chloride secretion by diclofenac: cellular mechanism and potential application in cholera.

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    Pongkorpsakol, Pawin; Pathomthongtaweechai, Nutthapoom; Srimanote, Potjanee; Soodvilai, Sunhapas; Chatsudthipong, Varanuj; Muanprasat, Chatchai

    2014-09-01

    Cyclic AMP-activated intestinal Cl- secretion plays an important role in pathogenesis of cholera. This study aimed to investigate the effect of diclofenac on cAMP-activated Cl- secretion, its underlying mechanisms, and possible application in the treatment of cholera. Diclofenac inhibited cAMP-activated Cl- secretion in human intestinal epithelial (T84) cells with IC50 of ∼ 20 µM. The effect required no cytochrome P450 enzyme-mediated metabolic activation. Interestingly, exposures of T84 cell monolayers to diclofenac, either in apical or basolateral solutions, produced similar degree of inhibitions. Analyses of the apical Cl- current showed that diclofenac reversibly inhibited CFTR Cl- channel activity (IC50 ∼ 10 µM) via mechanisms not involving either changes in intracellular cAMP levels or CFTR channel inactivation by AMP-activated protein kinase and protein phosphatase. Of interest, diclofenac had no effect on Na(+)-K(+) ATPases and Na(+)-K(+)-Cl- cotransporters, but inhibited cAMP-activated basolateral K(+) channels with IC50 of ∼ 3 µM. In addition, diclofenac suppressed Ca(2+)-activated Cl- channels, inwardly rectifying Cl- channels, and Ca(2+)-activated basolateral K(+) channels. Furthermore, diclofenac (up to 200 µM; 24 h of treatment) had no effect on cell viability and barrier function in T84 cells. Importantly, cholera toxin (CT)-induced Cl- secretion across T84 cell monolayers was effectively suppressed by diclofenac. Intraperitoneal administration of diclofenac (30 mg/kg) reduced both CT and Vibrio cholerae-induced intestinal fluid secretion by ∼ 70% without affecting intestinal fluid absorption in mice. Collectively, our results indicate that diclofenac inhibits both cAMP-activated and Ca(2+)-activated Cl- secretion by inhibiting both apical Cl- channels and basolateral K+ channels in intestinal epithelial cells. Diclofenac may be useful in the treatment of cholera and other types of secretory diarrheas resulting from intestinal

  11. Inhibition of cAMP-activated intestinal chloride secretion by diclofenac: cellular mechanism and potential application in cholera.

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    Pawin Pongkorpsakol

    2014-09-01

    Full Text Available Cyclic AMP-activated intestinal Cl- secretion plays an important role in pathogenesis of cholera. This study aimed to investigate the effect of diclofenac on cAMP-activated Cl- secretion, its underlying mechanisms, and possible application in the treatment of cholera. Diclofenac inhibited cAMP-activated Cl- secretion in human intestinal epithelial (T84 cells with IC50 of ∼ 20 µM. The effect required no cytochrome P450 enzyme-mediated metabolic activation. Interestingly, exposures of T84 cell monolayers to diclofenac, either in apical or basolateral solutions, produced similar degree of inhibitions. Analyses of the apical Cl- current showed that diclofenac reversibly inhibited CFTR Cl- channel activity (IC50 ∼ 10 µM via mechanisms not involving either changes in intracellular cAMP levels or CFTR channel inactivation by AMP-activated protein kinase and protein phosphatase. Of interest, diclofenac had no effect on Na(+-K(+ ATPases and Na(+-K(+-Cl- cotransporters, but inhibited cAMP-activated basolateral K(+ channels with IC50 of ∼ 3 µM. In addition, diclofenac suppressed Ca(2+-activated Cl- channels, inwardly rectifying Cl- channels, and Ca(2+-activated basolateral K(+ channels. Furthermore, diclofenac (up to 200 µM; 24 h of treatment had no effect on cell viability and barrier function in T84 cells. Importantly, cholera toxin (CT-induced Cl- secretion across T84 cell monolayers was effectively suppressed by diclofenac. Intraperitoneal administration of diclofenac (30 mg/kg reduced both CT and Vibrio cholerae-induced intestinal fluid secretion by ∼ 70% without affecting intestinal fluid absorption in mice. Collectively, our results indicate that diclofenac inhibits both cAMP-activated and Ca(2+-activated Cl- secretion by inhibiting both apical Cl- channels and basolateral K+ channels in intestinal epithelial cells. Diclofenac may be useful in the treatment of cholera and other types of secretory diarrheas resulting from intestinal

  12. Dissecting the role of AMP-activated protein kinase in human diseases

    Institute of Scientific and Technical Information of China (English)

    Jin Li; Liping Zhong; Fengzhong Wang; Haibo Zhu

    2017-01-01

    AMP-activated protein kinase (AMPK),known as a sensor and a master of cellular energy balance,integrates various regulatory signals including anabolic and catabolic metabolic processes.Accompanying the application of genetic methods and a plethora of AMPK agonists,rapid progress has identified AMPK as an attractive therapeutic target for several human diseases,such as cancer,type 2 diabetes,atherosclerosis,myocardial ischemia/reperfusion injury and neurodegenerative disease.The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere.In the present review,we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered.Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.

  13. Regulation of autophagy by AMP-activated protein kinase/ sirtuin 1 pathway reduces spinal cord neurons damage

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    Peng Yan

    2017-09-01

    Full Text Available Objective(s: AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1 signaling pathway has been proved to be involved in the regulation of autophagy in various models. The aim of this study was to evaluate the effect of AMPK/SIRT1 pathway on autophagy after spinal cord injury (SCI. Materials and Methods:The SCI model was established in rats in vivo and the primary spinal cord neurons were subjected to mechanical injury (MI in vitro. The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst 33342 staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation of AMPK/SIRT1 pathway was determined by Western blot and immunohistochemical staining. Results: We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC3II/LC3I and level of p62 were first increased significantly and then decreased after the trauma in vivo and in vitro, indicating the defect in autophagy. The levels of p-AMPK and SIRT1 were increased obviously after the trauma in vivo and in vitro. Further activation of the AMPK/SIRT1 pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT1 pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p62 in spinal cord neurons at 24 hr after MI. Conclusion: Our results demonstrate that regulation of autophagy by AMPK/SIRT1 pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.

  14. Regulation of autophagy by AMP-activated protein kinase/sirtuin 1 pathway reduces spinal cord neurons damage.

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    Yan, Peng; Bai, Liangjie; Lu, Wei; Gao, Yuzhong; Bi, Yunlong; Lv, Gang

    2017-09-01

    AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1) signaling pathway has been proved to be involved in the regulation of autophagy in various models. The aim of this study was to evaluate the effect of AMPK/SIRT1 pathway on autophagy after spinal cord injury (SCI). The SCI model was established in rats in vivo and the primary spinal cord neurons were subjected to mechanical injury (MI) in vitro . The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst 33342 staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation of AMPK/SIRT1 pathway was determined by Western blot and immunohistochemical staining. We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC3II/LC3I and level of p62 were first increased significantly and then decreased after the trauma in vivo and in vitro , indicating the defect in autophagy. The levels of p-AMPK and SIRT1 were increased obviously after the trauma in vivo and in vitro . Further activation of the AMPK/SIRT1 pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT1 pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p62 in spinal cord neurons at 24 hr after MI. Our results demonstrate that regulation of autophagy by AMPK/SIRT1 pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.

  15. Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury.

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    Dai, Jie; Liu, Mingwei; Ai, Qing; Lin, Ling; Wu, Kunwei; Deng, Xinyu; Jing, Yuping; Jia, Mengying; Wan, Jingyuan; Zhang, Li

    2014-06-05

    Metformin is a commonly used anti-diabetic drug with AMP-activated protein kinase (AMPK)-dependent hypoglycemic activities. Recent studies have revealed its anti-inflammatory and anti-oxidative properties. In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl₂)-induced severe oxidative liver injury. Our results showed that treatment with metformin significantly attenuated CCl₂-induced elevation of serum aminotransferases and hepatic histological abnormalities. The alleviated liver injury was associated with decreased hepatic contents of oxidized glutathione (GSSG) and malondialdehyde (MDA). In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl₄-induced elevation of hepatic H₂O₂ levels, but it had no obvious effects on the protein level of CAT. We also found that metformin increased the level of phosphorylated AMP-activated protein kinase (AMPK), but treatment with AMPK activator AICAR had no obvious effects on CAT activity. A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds. These data suggested that metformin effectively alleviated CCl₄-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity

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    Andersson, Ulrika; Treebak, Jonas Thue; Nielsen, Jakob Nis

    2005-01-01

    . In recovery, glucose feeding increased plasma glucose and insulin concentrations whereas ghrelin and PYY decreased to (ghrelin) or below (PPY) resting levels. It is concluded that 1 h of strenuous exercise in rats does not elicit significant changes in hypothalamic AMPK activity despite an increase in plasma...... ghrelin. Thus, changes in energy metabolism during or after exercise are likely not coordinated by changes in hypothalamic AMPK activity.......Recent studies have demonstrated that AMP-activated protein kinase (AMPK) in the hypothalamus is involved in the regulation of food intake. Because exercise is known to influence appetite and cause substrate depletion, it may also influence AMPK in the hypothalamus. Male rats that either rested...

  17. Impact of 5'-amp-activated Protein Kinase on Male Gonad and Spermatozoa Functions.

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    Nguyen, Thi Mong Diep

    2017-01-01

    As we already know, the male reproductive system requires less energetic investment than the female one. Nevertheless, energy balance is an important feature for spermatozoa production in the testis and for spermatozoa properties after ejaculation. The 5'-AMP-activated protein kinase, AMPK, is a sensor of cell energy, that regulates many metabolic pathways and that has been recently shown to control spermatozoa quality and functions. It is indeed involved in the regulation of spermatozoa quality through its action on the proliferation of testicular somatic cells (Sertoli and Leydig), on spermatozoa motility and acrosome reaction. It also favors spermatozoa quality through the management of lipid peroxidation and antioxidant enzymes. I review here the most recent data available on the roles of AMPK in vertebrate spermatozoa functions.

  18. Redox regulation of the AMP-activated protein kinase.

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    Yingying Han

    2010-11-01

    Full Text Available Redox state is a critical determinant of cell function, and any major imbalances can cause severe damage or death.The aim of this study is to determine if AMP-activated protein kinase (AMPK, a cellular energy sensor, is activated by oxidants generated by Berberine in endothelial cells (EC.Bovine aortic endothelial cells (BAEC were exposed to Berberine. AMPK activity and reactive oxygen species were monitored after the incubation.In BAEC, Berberine caused a dose- and time-dependent increase in the phosphorylation of AMPK at Thr172 and acetyl CoA carboxylase (ACC at Ser79, a well characterized downstream target of AMPK. Concomitantly, Berberine increased peroxynitrite, a potent oxidant formed by simultaneous generation of superoxide and nitric oxide. Pre-incubation of BAEC with anti-oxidants markedly attenuated Berberine-enhanced phosphorylation of both AMPK and ACC. Consistently, adenoviral expression of superoxide dismutase and pretreatment of L-N(G-Nitroarginine methyl ester (L-NAME; a non-selective NOS inhibitor blunted Berberine-induced phosphorylation of AMPK. Furthermore, mitochondria-targeted tempol (mito-tempol pretreatment or expression of uncoupling protein attenuated AMPK activation caused by Berberine. Depletion of mitochondria abolished the effects of Berberine on AMPK in EC. Finally, Berberine significantly increased the phosphorylation of LKB1 at Ser307 and gene silencing of LKB1 attenuated Berberine-enhanced AMPK Thr172 phosphorylation in BAEC.Our results suggest that mitochondria-derived superoxide anions and peroxynitrite are required for Berberine-induced AMPK activation in endothelial cells.

  19. Electrical injury involving the immature skeleton

    International Nuclear Information System (INIS)

    Ogden, J.A.; Southwick, W. O.; Yale Univ., New Haven, CT; Yale Univ., New Haven, CT

    1981-01-01

    Two patients are presented with significant problems of skeletal development and function consequent to electrical impulse propagation through the immature skeleton. Amputation stump revision in the first case allowed an opportunity to assess specific histological and morphologic changes. Electrical damage completeley destroyed portions of trabecular bone in the metaphyses and epiphyseal ossification centers. There were morphologic irregularities in the physis of the distal femur, while in the proximal tibia complete cessation of growth occurred through presumed electrical ablation of the physis. There was virtually no endosteal or periosteal callus, no intertrabecular inflammatory response, and no new bone formation well over a year following the original injury. The knee joint exhibited severe fibrous ankylosis. In the second case localized arrest of the posterolateral portion of the proximal tibial physis caused a valgus/recurvatum deformation, and probably slowed down distal growth sufficiently in the stump end to prevent irregular terminal overgrowth of the tibia, although it did occur in the fibula. (orig.)

  20. Injury patterns among obese children involved in motor vehicle collisions.

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    Haricharan, Ramanath N; Griffin, Russell L; Barnhart, Douglas C; Harmon, Carroll M; McGwin, Gerald

    2009-06-01

    The purpose of this study was to compare injury patterns among obese children to their nonobese counterparts involved in motor vehicle collisions. A nationwide data collection program containing occupant, collision, and injury details from police-reported tow-away crashes between 1997 and 2006 were used. Risk ratios (RRs) and associated 95% confidence intervals (CIs) were adjusted for age, sex, restraint, seat track position, vehicle curb weight, and total velocity change. An estimated 9 million children aged 2 to 17 years (20.2% obese) were involved in motor vehicle collisions during the study period. Among 2-to-5-year-olds, obesity increased the risk of severe head (RR, 3.67; 95% CI, 1.03-13.08) and thoracic (2.27; 1.01-5.08) injuries. Among 6-to-9-year-olds, obesity increased risk of thoracic (2.31; 1.08-4.95) and lower extremity (LE) injuries (1.89; 1.03-3.47). Among 10-to-13-year-olds, obesity increased the risk of severe thoracic (1.98; 1.08-3.65) and LE (6.06; 2.23-16.44) injuries. Among 14-to-17-year-olds, obesity increased risk of severe LE injuries (1.44; 1.04-2.00) but decreased risk of abdominal (0.20; 0.07-0.60) and head (0.33; 0.18-0.60) injuries, very similar to the pattern reported in obese adults. The pattern of obesity-associated injuries changes from a higher risk of head and thoracic injuries among young children to a pattern in late teenagers that is similar to obese adults.

  1. AMP-activated protein kinase: Role in metabolism and therapeutic implications.

    Science.gov (United States)

    Schimmack, Greg; Defronzo, Ralph A; Musi, Nicolas

    2006-11-01

    AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge which becomes activated in situations of energy consumption. AMPK functions to restore cellular ATP levels by modifying diverse metabolic and cellular pathways. In the skeletal muscle, AMPK is activated during exercise and is involved in contraction-stimulated glucose transport and fatty acid oxidation. In the heart, AMPK activity increases during ischaemia and functions to sustain ATP, cardiac function and myocardial viability. In the liver, AMPK inhibits the production of glucose, cholesterol and triglycerides and stimulates fatty acid oxidation. Recent studies have shown that AMPK is involved in the mechanism of action of metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin. These data, along with evidence that pharmacological activation of AMPK in vivo improves blood glucose homeostasis, cholesterol concentrations and blood pressure in insulin-resistant rodents, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes, ischaemic heart disease and other metabolic diseases.

  2. AMP-activated protein kinase phosphorylates CtBP1 and down-regulates its activity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Hwan; Choi, Soo-Youn; Kang, Byung-Hee; Lee, Soon-Min [National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Park, Hyung Soon; Kang, Gum-Yong; Bang, Joo Young [Center for Biomedical Mass Spectrometry, Diatech Korea Co., Ltd., Seoul (Korea, Republic of); Cho, Eun-Jung [National Research Laboratory for Chromatin Dynamics, College of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Youn, Hong-Duk, E-mail: hdyoun@snu.ac.kr [National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence and Technology, Seoul National University, Seoul (Korea, Republic of)

    2013-02-01

    Highlights: ► AMPK phosphorylates CtBP1 on serine 158. ► AMPK-mediated phosphorylation of CtBP1 causes the ubiquitination and nuclear export of CtBP1. ► AMPK downregulates the CtBP1-mediated repression of Bax transcription. -- Abstract: CtBP is a transcriptional repressor which plays a significant role in the regulation of cell proliferation and tumor progression. It was reported that glucose withdrawal causes induction of Bax due to the dissociation of CtBP from the Bax promoter. However, the precise mechanism involved in the regulation of CtBP still remains unclear. In this study, we found that an activated AMP-activated protein kinase (AMPK) phosphorylates CtBP1 on Ser-158 upon metabolic stresses. Moreover, AMPK-mediated phosphorylation of CtBP1 (S158) attenuates the repressive function of CtBP1. We also confirmed that triggering activation of AMPK by various factors resulted in an increase of Bax gene expression. These findings provide connections of AMPK with CtBP1-mediated regulation of Bax expression for cell death under metabolic stresses.

  3. Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death

    International Nuclear Information System (INIS)

    Nakatsu, Yusuke; Kotake, Yaichiro; Hino, Atsuko; Ohta, Shigeru

    2008-01-01

    AMP-activated protein kinase (AMPK), a member of the metabolite-sensing protein kinase family, is activated by energy deficiency and is abundantly expressed in neurons. The environmental pollutant, tributyltin chloride (TBT), is a neurotoxin, and has been reported to decrease cellular ATP in some types of cells. Therefore, we investigated whether TBT activates AMPK, and whether its activation contributes to neuronal cell death, using primary cultures of cortical neurons. Cellular ATP levels were decreased 0.5 h after exposure to 500 nM TBT, and the reduction was time-dependent. It was confirmed that most neurons in our culture system express AMPK, and that TBT induced phosphorylation of AMPK. Compound C, an AMPK inhibitor, reduced the neurotoxicity of TBT, suggesting that AMPK is involved in TBT-induced cell death. Next, the downstream target of AMPK activation was investigated. Nitric oxide synthase, p38 phosphorylation and Akt dephosphorylation were not downstream of TBT-induced AMPK activation because these factors were not affected by compound C, but glutamate release was suggested to be controlled by AMPK. Our results suggest that activation of AMPK by TBT causes neuronal death through mediating glutamate release

  4. Beyond AICA Riboside: In Search of New Specific AMP-activated Protein Kinase Activators

    Science.gov (United States)

    Guigas, Bruno; Sakamoto, Kei; Taleux, Nellie; Reyna, Sara M.; Musi, Nicolas; Viollet, Benoit; Hue, Louis

    2010-01-01

    Summary 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICA riboside) has been extensively used in vitro and in vivo to activate the AMP-activated protein kinase (AMPK), a metabolic sensor involved in both cellular and whole body energy homeostasis. However, it has been recently highlighted that AICA riboside also exerts AMPK-independent effects, mainly on AMP-regulated enzymes and mitochondrial oxidative phosphorylation (OXPHOS), leading to the conclusion that new compounds with reduced off target effects are needed to specifically activate AMPK. Here, we review recent findings on newly discovered AMPK activators, notably on A-769662, a nonnucleoside compound from the thienopyridone family. We also report that A-769662 is able to activate AMPK and stimulate glucose uptake in both L6 cells and primary myotubes derived from human satellite cells. In addition, A-769662 increases AMPK activity and phosphorylation of its main downstream targets in primary cultured rat hepatocytes but, by contrast with AICA riboside, does neither affect mitochondrial OXPHOS nor change cellular AMP:ATP ratio. We conclude that A-769662 could be one of the new promising chemical agents to activate AMPK with limited AMPK-independent side effects. PMID:18798311

  5. Protein phosphatase 5 promotes hepatocarcinogenesis through interaction with AMP-activated protein kinase.

    Science.gov (United States)

    Chen, Yao-Li; Hung, Man-Hsin; Chu, Pei-Yi; Chao, Tzu-I; Tsai, Ming-Hsien; Chen, Li-Ju; Hsiao, Yung-Jen; Shih, Chih-Ting; Hsieh, Feng-Shu; Chen, Kuen-Feng

    2017-08-15

    The serine-threonine protein phosphatase family members are known as critical regulators of various cellular functions, such as survival and transformation. Growing evidence suggests that pharmacological manipulation of phosphatase activity exhibits therapeutic benefits. Ser/Thr protein phosphatase 5 (PP5) is known to participate in glucocorticoid receptor (GR) and stress-induced signaling cascades that regulate cell growth and apoptosis, and has been shown to be overexpressed in various human malignant diseases. However, the role of PP5 in hepatocellular carcinoma (HCC) and whether PP5 may be a viable therapeutic target for HCC treatment are unknown. Here, by analyzing HCC clinical samples obtained from 215 patients, we found that overexpression of PP5 is tumor specific and associated with worse clinical outcomes. We further characterized the oncogenic properties of PP5 in HCC cells. Importantly, both silencing of PP5 with lentiviral-mediated short hairpin RNA (shRNA) and chemical inhibition of PP5 phosphatase activity using the natural compound cantharidin/norcantharidin markedly suppressed the growth of HCC cells and tumors in vitro and in vivo. Moreover, we identified AMP-activated protein kinase (AMPK) as a novel downstream target of oncogenic PP5 and demonstrated that the antitumor mechanisms underlying PP5 inhibition involve activation of AMPK signaling. Overall, our results establish a pathological function of PP5 in hepatocarcinogenesis via affecting AMPK signaling and suggest that PP5 inhibition is an attractive therapeutic approach for HCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The dynamical mechanism of auto-inhibition of AMP-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Cheng Peng

    2011-07-01

    Full Text Available We use a novel normal mode analysis of an elastic network model drawn from configurations generated during microsecond all-atom molecular dynamics simulations to analyze the mechanism of auto-inhibition of AMP-activated protein kinase (AMPK. A recent X-ray and mutagenesis experiment (Chen, et al Nature 2009, 459, 1146 of the AMPK homolog S. Pombe sucrose non-fermenting 1 (SNF1 has proposed a new conformational switch model involving the movement of the kinase domain (KD between an inactive unphosphorylated open state and an active or semi-active phosphorylated closed state, mediated by the autoinhibitory domain (AID, and a similar mutagenesis study showed that rat AMPK has the same auto-inhibition mechanism. However, there is no direct dynamical evidence to support this model and it is not clear whether other functionally important local structural components are equally inhibited. By using the same SNF1 KD-AID fragment as that used in experiment, we show that AID inhibits the catalytic function by restraining the KD into an unproductive open conformation, thereby limiting local structural rearrangements, while mutations that disrupt the interactions between the KD and AID allow for both the local structural rearrangement and global interlobe conformational transition. Our calculations further show that the AID also greatly impacts the structuring and mobility of the activation loop.

  7. Prevention of burn injuries to children involving nightwear.

    Science.gov (United States)

    Laing, R M; Bryant, V

    1991-08-28

    The effectiveness of legislative intervention in the New Zealand market for children's nightclothes as an injury prevention strategy has been reassessed by examining those hospital admissions for the period 1980-8 (with emphasis on the 1985-8 period) in which clothing and/or nightclothes were involved. The profiles of the production of children's nightclothes (1977-86) and domestic heating (1984-8) were also examined. Ninety-five cases of burn injury discharges were identified (1985-8), and of those cases involving clothing 42% involved nightwear (49% 1981-4). Some of the 27% unspecified cases may have also involved nightwear (23%, 1981-4). A very strong linear downward trend for nightwear incidents was noted (chi 2 slope = 31.06, p less than 0.001). Forty-eight percent of cases involved children aged 1-6 years, and 68% involved pajamas. Stoves were the main specified ignition agent for nightclothes (36%). Open fires as a form of household heating decreased from 49% to 34% of households (1984-8). Estimated production of nightdresses in New Zealand also decreased (460,000 to 80,000 units, 1973-86). The pronounced decrease in injuries attributable to ignition of children's nightclothes is likely to be the result of mandatory controls on children's nightclothes, increased use of pyjamas, and a steady decrease in use of open fires and portable electric heaters. The typical injury event portrayed to the public of a girl in front of a heater or open fire needs to be corrected.

  8. Fueling the engine: induction of AMP-activated protein kinase in trout skeletal muscle by swimming

    NARCIS (Netherlands)

    Magnoni, L.J.; Palstra, A.P.; Planas, J.V.

    2014-01-01

    AMP-activated protein kinase (AMPK) is well known to be induced by exercise and to mediate important metabolic changes in the skeletal muscle of mammals. Despite the physiological importance of exercise as a modulator of energy use by locomotory muscle, the regulation of this enzyme by swimming has

  9. Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes

    DEFF Research Database (Denmark)

    Gormand, Amélie; Henriksson, Emma; Ström, Kristoffer

    2011-01-01

    AMP-activated protein kinase (AMPK) is a serine/threonine kinase that regulates cellular and whole body energy homeostasis. In adipose tissue, activation of AMPK has been demonstrated in response to a variety of extracellular stimuli. However, the upstream kinase that activates AMPK in adipocytes...

  10. Ionizing Radiation Activates AMP-Activated Kinase (AMPK): A Target for Radiosensitization of Human Cancer Cells

    International Nuclear Information System (INIS)

    Sanli, Toran; Rashid, Ayesha; Liu Caiqiong

    2010-01-01

    Purpose: Adenosine monophosphate (AMP)-activated kinase (AMPK) is a molecular energy sensor regulated by the tumor suppressor LKB1. Starvation and growth factors activate AMPK through the DNA damage sensor ataxia-telangiectasia mutated (ATM). We explored the regulation of AMPK by ionizing radiation (IR) and its role as a target for radiosensitization of human cancer cells. Methods and Materials: Lung, prostate, and breast cancer cells were treated with IR (2-8 Gy) after incubation with either ATM or AMPK inhibitors or the AMPK activator metformin. Then, cells were subjected to either lysis and immunoblotting, immunofluorescence microscopy, clonogenic survival assays, or cell cycle analysis. Results: IR induced a robust phosphorylation and activation of AMPK in all tumor cells, independent of LKB1. IR activated AMPK first in the nucleus, and this extended later into cytoplasm. The ATM inhibitor KU-55933 blocked IR activation of AMPK. AMPK inhibition with Compound C or anti-AMPK α subunit small interfering RNA (siRNA) blocked IR induction of the cell cycle regulators p53 and p21 waf/cip as well as the IR-induced G2/M arrest. Compound C caused resistance to IR, increasing the surviving fraction after 2 Gy, but the anti-diabetic drug metformin enhanced IR activation of AMPK and lowered the surviving fraction after 2 Gy further. Conclusions: We provide evidence that IR activates AMPK in human cancer cells in an LKB1-independent manner, leading to induction of p21 waf/cip and regulation of the cell cycle and survival. AMPK appears to (1) participate in an ATM-AMPK-p21 waf/cip pathway, (2) be involved in regulation of the IR-induced G2/M checkpoint, and (3) may be targeted by metformin to enhance IR responses.

  11. AMP-activated protein kinase in contraction regulation of skeletal muscle metabolism: necessary and/or sufficient?

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Wojtaszewski, Jørgen; Richter, Erik

    2009-01-01

    In skeletal muscle, the contraction-activated heterotrimeric 5'-AMP-activated protein kinase (AMPK) protein is proposed to regulate the balance between anabolic and catabolic processes by increasing substrate uptake and turnover in addition to regulating the transcription of proteins involved...... in mitochondrial biogenesis and other aspects of promoting an oxidative muscle phenotype. Here, the current knowledge on the expression of AMPK subunits in human quadriceps muscle and evidence from rodent studies suggesting distinct AMPK subunit expression pattern in different muscle types is reviewed. Then......, the intensity and time dependence of AMPK activation in human quadriceps and rodent muscle are evaluated. Subsequently, a major part of this review critically examines the evidence supporting a necessary and/or sufficient role of AMPK in a broad spectrum of skeletal muscle contraction-relevant processes...

  12. Pedestrian fatalities and injuries involving Irish older people.

    LENUS (Irish Health Repository)

    Martin, A J

    2012-02-01

    BACKGROUND: It has been established internationally that road traffic accidents (RTAs) involving older drivers follow clearly different patterns of timing, location and outcomes from those of younger age groups. Older pedestrians are also a vulnerable group and fewer analyses have been undertaken of the phenomenology of their injuries and fatalities. We studied the pattern of pedestrian RTAs in Ireland over a five-year period with the aim of identifying differences between older pedestrians (aged 65 or older) and younger adults. METHODS: We examined the datasets of the Irish National Road Authority (now the Road Safety Authority) from 1998-2002. We analysed patterns of crashes involving older pedestrians (aged 65) and compared them with younger adults (aged 18-64). RESULTS: Older people represented 36% (n = 134) of pedestrian fatalities and 23% of serious injuries while they only account for 19% of total RTAs. Mortality in RTA is more than doubled for older pedestrians compared to younger adults (RR 2.30). Most accidents involving older pedestrians happen in daylight with good visibility (56%) and in good weather conditions (77%). CONCLUSIONS: Older pedestrians are particularly vulnerable in RTAs. These occur more frequently during daylight hours and in good weather conditions. This may point to a need for prevention strategies that are targeted at the traffic environment and other road users rather than at older people.

  13. Peripheral nervous system involvement in chronic spinal cord injury

    DEFF Research Database (Denmark)

    Tankisi, Hatice; Pugdahl, Kirsten; Rasmussen, Mikkel Mylius

    2015-01-01

    Introduction: Upper motor neuron disorders are believed to leave the peripheral nervous system (PNS) intact. In this study we examined whether there is evidence of PNS involvement in spinal cord injury (SCI). Methods: Twelve subjects with chronic low cervical or thoracic SCI were included......), and the amount of SA correlated inversely with reflex activity and nerve length. Fibular nerve entrapment across the knee was seen in 6 subjects, and sciatic nerve entrapment was seen in 1. Apart from entrapment neuropathies, NCS changes were found predominantly in motor nerves. Conclusion: The presence...

  14. Mechanisms and factors involved in hip injuries during frontal crashes.

    Science.gov (United States)

    Yoganandan, N; Pintar, F A; Gennarelli, T A; Maltese, M R; Eppinger, R H

    2001-11-01

    This study was conducted to collect data and gain insights relative to the mechanisms and factors involved in hip injuries during frontal crashes and to study the tolerance of hip injuries from this type of loading. Unembalmed human cadavers were seated on a standard automotive seat (reinforced) and subjected to knee impact test to each lower extremity. Varying combinations of flexion and adduction/abduction were used for initial alignment conditions and pre-positioning. Accelerometers were fixed to the iliac wings and twelfth thoracic vertebral spinous process. A 23.4-kg padded pendulum impacted the knee at velocities ranging from 4.3 to 7.6 m/s. The impacting direction was along the anteroposterior axis, i.e., the global X-axis, in the body-fixed coordinate system. A load cell on the front of the pendulum recorded the impact force. Peak impact forces ranged from 2,450 to 10,950 N. The rate of loading ranged from 123 to 7,664 N/msec. The impulse values ranged from 12.4 to 31.9 Nsec. Injuries were not apparent in three tests. Eight tests resulted in trauma. Fractures involving the pelvis including the acetabulum and proximal femur occurred in five out of the eight tests, and distal femoral bone fracture occurred in one test. These results underscore the importance of leg pre-positioning and the orientation of the impacting axis to produce specific types of trauma to the pelvic region of the lower extremity.

  15. Glycogen synthase kinase 3β promotes liver innate immune activation by restraining AMP-activated protein kinase activation.

    Science.gov (United States)

    Zhou, Haoming; Wang, Han; Ni, Ming; Yue, Shi; Xia, Yongxiang; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

    2018-02-13

    Glycogen synthase kinase 3β (Gsk3β [Gsk3b]) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischaemia and reperfusion injuries (IRIs) have been well documented, the underlying mechanisms remain ambiguous, in part because of the lack of cell-specific tools in vivo. We created a myeloid-specific Gsk3b knockout (KO) strain to study the function of Gsk3β in macrophages in a murine liver partial warm ischaemia model. Compared with controls, myeloid Gsk3b KO mice were protected from IRI, with diminished proinflammatory but enhanced anti-inflammatory immune responses in livers. In bone marrow-derived macrophages, Gsk3β deficiency resulted in an early reduction of Tnf gene transcription but sustained increase of Il10 gene transcription on Toll-like receptor 4 stimulation in vitro. These effects were associated with enhanced AMP-activated protein kinase (AMPK) activation, which led to an accelerated and higher level of induction of the novel innate immune negative regulator small heterodimer partner (SHP [Nr0b2]). The regulatory function of Gsk3β on AMPK activation and SHP induction was confirmed in wild-type bone marrow-derived macrophages with a Gsk3 inhibitor. Furthermore, we found that this immune regulatory mechanism was independent of Gsk3β Ser9 phosphorylation and the phosphoinositide 3-kinase-Akt signalling pathway. In vivo, myeloid Gsk3β deficiency facilitated SHP upregulation by ischaemia-reperfusion in liver macrophages. Treatment of Gsk3b KO mice with either AMPK inhibitor or SHP small interfering RNA before the onset of liver ischaemia restored liver proinflammatory immune activation and IRI in these otherwise protected hosts. Additionally, pharmacological activation of AMPK protected wild-type mice from liver IRI, with reduced proinflammatory immune activation. Inhibition of the AMPK-SHP pathway by liver ischaemia was demonstrated in tumour resection

  16. Fatal work injuries involving natural disasters, 1992-2006.

    Science.gov (United States)

    Fayard, Gregory M

    2009-12-01

    Although a goal of disaster preparedness is to protect vulnerable populations from hazards, little research has explored the types of risks that workers face in their encounters with natural disasters. This study examines how workers are fatally injured in severe natural events. A classification structure was created that identified the physical component of the disaster that led to the death and the pursuit of the worker as it relates to the disaster. Data on natural disasters from the Census of Fatal Occupational Injuries for the years 1992 through 2006 were analyzed. A total of 307 natural disaster deaths to workers were identified in 1992-2006. Most fatal occupational injuries were related to wildfires (80 fatalities), hurricanes (72 fatalities), and floods (62 fatalities). Compared with fatal occupational injuries in general, natural disaster fatalities involved more workers who were white and more workers who were working for the government. Most wildfire fatalities stemmed directly from exposure to fire and gases and occurred to those engaged in firefighting, whereas hurricane fatalities tended to occur more independently of disaster-produced hazards and to workers engaged in cleanup and reconstruction. Those deaths related to the 2005 hurricanes occurred a median of 36.5 days after landfall of the associated storm. Nearly half of the flood deaths occurred to passengers in motor vehicles. Other disasters included tornadoes (33 fatalities), landslides (17), avalanches (16), ice storms (14), and blizzards (9). Despite an increasing social emphasis on disaster preparation and response, there has been little increase in expert knowledge about how people actually perish in these large-scale events. Using a 2-way classification structure, this study identifies areas of emphasis in preventing occupational deaths from various natural disasters.

  17. Inhibition of cAMP-Activated Intestinal Chloride Secretion by Diclofenac: Cellular Mechanism and Potential Application in Cholera

    OpenAIRE

    Pongkorpsakol, Pawin; Pathomthongtaweechai, Nutthapoom; Srimanote, Potjanee; Soodvilai, Sunhapas; Chatsudthipong, Varanuj; Muanprasat, Chatchai

    2014-01-01

    Cyclic AMP-activated intestinal Cl- secretion plays an important role in pathogenesis of cholera. This study aimed to investigate the effect of diclofenac on cAMP-activated Cl- secretion, its underlying mechanisms, and possible application in the treatment of cholera. Diclofenac inhibited cAMP-activated Cl- secretion in human intestinal epithelial (T84) cells with IC50 of ∼ 20 µM. The effect required no cytochrome P450 enzyme-mediated metabolic activation. Interestingly, exposures of T84 cell...

  18. Protective features of resveratrol on human spermatozoa cryopreservation may be mediated through 5' AMP-activated protein kinase activation.

    Science.gov (United States)

    Shabani Nashtaei, M; Amidi, F; Sedighi Gilani, M A; Aleyasin, A; Bakhshalizadeh, Sh; Naji, M; Nekoonam, S

    2017-03-01

    Biochemical and physical modifications during the freeze-thaw process adversely influence the restoration of energy-dependent sperm functions required for fertilization. Resveratrol, a phytoalexin, has been introduced to activate 5' AMP-activated protein kinase which is a cell energy sensor and a cell metabolism regulator. The cryoprotection of resveratrol on sperm cryoinjury via activation of AMP-activated protein kinase also remains to be elucidated. Our aim, thus, was to investigate: (i) the presence and intracellular localization of AMP-activated protein kinase protein; (ii) whether resveratrol may exert a protective effect on certain functional properties of fresh and post-thaw human spermatozoa through modulation of AMP-activated protein kinase. Spermatozoa from normozoospermic men were incubated with or without different concentrations of Compound C as an AMP-activated protein kinase inhibitor or resveratrol as an AMP-activated protein kinase activator for different lengths of time and were then cryopreserved. AMP-activated protein kinase is expressed essentially in the entire flagellum and the post-equatorial region. Viability of fresh spermatozoa was not significantly affected by the presence of Compound C or resveratrol. However, although Compound C caused a potent inhibition of spermatozoa motility parameters, resveratrol did not induce negative effect, except a significant reduction in motility at 25 μm for 1 h. Furthermore, resveratrol significantly increased AMP-activated protein kinase phosphorylation and mitochondrial membrane potential and decreased reactive oxygen species and apoptosis-like changes in frozen-thawed spermatozoa. Nevertheless, it was not able to compensate decreased sperm viability and motility parameters following cryopreservation. In contrast, Compound C showed opposite effects to resveratrol on AMP-activated protein kinase phosphorylation, reactive oxygen species, apoptosis-like changes, mitochondrial membrane potential, and

  19. Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.

    Directory of Open Access Journals (Sweden)

    Jong Hyun Kim

    2010-03-01

    Full Text Available Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated.Here, we found that AMPK-induced phospholipase D1 (PLD1 activation is required for (14C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT stimulates PLD activity, while AMPK-dominant negative (DN inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA, which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator regulate (14C-glucose uptake and cell surface glucose transport (GLUT 4 through ERK stimulation by AMPK-mediated PLD1 activation.These results suggest that AMPK-mediated PLD1 activation is required for (14C

  20. Involvement of AMP-activated protein kinase in control of adipocyte metabolism during starvation

    Czech Academy of Sciences Publication Activity Database

    Kopecký, Jan; Šponarová, Jana; Mustard, K. J.; Flachs, Pavel; Horáková, Olga; Rossmeisl, Martin; Bardová, Kristina; Thomason-Hughes, M.; Braunerová, Radka; Hardie, D. G.

    2005-01-01

    Roč. 6, č. S1 (2005), s. 52-52 ISSN 1467-7881. [European Congress on Obesity /14./. 01.06.2005-04.06.2005, Athens] R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GA303/05/2580 Institutional research plan: CEZ:AV0Z50110509 Keywords : AMPK * adipocyte * starvation * fatty acid oxidation Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  1. Involvement of AMP - activated protein kinase in fat depot-specific metabolic changes during starvation

    Czech Academy of Sciences Publication Activity Database

    Šponarová, Jana; Mustard, K. J.; Horáková, Olga; Flachs, Pavel; Rossmeisl, Martin; Brauner, Petr; Bardová, Kristina; Thomason-Hughes, M.; Braunerová, Radka; Janovská, Petra; Hardie, D. G.; Kopecký, Jan

    2005-01-01

    Roč. 579, č. 27 (2005), s. 6105-6110 ISSN 0014-5793 R&D Projects: GA ČR(CZ) GA303/05/2580; GA AV ČR(CZ) KJB5011303 Grant - others:Wellcome Trust(GB) 02760; European Commission(XE) LSHM-CT-2004-005272; Diabetes UK(GB) Project Grant; Biotechnology and Biological Sciences Research Council(GB) Research Studentship; GA-(GB) Novo-Nordisk Institutional research plan: CEZ:AV0Z50110509 Keywords : lipid metabolism * AMPK * starvation Subject RIV: ED - Physiology Impact factor: 3.415, year: 2005

  2. Patterns of Injuries After Road Traffic Crashes Involving Bodabodas

    African Journals Online (AJOL)

    2010-01-12

    Jan 12, 2010 ... Globally, trauma resulting from road traffic crashes is a major cause of death and disability with majority occur- ... Bodabodas are a major form of transport in the city of. Kampala and in other towns in East Africa. .... Injury Control Injury Surveillance Reports (2000 – 2003). Injury Control Centre, Kampala. 4.

  3. Role of 5'AMP-activated protein kinase in skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Wojtaszewski, Jørgen F. P.

    2008-01-01

    5'AMP-activated protein kinase (AMPK) is recognized as an important intracellular energy sensor, shutting down energy-consuming processes and turning on energy-generating processes. Discovery of target proteins of AMPK has dramatically increased in the past 10 years. Historically, AMPK was first...... shown to regulate fatty acid and cholesterol synthesis, but is now hypothesized to take part in the regulation of energy/fuel balance not only at the cellular level but also at the level of the whole organism. In this brief review we will discuss some of the roles of AMPK in skeletal muscle....

  4. AMP-activated protein kinase downregulates Kv7.1 cell surface expression

    DEFF Research Database (Denmark)

    Andersen, Martin N; Krzystanek, Katarzyna; Jespersen, Thomas

    2012-01-01

    in response to polarization of the epithelial Madin-Darby canine kidney (MDCK) cell line and that this was mediated by activation of protein kinase C (PKC). In this study, the pathway downstream of PKC, which leads to internalization of Kv7.1 upon cell polarization, is elucidated. We show by confocal...... microscopy that Kv7.1 is endocytosed upon initiation of the polarization process and sent for degradation by the lysosomal pathway. The internalization could be mimicked by pharmacological activation of the AMP-activated protein kinase (AMPK) using three different AMPK activators. We demonstrate...

  5. Glucose Regulates Hypothalamic Long-chain Fatty Acid Metabolism via AMP-activated Kinase (AMPK) in Neurons and Astrocytes*

    Science.gov (United States)

    Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

    2013-01-01

    Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance. PMID:24240094

  6. Glucose regulates hypothalamic long-chain fatty acid metabolism via AMP-activated kinase (AMPK) in neurons and astrocytes.

    Science.gov (United States)

    Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

    2013-12-27

    Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance.

  7. Regorafenib impairs mitochondrial functions, activates AMP-activated protein kinase, induces autophagy, and causes rat hepatocyte necrosis.

    Science.gov (United States)

    Weng, Zuquan; Luo, Yong; Yang, Xi; Greenhaw, James J; Li, Haibo; Xie, Liming; Mattes, William B; Shi, Qiang

    2015-01-02

    The tyrosine kinase inhibitor regorafenib was approved by regulatory agencies for cancer treatment, albeit with strong warnings of severe hepatotoxicity included in the product label. The basis of this toxicity is unknown; one possible mechanism, that of mitochondrial damage, was tested. In isolated rat liver mitochondria, regorafenib directly uncoupled oxidative phosphorylation (OXPHOS) and promoted calcium overload-induced swelling, which were respectively prevented by the recoupler 6-ketocholestanol (KC) and the mitochondrial permeability transition (MPT) pore blocker cyclosporine A (CsA). In primary hepatocytes, regorafenib uncoupled OXPHOS, disrupted mitochondrial inner membrane potential (MMP), and decreased cellular ATP at 1h, and triggered MPT at 3h, which was followed by necrosis but not apoptosis at 7h and 24h, all of which were abrogated by KC. The combination of the glycolysis enhancer fructose plus the mitochondrial ATPase synthase inhibitor oligomycin A abolished regorafenib induced necrosis at 7h. This effect was not seen at 24h nor with the fructose or oligomycin A separately. CsA in combination with trifluoperazine, both MPT blockers, showed similar effects. Two compensatory mechanisms, activation of AMP-activated protein kinase (AMPK) to ameliorate ATP shortage and induction of autophagy to remove dysfunctional mitochondria, were found to be mobilized. Hepatocyte necrosis was enhanced either by the AMPK inhibitor Compound C or the autophagy inhibitor chloroquine, while autophagy inducer rapamycin was strongly cytoprotective. Remarkably, all toxic effects were observed at clinically-relevant concentrations of 2.5-15μM. These data suggest that uncoupling of OXPHOS and the resulting ATP shortage and MPT induction are the key mechanisms for regorafenib induced hepatocyte injury, and AMPK activation and autophagy induction serve as pro-survival pathways against such toxicity. Published by Elsevier Ireland Ltd.

  8. School Liability: Student to Student Injuries Involving Students with Disabilities.

    Science.gov (United States)

    Bettenhausen, Sherrie

    In the absence of immunity, courts have held schools and school personnel liable for personal injury by a student with a disability that resulted from negligent failure to provide a reasonable safe environment, failure to warn of known hazards, or failure to provide adequate supervision. Case law is presented to demonstrate the extent that school…

  9. Functional role of AMP-activated protein kinase in the heart during exercise.

    Science.gov (United States)

    Musi, Nicolas; Hirshman, Michael F; Arad, Michael; Xing, Yanqiu; Fujii, Nobuharu; Pomerleau, Jason; Ahmad, Ferhaan; Berul, Charles I; Seidman, Jon G; Tian, Rong; Goodyear, Laurie J

    2005-04-11

    AMP-activated protein kinase (AMPK) plays a critical role in maintaining energy homeostasis and cardiac function during ischemia in the heart. However, the functional role of AMPK in the heart during exercise is unknown. We examined whether acute exercise increases AMPK activity in mouse hearts and determined the significance of these increases by studying transgenic (TG) mice expressing a cardiac-specific dominant-negative (inactivating) AMPKalpha2 subunit. Exercise increased cardiac AMPKalpha2 activity in the wild type mice but not in TG. We found that inactivation of AMPK did not result in abnormal ATP and glycogen consumption during exercise, cardiac function assessed by heart rhythm telemetry and stress echocardiography, or in maximal exercise capacity.

  10. The AMP-activated protein kinase beta 1 subunit modulates erythrocyte integrity.

    Science.gov (United States)

    Cambridge, Emma L; McIntyre, Zoe; Clare, Simon; Arends, Mark J; Goulding, David; Isherwood, Christopher; Caetano, Susana S; Reviriego, Carmen Ballesteros; Swiatkowska, Agnieszka; Kane, Leanne; Harcourt, Katherine; Adams, David J; White, Jacqueline K; Speak, Anneliese O

    2017-01-01

    Failure to maintain a normal in vivo erythrocyte half-life results in the development of hemolytic anemia. Half-life is affected by numerous factors, including energy balance, electrolyte gradients, reactive oxygen species, and membrane plasticity. The heterotrimeric AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that acts as a critical regulator of cellular energy balance. Previous roles for the alpha 1 and gamma 1 subunits in the control of erythrocyte survival have been reported. In the work described here, we studied the role of the beta 1 subunit in erythrocytes and observed microcytic anemia with compensatory extramedullary hematopoiesis together with splenomegaly and increased osmotic resistance. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  11. AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System.

    Science.gov (United States)

    Salt, Ian P; Hardie, D Grahame

    2017-05-26

    The AMP-activated protein kinase (AMPK) is a key regulator of cellular and whole-body energy homeostasis, which acts to restore energy homoeostasis whenever cellular energy charge is depleted. Over the last 2 decades, it has become apparent that AMPK regulates several other cellular functions and has specific roles in cardiovascular tissues, acting to regulate cardiac metabolism and contractile function, as well as promoting anticontractile, anti-inflammatory, and antiatherogenic actions in blood vessels. In this review, we discuss the role of AMPK in the cardiovascular system, including the molecular basis of mutations in AMPK that alter cardiac physiology and the proposed mechanisms by which AMPK regulates vascular function under physiological and pathophysiological conditions. © 2017 American Heart Association, Inc.

  12. Assessing injury severity in bicyclists involved in traffic accidents to more effectively prevent fatal bicycle injuries in Japan.

    Science.gov (United States)

    Gomei, Sayaka; Hitosugi, Masahito; Ikegami, Keiichi; Tokudome, Shogo

    2013-10-01

    The objective of this study was to clarify the relationship between injury severity in bicyclists involved in traffic accidents and patient outcome or type of vehicle involved in order to propose effective measures to prevent fatal bicycle injuries. Hospital records were reviewed for all patients from 2007 to 2010 who had been involved in a traffic accident while riding a bicycle and were subsequently transferred to the Shock Trauma Center of Dokkyo Medical University Koshigaya Hospital. Patient outcomes and type of vehicle that caused the injury were examined. The mechanism of injury, Abbreviated Injury Scale (AIS) score, and Injury Severity Score (ISS) of the patient were determined. A total of 115 patients' records were reviewed. The mean patient age was 47.1 ± 27.4 years. The average ISS was 23.9, with an average maximum AIS (MAIS) score of 3.7. The ISS, MAIS score, head AIS score, and chest AIS score were well correlated with patient outcome. The head AIS score was significantly higher in patients who had died (mean of 4.4); however, the ISS, MAIS score, and head AIS score did not differ significantly according to the type of vehicle involved in the accident. The mean head AIS scores were as high as 2.4 or more for accidents involving any type of vehicle. This study provides useful information for forensic pathologists who suspect head injuries in bicyclists involved in traffic accidents. To effectively reduce bicyclist fatalities from traffic accidents, helmet use should be required for all bicyclists.

  13. AMP-activated protein kinase (AMPK mediates nutrient regulation of thioredoxin-interacting protein (TXNIP in pancreatic beta-cells.

    Directory of Open Access Journals (Sweden)

    Maayan Shaked

    Full Text Available Thioredoxin-interacting protein (TXNIP regulates critical biological processes including inflammation, stress and apoptosis. TXNIP is upregulated by glucose and is a critical mediator of hyperglycemia-induced beta-cell apoptosis in diabetes. In contrast, the saturated long-chain fatty acid palmitate, although toxic to the beta-cell, inhibits TXNIP expression. The mechanisms involved in the opposing effects of glucose and fatty acids on TXNIP expression are unknown. We found that both palmitate and oleate inhibited TXNIP in a rat beta-cell line and islets. Palmitate inhibition of TXNIP was independent of fatty acid beta-oxidation or esterification. AMP-activated protein kinase (AMPK has an important role in cellular energy sensing and control of metabolic homeostasis; therefore we investigated its involvement in nutrient regulation of TXNIP. As expected, glucose inhibited whereas palmitate stimulated AMPK. Pharmacologic activators of AMPK mimicked fatty acids by inhibiting TXNIP. AMPK knockdown increased TXNIP expression in presence of high glucose with and without palmitate, indicating that nutrient (glucose and fatty acids effects on TXNIP are mediated in part via modulation of AMPK activity. TXNIP is transcriptionally regulated by carbohydrate response element-binding protein (ChREBP. Palmitate inhibited glucose-stimulated ChREBP nuclear entry and recruitment to the Txnip promoter, thereby inhibiting Txnip transcription. We conclude that AMPK is an important regulator of Txnip transcription via modulation of ChREBP activity. The divergent effects of glucose and fatty acids on TXNIP expression result in part from their opposing effects on AMPK activity. In light of the important role of TXNIP in beta-cell apoptosis, its inhibition by fatty acids can be regarded as an adaptive/protective response to glucolipotoxicity. The finding that AMPK mediates nutrient regulation of TXNIP may have important implications for the pathophysiology and treatment

  14. AMP-activated protein kinase activation mediates CCL3-induced cell migration and matrix metalloproteinase-2 expression in human chondrosarcoma

    Science.gov (United States)

    2013-01-01

    Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1α, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells. Chondrosarcoma is a highly malignant tumor that causes distant metastasis. However, the effect of CCL3 on human chondrosarcoma metastasis is still unknown. Here, we found that CCL3 increased cellular migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. Pre-treatment of cells with the MMP-2 inhibitor or transfection with MMP-2 specific siRNA abolished CCL3-induced cell migration. CCL3 has been reported to exert its effects through activation of its specific receptor, CC chemokine receptor 5 (CCR5). The CCR5 and AMP-activated protein kinase (AMPK) inhibitor or siRNA also attenuated CCL3-upregulated cell motility and MMP-2 expression. CCL3-induced expression of MMP-2 and migration were also inhibited by specific inhibitors, and inactive mutants of AMPK, p38 mitogen activated protein kinase (p38 or p38-MAPK), and nuclear factor κB (NF-κB) cascades. On the other hand, CCL3 treatment demonstrably activated AMPK, p38, and NF-κB signaling pathways. Furthermore, the expression levels of CCL3, CCR5, and MMP-2 were correlated in human chondrosarcoma specimens. Taken together, our results indicate that CCL3 enhances the migratory ability of human chondrosarcoma cells by increasing MMP-2 expression via the CCR5, AMPK, p38, and NF-κB pathways. PMID:24047437

  15. AMP-activated kinase in human spermatozoa: identification, intracellular localization, and key function in the regulation of sperm motility

    Directory of Open Access Journals (Sweden)

    Violeta Calle-Guisado

    2017-01-01

    Full Text Available AMP-activated kinase (AMPK, a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work′s aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho-Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%-80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS in the presence or absence of the AMPK inhibitor compound C (CC. AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho-Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied.

  16. AMP-activated kinase in human spermatozoa: identification, intracellular localization, and key function in the regulation of sperm motility

    Science.gov (United States)

    Calle-Guisado, Violeta; de Llera, Ana Hurtado; Martin-Hidalgo, David; Mijares, Jose; Gil, Maria C; Alvarez, Ignacio S; Bragado, Maria J; Garcia-Marin, Luis J

    2017-01-01

    AMP-activated kinase (AMPK), a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work's aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho-Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%–80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS) in the presence or absence of the AMPK inhibitor compound C (CC). AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho-Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied. PMID:27678462

  17. [Occupational injury risk in the shoe industry: frequency, types of injuries and equipment involved, improvement interventions].

    Science.gov (United States)

    Tognon, Ilaria Desirée

    2012-01-01

    The aim of the work has been to evaluate the risk of injuries connected to the use of machinery and work tools in the footwear industry. The analysis of the data related to injuries in the footwear industry, deduced from the registers of injuries collected in the investigated factories, shows that most accidents arise from the contact of the operator's hands with tools and machinery parts during their use. Risk factors generally include the inherent specific danger of some work tools and machines, the lack or inadequacy of safety devices, the obsolescence of the equipment, the imprudence and underestimation of risk.

  18. Etiologies of pediatric craniofacial injuries: a comparison of injuries involving all-terrain vehicles and golf carts.

    Science.gov (United States)

    White, Lauren C; McKinnon, Brian J; Hughes, C Anthony

    2013-03-01

    To determine incidence and etiologies of craniofacial injuries in the pediatric population through comparison of injuries caused by all-terrain vehicles and golf cart trauma. Case series with chart review. Level 1 trauma center. Retrospective review of pediatric traumas at a tertiary academic medical center from 2003 to 2012 identified 196 patients whose injuries resulted from accidents involving either all-terrain vehicles or golf carts. Data was collected and variables such as age, gender, driver vs. passenger, location of accident, Glasgow coma scale, Injury severity scale, Abbreviated injury scale, and presence or absence of helmet use were examined. 196 pediatric patients were identified: 68 patients had injuries resulting from golf cart accidents, and 128 patients from ATV accidents. 66.4% of ATV-related traumas were male, compared to 52.9% of golf cart-related traumas. Ages of injured patients were similar between the two modalities with average age of ATV traumas 10.8 (±4.0) years and golf cart traumas 10.0 (±4.6) years. Caucasians were most commonly involved in both ATV (79.7%) and golf cart traumas (85.3%). 58.6% of all ATV related trauma and 69.1% of all golf cart trauma resulted in craniofacial injuries. The most common craniofacial injury was a closed head injury with brief loss of consciousness, occurring in 46.1% of the ATV traumas and 54.4% of the golf cart traumas. Temporal bone fractures were the second most common type of craniofacial injury, occurring in 5.5% of ATV accidents and 7.4% of the golf cart traumas. Length of hospital stay and, cases requiring surgery and severity scores were similar between both populations. Intensive care admissions and injury severity scores approached but not reach statistical significance (0.096 and 0.083, respectively). The only statistically significant differences between the two modalities were helmet use (P=0.00018%) and days requiring ventilator assistance (P=0.025). ATVs and golf carts are often exempt

  19. Regulation of AMP-activated protein kinase by natural and synthetic activators

    Directory of Open Access Journals (Sweden)

    David Grahame Hardie

    2016-01-01

    Full Text Available The AMP-activated protein kinase (AMPK is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function.

  20. Antidiabetic effect of gomisin N via activation of AMP-activated protein kinase.

    Science.gov (United States)

    Jung, Dae Young; Kim, Ji-Hyun; Lee, Hoyoung; Jung, Myeong Ho

    2017-12-16

    Gomisin N (GN) is a lignan derived from Schisandra chinensis. AMP-activated kinase (AMPK) has gained attention as a therapeutic target for the treatment of metabolic syndrome. Previously, we reported that GN activated the AMPK pathway and ameliorated high-fat diet (HFD)-induced hepatic steatosis. In this study, we investigated the anti-diabetic effects of GN in C2C12 myotubes and HFD obese mice. GN enhanced the phosphorylation of AMPK/acetyl-CoA carboxylase (ACC) and Akt. In addition, GN promoted glucose uptake in C2C12 myotubes, which was accompanied by the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Treatment with compound C, an AMPK inhibitor, suppressed GN-mediated stimulation of glucose uptake. Furthermore, GN increased the expression of mitochondria biogenesis and fatty acid oxidation genes in C2C12 myotubes. In the in vivo study, administration of GN to HFD mice decreased the levels of fasting blood glucose and insulin, and improved glucose tolerance in HFD obese mice. GN administration rescued the decreased phosphorylation of AMPK and Akt and stimulated the expression of mitochondria biogenesis genes in the skeletal muscle of HFD mice. These findings suggested that GN exerted anti-hyperglycemic effects through AMPK activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. AMP-activated Protein Kinase As a Target For Pathogens: Friends Or Foes?

    Science.gov (United States)

    Moreira, Diana; Silvestre, Ricardo; Cordeiro-da-Silva, Anabela; Estaquier, Jérôme; Foretz, Marc; Viollet, Benoit

    2016-01-01

    Intracellular pathogens are known to manipulate host cell regulatory pathways to establish an optimal environment for their growth and survival. Pathogens employ active mechanisms to hijack host cell metabolism and acquire existing nutrient and energy store. The role of the cellular energy sensor AMP-activated protein kinase (AMPK) in the regulation of cellular energy homeostasis is well documented. Here, we highlight recent advances showing the importance of AMPK signaling in pathogen-host interactions. Pathogens interact with AMPK by a variety of mechanisms aimed at reprogramming host cell metabolism to their own benefit. Stimulation of AMPK activity provides an efficient process to rapidly adapt pathogen metabolism to the major nutritional changes often encountered during the different phases of infection. However, inhibition of AMPK is also used by pathogens to manipulate innate host response, indicating that AMPK appears relevant to restriction of pathogen infection. We also document the effects of pharmacological AMPK modulators on pathogen proliferation and survival. This review illustrates intricate pathogen-AMPK interactions that may be exploited to the development of novel anti-pathogen therapies.

  2. Xanthene derivatives increase glucose utilization through activation of LKB1-dependent AMP-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Yonghoon Kwon

    Full Text Available 5' AMP-activated protein kinase (AMPK is a highly conserved serine-threonine kinase that regulates energy expenditure by activating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. Therefore AMPK activators are considered to be drug targets for treatment of metabolic diseases such as diabetes mellitus. To identify novel AMPK activators, we screened xanthene derivatives. We determined that the AMPK activators 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-nitro-phenyl-thioureido]-ethyl}-amide (Xn and 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-cyano-phenyl-thioureido]-ethyl}-amide (Xc elevated glucose uptake in L6 myotubes by stimulating translocation of glucose transporter type 4 (GLUT4. Treatment with the chemical AMPK inhibitor compound C and infection with dominant-negative AMPKa2-virus inhibited AMPK phosphorylation and glucose uptake in myotubes induced by either Xn or Xc. Of the two major upstream kinases of AMPK, we found that Xn and Xc showed LKB1 dependency by knockdown of STK11, an ortholog of human LKB1. Single intravenous administration of Xn and Xc to high-fat diet-induced diabetic mice stimulated AMPK phosphorylation of skeletal muscle and improved glucose tolerance. Taken together, these results suggest that Xn and Xc regulate glucose homeostasis through LKB1-dependent AMPK activation and that the compounds are potential candidate drugs for the treatment of type 2 diabetes mellitus.

  3. Berberine promotes glucose consumption independently of AMP-activated protein kinase activation.

    Directory of Open Access Journals (Sweden)

    Miao Xu

    Full Text Available Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1 inhibition of AMPK activity by Compound C, (2 suppression of AMPKα expression by siRNA, and (3 blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.

  4. Role of AMP-activated protein kinase in mechanism of metformin action.

    Science.gov (United States)

    Zhou, G; Myers, R; Li, Y; Chen, Y; Shen, X; Fenyk-Melody, J; Wu, M; Ventre, J; Doebber, T; Fujii, N; Musi, N; Hirshman, M F; Goodyear, L J; Moller, D E

    2001-10-01

    Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders.

  5. Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway.

    Science.gov (United States)

    Kim, Tae Sung; Shin, Yern-Hyerk; Lee, Hye-Mi; Kim, Jin Kyung; Choe, Jin Ho; Jang, Ji-Chan; Um, Soohyun; Jin, Hyo Sun; Komatsu, Masaaki; Cha, Guang-Ho; Chae, Han-Jung; Oh, Dong-Chan; Jo, Eun-Kyeong

    2017-06-13

    The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs. Using a Drosophila melanogaster-Mycobacterium marinum infection model, we showed that OMS-A-induced autophagy contributed to the increased survival of infected flies and the limitation of bacterial load. We further showed that OMS triggered AMP-activated protein kinase (AMPK) activation, which was required for OMS-mediated phagosome maturation and antimicrobial responses against Mtb. Moreover, treating BMDMs with OMS led to dose-dependent inhibition of macrophage inflammatory responses, which was also dependent on AMPK activation. Collectively, these data show that OMS is a promising candidate for new anti-mycobacterial therapeutics by activating antibacterial autophagy via AMPK-dependent signaling and suppressing excessive inflammation during Mtb infections.

  6. AMP-activated protein kinase induces actin cytoskeleton reorganization in epithelial cells

    International Nuclear Information System (INIS)

    Miranda, Lisa; Carpentier, Sarah; Platek, Anna; Hussain, Nusrat; Gueuning, Marie-Agnes; Vertommen, Didier; Ozkan, Yurda; Sid, Brice; Hue, Louis; Courtoy, Pierre J.; Rider, Mark H.; Horman, Sandrine

    2010-01-01

    AMP-activated protein kinase (AMPK), a known regulator of cellular and systemic energy balance, is now recognized to control cell division, cell polarity and cell migration, all of which depend on the actin cytoskeleton. Here we report the effects of A769662, a pharmacological activator of AMPK, on cytoskeletal organization and signalling in epithelial Madin-Darby canine kidney (MDCK) cells. We show that AMPK activation induced shortening or radiation of stress fibers, uncoupling from paxillin and predominance of cortical F-actin. In parallel, Rho-kinase downstream targets, namely myosin regulatory light chain and cofilin, were phosphorylated. These effects resembled the morphological changes in MDCK cells exposed to hyperosmotic shock, which led to Ca 2+ -dependent AMPK activation via calmodulin-dependent protein kinase kinase-β(CaMKKβ), a known upstream kinase of AMPK. Indeed, hypertonicity-induced AMPK activation was markedly reduced by the STO-609 CaMKKβ inhibitor, as was the increase in MLC and cofilin phosphorylation. We suggest that AMPK links osmotic stress to the reorganization of the actin cytoskeleton.

