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Sample records for prevent neural damage

  1. Neural networks for damage identification

    SciTech Connect

    Paez, T.L.; Klenke, S.E.

    1997-11-01

    Efforts to optimize the design of mechanical systems for preestablished use environments and to extend the durations of use cycles establish a need for in-service health monitoring. Numerous studies have proposed measures of structural response for the identification of structural damage, but few have suggested systematic techniques to guide the decision as to whether or not damage has occurred based on real data. Such techniques are necessary because in field applications the environments in which systems operate and the measurements that characterize system behavior are random. This paper investigates the use of artificial neural networks (ANNs) to identify damage in mechanical systems. Two probabilistic neural networks (PNNs) are developed and used to judge whether or not damage has occurred in a specific mechanical system, based on experimental measurements. The first PNN is a classical type that casts Bayesian decision analysis into an ANN framework; it uses exemplars measured from the undamaged and damaged system to establish whether system response measurements of unknown origin come from the former class (undamaged) or the latter class (damaged). The second PNN establishes the character of the undamaged system in terms of a kernel density estimator of measures of system response; when presented with system response measures of unknown origin, it makes a probabilistic judgment whether or not the data come from the undamaged population. The physical system used to carry out the experiments is an aerospace system component, and the environment used to excite the system is a stationary random vibration. The results of damage identification experiments are presented along with conclusions rating the effectiveness of the approaches.

  2. Folic Acid Helps Prevent Neural Tube Defects

    MedlinePlus

    ... Features Folic Acid Helps Prevent Neural Tube Defects Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir The feature you selected is no longer available. In 10 seconds you will be automatically redirected to the CDC. ...

  3. Modeling neural activity with cumulative damage distributions.

    PubMed

    Leiva, Víctor; Tejo, Mauricio; Guiraud, Pierre; Schmachtenberg, Oliver; Orio, Patricio; Marmolejo-Ramos, Fernando

    2015-10-01

    Neurons transmit information as action potentials or spikes. Due to the inherent randomness of the inter-spike intervals (ISIs), probabilistic models are often used for their description. Cumulative damage (CD) distributions are a family of probabilistic models that has been widely considered for describing time-related cumulative processes. This family allows us to consider certain deterministic principles for modeling ISIs from a probabilistic viewpoint and to link its parameters to values with biological interpretation. The CD family includes the Birnbaum-Saunders and inverse Gaussian distributions, which possess distinctive properties and theoretical arguments useful for ISI description. We expand the use of CD distributions to the modeling of neural spiking behavior, mainly by testing the suitability of the Birnbaum-Saunders distribution, which has not been studied in the setting of neural activity. We validate this expansion with original experimental and simulated electrophysiological data. PMID:25998210

  4. Avionics Box Cold Plate Damage Prevention

    NASA Technical Reports Server (NTRS)

    Stambolian, Damon; Larcher, Steven; Henderson, Gena; Tran, Donald

    2011-01-01

    Over the years there have been several occurrences of damage to Space Shuttle Orbiter cold plates during removal and replacement of avionics boxes. Thus a process improvement team was put together to determine ways to prevent these kinds of damage. From this effort there were many solutions including, protective covers, training, and improved operations instructions. The focus of this paper is to explain the cold plate damage problem and the corrective actions for preventing future damage to aerospace avionics cold plate designs.

  5. Neural Stability, Sparing, and Behavioral Recovery Following Brain Damage

    ERIC Educational Resources Information Center

    LeVere, T. E.

    1975-01-01

    The present article discusses the possibility that behavioral recovery following brain damage is not dependent on the functional reorganization of neural tissue but is rather the result of the continued normal operation of spared neural mechanisms. (Editor)

  6. Prevention of chemotherapy-induced ovarian damage.

    PubMed

    Roness, Hadassa; Kashi, Oren; Meirow, Dror

    2016-01-01

    Recent advances in our understanding of the mechanisms underlying the impact of cytotoxic drugs on the ovary have opened up new directions for the protection of the ovary from chemotherapy-induced damage. These advances have spurred the investigation of pharmacological agents to prevent ovarian damage at the time of treatment. Prevention of ovarian damage and follicle loss would provide significant advantages over existing fertility preservation techniques. This manuscript reviews new methods for the prevention of chemotherapy-induced ovarian damage, including agents that act on the PI3K/PTEN/Akt follicle activation pathway, apoptotic pathways, the vascular system, and other potential methods of reducing chemotherapy-induced ovotoxicity. PMID:26677788

  7. Genetic optimisation of a neural damage locator

    NASA Astrophysics Data System (ADS)

    Worden, K.; Manson, G.; Hilson, G.; Pierce, S. G.

    2008-01-01

    A critical problem in structural health monitoring (SHM) based on pattern recognition methods is the correct selection of features, i.e. measured and processed data for the diagnosis. Various selection strategies have been applied in the past and one approach that has proved effective is the use of combinatorial optimisation methods. This paper presents a case study based on a scheme for damage location in an aircraft wing. The feature selection algorithm is a Genetic Algorithm and the locator (classifier) is an artificial neural network. A comparison is made with the results obtained when the features are selected on the basis of engineering judgement. The study is seen to raise some issues relating to model complexity and generalisation and these matters are discussed in some detail.

  8. 77 FR 31827 - Pipeline Safety: Pipeline Damage Prevention Programs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-30

    ... Safety: Pipeline Damage Prevention Programs AGENCY: Pipeline and Hazardous Materials Safety... excavation damage prevention law enforcement programs; establish an administrative process for making... excavation damage prevention law enforcement programs; and establish the adjudication process...

  9. Apparent damage accumulation in cancellous bone using neural networks.

    PubMed

    Hambli, Ridha

    2011-08-01

    In this paper, a neural network model is developed to simulate the accumulation of apparent fatigue damage of 3D trabecular bone architecture at a given bone site during cyclic loading. The method is based on five steps: (i) performing suitable numerical experiments to simulate fatigue accumulation of a 3D micro-CT trabecular bone samples taken from proximal femur for different combinations of loading conditions; (ii) averaging the sample outputs in terms of apparent damage at whole specimen level based on local tissue damage; (iii) preparation of a proper set of corresponding input-output data to train the network to identify apparent damage evolution; (iv) training the neural network based on the results of step (iii); (v) application of the neural network as a tool to estimate rapidly the apparent damage evolution at a given bone site. The proposed NN model can be incorporated into finite element codes to perform fatigue damage simulation at continuum level including some morphological factors and some bone material properties. The proposed neural network based multiscale approach is the first model, to the author's knowledge, that incorporates both finite element analysis and neural network computation to rapidly simulate multilevel fatigue of bone. This is beneficial to develop enhanced finite element models to investigate the role of damage accumulation on bone damage repair during remodelling. PMID:21616468

  10. Avionics Box Cold Plate Damage Prevention

    NASA Technical Reports Server (NTRS)

    Stambolian, Damon B.; Larchar, Steven W.; Henderson, Gena; Tran, Donald; Barth, Tim

    2012-01-01

    Problem Introduction: 1. Prevent Cold Plate Damage in Space Shuttle. 1a. The number of cold plate problems had increased from an average of 16.5 per/year between 1990 through 2000, to an average of 39.6 per year between 2001through 2005. 1b. Each complete set of 80 cold plates cost approximately $29 million, an average of $362,500 per cold plate. 1c It takes four months to produce a single cold plate. 2. Prevent Cold Plate Damage in Future Space Vehicles.

  11. 49 CFR 192.614 - Damage prevention program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Damage prevention program. 192.614 Section 192.614... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Operations § 192.614 Damage prevention program. (a... section (b)(1) or (b)(2) of this section. (1) The state has adopted a one-call damage prevention...

  12. 49 CFR 195.442 - Damage prevention program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Damage prevention program. 195.442 Section 195.442... PIPELINE Operation and Maintenance § 195.442 Damage prevention program. (a) Except as provided in paragraph... section. (1) The state has adopted a one-call damage prevention program under § 198.37 of this chapter;...

  13. Restoration of function after brain damage using a neural prosthesis

    PubMed Central

    Guggenmos, David J.; Azin, Meysam; Barbay, Scott; Mahnken, Jonathan D.; Dunham, Caleb; Mohseni, Pedram; Nudo, Randolph J.

    2013-01-01

    Neural interface systems are becoming increasingly more feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as a communication link between distant locations in the cerebral cortex. The primary motor area in the cerebral cortex was injured in a rat model of focal brain injury, disrupting communication between motor and somatosensory areas and resulting in impaired reaching and grasping abilities. After implantation of microelectrodes in cerebral cortex, a neural prosthesis discriminated action potentials (spikes) in premotor cortex that triggered electrical stimulation in somatosensory cortex continuously over subsequent weeks. Within 1 wk, while receiving spike-triggered stimulation, rats showed substantially improved reaching and grasping functions that were indistinguishable from prelesion levels by 2 wk. Post hoc analysis of the spikes evoked by the stimulation provides compelling evidence that the neural prosthesis enhanced functional connectivity between the two target areas. This proof-of-concept study demonstrates that neural interface systems can be used effectively to bridge damaged neural pathways functionally and promote recovery after brain injury. PMID:24324155

  14. Partially flexible MEMS neural probe composed of polyimide and sucrose gel for reducing brain damage during and after implantation

    NASA Astrophysics Data System (ADS)

    Jeon, Myounggun; Cho, Jeiwon; Kim, Yun Kyung; Jung, Dahee; Yoon, Eui-Sung; Shin, Sehyun; Cho, Il-Joo

    2014-02-01

    This paper presents a flexible microelectromechanical systems (MEMS) neural probe that minimizes neuron damage and immune response, suitable for chronic recording applications. MEMS neural probes with various features such as high electrode densities have been actively investigated for neuron stimulation and recording to study brain functions. However, successful recording of neural signals in chronic application using rigid silicon probes still remains challenging because of cell death and macrophages accumulated around the electrodes over time from continuous brain movement. Thus, in this paper, we propose a new flexible MEMS neural probe that consists of two segments: a polyimide-based, flexible segment for connection and a rigid segment composed of thin silicon for insertion. While the flexible connection segment is designed to reduce the long-term chronic neuron damage, the thin insertion segment is designed to minimize the brain damage during the insertion process. The proposed flexible neural probe was successfully fabricated using the MEMS process on a silicon on insulator wafer. For a successful insertion, a biodegradable sucrose gel is coated on the flexible segment to temporarily increase the probe stiffness to prevent buckling. After the insertion, the sucrose gel dissolves inside the brain exposing the polyimide probe. By performing an insertion test, we confirm that the flexible probe has enough stiffness. In addition, by monitoring immune responses and brain histology, we successfully demonstrate that the proposed flexible neural probe incurs fivefold less neural damage than that incurred by a conventional silicon neural probe. Therefore, the presented flexible neural probe is a promising candidate for recording stable neural signals for long-time chronic applications.

  15. Preventing Electrostatic-Discharge Damage to Electronics

    NASA Technical Reports Server (NTRS)

    Read, W. S.; Dozois, P. C.; Lonborg, J. O.

    1986-01-01

    Booklet discusses damage to electronic components caused by electrostatic discharges during assembly. Describes procedure for setting up static-free workplace for handling and assembling electronic components.

  16. Folic Acid for the Prevention of Infant Neural Tube Defects: U.S. Preventive Services Task Force Recommendation

    MedlinePlus

    Annals of Internal Medicine Summaries for Patients Folic Acid for the Prevention of Infant Neural Tube Defects: ... modern medicine. The full reports are titled “Folic Acid for the Prevention of Neural Tube Defects: U.S. ...

  17. Damage Identification in Cable-Stayed Bridge Based on Modal Analysis and Neural Networks

    NASA Astrophysics Data System (ADS)

    Zhang, Xiedong; Zhang, Zhiguo; Li, Xiaofan; Zhan, Hao

    2007-03-01

    A damage-detection-oriented finite element model of a cable-stayed highway bridge is established and the modal analysis is then carried out. Modal frequency, displacement modal shape and curvature modal shape are included in BP neural network input vector. BP neural network models are established for bridge damage detection. The result indicates that the method based on vibration modal analysis theory and BP neural networks can detect both the position and degree of the damage.