  7. Analysis of factors associated with injury severity in crashes involving young New Zealand drivers

    DEFF Research Database (Denmark)

    Weiss, Harold B.; Kaplan, Sigal; Prato, Carlo Giacomo

    2014-01-01

    measures within youth-oriented road safety programs. The current study estimates discrete choice models of injury severity of crashes involving young drivers conditional on these crashes having occurred. The analysis examined a comprehensive set of single-vehicle and two-vehicle crashes involving at least...

  8. Regulation of proximal tubule vacuolar H+-ATPase by PKA and AMP-activated protein kinase

    Science.gov (United States)

    Al-bataineh, Mohammad M.; Gong, Fan; Marciszyn, Allison L.; Myerburg, Michael M.

    2014-01-01

    The vacuolar H+-ATPase (V-ATPase) mediates ATP-driven H+ transport across membranes. This pump is present at the apical membrane of kidney proximal tubule cells and intercalated cells. Defects in the V-ATPase and in proximal tubule function can cause renal tubular acidosis. We examined the role of protein kinase A (PKA) and AMP-activated protein kinase (AMPK) in the regulation of the V-ATPase in the proximal tubule as these two kinases coregulate the V-ATPase in the collecting duct. As the proximal tubule V-ATPases have different subunit compositions from other nephron segments, we postulated that V-ATPase regulation in the proximal tubule could differ from other kidney tubule segments. Immunofluorescence labeling of rat ex vivo kidney slices revealed that the V-ATPase was present in the proximal tubule both at the apical pole, colocalizing with the brush-border marker wheat germ agglutinin, and in the cytosol when slices were incubated in buffer alone. When slices were incubated with a cAMP analog and a phosphodiesterase inhibitor, the V-ATPase accumulated at the apical pole of S3 segment cells. These PKA activators also increased V-ATPase apical membrane expression as well as the rate of V-ATPase-dependent extracellular acidification in S3 cell monolayers relative to untreated cells. However, the AMPK activator AICAR decreased PKA-induced V-ATPase apical accumulation in proximal tubules of kidney slices and decreased V-ATPase activity in S3 cell monolayers. Our results suggest that in proximal tubule the V-ATPase subcellular localization and activity are acutely coregulated via PKA downstream of hormonal signals and via AMPK downstream of metabolic stress. PMID:24553431

  9. Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin

    International Nuclear Information System (INIS)

    Yang, Chen-Chieh; Chang, Shun-Fu; Chao, Jian-Kang; Lai, Yi-Liang; Chang, Wei-En; Hsu, Wen-Hsiu; Kuo, Wu-Hsien

    2014-01-01

    Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects. Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs. These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis

  10. Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated protein kinase (AMPK.

    Directory of Open Access Journals (Sweden)

    Xiao Xiao Tang

    2010-08-01

    Full Text Available The tight junctions (TJs, characteristically located at the apicolateral borders of adjacent epithelial cells, are required for the proper formation of epithelial cell polarity as well as for sustaining the mucosal barrier to the external environment. The observation that lymphocytes are recruited by epithelial cells to the sites of infection [1] suggests that they may play a role in the modulation of epithelial barrier function and thus contribute to host defense. To test the ability of lymphocytes to modulate tight junction assembly in epithelial cells, we set up a lymphocyte-epithelial cell co-culture system, in which Madin-Darby canine kidney (MDCK cells, a well-established model cell line for studying epithelial TJ assembly [2], were co-cultured with mouse lymphocytes to mimic an infection state. In a typical calcium switch experiment, the TJ assembly in co-culture was found to be accelerated compared to that in MDCK cells alone. This accelaration was found to be mediated by AMP-activated protein kinase (AMPK. AMPK activation was independent of changes in cellular ATP levels but it was found to be activated by the pro-inflammatory cytokine TNF-alpha. Forced suppression of AMPK, either with a chemical inhibitor or by knockdown, abrogated the accelerating effect of lymphocytes on TJ formation. Similar results were also observed in a co-culture with lymphocytes and Calu-3 human airway epithelial cells, suggesting that the activation of AMPK may be a general mechanism underlying lymphocyte-accelerated TJ assembly in different epithelia. These results suggest that signals from lymphocytes, such as cytokines, facilitate TJ assembly in epithelial cells via the activation of AMPK.

  11. Histone acetyltransferase inhibitors antagonize AMP-activated protein kinase in postmortem glycolysis

    Directory of Open Access Journals (Sweden)

    Qiong Li

    2017-06-01

    Full Text Available Objective The purpose of this study was to investigate the influence of AMP-activated protein kinase (AMPK activation on protein acetylation and glycolysis in postmortem muscle to better understand the mechanism by which AMPK regulates postmortem glycolysis and meat quality. Methods A total of 32 mice were randomly assigned to four groups and intraperitoneally injected with 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR, a specific activator of AMPK, AICAR and histone acetyltransferase inhibitor II, or AICAR, Trichostatin A (TSA, an inhibitor of histone deacetylase I and II and Nicotinamide (NAM, an inhibitor of the Sirt family deacetylases. After mice were euthanized, the Longissimus dorsi muscle was collected at 0 h, 45 min, and 24 h postmortem. AMPK activity, protein acetylation and glycolysis in postmortem muscle were measured. Results Activation of AMPK by AICAR significantly increased glycolysis in postmortem muscle. At the same time, it increased the total acetylated proteins in muscle 45 min postmortem. Inhibition of protein acetylation by histone acetyltransferase inhibitors reduced AMPK activation induced increase in the total acetylated proteins and glycolytic rate in muscle early postmortem, while histone deacetylase inhibitors further promoted protein acetylation and glycolysis. Several bands of proteins were detected to be differentially acetylated in muscle with different glycolytic rates. Conclusion Protein acetylation plays an important regulatory role in postmortem glycolysis. As AMPK mediates the effects of pre-slaughter stress on postmortem glycolysis, protein acetylation is likely a mechanism by which antemortem stress influenced postmortem metabolism and meat quality though the exact mechanism is to be elucidated.

  12. Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation*

    Science.gov (United States)

    Sundararaman, Ananthalakshmy; Amirtham, Usha; Rangarajan, Annapoorni

    2016-01-01

    The AMP-activated protein kinase (AMPK) has recently been implicated in anoikis resistance. However, the molecular mechanisms that activate AMPK upon matrix detachment remain unexplored. In this study, we show that AMPK activation is a rapid and sustained phenomenon upon matrix deprivation, whereas re-attachment to the matrix leads to its dephosphorylation and inactivation. Because matrix detachment leads to loss of integrin signaling, we investigated whether integrin signaling negatively regulates AMPK activation. However, modulation of focal adhesion kinase or Src, the major downstream components of integrin signaling, failed to cause a corresponding change in AMPK signaling. Further investigations revealed that the upstream AMPK kinases liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) contribute to AMPK activation upon detachment. In LKB1-deficient cells, we found AMPK activation to be predominantly dependent on CaMKKβ. We observed no change in ATP levels under detached conditions at early time points suggesting that rapid AMPK activation upon detachment was not triggered by energy stress. We demonstrate that matrix deprivation leads to a spike in intracellular calcium as well as oxidant signaling, and both these intracellular messengers contribute to rapid AMPK activation upon detachment. We further show that endoplasmic reticulum calcium release-induced store-operated calcium entry contributes to intracellular calcium increase, leading to reactive oxygen species production, and AMPK activation. We additionally show that the LKB1/CaMKK-AMPK axis and intracellular calcium levels play a critical role in anchorage-independent cancer sphere formation. Thus, the Ca2+/reactive oxygen species-triggered LKB1/CaMKK-AMPK signaling cascade may provide a quick, adaptable switch to promote survival of metastasizing cancer cells. PMID:27226623

  13. AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue

    Science.gov (United States)

    Wu, Lingyan; Zhang, Lina; Li, Bohan; Jiang, Haowen; Duan, Yanan; Xie, Zhifu; Shuai, Lin; Li, Jia; Li, Jingya

    2018-01-01

    Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic “brown-like” cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK α1/α2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a β3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPKα induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively

  14. Elevated NF-κB activation is conserved in human myocytes cultured from obese type 2 diabetic patients and attenuated by AMP-activated protein kinase

    DEFF Research Database (Denmark)

    Green, Charlotte Jane; Pedersen, Maria; Pedersen, Bente K

    2011-01-01

    To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes....

  15. Involvement of immune-related factors in diclofenac-induced acute liver injury in mice

    International Nuclear Information System (INIS)

    Yano, Azusa; Higuchi, Satonori; Tsuneyama, Koichi; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-01-01

    Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical drug therapy. However, the underlying mechanism of DILI is little known. It is difficult to predict DILI in humans due to the lack of experimental animal models. Diclofenac, a non-steroidal anti-inflammatory drug rarely causes severe liver injury in human, but there is some evidence for immunoallergic idiosyncratic reactions. In this study, the mechanism of diclofenac-induced liver injury in mice was investigated. First, we established the dosing condition for liver injury in normal mice. Plasma ALT and AST levels were significantly increased in diclofenac-administered (80 mg/kg, i.p.) mice in a dose- and time-dependent manner. Among several interleukins (ILs) and chemokines, mRNA expression of helper T (Th) 17 cell-mediated factors, such as retinoid orphan receptor (ROR)-γt, and signal transducers and activators of transcription factor (STAT) 3 in the liver, and the plasma IL-17 level were significantly increased. Neutralization of IL-17 tended to suppress the hepatotoxicity of diclofenac, suggesting that IL-17 was partly involved. Gadolinium chloride (GdCl 3 ) administration demonstrated that Kupffer cells are not likely to be involved in diclofenac hepatotoxicity. Hepatic expressions of IL-1β mRNA and plasma IL-1β were significantly increased soon after the diclofenac administration. Then, the results of an in vivo neutralization study of IL-1β suggested that IL-1β was involved early in the time of pathogenesis of the diclofenac-induced liver injury. In conclusion, we firstly developed a diclofenac-induced acute liver injury model in normal mice, and the involvement of IL-17 and IL-1β was clarified.

  16. Involvement of immune-related factors in diclofenac-induced acute liver injury in mice.

    Science.gov (United States)

    Yano, Azusa; Higuchi, Satonori; Tsuneyama, Koichi; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-03-11

    Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical drug therapy. However, the underlying mechanism of DILI is little known. It is difficult to predict DILI in humans due to the lack of experimental animal models. Diclofenac, a non-steroidal anti-inflammatory drug rarely causes severe liver injury in human, but there is some evidence for immunoallergic idiosyncratic reactions. In this study, the mechanism of diclofenac-induced liver injury in mice was investigated. First, we established the dosing condition for liver injury in normal mice. Plasma ALT and AST levels were significantly increased in diclofenac-administered (80 mg/kg, i.p.) mice in a dose- and time-dependent manner. Among several interleukins (ILs) and chemokines, mRNA expression of helper T (Th) 17 cell-mediated factors, such as retinoid orphan receptor (ROR)-γt, and signal transducers and activators of transcription factor (STAT) 3 in the liver, and the plasma IL-17 level were significantly increased. Neutralization of IL-17 tended to suppress the hepatotoxicity of diclofenac, suggesting that IL-17 was partly involved. Gadolinium chloride (GdCl₃) administration demonstrated that Kupffer cells are not likely to be involved in diclofenac hepatotoxicity. Hepatic expressions of IL-1β mRNA and plasma IL-1β were significantly increased soon after the diclofenac administration. Then, the results of an in vivo neutralization study of IL-1β suggested that IL-1β was involved early in the time of pathogenesis of the diclofenac-induced liver injury. In conclusion, we firstly developed a diclofenac-induced acute liver injury model in normal mice, and the involvement of IL-17 and IL-1β was clarified. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

    Science.gov (United States)

    Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

  18. Fatal injuries in the United States construction industry involving cranes 1984-1994.

    Science.gov (United States)

    Suruda, A; Liu, D; Egger, M; Lillquist, D

    1999-12-01

    There is little published information concerning the epidemiology of injuries in the construction industry involving cranes other than for electrical injury from power line contact. For the 11-year period of 1984 through 1994, the US Occupational Safety and Health Administration (OSHA) investigated 502 deaths in 479 incidents involving cranes in the construction industry. Electrocution was the largest category, with 198 deaths (39%) reported. Other major categories were assembly/dismantling (58 deaths, 12%), boom buckling (41 deaths, 8%), crane upset/overturn (37 deaths, 7%), and rigging failure (36 deaths, 7%). The majority of the deaths during assembly/dismantling involved removal of the boom pins from lattice boom cranes. Only 34% of the construction firms employing the fatally injured workers had ever been inspected by OSHA. OSHA cited the employer for safety violations in 436 deaths (83%). Additional worker training, increased OSHA inspections, and crane inspection programs could prevent many crane-related deaths.

  19. Possible involvement of AMP-activated protein kinase in obesity resistance induced by respiratory uncoupling in white fat

    Czech Academy of Sciences Publication Activity Database

    Matějková, Olga; Mustard, K. J.; Šponarová, Jana; Flachs, Pavel; Rossmeisl, Martin; Mikšík, Ivan; Thomason-Hughes, M.; Hardie, D. G.; Kopecký, Jan

    2004-01-01

    Roč. 569, č. 1-3 (2004), s. 245-248 ISSN 0014-5793 R&D Projects: GA ČR GA303/02/1220; GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5011922 Keywords : ATP * lipid metabolism * mitochondrion Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.843, year: 2004

  20. The cAMP-activated GTP exchange factor, Epac1 Upregulates Plasma Membrane and Nuclear Akt Kinase Activities in 8-CPT-2-O-Me-cAMP-Stimulated Macrophages: Gene silencing of the cAMP-activated GTP exchange Epac1 prevents 8-CPT-2-O-Me-cAMP activation of Akt activity in macrophages*

    OpenAIRE

    Misra, Uma K.; Kaczowka, Steven; Pizzo, Salvatore V.

    2008-01-01

    cAMP regulates a wide range of processes through its downstream effectors including PKA, and the family of guanine nucleotide exchange factors. Depending on the cell type, cAMP inhibits or stimulates growth and proliferation in a PKA-dependent or independent manner. PKA-independent effects are mediated by PI 3-kinases-Akt signaling and EPAC1 (exchange protein directly activated by cAMP) activation. Recently, we reported PKA-independent activation of the protein kinase Akt as well co-immunopre...

  1. Early surgical managment of penetrating ocular injuries involving the posterior segment.

    Science.gov (United States)

    Michels, R G

    1976-09-01

    Pars plana vitrectomy technic can be used in the early management of certain penetrating ocular injuries involving the posterior segment, including selected intraocular foreign bodies. This study reports the results of ten consecutive cases of intraocular foreign bodies in the posterior segment treated by a combination of vitrectomy (including lensectomy when necessary) and foreign-body extraction with forceps. The foreign body was successfully removed in nine of ten eyes, and nine of ten eyes were salvaged. This favorable experience using early vitreous surgery suggests that the vitrectomy technic can be used in other penetrating injuries involving the posterior segment that are not associated with intraocular foreign bodies. Possible indications for early vitrectomy are presented, including cases with a poor prognosis when managed by conventional methods.

  2. Intramuscular tendon involvement on MRI has limited value for predicting time to return to play following acute hamstring injury.

    Science.gov (United States)

    van der Made, Anne D; Almusa, Emad; Whiteley, Rod; Hamilton, Bruce; Eirale, Cristiano; van Hellemondt, Frank; Tol, Johannes L

    2018-01-01

    Hamstring injury with intramuscular tendon involvement is regarded as a serious injury with a delay in return to play (RTP) of more than 50 days and reinjury rates up to 63%. However, this reputation is based on retrospective case series with high risk of bias. Determine whether intramuscular tendon involvement is associated with delayed RTP and elevated rates of reinjury. MRI of male athletes with an acute hamstring injury was obtained within 5 days of injury. Evaluation included standardised MRI scoring and scoring of intramuscular tendon involvement. Time to RTP and reinjury rate were prospectively recorded. Out of 70 included participants, intramuscular tendon disruption was present in 29 (41.4%) injuries. Injuries without intramuscular tendon disruption had a mean time to RTP of 22.2±7.4 days. Injuries with Injuries with full-thickness disruption took longer to RTP compared with injuries without disruption (p=0.025). Longitudinal intramuscular tendon disruption was not significantly associated with time to RTP. Waviness was present in 17 (24.3%) injuries. Mean time to RTP for injuries without and with waviness was 22.6±7.5 and 30.2±10.8 days (p=0.014). There were 11 (15.7%) reinjuries within 12 months, five (17.2%) in the group with intramuscular tendon disruption and six (14.6%) in the group without intramuscular tendon disruption. Time to RTP for injuries with full-thickness disruption of the intramuscular tendon and waviness is significantly longer (by slightly more than 1 week) compared with injuries without intramuscular tendon involvement. However, due to the considerable overlap in time to RTP between groups with and without intramuscular tendon involvement, its clinical significance for the individual athlete is limited. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. AMP-Activated Protein Kinase Alleviates Extracellular Matrix Accumulation in High Glucose-Induced Renal Fibroblasts through mTOR Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xia Luo

    2015-01-01

    Full Text Available Background/Aims: Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined. Methods: Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f. Results: Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1312 (encoding constitutively active AMPKα1 whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1. In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Conclusion: Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.

  4. AMP-Activated Protein Kinase Interacts with the Peroxisome Proliferator-Activated Receptor Delta to Induce Genes Affecting Fatty Acid Oxidation in Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Marina Kemmerer

    Full Text Available AMP-activated protein kinase (AMPK maintains energy homeostasis by suppressing cellular ATP-consuming processes and activating catabolic, ATP-producing pathways such as fatty acid oxidation (FAO. The transcription factor peroxisome proliferator-activated receptor δ (PPARδ also affects fatty acid metabolism, stimulating the expression of genes involved in FAO. To question the interplay of AMPK and PPARδ in human macrophages we transduced primary human macrophages with lentiviral particles encoding for the constitutively active AMPKα1 catalytic subunit, followed by microarray expression analysis after treatment with the PPARδ agonist GW501516. Microarray analysis showed that co-activation of AMPK and PPARδ increased expression of FAO genes, which were validated by quantitative PCR. Induction of these FAO-associated genes was also observed upon infecting macrophages with an adenovirus coding for AMPKγ1 regulatory subunit carrying an activating R70Q mutation. The pharmacological AMPK activator A-769662 increased expression of several FAO genes in a PPARδ- and AMPK-dependent manner. Although GW501516 significantly increased FAO and reduced the triglyceride amount in very low density lipoproteins (VLDL-loaded foam cells, AMPK activation failed to potentiate this effect, suggesting that increased expression of fatty acid catabolic genes alone may be not sufficient to prevent macrophage lipid overload.

  5. Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway.

    Science.gov (United States)

    Kurokawa, Hirofumi; Sugiyama, Seigo; Nozaki, Toshimitsu; Sugamura, Koichi; Toyama, Kensuke; Matsubara, Junichi; Fujisue, Koichiro; Ohba, Keisuke; Maeda, Hirofumi; Konishi, Masaaki; Akiyama, Eiichi; Sumida, Hitoshi; Izumiya, Yasuhiro; Yasuda, Osamu; Kim-Mitsuyama, Shokei; Ogawa, Hisao

    2015-04-01

    Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs). In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK. Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Oral glucose ingestion attenuates exercise-induced activation of 5'-AMP-activated protein kinase in human skeletal muscle

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Birk, Jesper Bratz; Klein, Ditte Kjærsgaard

    2006-01-01

    5'-AMP-activated protein kinase (AMPK) has been suggested to be a 'metabolic master switch' regulating various aspects of muscle glucose and fat metabolism. In isolated rat skeletal muscle, glucose suppresses the activity of AMPK and in human muscle glycogen loading decreases exercise-induced AMPK...... activation. We hypothesized that oral glucose ingestion during exercise would attenuate muscle AMPK activation. Nine male subjects performed two bouts of one-legged knee-extensor exercise at 60% of maximal workload. The subjects were randomly assigned to either consume a glucose containing drink or a placebo...... drink during the two trials. Muscle biopsies were taken from the vastus lateralis before and after 2 h of exercise. Plasma glucose was higher (6.0 +/- 0.2 vs. 4.9 +/- 0.1 mmol L-1, P

  7. AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD

    DEFF Research Database (Denmark)

    Brandauer, Josef; Andersen, Marianne A; Kellezi, Holti

    2015-01-01

    , the acetylation status of SIRT3 target lysine residues on MnSOD (K122) or oligomycin-sensitivity conferring protein (OSCP; K139) was not altered in either mouse or human skeletal muscle in response to acute exercise. We propose an important role for AMPK in regulating mitochondrial function and ROS handling......The mitochondrial protein deacetylase sirtuin (SIRT) 3 may mediate exercise training-induced increases in mitochondrial biogenesis and improvements in reactive oxygen species (ROS) handling. We determined the requirement of AMP-activated protein kinase (AMPK) for exercise training-induced increases...... in skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise training for 6.5 weeks increased SIRT3 (p

  8. 5'AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes

    DEFF Research Database (Denmark)

    Wojtaszewski, Jørgen; Birk, Jesper Bratz; Frøsig, Christian

    2005-01-01

    adaptations within the AMPK system itself. We investigated the effect of strength training and T2DM on the isoform expression and the heterotrimeric composition of the AMPK in human skeletal muscle. Ten patients with T2DM and seven healthy subjects strength trained (T) one leg for 6 weeks, while the other leg......Strength training enhances insulin sensitivity and represents an alternative to endurance training for patients with type 2 diabetes (T2DM). The 5'AMP-activated protein kinase (AMPK) may mediate adaptations in skeletal muscle in response to exercise training; however, little is known about...... remained untrained (UT). Muscle biopsies were obtained before and after the training period. Basal AMPK activity and protein/mRNA expression of both catalytic (alpha1 and alpha2) and regulatory (beta1, beta2, gamma1, gamma2a, gamma2b and gamma3) AMPK isoforms were independent of T2DM, whereas the protein...

  9. AMP-Activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Yen-Hsing Li

    2015-07-01

    Full Text Available The Hedgehog (Hh pathway regulates cell differentiation and proliferation during development by controlling the Gli transcription factors. Cell fate decisions and progression toward organ and tissue maturity must be coordinated, and how an energy sensor regulates the Hh pathway is not clear. AMP-activated protein kinase (AMPK is an important sensor of energy stores and controls protein synthesis and other energy-intensive processes. AMPK is directly responsive to intracellular AMP levels, inhibiting a wide range of cell activities if ATP is low and AMP is high. Thus, AMPK can affect development by influencing protein synthesis and other processes needed for growth and differentiation. Activation of AMPK reduces GLI1 protein levels and stability, thus blocking Sonic-hedgehog-induced transcriptional activity. AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

  10. Intramuscular tendon involvement on MRI has limited value for predicting time to return to play following acute hamstring injury

    NARCIS (Netherlands)

    van der Made, Anne D.; Almusa, Emad; Whiteley, Rod; Hamilton, Bruce; Eirale, Cristiano; van Hellemondt, Frank; Tol, Johannes L.

    2018-01-01

    Background Hamstring injury with intramuscular tendon involvement is regarded as a serious injury with a delay in return to play (RTP) of more than 50 days and reinjury rates up to 63%. However, this reputation is based on retrospective case series with high risk of bias. Objective Determine whether

  11. Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway.

    Directory of Open Access Journals (Sweden)

    Jingxian Wu

    Full Text Available Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of curcumin against experimental stroke. Oxygen and glucose deprivation/reoxygenation (OGD/R was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular expression of NAD(PH: quinone oxidoreductase1 (NQO1 induced by OGD was counteracted by curcumin post-treatment, which paralleled attenuated cell injury. The reduction of phosphorylation Akt induced by OGD was restored by curcumin. Consequently, NQO1 expression and the binding activity of nuclear factor-erythroid 2-related factor 2 (Nrf2 to antioxidant response element (ARE were increased. LY294002 blocked the increase in phospho-Akt evoked by curcumin and abolished the associated protective effect. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 60 minutes. Curcumin administration significantly reduced infarct size. Curcumin also markedly reduced oxidative stress levels in middle cerebral artery occlusion (MCAO rats; hence, these effects were all suppressed by LY294002. Taken together, these findings provide evidence that curcumin protects neurons against ischemic injury, and this neuroprotective effect involves the Akt/Nrf2 pathway. In addition, Nrf2 is involved in the neuroprotective effects of curcumin against oxidative damage.

  12. Neuroprotection by Curcumin in Ischemic Brain Injury Involves the Akt/Nrf2 Pathway

    Science.gov (United States)

    Wu, Jingxian; Li, Qiong; Wang, Xiaoyan; Yu, Shanshan; Li, Lan; Wu, Xuemei; Chen, Yanlin; Zhao, Jing; Zhao, Yong

    2013-01-01

    Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of curcumin against experimental stroke. Oxygen and glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular expression of NAD(P)H: quinone oxidoreductase1 (NQO1) induced by OGD was counteracted by curcumin post-treatment, which paralleled attenuated cell injury. The reduction of phosphorylation Akt induced by OGD was restored by curcumin. Consequently, NQO1 expression and the binding activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) to antioxidant response element (ARE) were increased. LY294002 blocked the increase in phospho-Akt evoked by curcumin and abolished the associated protective effect. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 60 minutes. Curcumin administration significantly reduced infarct size. Curcumin also markedly reduced oxidative stress levels in middle cerebral artery occlusion (MCAO) rats; hence, these effects were all suppressed by LY294002. Taken together, these findings provide evidence that curcumin protects neurons against ischemic injury, and this neuroprotective effect involves the Akt/Nrf2 pathway. In addition, Nrf2 is involved in the neuroprotective effects of curcumin against oxidative damage. PMID:23555802

  13. Swordfish bill injury involving abdomen and vertebral column: case report and review

    Directory of Open Access Journals (Sweden)

    Drossos Charalambos

    2010-10-01

    Full Text Available Abstract Background Penetrating injuries of the abdomen and spinal canal that involve organic material of animal origin are extremely rare and derive from domestic and wild animal attacks or fish attacks. Case presentation In this case report we present the unique, as far as the literature is concerned, unprovoked woman's injury to the abdomen by a swordfish. There are only four cases of swordfish attacks on humans in the literature - one resulted to thoracic trauma, two to head trauma and one to knee trauma, one of which was fatal - none of which were unprovoked. Three victims were professional or amateur fishermen whereas in the last reported case the victim was a bather as in our case. Our case is the only case where organic debris of animal's origin remained in the spinal canal after penetrating trauma. Conclusions Although much has been written about the management of penetrating abdominal and spinal cord trauma, controversy remains about the optimal management. Moreover, there is little experience in the management of patients with such spinal injuries, due to the fact that such cases are extremely rare. In this report we focus on the patient's treatment with regard to abdominal and spinal trauma and present a review of the literature.

  14. Specific deletion of AMP-activated protein kinase (α1AMPK in murine oocytes alters junctional protein expression and mitochondrial physiology.

    Directory of Open Access Journals (Sweden)

    Michael J Bertoldo

    Full Text Available Oogenesis and folliculogenesis are dynamic processes that are regulated by endocrine, paracrine and autocrine signals. These signals are exchanged between the oocyte and the somatic cells of the follicle. Here we analyzed the role of AMP-activated protein kinase (AMPK, an important regulator of cellular energy homeostasis, by using transgenic mice deficient in α1AMPK specifically in the oocyte. We found a decrease of 27% in litter size was observed in ZP3-α1AMPK-/- (ZP3-KO female mice. Following in vitro fertilization, where conditions are stressful for the oocyte and embryo, ZP3-KO oocytes were 68% less likely to pass the 2-cell stage. In vivo and in cumulus-oocyte complexes, several proteins involved in junctional communication, such as connexin37 and N-cadherin were down-regulated in the absence of α1AMPK. While the two signalling pathways (PKA and MAPK involved in the junctional communication between the cumulus/granulosa cells and the oocyte were stimulated in control oocytes, ZP3-KO oocytes exhibited only low phosphorylation of MAPK or CREB proteins. In addition, MII oocytes deficient in α1AMPK had a 3-fold lower ATP concentration, an increase in abnormal mitochondria, and a decrease in cytochrome C and PGC1α levels, suggesting perturbed energy production by mitochondria. The absence of α1AMPK also induced a reduction in histone deacetylase activity, which was associated with an increase in histone H3 acetylation (K9/K14 residues. Together, the results of the present study suggest that absence of AMPK, modifies oocyte quality through energy processes and oocyte/somatic cell communication. The limited effect observed in vivo could be partly due to a favourable follicle microenvironment where nutrients, growth factors, and adequate cell interaction were present. Whereas in a challenging environment such as that of in vitro culture following IVF, the phenotype is revealed.

  15. Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats.

    Science.gov (United States)

    Shiotani, Satoko; Shimada, Mitsuo; Suehiro, Taketoshi; Soejima, Yuji; Yosizumi, Tomoharu; Shimokawa, Hiroaki; Maehara, Yoshihiko

    2004-08-15

    Reperfusion of ischemic tissues is known to cause the generation of reactive oxygen species (ROS) with resultant tissue damage. However, the sources of ROS in reperfused tissues are not fully characterized. We hypothesized that the small GTPase Rho and its target effector Rho-kinase/ROK/ROCK are involved in the oxidative burst in reperfused tissue with resultant reperfusion injury. In an in vivo rat model of liver transplantation using cold ischemia for 12 hr followed by reperfusion, a specific Rho-kinase inhibitor, fasudil (30 mg/kg), was administered orally 1 hr before the transplantation. Fasudil suppressed the ischemia-reperfusion (I/R)-induced generation of ROS after reperfusion (P<0.01) and also suppressed the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) 3 hr after reperfusion, resulting in a significant reduction of I/R-induced hepatocellular injury (P<0.05), necrosis, apoptosis (P<0.01), and neutrophil infiltration (P<0.0001) 12 hr after reperfusion. All animals receiving a graft without fasudil died within 3 days, whereas 40% of those receiving fasudil survived (P<0.001). The present study demonstrates that Rho-kinase-mediated production of ROS and inflammatory cytokines are substantially involved in the pathogenesis of hepatocellular necrosis and apoptosis induced by cold I/R in vivo and that Rho-kinase may be regarded as a novel therapeutic target for the disorder.

  16. The alpha2-5'AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian B; Nielsen, Jakob N.; Birk, Jesper Bratz

    2004-01-01

    The 5'AMP-activated protein kinase (AMPK) is a potential antidiabetic drug target. Here we show that the pharmacological activation of AMPK by 5-aminoimidazole-1-beta-4-carboxamide ribofuranoside (AICAR) leads to inactivation of glycogen synthase (GS) and phosphorylation of GS at Ser 7 (site 2). ...

  17. Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation

    DEFF Research Database (Denmark)

    Mancini, Sarah J; White, Anna D; Bijland, Silvia

    2017-01-01

    Inflammation of adipose tissue in obesity is associated with increased IL-1β, IL-6 and TNF-α secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-inflammatory actions in adipose tissue, yet the m...

  18. AMP activated protein kinase α2 controls substrate metabolism during post-exercise recovery via regulation of pyruvate dehydrogenase kinase 4

    DEFF Research Database (Denmark)

    Fritzen, Andreas Mæchel; Lundsgaard, Annemarie; Jeppesen, Jacob

    2015-01-01

    after prolonged exercise and during the following six hours post exercise in 5´AMP activated protein kinase (AMPK)α2 and α1 knock-out (KO) and wild type (WT) mice with free access to food. Substrate oxidation was similar during exercise at the same relative intensity between genotypes. During post...

  19. Nordihydroguaiaretic acid protects against high-fat diet-induced fatty liver by activating AMP-activated protein kinase in obese mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung-Su; Kim, Daeyoung; Jo, Keunae [Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Hwang, Jae-Kwan, E-mail: jkhwang@yonsei.ac.kr [Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Translational Research Center for Protein Function Control, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)

    2010-10-08

    Research highlights: {yields} NDGA decreases high-fat diet-induced body weight gain and adiposity. {yields} NDGA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} NDGA improves lipid storage in vitro through altering lipid regulatory proteins. {yields} Inhibition of lipid storage in vivo and in vitro is mediated by AMPK activation. -- Abstract: Nonalcoholic fatty liver disease, one of the most common causes of chronic liver disease, is strongly associated with metabolic syndrome. Nordihydroguaiaretic acid (NDGA) has been reported to inhibit lipoprotein lipase; however, the effect of NDGA on hepatic lipid metabolism remains unclear. We evaluated body weight, adiposity, liver histology, and hepatic triglyceride content in high-fat diet (HFD)-fed C57BL/6J mice treated with NDGA. In addition, we characterized the underlying mechanism of NDGA's effects in HepG2 hepatocytes by Western blot and RT-PCR analysis. NDGA (100 or 200 mg/kg/day) reduced weight gain, fat pad mass, and hepatic triglyceride accumulation, and improved serum lipid parameters in mice fed a HFD for 8 weeks. NDGA significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the liver and in HepG2 hepatocytes. NDGA downregulated the level of mature SREBP-1 and its target genes (acetyl-CoA carboxylase and fatty acid synthase), but, it upregulated expression of genes involved in fatty acid oxidation, such as peroxisome proliferator-activated receptor (PPAR){alpha}, PPAR{gamma} coactivator-1, carnitine palmitoyl transferase-1, and uncoupling protein-2. The specific AMPK inhibitor compound C attenuated the effects of NDGA on expression of lipid metabolism-related proteins in HepG2 hepatocytes. The beneficial effects of NDGA on HFD-induced hepatic triglyceride accumulation are mediated through AMPK signaling pathways, suggesting a potential target for preventing NAFLD.

  20. In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway.

    Science.gov (United States)

    Pantovic, Aleksandar; Bosnjak, Mihajlo; Arsikin, Katarina; Kosic, Milica; Mandic, Milos; Ristic, Biljana; Tosic, Jelena; Grujicic, Danica; Isakovic, Aleksandra; Micic, Nikola; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2017-02-01

    We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and G 2 M cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis. Indomethacin increased the phosphorylation of AMPK and its targets Raptor and acetyl-CoA carboxylase (ACC), and reduced the phosphorylation of mTOR and mTOR complex 1 (mTORC1) substrates p70S6 kinase and PRAS40 (Ser183). AMPK knockdown by RNA interference, as well as the treatment with the mTORC1 activator leucine, prevented indomethacin-mediated mTORC1 inhibition and cytotoxic action, while AMPK activators metformin and AICAR mimicked the effects of the drug. AMPK activation by indomethacin correlated with intracellular ATP depletion and increase in AMP/ATP ratio, and was apparently independent of COX inhibition or the increase in intracellular calcium. Finally, the toxicity of indomethacin towards primary human glioma cells was associated with the activation of AMPK/Raptor/ACC and subsequent suppression of mTORC1/S6K. By demonstrating the involvement of AMPK/mTORC1 pathway in the antiglioma action of indomethacin, our results support its further exploration in glioma therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Resveratrol-Induced AMP-Activated Protein Kinase Activation Is Cell-Type Dependent: Lessons from Basic Research for Clinical Application.

    Science.gov (United States)

    Lan, Fan; Weikel, Karen A; Cacicedo, Jose M; Ido, Yasuo

    2017-07-14

    Despite the promising effects of resveratrol, its efficacy in the clinic remains controversial. We were the first group to report that the SIRT1 activator resveratrol activates AMP-activated protein kinase (AMPK) (Diabetes 2005; 54: A383), and we think that the variability of this cascade may be responsible for the inconsistency of resveratrol's effects. Our current studies suggest that the effect of SIRT1 activators such as resveratrol may not be solely through activation of SIRT1, but also through an integrated effect of SIRT1-liver kinase B1 (LKB1)-AMPK. In this context, resveratrol activates SIRT1 (1) by directly binding to SIRT1; and (2) by increasing NAD⁺ levels by upregulating the salvage pathway through Nampt activation, an effect mediated by AMPK. The first mechanism promotes deacetylation of a limited number of SIRT1 substrate proteins (e.g., PGC-1). The second mechanism (which may be more important than the first) activates other sirtuins in addition to SIRT1, which affects a broad spectrum of substrates. Despite these findings, detailed mechanisms of how resveratrol activates AMPK have not been reported. Here, we show that (1) resveratrol-induced activation of AMPK requires the presence of functional LKB1; (2) Resveratrol increases LKB1 activity, which involves translocation and phosphorylation at T336 and S428; (3) Activation of LKB1 causes proteasomal degradation of LKB1; (4) At high concentrations (50-100 µM), resveratrol also activates AMPK through increasing AMP levels; and (5) The above-mentioned activation mechanisms vary among cell types, and in some cell types, resveratrol fails to activate AMPK. These results suggest that resveratrol-induced activation of AMPK is not a ubiquitous phenomenon. In addition, AMPK-mediated increases in NAD⁺ in the second mechanism require several ATPs, which may not be available in many pathological conditions. These phenomena may explain why resveratrol is not always consistently beneficial in a clinical

  2. Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

    International Nuclear Information System (INIS)

    Hwang, Yong Pil; Kim, Hyung Gyun; Hien, Tran Thi; Jeong, Myung Ho; Jeong, Tae Cheon; Jeong, Hye Gwang

    2011-01-01

    The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-α-stimulated monocytes to endothelial cells and suppressed the TNF-α induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-α-induced nuclear factor-κB activation, which was attenuated by pretreatment with N G -nitro-L-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease. -- Highlights: ► Puerarin induced the phosphorylation of eNOS and the production of NO. ► Puerarin activated eNOS through ER-dependent PI3-kinase and Ca 2+ -dependent AMPK. ► Puerarin-induced NO was involved in the inhibition of NF-kB activation. ► Puerarin may help for prevention of vascular dysfunction and diabetes.

  3. Inhibition of Cholesterol Synthesis in HepG2 Cells by GINST-Decreasing HMG-CoA Reductase Expression Via AMP-Activated Protein Kinase.

    Science.gov (United States)

    Han, Joon-Seung; Sung, Jong Hwan; Lee, Seung Kwon

    2017-11-01

    GINST, a hydrolyzed ginseng extract, has been reported to have antidiabetic effects and to reduce hyperglycemia and hyperlipidemia. Hypercholesterolemia is caused by diet or genetic factors and can lead to atherosclerosis and coronary heart disease. Thus, the purpose of this study is to determine whether GINST and the ginsenoside metabolite, IH-901 (compound K), reduce cholesterol synthesis in HepG2 cells and the signal transduction pathways involved. Concentrations of cholesterol were measured by using an enzymatic method. Expression levels of sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR), peroxisome proliferators-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins α (C/EBPα), GAPDH, and phosphorylation of AMP-activated protein kinase α (AMPKα), protein kinase B (PKB, also known as Akt), and mechanistic target of rapamycin complex 1 (mTORC1) were measured using western blot. Total cholesterol concentration decreased after GINST treatment for 24 and 48 h. Expression of HMGCR decreased more with GINST than with the inhibitors, U18666A and atorvastatin, after 48 h in a dose-dependent manner. Phosphorylation of AMPKα increased 2.5x by GINST after 360 min of treatment, and phosphorylation of Akt decreased after 120 and 360 min. We separated compound K from GINST extracts flash chromatography. Compound K decreased cholesterol synthesis in HepG2 cells at 24 and 48 h. Therefore, we conclude that GINST inhibits cholesterol synthesis in HepG2 cells by decreasing HMGCR expression via AMPKα activation. GINST, a hydrolyzed ginseng extract, can inhibit cholesterol synthesis in liver cells via activation of AMPKα. IH-901 (compound K), which is the main component with bioactivity in GINST, also has anticholesterol effects. Thus, we suggest that GINST can be used to reduce hypercholesterolemia. © 2017 Institute of Food Technologists®.

  4. Phosphorylation of translation factors in response to anoxia in turtles, Trachemys scripta elegans: role of the AMP-activated protein kinase and target of rapamycin signalling pathways.

    Science.gov (United States)

    Rider, Mark H; Hussain, Nusrat; Dilworth, Stephen M; Storey, Kenneth B

    2009-12-01

    Long-term survival of oxygen deprivation by animals with well-developed anoxia tolerance depends on multiple biochemical adaptations including strong metabolic rate depression. We investigated whether the AMP-activated protein kinase (AMPK) could play a regulatory role in the suppression of protein synthesis that occurs when turtles experience anoxic conditions. AMPK activity and the phosphorylation state of ribosomal translation factors were measured in liver, heart, red muscle and white muscle of red-eared slider turtles (Trachemys scripta elegans) subjected to 20 h of anoxic submergence. AMPK activity increased twofold in white muscle of anoxic turtles compared with aerobic controls but remained unchanged in liver and red muscle, whereas in heart AMPK activity decreased by 40%. Immunoblotting with phospho-specific antibodies revealed that eukaryotic elongation factor-2 phosphorylation at the inactivating Thr56 site increased six- and eightfold in red and white muscles from anoxic animals, respectively, but was unchanged in liver and heart. The phosphorylation state of the activating Thr389 site of p70 ribosomal protein S6 kinase was reduced under anoxia in red muscle and heart but was unaffected in liver and white muscle. Exposure to anoxia decreased 40S ribosomal protein S6 phosphorylation in heart and promoted eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) dephosphorylation in red muscle, but surprisingly increased 4E-BP1 phosphorylation in white muscle. The changes in phosphorylation state of translation factors suggest that organ-specific patterns of signalling and response are involved in achieving the anoxia-induced suppression of protein synthesis in turtles.

  5. Nordihydroguaiaretic acid protects against high-fat diet-induced fatty liver by activating AMP-activated protein kinase in obese mice

    International Nuclear Information System (INIS)

    Lee, Myoung-Su; Kim, Daeyoung; Jo, Keunae; Hwang, Jae-Kwan

    2010-01-01

    Research highlights: → NDGA decreases high-fat diet-induced body weight gain and adiposity. → NDGA reduces high-fat diet-induced triglyceride accumulation in liver. → NDGA improves lipid storage in vitro through altering lipid regulatory proteins. → Inhibition of lipid storage in vivo and in vitro is mediated by AMPK activation. -- Abstract: Nonalcoholic fatty liver disease, one of the most common causes of chronic liver disease, is strongly associated with metabolic syndrome. Nordihydroguaiaretic acid (NDGA) has been reported to inhibit lipoprotein lipase; however, the effect of NDGA on hepatic lipid metabolism remains unclear. We evaluated body weight, adiposity, liver histology, and hepatic triglyceride content in high-fat diet (HFD)-fed C57BL/6J mice treated with NDGA. In addition, we characterized the underlying mechanism of NDGA's effects in HepG2 hepatocytes by Western blot and RT-PCR analysis. NDGA (100 or 200 mg/kg/day) reduced weight gain, fat pad mass, and hepatic triglyceride accumulation, and improved serum lipid parameters in mice fed a HFD for 8 weeks. NDGA significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the liver and in HepG2 hepatocytes. NDGA downregulated the level of mature SREBP-1 and its target genes (acetyl-CoA carboxylase and fatty acid synthase), but, it upregulated expression of genes involved in fatty acid oxidation, such as peroxisome proliferator-activated receptor (PPAR)α, PPARγ coactivator-1, carnitine palmitoyl transferase-1, and uncoupling protein-2. The specific AMPK inhibitor compound C attenuated the effects of NDGA on expression of lipid metabolism-related proteins in HepG2 hepatocytes. The beneficial effects of NDGA on HFD-induced hepatic triglyceride accumulation are mediated through AMPK signaling pathways, suggesting a potential target for preventing NAFLD.

  6. Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line.

    Science.gov (United States)

    Ishimura, Emi; Nakagawa, Takatoshi; Moriwaki, Kazumasa; Hirano, Seiichi; Matsumori, Yoshinobu; Asahi, Michio

    2017-12-01

    Increasing incidence of various cancers has been reported in diabetic patients. O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. However, the mechanisms by which O-GlcNAcylation promotes tumor growth remain unclear. Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. O-GlcNAc transferase overexpression also increased the growth. These treatments increased AMPK O-GlcNAcylation in a dose-dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. In addition, TMG-mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. To examine the effects of AMPK O-GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c-nu/nu mice. Injection of TMG promoted the growth and enhanced O-GlcNAcylation of the tumors of the mice. Consistent with in vitro data, AMPK O-GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Yong Pil; Kim, Hyung Gyun [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Hien, Tran Thi [College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Jeong, Myung Ho [Heart Research Center, Chonnam National University Hospital, Gwangju (Korea, Republic of); Jeong, Tae Cheon, E-mail: taecheon@ynu.ac.kr [College of Pharmacy, Yeungnam University, Gyungsan (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2011-11-15

    The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-{alpha}-stimulated monocytes to endothelial cells and suppressed the TNF-{alpha} induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-{alpha}-induced nuclear factor-{kappa}B activation, which was attenuated by pretreatment with N{sup G}-nitro-L-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease. -- Highlights: Black-Right-Pointing-Pointer Puerarin induced the phosphorylation of eNOS and the production of NO. Black-Right-Pointing-Pointer Puerarin activated eNOS through ER-dependent PI3-kinase and Ca{sup 2+}-dependent AMPK. Black-Right-Pointing-Pointer Puerarin-induced NO was involved in the inhibition of NF-kB activation. Black-Right-Pointing-Pointer Puerarin may help for prevention of vascular dysfunction and diabetes.

  8. The importance of regulation of blood glucose levels through activation of peripheral 5'-AMP-activated protein kinase on ischemic neuronal damage.

    Science.gov (United States)

    Harada, Shinichi; Fujita-Hamabe, Wakako; Tokuyama, Shogo

    2010-09-10

    5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that plays a key role in energy homeostasis. Recently, it was reported that centrally activated AMPK is involved in the development of ischemic neuronal damage, while the effect of peripherally activated AMPK on ischemic neuronal damage is not known. In addition, we have previously reported that the development of post-ischemic glucose intolerance could be one of the triggers for the aggravation of neuronal damage. In this study, we focused on effect of activation of peripheral or central AMPK on the development of ischemic neuronal damage. Male ddY mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated by histological and behavioral analysis after MCAO. In the liver and skeletal muscle, AMPK activity was not affected by MCAO. But, application of intraperitoneal metformin (250 mg/kg), an AMPK activator, significantly suppressed the development of post-ischemic glucose intolerance and ischemic neuronal damage without alteration of central AMPK activity. On the other hand, application of intracerebroventricular metformin (25, 100 microg/mouse) significantly exacerbated the development of neuronal damage observed on day 1 after MCAO, in a dose-dependent manner. These effects were significantly blocked by compound C, a specific AMPK inhibitor. These results suggest that central AMPK was activated by ischemic stress per se, however, peripheral AMPK was not altered. Furthermore, the regulation of post-ischemic glucose intolerance by activation of peripheral AMPK is of assistance for the suppression of cerebral ischemic neuronal damage. 2010 Elsevier B.V. All rights reserved.

  9. Role of AMP-activated protein kinase for regulating post-exercise insulin sensitivity

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Wojtaszewski, Jørgen; Treebak, Jonas Thue

    2016-01-01

    Skeletal muscle insulin resistance precedes development of type 2 diabetes (T2D). As skeletal muscle is a major sink for glucose disposal, understanding the molecular mechanisms involved in maintaining insulin sensitivity of this tissue could potentially benefit millions of people that are diagno......Skeletal muscle insulin resistance precedes development of type 2 diabetes (T2D). As skeletal muscle is a major sink for glucose disposal, understanding the molecular mechanisms involved in maintaining insulin sensitivity of this tissue could potentially benefit millions of people...... that are diagnosed with insulin resistance. Regular physical activity in both healthy and insulin-resistant individuals is recognized as the single most effective intervention to increase whole-body insulin sensitivity and thereby positively affect glucose homeostasis. A single bout of exercise has long been known...... to increase glucose disposal in skeletal muscle in response to physiological insulin concentrations. While this effect is identified to be restricted to the previously exercised muscle, the molecular basis for an apparent convergence between exercise- and insulin-induced signaling pathways is incompletely...

  10. Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat.

    Science.gov (United States)

    Due, Michael R; Park, Jonghyuck; Zheng, Lingxing; Walls, Michael; Allette, Yohance M; White, Fletcher A; Shi, Riyi

    2014-03-01

    Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here, we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound's pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggest that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. Following spinal cord injury (SCI), acrolein involvement in neuropathic pain is likely through direct activation and elevated levels of pro-nociceptive channel TRPA1. While acrolein elevation correlates with neuropathic pain, suppression of this aldehyde by hydralazine leads to an analgesic effect. Acrolein may serve as a novel therapeutic target for preclinical and clinical SCI to relieve both acute and chronic post-SCI neuropathic pain. © 2013 International Society for Neurochemistry.

  11. Down-Regulation of the Na+-Coupled Phosphate Transporter NaPi-IIa by AMP-Activated Protein Kinase

    Directory of Open Access Journals (Sweden)

    Miribane Dërmaku-Sopjani

    2013-11-01

    Full Text Available Background/Aims: The Na+-coupled phosphate transporter NaPi-IIa is the main carrier accomplishing renal tubular phosphate reabsorption. It is driven by the electrochemical Na+ gradient across the apical cell membrane, which is maintained by Na+ extrusion across the basolateral cell membrane through the Na+/K+ ATPase. The operation of NaPi-IIa thus requires energy in order to avoid cellular Na+ accumulation and K+ loss with eventual decrease of cell membrane potential, Cl- entry and cell swelling. Upon energy depletion, early inhibition of Na+-coupled transport processes may delay cell swelling and thus foster cell survival. Energy depletion is sensed by the AMP-activated protein kinase (AMPK, a serine/threonine kinase stimulating several cellular mechanisms increasing energy production and limiting energy utilization. The present study explored whether AMPK influences the activity of NAPi-IIa. Methods: cRNA encoding NAPi-IIa was injected into Xenopus oocytes with or without additional expression of wild-type AMPK (AMPKα1-HA+AMPKβ1-Flag+AMPKγ1-HA, of inactive AMPKαK45R (AMPKα1K45R+AMPKβ1-Flag+AMPKγ1-HA or of constitutively active AMPKγR70Q (AMPKα1-HA+AMPKβ1-Flag+AMPKγ1R70Q. NaPi-IIa activity was estimated from phosphate-induced current in dual electrode voltage clamp experiments. Results: In NaPi-IIa-expressing, but not in water-injected Xenopus oocytes, the addition of phosphate (1 mM to the extracellular bath solution generated a current (Ip, which was significantly decreased by coexpression of wild-type AMPK and of AMPKγR70Q but not of AMPKαK45R. The phosphate-induced current in NaPi-IIa- and AMPK-expressing Xenopus ooocytes was significantly increased by AMPK inhibitor Compound C (20 µM. Kinetic analysis revealed that AMPK significantly decreased the maximal transport rate. Conclusion: The AMP-activated protein kinase AMPK is a powerful regulator of NaPi-IIa and thus of renal tubular phosphate transport.

  12. Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.

    Directory of Open Access Journals (Sweden)

    Diego C Reino

    Full Text Available Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI and multiple organ dysfunction syndrome (MODS. Since Toll-like receptors (TLR act as sensors of tissue injury as well as microbial invasion and TLR4 signaling occurs in both sepsis and noninfectious models of ischemia/reperfusion (I/R injury, we hypothesized that factors in the intestinal mesenteric lymph after trauma hemorrhagic shock (T/HS mediate gut-induced lung injury via TLR4 activation.The concept that factors in T/HS lymph exiting the gut recreates ALI is evidenced by our findings that the infusion of porcine lymph, collected from animals subjected to global T/HS injury, into naïve wildtype (WT mice induced lung injury. Using C3H/HeJ mice that harbor a TLR4 mutation, we found that TLR4 activation was necessary for the development of T/HS porcine lymph-induced lung injury as determined by Evan's blue dye (EBD lung permeability and myeloperoxidase (MPO levels as well as the induction of the injurious pulmonary iNOS response. TRIF and Myd88 deficiency fully and partially attenuated T/HS lymph-induced increases in lung permeability respectively. Additional studies in TLR2 deficient mice showed that TLR2 activation was not involved in the pathology of T/HS lymph-induced lung injury. Lastly, the lymph samples were devoid of bacteria, endotoxin and bacterial DNA and passage of lymph through an endotoxin removal column did not abrogate the ability of T/HS lymph to cause lung injury in naïve mice.Our findings suggest that non-microbial factors in the intestinal mesenteric lymph after T/HS are capable of recreating T/HS-induced lung injury via TLR4 activation.

  13. Extracellular cAMP activates molecular signalling pathways associated with sperm capacitation in bovines.

    Science.gov (United States)

    Alonso, Carlos Agustín I; Osycka-Salut, Claudia E; Castellano, Luciana; Cesari, Andreína; Di Siervi, Nicolás; Mutto, Adrián; Johannisson, Anders; Morrell, Jane M; Davio, Carlos; Perez-Martinez, Silvina

    2017-08-01

    Is extracellular cAMP involved in the regulation of signalling pathways in bovine sperm capacitation? Extracellular cAMP induces sperm capacitation through the activation of different signalling pathways that involve phospholipase C (PLC), PKC/ERK1-2 signalling and an increase in sperm Ca2+ levels, as well as soluble AC and cAMP/protein kinase A (PKA) signalling. In order to fertilize the oocyte, ejaculated spermatozoa must undergo a series of changes in the female reproductive tract, known as capacitation. This correlates with a number of membrane and metabolic modifications that include an increased influx of bicarbonate and Ca2+, activation of a soluble adenylyl cyclase (sAC) to produce cAMP, PKA activation, protein tyrosine phosphorylation and the development of hyperactivated motility. We previously reported that cAMP efflux by Multidrug Resistance Protein 4 (MRP4) occurs during sperm capacitation and the pharmacological blockade of this inhibits the process. Moreover, the supplementation of incubation media with cAMP abolishes the inhibition and leads to sperm capacitation, suggesting that extracellular cAMP regulates crucial signalling cascades involved in this process. Bovine sperm were selected by the wool glass column method, and washed by centrifugation in BSA-Free Tyrode's Albumin Lactate Pyruvate (sp-TALP). Pellets were resuspended then diluted for each treatment. For in vitro capacitation, 10 to 15 × 106 SPZ/ml were incubated in 0.3% BSA sp-TALP at 38.5°C for 45 min under different experimental conditions. To evaluate the role of extracellular cAMP on different events associated with sperm capacitation, 10 nM cAMP was added to the incubation medium as well as different inhibitors of enzymes associated with signalling transduction pathways: U73122 (PLC inhibitor, 10 μM), Gö6983 (PKC inhibitor, 10 μM), PD98059 (ERK-1/2 inhibitor, 30 μM), H89 and KT (PKA inhibitors, 50 μM and 100 nM, respectively), KH7 (sAC inhibitor, 10 μM), BAPTA

  14. AMP-Activated Kinase Regulates Lipid Droplet Localization and Stability of Adipose Triglyceride Lipase in C. elegans Dauer Larvae.

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    Meng Xie

    Full Text Available Animals have developed diverse mechanisms to adapt to their changing environment. Like many organisms the free-living nematode C. elegans can alternate between a reproductive mode or a diapause-like "dauer" stage during larval development to circumvent harsh environmental conditions. The master metabolic regulator AMP-activated protein kinase (AMPK is critical for survival during the dauer stage, where it phosphorylates adipose triglyceride lipase (ATGL-1 at multiple sites to block lipid hydrolysis and ultimately protect the cellular triglyceride-based energy depot from rapid depletion. However, how the AMPK-mediated phosphorylation affects the function of ATGL-1 has not been characterised at the molecular level. Here we show that AMPK phosphorylation leads to the generation of 14-3-3 binding sites on ATGL-1, which are recognized by the C. elegans 14-3-3 protein orthologue PAR-5. Physical interaction of ATGL-1 with PAR-5 results in sequestration of ATGL-1 away from the lipid droplets and eventual proteasome-mediated degradation. In addition, we also show that the major AMPK phosphorylation site on ATGL-1, Ser 303, is required for both modification of its lipid droplet localization and its degradation. Our data provide mechanistic insight as to how AMPK functions to enhance survival through its ability to protect the accumulated triglyceride deposits from rapid hydrolysis to preserve the energy stores during periods of extended environmental duress.

  15. AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells.

    Science.gov (United States)

    Yamada, Shigeru; Kotake, Yaichiro; Sekino, Yuko; Kanda, Yasunari

    2013-05-01

    Organotin compounds such as tributyltin (TBT) are known to cause various forms of cytotoxicity, including developmental toxicity and neurotoxicity. However, the molecular target of the toxicity induced by nanomolar levels of TBT has not been identified. In the present study, we found that exposure to 100 nM TBT induced growth arrest in human pluripotent embryonic carcinoma cell line NT2/D1. Since glucose provides metabolic energy, we focused on the glycolytic system. We found that exposure to TBT reduced the levels of both glucose-6-phosphate and fructose-6-phosphate. To investigate the effect of TBT exposure on glycolysis, we examined glucose transporter (GLUT) activity. TBT exposure inhibited glucose uptake via a decrease in the level of cell surface-bound GLUT1. Furthermore, we examined the effect of AMP-activated protein kinase (AMPK), which is known to regulate glucose transport by facilitating GLUT translocation. Treatment with the potent AMPK activator, AICAR, restored the TBT-induced reduction in cell surface-bound GLUT1 and glucose uptake. In conclusion, these results suggest that exposure to nanomolar levels of TBT causes growth arrest by targeting glycolytic systems in human embryonic carcinoma cells. Thus, understanding the energy metabolism may provide new insights into the mechanisms of metal-induced cytotoxicity.

  16. Silibinin activates AMP-activated protein kinase to protect neuronal cells from oxygen and glucose deprivation-re-oxygenation.

    Science.gov (United States)

    Xie, Zhi; Ding, Sheng-quan; Shen, Ya-fang

    2014-11-14

    In this study, we explored the cytoprotective potential of silibinin against oxygen-glucose deprivation (OGD)-induced neuronal cell damages, and studied underling mechanisms. In vitro model of ischemic stroke was created by keeping neuronal cells (SH-SY5Y cells and primary mouse cortical neurons) in an OGD condition followed by re-oxygenation. Pre-treatment of silibinin significantly inhibited OGD/re-oxygenation-induced necrosis and apoptosis of neuronal cells. OGD/re-oxygenation-induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) reduction were also inhibited by silibinin. At the molecular level, silibinin treatment in SH-SY5Y cells and primary cortical neurons led to significant AMP-activated protein kinase (AMPK) signaling activation, detected by phosphorylations of AMPKα1, its upstream kinase liver kinase B1 (LKB1) and the downstream target acetyl-CoA Carboxylase (ACC). Pharmacological inhibition or genetic depletion of AMPK alleviated the neuroprotective ability of silibinin against OGD/re-oxygenation. Further, ROS scavenging ability by silibinin was abolished with AMPK inhibition or silencing. While A-769662, the AMPK activator, mimicked silibinin actions and suppressed ROS production and neuronal cell death following OGD/re-oxygenation. Together, these results show that silibinin-mediated neuroprotection requires activation of AMPK signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. β-subunit myristoylation functions as an energy sensor by modulating the dynamics of AMP-activated Protein Kinase.

    Science.gov (United States)

    Ali, Nada; Ling, Naomi; Krishnamurthy, Srinath; Oakhill, Jonathan S; Scott, John W; Stapleton, David I; Kemp, Bruce E; Anand, Ganesh Srinivasan; Gooley, Paul R

    2016-12-21

    The heterotrimeric AMP-activated protein kinase (AMPK), consisting of α, β and γ subunits, is a stress-sensing enzyme that is activated by phosphorylation of its activation loop in response to increases in cellular AMP. N-terminal myristoylation of the β-subunit has been shown to suppress Thr172 phosphorylation, keeping AMPK in an inactive state. Here we use amide hydrogen-deuterium exchange mass spectrometry (HDX-MS) to investigate the structural and dynamic properties of the mammalian myristoylated and non-myristoylated inactivated AMPK (D139A) in the presence and absence of nucleotides. HDX MS data suggests that the myristoyl group binds near the first helix of the C-terminal lobe of the kinase domain similar to other kinases. Our data, however, also shows that ATP.Mg 2+ results in a global stabilization of myristoylated, but not non-myristoylated AMPK, and most notably for peptides of the activation loop of the α-kinase domain, the autoinhibitory sequence (AIS) and the βCBM. AMP does not have that effect and HDX measurements for myristoylated and non-myristoylated AMPK in the presence of AMP are similar. These differences in dynamics may account for a reduced basal rate of phosphorylation of Thr172 in myristoylated AMPK in skeletal muscle where endogenous ATP concentrations are very high.

  18. Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes.

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    Xinwei Li

    Full Text Available The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic acid and BML-275 (an AMPKα inhibitor. Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.

  19. C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism.

    Science.gov (United States)

    Landree, Leslie E; Hanlon, Andrea L; Strong, David W; Rumbaugh, Gavin; Miller, Ian M; Thupari, Jagan N; Connolly, Erin C; Huganir, Richard L; Richardson, Christine; Witters, Lee A; Kuhajda, Francis P; Ronnett, Gabriele V

    2004-01-30

    C75, a synthetic inhibitor of fatty acid synthase (FAS), is hypothesized to alter the metabolism of neurons in the hypothalamus that regulate feeding behavior to contribute to the decreased food intake and profound weight loss seen with C75 treatment. In the present study, we characterize the suitability of primary cultures of cortical neurons for studies designed to investigate the consequences of C75 treatment and the alteration of fatty acid metabolism in neurons. We demonstrate that in primary cortical neurons, C75 inhibits FAS activity and stimulates carnitine palmitoyltransferase-1 (CPT-1), consistent with its effects in peripheral tissues. C75 alters neuronal ATP levels and AMP-activated protein kinase (AMPK) activity. Neuronal ATP levels are affected in a biphasic manner with C75 treatment, decreasing initially, followed by a prolonged increase above control levels. Cerulenin, a FAS inhibitor, causes a similar biphasic change in ATP levels, although levels do not exceed control. C75 and cerulenin modulate AMPK phosphorylation and activity. TOFA, an inhibitor of acetyl-CoA carboxylase, increases ATP levels, but does not affect AMPK activity. Several downstream pathways are affected by C75 treatment, including glucose metabolism and acetyl-CoA carboxylase (ACC) phosphorylation. These data demonstrate that C75 modulates the levels of energy intermediates, thus, affecting the energy sensor AMPK. Similar effects in hypothalamic neurons could form the basis for the effects of C75 on feeding behavior.

  20. Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes

    Science.gov (United States)

    Koh, Ho-Jin; Hirshman, Michael F.; He, Huamei; Li, Yangfeng; Manabe, Yasuko; Balschi, James A.; Goodyear, Laurie J.