  18. [Folic acid: Primary prevention of neural tube defects. Literature Review].

    PubMed

    Llamas Centeno, M J; Miguélez Lago, C

    2016-03-01

    Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects. PMID:26959966

  19. Can neural blocks prevent phantom limb pain?

    PubMed

    Borghi, Battista; D'Addabbo, Marco; Borghi, Raffaele

    2014-07-01

    Phantom limb syndrome (PLS) is a syndrome including stump pain, phantom limb pain and not-painful phantom sensations, which involves a large part of amputee patients and often has devastating effects on their quality of life. The efficacy of standard therapies is very poor. Nerve blocks have been investigated for the treatment and prevention of PLS. Epidural and peripheral blocks limited to the first three postamputation days can only reduce acute pain but cannot prevent the later development of PLS. Recent studies have shown that ambulatory prolonged peripheral nerve block (up to 30 days postamputation) may represent a new possible option to treat phantom pain and prevent the development of PLS and chronic pain. PMID:25300383

  20. Preventing Arc Welding From Damaging Electronics

    NASA Technical Reports Server (NTRS)

    Sargent, Noel; Mareen, D.

    1988-01-01

    Shielding technique developed to protect sensitive electronic equipment from damage due to electromagnetic disturbances produced by arc welding. Established acceptable alternative in instances in which electronic equipment cannot be removed prior to arc welding. Guidelines established for open, unshielded welds. Procedure applicable to robotics or computer-aided manufacturing.

  1. Preventing Ultraviolet Light-Induced Damage: The Benefits of Antioxidants

    ERIC Educational Resources Information Center

    Yip, Cheng-Wai

    2007-01-01

    Extracts of fruit peels contain antioxidants that protect the bacterium "Escherichia coli" against damage induced by ultraviolet light. Antioxidants neutralise free radicals, thus preventing oxidative damage to cells and deoxyribonucleic acid. A high survival rate of UV-exposed cells was observed when grapefruit or grape peel extract was added,…

  2. Identification process of corn and barley kernel damages using neural image analysis

    NASA Astrophysics Data System (ADS)

    Nowakowski, K.; Boniecki, P.; Tomczak, R. J.; Raba, B.

    2011-06-01

    The subject of the study was to develop a neural model for the identification of mechanical damage in grain caryopses based on digital photographs. The authors has selected a set of universal features that distinguish between damaged and healthy caryopses. The study has produced an artificial neural network of a multilayer perceptron type whose identification capacity approximates that of a human.

  3. Pattern Learning, Damage and Repair within Biological Neural Networks

    NASA Astrophysics Data System (ADS)

    Siu, Theodore; Fitzgerald O'Neill, Kate; Shinbrot, Troy

    2015-03-01

    Traumatic brain injury (TBI) causes damage to neural networks, potentially leading to disability or even death. Nearly one in ten of these patients die, and most of the remainder suffer from symptoms ranging from headaches and nausea to convulsions and paralysis. In vitro studies to develop treatments for TBI have limited in vivo applicability, and in vitro therapies have even proven to worsen the outcome of TBI patients. We propose that this disconnect between in vitro and in vivo outcomes may be associated with the fact that in vitro tests assess indirect measures of neuronal health, but do not investigate the actual function of neuronal networks. Therefore in this talk, we examine both in vitro and in silico neuronal networks that actually perform a function: pattern identification. We allow the networks to execute genetic, Hebbian, learning, and additionally, we examine the effects of damage and subsequent repair within our networks. We show that the length of repaired connections affects the overall pattern learning performance of the network and we propose therapies that may improve function following TBI in clinical settings.

  4. Retrospective review of thoracic neural damage during lung ablation - what the interventional radiologist needs to know about neural thoracic anatomy

    SciTech Connect

    Palussiere, Jean; Canella, Mathieu; Cornelis, Francois; Catena, Vittorio; Descat, Edouard; Brouste, Veronique; Montaudon, Michel

    2013-12-15

    Background and Purpose: Radiofrequency ablation (RFA) is associated with low neural morbidity compared with surgery, which commonly causes debilitating long-term pain. The purpose was to review the thoracic neural anatomy relevant to percutaneous RFA and to retrospectively review symptomatic nerve injury after lung RFA at our institution. Materials and Methods: We retrospectively examined all symptomatic nerve injuries occurring after computed tomography (CT)-guided RFA treatment of lung tumors for 462 patients/509 procedures/708 lesions treated at our large tertiary referral centre during 10 years. Results: Eight patients experienced neurological complications after heating during the RFA procedure. These complications occurred in the phrenic (n = 1), brachial (n = 3), left recurrent (n = 1), and intercostal nerves (n = 2) and the stellate ganglion (n = 1). Three were grade 2, four grade 3 and one grade 4 injuries (CTCAE v3). Conclusion: Although rare, neurological complications can occur after RFA, and they can occasionally be severe. To prevent these complications, it is important for the interventional radiologist to be aware of the anatomy of nervous structures and to attempt to identify nerves on CT scans during the RFA procedure. Creating a pneumothorax can be useful to avoid nerve damage and related clinical complications.

  5. The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats.

    PubMed

    Seghatoleslam, Masoumeh; Alipour, Fatemeh; Shafieian, Reihaneh; Hassanzadeh, Zahra; Edalatmanesh, Mohammad Amin; Sadeghnia, Hamid Reza; Hosseini, Mahmoud

    2016-07-01

    Nigella sativa (NS) has been suggested to have neuroprotective and anti-seizures properties. The aim of current study was to investigate the effects of NS hydro-alcoholic extract on neural damage after pentylenetetrazole (PTZ) - induced repeated seizures. The rats were divided into five groups: (1) control (saline), (2) PTZ (50 mg/kg, i.p.), (3-5) PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 (100, 200 and 400 mg/kg of NS extract respectively, 30 min prior to each PTZ injection on 5 consecutive days). The passive avoidance (PA) test was done and the brains were then removed for histological measurements. The PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 groups had lower seizure scores than PTZ group (P < 0.01 and P < 0.001). The latency to enter the dark compartment by the animals of PTZ group was lower than control in PA test (P < 0.01). Pre-treatment by 400 mg/kg of the extract increased the latency to enter the dark compartment (P < 0.05). Meanwhile, different doses of the extract inhibited production of dark neurons in different regions of hippocampus (P < 0.001). The present study allows us to suggest that the NS possesses a potential ability to prevent hippocampal neural damage which is accompanied with improving effects on memory. PMID:27419091

  6. Electrostatic risks to reticles and damage prevention methodology

    NASA Astrophysics Data System (ADS)

    Rider, Gavin C.

    2016-03-01

    In recent years a great deal of effort has been expended to try and reduce the reticle ESD damage problem. Methods are almost all based on the standard principles developed for the protection of ESD sensitive electronic devices - but reticles are not the same as electronic devices. Reticles are predominantly damaged by electric field rather than the conductive transfer of static charge, and the physical mechanisms that damage reticles are different from those that damage electronic devices. This paper explains why some of the established methods for ESD prevention are not the best way to protect reticles and in some cases actually increase the risk of reticle damage. Measurements are presented showing that, contrary to the widely held opinion and current practice in semiconductor manufacturing, static dissipative plastic is not the best material to use for the construction of reticle pods. An appropriate combination of insulating material and metallic shielding is shown to provide the best electrostatic protection for reticles.

  7. Adapter assembly prevents damage to tubing during high pressure tests

    NASA Technical Reports Server (NTRS)

    Stinett, L. L.

    1965-01-01

    Portable adapter assembly prevents damage to tubing and injury to personnel when pressurizing a system or during high pressure tests. The assembly is capable of withstanding high pressure. It is securely attached to the tubing stub end and may be removed without brazing, cutting or cleaning the tube.

  8. A fatigue damage estimator using RBF, backpropagation, and CID4 neural algorithms

    NASA Technical Reports Server (NTRS)

    Cios, Krzysztof J.; Tjia, Robert E.; Liu, Ning

    1992-01-01

    Fatigue damage estimation using neural networks is described in the paper. Attention is focused on the method of data generation for both the training and test data used by radial basis function (RBF), backpropagation, and CID4 algorithms used in this study. The performance results of the three neural algorithms are analyzed in terms of their strengths and weaknesses in training.

  9. Model-Trained Neural Networks and Electronic Holography Demonstrated to Detect Damage in Blades

    NASA Technical Reports Server (NTRS)

    Decker, Arthur J.; Fite, E. Brian; Mehmed, Oral; Thorp, Scott A.

    1998-01-01

    Detect Damage in Blades Electronic holography can show damaged regions in fan blades at 30 frames/sec. The electronic holograms are transformed by finite-element-model-trained artificial neural networks to visualize the damage. The trained neural networks are linked with video and graphics to visualize the bending-induced strain distribution, which is very sensitive to damage. By contrast, it is very difficult to detect damage by viewing the raw, speckled, characteristic fringe patterns. For neural-network visualization of damage, 2 frames or 2 fields are used, rather than the 12 frames normally used to compute the displacement distribution from electronic holograms. At the NASA Lewis Research Center, finite element models are used to compute displacement and strain distributions for the vibration modes of undamaged and cracked blades. A model of electronic time-averaged holography is used to transform the displacement distributions into finite-element-resolution characteristic fringe patterns. Then, a feedforward neural network is trained with the fringe-pattern/strain-pattern pairs, and the neural network, electronic holography, and video are implemented on a workstation. Now that the neural networks have been tested successfully at 30 frames/sec on undamaged and cracked cantilevers, the electronic holography and neural-network processing are being adapted for onsite damage inspection of twisted fan blades and rotormounted blades. Our conclusion is that model-trained neural nets are effective when they are trained with good models whose application is well understood. This work supports the aeromechanical testing portion of the Advanced Subsonic Technology Project.

  10. Metformin Treatment Prevents Sedentariness Related Damages in Mice

    PubMed Central

    Senesi, Pamela; Montesano, Anna; Luzi, Livio; Codella, Roberto; Benedini, Stefano; Terruzzi, Ileana

    2016-01-01

    Metformin (METF), historical antihyperglycemic drug, is a likely candidate for lifespan extension, treatment and prevention of sedentariness damages, insulin resistance, and obesity. Skeletal muscle is a highly adaptable tissue, capable of hypertrophy response to resistance training and of regeneration after damage. Aims of this work were to investigate METF ability to prevent sedentariness damage and to enhance skeletal muscle function. Sedentary 12-week-old C57BL/6 mice were treated with METF (250 mg/kg per day, in drinking water) for 60 days. METF role on skeletal muscle differentiation was studied in vitro using murine C2C12 myoblasts. Muscular performance evaluation revealed that METF enhanced mice physical performance (Estimated VO2max). Biochemical analyses of hepatic and muscular tissues indicated that in liver METF increased AMPK and CAMKII signaling. In contrast, METF inactivated ERKs, the principal kinases involved in hepatic stress. In skeletal muscle, METF activated AKT, key kinase in skeletal muscle mass maintenance. In in vitro studies, METF did not modify the C2C12 proliferation capacity, while it positively influenced the differentiation process and myotube maturation. In conclusion, our novel results suggest that METF has a positive action not only on the promotion of healthy aging but also on the prevention of sedentariness damages. PMID:26697506