    2007-01-01

    Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPKα1 and α2 activities and ACC (acetyl-CoA carboxylase) Ser79 phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the β-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPKα1 and α2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPKα1 and α2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis. PMID:17253964

  1. Single-vehicle and Multi-vehicle Accidents Involving Motorcycles in a Small City in China: Characteristics and Injury Patterns

    Directory of Open Access Journals (Sweden)

    Lili Xiong

    2015-03-01

    Full Text Available Introduction: There is a gap that involves examining differences between patients in single-vehicle (SV versus multi-vehicle (MV accidents involving motorcycles in Shantou, China, regarding the injury patterns and mortality the patients sustained. This study aims to address this gap and provide a basis and reference for motorcycle injury prevention. Method: Medical record data was collected between October 2002 and June 2012 on all motorcycle injury patients admitted to a hospital in the city of Shantou of the east Guangdong province in China. Comparative analysis was conducted between patients in SV accidents and patients in MV accidents regarding demographic and clinic characteristics, mortality, and injury patterns. Results: Approximately 48% (n = 1977 of patients were involved in SV accidents and 52% (n = 2119 were involved in MV accidents. The average age was 34 years. Collision of a motorcycle with a heavy vehicle/bus (4% was associated with a 34 times greater risk of death (RR: 34.32|95% CI: 17.43–67.57. Compared to patients involved in MV accidents, those involved in SV accidents were more likely to sustain a skull fracture (RR: 1.47|95% CI: 1.22–1.77, an open head wound (RR: 1.46|95% CI: 1.23–1.74, an intracranial injury (RR: 1.39|95% CI: 1.26–1.53, a superficial head injury (RR: 1.37|95% CI: 1.01–1.86, an injury to an organ (RR: 2.01|95% CI: 1.24–3.26, and a crushing injury (RR: 1.98|95% CI: 1.06–3.70 to the thorax or abdomen. However, they were less likely to sustain a spinal fracture (RR: 0.58|95% CI: 0.39–0.85, a pelvic fracture (RR: 0.22|95% CI: 0.11–0.46, an upper extremity fracture (RR: 0.75|95% CI: 0.59–0.96, or injuries to their lower extremities, except for a dislocation, sprain, or injury to a joint or ligament (RR: 0.82|95% CI: 0.49–1.36. Conclusion: The relative risk of death is higher for patients involved in multi-vehicle accidents than patients in single-vehicle accidents, especially when a

  2. Factors Influencing Helmet Use, Head Injury, and Hospitalization Among Children Involved in Skateboarding and Snowboarding Accidents.

    Science.gov (United States)

    Sadeghian, Homa; Nguyen, Brian; Huynh, Nhan; Rouch, Joshua; Lee, Steven L; Bazargan-Hejazi, Shahrzad

    2017-01-01

    Up to 75% of skateboarders and snowboarders admitted to the hospital sustain head injuries. It is unclear why not all children and teenagers wear helmets while snowboarding and skateboarding given the protection they afford. To report on the prevalence of, and factors associated with, skateboarding and snowboarding in injured children and to explore factors that influence helmet use, head injury, and hospitalization in this sample. A cross-sectional study of skateboard- and snowboard-associated injuries from 2003 to 2012 among individuals younger than age 18 years using National Electronic Injury Surveillance System (NEISS) data from approximately 100 hospitals. Helmet use, head injury, and hospitalization. Of 1742 patients in the study, 852 (48.9%) and 890 (51.1%) were skateboarders and snowboarders, respectively. Overall, 907 (52.1%) did not use helmets, and 704 (40.4%) sustained head injuries. Multiple logistic regression analysis showed that age, race/ethnicity, location of boarding, and engaging in skateboarding influenced helmet use. Sex, race/ethnicity, helmet use, and skateboarding predicted head injury. Age, sex, skateboarding, and head injury predicted hospital admission. Statistically significant differences exist in helmet use, head injury, and hospitalization rates between skateboarders and snowboarders. Our findings suggest that injury prevention and outreach programs are needed to increase helmet use and reduce the risk of head injury and hospitalization in skateboarders and other at-risk groups. Further studies are needed to clarify the association between race/ethnicity and helmet use among skateboarders and snowboarders.

  3. Endoplasmic reticulum stress is involved in arsenite-induced oxidative injury in rat brain

    International Nuclear Information System (INIS)

    Lin, Anya M.Y.; Chao, P.L.; Fang, S.F.; Chi, C.W.; Yang, C.H.

    2007-01-01

    The mechanism underlying sodium arsenite (arsenite)-induced neurotoxicity was investigated in rat brain. Arsenite was locally infused in the substantia nigra (SN) of anesthetized rat. Seven days after infusion, lipid peroxidation in the infused SN was elevated and dopamine level in the ipsilateral striatum was reduced in a concentration-dependent manner (0.3-5 nmol). Furthermore, local infusion of arsenite (5 nmol) decreased GSH content and increased expression of heat shock protein 70 and heme oxygenase-1 in the infused SN. Aggregation of α-synuclein, a putative pathological protein involved in several CNS neurodegenerative diseases, was elevated in the arsenite-infused SN. From the breakdown pattern of α-spectrin, both necrosis and apoptosis were involved in the arsenite-induced neurotoxicity. Pyknotic nuclei, cellular shrinkage and cytoplasmic disintegration, indicating necrosis, and TUNEL-positive cells and DNA ladder, indicating apoptosis was observed in the arsenite-infused SN. Arsenite-induced apoptosis was mediated via two different organelle pathways, mitochondria and endoplasmic reticulum (ER). For mitochondrial activation, cytosolic cytochrome c and caspase-3 levels were elevated in the arsenite-infused SN. In ER pathway, arsenite increased activating transcription factor-4, X-box binding protein 1, C/EBP homologues protein (CHOP) and cytosolic immunoglobulin binding protein levels. Moreover, arsenite reduced procaspase 12 levels, an ER-specific enzyme in the infused SN. Taken together, our study suggests that arsenite is capable of inducing oxidative injury in CNS. In addition to mitochondria, ER stress was involved in the arsenite-induced apoptosis. Arsenite-induced neurotoxicity clinically implies a pathophysiological role of arsenite in CNS neurodegeneration

  4. AMP (Activity Manipulation Program)

    International Nuclear Information System (INIS)

    Engle, W.W. Jr.

    1976-03-01

    AMP is a FORTRAN IV program written to handle energy-group structured activity factors such as sources, conversion factors, and response functions, as used by ANISN, DOT III, and other nuclear reactor and shielding codes. Activities may be retrieved from ANISN-type cross-section and activity sets found on cards and tapes, and from tabular-type sets on cards. They may be altered by change of group structure, multiplication by a constant, or multiplication by delta E (the group-energy interval), and then output to ANISN-type cards or tape and tabular-type cards. A full edit of input and output activities is always printed by group and activity number

  5. Regulation of energy metabolism during social interactions in rainbow trout: a role for AMP-activated protein kinase.

    Science.gov (United States)

    Gilmour, K M; Craig, P M; Dhillon, R S; Lau, G Y; Richards, J G

    2017-11-01

    Rainbow trout ( Oncorhynchus mykiss ) confined in pairs form social hierarchies in which subordinate fish typically experience fasting and high circulating cortisol levels, resulting in low growth rates. The present study investigated the role of AMP-activated protein kinase (AMPK) in mediating metabolic adjustments associated with social status in rainbow trout. After 3 days of social interaction, liver AMPK activity was significantly higher in subordinate than dominant or sham (fish handled in the same fashion as paired fish but held individually) trout. Elevated liver AMPK activity in subordinate fish likely reflected a significantly higher ratio of phosphorylated AMPK (phospho-AMPK) to total AMPK protein, which was accompanied by significantly higher AMPKα 1 relative mRNA abundance. Liver ATP and creatine phosphate concentrations in subordinate fish also were elevated, perhaps as a result of AMPK activity. Sham fish that were fasted for 3 days exhibited effects parallel to those of subordinate fish, suggesting that low food intake was an important trigger of elevated AMPK activity in subordinate fish. Effects on white muscle appeared to be influenced by the physical activity associated with social interaction. Overall, muscle AMPK activity was significantly higher in dominant and subordinate than sham fish. The ratio of phospho-AMPK to total AMPK protein in muscle was highest in subordinate fish, while muscle AMPKα 1 relative mRNA abundance was elevated by social dominance. Muscle ATP and creatine phosphate concentrations were high in dominant and subordinate fish at 6 h of interaction and decreased significantly thereafter. Collectively, the findings of the present study support a role for AMPK in mediating liver and white muscle metabolic adjustments associated with social hierarchy formation in rainbow trout. Copyright © 2017 the American Physiological Society.

  6. Loss of a neural AMP-activated kinase mimics the effects of elevated serotonin on fat, movement, and hormonal secretions.

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    Katherine A Cunningham

    2014-06-01

    Full Text Available AMP-activated protein kinase (AMPK is an evolutionarily conserved master regulator of metabolism and a therapeutic target in type 2 diabetes. As an energy sensor, AMPK activity is responsive to both metabolic inputs, for instance the ratio of AMP to ATP, and numerous hormonal cues. As in mammals, each of two genes, aak-1 and aak-2, encode for the catalytic subunit of AMPK in C. elegans. Here we show that in C. elegans loss of aak-2 mimics the effects of elevated serotonin signaling on fat reduction, slowed movement, and promoting exit from dauer arrest. Reconstitution of aak-2 in only the nervous system restored wild type fat levels and movement rate to aak-2 mutants and reconstitution in only the ASI neurons was sufficient to significantly restore dauer maintenance to the mutant animals. As in elevated serotonin signaling, inactivation of AAK-2 in the ASI neurons caused enhanced secretion of dense core vesicles from these neurons. The ASI neurons are the site of production of the DAF-7 TGF-β ligand and the DAF-28 insulin, both of which are secreted by dense core vesicles and play critical roles in whether animals stay in dauer or undergo reproductive development. These findings show that elevated levels of serotonin promote enhanced secretions of systemic regulators of pro-growth and differentiation pathways through inactivation of AAK-2. As such, AMPK is not only a recipient of hormonal signals but can also be an upstream regulator. Our data suggest that some of the physiological phenotypes previously attributed to peripheral AAK-2 activity on metabolic targets may instead be due to the role of this kinase in neural serotonin signaling.

  7. Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells.

    Science.gov (United States)

    Ye, Xueting; Xie, Jing; Huang, Hang; Deng, Zhexian

    2018-01-01

    Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling. © 2018 The Author(s). Published by S. Karger AG, Basel.

  8. Chrysophanic Acid Suppresses Adipogenesis and Induces Thermogenesis by Activating AMP-activated Protein Kinase Alpha in vivo and in vitro

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    Hara Lim

    2016-12-01

    Full Text Available Chrysophanic acid (CA is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Korean Medicine. Though several studies have indicated numerous features of CA, no study has yet reported the effect of CA on obesity. In this study, we tried to identify the anti-obesity effects of CA. By using 3T3-L1 adipocytes and primary cultured brown adipocytes as in vitro models, high-fat diet (HFD-induced obese mice, and zebrafish as in vivo models, we determined the anti-obesity effects of CA. CA reduced weight gain in HFD-induced obese mice. They also decreased lipid accumulation and the expressions of adipogenesis factors including peroxisome proliferator-activated receptor gamma (PPARγ and CCAAT/enhancer-binding protein alpha (C/EBPα in 3T3-L1 adipocytes. In addition, uncoupling protein 1 (UCP1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α, the brown fat specific thermogenic genes, were up-regulated in brown adipocytes by CA treatment. Furthermore, when co-treated with Compound C, the AMP-activated protein kinase (AMPK inhibitor, CA was able to restore the activation of AMPKα in both types of adipocytes, indicating the multi-controlling effect of CA was partially via the AMPKα pathway. Given all together, these results indicate that CA can ameliorate obesity by controlling the adipogenic and thermogenic pathway at the same time. On these bases we suggest the new potential of CA as an anti-obese pharmacotherapy.

  9. Suppressive effect of AMP-activated protein kinase on the epithelial-mesenchymal transition in retinal pigment epithelial cells.

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    Ryo Matoba

    Full Text Available The epithelial-mesenchymal transition (EMT in retinal pigment epithelial (RPE cells plays a central role in the development of proliferative vitreoretinopathy (PVR. The purpose of this study was to investigate the effect of AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis, on the EMT in RPE cells. In this study, EMT-associated formation of cellular aggregates was induced by co-stimulation of cultured ARPE-19 cells with tumor necrosis factor (TNF-α (10 ng/ml and transforming growth factor (TGF-β2 (5 ng/ml. 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, a potent activator of AMPK, significantly suppressed TNF-α and TGF-β2-induced cellular aggregate formation (p < 0.01. Dipyridamole almost completely reversed the suppressive effect of AICAR, whereas 5'-amino-5'-deoxyadenosine restored aggregate formation by approximately 50%. AICAR suppressed the downregulation of E-cadherin and the upregulation of fibronectin and α-smooth muscle actin by TNF-α and TGF-β2. The levels of matrix metalloproteinase (MMP-2, MMP-9, interleukin-6, and vascular endothelial growth factor were significantly decreased by AICAR. Activation of the mitogen-activated protein kinase and mammalian target of rapamycin pathways, but not the Smad pathway, was inhibited by AICAR. These findings indicate that AICAR suppresses the EMT in RPE cells at least partially via activation of AMPK. AMPK is a potential target molecule for the prevention and treatment of PVR, so AICAR may be a promising candidate for PVR therapy.

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

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    Hsiao-Ya Tsai

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  12. The Floating Upper Limb: Multiple Injuries Involving Ipsilateral, Proximal, Humeral, Supracondylar, and Distal Radial Limb.

    Science.gov (United States)

    Manaan, Qazi; Bashir, Adil; Zahoor, Adnan; Mokhdomi, Taseem A; Danish, Qazi

    2016-09-01

    Floating arm injury represents a common yet complicated injury of the childhood severely associated with limb deformation and even morbidity, if not precisely addressed and credibly operated. Here, we report a rare floating upper limb case of a 9-year-old boy with multiple injuries of ipsilateral proximal humeral, supracondylar and distal radial limb. This is the first report to document such a combined floating elbow and floating arm injury in the same limb. In this report, we discuss the surgical procedures used and recovery of the patient monitored to ascertain the effectiveness of the method in limb reorganisation.

  13. Neural Resilience to Traumatic Brain Injury: Identification of Bioactive Metabolites of Docosahexaenoic Acids Involved in Neuroprotection and Recovery

    Science.gov (United States)

    2015-05-01

    Involved in Neuroprotection and Recovery PRINCIPAL INVESTIGATOR: Hee-Yong Kim CONTRACTING ORGANIZATION: Henry M. Jackson Foundation for the...O’Dell DM, Lyeth BG, Jenkins LW (1994) The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury

  14. Ca2+/Calmodulin-Dependent Protein Kinase Kinases (CaMKKs) Effects on AMP-Activated Protein Kinase (AMPK) Regulation of Chicken Sperm Functions.

    Science.gov (United States)

    Nguyen, Thi Mong Diep; Combarnous, Yves; Praud, Christophe; Duittoz, Anne; Blesbois, Elisabeth

    2016-01-01

    Sperm require high levels of energy to ensure motility and acrosome reaction (AR) accomplishment. The AMP-activated protein kinase (AMPK) has been demonstrated to be strongly involved in the control of these properties. We address here the question of the potential role of calcium mobilization on AMPK activation and function in chicken sperm through the Ca(2+)/calmodulin-dependent protein kinase kinases (CaMKKs) mediated pathway. The presence of CaMKKs and their substrates CaMKI and CaMKIV was evaluated by western-blotting and indirect immunofluorescence. Sperm were incubated in presence or absence of extracellular Ca(2+), or of CaMKKs inhibitor (STO-609). Phosphorylations of AMPK, CaMKI, and CaMKIV, as well as sperm functions were evaluated. We demonstrate the presence of both CaMKKs (α and β), CaMKI and CaMKIV in chicken sperm. CaMKKα and CaMKI were localized in the acrosome, the midpiece, and at much lower fluorescence in the flagellum, whereas CaMKKβ was mostly localized in the flagellum and much less in the midpiece and the acrosome. CaMKIV was only present in the flagellum. The presence of extracellular calcium induced an increase in kinases phosphorylation and sperm activity. STO-609 reduced AMPK phosphorylation in the presence of extracellular Ca(2+) but not in its absence. STO-609 did not affect CaMKIV phosphorylation but decreased CaMKI phosphorylation and this inhibition was quicker in the presence of extracellular Ca(2+) than in its absence. STO-609 efficiently inhibited sperm motility and AR, both in the presence and absence of extracellular Ca(2+). Our results show for the first time the presence of CaMKKs (α and β) and one of its substrate, CaMKI in different subcellular compartments in germ cells, as well as the changes in the AMPK regulation pathway, sperm motility and AR related to Ca(2+) entry in sperm through the Ca(2+)/CaM/CaMKKs/CaMKI pathway. The Ca(2+)/CaMKKs/AMPK pathway is activated only under conditions of extracellular Ca(2+) entry

  15. Ca2+/Calmodulin-Dependent Protein Kinase Kinases (CaMKKs Effects on AMP-Activated Protein Kinase (AMPK Regulation of Chicken Sperm Functions.

    Directory of Open Access Journals (Sweden)

    Thi Mong Diep Nguyen

    Full Text Available Sperm require high levels of energy to ensure motility and acrosome reaction (AR accomplishment. The AMP-activated protein kinase (AMPK has been demonstrated to be strongly involved in the control of these properties. We address here the question of the potential role of calcium mobilization on AMPK activation and function in chicken sperm through the Ca(2+/calmodulin-dependent protein kinase kinases (CaMKKs mediated pathway. The presence of CaMKKs and their substrates CaMKI and CaMKIV was evaluated by western-blotting and indirect immunofluorescence. Sperm were incubated in presence or absence of extracellular Ca(2+, or of CaMKKs inhibitor (STO-609. Phosphorylations of AMPK, CaMKI, and CaMKIV, as well as sperm functions were evaluated. We demonstrate the presence of both CaMKKs (α and β, CaMKI and CaMKIV in chicken sperm. CaMKKα and CaMKI were localized in the acrosome, the midpiece, and at much lower fluorescence in the flagellum, whereas CaMKKβ was mostly localized in the flagellum and much less in the midpiece and the acrosome. CaMKIV was only present in the flagellum. The presence of extracellular calcium induced an increase in kinases phosphorylation and sperm activity. STO-609 reduced AMPK phosphorylation in the presence of extracellular Ca(2+ but not in its absence. STO-609 did not affect CaMKIV phosphorylation but decreased CaMKI phosphorylation and this inhibition was quicker in the presence of extracellular Ca(2+ than in its absence. STO-609 efficiently inhibited sperm motility and AR, both in the presence and absence of extracellular Ca(2+. Our results show for the first time the presence of CaMKKs (α and β and one of its substrate, CaMKI in different subcellular compartments in germ cells, as well as the changes in the AMPK regulation pathway, sperm motility and AR related to Ca(2+ entry in sperm through the Ca(2+/CaM/CaMKKs/CaMKI pathway. The Ca(2+/CaMKKs/AMPK pathway is activated only under conditions of extracellular Ca(2

  16. Molecular Pathways Involved in the Amelioration of Myocardial Injury in Diabetic Rats by Kaempferol.

    Science.gov (United States)

    Suchal, Kapil; Malik, Salma; Khan, Sana Irfan; Malhotra, Rajiv Kumar; Goyal, Sameer N; Bhatia, Jagriti; Ojha, Shreesh; Arya, Dharamvir Singh

    2017-05-15

    There is growing evidence that chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs) which exerts its effect via interaction with the receptor for advanced glycation end products (RAGE). AGE-RAGE activation results in oxidative stress and inflammation. It is well known that this mechanism is involved in the pathogenesis of cardiovascular disease in diabetes. Kaempferol, a dietary flavonoid, is known to possess antioxidant, anti-apoptotic, and anti-inflammatory activities. However, little is known about the effect of kaempferol on myocardial ischemia-reperfusion (IR) injury in diabetic rats. Diabetes was induced in male albino Wistar rats using streptozotocin (70 mg/kg; i.p.), and rats with glucose level >250 mg/dL were considered as diabetic. Diabetic rats were treated with vehicle (2 mL/kg; i.p.) and kaempferol (20 mg/kg; i.p.) daily for a period of 28 days and on the 28th day, ischemia was produced by one-stage ligation of the left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed and the heart tissue was processed for biochemical, morphological, and molecular studies. Kaempferol pretreatment significantly reduced hyperglycemia, maintained hemodynamic function, suppressed AGE-RAGE axis activation, normalized oxidative stress, and preserved morphological alterations. In addition, there was decreased level of inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and NF-κB), inhibition of active c-Jun N-terminal kinase (JNK) and p38 proteins, and activation of Extracellular signal regulated kinase 1/2 (ERK1/2) a prosurvival kinase. Furthermore, it also attenuated apoptosis by reducing the expression of pro-apoptotic proteins (Bax and Caspase-3), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells, and increasing the level of anti-apoptotic protein (Bcl-2). In conclusion, kaempferol attenuated

  17. Signal Transduction Pathways Involved in Brain Death-Induced Renal Injury

    NARCIS (Netherlands)

    Bouma, H. R.; Ploeg, R. J.; Schuurs, T. A.

    Kidneys derived from brain death organ donors show an inferior survival when compared to kidneys derived from living donors. Brain death is known to induce organ injury by evoking an inflammatory response in the donor. Neuronal injury triggers an inflammatory response in the brain, leading to

  18. Involving Parents in Indicated Early Intervention for Childhood PTSD Following Accidental Injury

    Science.gov (United States)

    Cobham, Vanessa E.; March, Sonja; De Young, Alexandra; Leeson, Fiona; Nixon, Reginald; McDermott, Brett; Kenardy, Justin

    2012-01-01

    Accidental injuries represent the most common type of traumatic event to which a youth is likely to be exposed. While the majority of youth who experience an accidental injury will recover spontaneously, a significant proportion will go on to develop Post-Traumatic Stress Disorder (PTSD). And yet, there is little published treatment outcome…

  19. Nonsteroidal anti-inflammatory drug flufenamic acid is a potent activator of AMP-activated protein kinase.

    Science.gov (United States)

    Chi, Yuan; Li, Kai; Yan, Qiaojing; Koizumi, Schuichi; Shi, Liye; Takahashi, Shuhei; Zhu, Ying; Matsue, Hiroyuki; Takeda, Masayuki; Kitamura, Masanori; Yao, Jian

    2011-10-01

    Flufenamic acid (FFA) is a nonsteroidal anti-inflammatory drug (NSAID). It has anti-inflammatory and antipyretic properties. In addition, it modulates multiple channel activities. The mechanisms underlying the pharmacological actions of FFA are presently unclear. Given that AMP-activated protein kinase (AMPK) has both anti-inflammatory and channel-regulating functions, we examined whether FFA induces AMPK activation. 1) Exposure of several different types of cells to FFA resulted in an elevation of AMPKα phosphorylation at Thr172. This effect of FFA was reproduced by functionally and structurally similar mefenamic acid, tolfenamic acid, niflumic acid, and meclofenamic acid. 2) FFA-induced activation of AMPK was largely abolished by the treatment of cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (an intracellular Ca(2+) chelator) or depletion of extracellular Ca(2+), whereas it was mimicked by stimulation of cells with the Ca(2+) ionophore 5-(methylamino)-2-({(2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]-1,7-dioxaspiro[5.5]undec-2-yl}methyl)-1,3-benzoxazole-4-carboxylic acid (A23187) or ionomycin. 3) FFA triggered a rise in intracellular Ca(2+), which was abolished by cyclosporine, a blocker of mitochondrial permeability transition pore. Cyclosporine also abolished FFA-induced activation of AMPK. 4) Inhibition of Ca(2+)/calmodulin-dependent kinase kinase β (CaMKKβ) with 7-oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic acid acetate (STO-609) or down-regulation of CaMKKβ with short interfering RNA largely abrogated FFA-induced activation of AMPK. 5) FFA significantly suppressed nuclear factor-κB activity and inducible nitric-oxide synthase expression triggered by interleukin-1β and tumor necrosis factor α. This suppression was also largely abrogated by STO-609. Taken together, we conclude that FFA induces AMPK activation through the Ca(2+)-CaMKKβ pathway

  20. AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD

    Directory of Open Access Journals (Sweden)

    Josef eBrandauer

    2015-03-01

    Full Text Available The mitochondrial protein deacetylase sirtuin (SIRT 3 may mediate exercise training-induced increases in mitochondrial biogenesis and improvements in reactive oxygen species (ROS handling. We determined the requirement of AMP-activated protein kinase (AMPK for exercise training-induced increases in skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise training for 6.5 weeks increased SIRT3 (p<0.01 and superoxide dismutase 2 (MnSOD; p<0.05 protein abundance in quadriceps muscle of wild-type (WT; n=13-15, but not AMPK α2 kinase dead (KD; n=12-13 mice. We also observed a strong trend for increased MnSOD abundance in exercise-trained skeletal muscle of healthy humans (p=0.051; n=6. To further elucidate a role for AMPK in mediating these effects, we treated WT (n=7-8 and AMPK α2 KD (n=7-9 mice with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR. Four weeks of daily AICAR injections (500 mg/kg resulted in AMPK-dependent increases in SIRT3 (p<0.05 and MnSOD (p<0.01 in WT, but not AMPK α2 KD mice. We also tested the effect of repeated AICAR treatment on mitochondrial protein levels in mice lacking the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PGC-1α KO; n=9-10. Skeletal muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1α KO mice (p<0.01 and AICAR-induced increases in SIRT3 and MnSOD protein abundance was only observed in WT mice (p<0.05. Finally, the acetylation status of SIRT3 target lysine residues on MnSOD (K122 or oligomycin-sensitivity conferring protein (OSCP; K139 was not altered in either mouse or human skeletal muscle in response to acute exercise. We propose an important role for AMPK in regulating mitochondrial function and ROS handling in skeletal muscle in response to exercise training.

  1. Analyzing injury severity factors at highway railway grade crossing accidents involving vulnerable road users: A comparative study.

    Science.gov (United States)

    Ghomi, Haniyeh; Bagheri, Morteza; Fu, Liping; Miranda-Moreno, Luis F

    2016-11-16

    The main objective of this study is to identify the main factors associated with injury severity of vulnerable road users (VRUs) involved in accidents at highway railroad grade crossings (HRGCs) using data mining techniques. This article applies an ordered probit model, association rules, and classification and regression tree (CART) algorithms to the U.S. Federal Railroad Administration's (FRA) HRGC accident database for the period 2007-2013 to identify VRU injury severity factors at HRGCs. The results show that train speed is a key factor influencing injury severity. Further analysis illustrated that the presence of illumination does not reduce the severity of accidents for high-speed trains. In addition, there is a greater propensity toward fatal accidents for elderly road users compared to younger individuals. Interestingly, at night, injury accidents involving female road users are more severe compared to those involving males. The ordered probit model was the primary technique, and CART and association rules act as the supporter and identifier of interactions between variables. All 3 algorithms' results consistently show that the most influential accident factors are train speed, VRU age, and gender. The findings of this research could be applied for identifying high-risk hotspots and developing cost-effective countermeasures targeting VRUs at HRGCs.

  2. Cannabis Involvement and Nonsuicidal Self-Injury: A Discordant Twin Approach.

    Science.gov (United States)

    Few, Lauren R; Grant, Julia D; Nelson, Elliot C; Trull, Timothy J; Grucza, Richard A; Bucholz, Kathleen K; Verweij, Karin J H; Martin, Nicholas G; Statham, Dixie J; Madden, Pamela A F; Heath, Andrew C; Lynskey, Michael T; Agrawal, Arpana

    2016-11-01

    Cannabis use, particularly at an early age, has been linked to suicidal thoughts and behavior, but minimal work has examined the association between cannabis use and lifetime nonsuicidal self-injury (NSSI). The current study aims to characterize the overlap between lifetime and early cannabis use and NSSI and to examine genetic and environmental mechanisms of this association. Adult male and female twins from the Australian Twin Registry (N = 9,583) were used to examine the odds of NSSI associated with lifetime cannabis use and early cannabis use (i.e., accounting for the age at onset of cannabis use and NSSI. Lifetime cannabis use (odds ratio [OR] = 2.84, 95% CI [2.23, 3.61]) and early cannabis use were associated with increased odds of NSSI (OR = 2.15, 95% CI [1.75, 2.65]), and this association remained when accounting for covariates. The association was only significant, however, in MZ twin pairs discordant for early cannabis use (OR = 3.20, 95% CI [1.17, 8.73]). Replication analyses accounting for the temporal ordering of cannabis use and NSSI yielded similar findings of nominal significance. Results suggest that NSSI is associated with cannabis involvement via differing mechanisms. For lifetime cannabis use, the lack of association in discordant pairs suggests the role of shared genes and family environment. However, in addition to such shared familial influences, person-specific and putatively causal factors contribute to the relationship between early cannabis use and NSSI. Therefore, delaying the onset of cannabis use may reduce exposure to influences that exacerbate vulnerabilities to NSSI.

  3. TAEKWONDO TECHNIQUES AND COMPETITION CHARACTERISTICS INVOLVED IN TIME-LOSS INJURIES

    Directory of Open Access Journals (Sweden)

    Konstantinos Beis

    2007-10-01

    Full Text Available The purpose of this study was to assess time-loss injuries in young and adult taekwondo athletes. Participants were 2739 children (11-13 years, Junior (14-17 years and adult males and females (18 years and older competing in the national Greek championships. Injury data were collected by project staff with all diagnoses made by the tournament physician. Odds ratios were computed as well as 95% confidence intervals around the injury rates. The female Juniors had a higher time-loss injury rate (Fisher's Exact Test p = 0.033 than their adult counterparts. However, they were not at a higher risk of incurring a time-loss injury: OR = 0.143, 95% CI: 0.018-1.124. Collapsed over age, the females as a group recorded more time-loss injuries [11.36/1,000 A-E (95% CI: 6.25-16.47 versus 7.40/1,000 A-E (95% CI: 4.44-10.36], but this was not significant (OR = 0.703, 95% CI: 0.383-1.293. In the Juniors, the boys only incurred time-loss injuries to the head and neck. There was no difference in the Junior girls in the distribution of time-loss injuries across body region, although they were at higher risk of sustaining an injury to the head and neck (OR = 1.510, 95% CI: 0.422-5.402 but this was not statistically significant. Although there were no statistical differences among age groups within gender, the Junior boys and girls (11-13 years sustained more cerebral concussions. The Junior boys were at a higher risk of incurring a cerebral concussion than the boys (OR = 7.871, 95% CI: 0.917-67.583, Fisher's Exact Test p = 0.036. In the males, there was no difference between the men and Junior boys in injury rate for swing kicks compared to other techniques (OR = 2.000, 95% CI = 0.397-28.416. There also was no difference between the men and boys (OR = 4.800, 95% CI: 0.141-58.013. To help reduce the incidence of time-loss injuries in taekwondo, especially cerebral concussions, it is suggested for coaches to emphasize blocking skills. Educating referees, coaches and

  4. Factors related to serious injury in post-NCAP European cars involved in frontal crashes.

    Science.gov (United States)

    Frampton, Richard; Williams, Owen; Thomas, Pete

    2004-01-01

    ABSTRACT This study examined the relationship between EuroNCAP ratings for body region protection and real world injury risk for 653 belted drivers in frontal crashes. It was also able to comment on further improvements in crash protection for post-EuroNCAP cars. Protection for the head and lower leg appeared good. In terms of life threatening injury, results showed a need to prioritise chest protection, whilst for impairment, protection for the upper leg and ankle/foot should be considered. The EuroNCAP body region scoring system reflects trends in real crash injury risks to all body regions, except for the chest, where there is no clear trend. More generally, further development in the testing regime could usefully concentrate on a restraint system test and the use of smaller dummies seated appropriately, rather than an increase of the test speed.

  5. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase

    DEFF Research Database (Denmark)

    Matthews, V B; Åström, Maj-Brit; Chan, M H S

    2009-01-01

    C12 skeletal muscle cells were electrically stimulated to mimic contraction. L6 myotubes and isolated rat extensor digitorum longus muscles were treated with BDNF and phosphorylation of the proteins AMP-activated protein kinase (AMPK) (Thr(172)) and acetyl coenzyme A carboxylase beta (ACCbeta) (Ser...... kinase (p44/42 Thr(202)/Tyr(204)) phosphorylation in these muscles. In addition, phosphorylation of ACCbeta was markedly elevated in the Bdnf electroporated muscles. CONCLUSIONS/INTERPRETATION: These data identify BDNF as a contraction-inducible protein in skeletal muscle that is capable of enhancing...

  6. The rational design of a novel potent analogue of the 5’-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity

    Science.gov (United States)

    Machrouhi, Fouzia; Ouhamou, Nouara; Laderoute, Keith; Calaoagan, Joy; Bukhtiyarova, Marina; Ehrlich, Paula J.; Klon, Anthony E.

    2010-01-01

    We have designed and synthesized analogues of compound C, a non-specific inhibitor of 5’-AMP-activated protein kinase (AMPK), using a computational fragment-based drug design (FBDD) approach. Synthesizing only twenty-seven analogues yielded a compound that was equipotent to compound C in the inhibition of the human AMPK (hAMPK) α2 subunit in the heterotrimeric complex in vitro, exhibited significantly improved selectivity against a subset of relevant kinases, and demonstrated enhanced cellular inhibition of AMPK. PMID:20932747

  7. Cannabis involvement and non-suicidal self-injury: A discordant twin approach

    NARCIS (Netherlands)

    Few, L.R.; Grant, J.D.; Nelson, E.C.; Trull, T.J.; Grucza, R.A.; K.K., Bucholz; Verweij, C.J.H.; Martin, N.G.; Statham, D.J.; Madden, P.A.F.; Heath, A.C.; Lynskey, M.T.; Agrawal, A.

    2016-01-01

    Objective: Cannabis use, particularly at an early age, has been linked to suicidal thoughts and behavior, but minimal work has examined the association between cannabis use and lifetime nonsuicidal self-injury (NSSI). The current study aims to characterize the overlap between lifetime and early

  8. Cannabis involvement and nonsuicidal self-injury: A discordant twin approach

    NARCIS (Netherlands)

    Few, L.R.; Grant, J.D.; Nelson, E.C.; Trull, T.J.; Grucza, R.A.; Bucholz, K.K.; Verweij, K.J.H.; Martin, N.G.; Statham, D.J.; Madden, P.A.F.; Heath, A.C.; Lynskey, M.T.; Agrawal, A.

    2016-01-01

    OBJECTIVE: Cannabis use, particularly at an early age, has been linked to suicidal thoughts and behavior, but minimal work has examined the association between cannabis use and lifetime nonsuicidal self-injury (NSSI). The current study aims to characterize the overlap between lifetime and early

  9. Serious injury and fatality investigations involving pneumatic nail guns, 1985-2012.

    Science.gov (United States)

    Lowe, Brian D; Albers, James T; Hudock, Stephen D; Krieg, Edward F

    2016-02-01

    This article examines serious and fatal pneumatic nail gun (PNG) injury investigations for workplace, tool design, and human factors relevant to causation and resulting OS&H authorities' responses in terms of citations and penalties. The U.S. Occupational Safety and Health Administration (OSHA) database of Fatality and Catastrophe Investigation Summaries (F&CIS) were reviewed (1985-2012) to identify n = 258 PNG accidents. 79.8% of investigations, and 100% of fatalities, occurred in the construction industry. Between 53-71% of injuries appear to have been preventable had a safer sequential trigger tool been used. Citations and monetary penalties were related to injury severity, body part injured, disabling of safety devices, and insufficient personal protective equipment (PPE). Differences may exist between construction and other industries in investigators interpretations of PNG injury causation and resulting citations/penalties. Violations of PPE standards were penalized most severely, yet the preventive effect of PPE would likely have been less than that of a safer sequential trigger. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  10. Serious Injury and Fatality Investigations Involving Pneumatic Nail Guns, 1985-2012

    Science.gov (United States)

    Lowe, Brian D.; Albers, James T.; Hudock, Stephen D.; Krieg, Edward F.

    2016-01-01

    Background This paper examines serious and fatal pneumatic nail gun (PNG) injury investigations for workplace, tool design, and human factors relevant to causation and resulting OS&H authorities’ responses in terms of citations and penalties. Methods The U.S. OSHA database of Fatality and Catastrophe Investigation Summaries (F&CIS) were reviewed (1985 - 2012) to identify n=258 PNG accidents. Results 79.8% of investigations, and 100% of fatalities, occurred in the Construction industry. Between 53-71% of injuries appear preventable had a safer sequential trigger tool been used. Citations and monetary penalties were related to injury severity, body part injured, disabling of safety devices, and insufficient personal protective equipment (PPE). Conclusions Differences may exist between Construction and other industries in investigators interpretations of PNG injury causation and resulting citations/penalties. Violations of PPE standards were penalized most severely, yet the preventive effect of PPE would likely have been less than that of a safer sequential trigger. PMID:26725335

  11. Lack of evidence of CD40 ligand involvement in transfusion-related acute lung injury

    NARCIS (Netherlands)

    Tuinman, P. R.; Gerards, M. C.; Jongsma, G.; Vlaar, A. P.; Boon, L.; Juffermans, N. P.

    2011-01-01

    Activated platelets have been implicated in playing a major role in transfusion-related acute lung injury (TRALI), as platelets can trigger neutrophils, resulting in vascular damage. We hypothesized that binding of platelet CD40 ligand (CD40L) to endothelial CD40 is essential in the onset of TRALI.

  12. Crystallization of the glycogen-binding domain of the AMP-activated protein kinase β subunit and preliminary X-ray analysis

    Energy Technology Data Exchange (ETDEWEB)

    Polekhina, Galina, E-mail: gpolekhina@svi.edu.au; Feil, Susanne C.; Gupta, Abhilasha [St Vincent’s Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065 (Australia); O’Donnell, Paul [Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville 3010 (Australia); Stapleton, David; Parker, Michael W. [St Vincent’s Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065 (Australia)

    2005-01-01

    The glycogen-binding domain of the AMP-activated kinase β subunit has been crystallized in the presence of β-cyclodextrin. The structure has been determined by single isomorphous replacement and threefold averaging using in-house X-ray data collected from selenomethionine-substituted protein. AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolism in response to energy demand and supply by adjusting the ATP-generating and ATP-consuming pathways. AMPK potentially plays a critical role in diabetes and obesity as it is known to be activated by metforin and rosiglitazone, drugs used for the treatment of type II diabetes. AMPK is a heterotrimer composed of a catalytic α subunit and two regulatory subunits, β and γ. Mutations in the γ subunit are known to cause glycogen accumulation, leading to cardiac arrhythmias. Recently, a functional glycogen-binding domain (GBD) has been identified in the β subunit. Here, the crystallization of GBD in the presence of β-cyclodextrin is reported together with preliminary X-ray data analysis allowing the determination of the structure by single isomorphous replacement and threefold averaging using in-house X-ray data collected from a selenomethionine-substituted protein.

  13. Crystallization of the glycogen-binding domain of the AMP-activated protein kinase β subunit and preliminary X-ray analysis

    International Nuclear Information System (INIS)

    Polekhina, Galina; Feil, Susanne C.; Gupta, Abhilasha; O’Donnell, Paul; Stapleton, David; Parker, Michael W.

    2004-01-01

    The glycogen-binding domain of the AMP-activated kinase β subunit has been crystallized in the presence of β-cyclodextrin. The structure has been determined by single isomorphous replacement and threefold averaging using in-house X-ray data collected from selenomethionine-substituted protein. AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolism in response to energy demand and supply by adjusting the ATP-generating and ATP-consuming pathways. AMPK potentially plays a critical role in diabetes and obesity as it is known to be activated by metforin and rosiglitazone, drugs used for the treatment of type II diabetes. AMPK is a heterotrimer composed of a catalytic α subunit and two regulatory subunits, β and γ. Mutations in the γ subunit are known to cause glycogen accumulation, leading to cardiac arrhythmias. Recently, a functional glycogen-binding domain (GBD) has been identified in the β subunit. Here, the crystallization of GBD in the presence of β-cyclodextrin is reported together with preliminary X-ray data analysis allowing the determination of the structure by single isomorphous replacement and threefold averaging using in-house X-ray data collected from a selenomethionine-substituted protein

  14. [Application of three-dimensional printing in the operation of distal tibia fracture involving epiphyseal plate injury for teenagers].

    Science.gov (United States)

    Zhao, Jingxin; Ma, Yachang; Han, Dong; Jin, Yu

    2017-10-01

    To investigate the application value of three-dimensional (3-D) printing technology in the operation of distal tibia fracture involving epiphyseal plate injury for teenagers. The retrospective analysis was conducted on the clinical data of 16 cases of children patients with distal tibia fracture involving epiphyseal plate injury undergoing the operation by using of 3-D printing technology between January 2014 and December 2015. There were 12 males and 4 females with an age of 9-14 years (mean, 12.8 years). The causes of injury included traffic accident injury in 9 cases, heavy pound injury in 3 cases, and sport injury in 4 cases. The time from injury to operation was 3-92 hours (mean, 25.8 hours). According to Salter-Harris typing standard, the typing for epiphyseal injury was classified as type Ⅱ in 11 cases, type Ⅲ in 4 cases, and type Ⅳ in 1 case. The thin slice CT scan on the affected limb was performed before operation, and the Mimics14.0 medical software was applied for the design and the 1∶1 fracture model was printed by the 3-D printer; the stimulation of operative reduction was made in the fracture model, and bone plate, Kirschner wire, and hollow screw with the appropriate size were chosen, then the complete operative approach and method were designed and the internal fixator regimen was chosen, then the practical operation was performed based on the preoperative design regimen. The operation time was 40-68 minutes (mean, 59.1 minutes); the intraoperative blood loss was 5-102 mL (mean, 35 mL); the intraoperative fluoroscopy times was 2-6 times (mean, 2.8 times). All the patiens were followed up 12-24 months (mean, 15 months). The fracture of 15 cases reached anatomic reduction, and 1 cases had no anatomic reduction with the displaced end less than 1 mm. All the fractures reached bony union with the healing time of 2-4 months (mean, 2.6 months). There was no deep vein thrombosis, premature epiphyseal closure and oblique, or uneven ankle surface

  15. Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat

    OpenAIRE

    Due, Michael R.; Park, Jonghyuck; Zheng, Lingxing; Walls, Michael; Allette, Yohance M.; White, Fletcher A.; Shi, Riyi

    2013-01-01

    Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here we report that there are enhanced levels of acrolein and increased neuronal sensitivity t...

  16. Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Nozomi Yabuuchi

    2016-12-01

    Full Text Available High mortality of acute kidney injury (AKI is associated with acute lung injury (ALI, which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS, in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5, in bilateral nephrectomy (BNx-induced AKI model rats. BNx evoked AKI with the increases in serum creatinine (SCr, blood urea nitrogen (BUN and serum IS levels and exhibited thickening of interstitial tissue in the lung. Administration of AST-120, clinically-used oral spherical adsorptive carbon beads, resulted in a significant decrease in serum IS level and thickening of interstitial tissue, which was accompanied with the decreases in IS accumulation in various tissues, especially lung. Interestingly, a significant decrease in AQP-5 expression of lung was observed in BNx rats. Moreover, the BNx-induced decrease in pulmonary AQP-5 protein expression was markedly restored by oral administration of AST-120. These results suggest that BNx-induced AKI causes dysregulation of pulmonary AQP-5 expression, in which IS could play a toxico-physiological role as a mediator involved in renopulmonary crosstalk.

  17. Medical consultations and the sharing of medical images involving spinal injury over mobile phone networks.

    Science.gov (United States)

    Filip, Michal; Linzer, Petr; Šámal, Filip; Tesař, Jiří; Herzig, Roman; Školoudík, David

    2012-07-01

    The transmission of medical images and other data over mobile phone networks may facilitate remote medical consultations between neurosurgeons and regional hospitals treating spinal injury patients. The aim of this study was to compare the efficacy of mobile phone consultations with standard hospital workstation consultations in spinal injury patients. The images were exported over the Internet from surrounding local hospitals through the Picture Archiving and Communication System, in DICOM III format, to the central hospital server. The xVision browser was used to view the acquired images on a standard workstation. The data were also exported to the secured hospital Web server IIS60 and converted to JPEG format to enable remote physician access and consultation. The remote consulting physician connected to this server by mobile phone using the phone's Internet browser. A second physician, blind to the mobile phone results, evaluated the same images at a workstation in the hospital. The results of the mobile phone consultations were compared with the results from standard workstation consultations. There was no difference in the quality of spinal computed tomographic/magnetic resonance images viewed on the phone screen compared with on the workstation. More importantly, the final diagnoses made by mobile phone did not differ from those made by workstation consultations. A transfer to the department of neurosurgery was required after consultation in 11 patients. Mobile phone consultations for patients with spinal injuries was as effective as workstation consultations. Mobile phone consultations can increase the expertise available to regional hospitals, which are often the first responders to medical emergencies. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat

    Science.gov (United States)

    Zheng, Lingxing; Walls, Michael; Allette, Yohance M.; White, Fletcher A.; Shi, Riyi

    2013-01-01

    Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound’s pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggests that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. PMID:24147766

  19. Advanced glycation end product Nε-carboxymethyllysine induces endothelial cell injury: the involvement of SHP-1-regulated VEGFR-2 dephosphorylation.

    Science.gov (United States)

    Liu, Shing Hwa; Sheu, Wayne Huey Herng; Lee, Maw Rong; Lee, Wen Jane; Yi, Yu Chiao; Yang, Tzung Jie; Jen, Jen Fon; Pan, Hung Chuan; Shen, Chin Chang; Chen, Wen Bao; Tien, Hsing Ru; Sheu, Meei Ling

    2013-06-01

    N(ε)-carboxymethyllysine (CML), a major advanced glycation end product, plays a crucial role in diabetes-induced vascular injury. The roles of protein tyrosine phosphatases and vascular endothelial growth factor (VEGF) receptors in CML-related endothelial cell injury are still unclear. Human umbilical vein endothelial cells (HUVECs) are a commonly used human EC type. Here, we tested the hypothesis that NADPH oxidase/reactive oxygen species (ROS)-mediated SH2 domain-containing tyrosine phosphatase-1 (SHP-1) activation by CML inhibits the VEGF receptor-2 (VEGFR-2, KDR/Flk-1) activation, resulting in HUVEC injury. CML significantly inhibited cell proliferation and induced apoptosis and reduced VEGFR-2 activation in parallel with the increased SHP-1 protein expression and activity in HUVECs. Adding recombinant VEGF increased forward biological effects, which were attenuated by CML. The effects of CML on HUVECs were abolished by SHP-1 siRNA transfection. Exposure of HUVECs to CML also remarkably escalated the integration of SHP-1 with VEGFR-2. Consistently, SHP-1 siRNA transfection and pharmacological inhibitors could block this interaction and elevating [(3)H]thymidine incorporation. CML also markedly activated the NADPH oxidase and ROS production. The CML-increased SHP-1 activity in HUVECs was effectively attenuated by antioxidants. Moreover, the immunohistochemical staining of SHP-1 and CML was increased, but phospho-VEGFR-2 staining was decreased in the aortic endothelium of streptozotocin-induced and high-fat diet-induced diabetic mice. We conclude that a pathway of tyrosine phosphatase SHP-1-regulated VEGFR-2 dephosphorylation through NADPH oxidase-derived ROS is involved in the CML-triggered endothelial cell dysfunction/injury. These findings suggest new insights into the development of therapeutic approaches to reduce diabetic vascular complications. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. Polydatin Protects Bone Marrow Stem Cells against Oxidative Injury: Involvement of Nrf 2/ARE Pathways

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    Meihui Chen

    2016-01-01

    Full Text Available Polydatin, a glucoside of resveratrol, has been reported to possess potent antioxidative effects. In the present study, we aimed to investigate the effects of polydatin in bone marrow-derived mesenchymal stem cells (BMSCs death caused by hydrogen peroxide (H2O2, imitating the microenvironment surrounding transplanted cells in the injured spinal cord in vitro. In our study, MTT results showed that polydatin effectively prevented the decrease of cell viability caused by H2O2. Hochest 33258, Annexin V-PI, and Western blot assay showed H2O2-induced apoptosis in BMSCs, which was attenuated by polydatin. Further studies indicated that polydatin significantly protects BMSCs against apoptosis due to its antioxidative effects and the regulation of Nrf 2/ARE pathway. Taken together, our results indicate that polydatin could be used in combination with BMSCs for the treatment of spinal cord injury by improving the cell survival and oxidative stress microenvironments.

  1. THE INJURY SEVERITY RATE DIFFERENCES IN PASSENGER CARS AND PICK UP TRUCKS RELATED TWO VEHICLE INVOLVED MOTOR VEHICLE CRASHES IN BRITISH COLUMBIA, CANADA

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    E.B.R. DESAPRIYA

    2004-01-01

    Full Text Available The effect of large vehicle involvement on motor vehicle crash (MVC rates and severity has long been a concern in MVC analysis literature. Injuries in drivers and occupants are related to several key factors: the mass of the case vehicle and mass of its collision partner and speed of case vehicle and collision partner at the time of the crash. Objective: To evaluate the relative risk of injury occurrence in collisions between picks up trucks (PU and passenger sedan cars (PS. Methods: Data from the Insurance Corporation of British Columbia (ICBC crash data base was used to determine MVC rates and injury occurrence. Descriptive characteristics of the injury location and injury type were analyzed comparing the Odds Ratios and chi-squares. Results: PS occupants received more injuries; Odds Ratio was 2.49 (95% confidence interval: 2.15–2.88. Conclusion: Occupants in PS which collide with PU were at twice the risk of injuries. Concussion, whiplash, lacerations and abrasion were more frequent in PS drivers and occupants than in PU drivers and occupants. Overall, PS drivers/occupants experienced greater injuries than PU drivers/occupants in PU-PS collisions. In this paper, results are shown as odds ratios comparing occupants injuries in PS (case group with occupant injuries in PU (control group.

  2. Green tea polyphenols alter lipid metabolism in the livers of broiler chickens through increased phosphorylation of AMP-activated protein kinase.

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    Jinbao Huang

    Full Text Available Our previous results showed that green tea polyphenols (GTPs significantly altered the expression of lipid-metabolizing genes in the liver of chickens. However, the underlying mechanism was not elucidated. In this study, we further characterized how GTPs influence AMP-activated protein kinase (AMPK in the regulation of hepatic fat metabolism. Thirty-six male chickens were fed GTPs at a daily dose of 0, 80 or 160 mg/kg of body weight for 4 weeks. The results demonstrated that oral administration of GTPs significantly reduced hepatic lipid content and abdominal fat mass, enhanced the phosphorylation levels of AMPKα and ACACA, and altered the mRNA levels and enzymatic activities of lipid-metabolizing enzymes in the liver. These results suggested that the activation of AMPK is a potential mechanism by which GTPs regulate hepatic lipid metabolism in such a way that lipid synthesis is reduced and fat oxidation is stimulated.

  3. Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation

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    Zhou, Yan; Ruan, Zheng; Zhou, Lili; Shu, Xugang; Sun, Xiaohong; Mi, Shumei; Yang, Yuhui; Yin, Yulong

    2016-01-01

    Acute or chronic hepatic injury is a common pathology worldwide. Mitochondrial dysfunction and the depletion of adenosine triphosphate (ATP) play important roles in liver injury. Chlorogenic acids (CGA) are some of the most abundant phenolic acids in human diet. This study was designed to test the hypothesis that CGA may protect against chronic lipopolysaccharide (LPS)-induced liver injury by modulating mitochondrial energy generation. CGA decreased the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The contents of ATP and adenosine monophosphate (AMP), as well as the ratio of AMP/ATP, were increased after CGA supplementation. The activities of enzymes that are involved in glycolysis were reduced, while those of enzymes involved in oxidative phosphorylation were increased. Moreover, phosphorylated AMP-activated protein kinase (AMPK), and mRNA levels of AMPK-α, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial DNA transcription factor A were increased after CGA supplementation. Collectively, these findings suggest that the hepatoprotective effect of CGA might be associated with enhanced ATP production, the stimulation of mitochondrial oxidative phosphorylation and the inhibition of glycolysis. - Highlights: • Dietary supplementation with chlorogenic acid (CGA) improved endotoxin-induced liver injury. • Chlorogenic acid enhances ATP increase and shifts energy metabolism, which is correlated with up-regulation AMPK and PGC-1α. • The possible mechanism of CGA on mitochondrial biogenesis was correlated with up-regulation AMPK and PGC-1α.

  4. Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yan [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); College of Food Safety, Guizhou Medical University, Guiyang 550025 (China); Ruan, Zheng, E-mail: ruanzheng@ncu.edu.cn [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); Zhou, Lili; Shu, Xugang [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); Sun, Xiaohong [College of Food Safety, Guizhou Medical University, Guiyang 550025 (China); Mi, Shumei; Yang, Yuhui [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); Yin, Yulong, E-mail: yinyulong@isa.ac.cn [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125 (China)

    2016-01-22

    Acute or chronic hepatic injury is a common pathology worldwide. Mitochondrial dysfunction and the depletion of adenosine triphosphate (ATP) play important roles in liver injury. Chlorogenic acids (CGA) are some of the most abundant phenolic acids in human diet. This study was designed to test the hypothesis that CGA may protect against chronic lipopolysaccharide (LPS)-induced liver injury by modulating mitochondrial energy generation. CGA decreased the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The contents of ATP and adenosine monophosphate (AMP), as well as the ratio of AMP/ATP, were increased after CGA supplementation. The activities of enzymes that are involved in glycolysis were reduced, while those of enzymes involved in oxidative phosphorylation were increased. Moreover, phosphorylated AMP-activated protein kinase (AMPK), and mRNA levels of AMPK-α, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial DNA transcription factor A were increased after CGA supplementation. Collectively, these findings suggest that the hepatoprotective effect of CGA might be associated with enhanced ATP production, the stimulation of mitochondrial oxidative phosphorylation and the inhibition of glycolysis. - Highlights: • Dietary supplementation with chlorogenic acid (CGA) improved endotoxin-induced liver injury. • Chlorogenic acid enhances ATP increase and shifts energy metabolism, which is correlated with up-regulation AMPK and PGC-1α. • The possible mechanism of CGA on mitochondrial biogenesis was correlated with up-regulation AMPK and PGC-1α.

  5. Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cheng Tien [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Weng, Te I. [Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Chen, Li Ping [Department of Dentistry, Chang Gang Memorial Hospital, Chang Gang University, Taoyuan, Taiwan (China); Chiang, Chih Kang [Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Liu, Shing Hwa, E-mail: shinghwaliu@ntu.edu.tw [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)

    2013-01-01

    Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

  6. Involvement of the nitric oxide in melatonin-mediated protection against injury.

    Science.gov (United States)

    Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

    2018-05-01

    Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys.

    Science.gov (United States)

    Cui, Jing; Shi, Suozhu; Sun, Xuefeng; Cai, Guangyan; Cui, Shaoyuan; Hong, Quan; Chen, Xiangmei; Bai, Xue-Yuan

    2013-01-01

    A high-calorie (HC) diet induces renal injury and promotes aging, and calorie restriction (CR) may ameliorate these responses. However, the effects of long-term HC and CR on renal damage and aging have been not fully determined. Autophagy plays a crucial role in removing protein aggregates and damaged organelles to maintain intracellular homeostasis and function. The role of autophagy in HC-induced renal damage is unknown. We evaluated the expression of LC3/Atg8 as a marker of the autophagosome; p62/SQSTM1; polyubiquitin aggregates as markers of autophagy flux; Ambra1, PINK1, Parkin and Bnip3 as markers of mitophagy; 8-hydroxydeoxyguanosine (8-OHdG) as a marker of DNA oxidative damage; and p16 as a marker of organ aging by western blot and immunohistochemical staining in the kidneys of 24-month-old Fischer 344 rats. We also observed mitochondrial structure and autolysosomes by transmission electron microscopy. Expression of the autophagosome formation marker LC3/Atg8 and markers of mitochondrial autophagy (mitophagy) were markedly decreased in the kidneys of the HC group, and markedly increased in CR kidneys. p62/SQSTM1 and polyubiquitin aggregates increased in HC kidneys, and decreased in CR kidneys. Transmission electron microscopy demonstrated that HC kidneys showed severe abnormal mitochondrial morphology with fewer autolysosomes, while CR kidneys exhibited normal mitochondrial morphology with numerous autolysosomes. The level of 8-hydroxydeoxyguanosine was increased in HC kidneys and decreased in CR kidneys. Markers of aging, such as p16 and senescence-associated-galactosidase, were increased significantly in the HC group and decreased significantly in the CR group. The study firstly suggests that HC diet inhibits renal autophagy and aggravates renal oxidative damage and aging, while CR enhances renal autophagy and ameliorates oxidative damage and aging in the kidneys.

  8. Podocyte expression of membrane transporters involved in puromycin aminonucleoside-mediated injury.

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    Cristina Zennaro

    Full Text Available Several complex mechanisms contribute to the maintenance of the intricate ramified morphology of glomerular podocytes and to interactions with neighboring cells and the underlying basement membrane. Recently, components of small molecule transporter families have been found in the podocyte membrane, but expression and function of membrane transporters in podocytes is largely unexplored. To investigate this complex field of investigation, we used two molecules which are known substrates of membrane transporters, namely Penicillin G and Puromycin Aminonucleoside (PA. We observed that Penicillin G pre-administration prevented both in vitro and in vivo podocyte damage caused by PA, suggesting the engagement of the same membrane transporters by the two molecules. Indeed, we found that podocytes express a series of transporters which are known to be used by Penicillin G, such as members of the Organic Anion Transporter Polypeptides (OATP/Oatp family of influx transporters, and P-glycoprotein, a member of the MultiDrug Resistance (MDR efflux transporter family. Expression of OATP/Oatp transporters was modified by PA treatment. Similarly, in vitro PA treatment increased mRNA and protein expression of P-glycoprotein, as well as its activity, confirming the engagement of the molecule upon PA administration. In summary, we have characterized some of the small molecule transporters present at the podocyte membrane, focusing on those used by PA to enter and exit the cell. Further investigation will be needed to understand precisely the role of these transporter families in maintaining podocyte homeostasis and in the pathogenesis of podocyte injury.

  9. The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium regeneration after intestinal ischemia-reperfusion injury.

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    Guoqing Chen

    Full Text Available Notch signaling plays a critical role in the maintenance of intestinal crypt epithelial cell proliferation. The aim of this study was to investigate the role of Notch signaling in the proliferation and regeneration of intestinal epithelium after intestinal ischemia reperfusion (I/R injury.Male Sprague-Dawley rats were subjected to sham operation or I/R by occlusion of the superior mesenteric artery (SMA for 20 min. Intestinal tissue samples were collected at 0, 1, 2, 4, and 6 h after reperfusion. Proliferation of the intestinal epithelium was evaluated by immunohistochemical staining of proliferating nuclear antigen (PCNA. The mRNA and protein expression levels of Notch signaling components were examined using Real-time PCR and Western blot analyses. Immunofluorescence was also performed to detect the expression and location of Jagged-2, cleaved Notch-1, and Hes-1 in the intestine. Finally, the γ-secretase inhibitor DAPT and the siRNA for Jagged-2 and Hes-1 were applied to investigate the functional role of Notch signaling in the proliferation of intestinal epithelial cells in an in vitro IEC-6 culture system.I/R injury caused increased intestinal crypt epithelial cell proliferation and increased mRNA and protein expression of Jagged-2, Notch-1, and Hes-1. The immunofluorescence results further confirmed increased protein expression of Jagged-2, cleaved Notch-1, and Hes-1 in the intestinal crypts. The inhibition of Notch signaling with DAPT and the suppression of Jagged-2 and Hes-1 expression using siRNA both significantly inhibited the proliferation of IEC-6 cells.The Jagged-2/Notch-1/Hes-1 signaling pathway is involved in intestinal epithelium regeneration early after I/R injury by increasing crypt epithelial cell proliferation.

  10. The involvement of galectin-3 in skin injury in systemic lupus erythematosus patients.

    Science.gov (United States)

    Shi, Z; Meng, Z; Han, Y; Cao, C; Tan, G; Wang, L

    2018-04-01

    Objective Our previous research suggested that anti-galectin-3 antibody was highly associated with the development of lupus skin lesions in systemic lupus erythematosus (SLE). In this study we aimed to investigate the involvement of galectin-3 in SLE skin damage. Methods The study consisted of 49 patients with SLE, 16 with dermatomyositis and 11 with systemic scleroderma and 20 healthy controls. Galectin-3 was examined by ELISA and immunohistochemical staining in serum and skin, respectively. Results Serum galectin-3 was significantly higher in patients with SLE than in those with dermatomyositis ( P  0.05). As for subtypes of skin lesions in SLE, galectin-3 expression was lower in chronic cutaneous lupus erythematosus than in acute cutaneous lupus erythematosus ( P = 0.0439). Conclusion Serum galectin-3 is unlikely to play a role in the pathogenesis of lupus skin damage, but can be a potential biomarker for the measurement of SLE disease activity. Galectin-3 is greatly reduced in patients with lupus lesions compared with healthy controls, which may contribute to the recruitment of inflammatory cells in the skin.

  11. Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury.

    Science.gov (United States)

    Li, Guangke; Sang, Nan

    2009-01-01

    Recent studies implicate the possible neurotoxicity of SO(2), however, its mechanisms remain unclear. In the present study, we investigated SO(2) derivative-induced effect on delayed rectifier potassium channels (I(K)) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO(2) derivatives (NaHSO(3) and Na(2)SO(3), 3:1M/M) effectively augmented I(K) and promoted the activation of delayed rectifier potassium channels. Also, SO(2) derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO(2) derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not by the transient outward potassium channel blocker (4-aminopyridine, 4-AP). It implies that stimulating delayed rectifier potassium channels were involved in SO(2) derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO(2)-caused neuronal dysfunction.

  12. Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet.

    Science.gov (United States)

    Pu, Peng; Gao, Dong-Mei; Mohamed, Salim; Chen, Jing; Zhang, Jing; Zhou, Xiao-Ya; Zhou, Nai-Jing; Xie, Jing; Jiang, Hong

    2012-02-01

    Metabolic syndrome is a low-grade inflammatory state in which oxidative stress is involved. Naringin, isolated from the Citrussinensis, is a phenolic compound with anti-oxidative and anti-inflammatory activities. The aim of this study was to explore the effects of naringin on metabolic syndrome in mice. The animal models, induced by high-fat diet in C57BL/6 mice, developed obesity, dyslipidemia, fatty liver, liver dysfunction and insulin resistance. These changes were attenuated by naringin. Further investigations revealed that the inhibitory effect on inflammation and insulin resistance was mediated by blocking activation of the MAPKs pathways and by activating IRS1; the lipid-lowering effect was attributed to inhibiting the synthesis way and increasing fatty acid oxidation; the hypoglycemic effect was due to the regulation of PEPCK and G6pase. The anti-oxidative stress of naringin also participated in the improvement of insulin resistance and lipogenesis. All of these depended on the AMPK activation. To confirm the results of the animal experiment, we tested primary hepatocytes exposed to high glucose system. Naringin was protective by phosphorylating AMPKα and IRS1. Taken together, these results suggested that naringin protected mice exposed to a high-fat diet from metabolic syndrome through an AMPK-dependent mechanism involving multiple types of intracellular signaling and reduction of oxidative damage. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

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    Chai Bryan

    2012-10-01

    Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

  14. Involvement of ERK phosphorylation of trigeminal spinal subnucleus caudalis neurons in thermal hypersensitivity in rats with infraorbital nerve injury.