  11. Trehalose prevents neural tube defects by correcting maternal diabetes-suppressed autophagy and neurogenesis

    PubMed Central

    Xu, Cheng; Li, Xuezheng; Wang, Fang; Weng, Hongbo

    2013-01-01

    Preexisting maternal diabetes increases the risk of neural tube defects (NTDs). The mechanism underlying maternal diabetes-induced NTDs is not totally defined, and its prevention remains a challenge. Autophagy, an intracellular process to degrade dysfunction protein and damaged cellular organelles, regulates cell proliferation, differentiation, and apoptosis. Because autophagy impairment causes NTDs reminiscent of those observed in diabetic pregnancies, we hypothesize that maternal diabetes-induced autophagy impairment causes NTD formation by disrupting cellular homeostasis, leading to endoplasmic reticulum (ER) stress and apoptosis, and that restoration of autophagy by trehalose, a natural disaccharide, prevents diabetes-induced NTDs. Embryos from nondiabetic and type 1 diabetic mice fed with or without 2 or 5% trehalose water were used to assess markers of autophagy, ER stress, and neurogenesis, numbers of autophagosomes, gene expression that regulates autophagy, NTD rates, indices of mitochondrial dysfunction, and neuroepithelial cell apoptosis. Maternal diabetes suppressed autophagy by significantly reducing LC3-II expression, autophagosome numbers, and GFP-LC3 punctate foci in neuroepithelial cells and by altering autophagy-related gene expression. Maternal diabetes delayed neurogenesis by blocking Sox1 neural progenitor differentiation. Trehalose treatment reversed autophagy impairment and prevented NTDs in diabetic pregnancies. Trehalose resolved homeostatic imbalance by correcting mitochondrial defects, dysfunctional proteins, ER stress, apoptosis, and delayed neurogenesis in the neural tubes exposed to hyperglycemia. Our study demonstrates for the first time that maternal diabetes suppresses autophagy in neuroepithelial cells of the developing neural tube, leading to NTD formation, and provides evidence for the potential efficacy of trehalose as an intervention against hyperglycemia-induced NTDs. PMID:23880312

  12. Mouse models of neural tube defects: investigating preventive mechanisms.

    PubMed

    Greene, Nicholas D E; Copp, Andrew J

    2005-05-15

    Neural tube defects (NTD), including anencephaly and spina bifida, are a group of severe congenital abnormalities in which the future brain and/or spinal cord fail to close. In mice, NTD may result from genetic mutations or knockouts, or from exposure to teratogenic agents, several of which are known risk factors in humans. Among the many mouse NTD models that have been identified to date, a number have been tested for possible primary prevention of NTD by exogenous agents, such as folic acid. In genetic NTD models such as Cart1, splotch, Cited2, and crooked tail, and NTD induced by teratogens including valproic acid and fumonisins, the incidence of defects is reduced by maternal folic acid supplementation. These folate-responsive models provide an opportunity to investigate the possible mechanisms underlying prevention of NTD by folic acid in humans. In another group of mouse models, that includes curly tail, axial defects, and the Ephrin-A5 knockout, NTD are not preventable by folic acid, reflecting the situation in humans in which a subset of NTD appear resistant to folic acid therapy. In this group of mutants alternative preventive agents, including inositol and methionine, have been shown to be effective. Overall, the data from mouse models suggests that a broad-based in utero therapy may offer scope for prevention of a greater proportion of NTD than is currently possible. PMID:15800852

  13. Epidemiology, prenatal management, and prevention of neural tube defects

    PubMed Central

    Salih, Mustafa A.; Murshid, Waleed R.; Seidahmed, Mohammed Z.

    2014-01-01

    This review article discusses the epidemiology, risk factors, prenatal screening, diagnosis, prevention potentials, and epidemiologic impact of neural tube defects (NTDs). The average incidence of NTDs is 1/1000 births, with a marked geographic variation. In the developed countries, the incidence of NTDs has fallen over recent decades. However, it still remains high in the less-developed countries in Latin America, Africa, the Middle East, Asia, and the Far East (>1 to 11/1000 births). Recognized NTDs risks include maternal diabetes, obesity, lower socioeconomic status, hyperthermia, and exposure to certain teratogens during the periconceptional period. Periconceptional folic acid supplementation decreased the prevalence of NTDs by 50-70%, and an obligatory folic acid fortification of food was adopted in several countries to reach women with unplanned pregnancies and those facing social deprivation. Prevention of NTDs can be accelerated if more, especially low income countries, adopted fortification of the staple food in their communities. PMID:25551106

  14. 49 CFR 198.37 - State one-call damage prevention program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false State one-call damage prevention program. 198.37... REGULATIONS FOR GRANTS TO AID STATE PIPELINE SAFETY PROGRAMS Adoption of One-Call Damage Prevention Program § 198.37 State one-call damage prevention program. A State must adopt a one-call damage...

  15. High-density lipoprotein prevents organ damage in endotoxemia.

    PubMed

    Lee, Ru-Ping; Lin, Nien-Tsung; Chao, Yann-Fen Chiou; Lin, Chia-Chin; Harn, Horng-Jyh; Chen, Hsing-I

    2007-06-01

    High-density lipoprotein (HDL) may decrease organ injury in sepsis. This study was designed using an animal model to mimic people who had a high HDL level and to test HDL effects on preventing organ damage in endotoxemia. Endotoxemia was induced by an infusion of lipopolysac-charide (LPS) after HDL or LDL administration. Levels of blood biochemical substances, nitrate/nitrite, and TNF-alpha in sera were measured. Pathological examinations were performed 72 hours after LPS infusion. HDL decreased the endotoxin-induced elevation of AST, ALT, BUN, creatinine, LDH, CPK, nitrate/nitrite, and TNF-alpha. On histological examination, neutrophil infiltration was lower in the HDL group. HDL had a significant effect in preventing endotoxin-induced organ damage. PMID:17514720

  16. Prevention of Neural Tube Defects. ARC Q&A #101-45.

    ERIC Educational Resources Information Center

    Arc, Arlington, TX.

    This fact sheet uses a question-and-answer format to summarize issues related to the prevention of neural tube defects. Questions and answers address the following topics: what neural tube defects are and the most common types (spina bifida and anencephaly); occurrence of neural tube defects during the first month of pregnancy; the frequency of…

  17. Pathophysiology, prevention, and potential treatment of neural tube defects.

    PubMed

    Manning, S M; Jennings, R; Madsen, J R

    2000-01-01

    Neural tube defects (NTD) remain a major cause of morbidity in spite of the reduction in liveborn incidence with periconceptional folic acid. However, the etiology remains unknown. This article reviews studies that address causation and potential treatment of NTD in humans and in animal models that resemble aspects of the common human NTD. Studies of nutritional markers of vitamin B12 and folic acid support a defect in homocysteine metabolism; a thermolabile variant of methylene tetrahydrofolate reductase, an enzyme that remethylates homocysteine to methionine, correlates with a risk of NTD in some human populations. Numerous mouse mutant models of NTD exist, attesting to the ease of disruption of neurulation, and a genetic basis for this malformation. Of these models, the curly tail mouse mutant most closely resembles the common human NTD. Folic acid does not prevent NTD in this model; however inositol supplementation does result in a significant reduction in incidence. Recent advances in fetal surgery, and evidence from mechanically created myelomeningocele in large animals amenable to surgical intervention suggest that the handicaps associated with myelomeningocele and associated Chiari Type II malformation may be prevented by in utero NTD closure. Success will depend on preservation of neurological tissue until such intervention is possible. Further research in animal models at the genetic and cellular levels, together with technological surgical advances, provide hope that prevention of more NTD and the associated handicaps may be possible. MRDD Research Reviews 6:6-14, 2000. PMID:10899792

  18. NBQX and TCP prevent soman-induced hippocampal damage

    SciTech Connect

    Lallement, G.; Carpentier, P.; Pernot-Marino, I.; Baubichon, D.; Blanchet, G.

    1993-05-13

    In a previous investigation we demonstrated that the measurement of w3 (peripheral-type benzodiazepine) binding site densities could be of widespread applicability in the localization and quantification of soman-induced damage in the central nervous system. We thus used this marker to assess, in mouse hippocampus, the neuroprotective activity against soman-induced brain damage of NBQX and TCP which are respective antagonists of non-NMDA and NMDA glutamatergic receptors. Injection of NBQX at 20 or 40 mg/kg 5 min prior to soman totally prevented the neuronal damage. Comparatively, TCP had neuroprotective efficacy when administered at l mg/kg 5 min prior to soman followed by a reinjection 1 hour after. These results demonstrate that both NBQX and TCP afford a satisfactory neuroprotection against soman-induced brain damage. Since it is known that the neuropathology due to soman is closely seizure-related, it is likely that the neuroprotective activities of NBQX and TCP are related to the respective roles of non-NMDA and NMDA receptors in the onset and maintenance of soman-induced seizures.

  19. Neural tube defects: prevention by folic acid and other vitamins.

    PubMed

    Copp, A J; Greene, N D

    2000-12-01

    Folic acid has been demonstrated in clinical trials to reduce significantly the recurrence (and probably occurrence) of neural tube defects (NTD). In the U.K., there has been no decline in prevalence of NTD since the publication of the findings with folic acid. This article examines a series of questions relating to the action of folic acid, with emphasis on the use of mouse models as a source of experimental information which cannot easily be obtained by direct study of humans. Several mouse genetic NTD models exhibit sensitivity to prevention by folic acid, whereas other mice which develop morphologically similar NTD are resistant. Folic acid normalises neurulation in the sensitive mouse strains, providing evidence for a direct effect on the developing embryo, not on the pregnant female: Mouse studies do not support the proposed action of folic acid in encouraging the in utero demise of affected fetuses (i.e. terathanasia). Polymorphic variants of several folate-related enzymes have been shown to influence risk of NTD in humans and an inherited abnormality of folate metabolism has been demonstrated in one mouse NTD model. However, the biochemical basis of the action of folic acid in preventing NTD remains to be determined in detail. NTD in one folate-resistant mouse strain can be prevented by myo-inositol, both in utero and in vitro, raising the possibility of a therapeutic role also in humans. Gene-gene interactions seem likely to underlie the majority of NTD, suggesting that poly-therapy involving folic acid and other agents, such as myo-inositol, may prove more effective in preventing NTD than folic acid treatment alone. PMID:11262991

  20. Structural Damage Identification Based on Rough Sets and Artificial Neural Network

    PubMed Central

    Liu, Chengyin; Wu, Xiang; Wu, Ning; Liu, Chunyu

    2014-01-01

    This paper investigates potential applications of the rough sets (RS) theory and artificial neural network (ANN) method on structural damage detection. An information entropy based discretization algorithm in RS is applied for dimension reduction of the original damage database obtained from finite element analysis (FEA). The proposed approach is tested with a 14-bay steel truss model for structural damage detection. The experimental results show that the damage features can be extracted efficiently from the combined utilization of RS and ANN methods even the volume of measurement data is enormous and with uncertainties. PMID:25013847

  1. Structural damage identification based on rough sets and artificial neural network.

    PubMed

    Liu, Chengyin; Wu, Xiang; Wu, Ning; Liu, Chunyu

    2014-01-01

    This paper investigates potential applications of the rough sets (RS) theory and artificial neural network (ANN) method on structural damage detection. An information entropy based discretization algorithm in RS is applied for dimension reduction of the original damage database obtained from finite element analysis (FEA). The proposed approach is tested with a 14-bay steel truss model for structural damage detection. The experimental results show that the damage features can be extracted efficiently from the combined utilization of RS and ANN methods even the volume of measurement data is enormous and with uncertainties. PMID:25013847

  2. Devices prevent ice damage to trusses of semi

    SciTech Connect

    Marthinsen, A.

    1985-04-01

    Much exploration drilling is done in subarctic waters around the world, and this will be important in the future. Special demands will be made on the drilling structures to enable them to withstand collisions with drifting ice. A Newfoundland Certificate of Fitness, for example, says a vessel must be able to tolerate collision with the largest iceberg that can be undetectable by radar, with out the danger of platform collapse. The iceberg in this case is defined as having a weight of 5000 tons and a drifting velocity of 2 meters/second. Devices to prevent ice damage to the trusses of semisubmersibles are discussed.

  3. 49 CFR 198.35 - Grants conditioned on adoption of one-call damage prevention program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... prevention program. 198.35 Section 198.35 Transportation Other Regulations Relating to Transportation... Prevention Program § 198.35 Grants conditioned on adoption of one-call damage prevention program. In... considers whether a State has adopted or is seeking to adopt a one-call damage prevention program...

  4. Moisture-associated skin damage: aetiology, prevention and treatment.

    PubMed

    Voegeli, David

    The concept of excessive moisture causing damage to the skin is not a new one, and provides a rationale for many fundamental nursing interventions. Although traditionally thought of as a specific problem of continence care, it is a common problem encountered in many different patient groups. As a consequence the umbrella term moisture-associated skin damage (MASD) has been introduced to describe the spectrum of damage that occurs in response to the prolonged exposure of a patient's skin to perspiration, urine, faeces or wound exudate. It is generally accepted that MASD consists of four main separate conditions, each having slightly different aetiologies, all of which will be explored in this paper. Careful assessment can help distinguish between the four and enable appropriate prevention and treatment interventions to be implemented. Whatever causes the excessive moisture, effective interventions should consist of the adoption of a structured skin care regime to cleanse and protect, methods to keep the skin dry, controlling the source of the excessive moisture and treating any secondary infection. PMID:22585263

  5. Bee Products Prevent Agrichemical-Induced Oxidative Damage in Fish

    PubMed Central

    Ferreira, Daiane; Rocha, Helio Carlos; Kreutz, Luiz Carlos; Loro, Vania Lucia; Marqueze, Alessandra; Koakoski, Gessi; Santos da Rosa, João Gabriel; Gusso, Darlan; Oliveira, Thiago Acosta; de Abreu, Murilo Sander; Barcellos, Leonardo José Gil

    2013-01-01

    In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g) were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™) and a group that was exposed to 0.88 mg L−1 of TEB alone (corresponding to 16.6% of the 96-h LC50). We show that waterborne bee products, including royal jelly (RJ), honey (H), bee pollen (BP) and propolis (P), reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) are increased. PMID:24098336

  6. Hydrogen prevents corneal endothelial damage in phacoemulsification cataract surgery.

    PubMed

    Igarashi, Tsutomu; Ohsawa, Ikuroh; Kobayashi, Maika; Igarashi, Toru; Suzuki, Hisaharu; Iketani, Masumi; Takahashi, Hiroshi

    2016-01-01

    In phacoemulsification, ultrasound induces hydroxyl radical (·OH) formation, damaging corneal endothelium. Whether H2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H2 was dissolved in a commercial irrigating solution. The effects of H2 against ·OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude, and fluorescence intensity by oxidized HPF was significantly less in the H2-dissolved solution. The effects of H2 in phacoemulsification were evaluated in rabbits, comparing H2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H2 group. In conclusion, H2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage. PMID:27498755

  7. Hydrogen prevents corneal endothelial damage in phacoemulsification cataract surgery

    PubMed Central

    Igarashi, Tsutomu; Ohsawa, Ikuroh; Kobayashi, Maika; Igarashi, Toru; Suzuki, Hisaharu; Iketani, Masumi; Takahashi, Hiroshi

    2016-01-01

    In phacoemulsification, ultrasound induces hydroxyl radical (·OH) formation, damaging corneal endothelium. Whether H2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H2 was dissolved in a commercial irrigating solution. The effects of H2 against ·OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude, and fluorescence intensity by oxidized HPF was significantly less in the H2-dissolved solution. The effects of H2 in phacoemulsification were evaluated in rabbits, comparing H2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H2 group. In conclusion, H2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage. PMID:27498755

  8. Experience-Dependent Neural Plasticity in the Adult Damaged Brain

    ERIC Educational Resources Information Center

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

  9. Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage

    PubMed Central

    Kang, Bong Gu; Lee, Se Jeong; Kim, Kang Ho; Yang, Heekyoung; Lee, Young-Ae; Cho, Yu Jin; Im, Yong-Seok; Lee, Dong-Sup; Lim, Do-Hoon; Kim, Dong Hyun; Um, Hong-Duck; Lee, Sang-Hun; Lee, Jung-II; Nam, Do-Hyun

    2012-01-01

    Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases. PMID:22347993

  10. Principles of Experience-Dependent Neural Plasticity: Implications for Rehabilitation after Brain Damage

    ERIC Educational Resources Information Center

    Kleim, Jeffrey A.; Jones, Theresa A.

    2008-01-01

    Purpose: This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. Method: Neuroscience research using a variety of models of learning, neurological disease, and trauma are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the…

  11. Prevention of oxidative DNA damage in rats by brussels sprouts.

    PubMed

    Deng, X S; Tuo, J; Poulsen, H E; Loft, S

    1998-03-01

    The alleged cancer preventive effects of cruciferous vegetables could be related to protection from mutagenic oxidative DNA damage. We have studied the effects of Brussels sprouts, some non-cruciferous vegetables and isolated glucosinolates on spontaneous and induced oxidative DNA damage in terms of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in groups of 6-8 male Wistar rats. Excess oxidative DNA damage was induced by 2-nitropropane (2-NP 100 mg/kg). Four days oral administration of 3 g of cooked Brussels sprouts homogenate reduced the spontaneous urinary 8-oxodG excretion by 31% (p<0.05) whereas raw sprouts, beans and endive (1:1), isolated indolyl glucosinolates and breakdown products had no significant effect. An aqueous extract of cooked Brussels sprouts (corresponding to 6.7 g vegetable per day for 4 days) decreased the spontaneous 8-oxodG excretion from 92 +/- 12 to 52 +/- 15 pmol/24 h (p<0.05). After 2-NP administration the 8-oxodG excretion was increased to 132 +/- 26 pmol/24 h (p<0.05) whereas pretreatment with the sprouts extract reduced this to 102 +/- 30 pmol/24 h (p<0.05). The spontaneous level of 8-oxodG in nuclear DNA from liver and bone marrow was not significantly affected by the sprouts extract whereas the level decreased by 27% in the kidney (p<0.05). In the liver 2-NP increased the 8-oxodG levels in nuclear DNA 8.7 and 3.8 times (p<0.05) 6 and 24 h after dose, respectively. The sprouts extract reduced this increase by 57% (p<0.05) at 6 h whereas there was no significant effect at 24 h. In the kidneys 2-NP increased the 8-oxodG levels 2.2 and 1.2 times (p<0.05) 6 and 24 h after dose, respectively. Pretreatment with the sprouts extract abolished these increases (p<0.05). Similarly, in the bone marrow the extract protected completely (p<0.05) against a 4.9-fold 2-NP induced increase (p<0.05) in the 8-oxodG level. These findings demonstrate that cooked Brussels sprouts contain bioactive substance(s) with a potential for reducing the physiological

  12. Damage identification for large span structure based on multiscale inputs to artificial neural networks.

    PubMed

    Lu, Wei; Teng, Jun; Cui, Yan

    2014-01-01

    In structural health monitoring system, little research on the damage identification from different types of sensors applied to large span structure has been done in the field. In fact, it is significant to estimate the whole structural safety if the multitype sensors or multiscale measurements are used in application of structural health monitoring and the damage identification for large span structure. A methodology to combine the local and global measurements in noisy environments based on artificial neural network is proposed in this paper. For a real large span structure, the capacity of the methodology is validated, including the decision on damage placement, the discussions on the number of the sensors, and the optimal parameters for artificial neural networks. Furthermore, the noisy environments in different levels are simulated to demonstrate the robustness and effectiveness of the proposed approach. PMID:24977207

  13. Damage Identification for Large Span Structure Based on Multiscale Inputs to Artificial Neural Networks

    PubMed Central

    Teng, Jun; Cui, Yan

    2014-01-01

    In structural health monitoring system, little research on the damage identification from different types of sensors applied to large span structure has been done in the field. In fact, it is significant to estimate the whole structural safety if the multitype sensors or multiscale measurements are used in application of structural health monitoring and the damage identification for large span structure. A methodology to combine the local and global measurements in noisy environments based on artificial neural network is proposed in this paper. For a real large span structure, the capacity of the methodology is validated, including the decision on damage placement, the discussions on the number of the sensors, and the optimal parameters for artificial neural networks. Furthermore, the noisy environments in different levels are simulated to demonstrate the robustness and effectiveness of the proposed approach. PMID:24977207

  14. 49 CFR 198.35 - Grants conditioned on adoption of one-call damage prevention program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Grants conditioned on adoption of one-call damage...) PIPELINE SAFETY REGULATIONS FOR GRANTS TO AID STATE PIPELINE SAFETY PROGRAMS Adoption of One-Call Damage Prevention Program § 198.35 Grants conditioned on adoption of one-call damage prevention program....

  15. Garlic supplementation prevents oxidative DNA damage in essential hypertension.

    PubMed

    Dhawan, Veena; Jain, Sanjay

    2005-07-01

    Oxygen-free radicals and other oxygen/nitrogen species are constantly generated in the human body. Most are intercepted by antioxidant defences and perform useful metabolic roles, whereas others escape to damage biomolecules like DNA, lipids and proteins. Garlic has been shown to contain antioxidant phytochemicals that prevent oxidative damage. These include unique water-soluble organosulphur compounds, lipid-soluble organosulphur compounds and flavonoids. Therefore, in the present study, we have tried to explore the antioxidant effect of garlic supplementation on oxidative stress-induced DNA damage, nitric oxide (NO) and superoxide generation and on the total antioxidant status (TAS) in patients of essential hypertension (EH). Twenty patients of EH as diagnosed by JNC VI criteria (Group I) and 20 age and sex-matched normotensive controls (Group II) were enrolled in the study. Both groups were given garlic pearls (GP) in a dose of 250 mg per day for 2 months. Baseline samples were taken at the start of the study, i.e. 0 day, and thereafter 2 months follow-up. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), lipids, lipid peroxidation (MDA), NO and antioxidant vitamins A, E and C were determined. A moderate decline in blood pressure (BP) and a significant reduction in 8-OHdG, NO levels and lipid peroxidation were observed in Group I subjects with GP supplementation. Further, a significant increase in vitamin levels and TAS was also observed in this group as compared to the control subjects. These findings point out the beneficial effects of garlic supplementation in reducing blood pressure and counteracting oxidative stress, and thereby, offering cardioprotection in essential hypertensives. PMID:16335787

  16. Cognitive Flexibility through Metastable Neural Dynamics Is Disrupted by Damage to the Structural Connectome

    PubMed Central

    Hellyer, Peter J.; Scott, Gregory; Shanahan, Murray; Sharp, David J.

    2015-01-01

    Current theory proposes that healthy neural dynamics operate in a metastable regime, where brain regions interact to simultaneously maximize integration and segregation. Metastability may confer important behavioral properties, such as cognitive flexibility. It is increasingly recognized that neural dynamics are constrained by the underlying structural connections between brain regions. An important challenge is, therefore, to relate structural connectivity, neural dynamics, and behavior. Traumatic brain injury (TBI) is a pre-eminent structural disconnection disorder whereby traumatic axonal injury damages large-scale connectivity, producing characteristic cognitive impairments, including slowed information processing speed and reduced cognitive flexibility, that may be a result of disrupted metastable dynamics. Therefore, TBI provides an experimental and theoretical model to examine how metastable dynamics relate to structural connectivity and cognition. Here, we use complementary empirical and computational approaches to investigate how metastability arises from the healthy structural connectome and relates to cognitive performance. We found reduced metastability in large-scale neural dynamics after TBI, measured with resting-state functional MRI. This reduction in metastability was associated with damage to the connectome, measured using diffusion MRI. Furthermore, decreased metastability was associated with reduced cognitive flexibility and information processing. A computational model, defined by empirically derived connectivity data, demonstrates how behaviorally relevant changes in neural dynamics result from structural disconnection. Our findings suggest how metastable dynamics are important for normal brain function and contingent on the structure of the human connectome. PMID:26085630

  17. Detection, location, and quantification of structural damage by neural-net-processed moiré profilometry

    NASA Astrophysics Data System (ADS)

    Grossman, Barry G.; Gonzalez, Frank S.; Blatt, Joel H.; Hooker, Jeffery A.

    1992-03-01

    The development of efficient high speed techniques to recognize, locate, and quantify damage is vitally important for successful automated inspection systems such as ones used for the inspection of undersea pipelines. Two critical problems must be solved to achieve these goals: the reduction of nonuseful information present in the video image and automatic recognition and quantification of extent and location of damage. Artificial neural network processed moire profilometry appears to be a promising technique to accomplish this. Real time video moire techniques have been developed which clearly distinguish damaged and undamaged areas on structures, thus reducing the amount of extraneous information input into an inspection system. Artificial neural networks have demonstrated advantages for image processing, since they can learn the desired response to a given input and are inherently fast when implemented in hardware due to their parallel computing architecture. Video moire images of pipes with dents of different depths were used to train a neural network, with the desired output being the location and severity of the damage. The system was then successfully tested with a second series of moire images. The techniques employed and the results obtained are discussed.