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    Ikuko Suzuki

    Full Text Available To evaluate the involvement of the mitogen-activated protein kinase (MAPK cascade in orofacial neuropathic pain mechanisms, this study assessed nocifensive behavior evoked by mechanical or thermal stimulation of the whisker pad skin, phosphorylation of extracellular signal-regulated kinase (ERK in trigeminal spinal subnucleus caudalis (Vc neurons, and Vc neuronal responses to mechanical or thermal stimulation of the whisker pad skin in rats with the chronic constriction nerve injury of the infraorbital nerve (ION-CCI. The mechanical and thermal nocifensive behavior was significantly enhanced on the side ipsilateral to the ION-CCI compared to the contralateral whisker pad or sham rats. ION-CCI rats had an increased number of phosphorylated ERK immunoreactive (pERK-IR cells which also manifested NeuN-IR but not GFAP-IR and Iba1-IR, and were significantly more in ION-CCI rats compared with sham rats following noxious but not non-noxious mechanical stimulation. After intrathecal administration of the MEK1 inhibitor PD98059 in ION-CCI rats, the number of pERK-IR cells after noxious stimulation and the enhanced thermal nocifensive behavior but not the mechanical nocifensive behavior were significantly reduced in ION-CCI rats. The enhanced background activities, afterdischarges and responses of wide dynamic range neurons to noxious mechanical and thermal stimulation in ION-CCI rats were significantly depressed following i.t. administration of PD98059, whereas responses to non-noxious mechanical and thermal stimulation were not altered. The present findings suggest that pERK-IR neurons in the Vc play a pivotal role in the development of thermal hypersensitivity in the face following trigeminal nerve injury.

  15. Cinnamon Extract Enhances Glucose Uptake in 3T3-L1 Adipocytes and C2C12 Myocytes by Inducing LKB1-AMP-Activated Protein Kinase Signaling

    Science.gov (United States)

    Shen, Yan; Honma, Natsumi; Kobayashi, Katsuya; Jia, Liu Nan; Hosono, Takashi; Shindo, Kazutoshi; Ariga, Toyohiko; Seki, Taiichiro

    2014-01-01

    We previously demonstrated that cinnamon extract (CE) ameliorates type 1 diabetes induced by streptozotocin in rats through the up-regulation of glucose transporter 4 (GLUT4) translocation in both muscle and adipose tissues. This present study was aimed at clarifying the detailed mechanism(s) with which CE increases the glucose uptake in vivo and in cell culture systems using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Specific inhibitors of key enzymes in insulin signaling and AMP-activated protein kinase (AMPK) signaling pathways, as well as small interference RNA, were used to examine the role of these kinases in the CE-induced glucose uptake. The results showed that CE stimulated the phosphorylation of AMPK and acetyl-CoA carboxylase. An AMPK inhibitor and LKB1 siRNA blocked the CE-induced glucose uptake. We also found for the first time that insulin suppressed AMPK activation in the adipocyte. To investigate the effect of CE on type 2 diabetes in vivo, we further performed oral glucose tolerance tests and insulin tolerance tests in type 2 diabetes model rats administered with CE. The CE improved glucose tolerance in oral glucose tolerance tests, but not insulin sensitivity in insulin tolerance test. In summary, these results indicate that CE ameliorates type 2 diabetes by inducing GLUT4 translocation via the AMPK signaling pathway. We also found insulin antagonistically regulates the activation of AMPK. PMID:24551069

  16. AMP-activated protein kinase regulates lymphocyte responses to metabolic stress but is largely dispensable for immune cell development and function.

    Science.gov (United States)

    Mayer, Alice; Denanglaire, Sébastien; Viollet, Benoit; Leo, Oberdan; Andris, Fabienne

    2008-04-01

    AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, represents an energy sensor able to adapt cellular metabolism in response to nutritional environmental variations. TCR stimulation activates AMPK, a regulatory event that is known to stimulate ATP-producing processes, possibly in anticipation of the increased energetic needs associated with cell division and expression of effector function. Taking advantage of the selective expression of the AMPKalpha1 catalytic subunit in lymphoid cells, we have analyzed the in vitro and in vivo capacity of lymphocytes lacking AMPK activity (AMPKalpha1-KO cells) to respond to metabolic stress and to initiate and sustain an immune response. AMPKalpha1-KO cells displayed increasing sensitivity to energetic stress in vitro, and were found unable to maintain adequate ATP levels in response to ATP synthase inhibition. These cells were, however, able to respond to antigen stimulation in vitro, as shown by optimal proliferation and cytokine production. Similarly, AMPKalpha1-KO mice were fully immunocompetent in vivo and displayed normal cell proliferation, humoral, cytotoxic and delayed-type hypersensitivity (DTH) responses following antigen injection. In conclusion, AMPK represents an important enzyme allowing lymphocytes to resist a mild energy crisis in vitro, but is largely dispensable for activation and expression of effector function in response to antigen stimulation.

  17. Body weight management effect of burdock (Arctium lappa L.) root is associated with the activation of AMP-activated protein kinase in human HepG2 cells.

    Science.gov (United States)

    Kuo, Daih-Huang; Hung, Ming-Chi; Hung, Chao-Ming; Liu, Li-Min; Chen, Fu-An; Shieh, Po-Chuen; Ho, Chi-Tang; Way, Tzong-Der

    2012-10-01

    Burdock (Arcticum lappa L.) root is used in folk medicine and also as a vegetable in Asian countries. In the present study, burdock root treatment significantly reduced body weight in rats. To evaluate the bioactive compounds, we successively extracted the burdock root with ethanol (AL-1), and fractionated it with n-hexane (AL-2), ethyl acetate (AL-3), n-butanol (AL-4), and water (AL-5). Among these fractions, AL-2 contained components with the most effective hypolipidemic potential in human hepatoma HepG2 cells. AL-2 decreased the expression of fatty acid synthase (FASN) and inhibited the activity of acetyl-coenzyme A carboxylase (ACC) by stimulating AMP-activated protein kinase (AMPK) through the LKB1 pathway. Three active compounds were identified from the AL-2, namely α-linolenic acid, methyl α-linolenate, and methyl oleate. These results suggest that burdock root is expected to be useful for body weight management. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Activation of AMP-activated protein kinase in response to temperature elevation shows seasonal variation in the zebra mussel, Dreissena polymorpha.

    Science.gov (United States)

    Jost, Jennifer A; Keshwani, Sarah S; Abou-Hanna, Jacob J

    2015-04-01

    Global climate change is affecting ectothermic species, and a variety of studies are needed on thermal tolerances, especially from cellular and physiological perspectives. This study utilized AMP-activated protein kinase (AMPK), a key regulator of cellular energy levels, to examine the effects of high water temperatures on zebra mussel (Dreissena polymorpha) physiology. During heating, AMPK activity increased as water temperature increased to a point, and maximum AMPK activity was detected at high, but sublethal, water temperatures. This pattern varied with season, suggesting that cellular mechanisms of seasonal thermal acclimatization affect basic metabolic processes during sublethal heat stress. There was a greater seasonal variation in the water temperature at which maximum AMPK activity was measured than in lethal water temperature. Furthermore, baseline AMPK activity varied significantly across seasons, most likely reflecting altered metabolic states during times of growth and reproduction. In addition, when summer-collected mussels were lab-acclimated to winter and spring water temperatures, patterns of heat stress mirrored those of field-collected animals. These data suggest that water temperature is the main driver of the seasonal variation in physiology. This study concluded that AMPK activity, which reflects changes in energy supply and demand during heat stress, can serve as a sensitive and early indicator of temperature stress in mussels. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. 2-Deoxy-D-glucose treatment of endothelial cells induces autophagy by reactive oxygen species-mediated activation of the AMP-activated protein kinase.

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    Qilong Wang

    2011-02-01

    Full Text Available Autophagy is a cellular self-digestion process activated in response to stresses such as energy deprivation and oxidative stress. However, the mechanisms by which energy deprivation and oxidative stress trigger autophagy remain undefined. Here, we report that activation of AMP-activated protein kinase (AMPK by mitochondria-derived reactive oxygen species (ROS is required for autophagy in cultured endothelial cells. AMPK activity, ROS levels, and the markers of autophagy were monitored in confluent bovine aortic endothelial cells (BAEC treated with the glycolysis blocker 2-deoxy-D-glucose (2-DG. Treatment of BAEC with 2-DG (5 mM for 24 hours or with low concentrations of H(2O(2 (100 µM induced autophagy, including increased conversion of microtubule-associated protein light chain 3 (LC3-I to LC3-II, accumulation of GFP-tagged LC3 positive intracellular vacuoles, and increased fusion of autophagosomes with lysosomes. 2-DG-treatment also induced AMPK phosphorylation, which was blocked by either co-administration of two potent anti-oxidants (Tempol and N-Acetyl-L-cysteine or overexpression of superoxide dismutase 1 or catalase in BAEC. Further, 2-DG-induced autophagy in BAEC was blocked by overexpressing catalase or siRNA-mediated knockdown of AMPK. Finally, pretreatment of BAEC with 2-DG increased endothelial cell viability after exposure to hypoxic stress. Thus, AMPK is required for ROS-triggered autophagy in endothelial cells, which increases endothelial cell survival in response to cell stress.

  20. Physical activity in the prevention and treatment of diseases of affluence – the key role of AMP-activated protein kinase (AMPK

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    Ewa Grochowska

    2014-09-01

    Full Text Available In developed countries, we can observe an increasing number of people with obesity, type 2 diabetes, dyslipidemia, hypertension and arteriosclerosis. The main reason for this phenomenon is the abnormal energy balance due to sedentary lifestyles. Cardiovascular diseases are the leading cause of death in many countries around the world, nowadays. In this paper, the impact of physical activity on the effectiveness of treatment and prevention of metabolic diseases and cancer is considered. Exercise is one of the factors activating 5’AMP-activated protein kinase (AMPK. This enzyme is crucial in maintaining the energy balance of the cell and the entire organism, and its activation results in excluding the anabolic and switching on the catabolic processes. It is believed that the activation of AMPK is responsible for most of the positive effects resulting from physical exercise. Although there are pharmacological methods of activation of this enzyme, they seem to be not as effective as physical exercise. Therefore, physical activity should be the most important form of prevention and treatment of metabolic diseases.

  1. Combined Treatment of MCF-7 Cells with AICAR and Methotrexate, Arrests Cell Cycle and Reverses Warburg Metabolism through AMP-Activated Protein Kinase (AMPK and FOXO1.

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    Tamás Fodor

    Full Text Available Cancer cells are characterized by metabolic alterations, namely, depressed mitochondrial oxidation, enhanced glycolysis and pentose phosphate shunt flux to support rapid cell growth, which is called the Warburg effect. In our study we assessed the metabolic consequences of a joint treatment of MCF-7 breast cancer cells with AICAR, an inducer of AMP-activated kinase (AMPK jointly with methotrexate (MTX, a folate-analog antimetabolite that blunts de novo nucleotide synthesis. MCF7 cells, a model of breast cancer cells, were resistant to the individual application of AICAR or MTX, however combined treatment of AICAR and MTX reduced cell proliferation. Prolonged joint application of AICAR and MTX induced AMPK and consequently enhanced mitochondrial oxidation and reduced the rate of glycolysis. These metabolic changes suggest an anti-Warburg rearrangement of metabolism that led to the block of the G1/S and the G2/M transition slowing down cell cycle. The slowdown of cell proliferation was abolished when mitotropic transcription factors, PGC-1α, PGC-1β or FOXO1 were silenced. In human breast cancers higher expression of AMPKα and FOXO1 extended survival. AICAR and MTX exerts similar additive antiproliferative effect on other breast cancer cell lines, such as SKBR and 4T1 cells, too. Our data not only underline the importance of Warburg metabolism in breast cancer cells but nominate the AICAR+MTX combination as a potential cytostatic regime blunting Warburg metabolism. Furthermore, we suggest the targeting of AMPK and FOXO1 to combat breast cancer.

  2. When phosphorylated at Thr148, the β2-subunit of AMP-activated kinase does not associate with glycogen in skeletal muscle.

    Science.gov (United States)

    Xu, Hongyang; Frankenberg, Noni T; Lamb, Graham D; Gooley, Paul R; Stapleton, David I; Murphy, Robyn M

    2016-07-01

    The 5'-AMP-activated protein kinase (AMPK), a heterotrimeric complex that functions as an intracellular fuel sensor that affects metabolism, is activated in skeletal muscle in response to exercise and utilization of stored energy. The diffusibility properties of α- and β-AMPK were examined in isolated skeletal muscle fiber segments dissected from rat fast-twitch extensor digitorum longus and oxidative soleus muscles from which the surface membranes were removed by mechanical dissection. After the muscle segments were washed for 1 and 10 min, ∼60% and 75%, respectively, of the total AMPK pools were found in the diffusible fraction. After in vitro stimulation of the muscle, which resulted in an ∼80% decline in maximal force, 20% of the diffusible pool became bound in the fiber. This bound pool was not associated with glycogen, as determined by addition of a wash step containing amylase. Stimulation of extensor digitorum longus muscles resulted in 28% glycogen utilization and a 40% increase in phosphorylation of the downstream AMPK target acetyl carboxylase-CoA. This, however, had no effect on the proportion of total β2-AMPK that was phosphorylated in whole muscle homogenates measured by immunoprecipitation. These findings suggest that, in rat skeletal muscle, β2-AMPK is not associated with glycogen and that activation of AMPK by muscle contraction does not dephosphorylate β2-AMPK. These findings question the physiological relevance of the carbohydrate-binding function of β2-AMPK in skeletal muscle. Copyright © 2016 the American Physiological Society.

  3. Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas.

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    Brock, Stephanie E; Rendon, Beatriz E; Yaddanapudi, Kavitha; Mitchell, Robert A

    2012-11-02

    AMP-activated protein kinase (AMPK) is a nutrient- and metabolic stress-sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, d-dopachrome tautomerase (d-DT), have protumorigenic functions in non-small cell lung carcinomas (NSCLCs) but have AMPK-activating properties in nonmalignant cell types, we set out to investigate this apparent paradox. Our data now suggest that, in contrast to MIF and d-DTs AMPK-activating properties in nontransformed cells, MIF and d-DT act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant human NSCLC cell lines. Our data further indicate that MIF and d-DT, acting through their shared cell surface receptor, CD74, antagonize NSCLC AMPK activation by maintaining glucose uptake, ATP production, and redox balance, resulting in reduced Ca(2+)/calmodulin-dependent kinase kinase β-dependent AMPK activation. Combined, these studies indicate that MIF and d-DT cooperate to inhibit AMPK activation in an LKB1-independent manner.

  4. Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps.

    Science.gov (United States)

    García-Salcedo, Raúl; Lubitz, Timo; Beltran, Gemma; Elbing, Karin; Tian, Ye; Frey, Simone; Wolkenhauer, Olaf; Krantz, Marcus; Klipp, Edda; Hohmann, Stefan

    2014-04-01

    The AMP-activated protein kinase, AMPK, controls energy homeostasis in eukaryotic cells but little is known about the mechanisms governing the dynamics of its activation/deactivation. The yeast AMPK, SNF1, is activated in response to glucose depletion and mediates glucose de-repression by inactivating the transcriptional repressor Mig1. Here we show that overexpression of the Snf1-activating kinase Sak1 results, in the presence of glucose, in constitutive Snf1 activation without alleviating glucose repression. Co-overexpression of the regulatory subunit Reg1 of the Glc-Reg1 phosphatase complex partly restores glucose regulation of Snf1. We generated a set of 24 kinetic mathematical models based on dynamic data of Snf1 pathway activation and deactivation. The models that reproduced our experimental observations best featured (a) glucose regulation of both Snf1 phosphorylation and dephosphorylation, (b) determination of the Mig1 phosphorylation status in the absence of glucose by Snf1 activity only and (c) a regulatory step directing active Snf1 to Mig1 under glucose limitation. Hence it appears that glucose de-repression via Snf1-Mig1 is regulated by glucose via at least two independent steps: the control of activation of the Snf1 kinase and directing active Snf1 to inactivating its target Mig1. © 2014 FEBS.

  5. Contributory fault and level of personal injury to drivers involved in head-on collisions: Application of copula-based bivariate ordinal models.

    Science.gov (United States)

    Wali, Behram; Khattak, Asad J; Xu, Jingjing

    2018-01-01

    The main objective of this study is to simultaneously investigate the degree of injury severity sustained by drivers involved in head-on collisions with respect to fault status designation. This is complicated to answer due to many issues, one of which is the potential presence of correlation between injury outcomes of drivers involved in the same head-on collision. To address this concern, we present seemingly unrelated bivariate ordered response models by analyzing the joint injury severity probability distribution of at-fault and not-at-fault drivers. Moreover, the assumption of bivariate normality of residuals and the linear form of stochastic dependence implied by such models may be unduly restrictive. To test this, Archimedean copula structures and normal mixture marginals are integrated into the joint estimation framework, which can characterize complex forms of stochastic dependencies and non-normality in residual terms. The models are estimated using 2013 Virginia police reported two-vehicle head-on collision data, where exactly one driver is at-fault. The results suggest that both at-fault and not-at-fault drivers sustained serious/fatal injuries in 8% of crashes, whereas, in 4% of the cases, the not-at-fault driver sustained a serious/fatal injury with no injury to the at-fault driver at all. Furthermore, if the at-fault driver is fatigued, apparently asleep, or has been drinking the not-at-fault driver is more likely to sustain a severe/fatal injury, controlling for other factors and potential correlations between the injury outcomes. While not-at-fault vehicle speed affects injury severity of at-fault driver, the effect is smaller than the effect of at-fault vehicle speed on at-fault injury outcome. Contrarily, and importantly, the effect of at-fault vehicle speed on injury severity of not-at-fault driver is almost equal to the effect of not-at-fault vehicle speed on injury outcome of not-at-fault driver. Compared to traditional ordered probability

  6. Mannan-Binding Lectin Is Involved in the Protection against Renal Ischemia/Reperfusion Injury by Dietary Restriction.

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    Shushimita Shushimita

    Full Text Available Preoperative fasting and dietary restriction offer robust protection against renal ischemia/reperfusion injury (I/RI in mice. We recently showed that Mannan-binding lectin (MBL, the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on these findings, we investigated the effect of short-term DR (30% reduction of total food intake or three days of water only fasting on MBL in 10-12 weeks old male C57/Bl6 mice. Both dietary regimens significantly reduce the circulating levels of MBL as well as its mRNA expression in liver, the sole production site of MBL. Reconstitution of MBL abolished the protection afforded by dietary restriction, whereas in the fasting group the protection persisted. These data show that modulation of MBL is involved in the protection against renal I/RI induced by dietary restriction, and suggest that the mechanisms of protection induced by dietary restriction and fasting may be different.

  7. Protection Orders Protect Against Assault and Injury: A Longitudinal Study of Police-Involved Women Victims of Intimate Partner Violence

    Science.gov (United States)

    Kothari, Catherine L.; Rhodes, Karin V.; Wiley, James A.; Fink, Jeffrey; Overholt, Scott; Dichter, Melissa E.; Marcus, Steven C.; Cerulli, Catherine

    2014-01-01

    Objective To measure the efficacy of protection orders (POs) in reducing assault and injury-related outcomes using a matched comparison group and tracking outcomes over time. Methods This study was a retrospective review of police, emergency department, family court and prosecutor administrative records for a cohort of police-involved female IPV victims; all events over a four-year study period were abstracted. Victims who obtained protection orders (POs) were compared to a propensity-score-based match group without POs over three time periods: Before, during, and after the issuance of a PO. Results Having a PO in place was associated with significantly more calls to police for non-assaultive incidents, and more police charging requests that were multiple-count and felony-level. Comparing outcomes, PO victims had police incident rates that were more than double the matched group prior to the PO, but dropped to the level of the matched group during and after the order. ED visits dropped over time for both groups. Conclusion This study confirmed the protective effect of POs, which are associated with reduced police incidents and emergency department visits both during and after the order, and reduced police incidents compared to a matched comparison group. PMID:22491224

  8. Geranylgeranylacetone ameliorates lung ischemia/reperfusion injury by HSP70 and thioredoxin redox system: NF-kB pathway involved.

    Science.gov (United States)

    Cao, Weijun; Li, Manhui; Li, Jianxiong; Li, Chengwei; Xu, Xin; Gu, Weiqing

    2015-06-01

    Geranylgeranylacetone (GGA) has been clinically used as an anti-ulcer drug. In the present study, we explored the protective effects of GGA on lung ischemia/reperfusion injury (IRI) and the underlying mechanism. The results demonstrated that GGA ameliorated the lung biochemical and histological alterations induced by IRI, which was reversed by HSP70 inhibition. To further explore the mechanism of GGA action, we focused on NF-kB and thioredoxin (Trx) redox system. It was shown that GGA induced the HSP70 and Trx-1 expression, NF-kB nuclear translocation and activated thioredoxin reductase (TrxR). The Trx-1 expression and TrxR activity was suppressed by HSP70 and NF-kB inhibition, while the nuclear NF-kB p65 expression was suppressed by HSP70 inhibitor. These results indicated that GGA may protect rat lung against IRI by HSP70 and Trx redox system, in which NF-kB pathway may be involved. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Injury/Fatality-Causing Incidents Involving the Rearward Movement of Agricultural Machinery: Types, Causes, and Preventive Measures

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    Shawn G. Ehlers

    2017-02-01

    Full Text Available The research reported here sought to more fully understand the types and causative factors of injury/fatality incidents resulting from the rearward-movement of tractors and other self-propelled agricultural machinery, with the view that such findings might lead to the development, improvement, and/or better utilization of safety procedures, design principles, and technologies that would prevent—or at least markedly reduce—their occurrence. Thus, the scope of this study focused only on rearward-travel (not mechanical malfunction incidents, and principally on agricultural equipment (although cases involving similar equipment in industrial or construction settings were also drawn upon. Applying these two criteria, a search of published and online sources uncovered more than 100 documented cases, 35 of which could clearly be identified as rearward-movement incidents, of which 28 (80% were fatal. Each of these 35 cases were then assessed, based on the type of machine, type of worksite, and type/description of incident (i.e., ‘scenario’, which fell into one of three distinct categories or classifications—(1 co-worker run over/crushed/otherwise injured because operator loses visual contact with co-worker; (2 bystander run over/crushed/otherwise injured because operator is unaware of bystander’s presence; and (3 operator run over/crushed/otherwise injured because operator loses visual contact with, or is unaware of, a stationary object or a hazard. Then, from each scenario, a representative incident (i.e., case study was selected for a more in-depth analysis. The collective findings, from these three case studies and all 35 machinery rearward-movement incidents, were as follows: (1 The ‘victim’ could be the machine operator as well as a co-worker or a bystander; (2 The specific site of the co-worker or bystander injury/fatality was at the base of the machine’s rear tires or tracks, at the hitching point, or behind a towed implement; (3

  10. Dysphagia and Speech-Language Pathology Involvement Following Chemical Ingestion Injury: A Review of 44 Cases Admitted to a Quaternary Australian Hospital (2008-2012).

    Science.gov (United States)

    Rumbach, Anna F; Cremer, Rebecca

    2017-11-08

    This study aimed to explore the clinical characteristics of an adult chemical ingestion population and examine the course of return to oral intake post injury and speech-language pathologist (SLP) involvement during the initial acute-care admission. A retrospective chart review of adults admitted to a quaternary hospital for the treatment of an acute chemical ingestion injury between 2008 and 2012 was conducted. Forty-four adults (23 men, 21 women) were identified as receiving treatment for ingestion injury, of whom 18 (40.91%) required altered oral intake. Of those requiring altered oral intake, 50% were referred to SLPs. Individuals requiring altered oral intake were significantly (p < .05) older, more likely to be men, and present with more severe injuries requiring longer ICU and hospital admissions following intentional chemical ingestions than those who were able to commence a normal oral diet without any alteration or nonoral supplementation. By discharge, 15.91% (n = 7) of the total cohort had not resumed normal oral intake. Return to oral intake post chemical ingestion injury can be protracted and complex. Referrals to SLPs were limited. These data may aid prognostic insight as well as provide (a) collateral information to assist discharge planning and follow-up and (b) background for evaluating the potential for SLP involvement.

  11. Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation

    International Nuclear Information System (INIS)

    Wu, Hai-Lu; Gao, Xin; Jiang, Zong-Dan; Duan, Zhao-Tao; Wang, Shu-Kui; He, Bang-Shun; Zhang, Zhen-Yu; Xie, Hong-Guang

    2013-01-01

    epithelial cells is mediated by the p38 MAPK pathway. It is concluded that attenuated expression of the TJ proteins occludin and ZO-1 in human gastric epithelial cells could be involved in clopidogrel-induced gastric mucosal injury through activation of the p38 MAPK pathway

  12. Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Shiguang [Department of Intensive Care Unit, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Mao, Li [Department of Endocrinology, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Ji, Feng, E-mail: huaiaifengjidr@163.com [Department of Orthopedics, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Wang, Shouguo; Xie, Yue; Fei, Haodong [Department of Orthopedics, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Wang, Xiao-dong, E-mail: xiaodongwangsz@163.com [The Center of Diagnosis and Treatment for Children' s Bone Diseases, The Children' s Hospital Affiliated to Soochow University, Suzhou (China)

    2016-03-18

    Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13′ cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the other hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKα1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway. - Highlights: • Compound 13 (C13) attenuates dexamethasone (Dex)-induced osteoblast cell death. • C13-induced cytoprotective effect against Dex in osteoblasts requires AMPK activation. • Forced AMPK activation protects osteoblasts from Dex, nullifying C13's activities. • C13 increases NADPH activity and inhibits Dex-induced oxidative stress in osteoblasts.

  13. In silico study of protein to protein interaction analysis of AMP-activated protein kinase and mitochondrial activity in three different farm animal species

    Science.gov (United States)

    Prastowo, S.; Widyas, N.

    2018-03-01

    AMP-activated protein kinase (AMPK) is cellular energy censor which works based on ATP and AMP concentration. This protein interacts with mitochondria in determine its activity to generate energy for cell metabolism purposes. For that, this paper aims to compare the protein to protein interaction of AMPK and mitochondrial activity genes in the metabolism of known animal farm (domesticated) that are cattle (Bos taurus), pig (Sus scrofa) and chicken (Gallus gallus). In silico study was done using STRING V.10 as prominent protein interaction database, followed with biological function comparison in KEGG PATHWAY database. Set of genes (12 in total) were used as input analysis that are PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3, PPARGC1, ACC, CPT1B, NRF2 and SOD. The first 7 genes belong to gene in AMPK family, while the last 5 belong to mitochondrial activity genes. The protein interaction result shows 11, 8 and 5 metabolism pathways in Bos taurus, Sus scrofa and Gallus gallus, respectively. The top pathway in Bos taurus is AMPK signaling pathway (10 genes), Sus scrofa is Adipocytokine signaling pathway (8 genes) and Gallus gallus is FoxO signaling pathway (5 genes). Moreover, the common pathways found in those 3 species are Adipocytokine signaling pathway, Insulin signaling pathway and FoxO signaling pathway. Genes clustered in Adipocytokine and Insulin signaling pathway are PRKAA2, PPARGC1A, PRKAB1 and PRKAG2. While, in FoxO signaling pathway are PRKAA2, PRKAB1, PRKAG2. According to that, we found PRKAA2, PRKAB1 and PRKAG2 are the common genes. Based on the bioinformatics analysis, we can demonstrate that protein to protein interaction shows distinct different of metabolism in different species. However, further validation is needed to give a clear explanation.

  14. Adiponectin induced AMP-activated protein kinase impairment mediates insulin resistance in Bama mini-pig fed high-fat and high-sucrose diet

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    Miaomiao Niu

    2017-08-01

    Full Text Available Objective Adipose tissue is no longer considered as an inert storage organ for lipid, but instead is thought to play an active role in regulating insulin effects via secretion adipokines. However, conflicting reports have emerged regarding the effects of adipokines. In this study, we investigated the role of adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs. Methods An obesity model was established in Bama mini-pigs, by feeding with high-fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry levels were measured, and intravenous glucose tolerance test was performed. Adipokines, including adiponectin, interleukin-6 (IL-6, resistin and tumor necrosis factor alpha (TNF-α, and glucose-induced insulin secretion were also examined by radioimmunoassay. AMP-activated protein kinase (AMPK phosphorylation in skeletal muscle, which is a useful insulin resistance marker, was examined by immunoblotting. Additionally, associations of AMPK phosphorylation with plasma adipokines and homeostasis model assessment of insulin resistance (HOMA-IR index were assessed by Pearce’s correlation analysis. Results Obese pigs showed hyperglycemia, high triglycerides, and insulin resistance. Adiponectin levels were significantly decreased (p<0.05 and IL-6 amounts dramatically increased (p<0.05 in obese pigs both in serum and adipose tissue, corroborating data from obese mice and humans. However, circulating resistin and TNF-α showed no difference, while the values of TNF-α in adipose tissue were significantly higher in obese pigs, also in agreement with data from obese humans but not rodent models. Moreover, strong associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and HOMA-IR index were obtained. Conclusion AMPK impairment induced by adiponectin decrease mediates insulin resistance in high-fat and high-sucrose diet induction. In addition, Bama mini-pig has the possibility of a conformable

  15. Hypoxia Induces Changes in AMP-Activated Protein Kinase Activity and Energy Metabolism in Muscle Tissue of the Oriental River Prawn Macrobrachium nipponense

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    Shengming Sun

    2018-06-01

    Full Text Available Hypoxia has important effects on biological activity in crustaceans, and modulation of energy metabolism is a crucial aspect of crustaceans’ ability to respond to hypoxia. The adenosine 5′-monophosphate (AMP-activated protein kinase (AMPK enzyme is very important in cellular energy homeostasis; however, little information is known about the role of AMPK in the response of prawns to acute hypoxia. In the present study, three subunits of AMPK were cloned from the oriental river prawn, Macrobrachium nipponense. The full-length cDNAs of the α, β, and γ AMPK subunits were 1,837, 3,174, and 3,773 bp long, with open reading frames of 529, 289, and 961 amino acids, respectively. Primary amino acid sequence alignment of these three subunits revealed conserved similarity between the functional domains of the M. nipponense AMPK protein with AMPK proteins of other animals. The expression of the three AMPK subunits was higher in muscle tissue than in other tissues. Furthermore, the mRNA expression of AMPKα, AMPKβ, and AMPKγ were significantly up-regulated in M. nipponense muscle tissue after acute hypoxia. Probing with a phospho-AMPKα antibody revealed that AMPK is phosphorylated following hypoxia; this phosphorylation event was found to be essential for AMPK activation. Levels of glucose and lactic acid in hemolymph and muscle tissue were significantly changed over the course of hypoxia and recovery, indicating dynamic changes in energy metabolism in response to hypoxic stress. The activation of AMPK by hypoxic stress in M. nipponense was compared to levels of muscular AMP, ADP, and ATP, as determined by HPLC; it was found that activation of AMPK may not completely correlate with AMP:ATP ratios in prawns under hypoxic conditions. These findings confirm that the α, β, and γ subunits of the prawn AMPK protein are regulated at the transcriptional and protein levels during hypoxic stress to facilitate maintenance of energy homeostasis.

  16. Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis Factor-α-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes

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    Seok-Woo Hong

    2014-12-01

    Full Text Available BackgroundTumor necrosis factor (TNF-α and AMP-activated protein kinase (AMPK are known to stimulate and repress lipolysis in adipocytes, respectively; however, the mechanisms regulating these processes have not been completely elucidated.MethodsThe key factors and mechanism of action of TNF-α and AMPK in lipolysis were investigated by evaluating perilipin expression and activity of protein kinase RNA-like endoplasmic reticulum kinase (PERK/eukaryotic initiation factor 2 α (eIF2α by Western blot and an immunofluorescence assay in 24-hour TNF-α-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation.ResultsEnhancement of AMPK activity by the addition of activator minoimidazole carboxamide ribonucleotide (AICAR suppressed TNF-α-induced lipolysis, whereas the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-α and recovered following treatment with AICAR, showing a correlation with the antilipolytic effect of AICAR. Significant activation of PERK/eIF2α, a component of the unfolded protein response signaling pathway, was observed in TNF-α or vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of perilipin expression by AICAR in TNF-α-treated 3T3-L1 adipocytes were significantly diminished by treatment with 2-aminopurine, a specific inhibitor of eIF2α.ConclusionThese data indicated that AICAR-induced AMPK activation attenuates TNF-α-induced lipolysis via preservation of perilipin in 3T3-L1 adipocytes. In addition, PERK/eIF2α activity is a novel mechanism of the anti-lipolytic effect of AICAR.

  17. Regulation of Pancreatic β Cell Mass by Cross-Interaction between CCAAT Enhancer Binding Protein β Induced by Endoplasmic Reticulum Stress and AMP-Activated Protein Kinase Activity.

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    Tomokazu Matsuda

    Full Text Available During the development of type 2 diabetes, endoplasmic reticulum (ER stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK. However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein β (C/EBPβ expression levels. The effect of C/EBPβ phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBPβ transgenic mice to investigate the relationship between C/EBPβ expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBPβ lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPβ expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPβ transgenic mice decreased C/EBPβ expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBPβ expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure.

  18. Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows.

    Science.gov (United States)

    Min, Li; Cheng, Jian-bo; Shi, Bao-lu; Yang, Hong-jian; Zheng, Nan; Wang, Jia-qi

    2015-06-01

    Heat stress affects feed intake, milk production, and endocrine status in dairy cows. The temperature-humidity index (THI) is employed as an index to evaluate the degree of heat stress in dairy cows. However, it is difficult to ascertain whether THI is the most appropriate measurement of heat stress in dairy cows. This experiment was conducted to investigate the effects of heat stress on serum insulin, adipokines (leptin and adiponectin), AMP-activated protein kinase (AMPK), and heat shock signal molecules (heat shock transcription factor (HSF) and heat shock proteins (HSP)) in dairy cows and to research biomarkers to be used for better understanding the meaning of THI as a bioclimatic index. To achieve these objectives, two experiments were performed. The first experiment: eighteen lactating Holstein dairy cows were used. The treatments were: heat stress (HS, THI average=81.7, n=9) and cooling (CL, THI average=53.4, n=9). Samples of HS were obtained on August 16, 2013, and samples of CL were collected on April 7, 2014 in natural conditions. The second experiment: HS treatment cows (n=9) from the first experiment were fed for 8 weeks from August 16, 2013 to October 12, 2013. Samples for moderate heat stress, mild heat stress, and no heat stress were obtained, respectively, according to the physical alterations of the THI. Results showed that heat stress significantly increased the serum adiponectin, AMPK, HSF, HSP27, HSP70, and HSP90 (Pdairy cows. When heat stress treatment lasted 8 weeks, a higher expression of HSF and HSP70 was observed under moderate heat stress. Serum HSF and HSP70 are sensitive and accurate in heat stress and they could be potential indicators of animal response to heat stress. We recommend serum HSF and HSP70 as meaningful biomarkers to supplement the THI and evaluate moderate heat stress in dairy cows in the future.

  19. Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice.

    Science.gov (United States)

    Huang, S-L; Yu, R-T; Gong, J; Feng, Y; Dai, Y-L; Hu, F; Hu, Y-H; Tao, Y-D; Leng, Y

    2012-05-01

    Arctigenin is a natural compound that had never been previously demonstrated to have a glucose-lowering effect. Here it was found to activate AMP-activated protein kinase (AMPK), and the mechanism by which this occurred, as well as the effects on glucose and lipid metabolism were investigated. 2-Deoxyglucose uptake and AMPK phosphorylation were examined in L6 myotubes and isolated skeletal muscle. Gluconeogenesis and lipid synthesis were evaluated in rat primary hepatocytes. The acute and chronic effects of arctigenin on metabolic abnormalities were observed in C57BL/6J and ob/ob mice. Changes in mitochondrial membrane potential were measured using the J-aggregate-forming dye, JC-1. Analysis of respiration of L6 myotubes or isolated mitochondria was conducted in a channel oxygen system. Arctigenin increased AMPK phosphorylation and stimulated glucose uptake in L6 myotubes and isolated skeletal muscles. In primary hepatocytes, it decreased gluconeogenesis and lipid synthesis. The enhancement of glucose uptake and suppression of hepatic gluconeogenesis and lipid synthesis by arctigenin were prevented by blockade of AMPK activation. The respiration of L6 myotubes or isolated mitochondria was inhibited by arctigenin with a specific effect on respiratory complex I. A single oral dose of arctigenin reduced gluconeogenesis in C57BL/6J mice. Chronic oral administration of arctigenin lowered blood glucose and improved lipid metabolism in ob/ob mice. This study demonstrates a new role for arctigenin as a potent indirect activator of AMPK via inhibition of respiratory complex I, with beneficial effects on metabolic disorders in ob/ob mice. This highlights the potential value of arctigenin as a possible treatment of type 2 diabetes.

  20. Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death

    International Nuclear Information System (INIS)

    Guo, Shiguang; Mao, Li; Ji, Feng; Wang, Shouguo; Xie, Yue; Fei, Haodong; Wang, Xiao-dong

    2016-01-01

    Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13′ cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the other hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKα1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway. - Highlights: • Compound 13 (C13) attenuates dexamethasone (Dex)-induced osteoblast cell death. • C13-induced cytoprotective effect against Dex in osteoblasts requires AMPK activation. • Forced AMPK activation protects osteoblasts from Dex, nullifying C13's activities. • C13 increases NADPH activity and inhibits Dex-induced oxidative stress in osteoblasts.

  1. Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade

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    Alessi Dario R

    2003-09-01

    Full Text Available Abstract Background The AMP-activated protein kinase (AMPK cascade is a sensor of cellular energy charge that acts as a 'metabolic master switch' and inhibits cell proliferation. Activation requires phosphorylation of Thr172 of AMPK within the activation loop by upstream kinases (AMPKKs that have not been identified. Recently, we identified three related protein kinases acting upstream of the yeast homolog of AMPK. Although they do not have obvious mammalian homologs, they are related to LKB1, a tumor suppressor that is mutated in the human Peutz-Jeghers cancer syndrome. We recently showed that LKB1 exists as a complex with two accessory subunits, STRADα/β and MO25α/β. Results We report the following observations. First, two AMPKK activities purified from rat liver contain LKB1, STRADα and MO25α, and can be immunoprecipitated using anti-LKB1 antibodies. Second, both endogenous and recombinant complexes of LKB1, STRADα/β and MO25α/β activate AMPK via phosphorylation of Thr172. Third, catalytically active LKB1, STRADα or STRADβ and MO25α or MO25β are required for full activity. Fourth, the AMPK-activating drugs AICA riboside and phenformin do not activate AMPK in HeLa cells (which lack LKB1, but activation can be restored by stably expressing wild-type, but not catalytically inactive, LKB1. Fifth, AICA riboside and phenformin fail to activate AMPK in immortalized fibroblasts from LKB1-knockout mouse embryos. Conclusions These results provide the first description of a physiological substrate for the LKB1 tumor suppressor and suggest that it functions as an upstream regulator of AMPK. Our findings indicate that the tumors in Peutz-Jeghers syndrome could result from deficient activation of AMPK as a consequence of LKB1 inactivation.

  2. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Sung, Jin Young; Choi, Hyoung Chul

    2011-01-01

    Highlights: → Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. → Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. → Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. → Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. → Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  3. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Jin Young [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2011-05-06

    Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  4. Arctigenin protects against steatosis in WRL68 hepatocytes through activation of phosphoinositide 3-kinase/protein kinase B and AMP-activated protein kinase pathways.

    Science.gov (United States)

    Chen, Kung-Yen; Lin, Jui-An; Yao, Han-Yun; Hsu, An-Chih; Tai, Yu-Ting; Chen, Jui-Tai; Hsieh, Mao-Chih; Shen, Tang-Long; Hsu, Ren-Yi; Wu, Hong-Tan; Wang, Guey Horng; Ho, Bing-Ying; Chen, Yu-Pei

    2018-04-01

    Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation-associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays. Quantitative RT-PCR analysis demonstrated that ATG significantly mitigated the expression of acetylcoenzyme A carboxylase 1 and sterol regulatory element-binding protein-1 and significantly increased the expression of carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha. The 40 targets of the Human Inflammation Antibody Array indicated that ATG significantly inhibited the elevation of the U937 lymphocyte chemoattractant, ICAM-1, IL-1β, IL-6, IL-6sR, IL-7, and IL-8. ATG could activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways and could increase the phosphorylation levels of Akt and AMPK to mediate cell survival, lipid metabolism, oxidation stress, and inflammation. Thus, we demonstrated that ATG could inhibit NAFLD progression associated with lipid oxidation-associated lipotoxicity and inflammation, and we provided insights into the underlying mechanisms and revealed potential targets to enable a thorough understanding of NAFLD progression. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Magnolol Alleviates Inflammatory Responses and Lipid Accumulation by AMP-Activated Protein Kinase-Dependent Peroxisome Proliferator-Activated Receptor α Activation

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    Ye Tian

    2018-02-01

    Full Text Available Magnolol (MG is a kind of lignin isolated from Magnolia officinalis, which serves several different biological functions, such as antifungal, anticancer, antioxidant, and hepatoprotective functions. This study aimed to evaluate the protective effect of MG against oleic acid (OA-induced hepatic steatosis and inflammatory damage in HepG2 cells and in a tyloxapol (Ty-induced hyperlipidemia mouse model. Our findings indicated that MG can effectively inhibit OA-stimulated tumor necrosis factor α (TNF-α secretion, reactive oxygen species generation, and triglyceride (TG accumulation. Further study manifested that MG significantly suppressed OA-activated mitogen-activated protein kinase (MAPK and nuclear factor-kappa B (NF-κB signaling pathways and that these inflammatory responses can be negated by pretreatment with inhibitors of extracellular regulated protein kinase and c-Jun N-terminal kinase (U0126 and SP600125, respectively. In addition, MG dramatically upregulated peroxisome proliferator-activated receptor α (PPARα translocation and reduced sterol regulatory element-binding protein 1c (SREBP-1c protein synthesis and excretion, both of which are dependent upon the phosphorylation of adenosine monophosphate (AMP-activated protein kinase (AMPK, acetyl-CoA carboxylase, and AKT kinase (AKT. However, MG suspended the activation of PPARα expression and was thus blocked by pretreatment with LY294002 and compound c (specific inhibitors of AKT and AMPK. Furthermore, MG clearly alleviated serum TG and total cholesterol release; upregulated AKT, AMPK, and PPARα expression; suppressed SREBP-1c generation; and alleviated hepatic steatosis and dyslipidemia in Ty-induced hyperlipidemia mice. Taken together, these results suggest that MG exerts protective effects against steatosis, hyperlipidemia, and the underlying mechanism, which may be closely associated with AKT/AMPK/PPARα activation and MAPK/NF-κB/SREBP-1c inhibition.

  6. Oxyresveratrol ameliorates nonalcoholic fatty liver disease by regulating hepatic lipogenesis and fatty acid oxidation through liver kinase B1 and AMP-activated protein kinase.

    Science.gov (United States)

    Lee, Ju-Hee; Baek, Su Youn; Jang, Eun Jeong; Ku, Sae Kwang; Kim, Kyu Min; Ki, Sung Hwan; Kim, Chang-Eop; Park, Kwang Il; Kim, Sang Chan; Kim, Young Woo

    2018-06-01

    Oxyresveratrol (OXY) is a naturally occurring polyhydroxylated stilbene that is abundant in mulberry wood (Morus alba L.), which has frequently been supplied as a herbal medicine. It has been shown that OXY has regulatory effects on inflammation and oxidative stress, and may have potential in preventing or curing nonalcoholic fatty liver disease (NAFLD). This study examined the effects of OXY on in vitro model of NAFLD in hepatocyte by the liver X receptor α (LXRα)-mediated induction of lipogenic genes and in vivo model in mice along with its molecular mechanism. OXY inhibited the LXRα agonists-mediated sterol regulatory element binding protein-1c (SREBP-1c) induction and expression of the lipogenic genes and upregulated the mRNA of fatty acid β-oxidation-related genes in hepatocytes, which is more potent than genistein and daidzein. OXY also induced AMP-activated protein kinase (AMPK) activation in a time-dependent manner. Moreover, AMPK activation by the OXY treatment helped inhibit SREBP-1c using compound C as an AMPK antagonist. Oral administration of OXY decreased the Oil Red O stained-positive areas significantly, indicating lipid droplets and hepatic steatosis regions, as well as the serum parameters, such as fasting glucose, total cholesterol, and low density lipoprotein-cholesterol in high fat diet fed-mice, as similar with orally treatment of atorvastatin. Overall, this result suggests that OXY has the potency to inhibit hepatic lipogenesis through the AMPK/SREBP-1c pathway and can be used in the development of pharmaceuticals to prevent a fatty liver. Copyright © 2018. Published by Elsevier B.V.

  7. Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows*

    Science.gov (United States)

    Min, Li; Cheng, Jian-bo; Shi, Bao-lu; Yang, Hong-jian; Zheng, Nan; Wang, Jia-qi

    2015-01-01

    Heat stress affects feed intake, milk production, and endocrine status in dairy cows. The temperature-humidity index (THI) is employed as an index to evaluate the degree of heat stress in dairy cows. However, it is difficult to ascertain whether THI is the most appropriate measurement of heat stress in dairy cows. This experiment was conducted to investigate the effects of heat stress on serum insulin, adipokines (leptin and adiponectin), AMP-activated protein kinase (AMPK), and heat shock signal molecules (heat shock transcription factor (HSF) and heat shock proteins (HSP)) in dairy cows and to research biomarkers to be used for better understanding the meaning of THI as a bioclimatic index. To achieve these objectives, two experiments were performed. The first experiment: eighteen lactating Holstein dairy cows were used. The treatments were: heat stress (HS, THI average=81.7, n=9) and cooling (CL, THI average=53.4, n=9). Samples of HS were obtained on August 16, 2013, and samples of CL were collected on April 7, 2014 in natural conditions. The second experiment: HS treatment cows (n=9) from the first experiment were fed for 8 weeks from August 16, 2013 to October 12, 2013. Samples for moderate heat stress, mild heat stress, and no heat stress were obtained, respectively, according to the physical alterations of the THI. Results showed that heat stress significantly increased the serum adiponectin, AMPK, HSF, HSP27, HSP70, and HSP90 (Pheat-stressed dairy cows. When heat stress treatment lasted 8 weeks, a higher expression of HSF and HSP70 was observed under moderate heat stress. Serum HSF and HSP70 are sensitive and accurate in heat stress and they could be potential indicators of animal response to heat stress. We recommend serum HSF and HSP70 as meaningful biomarkers to supplement the THI and evaluate moderate heat stress in dairy cows in the future. PMID:26055916

  8. Inhibition of Vascular Smooth Muscle Growth via Signaling Crosstalk between AMP-Activated Protein Kinase and cAMP-Dependent Protein Kinase

    Directory of Open Access Journals (Sweden)

    Joshua Daniel Stone

    2012-10-01

    Full Text Available Abnormal vascular smooth muscle (VSM growth is central in the pathophysiology of vascular disease yet fully effective therapies to curb this growth are lacking. Recent findings from our lab and others support growth control of VSM by adenosine monophosphate (AMP-based approaches including the metabolic sensor AMP-activated protein kinase (AMPK and cAMP-dependent protein kinase (PKA. Molecular crosstalk between AMPK and PKA has been previously suggested, yet the extent to which this occurs and its biological significance in VSM remains unclear. Considering their common AMP backbone and similar signaling characteristics, we hypothesized that crosstalk exists between AMPK and PKA in the regulation of VSM growth. Using rat primary VSM cells, the AMPK agonist AICAR increased AMPK activity and phosphorylation of the catalytic Thr172 site on AMPK. Interestingly, AICAR also phosphorylated a suspected PKA-inhibitory Ser485 site on AMPK, and these cumulative events were reversed by the PKA inhibitor PKI suggesting possible PKA-mediated regulation of AMPK. AICAR also increased PKA activity in a reversible fashion. The cAMP stimulator forskolin increased PKA activity and completely ameliorated Ser/Thr protein phosphatase-2C activity, suggesting a potential mechanism of AMPK modulation by PKA since inhibition of PKA by PKI reduced AMPK activity. Functionally, AMPK inhibited serum-stimulated cell cycle progression and cellular proliferation; however, PKA failed to do so. Moreover, AMPK and PKA reduced PDGF-β-stimulated VSM cell migration. Collectively, these results show that AMPK is capable of reducing VSM growth in both anti-proliferative and anti-migratory fashions. Furthermore, these data suggest that AMPK may be modulated by PKA and that positive feedback may exist between these two systems. These findings reveal a discrete nexus between AMPK and PKA in VSM and provide basis for metabolically-directed targets in reducing pathologic VSM growth.

  9. Disruption of Fyn SH3 domain interaction with a proline-rich motif in liver kinase B1 results in activation of AMP-activated protein kinase.

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    Eijiro Yamada

    Full Text Available Fyn-deficient mice display increased AMP-activated Protein Kinase (AMPK activity as a result of Fyn-dependent regulation of Liver Kinase B1 (LKB1 in skeletal muscle. Mutation of Fyn-specific tyrosine sites in LKB1 results in LKB1 export into the cytoplasm and increased AMPK activation site phosphorylation. This study characterizes the structural elements responsible for the physical interaction between Fyn and LKB1. Effects of point mutations in the Fyn SH2/SH3 domains and in the LKB1 proline-rich motif on 1 Fyn and LKB1 binding, 2 LKB1 subcellular localization and 3 AMPK phosphorylation were investigated in C2C12 muscle cells. Additionally, novel LKB1 proline-rich motif mimicking cell permeable peptides were generated to disrupt Fyn/LKB1 binding and investigate the consequences on AMPK activity in both C2C12 cells and mouse skeletal muscle. Mutation of either Fyn SH3 domain or the proline-rich motif of LKB1 resulted in the disruption of Fyn/LKB1 binding, re-localization of 70% of LKB1 signal in the cytoplasm and a 2-fold increase in AMPK phosphorylation. In vivo disruption of the Fyn/LKB1 interaction using LKB1 proline-rich motif mimicking cell permeable peptides recapitulated Fyn pharmacological inhibition. We have pinpointed the structural elements within Fyn and LKB1 that are responsible for their binding, demonstrating the functionality of this interaction in regulating AMPK activity.

  10. The effect of stricter licensing on road traffic injury events involving 15 to 17-year-old moped drivers in Sweden: A time series intervention study.

    Science.gov (United States)

    Bonander, Carl; Andersson, Ragnar; Nilson, Finn

    2015-10-01

    This study aimed to evaluate and quantify the effect of the introduction of the AM driving license on non-fatal moped-related injuries in Sweden. With the introduction of the new license category in October 2009, prospective moped drivers are now required to pass a mandatory theory test following a practical and theoretical course. In addition, obtaining a license to operate a moped is now considerably more costly. Time series intervention analysis on monthly aggregated injury data (1st Jan 2007-31st Dec 2013) was performed using generalized additive models for location, shape and scale (GAMLSS) to quantify the effect size on injury events involving teenage (15-17 years) moped drivers, while controlling for trend and seasonality. Exposure was adjusted for by using the number of registered mopeds in traffic as a proxy. The introduction of AM license was associated with a 41% reduction in the rate of injury events involving 15-year-old moped drivers (IRR 0.59 [95% CI: 0.48-0.72]), and a 39% and 36% decrease in those involving 16-year-old (IRR 0.61 [95% CI: 0.48-0.79]) and 17-year-old drivers (IRR 0.64 [95% CI: 0.46-0.90]), respectively. The effect in the 15-year-old stratum was decreased roughly by half after adjusting for exposure, but remained significant, and the corresponding estimates in the other age groups did not change noticeably. This study provides quasi-experimental evidence of an effect on non-fatal moped-related injuries as a result of stricter licensing rules. Only part of the effect could be explained by a reduction in the number of mopeds in traffic, indicating that other mechanisms must be studied to fully understand the cause of the reduction in injuries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The experience of seeking, gaining and maintaining employment after traumatic spinal cord injury and the vocational pathways involved.

    Science.gov (United States)

    Hilton, Gillean; Unsworth, Carolyn A; Stuckey, Ruth; Murphy, Gregory C

    2018-01-01

    Vocational potential in people with spinal cord injury (SCI) are unrealised with rates of employment substantially lower than in the labour force participation of the general population and the pre-injury employment rates. To understand the experience and pathway of people achieving employment outcome after traumatic spinal cord injury by; classifying participants into employment outcome groups of stable, unstable and without employment; identifying pre and post-injury pathways for participants in each group and, exploring the experiences of people of seeking, gaining and maintaining employment. Thirty-one participants were interviewed. Mixed methods approach including interpretive phenomenological analysis and vocational pathway mapping of quantitative data. The most common pathway identified was from study and work pre-injury to stable employment post-injury. Four super-ordinate themes were identified from the interpretive phenomenological analysis; expectations of work, system impacts, worker identity and social supports. Implications for clinical practice include fostering cultural change, strategies for system navigation, promotion of worker identity and optimal use of social supports. The findings increase insight and understanding of the complex experience of employment after spinal cord injury. There is opportunity to guide experimental research, policy development and education concerning the complexity of the return to work experience and factors that influence pathways.

  12. 5-lipoxygenase activation is involved in the mechanisms of chronic hepatic injury in a rat model of chronic aluminum overload exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mai, Shaoshan [Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 (China); He, Qin [Department of Heptobiliary Surgery, 1st Affiliated Hospital, Chongqing Medical University, Chongqing 400016 (China); Wang, Hong; Hu, Xinyue; Luo, Ying; Yang, Yang; Kuang, Shengnan; Tian, Xiaoyan; Ma, Jie [Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 (China); Yang, Junqing, E-mail: 1139627371@qq.com [Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 (China)

    2016-08-15

    We previously confirmed that rats overloaded with aluminum exhibited hepatic function damage and increased susceptibility to hepatic inflammation. However, the mechanism of liver toxicity by chronic aluminum overload is poorly understood. In this study, we investigated changes in the 5-lipoxygenase (5-LO) signaling pathway and its effect on liver injury in aluminum-overloaded rats. A rat hepatic injury model of chronic aluminum injury was established via the intragastric administration of aluminum gluconate (Al{sup 3+} 200 mg/kg per day, 5 days a week for 20 weeks). The 5-LO inhibitor, caffeic acid (10 and 30 mg/kg), was intragastrically administered 1 h after aluminum administration. Hematoxylin and eosin staining was used to visualize pathological changes in rat liver tissue. A series of biochemical indicators were measured with biochemistry assay or ELISAs. Immunochemistry and RT-PCR methods were used to detect 5-LO protein and mRNA expression in the liver, respectively. Caffeic acid administration protected livers against histopathological injury, decreased plasma ALT, AST, and ALP levels, decreased TNF-α, IL-6, IL-1β and LTs levels, increased the reactive oxygen species content, and down-regulated the mRNA and protein expressions of 5-LO in aluminum overloaded rats. Our results indicate that 5-lipoxygenase activation is mechanistically involved in chronic hepatic injury in a rat model of chronic aluminum overload exposure and that the 5-LO signaling pathway, which associated with inflammation and oxidative stress, is a potential therapeutic target for chronic non-infection liver diseases. - Highlights: • 5-LO signaling contributes to mechanisms of hepatotoxicity of aluminum overload. • Oxidative and inflammatory reaction involve in chonic aluminum hepatotoxicity. • 5-LO inhibitor has a protective effect on aluminum-overload liver injury. • 5-LO signaling is a potential therapeutic target for non-infection liver diseases.

  13. MicroRNA-122 is involved in oxidative stress in isoniazid-induced liver injury in mice.

    Science.gov (United States)

    Song, L; Zhang, Z R; Zhang, J L; Zhu, X B; He, L; Shi, Z; Gao, L; Li, Y; Hu, B; Feng, F M

    2015-10-27

    Many studies have shown that the pathogenesis of liver injury includes oxidative stress. MicroRNA-122 may be a marker for the early diagnosis of drug-induced liver injury. However, the relationship between microRNA-122 and oxidative stress in anti-tuberculosis drug-induced liver injury remains unknown. We measured changes in tissue microRNA-122 levels and indices of oxidative stress during liver injury in mice after administration of isoniazid, a first-line anti-tuberculosis drug. We quantified microRNA-122 expression and indices of oxidative stress at 7 time points, including 1, 3, and 5 days and 1, 2, 3, and 4 weeks. The tissue microRNA-122 levels and oxidative stress significantly changed at 3 and 5 days, suggesting that isoniazid-induced liver injury reduces oxidative stress and microRNA-122 expression compared to in the control group (P microRNA-122, began to change at 5 days (P microRNA-122 profile may affect oxidative stress by regulating mitochondrial ribosome protein S11 gene during isoniazid-induced liver injury, which may contribute to the response mechanisms of microRNA-122 and oxidative stress.

  14. Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen-activated protein kinase signalling pathway.

    Science.gov (United States)

    Wei, Liang; Zhang, Yanfei; Yang, Cheng; Wang, Qi; Zhuang, Zhongwei; Sun, Zhiyang

    2014-02-01

    Previous investigations have found that ebselen is able to treat neurodegenerative diseases caused by radical and acute total cerebral ischaemia. The aim of the present study was to investigate the neuroprotective effects of ebselen in a traumatic brain injury (TBI) model. Ninety Sprague-Dawley rats were randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an injury model group; (iii) low-dose (3 mg/kg) ebselen-treated group; (iv) a moderate-dose (10 mg/kg) ebselen-treated group; and (v) a high-dose (30 mg/kg) ebselen-treated group. The TBI model was created according using a modified weight-drop model. Neurological severity score (NSS), brain water content and histopathological deficits were assessed as parameters of injury severity. Expression of nitric oxide (NO), inducible NO synthase (iNOS) mRNA, Toll-like receptor (TLR) and phosphorylated (p-) p38 mitogen-activated protein kinase (MAPK) were examined by chemical colorimetry, quantitative polymerase chain reaction and western blotting 24 h after intragastric ebselen administration. Rats in the TBI model group exhibited markedly more severe neurological injury (higher NSS, more brain water content and more histopathological deficits) than those in the sham-operated group. Ebselen treatment significantly ameliorated the neurological injury of TBI rats in a dose-dependent manner. Moreover, ebselen significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p-p38 MAPK expression, indicating the involvement of NO and p38 MAPK signalling pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen ameliorated neurological injury, possibly by reducing NO levels and modulating the TLR4-mediated p38 MAPK signalling pathway. Therefore, ebselen may have potential to treat secondary injuries of TBI. © 2013 Wiley Publishing Asia Pty Ltd.

  15. Sirtuin7 is involved in protecting neurons against oxygen-glucose deprivation and reoxygenation-induced injury through regulation of the p53 signaling pathway.

    Science.gov (United States)

    Lv, Jianrui; Tian, Junbin; Zheng, Guoxi; Zhao, Jing

    2017-10-01

    Sirtuin7 (SIRT7) is known to regulate apoptosis and stress responses. So far, very little is known about the role of SIRT7 in cerebral ischemia/reperfusion injury. In this study, we aimed to investigate the potential role of SIRT7 in regulating oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in neurons. We found a significant increase of SIRT7 expression in neurons in response to OGD/R treatment. Knockdown of SIRT7 aggravated OGD/R-induced injury. Knockdown of SIRT7 augmented the levels of total and acetylated p53 protein. Moreover, knockdown of SIRT7 markedly increased the transcriptional activity of p53 toward apoptosis and activated the p53-mediated proapoptotic signaling pathway. By contrast, overexpression of SIRT7 showed the opposite effects. Taken together, the results of our study suggest that SIRT7 is involved in protecting neurons against OGD/R-induced injury, possibly through regulation of the p53-mediated proapoptotic signaling pathway, indicating a potential therapeutic target for cerebral ischemia/reperfusion injury. © 2017 Wiley Periodicals, Inc.

  16. Nitric oxide stress and activation of AMP-activated protein kinase impair β-cell sarcoendoplasmic reticulum calcium ATPase 2b activity and protein stability.

    Science.gov (United States)

    Tong, X; Kono, T; Evans-Molina, C

    2015-06-18

    The sarcoendoplasmic reticulum Ca(2+) ATPase 2b (SERCA2b) pump maintains a steep Ca(2+) concentration gradient between the cytosol and ER lumen in the pancreatic β-cell, and the integrity of this gradient has a central role in regulated insulin production and secretion, maintenance of ER function and β-cell survival. We have previously demonstrated loss of β-cell SERCA2b expression under diabetic conditions. To define the mechanisms underlying this, INS-1 cells and rat islets were treated with the proinflammatory cytokine interleukin-1β (IL-1β) combined with or without cycloheximide or actinomycin D. IL-1β treatment led to increased inducible nitric oxide synthase (iNOS) gene and protein expression, which occurred concurrently with the activation of AMP-activated protein kinase (AMPK). IL-1β led to decreased SERCA2b mRNA and protein expression, whereas time-course experiments revealed a reduction in protein half-life with no change in mRNA stability. Moreover, SERCA2b protein but not mRNA levels were rescued by treatment with the NOS inhibitor l-NMMA (NG-monomethyl L-arginine), whereas the NO donor SNAP (S-nitroso-N-acetyl-D,L-penicillamine) and the AMPK activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) recapitulated the effects of IL-1β on SERCA2b protein stability. Similarly, IL-1β-induced reductions in SERCA2b expression were rescued by pharmacological inhibition of AMPK with compound C or by transduction of a dominant-negative form of AMPK, whereas β-cell death was prevented in parallel. Finally, to determine a functional relationship between NO and AMPK signaling and SERCA2b activity, fura-2/AM (fura-2-acetoxymethylester) Ca(2+) imaging experiments were performed in INS-1 cells. Consistent with observed changes in SERCA2b expression, IL-1β, SNAP and AICAR increased cytosolic Ca(2+) and decreased ER Ca(2+) levels, suggesting congruent modulation of SERCA activity under these conditions. In aggregate, these results show that SERCA2b

  17. Piperidine alkaloids from Piperretrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Jin [Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Myoung-Su; Jo, Keunae [Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Hwang, Jae-Kwan, E-mail: jkhwang@yonsei.ac.kr [Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Translational Research Center for Protein Functional Control, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2011-07-22

    Highlights: {yields} Piperidine alkaloids from Piperretrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, are isolated as the anti-obesity constituents. {yields} PRPA administration significantly reduces body weight gain without altering food intake and fat pad mass. {yields} PRPA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} PRPAs attenuate HFD-induced obesity by activating AMPK and PPAR{delta}, and regulate lipid metabolism, suggesting their potential anti-obesity effects. -- Abstract: The fruits of Piperretrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor {delta} (PPAR{delta}) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPAR{delta} protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also

  18. Antidiabetic and Antihyperlipidemic Effects of Clitocybe nuda on Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice

    Directory of Open Access Journals (Sweden)

    Mei-Hsing Chen

    2014-01-01

    Full Text Available The objective of this study was to evaluate the antihyperlipidemic and antihyperglycemic effects and mechanism of the extract of Clitocybe nuda (CNE, in high-fat- (HF- fed mice. C57BL/6J was randomly divided into two groups: the control (CON group was fed with a low-fat diet, whereas the experimental group was fed with a HF diet for 8 weeks. Then, the HF group was subdivided into five groups and was given orally CNE (including C1: 0.2, C2: 0.5, and C3: 1.0 g/kg/day extracts or rosiglitazone (Rosi or vehicle for 4 weeks. CNE effectively prevented HF-diet-induced increases in the levels of blood glucose, triglyceride, insulin (P<0.001, P<0.01, P<0.05, resp. and attenuated insulin resistance. By treatment with CNE, body weight gain, weights of white adipose tissue (WAT and hepatic triacylglycerol content were reduced; moreover, adipocytes in the visceral depots showed a reduction in size. By treatment with CNE, the protein contents of glucose transporter 4 (GLUT4 were significantly increased in C3-treated group in the skeletal muscle. Furthermore, CNE reduces the hepatic expression of glucose-6-phosphatase (G6Pase and glucose production. CNE significantly increases protein contents of phospho-AMP-activated protein kinase (AMPK in the skeletal muscle and adipose and liver tissues. Therefore, it is possible that the activation of AMPK by CNE leads to diminished gluconeogenesis in the liver and enhanced glucose uptake in skeletal muscle. It is shown that CNE exhibits hypolipidemic effect in HF-fed mice by increasing ATGL expression, which is known to help triglyceride to hydrolyze. Moreover, antidiabetic properties of CNE occurred as a result of decreased hepatic glucose production via G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic states by CNE in HF-fed mice occurred by regulation of GLUT4, G6Pase, ATGL, and AMPK phosphorylation.