  18. Electrochemically Reduced Water Protects Neural Cells from Oxidative Damage

    PubMed Central

    Hamasaki, Takeki; Kinjo, Tomoya; Nakamichi, Noboru; Teruya, Kiichiro; Kabayama, Shigeru

    2014-01-01

    Aging-related neurodegenerative disorders are closely associated with mitochondrial dysfunction and oxidative stresses and their incidence tends to increase with aging. Brain is the most vulnerable to reactive species generated by a higher rate of oxygen consumption and glucose utilization compared to other organs. Electrochemically reduced water (ERW) was demonstrated to scavenge reactive oxygen species (ROS) in several cell types. In the present study, the protective effect of ERW against hydrogen peroxide (H2O2) and nitric oxide (NO) was investigated in several rodent neuronal cell lines and primary cells. ERW was found to significantly suppress H2O2 (50–200 μM) induced PC12 and SFME cell deaths. ERW scavenged intracellular ROS and exhibited a protective effect against neuronal network damage caused by 200 μM H2O2 in N1E-115 cells. ERW significantly suppressed NO-induced cytotoxicity in PC12 cells despite the fact that it did not have the ability to scavenge intracellular NO. ERW significantly suppressed both glutamate induced Ca2+ influx and the resulting cytotoxicity in primary cells. These results collectively demonstrated for the first time that ERW protects several types of neuronal cells by scavenging ROS because of the presence of hydrogen and platinum nanoparticles dissolved in ERW. PMID:25383141

  19. Electrochemically reduced water protects neural cells from oxidative damage.

    PubMed

    Kashiwagi, Taichi; Yan, Hanxu; Hamasaki, Takeki; Kinjo, Tomoya; Nakamichi, Noboru; Teruya, Kiichiro; Kabayama, Shigeru; Shirahata, Sanetaka

    2014-01-01

    Aging-related neurodegenerative disorders are closely associated with mitochondrial dysfunction and oxidative stresses and their incidence tends to increase with aging. Brain is the most vulnerable to reactive species generated by a higher rate of oxygen consumption and glucose utilization compared to other organs. Electrochemically reduced water (ERW) was demonstrated to scavenge reactive oxygen species (ROS) in several cell types. In the present study, the protective effect of ERW against hydrogen peroxide (H2O2) and nitric oxide (NO) was investigated in several rodent neuronal cell lines and primary cells. ERW was found to significantly suppress H2O2 (50-200 μM) induced PC12 and SFME cell deaths. ERW scavenged intracellular ROS and exhibited a protective effect against neuronal network damage caused by 200 μM H2O2 in N1E-115 cells. ERW significantly suppressed NO-induced cytotoxicity in PC12 cells despite the fact that it did not have the ability to scavenge intracellular NO. ERW significantly suppressed both glutamate induced Ca(2+) influx and the resulting cytotoxicity in primary cells. These results collectively demonstrated for the first time that ERW protects several types of neuronal cells by scavenging ROS because of the presence of hydrogen and platinum nanoparticles dissolved in ERW. PMID:25383141

  20. Remote sensing-based neural network mapping of tsunami damage in Aceh, Indonesia.

    PubMed

    Aitkenhead, Matthew J; Lumsdon, Parivash; Miller, David R

    2007-09-01

    In addition to the loss of human life, the tsunami event of 26 December 2004 caused extensive damage to coastal areas. The scale of the disaster was such that remote sensing may be the only way to determine its effects on the landscape. This paper presents the results of a neural network-based mapping of part of the region of Aceh, Sumatra. Before-and-after satellite imagery, combined with a novel neural network methodology, enabled a characterisation of landscape change. The neural network technique used a threshold of acceptance for identification, in combination with a bootstrapped identification method for identifying problem pixels. Map analysis allowed identification of urban areas that were inaccessible by road, and which aid agencies could therefore only reach by air or sea. The methods used provide a rapid and effective mapping ability and would be a useful tool for aid agencies, insurance underwriters and environmental monitoring. PMID:17714164

  1. Offline and online detection of damage using autoregressive models and artificial neural networks

    NASA Astrophysics Data System (ADS)

    Omenzetter, Piotr; de Lautour, Oliver R.

    2007-04-01

    Developed to study long, regularly sampled streams of data, time series analysis methods are being increasingly investigated for the use of Structural Health Monitoring. In this research, Autoregressive (AR) models are used in conjunction with Artificial Neural Networks (ANNs) for damage detection, localisation and severity assessment. In the first reported experimental exercise, AR models were used offline to fit the acceleration time histories of a 3-storey test structure in undamaged and various damaged states when excited by earthquake motion simulated on a shake table. Damage was introduced into the structure by replacing the columns with those of a thinner thickness. Analytical models of the structure in both damaged and undamaged states were also developed and updated using experimental data in order to determine structural stiffness. The coefficients of AR models were used as damage sensitive features and input into an ANN to build a relationship between them and the remaining structural stiffness. In the second, analytical exercise, a system with gradually progressing damage was numerically simulated and acceleration AR models with exogenous inputs were identified recursively. A trained ANN was then required to trace the structural stiffness online. The results for the offline and online approach showed the efficiency of using AR coefficient as damage sensitive features and good performance of the ANNs for damage detection, localization and quantification.

  2. A Neural Network/Acoustic Emission Analysis of Impact Damaged Graphite/Epoxy Pressure Vessels

    NASA Technical Reports Server (NTRS)

    Walker, James L.; Hill, Erik v. K.; Workman, Gary L.; Russell, Samuel S.

    1995-01-01

    Acoustic emission (AE) signal analysis has been used to measure the effects of impact damage on burst pressure in 5.75 inch diameter, inert propellant filled, filament wound pressure vessels. The AE data were collected from fifteen graphite/epoxy pressure vessels featuring five damage states and three resin systems. A burst pressure prediction model was developed by correlating the AE amplitude (frequency) distribution, generated during the first pressure ramp to 800 psig (approximately 25% of the average expected burst pressure for an undamaged vessel) to known burst pressures using a four layered back propagation neural network. The neural network, trained on three vessels from each resin system, was able to predict burst pressures with a worst case error of 5.7% for the entire fifteen bottle set.

  3. Structural Health Monitoring and Impact Detection Using Neural Networks for Damage Characterization

    NASA Technical Reports Server (NTRS)

    Ross, Richard W.

    2006-01-01

    Detection of damage due to foreign object impact is an important factor in the development of new aerospace vehicles. Acoustic waves generated on impact can be detected using a set of piezoelectric transducers, and the location of impact can be determined by triangulation based on the differences in the arrival time of the waves at each of the sensors. These sensors generate electrical signals in response to mechanical motion resulting from the impact as well as from natural vibrations. Due to electrical noise and mechanical vibration, accurately determining these time differentials can be challenging, and even small measurement inaccuracies can lead to significant errors in the computed damage location. Wavelet transforms are used to analyze the signals at multiple levels of detail, allowing the signals resulting from the impact to be isolated from ambient electromechanical noise. Data extracted from these transformed signals are input to an artificial neural network to aid in identifying the moment of impact from the transformed signals. By distinguishing which of the signal components are resultant from the impact and which are characteristic of noise and normal aerodynamic loads, the time differentials as well as the location of damage can be accurately assessed. The combination of wavelet transformations and neural network processing results in an efficient and accurate approach for passive in-flight detection of foreign object damage.

  4. Multi-Level Interval Estimation for Locating damage in Structures by Using Artificial Neural Networks

    SciTech Connect

    Pan Danguang; Gao Yanhua; Song Junlei

    2010-05-21

    A new analysis technique, called multi-level interval estimation method, is developed for locating damage in structures. In this method, the artificial neural networks (ANN) analysis method is combined with the statistics theory to estimate the range of damage location. The ANN is multilayer perceptron trained by back-propagation. Natural frequencies and modal shape at a few selected points are used as input to identify the location and severity of damage. Considering the large-scale structures which have lots of elements, multi-level interval estimation method is developed to reduce the estimation range of damage location step-by-step. Every step, estimation range of damage location is obtained from the output of ANN by using the method of interval estimation. The next ANN training cases are selected from the estimation range after linear transform, and the output of new ANN estimation range of damage location will gained a reduced estimation range. Two numerical example analyses on 10-bar truss and 100-bar truss are presented to demonstrate the effectiveness of the proposed method.

  5. Multi-Level Interval Estimation for Locating damage in Structures by Using Artificial Neural Networks

    NASA Astrophysics Data System (ADS)

    Dan-guang, Pan; Yan-hua, Gao; Jun-lei, Song

    2010-05-01

    A new analysis technique, called multi-level interval estimation method, is developed for locating damage in structures. In this method, the artificial neural networks (ANN) analysis method is combined with the statistics theory to estimate the range of damage location. The ANN is multilayer perceptron trained by back-propagation. Natural frequencies and modal shape at a few selected points are used as input to identify the location and severity of damage. Considering the large-scale structures which have lots of elements, multi-level interval estimation method is developed to reduce the estimation range of damage location step-by-step. Every step, estimation range of damage location is obtained from the output of ANN by using the method of interval estimation. The next ANN training cases are selected from the estimation range after linear transform, and the output of new ANN estimation range of damage location will gained a reduced estimation range. Two numerical example analyses on 10-bar truss and 100-bar truss are presented to demonstrate the effectiveness of the proposed method.

  6. Detection and location of pipe damage by artificial-neural-net-processed moire error maps

    NASA Astrophysics Data System (ADS)

    Grossman, Barry G.; Gonzalez, Frank S.; Blatt, Joel H.; Cahall, Scott C.

    1993-05-01

    A novel automated inspection technique to recognize, locate, and quantify damage is developed. This technique is based on two already existing technologies: video moire metrology and artificial neural networks. Contour maps generated by video moire techniques provide an accurate description of surface structure that can then be automated by means of neutral networks. Artificial neural networks offer an attractive solution to the automated interpretation problem because they can generalize from the learned samples and provide an intelligent response for similar patterns having missing or noisy data. Two dimensional video moire images of pipes with dents of different depths, at several rotations, were used to train a multilayer feedforward neural network by the backpropagation algorithm. The backpropagation network is trained to recognize and classify the video moire images according to the dent's depth. Once trained, the network outputs give an indication of the probability that a dent has been found, a depth estimate, and the axial location of the center of the dent. This inspection technique has been demonstrated to be a powerful tool for the automatic location and quantification of structural damage, as illustrated using dented pipes.

  7. Etiology, pathogenesis and prevention of neural tube defects.

    PubMed

    Padmanabhan, Rengasamy

    2006-06-01

    Spina bifida, anencephaly, and encephalocele are commonly grouped together and termed neural tube defects (NTD). Failure of closure of the neural tube during development results in anencephaly or spina bifida aperta but encephaloceles are possibly post-closure defects. NTD are associated with a number of other central nervous system (CNS) and non-neural malformations. Racial, geographic and seasonal variations seem to affect their incidence. Etiology of NTD is unknown. Most of the non-syndromic NTD are of multifactorial origin. Recent in vitro and in vivo studies have highlighted the molecular mechanisms of neurulation in vertebrates but the morphologic development of human neural tube is poorly understood. A multisite closure theory, extrapolated directly from mouse experiments highlighted the clinical relevance of closure mechanisms to human NTD. Animal models, such as circle tail, curly tail, loop tail, shrm and numerous knockouts provide some insight into the mechanisms of NTD. Also available in the literature are a plethora of chemically induced preclosure and a few post-closure models of NTD, which highlight the fact that CNS malformations are of hetergeneitic nature. No Mendelian pattern of inheritance has been reported. Association with single gene defects, enhanced recurrence risk among siblings, and a higher frequency in twins than in singletons indicate the presence of a strong genetic contribution to the etiology of NTD. Non-availability of families with a significant number of NTD cases makes research into genetic causation of NTD difficult. Case reports and epidemiologic studies have implicated a number of chemicals, widely differing therapeutic drugs, environmental contaminants, pollutants, infectious agents, and solvents. Maternal hyperthermia, use of valproate by epileptic women during pregnancy, deficiency and excess of certain nutrients and chronic maternal diseases (e.g. diabetes mellitus) are reported to cause a manifold increase in the

  8. A Supramolecular Gel Approach to Minimize the Neural Cell Damage during Cryopreservation Process.

    PubMed

    Zeng, Jie; Yin, Yixia; Zhang, Li; Hu, Wanghui; Zhang, Chaocan; Chen, Wanyu

    2016-03-01

    The storage method for living cells is one of the major challenges in cell-based applications. Here, a novel supramolecular gel cryopreservation system (BDTC gel system) is introduced, which can observably increase the neural cell viability during cryopreservation process because this system can (1) confine the ice crystal growth in the porous of BDTC gel system, (2) decrease the amount of ice crystallization and cryopreservation system's freezing point, and (3) reduce the change rates of cell volumes and osmotic shock. In addition, thermoreversible BDTC supramolecular gel is easy to be removed after thawing so it does not hinder the adherence, growth, and proliferation of cells. The results of functionality assessments indicate that BDTC gel system can minimize the neural cell damage during cryopreservation process. This method will be potentially applied in cryopreservation of other cell types, tissues, or organs and will benefit cell therapy, tissue engineering, and organs transplantation. PMID:26611502

  9. Neural network/acoustic emission burst pressure prediction for impact damaged composite pressure vessels

    SciTech Connect

    Walker, J.L.; Workman, G.L.; Russell, S.S.; Hill, E.V.K.

    1997-08-01

    Acoustic emission signal analysis has been used to measure the effect impact damage has on the burst pressure of 146 mm (5.75 in.) diameter graphite/epoxy and the organic polymer, Kevlar/epoxy filament wound pressure vessels. Burst pressure prediction models were developed by correlating the differential acoustic emission amplitude distribution collected during low level hydroproof tests to known burst pressures using backpropagation artificial neural networks. Impact damage conditions ranging from barely visible to obvious fiber breakage, matrix cracking, and delamination were included in this work. A simulated (inert) propellant was also cast into a series of the vessels from each material class, before impact loading, to provide boundary conditions during impact that would simulate those found on solid rocket motors. The results of this research effort demonstrate that a quantitative assessment of the effects that impact damage has on burst pressure can be made for both organic polymer/epoxy and graphite/epoxy pressure vessels. Here, an artificial neural network analysis of the acoustic emission parametric data recorded during low pressure hydroproof testing is used to relate burst pressure to the vessel`s acoustic signature. Burst pressure predictions within 6.0% of the actual failure pressure are demonstrated for a series of vessels.

  10. Prevention of propeller foreign object damage - Theory and practice

    NASA Astrophysics Data System (ADS)

    Payne, C.; Vitale, D. J.

    Foreign object damage hazards to which ACV propellers are exposed, and the phenomena causing the damage, are discussed. Comparison of the effects of energy absorption in systems of hard, soft, smooth and rough particles impacting upon soft and hard propeller materials is made. Molded urethane strips were found to increase the life of the blades from 20 minutes between maintenance actions to nine hours between maintenance actions. Molded urethanes and sprayed or brushed urethanes are compared.

  11. Neural synchrony indexes impaired motor slowing after errors and novelty following white matter damage.

    PubMed

    Wessel, Jan R; Ullsperger, Markus; Obrig, Hellmuth; Villringer, Arno; Quinque, Eva; Schroeter, Matthias L; Bretschneider, Katharina J; Arelin, Katrin; Roggenhofer, Elisabeth; Frisch, Stefan; Klein, Tilmann A

    2016-02-01

    In humans, action errors and perceptual novelty elicit activity in a shared frontostriatal brain network, allowing them to adapt their ongoing behavior to such unexpected action outcomes. Healthy and pathologic aging reduces the integrity of white matter pathways that connect individual hubs of such networks and can impair the associated cognitive functions. Here, we investigated whether structural disconnection within this network because of small-vessel disease impairs the neural processes that subserve motor slowing after errors and novelty (post-error slowing, PES; post-novel slowing, PNS). Participants with intact frontostriatal circuitry showed increased right-lateralized beta-band (12-24 Hz) synchrony between frontocentral and frontolateral electrode sites in the electroencephalogram after errors and novelty, indexing increased neural communication. Importantly, this synchrony correlated with PES and PNS across participants. Furthermore, such synchrony was reduced in participants with frontostriatal white matter damage, in line with reduced PES and PNS. The results demonstrate that behavioral change after errors and novelty result from coordinated neural activity across a frontostriatal brain network and that such cognitive control is impaired by reduced white matter integrity. PMID:26563990

  12. A new method for beam-damage-diagnosis using adaptive fuzzy neural structure and wavelet analysis

    NASA Astrophysics Data System (ADS)

    Nguyen, Sy Dzung; Ngo, Kieu Nhi; Tran, Quang Thinh; Choi, Seung-Bok

    2013-08-01

    In this work, we present a new beam-damage-locating (BDL) method based on an algorithm which is a combination of an adaptive fuzzy neural structure (AFNS) and an average quantity solution to wavelet transform coefficient (AQWTC) of beam vibration signal. The AFNS is used for remembering undamaged-beam dynamic properties, while the AQWTC is used for signal analysis. Firstly, the beam is divided into elements and excited to be vibrated. Vibrating signal at each element, which is displacement in this work, is measured, filtered and transformed into wavelet signal with a used-scale-sheet to calculate the corresponding difference of AQWTC between two cases: undamaged status and the status at the checked time. Database about this difference is then used for finding out the elements having strange features in wavelet quantitative analysis, which directly represents the beam-damage signs. The effectiveness of the proposed approach which combines fuzzy neural structure and wavelet transform methods is demonstrated by experiment on measured data sets in a vibrated beam-type steel frame structure. `

  13. Multiple damage identification on a wind turbine blade using a structural neural system

    NASA Astrophysics Data System (ADS)

    Kirikera, Goutham R.; Schulz, Mark J.; Sundaresan, Mannur J.

    2007-04-01

    A large number of sensors are required to perform real-time structural health monitoring (SHM) to detect acoustic emissions (AE) produced by damage growth on large complicated structures. This requires a large number of high sampling rate data acquisition channels to analyze high frequency signals. To overcome the cost and complexity of having such a large data acquisition system, a structural neural system (SNS) was developed. The SNS reduces the required number of data acquisition channels and predicts the location of damage within a sensor grid. The sensor grid uses interconnected sensor nodes to form continuous sensors. The combination of continuous sensors and the biomimetic parallel processing of the SNS tremendously reduce the complexity of SHM. A wave simulation algorithm (WSA) was developed to understand the flexural wave propagation in composite structures and to utilize the code for developing the SNS. Simulation of AE responses in a plate and comparison with experimental results are shown in the paper. The SNS was recently tested by a team of researchers from University of Cincinnati and North Carolina A&T State University during a quasi-static proof test of a 9 meter long wind turbine blade at the National Renewable Energy Laboratory (NREL) test facility in Golden, Colorado. Twelve piezoelectric sensor nodes were used to form four continuous sensors to monitor the condition of the blade during the test. The four continuous sensors are used as inputs to the SNS. There are only two analog output channels of the SNS, and these signals are digitized and analyzed in a computer to detect damage. In the test of the wind turbine blade, multiple damages were identified and later verified by sectioning of the blade. The results of damage identification using the SNS during this proof test will be shown in this paper. Overall, the SNS is very sensitive and can detect damage on complex structures with ribs, joints, and different materials, and the system

  14. 77 FR 19799 - Pipeline Safety: Pipeline Damage Prevention Programs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-02

    ... the ANPRM on this subject that PHMSA published in the Federal Register on October 29, 2009 (74 FR..., Enforcement, and Safety (PIPES) Act of 2006, establishment of review criteria for state excavation damage... 2006 (PIPES Act), PHMSA is proposing criteria and procedures for determining whether a...

  15. Selecting brines and clay stabilizers to prevent formation damage

    SciTech Connect

    Evans, B.; Ali, S.

    1997-05-01

    Although many technical reports have been written about formation damage caused by brine/formation interactions, this article discusses the effects brines and chemical clay stabilizers have on pure samples of kaolinite, smectite, illite and chlorite clays. Analytical chemistry and geochemical models were not employed in this study; instead, capillary suction time tests were used to empirically compare clay migration and swelling characteristics when samples were exposed to certain brine/clay stabilizer combinations. Objective of the study was to determine which type of clay was most damaging in reservoir rocks, and whether one brine or chemical stabilizer could meet the needs of stabilizing all clay types. This information is provided with well completion operations in mind, especially when fluid cost/performance is a major concern. This article compares the unique brine/chemical stabilizer reaction characteristics of each clay type common to oil and gas reservoirs.

  16. Influence of Input Parameters on the Performance of an Artificial Neural Network Used to Detect Structural Damage

    NASA Astrophysics Data System (ADS)

    Villalba, Jesus Daniel; Gomez, Ivan Dario; Laier, Jose Elias

    2010-09-01

    Structural damage detection is a very important research topic and, currently, there are not specific tools to solve it. A promising tool that can be used is the artificial neural network, ANN, which can deal with hard problems. This paper uses a back propagation ANN with Bayesian regularization training to locate and quantify damage in truss structures. The input parameters corresponded to natural frequencies combined with shape modes, modal flexibilities or modal strain energies. The ANN was trained by considering only simple damage scenarios, random multiple damage scenarios or a combination of them. The results are shown in terms of the percentage of cases in which the ANN trained achieves a determined performance in assessing both the damage extension and the presence of damaged elements. The best performance for the ANN is obtained by using modal strain energies and multiple damage scenarios.

  17. A Red-Light Running Prevention System Based on Artificial Neural Network and Vehicle Trajectory Data

    PubMed Central

    Li, Pengfei; Li, Yan; Guo, Xiucheng

    2014-01-01

    The high frequency of red-light running and complex driving behaviors at the yellow onset at intersections cannot be explained solely by the dilemma zone and vehicle kinematics. In this paper, the author presented a red-light running prevention system which was based on artificial neural networks (ANNs) to approximate the complex driver behaviors during yellow and all-red clearance and serve as the basis of an innovative red-light running prevention system. The artificial neural network and vehicle trajectory are applied to identify the potential red-light runners. The ANN training time was also acceptable and its predicting accurate rate was over 80%. Lastly, a prototype red-light running prevention system with the trained ANN model was described. This new system can be directly retrofitted into the existing traffic signal systems. PMID:25435870

  18. The unanticipated resilience of trait self-knowledge in the face of neural damage.

    PubMed

    Klein, Stanley B; Lax, Moshe L

    2010-11-01

    This paper explores the question of what the self is by reviewing research conducted with both normal and neuropsychological participants. Findings converge on the idea that the self may be more complex and differentiated than some previous treatments of the topic have suggested. Although some aspects of self-knowledge such as episodic recollection may be compromised in individuals, other aspects-for instance, semantic trait summaries-appear largely intact. Taken together, these findings support the idea that the self is not a single, unified entity. Rather, it is a set of interrelated, functionally independent systems. In the process of reviewing neuropsychological findings, an unexpected result emerges: trait self-knowledge appears unusually robust with respect to neural and cognitive damage that render other aspects of self-knowledge dysfunctional in varying degrees. PMID:21108109

  19. Structural Damage Detection Using Artificial Neural Networks and Measured Frf Data Reduced via Principal Component Projection

    NASA Astrophysics Data System (ADS)

    ZANG, C.; IMREGUN, M.

    2001-05-01

    This paper deals with structural damage detection using measured frequency response functions (FRFs) as input data to artificial neural networks (ANNs). A major obstacle, the impracticality of using full-size FRF data with ANNs, was circumvented by applying a principal component analysis (PCA)-based data reduction technique to the measured FRFs. The compressed FRFs, represented by their projection onto the most significant principal components, were then used as the ANN input variables instead of the raw FRF data. The output is a prediction for the actual state of the specimen, i.e., healthy or damaged. A further advantage of this particular approach was found to be the ability to deal with relatively high measurement noise, which is of common occurrence when dealing with industrial structures. The methodology was applied to the measured FRFs of a railway wheel, each response function having 4096 spectral lines. The available FRF data were grouped into x, y and z direction FRFs and a compression ratio of about 400 was achieved for each direction. Three different networks, each corresponding to a co-ordinate direction, were trained and verified using 80 PCA-compressed FRFs. Twenty compressed FRFs, obtained from further measurements, were used for the actual damage detection tests. Half of the test FRFs were polluted further by adding 5% random noise in order to assess the robustness of the method in the presence of significant experimental noise. The results showed that, in all cases considered, it was possible to distinguish between the healthy and damaged states with very good accuracy and repeatability.