  19. AMP-Activated Kinase (AMPK Activation by AICAR in Human White Adipocytes Derived from Pericardial White Adipose Tissue Stem Cells Induces a Partial Beige-Like Phenotype.

    Directory of Open Access Journals (Sweden)

    Omar Abdul-Rahman

    Full Text Available Beige adipocytes are special cells situated in the white adipose tissue. Beige adipocytes, lacking thermogenic cues, morphologically look quite similar to regular white adipocytes, but with a markedly different response to adrenalin. White adipocytes respond to adrenergic stimuli by enhancing lipolysis, while in beige adipocytes adrenalin induces mitochondrial biogenesis too. A key step in the differentiation and function of beige adipocytes is the deacetylation of peroxisome proliferator-activated receptor (PPARγ by SIRT1 and the consequent mitochondrial biogenesis. AMP-activated protein kinase (AMPK is an upstream activator of SIRT1, therefore we set out to investigate the role of AMPK in beige adipocyte differentiation using human adipose-derived mesenchymal stem cells (hADMSCs from pericardial adipose tissue. hADMSCs were differentiated to white and beige adipocytes and the differentiation medium of the white adipocytes was supplemented with 100 μM [(2R,3S,4R,5R-5-(4-Carbamoyl-5-aminoimidazol-1-yl-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate (AICAR, a known activator of AMPK. The activation of AMPK with AICAR led to the appearance of beige-like morphological properties in differentiated white adipocytes. Namely, smaller lipid droplets appeared in AICAR-treated white adipocytes in a similar fashion as in beige cells. Moreover, in AICAR-treated white adipocytes the mitochondrial network was more fused than in white adipocytes; a fused mitochondrial system was characteristic to beige adipocytes. Despite the morphological similarities between AICAR-treated white adipocytes and beige cells, functionally AICAR-treated white adipocytes were similar to white adipocytes. We were unable to detect increases in basal or cAMP-induced oxygen consumption rate (a marker of mitochondrial biogenesis when comparing control and AICAR-treated white adipocytes. Similarly, markers of beige adipocytes such as TBX1, UCP1, CIDEA, PRDM16 and TMEM26 remained

  20. Piperidine alkaloids from Piperretrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase

    International Nuclear Information System (INIS)

    Kim, Kyung Jin; Lee, Myoung-Su; Jo, Keunae; Hwang, Jae-Kwan

    2011-01-01

    Highlights: → Piperidine alkaloids from Piperretrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, are isolated as the anti-obesity constituents. → PRPA administration significantly reduces body weight gain without altering food intake and fat pad mass. → PRPA reduces high-fat diet-induced triglyceride accumulation in liver. → PRPAs attenuate HFD-induced obesity by activating AMPK and PPARδ, and regulate lipid metabolism, suggesting their potential anti-obesity effects. -- Abstract: The fruits of Piperretrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor δ (PPARδ) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPARδ protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also protected against the development of

  1. Functional Outcome With Percutaneous Ilio-sacral Screw Fixation For Posterior Pelvic Ring Injuries In Patients Involved In Heavy Manual Laboring

    Directory of Open Access Journals (Sweden)

    Abhishek SM

    2015-11-01

    Full Text Available Introduction: Unstable posterior pelvic ring injuries are best treated with operative methods due to better post-op functional score. Our patient cohort was involved in heavy manual laboring frequently required ground level work in their activities of daily living. There are very few outcome studies dealing exclusively with such patients. Materials & Methods: Forty one patients who were treated with percutaneous sacroiliac screw fixation under fluoroscopic guidance and were followed-up for at least one year were analyzed retrospectively for functional outcome using the Majeed score. Results: Twenty one (51.22% and thirteen (31.70% patients were found to be in excellent and good categories respectively and majority of the patients (thirty/73.17% were able to return to their original occupation with or without minor adjustments. Conclusion: Percutaneous ilio-sacral screw fixation for posterior pelvic unstable injuries is an acceptable mode of treatment in patients involved in heavy manual laboring.

  2. Structural Injury after Lithium Treatment in Human and Rat Kidney involves Glycogen Synthase Kinase-3β Positive Epithelium

    DEFF Research Database (Denmark)

    Kjærsgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    2011-01-01

    Lithium is reabsorbed by distal nephron segments in sodium depleted states. It was hypothesized that lithium causes permanent injury to the developing kidney particularly in the sodium-retaining phase around weaning through entry into epithelial cells of the distal nephron and inhibition of glyco....... Lithium causes proliferation, structural injury and increases inactive pGSK-3β abundance in these segments. The data are compatible with epithelial entry of lithium and a causal role for GSK-3β in postnatal developing cortical collecting duct epithelium....

  3. Mannan-binding lectin is involved in the protection against renal ischemia/ reperfusion injury by dietary restriction

    NARCIS (Netherlands)

    Shushimita; P. van der Pol (Pieter); R.W.F. de Bruin (Ron); J.N.M. IJzermans (Jan); C. van Kooten (Cees); F.J.M.F. Dor (Frank)

    2015-01-01

    textabstractPreoperative fasting and dietary restriction offer robust protection against renal ischemia/ reperfusion injury (I/RI) in mice.We recently showed that Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on

  4. Documentation and analysis of traumatic injuries in clinical forensic medicine involving structured light three-dimensional surface scanning versus photography.

    Science.gov (United States)

    Shamata, Awatif; Thompson, Tim

    2018-05-10

    Non-contact three-dimensional (3D) surface scanning has been applied in forensic medicine and has been shown to mitigate shortcoming of traditional documentation methods. The aim of this paper is to assess the efficiency of structured light 3D surface scanning in recording traumatic injuries of live cases in clinical forensic medicine. The work was conducted in Medico-Legal Centre in Benghazi, Libya. A structured light 3D surface scanner and ordinary digital camera with close-up lens were used to record the injuries and to have 3D and two-dimensional (2D) documents of the same traumas. Two different types of comparison were performed. Firstly, the 3D wound documents were compared to 2D documents based on subjective visual assessment. Additionally, 3D wound measurements were compared to conventional measurements and this was done to determine whether there was a statistical significant difference between them. For this, Friedman test was used. The study established that the 3D wound documents had extra features over the 2D documents. Moreover; the 3D scanning method was able to overcome the main deficiencies of the digital photography. No statistically significant difference was found between the 3D and conventional wound measurements. The Spearman's correlation established strong, positive correlation between the 3D and conventional measurement methods. Although, the 3D surface scanning of the injuries of the live subjects faced some difficulties, the 3D results were appreciated, the validity of 3D measurements based on the structured light 3D scanning was established. Further work will be achieved in forensic pathology to scan open injuries with depth information. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  5. Investigation on occupant injury severity in rear-end crashes involving trucks as the front vehicle in Beijing area, China

    Directory of Open Access Journals (Sweden)

    Quan Yuan

    2017-02-01

    Conclusion: All the abovementioned significant factors should be improved, such as the conditions of lighting and the layout of lanes on roads. Two of the most common driver factors are drivers' age and drivers' original residence. Young drivers and outsiders have a higher injury severity. Therefore it is imperative to enhance the safety education and management on the young drivers who steer heavy duty truck from other cities to Beijing on weekdays.

  6. Specificity protein 1-zinc finger protein 179 pathway is involved in the attenuation of oxidative stress following brain injury

    Directory of Open Access Journals (Sweden)

    Jian-Ying Chuang

    2017-04-01

    Full Text Available After sudden traumatic brain injuries, secondary injuries may occur during the following days or weeks, which leads to the accumulation of reactive oxygen species (ROS. Since ROS exacerbate brain damage, it is important to protect neurons against their activity. Zinc finger protein 179 (Znf179 was shown to act as a neuroprotective factor, but the regulation of gene expression under oxidative stress remains unknown. In this study, we demonstrated an increase in Znf179 protein levels in both in vitro model of hydrogen peroxide (H2O2-induced ROS accumulation and animal models of traumatic brain injury. Additionally, we examined the sub-cellular localization of Znf179, and demonstrated that oxidative stress increases Znf179 nuclear shuttling and its interaction with specificity protein 1 (Sp1. Subsequently, the positive autoregulation of Znf179 expression, which is Sp1-dependent, was further demonstrated using luciferase reporter assay and green fluorescent protein (GFP-Znf179-expressing cells and transgenic mice. The upregulation of Sp1 transcriptional activity induced by the treatment with nerve growth factor (NGF led to an increase in Znf179 levels, which further protected cells against H2O2-induced damage. However, Sp1 inhibitor, mithramycin A, was shown to inhibit NGF effects, leading to a decrease in Znf179 expression and lower cellular protection. In conclusion, the results obtained in this study show that Znf179 autoregulation through Sp1-dependent mechanism plays an important role in neuroprotection, and NGF-induced Sp1 signaling may help attenuate more extensive (ROS-induced damage following brain injury.

  7. Involvement of poly(ADP-ribose polymerase-1 in development of spinal cord injury in Chinese individuals: a Chinese clinical study

    Directory of Open Access Journals (Sweden)

    Meng Q

    2017-12-01

    Full Text Available Qing-Tao Meng,* Guang Yang,* Ren-Bo Li, Jing-Xin Nie, Wei Zhou, Hong-De Yu, Bo Chen, Li Jiang, Jing-Bo Shang Department of Spine Surgery, The Third People’s Hospital of Dalian, Dalian, People’s Republic of China *These authors contributed equally to this work Objective: We aimed to evaluate whether the polymorphism of poly(ADP-ribose polymerase-1 (PARP-1 is involved as potential risk factor in the development of spinal cord injury (SCI among Chinese individuals.Patients and methods: Patients with a confirmed diagnosis of SCI (other than traumatic injury and healthy individuals with no clinical symptoms of SCI were enrolled at Spinal Cord Injury Care Center, The Third People’s Hospital of Dalian, China. Genetic polymorphisms were studied in plasma samples by polymerase chain reaction-restriction fragment length polymorphism assay.Results: A total of 130 Chinese patients with SCI and 130 healthy Chinese individuals were included. We found that patients with the GG genotype (odds ratio [OR]: 4.09, 95% confidence interval [CI] 2.42–6.90, P<0.001 and carriers of the G allele (OR 3.96, 95% CI 2.33–6.74, P<0.0001 were at high risk of developing SCI. A del/ins polymorphism of the NF-κB1 gene (OR 3.32, 95% CI 1.96–5.61, P<0.001 was also found to be associated with SCI.Conclusion: Our study suggests that PARP-1 polymorphisms are involved in the development of SCI in Chinese individuals. Thus, PARP-1 polymorphisms can be considered as one of the potential risk factors for developing SCI. Keywords: spinal cord injury, poly(ADP-ribose polymerase-1, polymorphism 

  8. Potential involvement of oxygen intermediates and glutathione depletion in UV-induced epidermal cell injury in vitro

    International Nuclear Information System (INIS)

    Hsieh, G.C.; Acosta, D.

    1991-01-01

    Generation of reactive oxygen species (ROS) and depletion of glutathione (GSH) are suggested as the cytotoxic mechanisms for UVB-induced cellular damage. Primary monolayer cultures of epidermal keratinocytes (KCs) prepared from the skin of neonatal rats were irradiated with UVB at levels of 0.25-3.0 J/cm 2 . Cytotoxicity was measured at 3, 6, and 12 hr after UVB radiation. Exposure of KCs to UVB resulted in time- and dose-related toxic responses as determined by plasma membrane integrity, lysosomal function and mitochondrial metabolic activity. Irradiated KCs generated superoxide in a dose-dependent manner when compared to sham-irradiated cells. Superoxide formation, which occurred before and concomitant with cell injury, was decreased by superoxide dismutase (SOD). Cell injury was also significantly prevented by ROS scavengers, SOD and catalase. Pretreatment of cells with endocytosis inhibitors, cytochalasin B and methylamine, suppressed the ability of SOD and catalase to protect keratinocytes from UVB-induced toxicity. Irradiation of cells with UVB caused rapid depletion of GSH to about 30% of unirradiated levels within 15 min. UVB-irradiation led to a rapid transient increase in GSH peroxidase activity, concomitant with a marked decrease in the GSH/GSSG ratio. After 1 hr., while the GSH/GSSG ratio remained low, the GSH peroxidase activity declined below the control levels in UVB-treated epidermal cells. Following extensive GSH depletion in cells preincubated with 0.1 mM buthiomine sulfoximine, KCs became strongly sensitized to the cytotoxic action of UVB. These results indicate that UVB-induced cell injury in cultured KCs may be mediated by ROs and that endogenous GSH may play an important protective role against the cytotoxic action of UVB

  9. Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model.

    Science.gov (United States)

    Rong, Jian; Ye, Sheng; Liang, Meng-ya; Chen, Guang-xian; Liu, Hai; Zhang, Jin-Xin; Wu, Zhong-kai

    2013-01-01

    Controlled oxygen reperfusion could protect the lung against ischemia-reperfusion injury in cardiopulmonary bypass (CPB) by downregulating high mobility group box 1 (HMGB1), a high affinity receptor of HMGB1. This study investigated the effect of controlled oxygen reperfusion on receptor for advanced glycation end products (RAGE) expression and its downstream effects on lung ischemia-reperfusion injury. Fourteen canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest followed by 90 minutes of reperfusion. Animals were randomized to receive 80% FiO2 during the entire procedure (control group) or to a test group receiving a controlled oxygen reperfusion protocol. Pathologic changes in lung tissues, RAGE expression, serum interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated. The lung pathologic scores after 25 and 90 minutes of reperfusion were significantly lower in the test group compared with the control group (p RAGE expression, TNF-α, and IL-6 were downregulated by controlled oxygen treatment (p RAGE might be involved in the lung ischemia-reperfusion injury in canine model of CPB, which was downregulated by controlled oxygen reperfusion.

  10. Tissue injury after lithium treatment in human and rat postnatal kidney involves glycogen synthase kinase 3β-positive epithelium

    DEFF Research Database (Denmark)

    Kjaersgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    2012-01-01

    plasma lithium concentration of 1.0 mmol/L. Kidneys from lithium-treated rat pups exhibited dilated distal nephron segments with microcysts. Stereological analysis showed reduced cortex and outer medullary volumes. Lithium increased pGSK-3β and the proliferation marker PCNA protein abundances in cortex...... concentration capacity and diminished outer medullary volume. Histological sections of nephrectomy samples and a biopsy from 3 long-term lithium-treated patients showed multiple cortical microcysts that originated from normally appearing tubules. Microcysts were lined by a cuboidal PCNA-, GSK-3β- and pGSK-3β......It was hypothesized that lithium causes accelerated and permanent injury to the postnatally developing kidney through entry into epithelial cells of the distal nephron and inhibition of glycogen synthase kinase-3β (GSK-3β). GSK-3β immunoreactivity was associated with glomeruli, thick ascending limb...

  11. Involvement of protein kinase B and mitogen-activated protein kinases in experimental normothermic liver ischaemia-reperfusion injury.

    Science.gov (United States)

    Cursio, R; Filippa, N; Miele, C; Van Obberghen, E; Gugenheim, J

    2006-06-01

    This study evaluated the role of protein kinase B (PKB), phosphatidylinositol 3-kinase (PI3-K), Bcl-2-associated death protein (BAD) and mitogen-activated protein kinases (MAPKs) in normothermic ischaemia-reperfusion (IR)-induced apoptosis in rat liver. Rats were divided into two groups that received either phosphate-buffered saline (control) or the caspase inhibitor Z-Asp-2,6-dichorobenzoyloxymethylketone (Z-Asp-cmk), injected intravenously 2 min before the induction of 120 min of normothermic liver ischaemia. Liver apoptosis was assessed by the terminal deoxyribonucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) method. PI3-K, PKB, BAD and MAPK activities were measured in ischaemic and non-ischaemic lobes at various times after reperfusion. The number of TUNEL-positive cells was significantly decreased after pretreatment with Z-Asp-cmk. In controls, PI3-K and PKB activities and BAD phosphorylation were inhibited in ischaemic liver lobes. The MAPKs (extracellular signal-regulated kinases, c-Jun N-terminal kinase and p38) showed different patterns of activation during IR. PKB activity was not modified by pretreatment with Z-Asp-cmk. Induction of apoptosis during IR liver injury might be triggered by inactivation of the antiapoptotic PI3-K-PKB pathway and activation of the proapoptotic MAPKs. Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  12. Role of cytochrome P450-mediated metabolism and involvement of reactive metabolite formations on antiepileptic drug-induced liver injuries.

    Science.gov (United States)

    Sasaki, Eita; Yokoi, Tsuyoshi

    2018-01-01

    Several drugs have been withdrawn from the market or restricted to avoid unexpected adverse outcomes. Drug-induced liver injury (DILI) is a serious issue for drug development. Among DILIs, idiosyncratic DILIs have been a serious problem in drug development and clinical uses. Idiosyncratic DILI is most often unrelated to pharmacological effects or the dosing amount of a drug. The number of drugs that cause idiosyncratic DILI continue to grow in part because no practical preclinical tests have emerged that can identify drug candidates with the potential for developing idiosyncratic DILIs. Nevertheless, the implications of drug metabolism-related factors and immune-related factors on idiosyncratic DILIs has not been fully clarified because this toxicity can not be reproduced in animals. Therefore, accumulated evidence for the mechanisms of the idiosyncratic toxicity has been limited to only in vitro studies. This review describes current knowledge of the effects of cytochrome P450 (CYP)-mediated metabolism and its detoxification abilities based on studies of idiosyncratic DILI animal models developed recently. This review also focused on antiepileptic drugs, phenytoin (diphenyl hydantoin, DPH) and carbamazepine (CBZ), which have rarely caused severe adverse reactions, such as fulminant hepatitis, and have been recognized as sources of idiosyncratic DILI. The studies of animal models of idiosyncratic DILIs have produced new knowledge of chronic administration, CYP inductions/inhibitions, glutathione contents, and immune-related factors for the initiation of idiosyncratic DILIs. Considering changes in the drug metabolic profile and detoxification abilities, idiosyncratic DILIs caused by antiepileptic drugs will lead to understanding the mechanisms of these DILIs.

  13. Signaling pathways involved in renal oxidative injury: role of the vasoactive peptides and the renal dopaminergic system.

    Science.gov (United States)

    Rukavina Mikusic, N L; Kravetz, M C; Kouyoumdzian, N M; Della Penna, S L; Rosón, M I; Fernández, B E; Choi, M R

    2014-01-01

    The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation.

  14. Stab injury to the preauricular region with laceration of the external carotid artery without involvement of the facial nerve: a case report.

    Science.gov (United States)

    Casal, Diogo; Pelliccia, Giovanni; Pais, Diogo; Carrola-Gomes, Diogo; Angélica-Almeida, Maria; Videira-Castro, José; Goyri-O'Neill, João

    2017-07-29

    Open injuries to the face involving the external carotid artery are uncommon. These injuries are normally associated with laceration of the facial nerve because this nerve is more superficial than the external carotid artery. Hence, external carotid artery lesions are usually associated with facial nerve dysfunction. We present an unusual case report in which the patient had an injury to this artery with no facial nerve compromise. A 25-year-old Portuguese man sustained a stab wound injury to his right preauricular region with a broken glass. Immediate profuse bleeding ensued. Provisory tamponade of the wound was achieved at the place of aggression by two off-duty doctors. He was initially transferred to a district hospital, where a large arterial bleeding was observed and a temporary compressive dressing was applied. Subsequently, the patient was transferred to a tertiary hospital. At admission in the emergency room, he presented a pulsating lesion in the right preauricular region and slight weakness in the territory of the inferior buccal branch of the facial nerve. The physical examination suggested an arterial lesion superficial to the facial nerve. However, in the operating theater, a section of the posterior and lateral flanks of the external carotid artery inside the parotid gland was identified. No lesion of the facial nerve was observed, and the external carotid artery was repaired. To better understand the anatomical rationale of this uncommon clinical case, we dissected the preauricular region of six cadavers previously injected with colored latex solutions in the vascular system. A small triangular space between the two main branches of division of the facial nerve in which the external carotid artery was not covered by the facial nerve was observed bilaterally in all cases. This clinical case illustrates that, in a preauricular wound, the external carotid artery can be injured without facial nerve damage. However, no similar description was found in

  15. Short frontal plane fractures involving the dorsoproximal articular surface of the proximal phalanx: Description of the injury and a technique for repair.

    Science.gov (United States)

    Wright, I M; Minshall, G J

    2018-01-01

    Chip fractures of the dorsoproximal articular margin of the proximal phalanx are common injuries in racehorses. Large fractures can extend distal to the joint capsule insertion and have been described as dorsal frontal fractures. To report the location and morphology of short frontal plane fractures involving the dorsoproximal articular surface of the proximal phalanx and describe a technique for repair under arthroscopic and radiographic guidance. Single centre retrospective case study. Case records of horses with frontal plane fractures restricted to the dorsoproximal epiphysis and metaphysis of the proximal phalanx referred to Newmarket Equine Hospital were retrieved, images reviewed and lesion morphology described. A technique for repair and the results obtained are reported. A total of 22 fractures in 21 horses commencing at the proximal articular surface exited the dorsal cortex of the proximal phalanx distal to the metacarpophalangeal/metatarsophalangeal joint capsule in 17 hind- and five forelimbs. All were in Thoroughbred racehorses. In 16 cases these were acute racing or training injuries; 20 fractures were medial, one lateral and one was midline. All were repaired with a single lag screw using arthroscopic and radiographically determined landmarks. A total of 16 horses raced after surgery with performance data similar to their preinjury levels. The study demonstrates substantial morphological similarities between individual lesions supporting a common pathophysiology, but does not identify precise causation. There are no cases managed differently that might permit assessment of the comparative efficacy of the treatment described. Short frontal plane fractures involving the dorsoproximal margin of the proximal phalanx that exit the bone distal to the metacarpophalangeal/metatarsophalangeal joint capsule have substantial morphological similarities, are amenable to minimally invasive repair and carry a good prognosis for return to training and racing.

  16. Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK.

    Directory of Open Access Journals (Sweden)

    Jordan J Toutounchian

    Full Text Available Radiation-induced damage to the retina triggers leukostasis, retinal endothelial cell (REC death, and subsequent hypoxia. Resultant ischemia leads to visual loss and compensatory retinal neovascularization (RNV. Using human RECs, we demonstrated that radiation induced leukocyte adhesion through mechanisms involving p38MAPK, p53, and ICAM-1 activation. Additional phenotypic changes included p38MAPK-dependent tyrosine phosphorylation of the focal adhesion scaffolding protein, paxillin (Tyr118. The quinic acid derivative KZ-41 lessened leukocyte adhesion and paxillin-dependent proliferation via inhibition of p38MAPK-p53-ICAM-1 signaling. Using the murine oxygen-induced retinopathy (OIR model, we examined the effect of KZ-41 on pathologic RNV. Daily ocular application of a KZ-41-loaded nanoemulsion significantly reduced both the avascular and neovascular areas in harvested retinal flat mounts when compared to the contralateral eye receiving vehicle alone. Our data highlight the potential benefit of KZ-41 in reducing both the retinal ischemia and neovascularization provoked by genotoxic insults. Further research into how quinic acid derivatives target and mitigate inflammation is needed to fully appreciate their therapeutic potential for the treatment of inflammatory retinal vasculopathies.

  17. Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Taylor, Eric B.; Witczak, Carol A.

    2010-01-01

    TBC1D4 (also known as AS160) regulates GLUT4 translocation and glucose uptake in adipocytes and skeletal muscle. Its mode of action involves phosphorylation of Serine (S)/Threonine (T) residues by upstream kinases resulting in inactivation of Rab-GAP activity leading to GLUT4 mobilization...

  18. Hamartoma fibroso infantil: lesão volumosa com envolvimento de plexo braquil Children's fibrous hamartoma: extensive injury involving brachial plexus

    Directory of Open Access Journals (Sweden)

    Lisieux Eyer de Jesus

    2006-01-01

    Full Text Available OBJETIVO: Apresentar um caso de hamartoma fibroso da infância em lactente ressecado tardiamente e se apresentando como lesão extensa, com envolvimento de elementos vasculares e neurais do plexo braquial. MÉTODOS: Estudo de caso clínico e revisão de literatura pertinente. RESULTADOS: Criança do sexo masculino, com massa tumoral axilar direita, irregular surgida aos 2 meses de idade e relacionada à administração da vacina BCG, sendo tratada com agentes anti-tuberculosos, sem resposta. Mediante biópsia a lesão foi diagnosticada como hamartoma fibroso infantil, e, após sofrer período de crescimento rápido, foi submetida à exérese cirúrgica completa. CONCLUSÃO: O hamartoma fibroso juvenil é um tumor benigno raro, tipicamente se apresentando no primeiro ano de vida em meninos, com localização mais comum no oco axilar. O diagnóstico diferencial se faz com tumores de partes moles em geral e, em casos de apresentação na axila direita, com adenopatias axilares causadas por reação à BCG. O tratamento é exerese completa da lesão e o prognóstico é favorável.OBJECTIVE: To present a case of fibrous hamartoma in a late-dried infant presenting as an extensive injury, involving vascular and neural elements of brachial plexus. METHODS: Clinical case study and pertinent literature review. RESULTS: Male child, with right axillary irregular tumoral mass, of which onset occurred at 2 months of age and related to BCG vaccine application, being treated with anti-tuberculosis agents, not responding to therapy. Upon biopsy, the injury was diagnosed as children’s fibrous hamartoma, and, after a fast growing period, was submitted to total surgical exeresis. CONCLUSION: The juvenile fibrous hamartoma is a rare benign tumor, typically occurring within the first year of life in boys, most commonly located at axillary gap. The differential diagnosis is performed with soft parts tumors in general, and, in right axillary location cases, with

  19. Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway.

    Science.gov (United States)

    Bavley, Charlotte C; Rice, Richard C; Fischer, Delaney K; Fakira, Amanda K; Byrne, Maureen; Kosovsky, Maria; Rizzo, Bryant K; Del Prete, Dolores; Alaedini, Armin; Morón, Jose A; Higgins, Joseph J; D'Adamio, Luciano; Rajadhyaksha, Anjali M

    2018-03-14

    A homozygous nonsense mutation in the cereblon ( CRBN ) gene results in autosomal recessive, nonsyndromic intellectual disability that is devoid of other phenotypic features, suggesting a critical role of CRBN in mediating learning and memory. In this study, we demonstrate that adult male Crbn knock-out ( Crbn KO ) mice exhibit deficits in hippocampal-dependent learning and memory tasks that are recapitulated by focal knock-out of Crbn in the adult dorsal hippocampus, with no changes in social or repetitive behavior. Cellular studies identify deficits in long-term potentiation at Schaffer collateral CA1 synapses. We further show that Crbn is robustly expressed in the mouse hippocampus and Crbn KO mice exhibit hyperphosphorylated levels of AMPKα (Thr172). Examination of processes downstream of AMP-activated protein kinase (AMPK) finds that Crbn KO mice have a selective impairment in mediators of the mTORC1 translation initiation pathway in parallel with lower protein levels of postsynaptic density glutamatergic proteins and higher levels of excitatory presynaptic markers in the hippocampus with no change in markers of the unfolded protein response or autophagy pathways. Acute pharmacological inhibition of AMPK activity in adult Crbn KO mice rescues learning and memory deficits and normalizes hippocampal mTORC1 activity and postsynaptic glutamatergic proteins without altering excitatory presynaptic markers. Thus, this study identifies that loss of Crbn results in learning, memory, and synaptic defects as a consequence of exaggerated AMPK activity, inhibition of mTORC1 signaling, and decreased glutamatergic synaptic proteins. Thus, Crbn KO mice serve as an ideal model of intellectual disability to further explore molecular mechanisms of learning and memory. SIGNIFICANCE STATEMENT Intellectual disability (ID) is one of the most common neurodevelopmental disorders. The cereblon ( CRBN ) gene has been linked to autosomal recessive, nonsyndromic ID, characterized by an

  20. CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles.

    Science.gov (United States)

    Rubio-Navarro, Alfonso; Carril, Mónica; Padro, Daniel; Guerrero-Hue, Melanie; Tarín, Carlos; Samaniego, Rafael; Cannata, Pablo; Cano, Ainhoa; Villalobos, Juan Manuel Amaro; Sevillano, Ángel Manuel; Yuste, Claudia; Gutiérrez, Eduardo; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

    2016-01-01

    Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis.

  1. Long-Term Chronic Intermittent Hypobaric Hypoxia Induces Glucose Transporter (GLUT4 Translocation Through AMP-Activated Protein Kinase (AMPK in the Soleus Muscle in Lean Rats

    Directory of Open Access Journals (Sweden)

    Patricia Siques

    2018-06-01

    Full Text Available Background: In chronic hypoxia (CH and short-term chronic intermittent hypoxia (CIH exposure, glycemia and insulin levels decrease and insulin sensitivity increases, which can be explained by changes in glucose transport at skeletal muscles involving GLUT1, GLUT4, Akt, and AMPK, as well as GLUT4 translocation to cell membranes. However, during long-term CIH, there is no information regarding whether these changes occur similarly or differently than in other types of hypoxia exposure. This study evaluated the levels of AMPK and Akt and the location of GLUT4 in the soleus muscles of lean rats exposed to long-term CIH, CH, and normoxia (NX and compared the findings.Methods: Thirty male adult rats were randomly assigned to three groups: a NX (760 Torr group (n = 10, a CIH group (2 days hypoxia/2 days NX; n = 10 and a CH group (n = 10. Rats were exposed to hypoxia for 30 days in a hypobaric chamber set at 428 Torr (4,600 m. Feeding (10 g daily and fasting times were accurately controlled. Measurements included food intake (every 4 days, weight, hematocrit, hemoglobin, glycemia, serum insulin (by ELISA, and insulin sensitivity at days 0 and 30. GLUT1, GLUT4, AMPK levels and Akt activation in rat soleus muscles were determined by western blot. GLUT4 translocation was measured with confocal microscopy at day 30.Results: (1 Weight loss and increases in hematocrit and hemoglobin were found in both hypoxic groups (p < 0.05. (2 A moderate decrease in glycemia and plasma insulin was found. (3 Insulin sensitivity was greater in the CIH group (p < 0.05. (4 There were no changes in GLUT1, GLUT4 levels or in Akt activation. (5 The level of activated AMPK was increased only in the CIH group (p < 0.05. (6 Increased GLUT4 translocation to the plasma membrane of soleus muscle cells was observed in the CIH group (p < 0.05.Conclusion: In lean rats experiencing long-term CIH, glycemia and insulin levels decrease and insulin sensitivity increases. Interestingly, there

  2. Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Wigenstam, Elisabeth; Elfsmark, Linda; Koch, Bo [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden); Bucht, Anders [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden); Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå (Sweden); Jonasson, Sofia, E-mail: sofia.jonasson@foi.se [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden)

    2016-10-15

    We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl{sub 2}) with the aim to understand the pathogenesis of the long-term sequelae of Cl{sub 2}-induced lung-injury. In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5 h up to 90 days after a single inhalation of Cl{sub 2}. A single dose of dexamethasone (10 mg/kg) was administered 1 h following Cl{sub 2}-exposure. A 15-min inhalation of 200 ppm Cl{sub 2} was non-lethal in Sprague-Dawley rats. At 24 h post exposure, Cl{sub 2}-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24 h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24 h but did not influence the AHR. Inhalation of Cl{sub 2} in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl{sub 2}-induced respiratory dysfunction. - Highlights: • Inhalation of Cl{sub 2} leads to acute lung inflammation and airway hyperreactivity. • Cl{sub 2} activates an inflammasome pathway of TGF-β induction. • Cl{sub 2} leads to a fibrotic respiratory disease. • Treatment

  3. Supplementation of chitosan alleviates high-fat diet-enhanced lipogenesis in rats via adenosine monophosphate (AMP)-activated protein kinase activation and inhibition of lipogenesis-associated genes.

    Science.gov (United States)

    Chiu, Chen-Yuan; Chan, Im-Lam; Yang, Tsung-Han; Liu, Shing-Hwa; Chiang, Meng-Tsan

    2015-03-25

    This study investigated the role of chitosan in lipogenesis in high-fat diet-induced obese rats. The lipogenesis-associated genes and their upstream regulatory proteins were explored. Diet supplementation of chitosan efficiently decreased the increased weights in body, livers, and adipose tissues in high-fat diet-fed rats. Chitosan supplementation significantly raised the lipolysis rate; attenuated the adipocyte hypertrophy, triglyceride accumulation, and lipoprotein lipase activity in epididymal adipose tissues; and decreased hepatic enzyme activities of lipid biosynthesis. Chitosan supplementation significantly activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and attenuated high-fat diet-induced protein expressions of lipogenic transcription factors (PPAR-γ and SREBP1c) in livers and adipose tissues. Moreover, chitosan supplementation significantly inhibited the expressions of downstream lipogenic genes (FAS, HMGCR, FATP1, and FABP4) in livers and adipose tissues of high-fat diet-fed rats. These results demonstrate for the first time that chitosan supplementation alleviates high-fat diet-enhanced lipogenesis in rats via AMPK activation and lipogenesis-associated gene inhibition.

  4. Activation of AMP-activated protein kinase by kainic acid mediates brain-derived neurotrophic factor expression through a NF-kappaB dependent mechanism in C6 glioma cells

    International Nuclear Information System (INIS)

    Yoon, Hana; Oh, Young Taek; Lee, Jung Yeon; Choi, Ji Hyun; Lee, Ju Hie; Baik, Hyung Hwan; Kim, Sung Soo; Choe, Wonchae; Yoon, Kyung-Sik; Ha, Joohun; Kang, Insug

    2008-01-01

    AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis. Kainic acid (KA), a prototype excitotoxin is known to induce brain-derived neurotrophic factor (BDNF) in brain. In this study, we examined the role of AMPK in KA-induced BDNF expression in C6 glioma cells. We showed that KA and KA receptor agonist induced activation of AMPK and KA-induced AMPK activation was blocked by inhibition of Ca 2+ /calmodulin-dependent protein kinase kinase (CaMKK) β. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPKα1 blocked KA-induced BDNF mRNA and protein expression. Inhibition of AMPK blocked KA-induced phosphorylation of CaMKII and I kappaB kinase (IKK) in C6 cells. Finally, we showed that inhibition of AMPK reduced DNA binding and transcriptional activation of nuclear factor-kappaB (NF-κB) in KA-treated cells. These results suggest that AMPK mediates KA-induced BDNF expression by regulating NF-κB activation

  5. Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na+/K+-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes

    Directory of Open Access Journals (Sweden)

    Stefanie Klinger

    2018-03-01

    Full Text Available Background: Beneficial effects of Resveratrol (RSV have been demonstrated, including effects on transporters and channels. However, little is known about how RSV influences intestinal transport. The aim of this study was to further characterize the effects of RSV on intestinal transport and the respective mechanisms. Methods: Porcine jejunum and ileum were incubated with RSV (300 µM, 30 min in Ussing chambers (functional studies and tissue bathes (detection of protein expression, phosphorylation, association with detergent resistant membranes (DRMs. Results: RSV reduced alanine and glucose-induced short circuit currents (ΔIsc and influenced forskolin-induced ΔIsc. The phosphorylation of sodium–glucose-linked transporter 1 (SGLT1, AMP-activated protein kinase (AMPK, protein kinase A substrates (PKA-S and liver kinase B1 (LKB1 increased but a causative relation to the inhibitory effects could not directly be established. The DRM association of SGLT1, peptide transporter 1 (PEPT1 and (phosphorylated Na+/H+-exchanger 3 (NHE3 did not change. Conclusion: RSV influences the intestinal transport of glucose, alanine and chloride and is likely to affect other transport processes. As the effects of protein kinase activation vary between the intestinal localizations, it would appear that increasing cyclic adenosine monophosphate (cAMP levels are part of the mechanism. Nonetheless, the physiological responses depend on cell type-specific structures.

  6. Mulberry (Morus alba L.) Fruit Extract Containing Anthocyanins Improves Glycemic Control and Insulin Sensitivity via Activation of AMP-Activated Protein Kinase in Diabetic C57BL/Ksj-db/db Mice.

    Science.gov (United States)

    Choi, Kyung Ha; Lee, Hyun Ah; Park, Mi Hwa; Han, Ji-Sook

    2016-08-01

    The effect of mulberry (Morus alba L.) fruit extract (MFE) on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes was evaluated. C57BL/Ksj-diabetic db/db mice were divided into three groups: diabetic control, rosiglitazone, and MFE groups. Blood glucose, plasma insulin, and intraperitoneal glucose were measured, and an insulin tolerance test was performed after MFE supplementation in db/db mice. In addition, the protein levels of various targets of insulin signaling were measured by western blotting. The blood levels of glucose and HbA1c were significantly lower in the MFE-supplemented group than in the diabetic control group. Moreover, glucose and insulin tolerance tests showed that MFE treatment increased insulin sensitivity. The homeostatic index of insulin resistance significantly decreased in the MFE-supplemented group relative to the diabetic control group. MFE supplementation significantly stimulated the levels of phosphorylated (p)-AMP-activated protein kinase (pAMPK) and p-Akt substrate of 160 kDa (pAS160) and enhanced the level of plasma membrane-glucose transporter 4 (GLUT4) in skeletal muscles. Further, dietary MFE significantly increased pAMPK and decreased the levels of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. MFE may improve hyperglycemia and insulin sensitivity via activation of AMPK and AS160 in skeletal muscles and inhibition of gluconeogenesis in the liver.

  7. AMP-activated protein kinase plays an important evolutionary conserved role in the regulation of glucose metabolism in fish skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Leonardo J Magnoni

    Full Text Available AMPK, a master metabolic switch, mediates the observed increase of glucose uptake in locomotory muscle of mammals during exercise. AMPK is activated by changes in the intracellular AMP:ATP ratio when ATP consumption is stimulated by contractile activity but also by AICAR and metformin, compounds that increase glucose transport in mammalian muscle cells. However, the possible role of AMPK in the regulation of glucose metabolism in skeletal muscle has not been investigated in other vertebrates, including fish. In this study, we investigated the effects of AMPK activators on glucose uptake, AMPK activity, cell surface levels of trout GLUT4 and expression of GLUT1 and GLUT4 as well as the expression of enzymes regulating glucose disposal and PGC1α in trout myotubes derived from a primary muscle cell culture. We show that AICAR and metformin significantly stimulated glucose uptake (1.6 and 1.3 fold, respectively and that Compound C completely abrogated the stimulatory effects of the AMPK activators on glucose uptake. The combination of insulin and AMPK activators did not result in additive nor synergistic effects on glucose uptake. Moreover, exposure of trout myotubes to AICAR and metformin resulted in an increase in AMPK activity (3.8 and 3 fold, respectively. We also provide evidence suggesting that stimulation of glucose uptake by AMPK activators in trout myotubes may take place, at least in part, by increasing the cell surface and mRNA levels of trout GLUT4. Finally, AICAR increased the mRNA levels of genes involved in glucose disposal (hexokinase, 6-phosphofructokinase, pyruvate kinase and citrate synthase and mitochondrial biogenesis (PGC-1α and did not affect glycogen content or glycogen synthase mRNA levels in trout myotubes. Therefore, we provide evidence, for the first time in non-mammalian vertebrates, suggesting a potentially important role of AMPK in stimulating glucose uptake and utilization in the skeletal muscle of fish.

  8. Qing-Qi Rickshaw : A Boon Or Bane For Public Transportation? A Study Of Road Traffic Injury Patterns Involving Qing-Qi Rickshaws In Karachi Pakistan.

    Science.gov (United States)

    Muzzammil, Muhammad; Minhas, Muhammad Saeed; Effendi, Jahanzeb; Jahanzeb, Syed; Mughal, Ayesha; Qadir, Abdul

    2017-01-01

    The three-wheeler Qing-qi and Compressed Natural Gas (CNG) auto-rickshaws were introduced in Karachi to meet the transportation demand of the growing population. These vehicles have directly or indirectly been implicated in a number of road traffic violations as well as road accidents. This study aims to describe the crash characteristics and injury patterns for Qing-qi rickshaw occupants and other road users hit by Qing-qi rickshaw in Karachi, Pakistan. An Observational/ Descriptive study was conducted at Accident & Emergency and Orthopaedic Surgery Department, Jinnah Post Graduate Medical Centre, Karachi Pakistan from July 2014 to June 2015.All patients who came with Qing-qi rickshaw accident in Accident & Emergency (A&E) of JPMC were included. Crash characteristics, details of injuries, injury severity parameters and outcome were documented in detailed interviews. Four hundred and eighty-six rickshaw related injuries were noted in road traffic accidents by Qing-gi rickshaw. Age range was 2-85 (43.5±58.68). 350 injured victims were males and 136 were females. By occupation most victims were laborers and daily wage workers (45%) and students (21%). Overloading of vehicle with more than two passengers was found in (28.5%). The most common cause of injury was collision with a moving vehicle (56%), followed by fall from rickshaw. The most common contributing factor was the overloading of rickshaw and roll over on turning (61%). Injury severity on arrival were mild (49%), moderate were (32%), and severe were (19%). Injuries related to head and neck (26%), face (14%), thorax and abdomen (5%), lower extremity and pelvic girdle (31%) and upper extremity (23%) were observed. Qing-qi rickshaw injuries are common and these vehicles are vulnerable to road traffic accidents. Occupants and road users are both at risk of injuries.

  9. High Fat Diet Attenuates the Anticontractile Activity of Aortic PVAT via a Mechanism Involving AMPK and Reduced Adiponectin Secretion

    Directory of Open Access Journals (Sweden)

    Tarek A. M. Almabrouk

    2018-02-01

    Full Text Available Background and aim: Perivascular adipose tissue (PVAT positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD on aortic PVAT and whether any changes involved AMPK.Methods: Wild type Sv129 (WT and AMPKα1 knockout (KO mice aged 8 weeks were fed normal diet (ND or HFD (42% kcal fat for 12 weeks. Adiponectin production by PVAT was assessed by ELISA and AMPK expression studied using immunoblotting. Macrophages in PVAT were identified using immunohistochemistry and markers of M1 and M2 macrophage subtypes evaluated using real time-qPCR. Vascular responses were measured in endothelium-denuded aortic rings with or without attached PVAT. Carotid wire injury was performed and PVAT inflammation studied 7 days later.Key results: Aortic PVAT from KO and WT mice was morphologically indistinct but KO PVAT had more infiltrating macrophages. HFD caused an increased infiltration of macrophages in WT mice with increased expression of the M1 macrophage markers Nos2 and Il1b and the M2 marker Chil3. In WT mice, HFD reduced the anticontractile effect of PVAT as well as reducing adiponectin secretion and AMPK phosphorylation. PVAT from KO mice on ND had significantly reduced adiponectin secretion and no anticontractile effect and feeding HFD did not alter this. Wire injury induced macrophage infiltration of PVAT but did not cause further infiltration in KO mice.Conclusions: High-fat diet causes an inflammatory infiltrate, reduced AMPK phosphorylation and attenuates the anticontractile effect of murine aortic PVAT. Mice lacking AMPKα1 phenocopy many of the changes in wild-type aortic PVAT after HFD, suggesting that AMPK may protect the vessel against deleterious changes in response to

  10. Renoprotective Effect of Lactoferrin against Chromium-Induced Acute Kidney Injury in Rats: Involvement of IL-18 and IGF-1 Inhibition.

    Directory of Open Access Journals (Sweden)

    Rehab Hegazy

    Full Text Available Hexavalent chromium (CrVI is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf against potassium dichromate (PDC-induced acute kidney injury (AKI in rats. Beside, because previous studies suggest that interlukin-18 (IL-18 and insulin-like growth factor-1 (IGF-1 play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200 mg/kg/day, p.o. or (300 mg/kg/day, p.o.; the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15 mg/kg, s.c.. PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFκB, IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1 levels. Moreover, normal expression IFN-γ mRNA and enhanced expression of TNF-α mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA, Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through

  11. Adiponectin promotes hyaluronan synthesis along with increases in hyaluronan synthase 2 transcripts through an AMP-activated protein kinase/peroxisome proliferator-activated receptor-α-dependent pathway in human dermal fibroblasts

    International Nuclear Information System (INIS)

    Yamane, Takumi; Kobayashi-Hattori, Kazuo; Oishi, Yuichi

    2011-01-01

    Highlights: ► Adiponectin promotes hyaluronan synthesis along with an increase in HAS2 transcripts. ► Adiponectin also increases the phosphorylation of AMPK. ► A pharmacological activator of AMPK increases mRNA levels of PPARα and HAS2. ► Adiponectin-induced HAS2 mRNA expression is blocked by a PPARα antagonist. ► Adiponectin promotes hyaluronan synthesis via an AMPK/PPARα-dependent pathway. -- Abstract: Although adipocytokines affect the functions of skin, little information is available on the effect of adiponectin on the skin. In this study, we investigated the effect of adiponectin on hyaluronan synthesis and its regulatory mechanisms in human dermal fibroblasts. Adiponectin promoted hyaluronan synthesis along with an increase in the mRNA levels of hyaluronan synthase 2 (HAS2), which plays a primary role in hyaluronan synthesis. Adiponectin also increased the phosphorylation of AMP-activated protein kinase (AMPK). A pharmacological activator of AMPK, 5-aminoimidazole-4-carboxamide-1β-ribofuranoside (AICAR), increased mRNA levels of peroxisome proliferator-activated receptor-α (PPARα), which enhances the expression of HAS2 mRNA. In addition, AICAR increased the mRNA levels of HAS2. Adiponectin-induced HAS2 mRNA expression was blocked by GW6471, a PPARα antagonist, in a concentration-dependent manner. These results show that adiponectin promotes hyaluronan synthesis along with increases in HAS2 transcripts through an AMPK/PPARα-dependent pathway in human dermal fibroblasts. Thus, our study suggests that adiponectin may be beneficial for retaining moisture in the skin, anti-inflammatory activity, and the treatment of a variety of cutaneous diseases.

  12. AMP-activated protein kinase α2 and E2F1 transcription factor mediate doxorubicin-induced cytotoxicity by forming a positive signal loop in mouse embryonic fibroblasts and non-carcinoma cells.

    Science.gov (United States)

    Yang, Wookyeom; Park, In-Ja; Yun, Hee; Im, Dong-Uk; Ock, Sangmi; Kim, Jaetaek; Seo, Seon-Mi; Shin, Ha-Yeon; Viollet, Benoit; Kang, Insug; Choe, Wonchae; Kim, Sung-Soo; Ha, Joohun

    2014-02-21

    Doxorubicin is one of the most widely used anti-cancer drugs, but its clinical application is compromised by severe adverse effects in different organs including cardiotoxicity. In the present study we explored mechanisms of doxorubicin-induced cytotoxicity by revealing a novel role for the AMP-activated protein kinase α2 (AMPKα2) in mouse embryonic fibroblasts (MEFs). Doxorubicin robustly induced the expression of AMPKα2 in MEFs but slightly reduced AMPKα1 expression. Our data support the previous notion that AMPKα1 harbors survival properties under doxorubicin treatment. In contrast, analyses of Ampkα2(-/-) MEFs, gene knockdown of AMPKα2 by shRNA, and inhibition of AMPKα2 activity with an AMPK inhibitor indicated that AMPKα2 functions as a pro-apoptotic molecule under doxorubicin treatment. Doxorubicin induced AMPKα2 at the transcription level via E2F1, a transcription factor that regulates apoptosis in response to DNA damage. E2F1 directly transactivated the Ampkα2 gene promoter. In turn, AMPKα2 significantly contributed to stabilization and activation of E2F1 by doxorubicin, forming a positive signal amplification loop. AMPKα2 directly interacted with and phosphorylated E2F1. This signal loop was also detected in H9c2, C2C12, and ECV (human epithelial cells) cells as well as mouse liver under doxorubicin treatment. Resveratrol, which has been suggested to attenuate doxorubicin-induced cytotoxicity, significantly blocked induction of AMPKα2 and E2F1 by doxorubicin, leading to protection of these cells. This signal loop appears to be non-carcinoma-specific because AMPKα2 was not induced by doxorubicin in five different tested cancer cell lines. These results suggest that AMPKα2 may serve as a novel target for alleviating the cytotoxicity of doxorubicin.

  13. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    International Nuclear Information System (INIS)

    Li, Wei; Fu, Jianfang; Zhang, Shun; Zhao, Jie; Xie, Nianlin; Cai, Guoqing

    2015-01-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  14. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wei [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Fu, Jianfang [Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Shun [Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Zhao, Jie [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Xie, Nianlin, E-mail: xienianlin@126.com [Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Cai, Guoqing, E-mail: firstchair@fmmu.edu.cn [Department of Gynaecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China)

    2015-06-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  15. (−-Epicatechin-3-O-β-d-allopyranoside from Davallia formosana, Prevents Diabetes and Hyperlipidemia by Regulation of Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice

    Directory of Open Access Journals (Sweden)

    Chun-Ching Shih

    2015-10-01

    Full Text Available The purpose of this experiment was to determine the antidiabetic and lipid-lowering effects of (−-epicatechin-3-O-β-d-allopyranoside (BB from the roots and stems of Davallia formosana in mice. Animal treatment was induced by high-fat diet (HFD or low-fat diet (control diet, CD. After eight weeks of HFD or CD exposure, the HFD mice were treating with BB or rosiglitazone (Rosi or fenofibrate (Feno or water through gavage for another four weeks. However, at 12 weeks, the HFD-fed group had enhanced blood levels of glucose, triglyceride (TG, and insulin. BB treatment significantly decreased blood glucose, TG, and insulin levels. Moreover, visceral fat weights were enhanced in HFD-fed mice, accompanied by increased blood leptin concentrations and decreased adiponectin levels, which were reversed by treatment with BB. Muscular membrane protein levels of glucose transporter 4 (GLUT4 were reduced in HFD-fed mice and significantly enhanced upon administration of BB, Rosi, and Feno. Moreover, BB treatment markedly increased hepatic and skeletal muscular expression levels of phosphorylation of AMP-activated (adenosine monophosphate protein kinase (phospho-AMPK. BB also decreased hepatic mRNA levels of phosphenolpyruvate carboxykinase (PEPCK, which are associated with a decrease in hepatic glucose production. BB-exerted hypotriglyceridemic activity may be partly associated with increased mRNA levels of peroxisome proliferator activated receptor α (PPARα, and with reduced hepatic glycerol-3-phosphate acyltransferase (GPAT mRNA levels in the liver, which decreased triacylglycerol synthesis. Nevertheless, we demonstrated BB was a useful approach for the management of type 2 diabetes and dyslipidemia in this animal model.

  16. Managing eye injuries

    Directory of Open Access Journals (Sweden)

    Dorothy Mutie

    2016-01-01

    Full Text Available Based on what you found during the eye examination, classify the injury as a non-mechanical injury (chemical or thermal injury, a non-globe injury (orbital or adnexal injury or as a mechanical globe injury. In the case of mechanical globe injuries, it is important to classify the injury according to the Birmingham Eye Trauma Terminology System (BETTS and write it down in the patient’s notes; this will help to ensure that everyone involved in caring for the patient will have a consistent understanding of the type of injury. The resulting uniformity of terminology also helps with research, making it possible to compare data and do audits of injuries – which is essential for prevention.

  17. Edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia injury: heme oxygenase-1 and PI3K/Akt pathway may be involved.

    Science.gov (United States)

    Cao, Huifang; Feng, Ying; Ning, Yunye; Zhang, Zinan; Li, Weihao; Li, Qiang

    2015-01-01

    Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. As yet, no specific treatment is available for HALI. The present study aims to investigate the effects of edaravone on hyperoxia-induced oxidative injury and the underlying mechanism. We treated rats and human pulmonary alveolar epithelial cells with hyperoxia and different concentration of edaravone, then examined the effects of edaravone on cell viability, cell injury and two oxidative products. The roles of heme oxygenase-1 (HO-1) and PI3K/Akt pathway were explored using Western blot and corresponding inhibitors. The results showed that edaravone reduced lung biochemical alterations induced by hyperoxia and mortality of rats, dose-dependently alleviated cell mortality, cell injury, and peroxidation of cellular lipid and DNA oxidative damage. It upregulated cellular HO-1 expression and activity, which was reversed by PI3K/Akt pathway inhibition. The administration of zinc protoporphyrin-IX, a HO-1 inhibitor, and LY249002, a PI3K/Akt pathway inhibitor, abolished the protective effects of edaravone in cells. This study indicates that edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia-induced injury and the antioxidant effect may be related to upregulation of HO-1, which is regulated by PI3K/Akt pathway.

  18. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

    Directory of Open Access Journals (Sweden)

    Daniela Hoeber

    2016-01-01

    Full Text Available Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg at the onset of hyperoxia (24 hours, 80% oxygen in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

  19. Throwing Injuries of the Shoulder.

    Science.gov (United States)

    McCue, Frank C., III; and Others

    The majority of shoulder injuries occurring in throwing sports involve the soft tissue structures. Injuries often occur when the unit is overstretched to a point near its greatest length, involving the elastic tissues. The other injury mechanism involves the contractural unit of the muscle, which occurs near the midpoint of contractions, involving…

  20. Ipsilateral simultaneous fracture of the trochlea involving the lateral end clavicle and distal end radius: a rare combination and a unique mechanism of injury

    Directory of Open Access Journals (Sweden)

    Gupta RK

    2014-07-01

    Full Text Available 【Abstract】Isolated trochlea fracture in adults is a rare surgical entity as compared to its capitellar counterpart. It has been only mentioned sporadically in the literature as case reports. Fracture of the trochlea is accompanied by other elbow injuries like elbow dislocation, capitellum fracture, ulnar fracture and extraarticular condylar fracture. Here we report a unique case of isolated displaced trochlea fracture associated with fractures of the lateral end clavicle and the distal end radius. We propose a unique mechanism for this rare combination of injuries: typical triad of injury, i.e. fracture of the distal end radius with trochlea and fracture of the lateral end of the clavicle. Nonoperative treatment is recommended for undisplaced humeral trochlea fractures; but for displaced ones, anatomical reduction and internal fixation are essential to maintain the congruous trochleacoronoid articulation and hence to maintain the intrinsic stability of the elbow. Key words: Isolated trochlea fracture; Clavicle; Radius fractures

  1. Dietary α-lactalbumin induced fatty liver by enhancing nuclear liver X receptor αβ/sterol regulatory element-binding protein-1c/PPARγ expression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinase α phosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice.

    Science.gov (United States)

    López-Oliva, María Elvira; Garcimartin, Alba; Muñoz-Martínez, Emilia

    2017-12-01

    The effect and the role played by dietary α-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously that α-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possible α-LAC-induced hepatic steatosis. We examine the ability of dietary α-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment. Male Balb/c mice (n 6) were fed with diets containing either chow or 14 % α-LAC for 4 weeks. The α-LAC-fed mice developed abdominal adiposity and IR. Moderate liver steatosis with increased TAG and NEFA contents was correlated with atherogenic dyslipidaemia. There was increased nuclear expression of liver X receptor αβ (LXRαβ), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγ transcription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepatic de novo lipogenesis. The opposite was found for the nuclear receptor PPARα and the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acid β-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinase α (AMPKα) (inactivation) and p-Ser79-ACC1 (activation) and with a more oxidative liver environment increasing lipid peroxidation and protein oxidation and reducing GSH:GSSG ratio in the α-LAC-fed mice. In conclusion, 4 weeks of 14 % α-LAC feeding induced liver steatosis associated with atherogenic dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRαβ/SREBP-1c/PPARγ expression and diminishing PPARα/CPT-1 expression and AMPKα phosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.

  2. Xanthohumol ameliorates lipopolysaccharide (LPS-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis

    Directory of Open Access Journals (Sweden)

    Hongming Lv

    2017-08-01

    Full Text Available Abundant natural flavonoids can induce nuclear factor-erythroid 2 related factor 2 (Nrf2 and/or AMP-activated protein kinase (AMPK activation, which play crucial roles in the amelioration of various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI. Xanthohumol (Xn, a principal prenylflavonoid, possesses anti-inflammation and anti-oxidant activities. However, whether Xn could protect from LPS-induced ALI through inducing AMPK/Nrf2 activation and its downstream signals, are still poorly elucidated. Accordingly, we focused on exploring the protective effect of Xn in the context of ALI and the involvement of underlying molecular mechanisms. Our findings indicated that Xn effectively alleviated lung injury by reduction of lung W/D ratio and protein levels, neutrophil infiltration, MDA and MPO formation, and SOD and GSH depletion. Meanwhile, Xn significantly lessened histopathological changes, reactive oxygen species (ROS generation, several cytokines secretion, and iNOS and HMGB1 expression, and inhibited Txnip/NLRP3 inflammasome and NF-κB signaling pathway activation. Additionally, Xn evidently decreased t-BHP-stimulated cell apoptosis, ROS generation and GSH depletion but increased various anti-oxidative enzymes expression regulated by Keap1-Nrf2/ARE activation, which may be associated with AMPK and GSK3β phosphorylation. However, Xn-mediated inflammatory cytokines and ROS production, histopathological changes, Txnip/NLRP3 inflammasome and NF-κB signaling pathway in WT mice were remarkably abrogated in Nrf2-/- mice. Our experimental results firstly provided a support that Xn effectively protected LPS-induced ALI against oxidative stress and inflammation damage which are largely dependent upon upregulation of the Nrf2 pathway via activation of AMPK/GSK3β, thereby suppressing LPS-activated Txnip/NLRP3 inflammasome and NF-κB signaling pathway. Keywords: Xanthohumol, Acute lung injury, Oxidative stress

  3. Dehydroeburicoic Acid from Antrodia camphorata Prevents the Diabetic and Dyslipidemic State via Modulation of Glucose Transporter 4, Peroxisome Proliferator-Activated Receptor α Expression and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice

    Directory of Open Access Journals (Sweden)

    Yueh-Hsiung Kuo

    2016-06-01

    Full Text Available This study investigated the potential effects of dehydroeburicoic acid (TT, a triterpenoid compound from Antrodia camphorata, in vitro and examined the effects and mechanisms of TT on glucose and lipid homeostasis in high-fat-diet (HFD-fed mice. The in vitro study examined the effects of a MeOH crude extract (CruE of A. camphorata and Antcin K (AnK; the main constituent of fruiting body of this mushroom on membrane glucose transporter 4 (GLUT4 and phospho-Akt in C2C12 myoblasts cells. The in vitro study demonstrated that treatment with CruE, AnK and TT increased the membrane levels of glucose transporter 4 (GLUT4 and phospho-Akt at different concentrations. The animal experiments were performed for 12 weeks. Diabetic mice were randomly divided into six groups after 8 weeks of HFD-induction and treated with daily oral gavage doses of TT (at three dose levels, fenofibrate (Feno (at 0.25 g/kg body weight, metformin (Metf (at 0.3 g/kg body weight or vehicle for another 4 weeks while on an HFD diet. HFD-fed mice exhibited increased blood glucose levels. TT treatment dramatically lowered blood glucose levels by 34.2%~43.4%, which was comparable to the antidiabetic agent-Metf (36.5%. TT-treated mice reduced the HFD-induced hyperglycemia, hypertriglyceridemia, hyperinsulinemia, hyperleptinemia, and hypercholesterolemia. Membrane levels of GLUT4 were significantly higher in CruE-treated groups in vitro. Skeletal muscle membrane levels of GLUT4 were significantly higher in TT-treated mice. These groups of mice also displayed lower mRNA levels of glucose-6-phosphatase (G6 Pase, an inhibitor of hepatic glucose production. The combination of these agents produced a net hypoglycemic effect in TT-treated mice. TT treatment enhanced the expressions of hepatic and skeletal muscle AMP-activated protein kinase (AMPK phosphorylation in mice. TT-treated mice exhibited enhanced expression of hepatic fatty acid oxidation enzymes, including peroxisome proliferator

  4. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jennifer M A Tullet

    2014-02-01

    Full Text Available The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK, which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be

  5. Malonyl-CoA decarboxylase (MCD) is differentially regulated in subcellular compartments by 5'AMP-activated protein kinase (AMPK). Studies using H9c2 cells overexpressing MCD and AMPK by adenoviral gene transfer technique.

    Science.gov (United States)

    Sambandam, Nandakumar; Steinmetz, Michael; Chu, Angel; Altarejos, Judith Y; Dyck, Jason R B; Lopaschuk, Gary D

    2004-07-01

    Malonyl-CoA, a potent inhibitor of carnitine pamitoyl transferase-I (CPT-I), plays a pivotal role in fuel selection in cardiac muscle. Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, removes a potent allosteric inhibition on CPT-I and thereby increases fatty acid oxidation in the heart. Although MCD has several Ser/Thr phosphorylation sites, whether it is regulated by AMP-activated protein kinase (AMPK) has been controversial. We therefore overexpressed MCD (Ad.MCD) and constitutively active AMPK (Ad.CA-AMPK) in H9c2 cells, using an adenoviral gene delivery approach in order to examine if MCD is regulated by AMPK. Cells infected with Ad.CA-AMPK demonstrated a fourfold increase in AMPK activity as compared with control cells expressing green fluorescent protein (Ad.GFP). MCD activity increased 40- to 50-fold in Ad.MCD + Ad.GFP cells when compared with Ad.GFP control. Co-expressing AMPK with MCD further augmented MCD expression and activity in Ad.MCD + Ad.CA-AMPK cells compared with the Ad.MCD + Ad.GFP control. Subcellular fractionation further revealed that 54.7 kDa isoform of MCD expression was significantly higher in cytosolic fractions of Ad.MCD + Ad.CA-AMPK cells than of the Ad.MCD +Ad.GFP control. However, the MCD activities in cytosolic fractions were not different between the two groups. Interestingly, in the mitochondrial fractions, MCD activity significantly increased in Ad.MCD + Ad.CA-AMPK cells when compared with Ad.MCD + Ad.GFP cells. Using phosphoserine and phosphothreonine antibodies, no phosphorylation of MCD by AMPK was observed. The increase in MCD activity in mitochondria-rich fractions of Ad.MCD + Ad.CA-AMPK cells was accompanied by an increase in the level of the 50.7 kDa isoform of MCD protein in the mitochondria. This differential regulation of MCD expression and activity in the mitochondria by AMPK may potentially regulate malonyl-CoA levels at sites nearby CPT-I on the mitochondria.