  20. Clean Assembly Practices to Prevent Contamination and Damage to Optics

    SciTech Connect

    Pryatel, J; Gourdin, W H

    2005-12-19

    A key lesson learned from the earliest optics installed in the National Ignition Facility (NIF) was that the traditional approach for maintaining cleanliness, such as the use of cleanrooms and associated garments and protocols, is inadequate. Assembly activities often negate the benefits provided by cleanrooms, and in fact generate contamination with high damage potential. As a result, NIF introduced ''clean assembly protocols'' and related practices to supplement the traditional clean room protocols. These new protocols included ''clean-as-you-go'' activities and regular bright light inspections. Introduction of these new protocols has greatly reduced the particle contamination found on more recently installed optics. In this paper we will describe the contamination mechanisms we have observed and the details of the clean assembly protocols we have successfully introduced to mitigate them.

  1. Vinpocetine prevent ischemic cell damage in rat hippocampus

    SciTech Connect

    Sauer, D.; Rischke, R.; Beck, T.; Roeberg, C.; Mennel, H.D.; Bielenberg, G.W.; Krieglstein, J.

    1988-01-01

    The effects of vinpocetine on hippocampal cell damage and local cerebral blood flow (LCBF) were measured in a rat model of forebrain ischemia. Duration of ischemia was 10 min. LCBF was determined after 2 min of recirculation using the /sup 14/C-iodoantipyrine technique. Hippocampal cell loss was quantified histologically 7 days post-ischemia. Intraperitoneal application of vinpocetine 15 min prior to ischemia significantly reduced neuronal cell loss in hippocampal CA 1 sector from 60% to 28%. The drug led to a marked increase in blood flow in cortical areas, whereas LCBF remained unchanged in hippocampus and all other structures measured. It is suggested that the protective effect of vinpocetine does not depend on increased postischemic blood flow.

  2. Disruption of the MacMARCKS gene prevents cranial neural tube closure and results in anencephaly.

    PubMed Central

    Chen, J; Chang, S; Duncan, S A; Okano, H J; Fishell, G; Aderem, A

    1996-01-01

    MacMARCKS is a member of the MARCKS family of protein kinase C (PKC) substrates. Biochemical evidence demonstrates that these proteins integrate calcium and PKC-dependent signals to regulate actin structure at the membrane. We report here that deletion of the MacMARCKS gene prevents cranial neural tube closure in the developing brain, resulting in anencephaly. This suggests a central role for MacMARCKS and the PKC signal transduction pathway in the folding of the anterior neural plate during the early phases of brain formation, and supports the hypothesis that actin-based motility directs cranial neural tube closure. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8692805

  3. Neural Substrates of Linguistic Prosody: Evidence from Syntactic Disambiguation in the Productions of Brain-Damaged Patients

    ERIC Educational Resources Information Center

    Shah, Amee P.; Baum, Shari R.; Dwivedi, Veena D.

    2006-01-01

    The present investigation focussed on the neural substrates underlying linguistic distinctions that are signalled by prosodic cues. A production experiment was conducted to examine the ability of left- (LHD) and right- (RHD) hemisphere-damaged patients and normal controls to use temporal and fundamental frequency cues to disambiguate sentences…

  4. Leaky lysosomes in lung transplant macrophages: azithromycin prevents oxidative damage

    PubMed Central

    2012-01-01

    Background Lung allografts contain large amounts of iron (Fe), which inside lung macrophages may promote oxidative lysosomal membrane permeabilization (LMP), cell death and inflammation. The macrolide antibiotic azithromycin (AZM) accumulates 1000-fold inside the acidic lysosomes and may interfere with the lysosomal pool of Fe. Objective Oxidative lysosomal leakage was assessed in lung macrophages from lung transplant recipients without or with AZM treatment and from healthy subjects. The efficiency of AZM to protect lysosomes and cells against oxidants was further assessed employing murine J774 macrophages. Methods Macrophages harvested from 8 transplant recipients (5 without and 3 with ongoing AZM treatment) and 7 healthy subjects, and J774 cells pre-treated with AZM, a high-molecular-weight derivative of the Fe chelator desferrioxamine or ammonium chloride were oxidatively stressed. LMP, cell death, Fe, reduced glutathione (GSH) and H-ferritin were assessed. Results Oxidant challenged macrophages from transplants recipients without AZM exhibited significantly more LMP and cell death than macrophages from healthy subjects. Those macrophages contained significantly more Fe, while GSH and H-ferritin did not differ significantly. Although macrophages from transplant recipients treated with AZM contained both significantly more Fe and less GSH, which would sensitize cells to oxidants, these macrophages resisted oxidant challenge well. The preventive effect of AZM on oxidative LMP and J774 cell death was 60 to 300 times greater than the other drugs tested. Conclusions AZM makes lung transplant macrophages and their lysososomes more resistant to oxidant challenge. Possibly, prevention of obliterative bronchiolitis in lung transplants by AZM is partly due to this action. PMID:23006592

  5. 20-Hydroxyecdysone prevents oxidative stress damage in adult Pyrrhocoris apterus.

    PubMed

    Krishnan, Natraj; Vecera, Josef; Kodrík, Dalibor; Sehnal, Frantisek

    2007-07-01

    Injections of 38 pmol paraquat (1,1'-dimethyl-4,4'-bypyridilium) into adult Pyrrhocoris apterus (average body weight 29.6 mg in males and 36.9 mg in females) caused a significant elevation of lipid peroxidation and protein carbonylation and a decline of membrane fluidity in the microsomal brain fraction. Another manifestation of oxidative stress was a depletion of the reduced glutathione pool and reduction of the gamma-glutamyl transpeptidase activity in the brain extracts. The damaging action of paraquat on the brain was counteracted by simultaneous injection of 1 pmol 20-hydroxyecdysone (20E). 20E restrained lipid peroxidation and the formation of protein carbonyls, ameliorated changes in microsomal membrane fluidity, enhanced the level of reduced glutathione, and upregulated the activity of gamma-glutamyl transpeptidase. At the organismic level, 20E curtailed three detrimental effects caused by paraquat injection: the disappearance of a blood protein, the suppression of fecundity and egg hatchability, and the shortening of adult life span. The data showed that 20E provided a systemic antioxidant protection but the significance of endogenous ecdysteroids in the management of oxidative stress remains to be shown. PMID:17570141

  6. Preventing Collateral Damage in Crohn's Disease: The Lémann Index.

    PubMed

    Fiorino, Gionata; Bonifacio, Cristiana; Peyrin-Biroulet, Laurent; Danese, Silvio

    2016-04-01

    Crohn's disease [CD] is a chronic progressive and destructive condition. Half of all CD patients will develop bowel damage at 10 years. As in rheumatic diseases, preventing the organ damage consequent to CD complications [fistula, abscess, and/or stricture] is emerging as a new therapeutic goal for these patients in clinical practice. This might be the only way to alter disease course, as surgery is often required for disease complications. Similar to the joint damage in rheumatoid arthritis, bowel damage has also emerged as a new endpoint in disease-modification trials such as the REACT trial. Recently, the Lemann Index [LI] has been developed to measure CD-related bowel damage, and to assess damage progression over time, in order to evaluate the impact of therapeutic strategies in terms of preventing bowel damage. While validation is pending, recent reports suggested that bowel damage is reversible by anti-tumour necrosis factor [TNF] therapy. The Lémann index may play a key role in CD management, and should be implemented in all upcoming disease-modification trials in CD. PMID:26744441

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

    PubMed

    Vásquez, Adriana Ordoñez; Suarez-Obando, Fernando

    2015-12-01

    This article gives a broad overview of part of the historical evolution of medical knowledge about neural tube defects (NTD) and the discovery of vitamin B9 or folic acid, as well as some relevant research events that, over the course of several centuries, defined the relationships between the understanding of central nervous system embryology, the discovery of the vitamin, the correlation between folic acid and cell proliferation and lastly the development of preventive measures for this type of defects. This narrative allows us to examine historically relevant concepts underlying clinical actions with a populational impact that prevent NTDs via folic acid consumption prior to conception. PMID:25650704

  8. Melatonin Has An Ergogenic Effect But Does Not Prevent Inflammation and Damage In Exhaustive Exercise

    PubMed Central

    Beck, Wladimir Rafael; Botezelli, José Diego; Pauli, José Rodrigo; Ropelle, Eduardo Rochete; Gobatto, Claudio Alexandre

    2015-01-01

    It is well documented that exhaustive physical exercise leads to inflammation and skeletal muscle tissue damage. With this in mind, melatonin has been acutely administered before physical exercise; nevertheless, the use of melatonin as an ergogenic agent to prevent tissue inflammation and damage remains uncertain. We evaluated the effects of melatonin on swimming performance, muscle inflammation and damage and several physiological parameters after exhaustive exercise at anaerobic threshold intensity (iLAn) performed during light or dark circadian periods. The iLAn was individually determined and two days later, the animals performed an exhaustive exercise bout at iLAn 30 minutes after melatonin administration. The exercise promoted muscle inflammation and damage, mainly during the dark period, and the exogenous melatonin promoted a high ergogenic effect. The expressive ergogenic effect of melatonin leads to longer periods of muscle contraction, which superimposes a possible melatonin protective effect on the tissue damage and inflammation. PMID:26669455

  9. The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells.

    PubMed

    Froldi, Francesca; Szuperak, Milan; Weng, Chen-Fang; Shi, Wei; Papenfuss, Anthony T; Cheng, Louise Y

    2015-01-15

    Cellular dedifferentiation is the regression of a cell from a specialized state to a more multipotent state and is implicated in cancer. However, the transcriptional network that prevents differentiated cells from reacquiring stem cell fate is so far unclear. Neuroblasts (NBs), the Drosophila neural stem cells, are a model for the regulation of stem cell self-renewal and differentiation. Here we show that the Drosophila zinc finger transcription factor Nervous fingers 1 (Nerfin-1) locks neurons into differentiation, preventing their reversion into NBs. Following Prospero-dependent neuronal specification in the ganglion mother cell (GMC), a Nerfin-1-specific transcriptional program maintains differentiation in the post-mitotic neurons. The loss of Nerfin-1 causes reversion to multipotency and results in tumors in several neural lineages. Both the onset and rate of neuronal dedifferentiation in nerfin-1 mutant lineages are dependent on Myc- and target of rapamycin (Tor)-mediated cellular growth. In addition, Nerfin-1 is required for NB differentiation at the end of neurogenesis. RNA sequencing (RNA-seq) and chromatin immunoprecipitation (ChIP) analysis show that Nerfin-1 administers its function by repression of self-renewing-specific and activation of differentiation-specific genes. Our findings support the model of bidirectional interconvertibility between neural stem cells and their post-mitotic progeny and highlight the importance of the Nerfin-1-regulated transcriptional program in neuronal maintenance. PMID:25593306

  10. Preventing Eye Damage from the Sun's Ultraviolet Light: What Health Educators Should Teach.

    ERIC Educational Resources Information Center

    Memmer, Mary Kelly

    1989-01-01

    Health educators are in an ideal position to teach individuals about dangers from the sun's ultraviolet light and how to prevent damage to eyes. Ultraviolet light is described, eye pathology which can be caused by it is outlined, and protective eyewear is discussed. (IAH)

  11. Hyaluronic acid prevents immunosuppressive drug-induced ovarian damage via up-regulating PGRMC1 expression

    PubMed Central

    Zhao, Guangfeng; Yan, Guijun; Cheng, Jie; Zhou, Xue; Fang, Ting; Sun, Haixiang; Hou, Yayi; Hu, Yali