  6. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    Science.gov (United States)

    Tullet, Jennifer M A; Araiz, Caroline; Sanders, Matthew J; Au, Catherine; Benedetto, Alexandre; Papatheodorou, Irene; Clark, Emily; Schmeisser, Kathrin; Jones, Daniel; Schuster, Eugene F; Thornton, Janet M; Gems, David

    2014-02-01

    The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be evolutionarily conserved.

  7. M3 receptor is involved in the effect of penehyclidine hydrochloride reduced endothelial injury in LPS-stimulated human pulmonary microvascular endothelial cell.

    Science.gov (United States)

    Yuan, Qinghong; Xiao, Fei; Liu, Qiangsheng; Zheng, Fei; Shen, Shiwen; He, Qianwen; Chen, Kai; Wang, Yanlin; Zhang, Zongze; Zhan, Jia

    2018-02-01

    LPS has been recently shown to induce muscarinic acetylcholine 3 receptor (M 3 receptor) expression and penehyclidine hydrochloride (PHC) is an anticholinergic drug which could block the expression of M 3 receptor. PHC has been demonstrated to perform protective effect on cell injury. This study is to investigate whether the effect of PHC on microvascular endothelial injury is related to its inhibition of M 3 receptor or not. HPMVECs were treated with specific M 3 receptor shRNA or PBS, and randomly divided into LPS group (A group), LPS+PHC group (B group), LPS + M 3 shRNA group (C group) and LPS + PHC + M 3 shRNA group (D group). Cells were collected at 60 min after LPS treatment to measure levels of LDH, endothelial permeability, TNF-α and IL-6 levels, NF-κB p65 activation, I-κB protein expression, p38MAPK, and ERK1/2 activations as well as M 3 mRNA expression. PHC could decrease LDH levels, cell permeability, TNF-α and IL-6 levels, p38 MAPK, ERK1/2, NF-κB p65 activations and M 3 mRNA expressions compared with LPS group. When M 3 receptor was silence, the changes of these indices were much more obvious. These findings suggest that M 3 receptor plays an important role in LPS-induced pulmonary microvascular endothelial injury, which is regulated through NF-κB p65 and MAPK activation. And knockout of M 3 receptor could attenuate LPS-induced pulmonary microvascular endothelial injury. Regulative effects of PHC on pulmonary microvascular permeability and NF-κB p65 as well as MAPK activations are including but not limited to inhibition of M 3 receptor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB.

    Science.gov (United States)

    Sun, Qi; Chen, Ling; Gao, Mengyu; Jiang, Wenwen; Shao, Fangxian; Li, Jingjing; Wang, Jun; Kou, Junping; Yu, Boyang

    2012-01-01

    Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. 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

  10. 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

  11. Mountain Biking Injuries.

    Science.gov (United States)

    Ansari, Majid; Nourian, Ruhollah; Khodaee, Morteza

    With the increasing popularity of mountain biking, also known as off-road cycling, and the riders pushing the sport into extremes, there has been a corresponding increase in injury. Almost two thirds of acute injuries involve the upper extremities, and a similar proportion of overuse injuries affect the lower extremities. Mountain biking appears to be a high-risk sport for severe spine injuries. New trends of injury patterns are observed with popularity of mountain bike trail parks and freeride cycling. Using protective gear, improving technical proficiency, and physical fitness may somewhat decrease the risk of injuries. Simple modifications in bicycle-rider interface areas and with the bicycle (bike fit) also may decrease some overuse injuries. Bike fit provides the clinician with postural correction during the sport. In this review, we also discuss the importance of race-day management strategies and monitoring the injury trends.

  12. [C1q/tumor necrosis factor related protein 6 (CTRP6) is involved in gentamicin-induced acute kidney injury in rats].

    Science.gov (United States)

    Li, Rong; Yang, Xiaoxia; Yu, Yan; Zhou, Meilan; Tian, Xiujuan; Feng, Shidong; Wang, Hanmin

    2016-11-01

    Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6 (CTRP6) in gentamicin-induced acute kidney injury in rats. Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups. The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg/(kg.d) for consecutive 2 days to induce acute renal injury. Two days before gentamicin injection, the rats in the 3 experimental groups were given pAd-CTRP6 at the doses of 0.5, 5 and 50 mg/kg, respectively. The serum levels of blood urea nitrogen (BUN) and creatinine (Cr) were respectively assayed with picric acid colorimetry and ultraviolet spectrophotometry; ELISA was used to detect serum CTRP6 content and the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the kidney homogenate; Western blotting was performed to detect the expressions of CTRP6, caspase-1 and pyrin domain containing 3 (NLRP3) proteins in the renal tissues of rats. Results Compared with control group, serum BUN and Cr contents increased in the model rats; the secretion of inflammatory factors IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also enhanced in the model group. Compared with the model group, serum BUN and Cr contents decreased in the experimental groups; the secretion of IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also attenuated in the experimental groups. Moreover, with the increase of the injection dosage of pAd-CTRP6, the suppressive effect was gradually strengthened. Conclusion CTRP6 can attenuate gentamicin-induced acute renal injury in rats in a dose-dependent manner.

  13. [Regression trends of neurologic damage in the surgical emergency management of patients with injuries of the cervical vertebrae with spinal cord involvement].

    Science.gov (United States)

    Kortmann, H R; Wolter, D; Meinecke, F W; Eggers, C

    1986-11-01

    Sixty-five patients with cervical spine injuries and varied neurological deficits were treated operatively. Evaluation revealed an improvement in neurological findings dependent upon the promptness of anatomical reduction in patients with incomplete lesions. The more frequent neurological improvement seen with open reduction and internal fixation as compared with closed reduction was not statistically significant but was felt to justify the additional resources required for internal fixation. In complete lesions, there was no evidence that the time of anatomical reduction was related to improvement in neurological findings.

  14. Dismounted Complex Blast Injury.

    Science.gov (United States)

    Andersen, Romney C; Fleming, Mark; Forsberg, Jonathan A; Gordon, Wade T; Nanos, George P; Charlton, Michael T; Ficke, James R

    2012-01-01

    The severe Dismounted Complex Blast Injury (DCBI) is characterized by high-energy injuries to the bilateral lower extremities (usually proximal transfemoral amputations) and/or upper extremity (usually involving the non-dominant side), in addition to open pelvic injuries, genitourinary, and abdominal trauma. Initial resuscitation and multidisciplinary surgical management appear to be the keys to survival. Definitive treatment follows general principals of open wound management and includes decontamination through aggressive and frequent debridement, hemorrhage control, viable tissue preservation, and appropriate timing of wound closure. These devastating injuries are associated with paradoxically favorable survival rates, but associated injuries and higher amputation levels lead to more difficult reconstructive challenges.

  15. Protection by the gross saponins of Tribulus terrestris against cerebral ischemic injury in rats involves the NF-κB pathway

    Directory of Open Access Journals (Sweden)

    En-ping Jiang

    2011-06-01

    Full Text Available The aim of this study was to investigate whether the gross saponins of Tribulus terrestris (GSTT, a traditional Chinese herbal medicine, have neuroprotective effects on rats subjected to middle cerebral artery occlusion (MCAO, through nuclear factor-κB (NF-κB pathway and inflammatory mediators. Cerebral ischemia was produced by MCAO in either untreated (control or GSTT-pretreated rats, and the animals were examined for infarct volume, cerebral edema, neuro-behavioral abnormality and pathological changes. Meanwhile, the expression of NF-κB protein in brain tissue was analyzed on Western blots and the serum levels of TNF-α and IL-1 were determined by ELISA. The experimental results demonstrated that, compared with the control MCAO group, GSTT-pretreated MCAO group had significantly reduced infarct volume, brain edema and neuro-behavioral abnormality, and lesser degree of pathologic changes in the brain, as well as had lower levels of serum TNF-α and IL-1β, and higher levels of brain NF-κB (P<0.05. Furthermore, treatment with an NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC abolished the protective effects of GSTT against MCAO-induced cerebral ischemic injury. These results indicated that GSTT's ability to protect against cerebral ischemic injury was mediated through the NF-κB signaling pathway, and that GSTT may act through inhibition of the production of inflammatory mediators.

  16. GSK3β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury

    Science.gov (United States)

    Park, Dae Won; Jiang, Shaoning; Liu, Yanping; Siegal, Gene P.; Inoki, Ken; Abraham, Edward

    2014-01-01

    Although AMP-activated protein kinase (AMPK) is involved in regulating carbohydrate and lipid metabolism, activated AMPK also plays an anti-inflammatory role in many cell populations. However, despite the ability of AMPK activation to diminish the severity of inflammatory responses, previous studies have found that AMPK activity is diminished in LPS-treated neutrophils and also in lungs of mice with LPS-induced acute lung injury (ALI). Since GSK3β participates in regulating AMPK activity, we examined potential roles for GSK3β in modulating LPS-induced activation of neutrophils and macrophages and in influencing severity of ALI. We found that GSK3β-dependent phosphorylation of T479-AMPK was associated with pT172 dephosphorylation and inactivation of AMPK following TLR4 engagement. GSK3β inhibitors BIO (6-bromoindirubin-3′-oxime), SB216763, or siRNA knockdown of GSK3β, but not the PI3K/AKT inhibitor LY294002, prevented Thr172-AMPK dephosphorylation. Exposure to LPS resulted in rapid binding between IKKβ and AMPKα, and phosphorylation of S485-AMPK by IKKβ. These results suggest that IKKβ-dependent phosphorylation of S485-AMPK was an essential step in subsequent phosphorylation and inactivation AMPK by GSK3β. Inhibition of GSK3β activity delayed IκBα degradation and diminished expression of the proinflammatory TNF-α in LPS-stimulated neutrophils and macrophages. In vivo, inhibition of GSK3β decreased the severity of LPS-induced lung injury as assessed by development of pulmonary edema, production of TNF-α and MIP-2, and release of the alarmins HMGB1 and histone 3 in the lungs. These results show that inhibition of AMPK by GSK3β plays an important contributory role in enhancing LPS-induced inflammatory responses, including worsening the severity of ALI. PMID:25239914

  17. Sequenced response of extracellular matrix deadhesion and fibrotic regulators after muscle damage is involved in protection against future injury in human skeletal muscle

    DEFF Research Database (Denmark)

    Mackey, Abigail; Brandstetter, Simon; Schjerling, Peter

    2011-01-01

    ) 30 d later, or 30 d after a single stimulation bout (RBc). A muscle biopsy was collected from the control leg for comparison with the stimulated leg. Satellite cell content, tenascin C, and muscle regeneration were assessed by immunohistochemistry; real-time PCR was used to measure mRNA levels...... of collagens, laminins, heat-shock proteins (HSPs), inflammation, and related growth factors. The large responses of HSPs, CCL2, and tenascin C detected 48 h after a single bout were attenuated in the RB trial, indicative of protection against injury. Satellite cell content and 12 target genes, including IGF-1......, were elevated 30 d after a single bout. Among those displaying the greatest difference vs. control muscle, ECM laminin-ß1 and collagen types I and III were elevated ~6- to 9-fold (P...

  18. Protective effects of n-6 fatty acids-enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor

    Science.gov (United States)

    Gobbetti, T; Ducheix, S; le Faouder, P; Perez, T; Riols, F; Boue, J; Bertrand-Michel, J; Dubourdeau, M; Guillou, H; Perretti, M; Vergnolle, N; Cenac, N

    2015-01-01

    Background and Purpose Long-term intake of dietary fatty acids is known to predispose to chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury is unknown. The aim of this study was to determine the consequences of a diet rich in n-3 or n-6 polyunsaturated fatty acids (PUFA) on intestinal I/R-induced damage. Experimental Approach Mice were fed three different isocaloric diets: a balanced diet used as a control and two different PUFA-enriched diets, providing either high levels of n-3 or of n-6 PUFA. Intestinal injury was evaluated after intestinal I/R. PUFA metabolites were quantitated in intestinal tissues by LC-MS/MS. Key Results In control diet-fed mice, intestinal I/R caused inflammation and increased COX and lipoxygenase-derived metabolites compared with sham-operated animals. Lipoxin A4 (LxA4) was significantly and selectively increased after ischaemia. Animals fed a high n-3 diet did not display a different inflammatory profile following intestinal I/R compared with control diet-fed animals. In contrast, intestinal inflammation was decreased in the I/R group fed with high n-6 diet and level of LxA4 was increased post-ischaemia compared with control diet-fed mice. Blockade of the LxA4 receptor (Fpr2), prevented the anti-inflammatory effects associated with the n-6 rich diet. Conclusions and Implications This study indicates that high levels of dietary n-6, but not n-3, PUFAs provides significant protection against intestinal I/R-induced damage and demonstrates that the endogenous production of LxA4 can be influenced by diet. PMID:25296998

  19. Protective effects of n-6 fatty acids-enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor.

    Science.gov (United States)

    Gobbetti, T; Ducheix, S; le Faouder, P; Perez, T; Riols, F; Boue, J; Bertrand-Michel, J; Dubourdeau, M; Guillou, H; Perretti, M; Vergnolle, N; Cenac, N

    2015-02-01

    Long-term intake of dietary fatty acids is known to predispose to chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury is unknown. The aim of this study was to determine the consequences of a diet rich in n-3 or n-6 polyunsaturated fatty acids (PUFA) on intestinal I/R-induced damage. Mice were fed three different isocaloric diets: a balanced diet used as a control and two different PUFA-enriched diets, providing either high levels of n-3 or of n-6 PUFA. Intestinal injury was evaluated after intestinal I/R. PUFA metabolites were quantitated in intestinal tissues by LC-MS/MS. In control diet-fed mice, intestinal I/R caused inflammation and increased COX and lipoxygenase-derived metabolites compared with sham-operated animals. Lipoxin A4 (LxA4 ) was significantly and selectively increased after ischaemia. Animals fed a high n-3 diet did not display a different inflammatory profile following intestinal I/R compared with control diet-fed animals. In contrast, intestinal inflammation was decreased in the I/R group fed with high n-6 diet and level of LxA4 was increased post-ischaemia compared with control diet-fed mice. Blockade of the LxA4 receptor (Fpr2), prevented the anti-inflammatory effects associated with the n-6 rich diet. This study indicates that high levels of dietary n-6, but not n-3, PUFAs provides significant protection against intestinal I/R-induced damage and demonstrates that the endogenous production of LxA4 can be influenced by diet. © 2014 The British Pharmacological Society.

  20. Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury

    Science.gov (United States)

    Sharma, Ashish Kumar; Munajjam, Arshee; Vaishnav, Bhawna; Sharma, Richa; Sharma, Ashok; Kishore, Kunal; Sharma, Akash; Sharma, Divya; Kumari, Rita; Tiwari, Ashish; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh; Srinivasan, Barthu Parthi; Agarwal, Shyam Sunder

    2012-01-01

    The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide. PMID:23554727

  1. Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Kouichi Isami

    Full Text Available Recent evidence suggests that transient receptor potential melastatin 2 (TRPM2 expressed in immune cells plays an important role in immune and inflammatory responses. We recently reported that TRPM2 expressed in macrophages and spinal microglia contributes to the pathogenesis of inflammatory and neuropathic pain aggravating peripheral and central pronociceptive inflammatory responses in mice. To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages into the injured nerve and spinal cord by using bone marrow (BM chimeric mice by crossing wildtype (WT and TRPM2-knockout (TRPM2-KO mice. Four types of BM chimeric mice were prepared, in which irradiated WT or TRPM2-KO recipient mice were transplanted with either WT-or TRPM2-KO donor mouse-derived green fluorescence protein-positive (GFP(+ BM cells (TRPM2(BM+/Rec+, TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2(BM+/Rec+ mice was attenuated in TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. The numbers of GFP(+ BM-derived cells and Iba1/GFP double-positive macrophages in the injured sciatic nerve did not differ among chimeric mice 14 days after the nerve injury. In the spinal cord, the number of GFP(+ BM-derived cells, particularly GFP/Iba1 double-positive macrophages, was significantly decreased in the three TRPM2-KO chimeric mouse groups compared with TRPM2(BM+/Rec+ mice. However, the numbers of GFP(-/Iba1(+ resident microglia did not differ among chimeric mice. These results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than the infiltration of peripheral immune cells into the injured nerves and activation of spinal

  2. Ethanol extract of Portulaca Oleracea L. reduced the carbon tetrachloride induced liver injury in mice involving enhancement of NF-κB activity

    Science.gov (United States)

    Shi, Hongguang; Liu, Xuefeng; Tang, Gusheng; Liu, Haiyan; Zhang, Yinghui; Zhang, Bo; Zhao, Xuezhi; Wang, Wanyin

    2014-01-01

    Acute hepatic injury causes high morbidity and mortality world-wide. Management of severe acute hepatic failure continues to be one of the most challenging problems in clinical medicine. In present study, carbon tetrachloride (CCl4) was used to induce acute liver damage in mice and the protective effects of ethanol extract of Portulaca Oleracea L. (PO) were examined. The aminotransferase activities were biochemical estimated and the liver damage was tested by morphological histological analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The role of PO on the activity of NF-κB was determined by luciferase reporter gene assay and immunohistochemistry. The level of p-p65 was tested by western blot. Our results showed that PO administration on mice would decrease the serum aminotransferase level and reduced the liver histological damage. We also found that nuclear translocation of p65 was enhanced in liver tissues of mice treated with PO compared with control animals. In addition, in cultured hepatic cells, PO increased the NF-κB luciferase reporter gene activity and upregulated the level of phosphorylation of p65, but had no effects on mice liver SOD activity and MDA level. Collectively, PO attenuated CCl4 induced mice liver damage by enhancement of NF-κB activity. PMID:25628785

  3. Kinases Involved in Both Autophagy and Mitosis.

    Science.gov (United States)

    Li, Zhiyuan; Zhang, Xin

    2017-08-31

    Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases), Aurora kinases, PLK-1 (polo-like kinase 1), BUB1 (budding uninhibited by benzimidazoles 1), MAPKs (mitogen-activated protein kinases), mTORC1 (mechanistic target of rapamycin complex 1), AMPK (AMP-activated protein kinase), PI3K (phosphoinositide-3 kinase) and protein kinase B (AKT). By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

  4. Kinases Involved in Both Autophagy and Mitosis

    Directory of Open Access Journals (Sweden)

    Zhiyuan Li

    2017-08-01

    Full Text Available Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases, Aurora kinases, PLK-1 (polo-like kinase 1, BUB1 (budding uninhibited by benzimidazoles 1, MAPKs (mitogen-activated protein kinases, mTORC1 (mechanistic target of rapamycin complex 1, AMPK (AMP-activated protein kinase, PI3K (phosphoinositide-3 kinase and protein kinase B (AKT. By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

  5. Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chien-Sheng [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Division of Thoracic Surgery, Department of Surgery, Taipei-Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Kawamura, Tomohiro; Peng, Ximei [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Tochigi, Naobumi [Department of Pathology, University of Pittsburgh Medical Center, PA (United States); Shigemura, Norihisa [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Billiar, Timothy R. [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Nakao, Atsunori, E-mail: anakao@imap.pitt.edu [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Toyoda, Yoshiya [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

    2011-05-06

    Highlights: {yields} Hydrogen is a regulatory molecule with antiinflammatory and antiapoptotic protective effects. {yields} There is very limited information on the pathways regulated in vivo by the hydrogen. {yields} Antiapoptotic abilities of hydrogen were explained by upregulation of the antiapoptotic gene. {yields} NF{kappa}B activation during hydrogen treatment was correlated with elevated antiapoptotic protein. {yields} NF{kappa}B activation associated with increase Bcl-2 may contribute to cytoprotection of hydrogen. -- Abstract: We recently demonstrated the inhalation of hydrogen gas, a novel medical therapeutic gas, ameliorates ventilator-induced lung injury (VILI); however, the molecular mechanisms by which hydrogen ameliorates VILI remain unclear. Therefore, we investigated whether inhaled hydrogen gas modulates the nuclear factor-kappa B (NF{kappa}B) signaling pathway. VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg or 10 ml/kg without positive end-expiratory pressure). The ventilator delivered either 2% nitrogen or 2% hydrogen in balanced air. NF{kappa}B activation, as indicated by NF{kappa}B DNA binding, was detected by electrophoretic mobility shift assays and enzyme-linked immunosorbent assay. Hydrogen gas inhalation increased NF{kappa}B DNA binding after 1 h of ventilation and decreased NF{kappa}B DNA binding after 2 h of ventilation, as compared with controls. The early activation of NF{kappa}B during hydrogen treatment was correlated with elevated levels of the antiapoptotic protein Bcl-2 and decreased levels of Bax. Hydrogen inhalation increased oxygen tension, decreased lung edema, and decreased the expression of proinflammatory mediators. Chemical inhibition of early NF{kappa}B activation using SN50 reversed these protective effects. NF{kappa}B activation and an associated increase in the expression of Bcl-2 may contribute, in part, to the

  6. Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation

    International Nuclear Information System (INIS)

    Huang, Chien-Sheng; Kawamura, Tomohiro; Peng, Ximei; Tochigi, Naobumi; Shigemura, Norihisa; Billiar, Timothy R.; Nakao, Atsunori; Toyoda, Yoshiya

    2011-01-01

    Highlights: → Hydrogen is a regulatory molecule with antiinflammatory and antiapoptotic protective effects. → There is very limited information on the pathways regulated in vivo by the hydrogen. → Antiapoptotic abilities of hydrogen were explained by upregulation of the antiapoptotic gene. → NFκB activation during hydrogen treatment was correlated with elevated antiapoptotic protein. → NFκB activation associated with increase Bcl-2 may contribute to cytoprotection of hydrogen. -- Abstract: We recently demonstrated the inhalation of hydrogen gas, a novel medical therapeutic gas, ameliorates ventilator-induced lung injury (VILI); however, the molecular mechanisms by which hydrogen ameliorates VILI remain unclear. Therefore, we investigated whether inhaled hydrogen gas modulates the nuclear factor-kappa B (NFκB) signaling pathway. VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg or 10 ml/kg without positive end-expiratory pressure). The ventilator delivered either 2% nitrogen or 2% hydrogen in balanced air. NFκB activation, as indicated by NFκB DNA binding, was detected by electrophoretic mobility shift assays and enzyme-linked immunosorbent assay. Hydrogen gas inhalation increased NFκB DNA binding after 1 h of ventilation and decreased NFκB DNA binding after 2 h of ventilation, as compared with controls. The early activation of NFκB during hydrogen treatment was correlated with elevated levels of the antiapoptotic protein Bcl-2 and decreased levels of Bax. Hydrogen inhalation increased oxygen tension, decreased lung edema, and decreased the expression of proinflammatory mediators. Chemical inhibition of early NFκB activation using SN50 reversed these protective effects. NFκB activation and an associated increase in the expression of Bcl-2 may contribute, in part, to the cytoprotective effects of hydrogen against apoptotic and inflammatory signaling pathway

  7. Alternative Approach to Traumatic Stensen’s Duct Injuries Accompanied by Glandular Involvement: Botulinum Toxin Injection to the Gland in Conjunction with Microsurgical Repair of the Duct in an Acute Setting

    Directory of Open Access Journals (Sweden)

    Mert Çalış

    2017-12-01

    Full Text Available Objective: The aim of this study was to evaluate the long-term results of a simultaneous application of botulinum toxin to the parotid gland in conjunction with the microsurgical repair of the duct in an acute setting and to encourage using botulinum toxin as a first-line option to prevent future complications associated with glandular involvement. Material and Methods: Three patients who were referred to the Plastic Surgery Clinic by the emergency room of the Hacettepe University Hospital after maxillofacial trauma are reviewed in this study. Exploration of the facial nerve and Stensen’s duct was planned for all patients within the first 72 hours after their injuries. After intraoral catheterization of the Stensen’s duct through the papilla using an epidural catheter, microsurgical end-to-end anastomosis was performed. Concurrently, 100 units of botulinum toxin A was injected at standardized eight points to the parotid gland. Results: Postoperative magnetic resonance (MR sialography revealed patency in all patients at the end of postoperative first year. The mean postoperative parotid volume of the injured and non-injured sides were 19.82±10.55 cm3 and 17.79±10.98 cm3, respectively, and the results were found to be comparable. Fibrillation potentials in the postoperative electromyography recordings and clinical examination demonstrated nerve regeneration. Conclusion: Botulinum toxin A appears to be effective in treating duct injuries accompanied by glandular involvement in an acute setting, as well as in preventing long-term complications.

  8. Alcohol and drug involvement in motorcycle driver injuries in the city of Sao Paulo, Brazil: Analysis of crash culpability and other associated factors.

    Science.gov (United States)

    de Carvalho, Heraclito Barbosa; Andreuccetti, Gabriel; Rezende, Marcelo Rosa; Bernini, Celso; Silva, Jorge Santos; Leyton, Vilma; D'Andréa Greve, Julia Maria

    2016-05-01

    Earlier studies have already identified that a greater proportion of injured drivers are under the effects of illicit drugs than alcohol in Brazil, but the crash risk attributable to each substance is still unknown. Injured motorcycle drivers who were involved in traffic accidents in the West Zone of the city of Sao Paulo were recruited for a cross-sectional study based on crash culpability analysis. Alcohol and drug positivity among drivers was evaluated according to their responsibility for the crash. Culpability ratios were generated based on the proportion of drivers who were deemed culpable in relation to those considered not culpable according to the use of drugs and alcohol. Of the 273 drivers recruited, 10.6% tested positive for alcohol. Among those who were also tested for drugs (n=232), 20.3% had consumed either alcohol and/or other drugs, 15.5% of whom were positive only for drugs other than alcohol, specifically cannabis and cocaine. Drivers who tested positive for alcohol were significantly less likely to possess a valid driver's license and to report driving professionally, whereas those who had consumed only drugs were more likely to drive professionally. The culpability ratio estimated for alcohol-positive drivers was three times higher than that for alcohol-free drivers, showing a superior ratio than drivers who had consumed only drugs other than alcohol, who presented a 1.7 times higher culpability ratio than drug-free drivers. Substance use was overrepresented among culpable motorcycle drivers, with alcohol showing a greater contribution to crash culpability than other drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Sports Injuries

    Science.gov (United States)

    ... sometimes you can injure yourself when you play sports or exercise. Accidents, poor training practices, or improper ... can also lead to injuries. The most common sports injuries are Sprains and strains Knee injuries Swollen ...

  10. Golf Injuries

    Science.gov (United States)

    ... Our Newsletter Donate Blog Skip breadcrumb navigation Preventing Golf Injuries Golf looks like an easy game to ... WHAT TYPES OF INJURIES ARE MOST COMMON IN GOLF? Acute injuries are usually the result of a ...

  11. Injuries in Irish dance.

    Science.gov (United States)

    Stein, Cynthia J; Tyson, Kesley D; Johnson, Victor M; Popoli, David M; d'Hemecourt, Pierre A; Micheli, Lyle J

    2013-12-01

    Irish dance is growing in popularity and competitiveness; however, very little research has focused specifically on this genre of dance. The purpose of this study was to analyze the types of dance injuries incurred by Irish dancers. A chart review was performed to identify all injuries associated with Irish dance seen in the sports medicine or orthopaedic clinics at the investigators' hospital over an 11-year period. "Injury" was defined as any dance-related pain or disorder that led to evaluation in the clinics. Survey data were also collected from study participants. Ultimately, 255 patients from over 30 different schools of dance were seen with injuries directly related (726 clinic visits) or partially related (199 visits) to Irish dance. Participants ranged in age from 4 to 47, with 95% (243/255) under the age of 19. These 255 patients received 437 diagnoses. Almost 80% of the injuries (348/437) were attributable to overuse, and 20.4% were acute and traumatic injuries (89/437). Ninety-five percent (95.9%) of injuries involved the hip or lower extremity. The most common sites were the foot (33.2%), ankle (22.7%), knee (19.7%), and hip (14.4%). Typical diagnoses were tendon injury (13.3%), apophysitis (11.4%), patellofemoral pain and instability (10.8%), stress injury (10.1%), and muscle injury (7.8%). The majority of traumatic injuries were seen in clinic within 3 weeks, but less than a quarter of overuse injuries were seen that quickly. The most common treatment, prescribed to 84.3% of patients, was physical therapy and home exercises, and the majority of dancers (64.3%) were able to return to full dance activity after injury.

  12. ORBITAL INJURIES

    Directory of Open Access Journals (Sweden)

    Andrej Kansky

    2002-12-01

    Full Text Available Background. Orbit is involved in 40% of all facial fractures. There is considerable variety in severity, ranging from simple nondisplaced to complex comminuted fractures. Complex comminuted fractures (up to 20% are responsible for the majority of complications and unfavorable results. Orbital fractures are classified as internal orbital fractures, zygomatico-orbital fractures, naso-orbito-ethmoidal fractures and combined fractures. The ophtalmic sequelae of midfacial fractures are usually edema and ecchymosis of the soft tissues, subconjuctival hemorrhage, diplopia, iritis, retinal edema, ptosis, enophthalmos, ocular muscle paresis, mechanical restriction of ocular movement and nasolacrimal disturbances. More severe injuries such as optic nerve trauma and retinal detachments have also been reported. Within the wide range of orbital fractures small group of complex fractures causes most of the sequelae. Therefore identification of severe injuries and adequate treatment is of major importance. The introduction of craniofacial techniques made possible a wide exposure even of large orbital wall defects and their reconstruction by bone grafts. In spite of significant progress, repair of complex orbital wall defects remains a problem even for the experienced surgeons.Results. In 1999 121 facial injuries were treated at our department (Clinical Centre Ljubljana Dept. Of Maxillofacial and Oral Surgery. Orbit was involved in 65% of cases. Isolated inner orbital fractures presented 4% of all fractures. 17 (14% complex cases were treated, 5 of them being NOE, 5 orbital (frame and inner walls, 3 zygomatico-orbital, 2 FNO and 2 maxillo-orbital fractures.Conclusions. Final result of the surgical treatment depends on severity of maxillofacial trauma. Complex comminuted fractures are responsable for most of the unfavorable results and ocular function is often permanently damaged (up to 75% in these fractures.

  13. Nasal avulsion injuries.

    Science.gov (United States)

    Denneny, J C

    1987-11-01

    The nose is the most frequently traumatized portion of the human face. High-speed motor vehicle accidents and interpersonal violence commonly produce bony pyramid and septal damage and occasional minor soft-tissue damage. Major soft-tissue injuries are much less commonly encountered. Avulsion injuries of this type may involve skin only or the bony and cartilaginous framework as well. The severity of these injuries can range from total avulsion to minor skin loss and anywhere within the spectrum between. My experience is reviewed, management guidelines and options are detailed, and selected cases are presented.

  14. Injuries in Cricket.

    Science.gov (United States)

    Pardiwala, Dinshaw N; Rao, Nandan N; Varshney, Ankit V

    Cricket is a popular global sport that requires a combination of physical fitness, skill, and strategy. Although a noncontact sport, overuse and impact injuries are common since players engage in a wide range of physical activities, including running, throwing, batting, bowling, catching, and diving. Significant or match time-loss injuries are defined as those that either prevent a player from being fully available for selection in a major match, or during a major match, cause a player to be unable to bat, bowl, or keep wicket when required by either the rules or the team's captain. This review describes the various region-wise injuries sustained in cricket along with their epidemiology, biomechanics, treatment, and prevention. Data were collected from peer-reviewed articles (obtained via PubMed search) published through November 2016 that involved the medical, biomechanical, and epidemiological aspects of cricket injuries. Clinical review. Level 4. Cricket was one of the first sports to publish recommended methods for injury surveillance in 2005 from England, South Africa, Australia, the West Indies, and India. While the incidence of injuries is about the same, the prevalence of injuries has increased due to game format changes, increasing number of matches played, and decreased rest between matches. Bowling (41.3%), fielding, and wicket keeping (28.6%) account for most injuries. Acute injuries are most common (64%-76%), followed by acute-on-chronic (16%-22.8%) and chronic ones (8%-22%). The most common modern-day cricket injury is hamstring strain, and the most severe is lumbar stress fracture in young fast bowlers. With improved understanding of the scientific and medical aspects of cricket, along with advances in surgical and nonsurgical treatment techniques, the time to return to play has shortened considerably. While the prevalence of cricket injuries has increased, their severity has decreased over the past decades.

  15. Injuries in Competitive Dragon Boating.

    Science.gov (United States)

    Mukherjee, Swarup; Leong, Hin Fong; Chen, Simin; Foo, Yong Xiang Wayne; Pek, Hong Kiat

    2014-11-01

    Dragon boating is a fast-growing team water sport and involves forceful repetitive motions that predispose athletes to overuse injuries. Despite the rising popularity of the sport, there is a lack of studies on injury epidemiology in dragon boating. To investigate the injury epidemiology in competitive dragon boating athletes. Descriptive epidemiological study. A total of 95 dragon boaters (49 males, 46 females) representing their respective universities took part in this study. Data were collected retrospectively using a reliable and valid self-report questionnaire. The study period was from August 2012 to July 2013. A total of 104 musculoskeletal injuries were reported (3.82 injuries/1000 athlete-exposures), 99% of which occurred during training. The most commonly injured regions were the lower back (22.1%), shoulder (21.1%), and wrist (17.3%). The majority of injuries were due to overuse (56.3%), and incomplete muscle-tendon strain was the most prevalent type of injury (50.5%). The time loss from injuries varied. In addition, a significant majority of the dragon boating athletes incurred nonmusculoskeletal injuries, with abrasions (90.5%), blisters (78.9%), and sunburns (72.6%) being the most common. Competitive dragon boating has a moderately high injury incidence, and there seems to be a direct relationship between exposure time and injury rate. A majority of the injuries are overuse in nature, and the body parts most actively involved in paddling movement are at higher risk of injuries. The high incidence of nonmusculoskeletal injuries in dragon boaters suggested that these injuries are likely outcomes of participation in the sport.

  16. Fast pitch softball injuries.

    Science.gov (United States)

    Meyers, M C; Brown, B R; Bloom, J A

    2001-01-01

    The popularity of fast pitch softball in the US and throughout the world is well documented. Along with this popularity, there has been a concomitant increase in the number of injuries. Nearly 52% of cases qualify as major disabling injuries requiring 3 weeks or more of treatment and 2% require surgery. Interestingly, 75% of injuries occur during away games and approximately 31% of traumas occur during nonpositional and conditioning drills. Injuries range from contusions and tendinitis to ligamentous disorders and fractures. Although head and neck traumas account for 4 to 12% of cases, upper extremity traumas account for 23 to 47% of all injuries and up to 19% of cases involve the knee. Approximately 34 to 42% of injuries occur when the athlete collides with another individual or object. Other factors involved include the quality of playing surface, athlete's age and experience level, and the excessive physical demands associated with the sport. Nearly 24% of injuries involve base running and are due to poor judgement, sliding technique, current stationary base design, unorthodox joint and extremity position during ground impact and catching of cleats. The increasing prevalence of overtraining syndrome among athletes has been attributed to an unclear definition of an optimal training zone, poor communication between player and coach, and the limited ability of bone and connective tissue to quickly respond to match the demands of the sport. This has led routinely to arm, shoulder and lumbar instability, chronic nonsteroidal anti-inflammatory drug (NSAID) use and time loss injuries in 45% of pitching staff during a single season. Specific attention to a safer playing environment, coaching and player education, and sport-specific training and conditioning would reduce the risk, rate and severity of fast pitch traumas. Padding of walls, backstops, rails and dugout areas, as well as minimising use of indoor facilities, is suggested to decrease the number of collision

  17. Mountain biking injuries: an update.

    Science.gov (United States)

    Kronisch, Robert L; Pfeiffer, Ronald P

    2002-01-01

    This article reviews the available literature regarding injuries in off-road bicyclists. Recent progress in injury research has allowed the description of several patterns of injury in this sport. Mountain biking remains popular, particularly among young males, although sales and participation figures have decreased in the last several years. Competition in downhill racing has increased, while cross-country racing has decreased somewhat in popularity. Recreational riders comprise the largest segment of participants, but little is known about the demographics and injury epidemiology of noncompetitive mountain cyclists. Most mountain bikers participating in surveys reported a history of previous injuries, but prospective studies conducted at mountain bike races have found injury rates of bike racing the risk of injury may be higher for women than men. Minor injuries such as abrasions and contusions occur frequently, but are usually of little consequence. Fractures usually involve the torso or upper extremities, and shoulder injuries are common. Head and face injuries are not always prevented by current helmet designs. Fatal injuries are rare but have been reported. Improvements in safety equipment, rider training and racecourse design are suggested injury prevention measures. The authors encourage continued research in this sport.

  18. Injury Characteristics of Low-Energy Lisfranc Injuries Compared With High-Energy Injuries.

    Science.gov (United States)

    Renninger, Christopher H; Cochran, Grant; Tompane, Trevor; Bellamy, Joseph; Kuhn, Kevin

    2017-09-01

    Lisfranc injuries result from high- and low-energy mechanisms though the literature has been more focused on high-energy mechanisms. A comparison of high-energy (HE) and low-energy (LE) injury patterns is lacking. The objective of this study was to report injury patterns in LE Lisfranc joint injuries and compare them to HE injury patterns. Operative Lisfranc injuries were identified over a 5-year period. Patient demographics, mechanism of injury, injury pattern, associated injuries, missed diagnoses, clinical course, and imaging studies were reviewed and compared. HE mechanism was defined as motor vehicle crash, motorcycle crash, direct crush, and fall from greater than 4 feet and LE mechanism as athletic activity, ground level twisting, or fall from less than 4 feet. Thirty-two HE and 48 LE cases were identified with 19.3 months of average follow-up. There were no differences in demographics or missed diagnosis frequency (21% HE vs 18% LE). Time to seek care was not significantly different. HE injuries were more likely to have concomitant nonfoot fractures (37% vs 6%), concomitant foot fractures (78% vs 4%), cuboid fractures (31% vs 6%), metatarsal base fractures (84% vs 29%), displaced intra-articular fractures (59% vs 4%), and involvement of all 5 rays (23% vs 6%). LE injuries were more commonly ligamentous (68% vs 16%), with fewer rays involved (2.7 vs 4.1). LE mechanisms were a more common cause of Lisfranc joint injury in this cohort. These mechanisms generally resulted in an isolated, primarily ligamentous injury sparing the lateral column. Both types had high rates of missed injury that could result in delayed treatment. Differences in injury patterns could help direct future research to optimize treatment algorithms. Level III, comparative series.

  19. Mechanisms involved in metformin action in the treatment of polycystic ovary syndrome.

    Science.gov (United States)

    Motta, A B

    2009-01-01

    The N, N' dimethyl-biguanide : Metformin is an antidiabetic drug that increases glucose utilization in insulin-sensitive tissues. As Polycystic Ovary Syndrome (PCOS) and diabetes share some altered parameters-such as abnormal glucose: insulin ratio, altered lipidic metabolism and insulin-resistance syndrome- the use of metformin has become increasingly accepted and widespread in the treatment of PCOS. Currently, metformin is used to induce ovulation and during early pregnancy in PCOS patients, however, a complete knowledge of the metformin action has not been achieved yet. This review describes beyond the classical reproductive action of metformin and explores other benefits of the drug. In addition, the present work discusses the molecular mechanisms involved further than the classical pathway that involves the AMP-activated protein kinase.

  20. Eye Injuries

    Science.gov (United States)

    ... that you could lose your vision. Most eye injuries are preventable. If you play sports or work in certain jobs, you may need protection. The most common type of injury happens when something irritates the ...

  1. Ocular Injuries

    African Journals Online (AJOL)

    GB

    2015-04-02

    Apr 2, 2015 ... KEYWORDS: Bangers, eye injuries, holidays, Nigeria ... antibiotic and cycloplegic eye drops, antibiotic ointment at night and .... Adeoti C. O, Bello T. O., Ashaye A. O. Blinding ... Can fireworks-related injuries to children during ...

  2. ACL Injuries

    Science.gov (United States)

    ... while doing things like skiing, playing soccer or football, and jumping on a trampoline. When you injure ... severity of the injury, age, physical condition, medical history, and other injuries or illnesses. People who are ...

  3. Knee Injuries

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Knee Injuries KidsHealth / For Teens / Knee Injuries What's in ... can do to protect them. What's in a Knee? The knee is a joint , actually the largest ...

  4. Diagnosis of Acute Groin Injuries

    DEFF Research Database (Denmark)

    Serner, Andreas; Tol, Johannes L; Jomaah, Nabil

    2015-01-01

    BACKGROUND: Acute groin injuries are common in high-intensity sports, but there are insufficient data on injury characteristics such as injury mechanisms and clinical and radiological findings. PURPOSE: To describe these characteristics in a cohort of athletes. STUDY DESIGN: Cross-sectional study......; Level of evidence, 3. METHODS: A total of 110 male athletes (mean age, 25.6 ± 4.7 years) with sports-related acute groin pain were prospectively included within 7 days of injury from August 2012 to April 2014. Standardized history taking, a clinical examination, magnetic resonance imaging (MRI), and....../or ultrasound (US) were performed. RESULTS: The most frequent injury mechanism in soccer was kicking (40%), and change of direction was most frequent in other sports (31%). Clinically, adductor injuries accounted for 66% of all injuries and primarily involved the adductor longus on imaging (91% US, 93% MRI...

  5. Hamstring Injury

    Science.gov (United States)

    Hamstring injury Overview A hamstring injury occurs when you strain or pull one of your hamstring muscles — the group of three muscles that run along ... You may be more likely to get a hamstring injury if you play soccer, basketball, football, tennis ...

  6. Orienteering injuries

    OpenAIRE

    Folan, Jean M.

    1982-01-01

    At the Irish National Orienteering Championships in 1981 a survey of the injuries occurring over the two days of competition was carried out. Of 285 individual competitors there was a percentage injury rate of 5.26%. The article discusses the injuries and aspects of safety in orienteering.

  7. Heelys injuries in children.

    Science.gov (United States)

    Oh, D; Arjandas, M; Lim, K B L; Lee, E H

    2006-05-01

    Heelys, a type of shoes with stealth wheels, are extremely popular among children in Singapore. The widespread availability of cheap imitations has led to a proliferation of young users. Coupled with a total lack of safety equipment and instructions, these shoes can lead to significant injuries. The purpose of this study was to examine the incidence and type of injuries sustained by children using Heelys. During a seven-month period from February to August 2004, all children treated at the Paediatric Orthopaedic Department of the KK Women's and Children's Hospital, were asked if the injury was sustained while "heeling". All the patients were reviewed by the authors. A total of 37 patients with significant injuries sustained while "heeling" were identified. Their radiographs and clinical charts were reviewed. The patients and/or their parents were also interviewed to obtain additional information. Upper limb injuries were by far the most common. Distal radius fractures and elbow injuries predominated. None of the children used safety gear. "Heeling" can lead to serious injuries despite the relatively low velocity involved. Children and their parents need to be educated on the use of safety gear.

  8. Skateboarding injuries: An updated review.

    Science.gov (United States)

    Shuman, Kristin M; Meyers, Michael C

    2015-07-01

    This in-depth literature review shows that skateboarding has experienced intermittent periods of popularity, with an estimated 6-15 million skateboarders in the US currently involved at all levels of recreational play and competition. Head trauma accounts for ∼ 3.5-13.1% of all skateboarding injuries. Injury occurs most often to the upper extremity (55-63%), whereas thoracoabdominal and spine injuries account for 1.5-2.9% of all trauma and lower extremity injuries occur 17-26% of the time. Few fatal injuries (1.1%) have been reported, oftentimes resulting from traumatic head injuries incurred from collisions with motor vehicles. Although skateparks may be perceived as a safer alternative to street skateboarding, injuries still occur when the skateboarder collides with an object or falls from the board. Factors leading to trauma include fatigue and overuse, age and skill level, inadequate medical care, environmental conditions, equipment concerns, lack of fitness and training, and the detrimental behavior of the competitor. Although not all skateboarding injuries are avoidable, numerous opportunities exist to instill safety involving education, instruction, and supervision and the proper use of protective gear to reduce predisposition to trauma. Future research recommendations include a more standardized data collection system, as well as an increased focus on kinetic analysis of the sport. Legislation involving helmet laws and the increased investment in a safer environment for the skateboarder may also assist in reducing injury in this sport.

  9. [Multidisciplinary approach of facial injuries

    NARCIS (Netherlands)

    Dubois, L.; Schreurs, R.; Lapid, O.; Saeed, P.; Adriaensen, G.F.; Hoefnagels, F.M.; Jong, V.M. de

    2017-01-01

    BACKGROUND: Approximately one quarter of polytrauma patients has facial injuries, which usually lead to loss of form and function. Several specialties are involved in the acute and reconstructive phases of facial injuries, such as oral and maxillofacial surgery, otorhinolaryngology, plastic surgery,

  10. Sesamoid Injuries in the Foot

    Science.gov (United States)

    ... on the ball of the foot when walking, running and jumping. Sesamoid injuries can involve the bones, tendons and/or surrounding ... on the ball of the foot, such as running, basketball, football, golf, tennis and ballet. ... of Sesamoid Injuries in the Foot There are three types of ...

  11. Sport injuries in adolescents

    Directory of Open Access Journals (Sweden)

    Susanne Habelt

    2011-11-01

    Full Text Available In spite of the wide range of injuries in adolescents during sports activities, there are only a few studies investigating the type and frequency of sport injuries in puberty. However, this information may help to prevent, diagnose and treat sports injuries among teens. 4468 injuries in adolescent patients were treated over a ten year period of time: 66,97% were boys and 32.88% girls. The most frequent sports injuries were football (31.13% followed by handball (8.89% and sports during school (8.77%. The lower extremity was involved in 68.71% of the cases. Knee problems were seen in 29.79% of the patients; 2.57% spine and 1.99% head injuries. Injuries consisted primarily of distortions (35.34% and ligament tears (18.76%; 9,00% of all injuries were fractures. We found more skin wounds (6:1 and fractures (7:2 in male patients compared to females. The risk of ligament tears was highest during skiing. Three of four ski injuries led to knee problems. Spine injuries were observed most often during horse riding (1:6. Head injuries were seen in bicycle accidents (1:3. Head injuries were seen in male patients much more often then in female patients (21:1. Fractures were noted during football (1:9, skiing (1:9, inline (2:3, and during school sports (1:11. Many adolescents participate in various sports. Notwithstanding the methodological problems with epidemiological data, there is no doubt about the large number of athletes sustain musculoskeletal injuries, sometimes serious. In most instances, the accident does not happened during professional sports and training. Therefore, school teachers and low league trainer play an important role preventing further accidence based on knowledge of individual risk patterns of different sports. It is imperative to provide preventive medical check-ups, to monitor the sport-specific needs for each individual sports, to observe the training skills as well as physical fitness needed and to evaluation coaches education.

  12. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal ... Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal ...

  13. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation ... Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation ...

  14. Badminton injuries in youth competitive players.

    Science.gov (United States)

    Goh, S L; Mokhtar, A H; Mohamad Ali, M R

    2013-02-01

    The aim of the study was to examine sports injury pattern and establish cost of injuries in relation to training of 58 competitive badminton players in a Malaysian National Sports School. This one-year prospective observational study recruited all the 13-16 year old students after obtaining informed consent from their appointed guardian. All participants were requested to report any injuries, which were pain or disabilities that occur within the study period (September 1, 2008 to August 31, 2009) either during training or competition. Injured students were to seek treatment from the researcher(s) who made weekly visits and they were then followed up accordingly until they return to full training. Details and progress of the injuries were documented during each visit. Sixty-three injuries were recorded. Soft tissue sprains/strains were the commonest injury (64%). About one third of the injuries occurred in the lower limb especially the knees and was followed by back injuries; 38% of the injuries did not require training modification, half of these injuries resumed training within one week. Upon full training, half of them were still symptomatic. Injury risk was 57%; injury rate was 0.9 injuries/ player/1000 training hours. Badminton injuries mostly involved the lower limb and almost all overuse injuries occurred in the lower limb. However, badminton injuries as a whole were predominantly sprains and strains, and not overuse in nature as widely believed.

  15. Sports injuries in Plus League volleyball players.

    Science.gov (United States)

    Cieśla, E; Dutkiewicz, R; Mgłosiek, M; Nowak-Starz, G; Markowska, M; Jasiński, P; Dudek, J

    2015-06-01

    Although physical activity brings a range of lifelong health benefits, it may also lead to injuries that pose a significant threat to health. It is particularly noticeable in people involved in professional sports where sport-related injuries commonly occur and are associated with intense exercise which aims to improve physical fitness. The article attempts to determine incidence of sports injuries reported by Plus League volleyball players, as well as to identify their most common types and causes. The research project involved 90 Plus League volleyball players aged 18-37 with the average age of 25.11 (SD±5.378). A method of diagnostic survey was applied to collect empirical data by means of questionnaire developed by the authors (researchers). The results were statistically analysed and verified with the analysis of variance (ANOVA) and χ2 test at the significance level (or critical P-value) of P≤0.05. Over 87% of the respondents suffered from at least one sport-related injury. In total, 362 injuries occurred, on average 4.02 injuries per one volleyball player. The most common sports injuries involved ankle or talocrural joint (46 injuries), knee and lower leg muscles (30), interphalangeal articulations of fingers (30) as well as shoulder joint. More than half of the injuries (57%) occurred twice or three times. Volleyball players commonly sustain injuries through contact with an opposing player in competition. Sport-specific injuries may also occur due to exhaustion, lack of rest and undertreated injuries. The most common volleyball-related injuries are primarily talocrural joint, hand and shoulder injuries. Common types of injuries that can affect volleyball players include muscles, joints and ligaments injuries, sprains and strains as well as bruises. Most of these injuries are caused by exhaustion, contact with an opposing player during competition and fatigue. The incidence of sport-related injuries seems to be influenced by such factors as somatic

  16. Cerebral damage caused by nail gun injury

    Directory of Open Access Journals (Sweden)

    Andersen Chris Hedeman

    2016-06-01

    Full Text Available Background Accidents with nail guns are rather common, especially in the construction industry. Most injuries involve the extremities and several present with intracerebral injuries. When the patient is unconscious, it can be a big challenge to determine whether the injury is an accident, self-inflicted or a criminal act.

  17. Paragliding injuries.

    OpenAIRE

    Krüger-Franke, M; Siebert, C H; Pförringer, W

    1991-01-01

    Regulations controlling the sport of paragliding were issued in April 1987 by the German Department of Transportation. The growing popularity of this sport has led to a steady increase in the number of associated injuries. This study presents the incidence, localization and degree of injuries associated with paragliding documented in Germany, Austria and Switzerland. The 283 injuries suffered by 218 paragliders were documented in the period 1987-1989: 181 occurred during landing, 28 during st...

  18. Paragliding injuries.

    Science.gov (United States)

    Krüger-Franke, M; Siebert, C H; Pförringer, W

    1991-06-01

    Regulations controlling the sport of paragliding were issued in April 1987 by the German Department of Transportation. The growing popularity of this sport has led to a steady increase in the number of associated injuries. This study presents the incidence, localization and degree of injuries associated with paragliding documented in Germany, Austria and Switzerland. The 283 injuries suffered by 218 paragliders were documented in the period 1987-1989: 181 occurred during landing, 28 during starting procedures and nine during flight. The mean patient age was 29.6 years. There were 34.9% spinal injuries, 13.4% upper extremity injuries and 41.3% lower limb injuries. Over half of these injuries were treated surgically and in 54 instances permanent disability remained. In paragliding the lower extremities are at greatest risk of injury during landing. Proper equipment, especially sturdy footwear, exact training in landing techniques as well as improved instruction in procedures during aborted or crash landings is required to reduce the frequency of these injuries.

  19. Cervical vertigo and dizziness after whiplash injury

    OpenAIRE

    Endo, Kenji; Ichimaru, Katsuji; Komagata, Mashashi; Yamamoto, Kengo

    2006-01-01

    Whiplash injury is not only limited to neck injury but also brainstem injury that does not involve direct damage to the neck or head. The symptoms of whiplash injury are polymorphous, with the most common complaints being cervical pain, headache and scapulodynia. Vertigo and dizziness are also reported in 25–50% of the cases. In otoneurologic studies, magnetic resonance angiography (MRA) is used for the evaluation of vertebrobasilar hemodynamics in patients who complain of dizziness and verti...

  20. Karate injuries in children and adolescents.

    Science.gov (United States)

    Zetaruk, M N; Violan, M A; Zurakowski, D; Micheli, L J

    2000-05-01

    To identify risk factors for injury and to establish safety guidelines for children in Uechi-Ryu karate. A 1-year retrospective survey of injuries. A private karate school (Uechi-Ryu style) in Plymouth, MA. A total of 68 athletes (age 6-16 years; mean age 10 years) who participated in karate during the 1995-1996 season. None. The presence or absence of injury, with grading of injuries as major, moderate or minor. The types of injuries and body region involved were also analyzed. Twenty eight percent of athletes sustained at least one injury. All injuries were minor, with no time off from training required. The injuries consisted primarily of bruises (11 of 19). Other injuries included mild sprains or strains (5 of 19) and having their 'wind knocked out' (3 of 19). Most injuries were localized to the extremities. Logistic regression analysis identified risk factors for injury. Risk of injury increased with number of years of training (odds ratio 2.95; 95% confidence interval 1.81-4.82; PKarate is a relatively safe sport for children and adolescents when properly taught. Risk of injury increases with experience; therefore, greater supervision is required of higher ranks. Injury increases with weekly training; however, 3 h a week or less appears to be associated with a low risk of significant injury in this age group.

  1. Parental involvement

    Directory of Open Access Journals (Sweden)

    Ezra S Simon

    2005-01-01

    Full Text Available Parent-Teacher Associations and other community groups can play a significant role in helping to establish and run refugee schools; their involvement can also help refugee adults adjust to their changed circumstances.

  2. Incidence and nature of karate injuries.

    Science.gov (United States)

    Destombe, Claire; Lejeune, Laurent; Guillodo, Yannick; Roudaut, Anne; Jousse, Sandrine; Devauchelle, Valérie; Saraux, Alain

    2006-03-01

    To determine the incidence and nature of karate injuries sustained in karate clubs and to identify risk factors for injuries. One hundred eighty-six individuals from three karate clubs in Brest, France, were entered in a retrospective study extending from September 2002 to June 2003. Each athlete was asked to complete a questionnaire on karate injuries sustained during the previous year (type, location, mechanism, exercise during which the injury occurred, number of days off training and work, and medical care). Injury types were described by number of injuries and risk factors per number of injured athletes. Forty-eight (28.8%) of the 186 athletes sustained 83 injuries (63 while training and 20 while competing). The annual injury rate was 44.6 per 100 athletes. Incidence rates were similar in males and females and across the three clubs but increased with age, time spent training (3.6+/-1.7 vs. 2.9+/-1.5 h/week; P=0.001), rank (lower ranks vs. brown and black belts, P=0.015), and years of practice (7.3+/-5.5 years in athletes with injuries vs. 5.1+/-4.8 in those without injuries; P=0.03). Injuries consisted of 43 (53%) hematomas, 16 (19%) sprains, seven (7%) muscle lesions, six (7%) fractures, four (5%) malaise episodes, and seven (7%) miscellaneous lesions. Time off training occurred for 26 (31.3%) injuries and ranged from 8 to >30 days. The body region involved was the head in 22 (26.5%) injuries, the torso in eight injuries (9.6%), the upper limb in 24 (28.9%) injuries, and the lower limb in 29 (35%) injuries. Karate injuries are fairly common but usually minor. They are more likely to occur during competitions than while training. The head and limbs are the main regions involved. Longer training times per week and higher rank are associated with an increased risk of injury. Prevention seems crucial.

  3. Emerging Roles of AMP-Activated Protein Kinase

    DEFF Research Database (Denmark)

    Fritzen, Andreas Mæchel

    or has focused on specific physiological situations and tissues. The present PhD thesis has addressed the role of AMPK in regulation of: 1) substrate utilisation during and in recovery from exercise, 2) adipose tissue metabolism during weight loss, and 3) autophagy in skeletal muscle during exercise...... during post exercise recovery. AMPK seems therefore to play a role in substrate selection post exercise. In adipose tissue, basal AMPK activity is decreased in obese and insulin resistant states and is increased in human adipose tissue during weight loss. The underlying mechanisms for increased AMPK...

  4. Whiplash injuries.

    Science.gov (United States)

    Malanga, Gerard; Peter, Jason

    2005-10-01

    Whiplash injuries are very common and usually are associated with rear-end collisions. However, a whiplash injury can be caused by any event that results in hyperextension and flexion of the cervical spine. These injuries are of serious concern to all consumers due to escalating cost of diagnosis, treatment, insurance, and litigation. Most acute whiplash injury cases respond well to conservative treatments, which result in resolution of symptoms usually within weeks to a few months after the injury occurred. Chronic whiplash injuries often are harder to diagnose and treat and often result in poor outcomes. Current research shows that various structures in the cervical spine receive nociceptive innervation and potentially may be the cause of chronic pain symptoms. One potential pain generator showing promise is the facet or zygapophyseal joints. Various researchers have proven that these joints are injured during whiplash injuries and that diagnosis and temporary pain relief can be obtained with facet joint injections. The initial evaluation of any patient should follow an organized and stepwise approach, and more serious causes of neck pain must first be ruled out through the history, physical examination, and diagnostic testing. Treatment regimens should be evidence-based, focusing on treatments that have proven to be effective in treating acute and chronic whiplash injuries.

  5. Ocular Injury

    Science.gov (United States)

    ... trauma can happen at home, school, play or sports. Most common injuries are scratches to the cornea or blunt trauma. Approved and tested eye and face protection is essential to prevent injuries. Sports such as hockey, baseball, racquet ball, squash, and ...

  6. Rowing Injuries

    DEFF Research Database (Denmark)

    Thornton, Jane S; Vinther, Anders; Wilson, Fiona

    2017-01-01

    understanding in pre-participation screening, training load, emerging concepts surrounding back and rib injury, and relative energy deficiency in sport. Through a better understanding of the nature of the sport and mechanisms of injury, physicians and other healthcare providers will be better equipped to treat...

  7. Trampoline injuries.

    Science.gov (United States)

    Nysted, M; Drogset, J O

    2006-12-01

    To describe the mechanism, location and types of injury for all patients treated for trampoline-associated injuries at St Olav's University Hospital, Trondheim, Norway, from March 2001to October 2004. Patients were identified from a National Injury Surveillance System. All patients were asked to complete a standard questionnaire at their first visit at the hospital. Most data were recorded prospectively, but data on the mechanism of injury, the number of participants on the trampoline at the time of injury, adult supervision and whether the activity occurred at school or in another organised setting were collected retrospectively. A total of 556 patients, 56% male and 44% female, were included. The mean age of patients was 11 (range 1-62) years. 77% of the injuries occurred on the body of the trampoline, including falls on to the mat, collisions with another jumper, falls on to the frame or the springs, and performing a somersault, whereas 22% of the people fell off the trampoline. In 74% of the cases, more than two people were on the trampoline, with as many as nine trampolinists noted at the time of injury. For children Trampolining can cause serious injuries, especially in the neck and elbow areas of young children. The use of a trampoline is a high-risk activity. However, a ban is not supported. The importance of having safety guidelines for the use of trampolines is emphasised.

  8. Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy)2] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38MAPK/p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment.

    Science.gov (United States)

    Filomeni, Giuseppe; Cardaci, Simone; Da Costa Ferreira, Ana Maria; Rotilio, Giuseppe; Ciriolo, Maria Rosa

    2011-08-01

    We have demonstrated previously that the complex bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N']copper(II), named [Cu(isaepy)(2)], induces AMPK (AMP-activated protein kinase)-dependent/p53-mediated apoptosis in tumour cells by targeting mitochondria. In the present study, we found that p38(MAPK) (p38 mitogen-activated protein kinase) is the molecular link in the phosphorylation cascade connecting AMPK to p53. Transfection of SH-SY5Y cells with a dominant-negative mutant of AMPK resulted in a decrease in apoptosis and a significant reduction in phospho-active p38(MAPK) and p53. Similarly, reverse genetics of p38(MAPK) yielded a reduction in p53 and a decrease in the extent of apoptosis, confirming an exclusive hierarchy of activation that proceeds via AMPK/p38(MAPK)/p53. Fuel supplies counteracted [Cu(isaepy)(2)]-induced apoptosis and AMPK/p38(MAPK)/p53 activation, with glucose being the most effective, suggesting a role for energetic imbalance in [Cu(isaepy)(2)] toxicity. Co-administration of 3BrPA (3-bromopyruvate), a well-known inhibitor of glycolysis, and succinate dehydrogenase, enhanced apoptosis and AMPK/p38(MAPK)/p53 signalling pathway activation. Under these conditions, no toxic effect was observed in SOD (superoxide dismutase)-overexpressing SH-SY5Y cells or in PCNs (primary cortical neurons), which are, conversely, sensitized to the combined treatment with [Cu(isaepy)(2)] and 3BrPA only if grown in low-glucose medium or incubated with the glucose-6-phosphate dehydrogenase inhibitor dehydroepiandrosterone. Overall, the results suggest that NADPH deriving from the pentose phosphate pathway contributes to PCN resistance to [Cu(isaepy)(2)] toxicity and propose its employment in combination with 3BrPA as possible tool for cancer treatment. © The Authors Journal compilation © 2011 Biochemical Society

  9. Injury - kidney and ureter

    Science.gov (United States)

    ... kidney; Ureteral injury; Pre-renal failure - injury, Post-renal failure - injury; Kidney obstruction - injury Images Kidney anatomy Kidney - blood and urine flow References Molitoris BA. Acute kidney injury. In: Goldman ...

  10. Spinal Cord Injury 101

    Medline Plus

    Full Text Available menu Understanding Spinal Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ...

  11. Repetitive Stress Injuries

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Repetitive Stress Injuries KidsHealth / For Teens / Repetitive Stress Injuries What's ... t had any problems since. What Are Repetitive Stress Injuries? Repetitive stress injuries (RSIs) are injuries that ...

  12. Badminton injuries.

    Science.gov (United States)

    Krøner, K; Schmidt, S A; Nielsen, A B; Yde, J; Jakobsen, B W; Møller-Madsen, B; Jensen, J

    1990-01-01

    In a one year period, from 1 January 1986 to 31 December 1986, 4303 patients with sports injuries were treated at Aarhus Amtssygehus and Aarhus Kommunehospital. The mean age was 21.6 years (range 7-72 years) and 2830 were men. Two hundred and seventeen badminton injuries occurred in 208 patients (136 men) with a mean age of 29.6 years (range 7-57 years), constituting 4.1 percent of all sport injuries in Aarhus. Joints and ligaments were injured in 58.5 percent of the patients, most frequently located in the lower limb and significantly more often among patients younger than 30 years of age. Muscle injury occurred in 19.8 percent of the patients. This type of injury was significantly more frequent among patients older than 30 years of age. Most injuries were minor. However, 6.8 percent of the patients were hospitalized and 30.9 percent received additional treatment by a physician. As the risk of injury varies with age, attempts to plan training individually and to institute prophylactic measures should be made. PMID:2078802

  13. Trampoline-related injuries.

    Science.gov (United States)

    Larson, B J; Davis, J W

    1995-08-01

    Two hundred and seventeen patients who had sustained an injury during the recreational use of a trampoline were managed in the emergency room of Logan Regional Hospital in Logan, Utah, from January 1991 through December 1992. We retrospectively reviewed the charts and radiographs of these patients to categorize the injuries. Additional details regarding the injuries of seventy-two patients (33 per cent) were obtained by means of a telephone interview with use of a questionnaire. The injuries occurred from February through November, with the peak incidence in July. The patients were eighteen months to forty-five years old (average, ten years old); ninety-four patients (43 per cent) were five to nine years old. Eighty-four patients (39 per cent) sustained a fracture; fifty-four (25 per cent), a sprain or strain; forty-five (21 per cent), a laceration; and thirty-four (16 per cent), a contusion. Fifty-seven injuries (26 per cent) involved the elbow or forearm; forty-six (21 per cent), the head or neck; forty (18 per cent), the ankle or foot; thirty-three (15 per cent), the knee or leg; nineteen (9 per cent), the trunk or back; thirteen (6 per cent), the shoulder or arm; and nine (4 per cent), the wrist or hand. Thirteen patients (6 per cent) had a back injury, but none of them had a permanent neurological deficit. One patient who had an ocular injury was transferred to a tertiary care center. One hundred and fifty-six patients (72 per cent) were evaluated radiographically, fifteen (7 per cent) were admitted to the hospital, and thirteen (6 per cent) had an operation.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Alda-1 Protects Against Acrolein-Induced Acute Lung Injury and Endothelial Barrier Dysfunction.

    Science.gov (United States)

    Lu, Qing; Mundy, Miles; Chambers, Eboni; Lange, Thilo; Newton, Julie; Borgas, Diana; Yao, Hongwei; Choudhary, Gaurav; Basak, Rajshekhar; Oldham, Mahogany; Rounds, Sharon

    2017-12-01

    Inhalation of acrolein, a highly reactive aldehyde, causes lung edema. The underlying mechanism is poorly understood and there is no effective treatment. In this study, we demonstrated that acrolein not only dose-dependently induced lung edema but also promoted LPS-induced acute lung injury. Importantly, acrolein-induced lung injury was prevented and rescued by Alda-1, an activator of mitochondrial aldehyde dehydrogenase 2. Acrolein also dose-dependently increased monolayer permeability, disrupted adherens junctions and focal adhesion complexes, and caused intercellular gap formation in primary cultured lung microvascular endothelial cells (LMVECs). These effects were attenuated by Alda-1 and the antioxidant N-acetylcysteine, but not by the NADPH inhibitor apocynin. Furthermore, acrolein inhibited AMP-activated protein kinase (AMPK) and increased mitochondrial reactive oxygen species levels in LMVECs-effects that were associated with impaired mitochondrial respiration. AMPK total protein levels were also reduced in lung tissue of mice and LMVECs exposed to acrolein. Activation of AMPK with 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside blunted an acrolein-induced increase in endothelial monolayer permeability, but not mitochondrial oxidative stress or inhibition of mitochondrial respiration. Our results suggest that acrolein-induced mitochondrial dysfunction may not contribute to endothelial barrier dysfunction. We speculate that detoxification of acrolein by Alda-1 and activation of AMPK may be novel approaches to prevent and treat acrolein-associated acute lung injury, which may occur after smoke inhalation.

  15. Spinal injury

    Science.gov (United States)

    ... Dallas, TX: American Red Cross; 2016. Kaji AH, Newton EJ, Hockberger RS. Spinal injuries. In: Marx JA, ... member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www. ...

  16. Chilling injury

    African Journals Online (AJOL)

    ahar

    2013-12-18

    Dec 18, 2013 ... ROS avoidance genes play pivotal role in defense mechanism against chilling injury derived oxidative stress. ... Low temperature storage is a postharvest technology ..... crops is highly dependent on ethylene production and.

  17. Injury Statistics

    Science.gov (United States)

    ... Power Saws for 2001 05/15/2002 Nail Gun Related Injuries and Deaths Home Maintenance & Construction 05/ ... Information (FOIA) Inspector General No Fear Act Data USA.gov Report an Unsafe Product Contact Us: 800- ...

  18. Electrical injury

    Science.gov (United States)

    ... RS, Gausche-Hill M, eds. Rosen's Emergency Medicine: Concepts and Clinical Practice. 9th ed. Philadelphia, PA: Elsevier; 2018:chap 134. Price LA, Loiacono LA. Electrical and lightning injury. In: Cameron JL, Cameron AM, eds. Current Surgical ...

  19. Ear Injury

    Science.gov (United States)

    ... of different injuries can affect the outer ear. Cauliflower ear (subperichondrial hematoma) A blunt blow to the ... to a deformed ear. This deformity, called a cauliflower ear, is common among wrestlers, boxers, and rugby ...

  20. Cold injuries.

    Science.gov (United States)

    Kruse, R J

    1995-01-01

    There are two categories of cold injury. The first is hypothermia, which is a systemic injury to cold, and the second is frostbite, which is a local injury. Throughout history, entire armies, from George Washington to the Germans on the Russian Front in World War II, have fallen prey to prolonged cold exposure. Cold injury is common and can occur in all seasons if ambient temperature is lower than the core body temperature. In the 1985 Boston Marathon, even though it was 76 degrees and sunny, there were 75 runners treated for hypothermia. In general, humans adapt poorly to cold exposure. Children are at particular risk because of their relatively greater surface area/body mass ratio, causing them to cool even more rapidly than adults. Because of this, the human's best defense against cold injury is to limit his/her exposure to cold and to dress appropriately. If cold injury has occurred and is mild, often simple passive rewarming such as dry blankets and a warm room are sufficient treatment.

  1. Sports injury of the pediatric musculoskeletal system.

    Science.gov (United States)

    Rosendahl, Karen; Strouse, Peter J

    2016-05-01

    Sports related injuries are common in children and adolescents, with a reported incidence of around one in ten children each year. Boys incur more and severer sports injuries than girls, and chance for injury is greater with contact or jumping sports. Sports injuries seen in children under 10-years of age are non-specific, including contusions, mild sprains, and extremity fractures, usually Salter fractures of the physes (growth plate) or plastic fractures. In the very young athlete, sports injury of the ligaments or muscle is rare as are spine or head injuries. With growth and adolescence, the intensity of sports involvement increases. Pre-pubertal children still have open physes that are prone to injury, both acute or due to stress from a repetitive activity. In addition to injury of the physes of the long bones, injuries to the physes of apophyses are common. Ligamentous injury is uncommon before physeal closure, but can occur. After the physes fuse, ligamentous injury is seen with patterns similar to adults. This review will include a description of sports related injuries seen in children and adolescents. We will concentrate on injuries that are specific for the growing skeleton, with a brief mention of those seen after fusion of the physes.

  2. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shiwei [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Dong, Yushu [Department of Neurosurgery, 463rd Hospital of PLA, Shenyang 110042 (China); Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Hou, Wugang, E-mail: gangwuhou@163.com [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Li, Wei, E-mail: liweipepeyato@163.com [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi’an 710032 (China)

    2013-11-01

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.

  3. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    International Nuclear Information System (INIS)

    Chen, Shiwei; Dong, Yushu; Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng; Hou, Wugang; Li, Wei

    2013-01-01

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury

  4. Management of Penetrating Spinal Cord Injuries in a Non Spinal ...

    African Journals Online (AJOL)

    Management of Penetrating Spinal Cord Injuries in a Non Spinal Centre: Experience at Enugu, Nigeria. ... The thoracic spine{9(41%)}was most often involved. ... Five (23%) patients with injury at cervical level died from respiratory failure.

  5. Chest Injuries Associated with Head Injury

    African Journals Online (AJOL)

    Traumatic brain injury (TBI) is a common cause of mortality and severe morbidity. Although there have been significant advances in management, associated severe injuries, in particular chest injuries, remain a major challenge. Extracranial injuries, especially chest injuries increase mortality in patients with TBI in both short.

  6. Polydatin Protects Rat Liver against Ethanol-Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF-κB p65 Pathway

    Directory of Open Access Journals (Sweden)

    Qiong-Hui Huang

    2017-01-01

    Full Text Available Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH in the serum, suppressed the malonaldehyde (MDA and triglyceride (TG content and the production of reactive oxygen species (ROS, and enhanced the activities of superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, catalase (CAT, andalcohol dehydrogenase (ADH, and aldehyde dehydrogenase (ALDH, paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1 and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2 and its target gene haem oxygenase-1 (HO-1. Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6 via downregulating toll-like receptor 4 (TLR4 and nuclear factor kappa B (NF-κB p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

  7. Meat Grinder Injury to the Hand: Serial Cases

    OpenAIRE

    Lubis, Nur Rachmat

    2012-01-01

    Introduction.Although meat grinder injury to the hand is not a common case, it causes a wide spectrum of injuries that result not only in tremendous physical and emotional pain but also substantial economic impact as well.Case presentation.Three cases of hand injury caused by meat grinders are presented. Two injuries involved non dominant hand and one involved dominant hand, result in varying degrees of deformity. All patients arrived in emergency room with injured hand still firmly...

  8. Child injury surveillance capabilities in NSW: informing policy and practice

    Directory of Open Access Journals (Sweden)

    Rebecca Mitchell

    2017-10-01

    Full Text Available Injury is one of the most common reasons why a child is hospitalised. Information gained from injury surveillance activities provides an estimate of the injury burden, describes injury event circumstances, can be used to monitor injury trends over time, and is used to design and evaluate injury prevention activities. This perspective article provides an overview of child injury surveillance capabilities within New South Wales (NSW, Australia, following a stocktake of population-based injury-related data collections using the Evaluation Framework for Injury Surveillance Systems. Information about childhood injury in NSW is obtained from multiple administrative data collections that were not specifically designed to conduct injury surveillance. Obtaining good information for child injury surveillance in NSW will involve better coordination of information from agencies that record information about childhood injury. Regular reporting about childhood injury to provide a comprehensive profile of injuries of children and young people in the state should be considered, along with the provision and/or linkage of child injury information from multiple data collections. This could support the development of a suite of injury performance indicators to monitor childhood injury reduction strategies across NSW.

  9. Involving women.

    Science.gov (United States)

    Agbo, J

    1994-01-01

    I am a primary health care (PHC) coordinator working with the May Day Rural project, a local NGO involved in integrated approaches and programs with rural communities in the Ga District of the Greater-Accra region in Ghana. When we talk about the community development approach we must first and foremost recognize that we are talking about women, because in the developing world frequent childbirths mean that her burden of mortality is higher than a man's; her workload is extremely heavy--whether in gardening, farming, other household duties, caring for the sick, or the rearing of children; she has a key role in PHC and community development, because men are always looking for greener pastures elsewhere, leaving the women behind. Women's concerns are critical in most health care projects and women and children are their main beneficiaries. Why not include women in the management team, project design, implementation and evaluation processes? That is what the May Day Rural project is practicing, encouraging women's participation and creating a relationship of trust. full text

  10. N-n-butyl haloperidol iodide ameliorates hypoxia/reoxygenation injury through modulating the LKB1/AMPK/ROS pathway in cardiac microvascular endothelial cells.

    Science.gov (United States)

    Lu, Binger; Wang, Bin; Zhong, Shuping; Zhang, Yanmei; Gao, Fenfei; Chen, Yicun; Zheng, Fuchun; Shi, Ganggang

    2016-06-07

    Endothelial cells are highly sensitive to hypoxia and contribute to myocardial ischemia/reperfusion injury. We have reported that N-n-butyl haloperidol iodide (F2) can attenuate hypoxia/reoxygenation (H/R) injury in cardiac microvascular endothelial cells (CMECs). However, the molecular mechanisms remain unclear. Neonatal rat CMECs were isolated and subjected to H/R. Pretreatment of F2 leads to a reduction in H/R injury, as evidenced by increased cell viability, decreased lactate dehydrogenase (LDH) leakage and apoptosis, together with enhanced AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1) phosphorylation in H/R ECs. Blockade of AMPK with compound C reversed F2-induced inhibition of H/R injury, as evidenced by decreased cell viability, increased LDH release and apoptosis. Moreover, compound C also blocked the ability of F2 to reduce H/R-induced reactive oxygen species (ROS) generation. Supplementation with the ROS scavenger N-acetyl-L-cysteine (NAC) reduced ROS levels, increased cell survival rate, and decreased both LDH release and apoptosis after H/R. In conclusion, our data indicate that F2 may mitigate H/R injury by stimulating LKB1/AMPK signaling pathway and subsequent suppression of ROS production in CMECs.

  11. Combat ocular trauma and systemic injury.

    Science.gov (United States)

    Weichel, Eric D; Colyer, Marcus H

    2008-11-01

    To review the recent literature regarding combat ocular trauma during hostilities in Operations Iraqi Freedom and Enduring Freedom, describe the classification of combat ocular trauma, and offer strategies that may assist in the management of eye injuries. Several recent publications have highlighted features of combat ocular trauma from Operation Iraqi Freedom. The most common cause of today's combat ocular injuries is unconventional fragmentary munitions causing significant blast injuries. These explosive munitions cause high rates of concomitant nonocular injuries such as traumatic brain injury, amputation, and other organ injuries. The most frequent ocular injuries include open-globe and adnexal lacerations. The extreme severity of combat-related open-globe injuries leads to high rates of primary enucleation and retained intraocular foreign bodies. Visual outcomes of intraocular foreign body injuries are similar to other series despite delayed removal, and no cases of endophthalmitis have occurred. Despite these advances, however, significant vision loss persists in cases of perforating globe injuries as well as open and closed-globe trauma involving the posterior segment. This review summarizes the recent literature describing ocular and systemic injuries sustained during Operations Iraqi and Enduring Freedom. An emphasis on classification of ocular injuries as well as a discussion of main outcome measures and complications is discussed.

  12. Injury incidence in hip hop dance.

    Science.gov (United States)

    Ojofeitimi, S; Bronner, S; Woo, H

    2012-06-01

    Hip hop dance has rapidly become a popular international art form. There is limited information on injury patterns in this population. The purpose of this study was to determine injury incidence and patterns among three groups of hip hop dancers. Three hundred and twelve intermediate, advanced, and expert hip hop dancers were recruited at battles, dance conferences, clubs, and on dance related web sites within the United States and internationally. A Web-based survey was conducted over a 6-month period. Inclusion criteria included intermediate and advanced level dancers over the age of 13. Dancers were divided into three main categories: Breakers, Popper/Lockers, and New Schoolers. Separate analysis of variances were used to compare injury pattern differences between groups. Two hundred and thirty-two dancers reported a total of 738 injuries. Five hundred and six of these (sustained by 205 dancers) were time-loss (TL) injuries. Annual injury incidence was 237% (162% involving TL). Lower extremity injuries were 52% and upper extremity injuries 32% of total injuries. Breakers had a higher injury incidence compared with Popper/Lockers, and New Schoolers. Hip hop dancers report injury rates that are higher than other dance forms but similar to gymnastics. These dancers should be educated concerning injury prevention, biomechanics, and use of protective equipment. © 2010 John Wiley & Sons A/S.

  13. OCULAR MANIFESTATIONS OF HEAD INJURIES

    Directory of Open Access Journals (Sweden)

    Kanukollu Venkata Madusudana Rao

    2016-12-01

    Full Text Available BACKGROUND This prospective study aimed to evaluate the incidence of ocular manifestations in head injury and their correlation with the intracranial lesions. MATERIALS AND METHODS A total of 108 consecutive cases of closed head injury admitted in the neurosurgical ward of a tertiary teaching hospital underwent a thorough ophthalmic assessment. Clinical examination, radiological imaging and Glasgow Coma Scale (GCS were applied to grade the severity of injury. RESULTS Total number of 108 patients of head injury were examined of which 38 patients had ocular manifestations (35.18%. Of these, 85.18% were males, 84% of injuries were due to road traffic accidents and 16% were due to fall from a height. The ocular manifestations were as follows- Orbital complications were seen in 6 patients (15.8%. Anterior segment manifestations included black eyes seen in 10 patients (26.3%, subconjunctival haemorrhage in 10.5% of patients (4 patients, corneal involvement in 21% of patients (8 patients and pupillary involvement in 50% of patients (19 patients. Posterior segment manifestations were seen in 26.3% of patients (10 patients and were as follows- Purtscher’s retinopathy in 2 patients and optic atrophy in 5 patients. Cranial nerve palsies were seen in 15 patients (39.47% and supranuclear movement disorders were seen in 3 patients (8%. CONCLUSION Even though, neurosurgeons perform comprehensive clinical examination including eye examination, the main purpose is limited to aid topical diagnosis of neurological lesions. This study emphasises the importance of a detailed eye examination by an ophthalmologist to prevent irreversible visual loss in addition to aiding in the neurological diagnosis. Pupillary involvement, papilloedema and ocular motor paresis pointed to a more severe head injury. This observational prospective study helped us to correlate the severity of head injuries in association with ocular findings in patients admitted in neurosurgical ward

  14. Environmental Subconcussive Injury, Axonal Injury, and Chronic Traumatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Wendy A. Morley

    2018-03-01

    is optimal resilience, capable of launching effective responses to injury with spontaneous recovery, and at the other end is diminished resilience with a compromised ability to respond and/or heal appropriately. Modulating factors such as one’s total cumulative and synergistic brain trauma load, bioavailability of key nutrients needed for proper functioning of restorative metabolic pathways (specifically those involved in the deactivation and clearance of metabolic by-products of brain injury are key to ultimately determining one’s brain resilience.

  15. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal ... Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal ...

  16. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal ... Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal ...

  17. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury Diane M. Rowles, MS, NP How Family Life Changes After Spinal Cord Injury Nancy Rosenberg, ... Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW ...

  18. Dealing with Sports Injuries

    Science.gov (United States)

    ... Videos for Educators Search English Español Dealing With Sports Injuries KidsHealth / For Teens / Dealing With Sports Injuries ... a long way toward preventing injuries. Types of Sports Injuries Common reasons why teens get injured playing ...

  19. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ... Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ...

  20. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 Adult Injuries Spinal Cord Injury 101 David ...

  1. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 Adult Injuries Spinal Cord Injury 101 ...

  2. Near miss and minor occupational injury: Does it share a common causal pathway with major injury?

    Science.gov (United States)

    Alamgir, Hasanat; Yu, Shicheng; Gorman, Erin; Ngan, Karen; Guzman, Jaime

    2009-01-01

    An essential assumption of injury prevention programs is the common cause hypothesis that the causal pathways of near misses and minor injuries are similar to those of major injuries. The rates of near miss, minor injury and major injury of all reported incidents and musculoskeletal incidents (MSIs) were calculated for three health regions using information from a surveillance database and productive hours from payroll data. The relative distribution of individual causes and activities involved in near miss, minor injury and major injury were then compared. For all reported incidents, there were significant differences in the relative distribution of causes for near miss, minor, and major injury. However, the relative distribution of causes and activities involved in minor and major MSIs were similar. The top causes and activities involved were the same across near miss, minor, and major injury. Finding from this study support the use of near miss and minor injury data as potential outcome measures for injury prevention programs. (c) 2008 Wiley-Liss, Inc.

  3. High power laser therapy treatment compared to simple segmental physical rehabilitation in whiplash injuries (1° and 2° grade of the Quebec Task Force classification) involving muscles and ligaments.

    Science.gov (United States)

    Conforti, Maria; Fachinetti, Giorgio Paolo

    2013-04-01

    whiplash is a frequent post traumatic pathology caused by muscle, tendon and capsular elements over stretching. The authors conducted a short term prospective randomised study to test the effectiveness of a multi wave High Power Laser Therapy (HPLT) versus conventional simple segmental physical rehabilitation (PT) included in Italian tariff nomenclature performance physiotherapy Study Design: prospective randomised study (Level II). the authors identified 135 homogeneous patients with whiplash grade 1 - 2 of the Quebec Task Force classification (QTFC). INAIL, the Italian National Workers Insurance, based in Milan, was reliable source for identifying patients. All patients with whiplash injuries grade 1 or 2 QTFC, were eligible for the study, starting from April 28 2010 to September 30 2010. Patients referred to a Coordinator (C.M.) who applied the inclusion and exclusion criteria. Patients who agreed to participate were randomly assigned to one of the two treatment groups. Dates for initial treatment session were arranged, including cervical spine X-ray, and assessment. Each patient gave informed consent for participation and agreed to adopt only the study treatment for 6 weeks. Group A (84 patients) was treated with High Power Laser Therapy (HPLT), Group B (51 patients) received conventional simple segmental physical rehabilitation (PT). During the treatment period, no other electro-medical therapy, analgesics or anti-inflammatory drugs were allowed. All patients were assessed at baseline (T0) and at the end of the treatment period (T1) using a Visual Analogical Scale (VAS), (T2) the date of return to work was registered afterwards. there was a reduction in VAS pain scores at T1. Group A (VAS = 20) Group B (VAS = 34,8) (p =0.0048). Laser treatment allowed quick recovery and return to work (T2). Group A after 48 days against 66 days of Group B (p=0.0005). results suggest that High Power Laser Therapy - is an effective treatment in patients with whiplash injury

  4. [Definition of hospital discharge, serious injury and death from traffic injuries].

    Science.gov (United States)

    Pérez, Katherine; Seguí-Gómez, María; Arrufat, Vita; Barberia, Eneko; Cabeza, Elena; Cirera, Eva; Gil, Mercedes; Martín, Carlos; Novoa, Ana M; Olabarría, Marta; Lardelli, Pablo; Suelves, Josep Maria; Santamariña-Rubio, Elena

    2014-01-01

    Road traffic injury surveillance involves methodological difficulties due, among other reasons, to the lack of consensus criteria for case definition. Police records have usually been the main source of information for monitoring traffic injuries, while health system data has hardly been used. Police records usually include comprehensive information on the characteristics of the crash, but often underreport injury cases and do not collect reliable information on the severity of injuries. However, statistics on severe traffic injuries have been based almost exclusively on police data. The aim of this paper is to propose criteria based on medical records to define: a) "Hospital discharge for traffic injuries", b) "Person with severe traffic injury", and c) "Death from traffic injuries" in order to homogenize the use of these sources. Copyright © 2014. Published by Elsevier Espana.

  5. Respiratory mechanics in brain injury: A review

    OpenAIRE

    Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

    2016-01-01

    Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case ...

  6. Osteochondral injuries of the foot and ankle.

    Science.gov (United States)

    Frost, Andrew; Roach, Richard

    2009-06-01

    Osteochondral injuries commonly affect the ankle joint and involve the dome of the talus. This article describes the etiology and pathogenesis of these injuries. Their clinical presentation is described and advice is given on how to diagnose and investigate suspected osteochondral injuries. The various treatment options currently available are briefly reviewed. There is some attempt made to give consensus on optimal treatment of this condition at the present time.

  7. Fingertip Injuries

    Science.gov (United States)

    ... All Topics A-Z Videos Infographics Symptom Picker Anatomy Bones Joints Muscles Nerves Vessels Tendons About Hand Surgery What is a Hand Surgeon? What is a Hand Therapist? Media Find a Hand Surgeon Home Anatomy Fingertip Injury Email to a friend * required fields ...

  8. Musculoskeletal injuries

    International Nuclear Information System (INIS)

    Gigirey, V

    2012-01-01

    This presentation is about musculoskeletal injuries and the diagnosis of osseous tumors. The use of the radiology, bone scintigraphy, computed tomography and magnetic resonance contribute to detect the localization of the osseous lesions as well as the density (lytic, sclerotic, mixed) and the benign and malignant tumors.

  9. Rollerblading and skateboarding injuries in children in northeast England.

    Science.gov (United States)

    Hassan, I; Dorani, B J

    1999-01-01

    OBJECTIVES: To establish the demographic profile and injury characteristics of children presenting with rollerblading or skateboarding associated injuries. This study also examines the circumstances leading to these injuries with a view to suggesting preventive measures. METHODS: A prospective study using a proforma to collect data from each child presenting with rollerblading or skateboarding related injuries. Injury details were obtained from clinical and radiological records. The injury severity score (ISS) was calculated for each child and statistical analysis was done using chi2. RESULTS: Eighty one children presented with rollerblading associated injuries accounting for 7% of childhood injuries seen during the eight month study period. The mean age was 10.3 years and sex distribution was equal. Soft tissue injuries accounted for 51% and fractures for 49% of the injuries. Wrist fractures alone accounted for 86% of all fractures seen. Seventy per cent of soft tissue injuries involved the upper limb. The overall mean ISS was 3.0 with a range from 1 to 9. Injury was attributed to fall secondary to loss of control or collision with an obstacle while rollerblading in the majority of children. Injury occurred while rollerblading in residential or public places in 99% of the children. In contrast skateboarding related injuries were much rarer and caused soft tissue injuries only. CONCLUSION: This study has revealed a higher incidence of rollerblading injuries than previously suspected. Effective management strategies should include not only the treatment of these injuries but also attention to their causes and prevention. PMID:10505916

  10. Temporomandibular disorders after whiplash injury

    DEFF Research Database (Denmark)

    Kasch, Helge; Hjorth, Tine; Svensson, Peter

    2002-01-01

    Aims: Whiplash injury to the neck, is often considered a significant risk factor for development of temporomandibular disorders (TMD), and has been proposed to produce internal derangements of the temporomandibular joint (TMJ). Few studies however have examined TMD-related pain in acute whiplash...... patients compared with a matched control group. The aim of the present study was to assess pain and sensorimotor function in the craniofacial region in an unselected group of patients sustaining a motor vehicle accident involving a rear collision. Methods: Prospectively, 19 acute whiplash patients exposed...... obtained at each visit. Results: One whiplash patient and I ankle-injury patient bad jaw pain at the first visit. Palpation scores of the TMJ and the summated palpation scores only tended to be higher in patients sustaining a whiplash injury than in ankle-injury controls at the first visit. However, MPQ...

  11. Trauma and sports injuries of the elbow

    NARCIS (Netherlands)

    Kodde, I.F.

    2016-01-01

    This thesis deals with current issues in the management of trauma and sports injuries of the elbow. Common sports injuries of the elbow involve ruptures of the distal biceps tendon and the ulnar collateral ligament. We evaluated one of the current thoughts, that the height of the radial bicipital

  12. Iatrogenic burns injury complicating neonatal resuscitation ...

    African Journals Online (AJOL)

    A case of iatrogenic thermal injury in a newborn infant during resuscitation for perinatal asphyxia at a secondary health facility is described. The injury, with surface area coverage of about 4%, involved the lower limbs. This report highlights the poor newborn resuscitation skills of traditional medical practice. Un cas d'une ...

  13. Impact of location on outcome after penetrating colon injuries.

    Science.gov (United States)

    Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Zarzaur, Ben L; Shahan, Charles P; Parks, Nancy A; Fabian, Timothy C; Croce, Martin A

    2012-12-01

    Most studies examining suture line failure after penetrating colon injuries have focused on right- versus left-sided injuries. In our institution, operative decisions (resection plus anastomosis vs. diversion) are based on a defined management algorithm regardless of injury location. The purpose of this study was to evaluate the effect of injury location on outcomes after penetrating colon injuries. Consecutive patients with full thickness penetrating colon injuries for 13 years were stratified by age, injury location and mechanism, and severity of shock. According to the algorithm, patients with nondestructive injuries underwent primary repair. Destructive wounds underwent resection plus anastomosis in the absence of comorbidities or large preoperative or intraoperative transfusion requirements (>6 U of packed red blood cells); otherwise, they were diverted. Injury location was defined as ascending, transverse, descending (including splenic flexure), and sigmoid. Multivariable logistic regression was performed to determine whether injury location was an independent predictor of either morbidity or mortality. Four hundred sixty-nine patients were identified: 314 (67%) underwent primary repair and 155 (33%) underwent resection. Most injuries involved the transverse colon (39%), followed by the ascending colon (26%), the descending colon (21%), and the sigmoid colon (14%). Overall, there were 13 suture line failures (3%) and 72 abscesses (15%). Most suture line failures involved injuries to the descending colon (p = 0.06), whereas most abscesses followed injuries to the ascending colon (p = 0.37). Multivariable logistic regression failed to identify injury location as an independent predictor of either morbidity or mortality after adjusting for 24-hour transfusions, base excess, shock index, injury mechanism, and operative management. Injury location did not affect morbidity or mortality after penetrating colon injuries. Nondestructive injuries should be primarily

  14. Biomaterials in the repair of sports injuries

    Science.gov (United States)

    Ducheyne, Paul; Mauck, Robert L.; Smith, Douglas H.

    2012-08-01

    The optimal stimulation of tissue regeneration in bone, cartilage and spinal cord injuries involves a judicious selection of biomaterials with tailored chemical compositions, micro- and nanostructures, porosities and kinetic release properties for the delivery of relevant biologically active molecules.

  15. Alternative Approach to Traumatic Stensen’s Duct Injuries Accompanied by Glandular Involvement: Botulinum Toxin Injection to the Gland in Conjunction with Microsurgical Repair of the Duct in an Acute Setting

    OpenAIRE

    Mert Çalış; Zeynep Öz; Hakan Uzun; Burçe Özgen; Alp Çetin3; Ali Emre Aksu

    2017-01-01

    Objective: The aim of this study was to evaluate the long-term results of a simultaneous application of botulinum toxin to the parotid gland in conjunction with the microsurgical repair of the duct in an acute setting and to encourage using botulinum toxin as a first-line option to prevent future complications associated with glandular involvement. Material and Methods: Three patients who were referred to the Plastic Surgery Clinic by the emergency room of the Hacettepe University Hospita...

  16. The trypanocidal benznidazole promotes adaptive response to oxidative injury: Involvement of the nuclear factor-erythroid 2-related factor-2 (Nrf2) and multidrug resistance associated protein 2 (MRP2)

    International Nuclear Information System (INIS)

    Rigalli, Juan Pablo; Perdomo, Virginia Gabriela; Ciriaci, Nadia; Francés, Daniel Eleazar Antonio; Ronco, María Teresa; Bataille, Amy Michele; Ghanem, Carolina Inés; Ruiz, María Laura; Manautou, José Enrique; Catania, Viviana Alicia

    2016-01-01

    Oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. Benznidazole (BZL) is the only trypanocidal agent available for treatment of Chagas disease in endemic areas. Its use is associated with side effects, including increases in biomarkers of hepatotoxicity. However, BZL potential to cause oxidative stress has been poorly investigated. Here, we evaluated the effect of a pharmacologically relevant BZL concentration (200 μM) at different time points on redox status and the counteracting mechanisms in the human hepatic cell line HepG2. BZL increased reactive oxygen species (ROS) after 1 and 3 h of exposure, returning to normality at 24 h. Additionally, BZL increased glutathione peroxidase activity at 12 h and the oxidized glutathione/total glutathione (GSSG/GSSG + GSH) ratio that reached a peak at 24 h. Thus, an enhanced detoxification of peroxide and GSSG formation could account for ROS normalization. GSSG/GSSG + GSH returned to control values at 48 h. Expression of the multidrug resistance-associated protein 2 (MRP2) and GSSG efflux via MRP2 were induced by BZL at 24 and 48 h, explaining normalization of GSSG/GSSG + GSH. BZL activated the nuclear erythroid 2-related factor 2 (Nrf2), already shown to modulate MRP2 expression in response to oxidative stress. Nrf2 participation was confirmed using Nrf2-knockout mice in which MRP2 mRNA expression was not affected by BZL. In summary, we demonstrated a ROS increase by BZL in HepG2 cells and a glutathione peroxidase- and MRP2 driven counteracting mechanism, being Nrf2 a key modulator of this response. Our results could explain hepatic alterations associated with BZL therapy. - Highlights: • BZL triggers a redox imbalance in the human hepatic cell line HepG2. • Concomitantly BZL triggers compensatory mechanisms to alleviate the redox injury. • Response mechanisms comprise an enhanced glutathione peroxidase and MRP2 activity. • Transcription factor Nrf2 plays a key role orchestrating

  17. The trypanocidal benznidazole promotes adaptive response to oxidative injury: Involvement of the nuclear factor-erythroid 2-related factor-2 (Nrf2) and multidrug resistance associated protein 2 (MRP2)

    Energy Technology Data Exchange (ETDEWEB)

    Rigalli, Juan Pablo [Institute of Experimental Physiology (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg (Germany); Perdomo, Virginia Gabriela; Ciriaci, Nadia; Francés, Daniel Eleazar Antonio; Ronco, María Teresa [Institute of Experimental Physiology (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Bataille, Amy Michele [University of Connecticut, School of Pharmacy, Department of Pharmaceutical Sciences, Storrs, CT (United States); Ghanem, Carolina Inés [Institute of Pharmacological Investigations (ININFA-CONICET), University of Buenos Aires, Buenos Aires (Argentina); Ruiz, María Laura [Institute of Experimental Physiology (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Manautou, José Enrique [University of Connecticut, School of Pharmacy, Department of Pharmaceutical Sciences, Storrs, CT (United States); Catania, Viviana Alicia, E-mail: vcatania@fbioyf.unr.edu.ar [Institute of Experimental Physiology (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina)

    2016-08-01

    Oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. Benznidazole (BZL) is the only trypanocidal agent available for treatment of Chagas disease in endemic areas. Its use is associated with side effects, including increases in biomarkers of hepatotoxicity. However, BZL potential to cause oxidative stress has been poorly investigated. Here, we evaluated the effect of a pharmacologically relevant BZL concentration (200 μM) at different time points on redox status and the counteracting mechanisms in the human hepatic cell line HepG2. BZL increased reactive oxygen species (ROS) after 1 and 3 h of exposure, returning to normality at 24 h. Additionally, BZL increased glutathione peroxidase activity at 12 h and the oxidized glutathione/total glutathione (GSSG/GSSG + GSH) ratio that reached a peak at 24 h. Thus, an enhanced detoxification of peroxide and GSSG formation could account for ROS normalization. GSSG/GSSG + GSH returned to control values at 48 h. Expression of the multidrug resistance-associated protein 2 (MRP2) and GSSG efflux via MRP2 were induced by BZL at 24 and 48 h, explaining normalization of GSSG/GSSG + GSH. BZL activated the nuclear erythroid 2-related factor 2 (Nrf2), already shown to modulate MRP2 expression in response to oxidative stress. Nrf2 participation was confirmed using Nrf2-knockout mice in which MRP2 mRNA expression was not affected by BZL. In summary, we demonstrated a ROS increase by BZL in HepG2 cells and a glutathione peroxidase- and MRP2 driven counteracting mechanism, being Nrf2 a key modulator of this response. Our results could explain hepatic alterations associated with BZL therapy. - Highlights: • BZL triggers a redox imbalance in the human hepatic cell line HepG2. • Concomitantly BZL triggers compensatory mechanisms to alleviate the redox injury. • Response mechanisms comprise an enhanced glutathione peroxidase and MRP2 activity. • Transcription factor Nrf2 plays a key role orchestrating

  18. Lightning Strike in Pregnancy With Fetal Injury.

    Science.gov (United States)

    Galster, Kellen; Hodnick, Ryan; Berkeley, Ross P

    2016-06-01

    Injuries from lightning strikes are an infrequent occurrence, and are only rarely noted to involve pregnant victims. Only 13 cases of lightning strike in pregnancy have been previously described in the medical literature, along with 7 additional cases discovered within news media reports. This case report presents a novel case of lightning-associated injury in a patient in the third trimester of pregnancy, resulting in fetal ischemic brain injury and long-term morbidity, and reviews the mechanics of lightning strikes along with common injury patterns of which emergency providers should be aware. Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  19. Traumatic Brain Injury Inpatient Rehabilitation

    Science.gov (United States)

    Im, Brian; Schrer, Marcia J.; Gaeta, Raphael; Elias, Eileen

    2010-01-01

    Traumatic brain injuries (TBI) can cause multiple medical and functional problems. As the brain is involved in regulating nearly every bodily function, a TBI can affect any part of the body and aspect of cognitive, behavioral, and physical functioning. However, TBI affects each individual differently. Optimal management requires understanding the…

  20. Diagnosis of climbing related overuse injuries

    International Nuclear Information System (INIS)

    Klauser, A.; Frauscher, F.; Helweg, G.; Nedden, D. zur; Hochholzer, T.; Kramer, J.

    2002-01-01

    Sport climbing shows an enormous increase in participation, evolving to more popularity, including even school sport activity on high standards. Therefore the number of climbing related injuries is increasing and becomes a more frequently encountered medical problem. Typical climbing associated injuries involve predominantly the upper limb. Overuse injuries are the most common climbing related injuries.The clinical examination is the first line investigation, which is often limited especially in the acute phase. However, an exact diagnosis is desireable for therapeutic management. Imaging modalities have shown to be capable for detection of climbing related injuries. An overview about the current use of x-ray, ultrasound and magnetic resonance imaging in different climbing related overuse injuries is presented. (orig.) [de

  1. Musculoskeletal injuries description of an under-recognized injury problem among military personnel.

    Science.gov (United States)

    Hauret, Keith G; Jones, Bruce H; Bullock, Steven H; Canham-Chervak, Michelle; Canada, Sara

    2010-01-01

    Although injuries are recognized as a leading health problem in the military, the size of the problem is underestimated when only acute traumatic injuries are considered. Injury-related musculoskeletal conditions are common in this young, active population. Many of these involve physical damage caused by micro-trauma (overuse) in recreation, sports, training, and job performance. The purpose of this analysis was to determine the incidence of injury-related musculoskeletal conditions in the military services (2006) and describe a standardized format in which to categorize and report them. The subset of musculoskeletal diagnoses found to be injury-related in previous military investigations was identified. Musculoskeletal injuries among nondeployed, active duty service members in 2006 were identified from military medical surveillance data. A matrix was used to report and categorize these conditions by injury type and body region. There were 743,547 injury-related musculoskeletal conditions in 2006 (outpatient and inpatient, combined), including primary and nonprimary diagnoses. In the matrix, 82% of injury-related musculoskeletal conditions were classified as inflammation/pain (overuse), followed by joint derangements (15%) and stress fractures (2%). The knee/lower leg (22%), lumbar spine (20%), and ankle/foot (13%) were leading body region categories. When assessing the magnitude of the injury problem in the military services, injury-related musculoskeletal conditions should be included. When these injuries are combined with acute traumatic injuries, there are almost 1.6 million injury-related medical encounters each year. The matrix provides a standardized format to categorize these injuries, make comparisons over time, and focus prevention efforts on leading injury types and/or body regions. Published by Elsevier Inc.

  2. An unusual presentation of whiplash injury: long thoracic and spinal accessory nerve injury

    Science.gov (United States)

    Omar, N.; Srinivasan, M. S.

    2007-01-01

    Whiplash injuries from motor vehicle accidents are very common. The usual presentation and course of this condition normally results in resolution of symptoms within a few weeks. Brachial plexus traction injuries without any bone or joint lesion of the cervical spine have been reported before. We report a case where a gentleman was involved in a rear end vehicle collision, sustained a whiplash injury and was later found to have a long thoracic nerve palsy and spinal accessory nerve palsy. Although isolated injuries of both nerves following a whiplash injury have been reported, combined injury of the two nerves following a whiplash injury is very uncommon and is being reported for the first time. PMID:17587067

  3. Preventing dance injuries: current perspectives

    Directory of Open Access Journals (Sweden)

    Russell JA

    2013-09-01

    Full Text Available Jeffrey A Russell Division of Athletic Training, School of Applied Health Sciences and Wellness, Ohio University, Athens, OH, USA Abstract: Dancers are clearly athletes in the degree to which sophisticated physical capacities are required to perform at a high level. The standard complement of athletic attributes – muscular strength and endurance, anaerobic and aerobic energy utilization, speed, agility, coordination, motor control, and psychological readiness – all are essential to dance performance. In dance, as in any athletic activity, injuries are prevalent. This paper presents the research background of dance injuries, characteristics that distinguish dance and dancers from traditional sports and athletes, and research-based perspectives into how dance injuries can be reduced or prevented, including the factors of physical training, nutrition and rest, flooring, dancing en pointe, and specialized health care access for dancers. The review concludes by offering five essential components for those involved with caring for dancers that, when properly applied, will assist them in decreasing the likelihood of dance-related injury and ensuring that dancers receive optimum attention from the health care profession: (1 screening; (2 physical training; (3 nutrition and rest; (4 specialized dance health care; and (5 becoming acquainted with the nature of dance and dancers. Keywords: dance, injuries, injury prevention, fitness, wellness, health

  4. Groin injuries in sports medicine.

    Science.gov (United States)

    Tyler, Timothy F; Silvers, Holly J; Gerhardt, Michael B; Nicholas, Stephen J

    2010-05-01

    An in-season groin injury may be debilitating for the athlete. Proper diagnosis and identification of the pathology are paramount in providing appropriate intervention. Furthermore, an adductor strain that is treated improperly can become chronic and career threatening. Any one of the 6 muscles of the adductor muscle group can be involved. The degree of injury can range from a minor strain (grade 1), where minimal playing time is lost, to a severe strain (grade 3), in which there is complete loss of muscle function. Persistent groin pain and muscle imbalance may lead to athletic pubalgia. Relevant studies were identified through a literature search of MEDLINE and the Cochrane database from 1990 to 2009, as well as a manual review of reference lists of identified sources. Ice hockey and soccer players seem particularly susceptible to adductor muscle strains. In professional ice hockey and soccer players throughout the world, approximately 10% to 11% of all injuries are groin strains. These injuries have been linked to hip muscle weakness, a previous injury to that area, preseason practice sessions, and level of experience. This injury may be prevented if these risk factors are addressed before each season. Despite the identification of risk factors and strengthening intervention for athletes, adductor strains continue to occur throughout sport. If groin pain persists, the possibility of athletic pubalgia needs to be explored, because of weakening or tears in the abdominal wall muscles. A diagnosis is confirmed by exclusion of other pathology.

  5. Traumatic Mitral Valve and Pericardial Injury

    Directory of Open Access Journals (Sweden)

    Nissar Shaikh

    2013-01-01

    Full Text Available Cardiac injury after blunt trauma is common but underreported. Common cardiac trauma after the blunt chest injury (BCI is cardiac contusion; it is very rare to have cardiac valve injury. The mitral valve injury during chest trauma occurs when extreme pressure is applied at early systole during the isovolumic contraction between the closure of the mitral valve and the opening of the aortic valve. Traumatic mitral valve injury can involve valve leaflet, chordae tendineae, or papillary muscles. For the diagnosis of mitral valve injury, a high index of suspicion is required, as in polytrauma patients, other obvious severe injuries will divert the attention of the treating physician. Clinical picture of patients with mitral valve injury may vary from none to cardiogenic shock. The echocardiogram is the main diagnostic modality of mitral valve injuries. Patient’s clinical condition will dictate the timing and type of surgery or medical therapy. We report a case of mitral valve and pericardial injury in a polytrauma patient, successfully treated in our intensive care unit.

  6. Epidemiology of Figure Skating Injuries: A Review of the Literature.

    Science.gov (United States)

    Han, Julie S; Geminiani, Ellen T; Micheli, Lyle J

    2018-05-01

    As the popularity and technical demands of figure skating increase, so will the number of athletes presenting with sport-related problems. Searches were performed across PubMed from 1980 to 2017. The keywords searched were skating, skaters, incidence, and injuries. The search was limited to English-language articles and human participants. Relevant articles were cross-referenced. Clinical review. Level 5. Previous studies suggest an increase in incidence of figure skating injuries from 1982 to 2003. When combining all disciplines of figure skating, there is a similar proportion of acute and overuse injuries. Within disciplines, overuse injuries appear to be more common in singles skating, while acute injuries are more common in pairs skating, ice dancing, and synchronized skating. Lower extremity injuries are more common than upper extremity injuries in all disciplines, and pairs skating accounts for the majority of upper extremity injuries. Ankle sprains are the most common skating injury, and patellar tendinitis is the most common overuse injury across all disciplines. Stress fractures are the most common overuse injury in female singles skaters. The predominance of overuse injuries in singles disciplines reflects their increasing technical difficulty, with more difficult jumps and longer training hours. Partner disciplines are more likely to involve acute injuries and upper extremity injuries due to high-risk throws and lifts. Emphasis should be placed on properly fitting skating boots, intrinsic foot and ankle strengthening, and lower extremity flexibility, which may prevent many of the common lower extremity and back injuries in figure skating.

  7. A Survey of Injuries Affecting Pre-Professional Ballet Dancers.

    Science.gov (United States)

    Caine, Dennis; Bergeron, Glen; Goodwin, Brett J; Thomas, Jessica; Caine, Caroline G; Steinfeld, Sam; Dyck, Kevin; André, Suzanne

    2016-01-01

    A cross-sectional design was employed retrospectively to evaluate injuries self-reported by 71 pre-professional ballet dancers over one season. Some of the descriptive findings of this survey were consistent with those of previous research and suggest particular demographic and injury trends in pre-professional ballet. These results include gender distribution, mean age and age range of participants, training hours, injury location, acute versus overuse injuries, as well as average number of physiotherapy treatments per dancer. Other results provide information that was heretofore unreported or inconsistent with previous investigations. These findings involved proportion of dancers injured, average number of injuries per dancer, overall injury incidence during an 8.5 month period, incidence rate by technique level, mean time loss per injury, proportion of recurrent injury, and activity practiced at time of injury. The results of univariate analyses revealed several significant findings, including a decrease in incidence rate of injury with increased months of experience in the pre-professional program, dancers having lower injury risk in rehearsal and performance than in class, and a reduced risk of injury for dancers at certain technique levels. However, only this latter finding remained significant in multivariate analysis. The results of this study underscore the importance of determining injury rates by gender, technique level, and activity setting in addition to overall injury rates. They also point to the necessity of looking at both overall and individual dancer-based injury risks.

  8. rLj-RGD3, a Novel Recombinant Toxin Protein from Lampetra japonica, Protects against Cerebral Reperfusion Injury Following Middle Cerebral Artery Occlusion Involving the Integrin-PI3K/Akt Pathway in Rats.

    Directory of Open Access Journals (Sweden)

    Qian Lu

    (Akt, PKB, caspase-3 and Bcl-2 in the brain using western blot analysis and RT-PCR assays. The research protocol was approved by the Institutional Ethics Committee of Dalian Medical University.The behavioral scores and cerebral infarct volumes of the rLj-RGD3 groups were markedly lower at 4 and 24 h/RF. The rLj-RGD3 protein significantly ameliorated pathological changes in the brain and reduced the number of apoptotic neurons. Furthermore, the FAK and PI3K/Akt pathways were activated. rLj-RGD3 significantly increased the expression of FAK, p-FAK and Bcl-2 proteins. In contrast, caspase-3 expression was inhibited.We conclude that recombinant Lampetra japonica RGD-peptide (rLj-RGD3 exerts a protective effect against cerebral ischemia/reperfusion injury in the brain. In addition, the mechanism of this protection is associated with the activation of the integrin-PI3K/Akt pathway. These results provide a theoretical foundation and an experimental basis for using RGD peptides as novel drugs for treating ischemic cerebral vascular diseases in addition to promoting the research and development of marine biotechnology drugs.

  9. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... About Media Donate Spinal Cord Injury Medical Expert Videos ... Home Kim Eberhardt Muir, MS Coping with a New Injury Robin Dorman, PsyD Sex and Fertility After Spinal Cord Injury Diane M. ...

  10. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... spinal cord injury? play_arrow What kind of surgery is common after a spinal cord injury? play_ ... How soon after a spinal cord injury should surgery be performed? play_arrow Is it common to ...

  11. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... L Sarah Harrison, OT Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury ... a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? ...

  12. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences ...

  13. Radiotherapy injuries in children

    International Nuclear Information System (INIS)

    Kalifa, G.; Bennet, J.; Couanet, D.; Masselot, J.

    1985-01-01

    Side effects of radiotherapy in pediatrics are reviewed including bone injuries and radio-induced bone tumors; nervous system injuries with emphasis on hypothalamus, pituitary gland, brain and spinal cord; lung, digestive system and urinary tract injuries [fr

  14. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury ... Jennifer Piatt, PhD David Chen, MD Read Bio Medical Director, Spinal Cord Injury Rehabilitation Program, Rehabilitation Institute ...

  15. Facial Sports Injuries

    Science.gov (United States)

    ... Marketplace Find an ENT Doctor Near You Facial Sports Injuries Facial Sports Injuries Patient Health Information News ... should receive immediate medical attention. Prevention Of Facial Sports Injuries The best way to treat facial sports ...

  16. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 ... arrow What is the “Spinal Cord Injury Model Systems” program? play_arrow What are the most promising ...

  17. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... RN Pediatric Injuries Pediatric Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation ... Rogers, PT Recreational Therapy after Spinal Cord Injury Jennifer Piatt, PhD David Chen, MD Read Bio Medical ...

  18. Preventing Knee Injuries

    Science.gov (United States)

    ... Our Newsletter Donate Blog Skip breadcrumb navigation Preventing Knee Injuries Knee injuries in children and adolescent athletes ... this PDF Share this page: WHAT ARE COMMON KNEE INJURIES? Pain Syndromes One of the most common ...

  19. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation Sara Klaas, MSW Transitions for Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW Rehabilitation ...

  20. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injury 101 David Chen, MD Preventing Pressure Sores Mary Zeigler, MS Transition from Hospital to ... a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? ...

  1. Imaging of orthopedic sports injuries

    International Nuclear Information System (INIS)

    Vanhoenacker, F.M.; Gielen, J.L.; Maas, M.

    2007-01-01

    This volume provides an updated review of imaging abnormalities in orthopedic sports injuries. The first part of the book contains background information on relevant basic science and general imaging principles in sports traumatology. The second part comprises a topographic discussion of sports injuries. Each chapter highlights the merit of different imaging techniques, focused on a specific clinical problem. In the third part, natural history, monitoring and follow-up by imaging are discussed. This well-illustrated book will be of value for musculoskeletal radiologists, orthopedic surgeons, sports physicians and everyone else involved in sports medicine. (orig.)

  2. MR imaging of rectus femoris origin injuries

    International Nuclear Information System (INIS)

    Ouellette, Hugue; Thomas, Bijoy J.; Nelson, Erik; Torriani, Martin

    2006-01-01

    To describe the MR imaging findings of acute and chronic rectus femoris origin (RFO) injuries. A retrospective review of pelvic and hip MR imaging procedures was performed over a 4-year period for detection of cases with injuries to the RFO. Subjects were classified as having either acute or chronic symptoms. MR imaging studies, radiographs, CT scans, radiology reports, medical records, and operative notes were reviewed. Imaging analysis was directed to assess injuries affecting the direct and indirect heads of the RFO. Concurrent osseous, cartilaginous and musculotendinous injuries were tabulated. The incidence of RFO injuries on MR imaging was 0.5% (17/3160). With the exception of one case of anterior inferior iliac spine apophysis avulsion and partial tear of the direct head of RFO, all subjects had indirect head of RFO injuries (acute injury 8/9, chronic injury 8/8). Partial tear of the direct head of RFO was less frequently seen (acute injury 3/9, chronic injury 2/8). Partial tears of the conjoint tendon were least frequent (acute 1/9, chronic 2/8). No full-thickness tears of the RFO were noted. Associated labral tears were seen in only one case, with no other concomitant abnormality of the articular cartilage or surrounding soft tissues. All RFO injuries were treated non-operatively. Injuries of the RFO are uncommon on MR examinations of pelvis/hips and may occur in a sequence progressing from indirect head injury to involvement of direct head and conjoint tendon in more severe cases. (orig.)

  3. Preventing unintentional injury in children and adolescents--the importance of local injury data collection.

    LENUS (Irish Health Repository)

    O'Carroll, C

    2012-02-01

    We sought to prospectively study all injuries in children and adolescents up to 16 years of age presenting to a regional Emergency Department (ED), to ascertain detailed injury patterns and to use this data to recommend injury prevention priorities. Electronic injury surveillance was prospectively collected over a 10 year period (1997-2007) in a hospital with a paediatric catchment population of 75,000 in a region with pockets of high social deprivation. All fatalities were obtained from data provided by the Central Statistics Office (CSO). Over a 10 year period, there were 31 fatalities, 5,408 admissions and 40,817 new attendances due to injury. Males outnumbered females in a 3:2 ratio. Of all injuries 24,317 (60%) occurred at home. Peak injury presentation time was in the evening between 18:00 and 20:00. Minor injuries (bruises, minor head injuries, lacerations and sprains) accounted for 32,456 (80%) of total. Fractures resulting from high falls (n=1,194) tended to result from bunk beds, staircases, horses, walls and playground equipment. Burns (n=630) involved hot liquids (tea, coffee), hot bath water, hot cooking oil and hot cooking plates. Pedestrian injuries (n=251) were predominantly \\'dart outs\\' in urban areas. Car passenger injuries (n=869) showed low rates of documented car restraint use. Poisonings (n= 1,153) were predominantly medicinal products. Cyclist injuries (n=477) indicated low documented use of appropriate helmet wear. Prevention priorities should focus on home injuries, hot liquid burn and scald injuries and high falls from walls, beds and playground equipment. To prevent road-related injuries and deaths, further legislation, urban planning and greater police enforcement is required.

  4. Mild Traumatic Brain Injury

    Science.gov (United States)

    ... mild Traumatic Brain Injury Resilience Families with Kids Depression Families & Friendships Tobacco Life Stress Spirituality Anger Physical Injury Stigma Health & Wellness Work Adjustment Community Peer-2-Peer Forum ...

  5. Baseball and softball injuries.

    Science.gov (United States)

    Wang, Quincy

    2006-05-01

    Baseball and softball injuries can be a result of both acute and overuse injuries. Soft tissue injuries include contusions, abrasions, and lacerations. Return to play is allowed when risk of further injury is minimized. Common shoulder injuries include those to the rotator cuff, biceps tendon, and glenoid labrum. Elbow injuries are common in baseball and softball and include medial epicondylitis, ulnar collateral ligament injury, and osteochondritis dissecans. Typically conservative treatment with relative rest, medication, and a rehabilitation program will allow return to play. Surgical intervention may be needed for certain injuries or conservative treatment failure.

  6. Spinal cord injury and its association with blunt head trauma

    OpenAIRE

    Paiva, Wellingson S; Oliveira, Arthur MP; Andrade, Almir F; Amorim, Robson LO; Lourenço, Leonardo JO; Teixeira, Manoel J

    2011-01-01

    Wellingson S Paiva, Arthur MP Oliveira, Almir F Andrade, Robson LO Amorim, Leonardo JO Lourenço, Manoel J TeixeiraDivision of Neurosurgery, University of São Paulo, BrazilBackground: Severe and moderate head injury can cause misdiagnosis of a spinal cord injury, leading to devastating long-term consequences. The objective of this study is to identify risk factors involving spine trauma and moderate-to-severe brain injury.Methods: A prospective study involving 1617 patien...

  7. Facial firework injury: a case series.

    Science.gov (United States)

    Tadisina, Kashyap K; Abcarian, Ariane; Omi, Ellen

    2014-07-01

    Fireworks are used to celebrate a variety of religious, patriotic, and cultural holidays and events around the world. Fireworks are common in the United States, with the most popular holiday for their use being national Independence Day, also known as July Fourth. The use of fireworks within the context of celebrations and holidays presents the ideal environment for accidents that lead to severe and dangerous injuries. Injuries to the face from explosions present a challenging problem in terms of restoring ideal ocular, oral, and facial function. Despite the well documented prevalence of firework use and injury, there is a relatively large deficit in the literature in terms of firework injury that involves the face. We present a unique case series that includes 4 adult male patients all with severe firework injuries to the face that presented at an urban level 1 trauma center. These four patients had an average age of 26.7 years old and presented within 5 hours of each other starting on July Fourth. Two patients died from their injuries and two patients underwent reconstructive surgical management, one of which had two follow up surgeries. We explore in detail their presentation, management, and subsequent outcomes as an attempt to add to the very limited data in the field of facial firework blast injury. In addition, the coincidence of their presentation within the same 5 hours brings into question the availability of the fireworks involved, and the possibility of similar injuries related to this type of firework in the future.

  8. Facial Firework Injury: A Case Series

    Directory of Open Access Journals (Sweden)

    Kashyap Tadisina

    2014-07-01

    Full Text Available Fireworks are used to celebrate a variety of religious, patriotic, and cultural holidays and events around the world. Fireworks are common in the United States, with the most popular holiday for their use being national Independence Day, also known as July Fourth. The use of fireworks within the context of celebrations and holidays presents the ideal environment for accidents that lead to severe and dangerous injuries. Injuries to the face from explosions present a challenging problem in terms of restoring ideal ocular, oral, and facial function. Despite the well documented prevalence of firework use and injury, there is a relatively large deficit in the literature in terms of firework injury that involves the face. We present a unique case series that includes 4 adult male patients all with severe firework injuries to the face that presented at an urban level 1 trauma center. These four patients had an average age of 26.7 years old and presented within 5 hours of each other starting on July Fourth. Two patients died from their injuries and two patients underwent reconstructive surgical management, one of which had two follow up surgeries. We explore in detail their presentation, management, and subsequent outcomes as an attempt to add to the very limited data in the field of facial firework blast injury. In addition, the coincidence of their presentation within the same 5 hours brings into question the availability of the fireworks involved, and the possibility of similar injuries related to this type of firework in the future.

  9. Holiday ornament-related injuries in children.

    Science.gov (United States)

    Kimia, Amir; Lee, Lois; Shannon, Michael; Capraro, Andrew; Mays, Donald; Johnston, Patrick; Hummel, David; Shuman, Margot

    2009-12-01

    Holiday ornament injuries in children have not been well documented in the medical literature. Our aim was to investigate the patterns of injuries sustained from these ornaments as a first measure toward prevention. This was a retrospective cohort analysis of all patients examined in an urban pediatric emergency department over a 13-year period ending in March 2008 for holiday ornament-related injuries. Cases were identified using a computer-assisted text query followed by a manual chart review. Data collected from each chart included the child's age, sex, injury characteristics, physical examination findings, radiographic imaging, interventions, and disposition. To analyze injury rates over the years, we used a multiplicative Poisson model allowing varying exposures. Over the study period, we identified 76 eligible patients. The median age was 2 years (interquartile range, 1.17-3.3 years); 44.7% were female. Forty-three of the 76 cases (53.9%) involved ingestions: 35 were of holiday ornaments, and 8 were of light bulbs. All but one of these ornaments were made of glass. In 28%, there was an associated bleed either from the mouth or as a delayed gastrointestinal bleed. Other patients experienced lacerations (27.6%), eye injuries (5.1%), and minor electrocution injury (2.5%). Imaging was performed in 85%. A subspecialty consult was obtained in 23%, primarily addressing a foreign body ingestion or removal after skin exploration. The incidence rate has not changed over the years. Holiday ornament-related injuries primarily involve foreign body ingestions and glass-related injuries. Over half of the injuries involved small light bulbs and ornaments made of glass placed at the level a toddler can reach. Pediatricians are advised to discuss these points with families during holiday season.

  10. Pregnancy outcome in women involved in road traffic accidents

    African Journals Online (AJOL)

    bbshehu

    December, 2002, was undertaken to determine the incidence, type of injury and pregnancy outcome. Results: One hundred and forty nine women ... road traffic accidents.6 Pregnant mothers could also be involved in road traffic accident.6 ... use of helmet lowers the risk of traumatic brain injury. 11 and a case is made for the ...

  11. Radiation injury

    International Nuclear Information System (INIS)

    Hubner, K.F.

    1988-01-01

    Radiation accidents and incidents continue to be of great interest and concern to the public. Issues such as the threat of nuclear war, the Chernobyl reactor accident, or reports of sporadic incidences of accidental radiation exposure keep this interest up and maintain a high level of fear among the public. In this climate of real concern and radiation phobia, physicians should not only be prepared to answer questions about acute or late effects of ionizing radiation, but also be able to participate in the initial assessment and management of individuals who have been exposed to ionizing radiation or contaminated with radioactive material. Some of the key facts about radiation injury and its medical treatment are discussed by the author

  12. The National Basketball Association eye injury study.

    Science.gov (United States)

    Zagelbaum, B M; Starkey, C; Hersh, P S; Donnenfeld, E D; Perry, H D; Jeffers, J B

    1995-06-01

    To investigate the epidemiology of eye injuries sustained by professional basketball players in the National Basketball Association (NBA). A prospective study involving all NBA athletes who sustained eye injuries between February 1, 1992, and June 20, 1993, was conducted. Twenty-seven NBA team athletic trainers, physicians, and ophthalmologists were provided data forms to complete for any player examined for an eye injury. Practice and game exposures during the preseason, regular season, playoffs, and championships were included. Of the 1092 injuries sustained by NBA players during the 17-month period, 59 (5.4%) involved the eye and adnexa. Eighteen (30.5%) of the injuries occurred while the player was in the act of rebounding, and 16 (27.1%) while the player was on offense. The most common diagnoses included 30 abrasions or lacerations to the eyelid (50.9%), 17 contusions (edema and/or ecchymosis) to the eyelid or periorbital region (28.8%), and seven corneal abrasions (11.9%). There were three orbital fractures (5.1%). Most injuries were caused by fingers (35.6%) or elbows (28.8%). Nine players (15.3%) missed subsequent games because of their injury. Fifty-seven players (96.6%) were not wearing protective eyewear at the time of injury. The incidence of eye injuries in NBA players during the 17-month period was 1.44 per 1000 game exposures. Frequent physical contact in professional basketball players leaves them at great risk for sustaining eye injuries. To prevent these injuries, protective eyewear is recommended.

  13. [Sports injuries of the face].

    Science.gov (United States)

    Chrzavzez, G; Chrzavzez, J P; D'Erceville, T; Kharrat, N; Barbillon, C; Pilz, F

    1984-01-01

    Of 249 patients with facial injuries admitted to the Department of Stomatology and Maxillofacial Surgery, Hôpital Bel Air, Thionville, France, between 1981 and 1982, 45 (18%) were cases of injury from sporting activities. The particular characteristics of the latter lesions were their predominance in males, their increased seasonal frequency in spring and early summer, the high incidence of damage to the nasal pyramid and maxillomalar complex, and the fact that the most implicated sport was football (71% of cases). Whereas most accidents resulted in relatively minor lesions, three cases--including two from riding--involved severe, complex injuries comparable to those seen in certain car accidents. Findings in this series confirm the natural "bumper" property of the face. Emphasis is placed on the importance of well-conducted training, and the need to eliminate consideration of sport as a means for expressing aggressiveness that is not always possible in daily life.

  14. Preventing gun injuries in children.

    Science.gov (United States)

    Crossen, Eric J; Lewis, Brenna; Hoffman, Benjamin D

    2015-02-01

    Firearms are involved in the injury and death of a large number of children each year from both intentional and unintentional causes. Gun ownership in homes with children is common, and pediatricians should incorporate evidence-based means to discuss firearms and protect children from gun-related injuries and violence. Safe storage of guns, including unloaded guns locked and stored separately from ammunition, can decrease risks to children, and effective tools are available that pediatricians can use in clinical settings to help decrease children's access to firearms. Furthermore, several community-based interventions led by pediatricians have effectively reduced firearm-related injury risks to children. Educational programs that focus on children's behavior around guns have not proven effective. © American Academy of Pediatrics, 2015. All rights reserved.

  15. Hip and Groin Injuries in Baseball Players.

    Science.gov (United States)

    Mlynarek, Ryan A; Coleman, Struan H

    2018-03-01

    To discuss the clinical significance of the most common hip and groin injuries in baseball players, as well as an algorithmic approach to diagnosis and treatment of these injuries. (a) Limitations in throwing velocity, pitch control, and bat swing speed may be secondary to decreased mobility and strength within the proximal kinetic chain, which must harness power from the lower extremities and core. (b) Approximately 5.5% of all baseball injuries per year involve the hip/groin and may lead to a significant amount of time spent on the disabled list. Injuries involving the hip and groin are relatively common in baseball players. Our knowledge of the mechanics of overhead throwing continues to evolve, as does our understanding of the contribution of power from the lower extremities and core. It is paramount that the team physician be able to accurately diagnose and treat injuries involving the hip/groin, as they may lead to significant disability and inability to return to elite levels of play. This review focuses on hip- and groin-related injuries in the baseball player, including femoroacetabular impingement, core muscle injury, and osteitis pubis.

  16. Sports injuries in physical education teacher education students.

    Science.gov (United States)

    Goossens, L; Verrelst, R; Cardon, G; De Clercq, D

    2014-08-01

    Sports injuries could be highly detrimental to the career of a physical education teacher education (PETE) student. To enable the development of future sports injury prevention programs, sports injuries in 128 first-year academic bachelor PETE students were registered prospectively during one academic year. Common risk factors for sports injuries, taken from the literature, were also evaluated by means of logistic regression analysis. We found an incidence rate of 1.91 and an injury risk of 0.85, which is higher than generally found in a sports-active population. Most injuries involved the lower extremities, were acute, newly occurring injuries, and took place in non-contact situations. More than half of all injuries lead to an inactivity period of 1 week or more and over 80% of all injuries required medical attention. A major part of these injuries happened during the intracurricular sports classes. Few differences were seen between women and men. A history of injury was a significant risk factor (P = 0.018) for the occurrence of injuries, and performance of cooling-down exercises was significantly related to a lower occurrence of ankle injuries (P = 0.031). These data can inform future programs for the prevention of sports injuries in PETE students. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Severe ocular injuries in Greek children.

    Science.gov (United States)

    Mela, Ephigenia K; Georgakopoulos, Constantinos D; Georgalis, Athanasios; Koliopoulos, John X; Gartaganis, Sotirios P

    2003-02-01

    To determine the epidemiological characteristics of severe eye injuries in childhood, in a mixed urban and rural Greek setting. Retrospective analysis of 95 cases (103 eyes) of eye injuries in children younger than 17 years of age admitted to the Department of Ophthalmology, University Hospital of Patras, Greece, during a five-year period. The data were analyzed with respect to age, sex, type, cause and mode of injury, method of management, duration of hospitalization and final visual deficit. The average age was 9.8 years and males were involved in 80% of the cases. The most common type of eye injury was mechanical closed-globe injury (71.8%). Mechanical open-globe injuries were found in 21.3% of the eyes, while burns comprised 6.7% of the injuries. Most injuries were agent-related, with blows and falls being responsible most often. Multiple operations were part of the treatment in 11.6% of the eyes; 14.5% of the eyes were blinded and 15.5% had significant final visual acuity loss. These hospital-based data suggest that there is a need for health education of both parents and children, since some injuries in children could easily have been prevented.

  18. Self-injurious behavior in anorexia nervosa.

    Science.gov (United States)

    Favaro, A; Santonastaso, P

    2000-08-01

    Recent reports have postulated the existence of two different types of self-injurious behavior: impulsive and compulsive. The aim of the present study is to analyze the dimensionality of self-injurious behavior and to study the link between self-injurious behavior and clinical features in anorexia nervosa. The study involved 236 consecutive patients with anorexia nervosa, diagnosed by DSM-IV criteria. Subjects were evaluated by means of a semistructured interview and self-reported questionnaires, such as the Eating Disorders Inventory and Hopkins Symptom Checklist. A principal component analysis was used to study the dimensionality of different types of self-injurious behavior, including purging. Our findings confirm the distinction between impulsive and compulsive self-injurious behavior. The dimensions appear to be represented as a continuum in both the anorexia nervosa diagnostic subgroups. A third distinct dimension emerged that included self-induced vomiting and laxative/diuretics abuse. Childhood sexual abuse and anxiety significantly predict the presence of impulsive self-injury, whereas obsessionality and age predict compulsive self-injury. The coexistence of a positive score on both dimensions of self-injurious behavior was the strongest predictor of treatment dropout. The present study highlights the importance of self-injurious behavior; it should be given due consideration in future outcome studies on anorexia nervosa

  19. Musculoskeletal injuries among Malaysian badminton players.

    Science.gov (United States)

    Shariff, A H; George, J; Ramlan, A A

    2009-11-01

    The purpose of this study was to investigate the pattern of musculoskeletal injuries sustained by Malaysian badminton players. This is a retrospective case notes review of all badminton players who attended the National Sports Institute (NSI) Clinic, Kuala Lumpur, Malaysia, and were diagnosed with musculoskeletal injuries. In a two and a half year period, from January 2005 to June 2007, 469 musculoskeletal injuries were diagnosed among badminton players at the NSI Clinic. The mean age of the players who attended the clinic was 19.2 (range 13-52) years. Approximately 60 percent of the injuries occurred in players younger than 20 years of age. The majority of injuries (91.5 percent) were categorised as mild overuse injury and mostly involved the knee. The majority of the injuries sustained by badminton players in this study were due to overuse, primarily in the knee. The majority of the injuries were diagnosed in younger players and occurred during training/practice sessions. There was no difference in terms of incidence and types of injuries between the genders.

  20. Too many pediatric trampoline injuries.

    Science.gov (United States)

    Furnival, R A; Street, K A; Schunk, J E

    1999-05-01

    Recent reports note a dramatic increase in the number of pediatric trampoline injuries (PTI) during the past several years. In 1996, the US Consumer Product Safety Commission estimates that 83 000 patients received treatment for trampoline injuries in US hospital emergency departments (EDs), and that approximately 75% of these patients were trampolines accounted for 99% of PTI. Most injuries (66%) occurred on the trampoline, 28% resulted from falls off, and 4% from imaginative mechanisms. One hundred eleven patients (15%) suffered severe injury (1990 Abbreviated Injury Scale value >/=3), usually of an extremity (89 out of 111). Fractures occurred in 324 patients (45%). Spinal injuries were common (12%), including 7 patients with cervical or thoracic fractures, and 1 with C7 paraplegia. Fractures were more frequently associated with falls off the trampoline, whereas spinal injuries more frequently occurred on the trampoline. Eighty patients (11%) required prehospital medical transport to our ED, 584 (80%) had ED radiographs, and 382 (53%) required pediatric surgical subspecialty involvement. Seventeen percent of PTI patients (125 out of 727) were admitted to the hospital, including 9 to the pediatric intensive care unit; 99 (14%) required one or more operations. Mean hospital stay was 2 days (range, 1-63 days); 24 stays (19%) were for >/=3 days. We estimate that the hospital charges for the acute medical care of PTI study patients at our institution totaled approximately $700 000. PTI are dramatically increasing in number, and result in considerable childhood morbidity. Most PTI occur on privately owned trampolines. Few, if any, safety recommendations for the trampoline are followed. We support recommendations for a ban on the recreational, school, and competitive pediatric use of trampolines.

  1. Mountain biking injuries in children and adolescents.

    Science.gov (United States)

    Aleman, Kylee B; Meyers, Michael C

    2010-01-01

    Over the last decade, the sport of mountain biking has experienced extensive growth in youth participation. Due to the unpredictable nature of outdoor sport, a lack of rider awareness and increased participation, the number of injuries has unnecessarily increased. Many believe that the actual incidence of trauma in this sport is underestimated and is just the 'tip of the iceberg'. The most common mechanism of injury is usually attributed to downhill riding and forward falling. Although rare, this type of fall can result in serious cranial and thoraco-abdominal trauma. Head and neck trauma continue to be documented, often resulting in concussions and the possibility of permanent neurological sequelae. Upper limb injuries range from minor dermal abrasions, contusions and muscular strains to complex particular fracture dislocations. These are caused by attempting to arrest the face with an outstretched hand, leading to additional direct injury. Common overuse injuries include repeated compression from the handlebars and vibration leading to neurovascular complications in the hands. Along with reports of blunt abdominal trauma and lumbar muscle strains, lower extremity injuries may include various hip/pelvic/groin contusions, patellofemoral inflammation, and various muscle strains. The primary causes of mountain biking injuries in children and adolescents include overuse, excessive fatigue, age, level of experience, and inappropriate or improperly adjusted equipment. Additional factors contributing to trauma among this age group involve musculoskeletal immaturity, collisions and falls, excessive speed, environmental conditions, conditioning and fitness status of the rider, nonconservative behavioural patterns, and inadequate medical care. The limited available data restrict the identification and understanding of specific paediatric mountain biking injuries and injury mechanisms. Education about unnecessary risk of injury, use of protective equipment, suitable bikes

  2. Impact of Bony Stress Injuries on Professional Basketball Performance

    Science.gov (United States)

    Khan, Moin; Madden, Kim; Rogowski, Joseph P.; Stotts, Jeff; Burrus, Matthew Tyrrell; Samani, Marisa; Sikka, Robby Singh; Bedi, Asheesh

    2017-01-01

    Objectives: Players in the National Basketball Association (NBA) subject their lower extremities to significant repetitive loading during the season as well as during off-season training. Little is known about the incidence and impact of lower extremity bony stress injuries in these athletes. Methods: Using the player injury database maintained by the NBA Players’ Association, all bony stress injuries from 1992 to May 2016 were identified. Those not involving the lower extremity were excluded from the study. Stress fractures and stress reactions were grouped together. Number of games missed due to the injury as well as player statistics including points per game (ppg), assists per game (apg), steals per game (spg), and blocks per game (bpg) were collected from two years prior to the injury to two years after the injury. Results: 76 lower extremity bony stress injuries were identified involving 75 different NBA players with an average player age of 25.4 ± 4.1 years. 55.3% (42/76) involved the foot, 21.1% (16/76) involved the ankle or fibula, 17.1% (13/76) involved the tibia, and 6.6% (5/76) involved either the knee or patella. The majority of injuries occurred in season 82.9% (63/76) with half of the injuries occurring within the first 6 weeks of the season. 38.2% (29/76) of these injuries were managed surgically. An average of 25.1 ± 21.3 games were missed. 19.7% (15/76) of patients who sustained a stress fracture also had a subsequent injury. 29.2% (21/76) of players were not able to return to professional basketball after the season in which the injury was sustained; however, those who were able to return to the same level of play did not see a significant change in performance as measured by ppg, apg, spg, or bpg when comparing the season prior to the injury and either one or two years after the injury. Stress injuries to the foot carried the worst prognosis, 57.1% (12/21) of those unable to return to professional basketball sustained such an injury

  3. Hypopituitarism after acute brain injury.

    Science.gov (United States)

    Urban, Randall J

    2006-07-01

    Acute brain injury has many causes, but the most common is trauma. There are 1.5-2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding 10 billion dollars. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30-40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7-21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.

  4. MR imaging of medial collateral ligament injury and associated internal knee joint injury

    International Nuclear Information System (INIS)

    Lim, Chae Ha; Lee, Sun Kyoung; Lim, Dong Hun; Kim, Young Sook; Byun, Ju Nam; Kim, Young Chul; Oh, Jae Hee

    1996-01-01

    To assess the value of MR imaging in the diagnosis of medial collateral ligament injury of the knee, we used MR imaging to evaluate the characteristic findings in MCL tears and the frequency of associated knee joint injury. We retrospectively reviewed 26 patients within four weeks of MCL injury, analysed MR findings and correlated them with surgical findings. We evaluated discontinuity, heterogeneous signal intensity of MCL, thin band- like low signal intensity at MCL, facial edema, loss of clear demarcation of adjacent fat also combined bone injury, meniscus injury and other ligament injury. Complete MCL tears were present in 14 patients and partial tears in 12. Complete tears showed discontinuity of MCL, fascial edema and loss of clear demarcation from adjacent fat in 11 patients(79%);proximal MCL tears are more common than distal tears. Partial tears showed thin band-like low signal intensity within MCL, fascial edema and loss of clear demarcation from adjacent fat in seven patients (58%);all patient s with MCL injury showed fascial edema;in 12 patients there was loss of clear demarcation from adjacent fat. We could not, however, distinguish between complete tears and partial tears when MCL showed heterogeneous high signal intensity. Combined bone injury in MCL tears was found in eight patients(62%);the most common sites of this were the lateral femoral condyle and lateral tibial plateau. There was associated injury involving other ligaments(ACL:50%;PCL:27%). Combined meniscus injury in MCL tears was present in 17 patients and the most common meniscus site(50%) is the posterior horn of the medial meniscus. Complete MCL tears showed discontinuity of MCL and partial tears showed a thin band-like low signal intensity within MCL. All patients with MCL injury showed fascial edema, and loss of clear demarcation from adjacent fat. Various other injuries combine with MCL tears. MR imaging is therefore useful in the evaluation of medial collateral ligament injury and

  5. Patterns of work injuries

    DEFF Research Database (Denmark)

    Lander, Flemming; Nielsen, Kent Jacob; Rasmussen, Kurt

    2014-01-01

    To compare work injuries treated in an emergency department (ED) and injuries reported to the Danish Working Environment Authority (DWEA).......To compare work injuries treated in an emergency department (ED) and injuries reported to the Danish Working Environment Authority (DWEA)....

  6. Sports-specific injuries.

    Science.gov (United States)

    Plancher, K D; Minnich, J M

    1996-04-01

    Injuries to the upper extremities can happen in any sport. Injury patterns are common to specific sports. Understanding which injuries occur with these sports allows the examiner to diagnose and treat the athlete easily. This article reviews some of the injuries common in sports such as bicycling, golf, gymnastics, martial arts, racquet sports, and weightlifting.

  7. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

  8. The management of complex pancreatic injuries.

    Science.gov (United States)

    Krige, J E J; Beningfield, S J; Nicol, A J; Navsaria, P

    2005-08-01

    Major injuries of the pancreas are uncommon, but may result in considerable morbidity and mortality because of the magnitude of associated vascular and duodenal injuries or underestimation of the extent of the pancreatic injury. Prognosis is influenced by the cause and complexity of the pancreatic injury, the amount of blood lost, duration of shock, speed of resuscitation and quality and nature of surgical intervention. Early mortality usually results from uncontrolled or massive bleeding due to associated vascular and adjacent organ injuries. Late mortality is a consequence of infection or multiple organ failure. Neglect of major pancreatic duct injury may lead to life-threatening complications including pseudocysts, fistulas, pancreatitis, sepsis and secondary haemorrhage. Careful operative assessment to determine the extent of gland damage and the likelihood of duct injury is usually sufficient to allow planning of further management. This strategy provides a simple approach to the management of pancreatic injuries regardless of the cause. Four situations are defined by the extent and site of injury: (i) minor lacerations, stabs or gunshot wounds of the superior or inferior border of the body or tail of the pancreas (i.e. remote from the main pancreatic duct), without visible duct involvement, are best managed by external drainage; (ii) major lacerations or gunshot or stab wounds in the body or tail with visible duct involvement or transection of more than half the width of the pancreas are treated by distal pancreatectomy; (iii) stab wounds, gunshot wounds and contusions of the head of the pancreas without devitalisation of pancreatic tissue are managed by external drainage, provided that any associated duodenal injury is amenable to simple repair; and (iv) non-reconstructable injuries with disruption of the ampullary-biliary-pancreatic union or major devitalising injuries of the pancreatic head and duodenum in stable patients are best treated by

  9. Management of lawn mower injuries to the foot and ankle.

    Science.gov (United States)

    Corcoran, J; Zamboni, W A; Zook, E G

    1993-09-01

    Seventy consecutive patients treated for lawn mower injuries to the foot and ankle were reviewed to determine optimal treatment, functional results, and complications. Injuries were classified into 1 or more functional-anatomical zones (I, digits; II, dorsum; III, plantar nonweight-bearing surface; IV, heel; and V, ankle) for a total of 96 injuries. Thirty-one patients were available for follow-up. Mean age was 36.7 years and 84% were males. Most injuries (67%) involved patients > 16 years old using a push mower; however, 18% involved children Lawn mower injuries to the foot and ankle can be closed primarily after adequate irrigation and debridement without compromise of infection rate or function. Antibiotic prophylaxis is recommended. One-sixth of these injuries involve children < 5 years of age and can be prevented.

  10. LATERAL ANKLE INJURY

    OpenAIRE

    Pollard, Henry; Sim, Patrick; McHardy, Andrew

    2002-01-01

    Background: Injury to the ankle joint is the most common peripheral joint injury. The sports that most commonly produce high ankle injury rates in their participating athletes include: basketball, netball, and the various codes of football. Objective: To provide an up to date understanding of manual therapy relevant to lateral ligament injury of the ankle. A discussion of the types of ligament injury and common complicating factors that present with lateral ankle pain is presented along with ...

  11. Trampoline Park and Home Trampoline Injuries.

    Science.gov (United States)

    Kasmire, Kathryn E; Rogers, Steven C; Sturm, Jesse J

    2016-09-01

    Trampoline parks, indoor recreational facilities with wall-to-wall trampolines, are increasing in number and popularity. The objective was to identify trends in emergency department visits for trampoline park injuries (TPIs) and compare TPI characteristics with home trampoline injuries (HTIs). Data on trampoline injuries from the National Electronic Injury Surveillance System from 2010 to 2014 were analyzed. Sample weights were applied to estimate yearly national injury trends; unweighted cases were used for comparison of injury patterns. Estimated US emergency department visits for TPI increased significantly, from 581 in 2010 to 6932 in 2014 (P = .045), whereas HTIs did not increase (P = .13). Patients with TPI (n = 330) were older than patients with HTI (n = 7933) (mean 13.3 vs 9.5 years, respectively, P trampoline parks and homes. Compared with HTIs, TPIs were less likely to involve head injury (odds ratio [OR] 0.64; 95% confidence interval [CI], 0.46-0.89), more likely to involve lower extremity injury (OR 2.39; 95% CI, 1.91-2.98), more likely to be a dislocation (OR 2.12; 95% CI, 1.10-4.09), and more likely to warrant admission (OR 1.76; 95% CI, 1.19-2.61). TPIs necessitating hospital admission included open fractures and spinal cord injuries. TPI mechanisms included falls, contact with other jumpers, and flips. TPI patterns differed significantly from HTIs. TPIs are an emerging concern; additional investigation and strategies are needed to prevent injury at trampoline parks. Copyright © 2016 by the American Academy of Pediatrics.

  12. Car surfing: an uncommon cause of traumatic injury.

    Science.gov (United States)

    Peterson, T; Timberlake, G; Yeager, A; Jadali, M; Royer, K

    1999-02-01

    Car surfing is an infrequent cause of traumatic injuries treated by emergency physicians. This very dangerous activity can result in serious injury or death. We report 5 cases of injuries caused by car surfing seen at our hospital during 1996 and 1997. All involved head injuries after a fall from a moving motor vehicle. There were 3 male and 2 female patients, and 3 cases were fatal. Health care providers should be aware of this type of injury and support efforts to prevent it.

  13. Distal radioulnar joint injuries

    Directory of Open Access Journals (Sweden)

    Binu P Thomas

    2012-01-01

    Full Text Available Distal radioulnar joint is a trochoid joint relatively new in evolution. Along with proximal radioulnar joint , forearm bones and interosseous membrane, it allows pronosupination and load transmission across the wrist. Injuries around distal radioulnar joint are not uncommon, and are usually associated with distal radius fractures,fractures of the ulnar styloid and with the eponymous Galeazzi or Essex_Lopresti fractures. The injury can be purely involving the soft tissue especially the triangular fibrocartilage or the radioulnar ligaments.The patients usually present with ulnar sided wrist pain, features of instability, or restriction of rotation. Difficulty in carrying loads in the hand is a major constraint for these patients. Thorough clinical examination to localize point of tenderness and appropriate provocative tests help in diagnosis. Radiology and MRI are extremely useful, while arthroscopy is the gold standard for evaluation. The treatment protocols are continuously evolving and range from conservative, arthroscopic to open surgical methods. Isolated dislocation are uncommon. Basal fractures of the ulnar styloid tend to make the joint unstable and may require operative intervention. Chronic instability requires reconstruction of the stabilizing ligaments to avoid onset of arthritis. Prosthetic replacement in arthritis is gaining acceptance in the management of arthritis.

  14. Computed tomography of projectile injuries

    International Nuclear Information System (INIS)

    Jeffery, A.J.; Rutty, G.N.; Robinson, C.; Morgan, B.

    2008-01-01

    Computed tomography (CT) is a gold standard in clinical imaging but forensic professions have been slow to embrace radiological advances. Forensic applications of CT are now exponentially expanding, replacing other imaging methods. As post-mortem cross-sectional imaging increases, radiologists will fall under increasing pressure to interpret complex forensic cases involving both living and deceased patients. This review presents a wide variety of weapon and projectile types aiding interpretation of projectile injuries both in forensic and clinical practice

  15. Prevention of Blast-Related Injuries

    Science.gov (United States)

    2015-07-14

    raised against β-APP (Cat # 51- 2700, Life Technologies , Grand Island, NY) and processed by routine avidin biotin peroxidase method. The presence of...pathology of traumatic axonal injury involves distinct injury processes, neurofilament compaction ( NFC ) and impaired axoplasmic transport (IAT)1. In rat...blunt trauma studies NFC was evidenced by immunoreactive axons that were thin, elongated and sometimes with vacuolations as revealed by RMO14

  16. Radiation injury claims: an overview and update

    International Nuclear Information System (INIS)

    Schaffer, W.G.

    1984-01-01

    The author reviews the radiation injury claims problem and summarizes the legal framework in which the claims are presently brought. Two cases are reviewed in which the decisions are troubling. The implications of these decisions are discussed in the overall radiation injury claims problem. The author notes that in the largest radiation injury case tried in the United States, the court was unable to resolve the claims within the confines of the existing law. The disregard for established norms of adjudication and the resultant decline in predictability of outcome portends grave consequences, not only for the nuclear industry but for other industries involved with potentially toxic substances

  17. Meat grinder injuries to the upper extremity.

    Science.gov (United States)

    Brandner, M; Bunkis, J; Trengove-Jones, G

    1985-05-01

    Three cases of hand injury caused by meat grinders are presented. All 3 injuries involved the dominant hand and resulted in varying degrees of deformity. Two of the 3 patients arrived in the emergency room with the injured hand still firmly wedged in the meat grinder. Although these injuries continue to prove very mutilating, maximum restoration of the injured hand can be accomplished by careful extrication, followed by preservation and reconstruction of all viable tissues. Perioperative antibiotics and wound irrigation with antibiotic solution are recommended. Microsurgical technique can be of value in treating selected patients.

  18. Acute injuries of the spinal cord and spine

    International Nuclear Information System (INIS)

    Heinemann, U.; Freund, M.

    2004-01-01

    Spinal injuries may result in severe neurological deficits, especially if the spinal cord or spinal nerve roots are involved. Patients may even die of a spinal shock. Besides presenting the important embryologic and anatomical basis underlying the typical radiological findings of spinal trauma, the trauma mechanisms and the resulting injuries are correlated. Special situations, such as the involvement of the alar ligaments and typical injuries in children, will be discussed as well as specific traumatic patters relevant for imaging. Based on the actual literature and recommendations of professional organizations, an approach is provided to the radiologic evaluation of spinal injuries. Advantages and disadvantages of the individual imaging modalities are presented and discussed. (orig.)

  19. Soleus muscle injury: sensitivity of ultrasound patterns

    Energy Technology Data Exchange (ETDEWEB)

    Balius, Ramon [Sport Catalan Council, Generalitat de Catalunya, Barcelona (Spain); Clinica CMI Diagonal, Barcelona (Spain); Rodas, Gil [F.C. Barcelona Medical Services, Barcelona (Spain); Pedret, Carles [Clinica CMI Diagonal, Barcelona (Spain); Clinica Mapfre de Medicina del Tenis, Sports Medicine and Imaging Department, Barcelona (Spain); Centre de Diagnostic per Imatge de Tarragona, Tarragona (Spain); Capdevila, Lluis [Universitat Autonoma de Barcelona, Laboratory of Sport Psychology, Barcelona (Spain); Alomar, Xavier [Clinica Creu Blanca, Barcelona (Spain); Bong, David A. [Instituto Poal de Reumatologia, Barcelona (Spain)

    2014-06-15

    To assess the sensitivity of ultrasound in detecting soleus muscle lesions diagnosed on magnetic resonance imaging (MRI) and to characterize their location, ultrasound pattern, and evolution. Ultrasound and MRI studies were performed between May 2009 and February 2013 on all patients who presented to the Medical Services Clinic of the Catalan Sport Council with the initial onset of sharp pain in the calf compatible with injury of the soleus muscle. An inter-observer ultrasound reliability study was also performed. A total of 55 cases of soleus injury were studied prospectively (22 with right leg involvement, 33 left) by ultrasound and MRI, which was utilized as the ''gold standard.'' In MRI studies, 24 cases (43.7 %) had myofascial injuries that were localized in the posterior aponeurosis (PMF) in 15 cases (27.3 %) and in the anterior aponeurosis (AMF) in 9 (16.4 %). Thirty-one cases (56.3 %) were musculotendinous injuries, with 9 cases (16.4 %) in the medial aponeurosis (MMT), 11 cases (20 %) in the lateral aponeurosis (LMT), and 11 cases (20 %) in the central tendon (CMT). In comparison to MRI, ultrasound was able to detect injury to the soleus in 27.2 % of cases. No injuries were detected by ultrasound alone. Posterior myofascial injuries were more likely to be detected by ultrasound than anterior myofascial injuries or all types of musculotendinous injuries. Ultrasound patterns for each type of injury were described. Ultrasound is not a sensitive technique for detecting and assessing soleus traumatic tears compared with MRI, although the sensitivity is enhanced by a thorough anatomically based ultrasound examination. Timing of the ultrasound examination may be of importance. Each type of soleus injury appears to have a characteristic ultrasound pattern based on a defect of connective expansions, the existence of small myofascial filiform collections, and the rarefaction of the fibrillar area. (orig.)

  20. Soleus muscle injury: sensitivity of ultrasound patterns.

    Science.gov (United States)

    Balius, Ramon; Rodas, Gil; Pedret, Carles; Capdevila, Lluís; Alomar, Xavier; Bong, David A

    2014-06-01

    To assess the sensitivity of ultrasound in detecting soleus muscle lesions diagnosed on magnetic resonance imaging (MRI) and to characterize their location, ultrasound pattern, and evolution. Ultrasound and MRI studies were performed between May 2009 and February 2013 on all patients who presented to the Medical Services Clinic of the Catalan Sport Council with the initial onset of sharp pain in the calf compatible with injury of the soleus muscle. An inter-observer ultrasound reliability study was also performed. A total of 55 cases of soleus injury were studied prospectively (22 with right leg involvement, 33 left) by ultrasound and MRI, which was utilized as the "gold standard." In MRI studies, 24 cases (43.7%) had myofascial injuries that were localized in the posterior aponeurosis (PMF) in 15 cases (27.3%) and in the anterior aponeurosis (AMF) in 9 (16.4%). Thirty-one cases (56.3%) were musculotendinous injuries, with 9 cases (16.4%) in the medial aponeurosis (MMT), 11 cases (20%) in the lateral aponeurosis (LMT), and 11 cases (20%) in the central tendon (CMT). In comparison to MRI, ultrasound was able to detect injury to the soleus in 27.2% of cases. No injuries were detected by ultrasound alone. Posterior myofascial injuries were more likely to be detected by ultrasound than anterior myofascial injuries or all types of musculotendinous injuries. Ultrasound patterns for each type of injury were described. Ultrasound is not a sensitive technique for detecting and assessing soleus traumatic tears compared with MRI, although the sensitivity is enhanced by a thorough anatomically based ultrasound examination. Timing of the ultrasound examination may be of importance. Each type of soleus injury appears to have a characteristic ultrasound pattern based on a defect of connective expansions, the existence of small myofascial filiform collections, and the rarefaction of the fibrillar area.

  1. Soleus muscle injury: sensitivity of ultrasound patterns

    International Nuclear Information System (INIS)

    Balius, Ramon; Rodas, Gil; Pedret, Carles; Capdevila, Lluis; Alomar, Xavier; Bong, David A.

    2014-01-01

    To assess the sensitivity of ultrasound in detecting soleus muscle lesions diagnosed on magnetic resonance imaging (MRI) and to characterize their location, ultrasound pattern, and evolution. Ultrasound and MRI studies were performed between May 2009 and February 2013 on all patients who presented to the Medical Services Clinic of the Catalan Sport Council with the initial onset of sharp pain in the calf compatible with injury of the soleus muscle. An inter-observer ultrasound reliability study was also performed. A total of 55 cases of soleus injury were studied prospectively (22 with right leg involvement, 33 left) by ultrasound and MRI, which was utilized as the ''gold standard.'' In MRI studies, 24 cases (43.7 %) had myofascial injuries that were localized in the posterior aponeurosis (PMF) in 15 cases (27.3 %) and in the anterior aponeurosis (AMF) in 9 (16.4 %). Thirty-one cases (56.3 %) were musculotendinous injuries, with 9 cases (16.4 %) in the medial aponeurosis (MMT), 11 cases (20 %) in the lateral aponeurosis (LMT), and 11 cases (20 %) in the central tendon (CMT). In comparison to MRI, ultrasound was able to detect injury to the soleus in 27.2 % of cases. No injuries were detected by ultrasound alone. Posterior myofascial injuries were more likely to be detected by ultrasound than anterior myofascial injuries or all types of musculotendinous injuries. Ultrasound patterns for each type of injury were described. Ultrasound is not a sensitive technique for detecting and assessing soleus traumatic tears compared with MRI, although the sensitivity is enhanced by a thorough anatomically based ultrasound examination. Timing of the ultrasound examination may be of importance. Each type of soleus injury appears to have a characteristic ultrasound pattern based on a defect of connective expansions, the existence of small myofascial filiform collections, and the rarefaction of the fibrillar area. (orig.)

  2. Prevalence of Injury in Ultra Trail Running

    Directory of Open Access Journals (Sweden)

    Malliaropoulos Nikolaos

    2015-06-01

    Full Text Available Purpose. The purpose of the study was to find the rate of musculoskeletal injuries in ultra-trail runners, investigate the most sensitive anatomical areas, and discover associated predicting factors to aid in the effective prevention and rapid rehabilitation of trail running injuries. Methods. Forty ultra trail runners responded to an epidemiological questionnaire. Results. At least one running injury was reported by 90% of the sample, with a total of 135 injuries were reported (111 overuse injuries, 24 appeared during competing. Lower back pain was the most common source of injury (42.5%. Running in the mountains (p = 0.0004 and following a personalized training schedule (p = 0.0995 were found to be protective factors. Runners involved in physical labor are associated with more injuries (p = 0.058. Higher-level runners are associated with more injuries than lower-level cohorts (p = 0.067, with symptoms most commonly arising in the lower back (p = 0.091, hip joint (p = 0.083, and the plantar surface of the foot (p = 0.054. Experienced runners (> 6 years are at greater risk of developing injuries (p = 0.001, especially in the lower back (p = 0.012, tibia (p = 0.049, and the plantar surface of the foot (p = 0 .028. Double training sessions could cause hip joint injury (p = 0.060. Conclusions. In order to avoid injury, it is recommended to train mostly on mountain trails and have a training program designed by professionals.

  3. Management of radiation injuries

    International Nuclear Information System (INIS)

    Roberto, Maria A.

    2003-01-01

    Injuries by exposure to ionizing radiation can be due to the detonation of a nuclear device in a military conflict, or it can occur following a large industrial accident (e.g. Chernobyl), or it can be the result of therapy (e.g. in a laboratory, in the case of cancer or other clinical situations). The severity of biological tissues damage depends on the energy deposited. The skin and subcutaneous tissue alone damaged may be related with an exposure to low energy radiation. In case of an exposure to high energy radiation the deeper structures will be involved. The treatment of the clinical situation after radiation requires special facilities (burn intensive care unit) and a massive support from a dedicated team. (author)

  4. Biomarkers of drug-induced vascular injury

    International Nuclear Information System (INIS)

    Brott, D.; Gould, S.; Jones, H.; Schofield, J.; Prior, H.; Valentin, J.P; Bjurstrom, S.; Kenne, K.; Schuppe-Koistinen, I.; Katein, A.; Foster-Brown, L.; Betton, G.; Richardson, R.; Evans, G.; Louden, C.

    2005-01-01

    In pre-clinical safety studies, drug-induced vascular injury is an issue of concern because there are no obvious diagnostic markers for pre-clinical or clinical monitoring and there is an intellectual gap in our understanding of the pathogenesis of this lesion. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary targets, smooth muscle and endothelial cells are unknown. However, evaluation of novel markers for potential clinical monitoring with a mechanistic underpinning would add value in risk assessment and management. This mini review focuses on the progress to identify diagnostic markers of drug-induced vascular injury. Von Willebrand factor (vWF), released upon perturbation of endothelial cells, is transiently increased in plasma prior to morphological evidence of damage in dogs or rats treated with vascular toxicants. Therefore, vWF might be a predictive biomarker of vascular injury. However, vWF is not an appropriate biomarker of lesion progression or severity since levels return to baseline values when there is morphological evidence of injury. A potential mechanistically linked biomarker of vascular injury is caveolin-1. Expression of this protein, localized primarily to smooth muscle and endothelial cells, decreases with the onset of vascular damage. Since vascular injury involves multiple mediators and cell types, evaluation of a panel rather than a single biomarker may be more useful in monitoring early and severe progressive vascular injury

  5. Blunt gastric injuries.

    Science.gov (United States)

    Oncel, Didem; Malinoski, Darren; Brown, Carlos; Demetriades, Demetrios; Salim, Ali

    2007-09-01

    Gastric rupture after blunt abdominal trauma is a rare injury with few reports in the literature. The purpose of this study was to review our experience with blunt gastric injuries and compare outcomes with small bowel or colon injuries. All patients with hollow viscus perforations after blunt abdominal trauma from 1992 to 2005 at our level I trauma center were reviewed. Of 35,033 blunt trauma admissions, there were 268 (0.7%) patients with a total of 319 perforating hollow viscus injuries, 25 (0.07%) of which were blunt gastric injuries. When compared with the small bowel or colon injuries, the blunt gastric injury group had a higher Injury Severity Score (22 versus 17, P = 0.04), more patients with a chest Abbreviated Injury Score greater than 2 (36% versus 12%, P < 0.01), and a shorter interval from injury to laparotomy (221 versus 366 minutes, P = 0.017). Multivariate analysis identified five independent risk factors for mortality: age older than 55 years, head Abbreviated Injury Score greater than 2, chest Abbreviated Injury Score greater than 2, the presence of hypotension on admission, and Glasgow Coma Scale 8 or less. The results of this study suggest that mortality in patients with blunt hollow viscus injuries can be attributed to concurrent head and chest injuries, but not the specific hollow viscus organ that is injured.

  6. The legal aspects involving repetitive strain injuries (RSI)

    OpenAIRE

    Techy, Antonio; Siena, Cesar; Helfenstein Junior, Milton [UNIFESP

    2009-01-01

    No relacionamento entre médico e paciente, além da boa prática da medicina, o médico está obrigado a conhecer e cumprir as leis, normas e convenções que podem garantir direitos a uns e gerar obrigações a outros, com base nas informações criadas e perenizadas em prontuários, atestados e pareceres, que servirão de referência às decisões de entidades públicas ou privadas na concessão ou na recusa de direitos e deveres legais. Apontamos como os médicos devem se comportar em relação aos pacientes ...

  7. "Reversibility of Cardiovascular Injury With CPAP Use: Mechanisms Involved"

    Science.gov (United States)

    2015-09-29

    Sleep Apnea, Obstructive; Hypoxia; Hypercapnia; Sleep Disorders; Obesity; Hypertension; Coronary Artery Vasospasm; Right Ventricular Overload; Left Ventricular Function Systolic Dysfunction; Ventricular Hypertrophy

  8. A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

    Directory of Open Access Journals (Sweden)

    Chen Xie

    Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

  9. Sports injuries in students aged 12-18 during physical education classes in Israel

    Directory of Open Access Journals (Sweden)

    Coleman R

    2003-12-01

    Full Text Available A retrospective study was made of sports injuries occurring in physical education classes in 51 junior and senior high schools in Israel during a period of 14 months (2000-2002. The survey covered a total population of 11439 students aged 12 to 18, 52% male, 48% female. The aim of the study was to assess the incidence, types and risk factors involving sports injuries among students in physical education classes. Physical education teachers were asked to complete questionnaires recording injuries that occurred during their lessons. Data included: socio-demographic parameters (gender, age, height and weight of the injured students, area and type of injury, time of injury during the class, type of sport activity, previous injuries, assessment of sport capabilities and performance. A total of 192 injuries were recorded in the survey (1.70%. Male and female students had fairly similar injury rates (49% female, 51% male. 12-14 year old students showed the greatest number of injuries (52%. The ankle was the most common site of injury in both genders (48% mostly involving ankle sprain. Athletics was the most common sport involving injury (38%. 45% of injuries were reported to occur in the start of the class, whereas 26% of injuries were repeat injuries. This survey showed that the incidence of injuries during supervised physical education classes in high schools in Israel is relatively low and is similar to that of other Western countries.

  10. Priorities for injury prevention in women's Australian football: a compilation of national data from different sources.

    Science.gov (United States)

    Fortington, Lauren V; Finch, Caroline F

    2016-01-01

    Participation in Australian football (AF) has traditionally been male dominated and current understanding of injury and priorities for prevention are based solely on reports of injuries in male players. There is evidence in other sports that indicates that injury types differ between males and females. With increasing participation in AF by females, it is important to consider their specific injury and prevention needs. This study aimed to provide a first injury profile from existing sources for female AF. Compilation of injury data from four prospectively recorded data sets relating to female AF: (1) hospital admissions in Victoria, 2008/09-13/14, n=500 injuries; (2) emergency department (ED) presentations in Victoria, 2008/09-2012/13, n=1,879 injuries; (3) insurance claims across Australia 2004-2013, n=522 injuries; (4) West Australian Women's Football League (WAWFL), 2014 season club data, n=49 injuries. Descriptive results are presented as injury frequencies, injury types and injury to body parts. Hospital admissions and ED presentations were dominated by upper limb injuries, representing 47% and 51% of all injuries, respectively, primarily to the wrist/hand at 32% and 40%. Most (65%) insurance claim injuries involved the lower limb, 27% of which were for knee ligament damage. A high proportion of concussions (33%) were reported in the club-collected data. The results provide the first compilation of existing data sets of women's AF injuries and highlight the need for a rigorous and systematic injury surveillance system to be instituted.

  11. Pediatric craniomaxillofacial injuries after road traffic crashes: characteristics of injuries and protective equipment use.

    Science.gov (United States)

    Yunus, Siti Salmiah Mohd; Ngeow, Wei Cheong; Ramli, Roszalina

    2015-09-01

    A cross-sectional study to determine the pattern of craniomaxillofacial (CMF) injuries among children involved in road traffic crashes was performed. The association of protective equipment use with the CMF injuries was evaluated. Retrospective records of children treated in the University Malaya Medical Centre, Kuala Lumpur, Malaysia, after road traffic crashes between January 1, 2008 and December 31, 2012 were reviewed, and, after that, telephone interviews were made. Seventy-one children were included in this study. Fifty-two (73.6%) were involved in a motorcycle injury and 19 (23.4%) in a car crash. Their mean age was 6.02 years; SD, 3.46 (range between 0 to 13 years old). More male children were observed (52.1%) compared with females (47.9%). Thirty-nine point four percent of the children sustained CMF injuries, 33.8% body injuries, and 23.9% had both CMF and other body parts injuries. The highest injury severity score was 26, whereas the lowest was 0. Many children did not use protective equipment during traveling, 44.2% of children among motorcycle pillion riders, and 78.9% among car passengers. The association between helmet use and CMF injuries was shown to be statistically significant (P belt. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Urological injuries following trauma

    International Nuclear Information System (INIS)

    Bent, C.; Iyngkaran, T.; Power, N.; Matson, M.; Hajdinjak, T.; Buchholz, N.; Fotheringham, T.

    2008-01-01

    Blunt renal trauma is the third most common injury in abdominal trauma following splenic and hepatic injuries, respectively. In the majority, such injuries are associated with other abdominal organ injuries. As urological injuries are not usually life-threatening, and clinical signs and symptoms are non-specific, diagnosis is often delayed. We present a practical approach to the diagnosis and management of these injuries based on our experience in a busy inner city trauma hospital with a review of the current evidence-based practice. Diagnostic imaging signs are illustrated

  13. Urological injuries following trauma

    Energy Technology Data Exchange (ETDEWEB)

    Bent, C. [Department of Diagnostic Imaging, Barts and The London NHS Trust, London (United Kingdom)], E-mail: clare.bent@bartsandthelondon.nhs.uk; Iyngkaran, T.; Power, N.; Matson, M. [Department of Diagnostic Imaging, Barts and The London NHS Trust, London (United Kingdom); Hajdinjak, T.; Buchholz, N. [Department of Urology, Barts and The London NHS Trust, London (United Kingdom); Fotheringham, T. [Department of Diagnostic Imaging, Barts and The London NHS Trust, London (United Kingdom)

    2008-12-15

    Blunt renal trauma is the third most common injury in abdominal trauma following splenic and hepatic injuries, respectively. In the majority, such injuries are associated with other abdominal organ injuries. As urological injuries are not usually life-threatening, and clinical signs and symptoms are non-specific, diagnosis is often delayed. We present a practical approach to the diagnosis and management of these injuries based on our experience in a busy inner city trauma hospital with a review of the current evidence-based practice. Diagnostic imaging signs are illustrated.

  14. Spinal injury in sport

    Energy Technology Data Exchange (ETDEWEB)

    Barile, Antonio [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy)]. E-mail: antonio.barile@cc.univaq.it; Limbucci, Nicola [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Splendiani, Alessandra [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Gallucci, Massimo [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Masciocchi, Carlo [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy)

    2007-04-15

    Spinal injuries are very common among professional or amateur athletes. Spinal sport lesions can be classified in overuse and acute injuries. Overuse injuries can be found after years of repetitive spinal load during sport activity; however specific overuse injuries can also be found in adolescents. Acute traumas are common in contact sports. Most of the acute injuries are minor and self-healing, but severe and catastrophic events are possible. The aim of this article is to review the wide spectrum of spinal injuries related to sport activity, with special regard to imaging finding.

  15. Trauma: Spinal Cord Injury.

    Science.gov (United States)

    Eckert, Matthew J; Martin, Matthew J

    2017-10-01

    Injuries to the spinal column and spinal cord frequently occur after high-energy mechanisms of injury, or with lower-energy mechanisms, in select patient populations like the elderly. A focused yet complete neurologic examination during the initial evaluation will guide subsequent diagnostic procedures and early supportive measures to help prevent further injury. For patients with injury to bone and/or ligaments, the initial focus should be spinal immobilization and prevention of inducing injury to the spinal cord. Spinal cord injury is associated with numerous life-threatening complications during the acute and long-term phases of care that all acute care surgeons must recognize. Published by Elsevier Inc.

  16. Upper extremity golf injuries.

    Science.gov (United States)

    Cohn, Michael A; Lee, Steven K; Strauss, Eric J

    2013-01-01

    Golf is a global sport enjoyed by an estimated 60 million people around the world. Despite the common misconception that the risk of injury during the play of golf is minimal, golfers are subject to a myriad of potential pathologies. While the majority of injuries in golf are attributable to overuse, acute traumatic injuries can also occur. As the body's direct link to the golf club, the upper extremities are especially prone to injury. A thorough appreciation of the risk factors and patterns of injury will afford accurate diagnosis, treatment, and prevention of further injury.

  17. Spinal injury in sport

    International Nuclear Information System (INIS)

    Barile, Antonio; Limbucci, Nicola; Splendiani, Alessandra; Gallucci, Massimo; Masciocchi, Carlo

    2007-01-01

    Spinal injuries are very common among professional or amateur athletes. Spinal sport lesions can be classified in overuse and acute injuries. Overuse injuries can be found after years of repetitive spinal load during sport activity; however specific overuse injuries can also be found in adolescents. Acute traumas are common in contact sports. Most of the acute injuries are minor and self-healing, but severe and catastrophic events are possible. The aim of this article is to review the wide spectrum of spinal injuries related to sport activity, with special regard to imaging finding

  18. Urological injuries following trauma.

    Science.gov (United States)

    Bent, C; Iyngkaran, T; Power, N; Matson, M; Hajdinjak, T; Buchholz, N; Fotheringham, T

    2008-12-01

    Blunt renal trauma is the third most common injury in abdominal trauma following splenic and hepatic injuries, respectively. In the majority, such injuries are associated with other abdominal organ injuries. As urological injuries are not usually life-threatening, and clinical signs and symptoms are non-specific, diagnosis is often delayed. We present a practical approach to the diagnosis and management of these injuries based on our experience in a busy inner city trauma hospital with a review of the current evidence-based practice. Diagnostic imaging signs are illustrated.

  19. Nail gun injuries among construction workers.

    Science.gov (United States)

    Dement, John M; Lipscomb, Hester; Li, Leiming; Epling, Carol; Desai, Tejas

    2003-05-01

    Pneumatic nail guns greatly increase worker productivity and are extensively used in wood frame building construction, with especially high use in residential construction. One surveillance report of nail gun injuries in Washington State has been published; however, other literature consists largely of case reports and case series in trauma journals. The major objective of the current study was to investigate the occurrence of nail gun-associated injuries among construction workers and to identify preventable work-related factors associated with these injuries. Nail gun-related injuries occurring among a cohort of 13,347 carpenters in Ohio who worked union hours during the time period January 1, 1994, until September 30, 1997, were identified by matching the cohort with workers' compensation claims made to the Ohio Bureau of Workers' Compensation. We also analyzed workers' compensation claims for North Carolina Home Builders Association members for the period July 1996-November 1999 to identify nail gun-related injuries. Analyses included stratified analyses of claims by nature and body part injured, calculation of nail gun injury rates, and analyses of free text descriptions of injuries. Overall, nail gun injuries were responsible for 3.9 percent of workers' compensation claims with 8.3 percent to 25.5 percent of claims involving paid lost work time. The overall rate of nail gun injuries (cases per 200,000 work hours) was 0.33 in North Carolina and 0.26 in Ohio, reflecting the greater concentration of wood frame construction workers in the North Carolina population studied. Higher rates of injury were observed for carpenters in North Carolina and among residential carpenters in Ohio. The predominant body part injured was the hands/fingers, with 80 to 89 percent of injuries being nail punctures. Analyses of free text information for puncture injuries found approximately 70 percent of injuries to occur during the framing/sheathing stage of construction. Our data

  20. Experienced emotional burden in caregivers: psychometric properties of the Involvement Evaluation Questionnaire in caregivers of brain injured patients

    NARCIS (Netherlands)

    Geurtsen, Gert J.; Meijer, Ron; van Heugten, Caroline M.; Martina, Juan D.; Geurts, Alexander C. H.

    2010-01-01

    To examine the psychometric properties (internal consistency, discriminant validity, and responsiveness) of the Involvement Evaluation Questionnaire for Brain Injury measuring emotional burden in caregivers of patients with chronic acquired brain injury. Inception cohort study. Caregivers of chronic

  1. Experienced emotional burden in caregivers: psychometric properties of the Involvement Evaluation Questionnaire in caregivers of brain injured patients.

    NARCIS (Netherlands)

    Geurtsen, G.J.; Meijer, R.; Heugten, C.M. van; Martina, J.D.; Geurts, A.C.H.

    2010-01-01

    OBJECTIVE: To examine the psychometric properties (internal consistency, discriminant validity, and responsiveness) of the Involvement Evaluation Questionnaire for Brain Injury measuring emotional burden in caregivers of patients with chronic acquired brain injury. DESIGN: Inception cohort study.

  2. [Severe trampoline injuries and their risk factors among children and the young].

    Science.gov (United States)

    Sinikumpu, Juha-Jaakko; Salokorpi, Niina; Suo-Palosaari, Maria; Pesälä, Juha; Serlo, Willy

    2016-01-01

    Although the majority of trampoline injuries in children are minor, severe injuries occur as well. We have analyzed the risk factors, treatment and outcome of severe trampoline injuries treated in the Oulu University Hospital in children and the young between April and November 2105. There was a total of eight severe injuries. Five injuries involved a danger of death. Almost all severe trampoline injuries resulted from an unsuccessful trick. A safety net was in use in half of the cases. All cervical spine injuries would have been avoided provided that the children would have refrained from doing a somersault on the trampoline.

  3. The prevention of injuries in contact flag football.

    Science.gov (United States)

    Kaplan, Yonatan; Myklebust, Grethe; Nyska, Meir; Palmanovich, Ezequiel; Victor, Jan; Witvrouw, Erik

    2014-01-01

    American flag football is a non-tackle, contact sport with many moderate to severe contact-type injuries reported. A previous prospective injury surveillance study by the authors revealed a high incidence of injuries to the fingers, face, knee, shoulder and ankle. The objectives of the study were to conduct a pilot-prospective injury prevention study in an attempt to significantly reduce the incidence and the severity of injuries as compared to a historical cohort, as well as to provide recommendations for a future prospective injury prevention study. A prospective injury prevention study was conducted involving 724 amateur male (mean age: 20.0 ± 3.1 years) and 114 female (mean age: 21.2 ± 7.2 years) players. Four prevention measures were implemented: the no-pocket rule, self-fitting mouth guards, ankle braces (for those players with recurrent ankle sprains) and an injury treatment information brochure. An injury surveillance questionnaire was administered to record all time-loss injuries sustained in game sessions. There was a statistically significant reduction in the number of injured players, the number of finger/hand injuries, the incidence rate and the incidence proportion between the two cohorts (p football. Prevention strategies for a longer, prospective, randomised-controlled injury prevention study should include the strict enforcement of the no-pocket rule, appropriate head gear, the use of comfortable-fitting ankle braces and mouth guards, and changing the blocking rules of the game.

  4. Gastric traumatic injuries: CT findings

    International Nuclear Information System (INIS)

    Lassandro, Francesco; Romano, Stefania; Rossi, Giovanni; Muto, Roberto; Cappabianca, Salvatore; Grassi, Roberto

    2006-01-01

    Objective: Gastric blunt traumatic injuries are uncommon and their radiological appearance has been infrequently reported in medical literature. These injuries are difficult to diagnose preoperatively, though they require immediate recognition to minimize their otherwise high mortality and morbidity. The aim of our study is to describe the radiological appearance of blunt gastric traumatic injuries. Materials and methods: Retrospective evaluation of a 25 patients series observed between January 1997 and May 2005. Results: We observed rupture of the stomach in 20% of cases, in 44% of cases a partial lesion of the stomach, in one case a necrotic post-traumatic volvulus, five patients (20%) had benign portal pneumatosis, in three patients the stomach was secondarily involved because of a diaphragmatic hernia. The fundus resulted to be the most frequently damaged part of the stomach (80%). Conclusions: Blunt traumatic injuries need a careful and systematic approach given their economical and social relevance. For these reasons uncommon lesions require attention and may be important to search for specific findings of gastric lesions

  5. Gastric traumatic injuries: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Lassandro, Francesco [Department of Diagnostic Imaging, ' A. Cardarelli' Hospital, I-80131 Naples (Italy)]. E-mail: francesco.lassandro@fastwebnet.it; Romano, Stefania [Department of Diagnostic Imaging, ' A. Cardarelli' Hospital, I-80131 Naples (Italy); Rossi, Giovanni [Department of Radiology, V. Monaldi Hospital, Naples (Italy); Muto, Roberto [Department of Radiology, V. Monaldi Hospital, Naples (Italy); Cappabianca, Salvatore [Magrassi-Lanzara Department, Institute of Radiology, Second University of Naples (Italy); Grassi, Roberto [Magrassi-Lanzara Department, Institute of Radiology, Second University of Naples (Italy)

    2006-09-15

    Objective: Gastric blunt traumatic injuries are uncommon and their radiological appearance has been infrequently reported in medical literature. These injuries are difficult to diagnose preoperatively, though they require immediate recognition to minimize their otherwise high mortality and morbidity. The aim of our study is to describe the radiological appearance of blunt gastric traumatic injuries. Materials and methods: Retrospective evaluation of a 25 patients series observed between January 1997 and May 2005. Results: We observed rupture of the stomach in 20% of cases, in 44% of cases a partial lesion of the stomach, in one case a necrotic post-traumatic volvulus, five patients (20%) had benign portal pneumatosis, in three patients the stomach was secondarily involved because of a diaphragmatic hernia. The fundus resulted to be the most frequently damaged part of the stomach (80%). Conclusions: Blunt traumatic injuries need a careful and systematic approach given their economical and social relevance. For these reasons uncommon lesions require attention and may be important to search for specific findings of gastric lesions.

  6. Key Injury and Violence Data

    Science.gov (United States)

    ... Traumatic Brain Injury Violence Prevention Key Injury and Violence Data Recommend on Facebook Tweet Share Compartir Injuries ... of death among persons 1-44. Injury- and violence-related deaths are only part of the problem ...

  7. Community-level football injury epidemiology: traumatic injuries treated at Swedish emergency medical facilities.

    Science.gov (United States)

    Timpka, Toomas; Schyllander, Jan; Stark Ekman, Diana; Ekman, Robert; Dahlström, Örjan; Hägglund, Martin; Kristenson, Karolina; Jacobsson, Jenny

    2018-02-01

    Despite the popularity of the sport, few studies have investigated community-level football injury patterns. This study examines football injuries treated at emergency medical facilities using data from three Swedish counties. An open-cohort design was used based on residents aged 0-59 years in three Swedish counties (pop. 645 520). Data were collected from emergency medical facilities in the study counties between 1 January 2007 and 31 December 2010. Injury frequencies and proportions for age groups stratified by sex were calculated with 95% confidence intervals (95% CIs) and displayed per diagnostic group and body location. Each year, more than 1/200 person aged 0-59 years sustained at least one injury during football play that required emergency medical care. The highest injury incidence was observed among adolescent boys [2009 injuries per 100 000 population years (95% CI 1914-2108)] and adolescent girls [1413 injuries per 100 000 population years (95% CI 1333-1498)]. For female adolescents and adults, knee joint/ligament injury was the outstanding injury type (20% in ages 13-17 years and 34% in ages 18-29 years). For children aged 7-12 years, more than half of the treated injuries involved the upper extremity; fractures constituted about one-third of these injuries. One of every 200 residents aged 0-59 years in typical Swedish counties each year sustained a traumatic football injury that required treatment in emergency healthcare. Further research on community-level patterns of overuse syndromes sustained by participation in football play is warranted. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  8. Head injury - first aid

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000028.htm Head injury - first aid To use the sharing features on this page, ... a concussion can range from mild to severe. First Aid Learning to recognize a serious head injury and ...

  9. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... of Spinal Cord Injury Rehabilitation Kristine Cichowski, MS Occupational Therapy after Spinal Cord Injury Katie Powell, OT ... does not provide medical advice, recommend or endorse health care products or services, or control the information ...

  10. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation Sara Klaas, MSW Transitions for Children ...

  11. Elbow Injuries and Disorders

    Science.gov (United States)

    ... Many things can make your elbow hurt. A common cause is tendinitis, an inflammation or injury to the tendons that attach muscle to bone. Tendinitis of the elbow is a sports injury, often from playing tennis or golf. You ...

  12. Posterior Cruciate Ligament Injury

    Science.gov (United States)

    ... your knee is bent also can cause this injury. Risk factors Being in a motor vehicle accident and participating in sports such as football and soccer are the most common risk factors for a PCL injury. Complications In ...

  13. Brain injury - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000163.htm Brain injury - discharge To use the sharing features on ... know was in the hospital for a serious brain injury. At home, it will take time for ...

  14. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... of spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

  15. Football injuries: current concepts.

    Science.gov (United States)

    Olson, David E; Sikka, Robby Singh; Hamilton, Abigail; Krohn, Austin

    2011-01-01

    Football is one of the most popular sports in the United States and is the leading cause of sports-related injury. A large focus in recent years has been on concussions, sudden cardiac death, and heat illness, all thought to be largely preventable health issues in the young athlete. Injury prevention through better understanding of injury mechanisms, education, proper equipment, and practice techniques and preseason screening may aid in reducing the number of injuries. Proper management of on-field injuries and health emergencies can reduce the morbidity associated with these injuries and may lead to faster return to play and reduced risk of future injury. This article reviews current concepts surrounding frequently seen football-related injuries.

  16. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

  17. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury Patti Rogers, SW Marguerite ... arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

  18. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences by Topic Resources ... Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences by Topic Resources ...

  19. Eye Injuries at Work

    Science.gov (United States)

    ... National Standards Institute (ANSI) to meet their eye protection standards. If an eye injury occurs, see an ophthalmologist or go to the emergency room immediately, even if the eye injury appears minor. Delaying medical attention can result in permanent vision ...

  20. Injury & Safety Report - Legacy

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Injury & Safety Report is a mandatory post trip legal document observers fill out to report any injuries they have incurred, illnesses they have had, or...

  1. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Injury Diane M. Rowles, MS, NP How Family Life Changes After Spinal Cord Injury Nancy Rosenberg, PsyD ... Rehabilitation Donald Peck Leslie, MD Adjusting to Social Life in a Wheelchair Lisa Rosen, MS Spasticity, Physical ...

  2. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Medical Experts People Living with SCI Personal Experiences by Topic Resources Peer ... Injuries Spinal Cord Injury 101 David Chen, MD Preventing Pressure Sores Mary Zeigler, MS Transition from Hospital to ...

  3. Skateboarding injuries of today

    OpenAIRE

    Forsman, L; Eriksson, A

    2001-01-01

    Background—Skateboarding injuries have increased with the rise in popularity of the sport, and the injury pattern can be expected to have changed with the development of both skateboard tricks and the materials used for skateboard construction.

  4. Traumatic Brain Injury

    Science.gov (United States)

    ... brain injury Some traumatic brain injuries have lasting effects, and some do not. You may be left with disabilities. These can be physical, behavioral, communicative, and/or mental. Customized treatment helps you to have as full ...

  5. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Living with SCI Personal Experiences by Topic Resources Peer ... Adult Injuries Spinal Cord Injury 101 David Chen, MD Preventing Pressure Sores Mary Zeigler, MS Transition from Hospital to ...

  6. Injury among adolescents with intellectual disability: A prospective cohort study.

    Science.gov (United States)

    White, David; McPherson, Lyn; Lennox, Nicholas; Ware, Robert S

    2018-04-12

    Injury is the leading cause of mortality and morbidity in adolescents worldwide, and injury rates have been shown to be higher among youth with intellectual disability. Despite this, injury among adolescents with intellectual disability remains poorly investigated. This study aimed to identify characteristics associated with injury among adolescents with intellectual disability living in the community. A cohort of adolescents with intellectual disability living in southern Queensland, Australia was investigated prospectively between January 2006 and June 2010. Personal characteristics were collected via postal questionnaire. Injury information, including mechanism and location of injury, was extracted from general practitioner records. The association between demographic, social and clinical characteristics of participants and episodes of injury was investigated using negative binomial regression. A total of 289 injuries were recorded from 432 participants over 1627.3 years of study-time. The overall annual injury incidence was 17.5 (95%CI 14.7, 20.9) per 100 person years. Presence of ADHD and less severe disability was associated with increased risk of injury. Down syndrome and reduced verbal communication capacity were associated with decreased risk of injury. Falls accounted for the highest single mechanism of injury (19.0%) with the majority (73.2%) of injuries involving either upper or lower limbs. ADHD is a co-morbidity that increases risk of injury among adolescents with intellectual disability. A critical component of injury prevention is avoidance of the great variety of environmental risk factors for injury relevant to this population. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Injuries in team sport tournaments during the 2004 Olympic Games.

    Science.gov (United States)

    Junge, Astrid; Langevoort, Gijs; Pipe, Andrew; Peytavin, Annie; Wong, Fook; Mountjoy, Margo; Beltrami, Gianfranco; Terrell, Robert; Holzgraefe, Manfred; Charles, Richard; Dvorak, Jiri

    2006-04-01

    Several authors have analyzed the incidence of injuries in a given sport, but only a few have examined the exposure-related incidence of injuries in different types of sports using the same methodology. Analysis of the incidence, circumstances, and characteristics of injuries in different team sports during the 2004 Olympic Games. Cohort study; Level of evidence, 2. During the 2004 Olympic Games, injuries in 14 team sport tournaments (men's and women's soccer, men's and women's handball, men's and women's basketball, men's and women's field hockey, baseball, softball, men's and women's water polo, and men's and women's volleyball) were analyzed. After each match, the physician of the participating teams or the official medical representative of the sport completed a standardized injury report form. The mean response rate was 93%. A total of 377 injuries were reported from 456 matches, an incidence of 0.8 injuries per match (95% confidence interval, 0.75-0.91) or 54 injuries per 1000 player matches (95% confidence interval, 49-60). Half of all injuries affected the lower extremity; 24% involved the head or neck. The most prevalent diagnoses were head contusion and ankle sprain. On average, 78% of injuries were caused by contact with another player. However, a significantly higher percentage of noncontact (57%) versus contact injuries (37%) was expected to prevent the player from participating in his or her sport. Significantly more injuries in male players (46%) versus female players (35%) were expected to result in absence from match or training. The incidence, diagnosis, and causes of injuries differed substantially between the team sports. The risk of injury in different team sports can be compared using standardized methodology. Even if the incidence and characteristics of injuries are not identical in all sports, prevention of injury and promotion of fair play are relevant topics for almost all team sports.

  8. Adventure tourism and adventure sports injury: the New Zealand experience.

    Science.gov (United States)

    Bentley, Tim A; Page, Stephen J; Macky, Keith A

    2007-11-01

    The primary aims of this study were to establish a client injury baseline for the New Zealand adventure tourism and adventure sport sector, and to examine patterns and trends in claims for injury during participation in adventure activities. Content analysis of narrative text data for compensated injuries occurring in a place for recreation and sport over a 12-month period produced over 15,000 cases involving adventure tourism and adventure sport. As found in previous studies in New Zealand, highest claim counts were observed for activities that are often undertaken independently, rather than commercially. Horse riding, tramping, surfing and mountain biking were found to have highest claim counts, while hang gliding/paragliding/parasailing and jet boating injuries had highest claim costs, suggesting greatest injury severity. Highest claim incidence was observed for horse riding, with female claimants over-represented for this activity. Younger male claimants comprised the largest proportion of adventure injuries, and falls were the most common injury mechanism.

  9. Cervical vertigo and dizziness after whiplash injury.

    Science.gov (United States)

    Endo, Kenji; Ichimaru, Katsuji; Komagata, Mashashi; Yamamoto, Kengo

    2006-06-01

    Whiplash injury is not only limited to neck injury but also brainstem injury that does not involve direct damage to the neck or head. The symptoms of whiplash injury are polymorphous, with the most common complaints being cervical pain, headache and scapulodynia. Vertigo and dizziness are also reported in 25-50% of the cases. In otoneurologic studies, magnetic resonance angiography (MRA) is used for the evaluation of vertebrobasilar hemodynamics in patients who complain of dizziness and vertigo. It is reported that vertebrobasilar artery insufficiency (VBI) leads to brainstem and cerebellar ischemia and infarction following cervical manipulation. Here we examined the correlation between vertigo or dizziness and the right and left side difference in vertebral arteries after whiplash injury using MRA. We studied 20 patients who complained of neck pain with vertigo or dizziness after whiplash injury and 13 healthy volunteers as a control. In the control group, abnormal MRA findings in the vertebral arteries such as occlusion, stenosis or slow blood flow were seen in 77% of the cases. In the patient group, abnormal MRA findings were seen in 60%. The side differ