    2015-01-01

    Chemotherapy treatment in women can frequently cause damage to the ovaries, which may lead to primary ovarian insufficiency (POI). In this study, we assessed the preventative effects of hyaluronic acid (HA) in immunosuppressive drug-induced POI-like rat models and investigated the possible mechanisms. We found that HA, which was reduced in primary and immunosuppressant-induced POI patients, could protect the immunosuppressant-induced damage to granulosa cells (GCs) in vitro. Then we found that HA blocked the tripterygium glycosides (TG) induced POI-like presentations in rats, including delayed or irregular estrous cycles, reduced 17 beta-estradiol(E2) concentration, decreased number of follicles, destruction of follicle structure, and damage of reproductive ability. Furthermore, we investigated the mechanisms of HA prevention effects on POI, which was associated with promotion of GC proliferation and PGRMC1 expression. In conclusion, HA prevents chemotherapy-induced ovarian damage by promoting PGRMC1 in GCs. This study may provide a new strategy for prevention and treatment of POI. PMID:25558795

  12. Tempol prevents genotoxicity induced by vorinostat: role of oxidative DNA damage.

    PubMed

    Alzoubi, Karem H; Khabour, Omar F; Jaber, Aya G; Al-Azzam, Sayer I; Mhaidat, Nizar M; Masadeh, Majed M

    2014-05-01

    Vorinostat is a member of histone deacetylase inhibitors, which represents a new class of anticancer agents for the treatment of solid and hematological malignancies. Studies have shown that these drugs induce DNA damage in blood lymphocytes, which is proposed to be due to the generation of oxidative lesions. The increase in DNA damage is sometimes associated with risk of developing secondary cancer. Thus, finding a treatment that limits DNA damage caused by anticancer drugs would be beneficial. Tempol is a potent antioxidant that was shown to prevent DNA damage induced by radiation. In this study, we aimed to investigate the harmful effects of vorinostat on DNA damage, and the possible protective effects of tempol against this damage. For that, the spontaneous frequency of sister chromatid exchanges (SCEs), chromosomal aberrations (CAs), and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels were measured in cultured human lymphocytes treated with vorinostat and/or tempol. The results showed that vorinostat significantly increases the frequency of SCEs, CAs and 8-OHdG levels in human lymphocytes as compared to control. These increases were normalized by the treatment of cells with tempol. In conclusion, vorinostat is genotoxic to lymphocytes, and this toxicity is reduced by tempol. Such results could set the stage for future studies investigating the possible usefulness of antioxidants co-treatment in preventing the genotoxicity of vorinostat when used as anticancer in human. PMID:23761013

  13. Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.

    PubMed

    Greene, Nicholas D E; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S; Copp, Andrew J

    2016-03-01

    Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised. PMID:26847388

  14. Prevention of neural tube defects with folic acid: The Chinese experience.

    PubMed

    Ren, Ai-Guo

    2015-08-01

    Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28(th) day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs. PMID:26261765

  15. Prevention of neural tube defects with folic acid: The Chinese experience

    PubMed Central

    Ren, Ai-Guo

    2015-01-01

    Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28th day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs. PMID:26261765

  16. Prediction of Damage Factor in end Milling of Glass Fibre Reinforced Plastic Composites Using Artificial Neural Network

    NASA Astrophysics Data System (ADS)

    Erkan, Ömer; Işık, Birhan; Çiçek, Adem; Kara, Fuat

    2013-08-01

    Glass fibre reinforced plastic (GFRP) composites are an economic alternative to engineering materials because of their superior properties. Some damages on the surface occur due to their complex cutting mechanics in cutting process. Minimisation of the damages is fairly important in terms of product quality. In this study, a GFRP composite material was milled to experimentally minimise the damages on the machined surfaces, using two, three and four flute end mills at different combinations of cutting parameters. Experimental results showed that the damage factor increased with increasing cutting speed and feed rate, on the other hand, it was found that the damage factor decreased with increasing depth of cut and number of the flutes. In addition, analysis of variance (ANOVA) results clearly revealed that the feed rate was the most influential parameter affecting the damage factor in end milling of GFRP composites. Also, in present study, Artificial Neural Network (ANN) models with five learning algorithms were used in predicting the damage factor to reduce number of expensive and time-consuming experiments. The highest performance was obtained by 4-10-1 network structure with LM learning algorithm. ANN was notably successful in predicting the damage factor due to higher R2 and lower RMSE and MEP.

  17. Nutriomes and personalised nutrition for DNA damage prevention, telomere integrity maintenance and cancer growth control.

    PubMed

    Fenech, Michael F

    2014-01-01

    DNA damage at the base sequence and chromosome level is a fundamental cause of developmental and degenerative diseases. Multiple micronutrients and their interactions with the inherited and/or acquired genome determine DNA damage and genomic instability rates. The challenge is to identify for each individual the combination of micronutrients and their doses (i.e. the nutriome) that optimises genome stability, including telomere integrity and functionality and DNA repair. Using nutrient array systems with high-content analysis diagnostics of DNA damage, cell death and cell growth, it is possible to define, on an individual basis, the optimal nutriome for DNA damage prevention and cancer growth control. This knowledge can also be used to improve culture systems for cells used in therapeutics such as stem cells to ensure that they are not genetically aberrant when returned to the body. Furthermore, this information could be used to design dietary patterns that deliver the micronutrient combinations and concentrations required for preventing DNA damage by micronutrient deficiency or excess. Using this approach, new knowledge could be obtained to identify the dietary restrictions and/or supplementations required to control specific cancers, which is particularly important given that reliable validated advice is not yet available for those diagnosed with cancer. PMID:24114494

  18. AZT treatment induces molecular and ultrastructural oxidative damage to muscle mitochondria. Prevention by antioxidant vitamins.

    PubMed

    de la Asunción, J G; del Olmo, M L; Sastre, J; Millán, A; Pellín, A; Pallardó, F V; Viña, J

    1998-07-01

    AIDS patients who receive zidovudine (AZT) frequently suffer from myopathy. This has been attributed to mitochondrial (mt) damage, and specifically to the loss of mtDNA. This study examines whether AZT causes oxidative damage to DNA in patients and to skeletal muscle mitochondria in mice, and whether this damage may be prevented by supranutritional doses of antioxidant vitamins. Asymptomatic HIV-infected patients treated with AZT have a higher urinary excretion (355+/-100 pmol/kg/d) of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxo-dG) (a marker of oxidative damage to DNA) than untreated controls (asymptomatic HIV-infected patients) (182+/-29 pmol/kg/d). This was prevented (110+/-79 pmol/kg/d) by simultaneous oral treatment with AZT plus antioxidant vitamins (C and E). Mice treated with AZT also had a significantly higher urinary excretion of 8-oxo-dG than controls. Skeletal muscle mtDNA of mice treated with AZT had more 8-oxo-dG than controls. mt lipoperoxidation was also increased and skeletal muscle glutathione was oxidized. These effects may be due to an increased peroxide production by muscle mitochondria of AZT-treated animals. Dietary supplements with vitamins C and E at supranutritional doses protect against oxidative damage to skeletal muscle mitochondria caused by AZT. PMID:9649550

  19. Neural Network Prediction of Failure of Damaged Composite Pressure Vessels from Strain Field Data Acquired by a Computer Vision Method

    NASA Technical Reports Server (NTRS)

    Russell, Samuel S.; Lansing, Matthew D.

    1997-01-01

    This effort used a new and novel method of acquiring strains called Sub-pixel Digital Video Image Correlation (SDVIC) on impact damaged Kevlar/epoxy filament wound pressure vessels during a proof test. To predict the burst pressure, the hoop strain field distribution around the impact location from three vessels was used to train a neural network. The network was then tested on additional pressure vessels. Several variations on the network were tried. The best results were obtained using a single hidden layer. SDVIC is a fill-field non-contact computer vision technique which provides in-plane deformation and strain data over a load differential. This method was used to determine hoop and axial displacements, hoop and axial linear strains, the in-plane shear strains and rotations in the regions surrounding impact sites in filament wound pressure vessels (FWPV) during proof loading by internal pressurization. The relationship between these deformation measurement values and the remaining life of the pressure vessels, however, requires a complex theoretical model or numerical simulation. Both of these techniques are time consuming and complicated. Previous results using neural network methods had been successful in predicting the burst pressure for graphite/epoxy pressure vessels based upon acoustic emission (AE) measurements in similar tests. The neural network associates the character of the AE amplitude distribution, which depends upon the extent of impact damage, with the burst pressure. Similarly, higher amounts of impact damage are theorized to cause a higher amount of strain concentration in the damage effected zone at a given pressure and result in lower burst pressures. This relationship suggests that a neural network might be able to find an empirical relationship between the SDVIC strain field data and the burst pressure, analogous to the AE method, with greater speed and simplicity than theoretical or finite element modeling. The process of testing SDVIC

  20. Melatonin prevents neural tube defects in the offspring of diabetic pregnancy.

    PubMed

    Liu, Shangming; Guo, Yuji; Yuan, Qiuhuan; Pan, Yan; Wang, Liyan; Liu, Qian; Wang, Fuwu; Wang, Jingjing; Hao, Aijun

    2015-11-01

    Melatonin, an endogenous neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. However, its protective role on the neural tube defects (NTDs) was not very clear. The aim of this study was to investigate the effects of melatonin on the incidence of NTDs (including anencephaly, encephalocele, and spina bifida) of offspring from diabetic pregnant mice as well as its underlying mechanisms. Pregnant mice were given 10 mg/kg melatonin by daily i.p. injection from embryonic day (E) 0.5 until being killed on E11.5. Here, we showed that melatonin decreased the NTDs (especially exencephaly) rate of embryos exposed to maternal diabetes. Melatonin stimulated proliferation of neural stem cells (NSCs) under hyperglycemic condition through the extracellular regulated protein kinases (ERK) pathway. Furthermore, as a direct free radical scavenger, melatonin decreased apoptosis of NSCs exposed to hyperglycemia. In the light of these findings, it suggests that melatonin supplementation may play an important role in the prevention of neural malformations in diabetic pregnancy. PMID:26475080

  1. Inositol prevents folate-resistant neural tube defects in the mouse.

    PubMed

    Greene, N D; Copp, A J

    1997-01-01

    Clinical trials demonstrate that up to 70% of neural tube defects (NTDs) can be prevented by folic acid supplementation in early pregnancy, whereas the remaining NTDs are resistant to folate. Here, we show that a second vitamin, myo-inositol, is capable of significantly reducing the incidence of spinal NTDs in curly tail mice, a genetic model of folate-resistant NTDs. Inositol increases flux through the inositol/lipid cycle, stimulating protein kinase C activity and upregulating expression of retinoic acid receptor beta, specifically in the caudal portion of the embryonic hindgut. This reduces the delay in closure of the posterior neuropore, the embryonic defect that is known to lead directly to spina bifida in curly tail embryos. Our findings reveal a molecular pathway of NTD prevention and suggest the possible efficacy of combined treatment with folate and inositol in overcoming the majority of human NTDs. PMID:8986742

  2. Damage detection in carbon composite material typical of wind turbine blades using auto-associative neural networks

    NASA Astrophysics Data System (ADS)

    Dervilis, N.; Barthorpe, R. J.; Antoniadou, I.; Staszewski, W. J.; Worden, K.

    2012-04-01

    The structure of a wind turbine blade plays a vital role in the mechanical and structural operation of the turbine. As new generations of offshore wind turbines are trying to achieve a leading role in the energy market, key challenges such as a reliable Structural Health Monitoring (SHM) of the blades is significant for the economic and structural efficiency of the wind energy. Fault diagnosis of wind turbine blades is a "grand challenge" due to their composite nature, weight and length. The damage detection procedure involves additional difficulties focused on aerodynamic loads, environmental conditions and gravitational loads. It will be shown that vibration dynamic response data combined with AANNs is a robust and powerful tool, offering on-line and real time damage prediction. In this study the features used for SHM are Frequency Response Functions (FRFs) acquired via experimental methods based on an LMS system by which identification of mode shapes and natural frequencies is accomplished. The methods used are statistical outlier analysis which allows a diagnosis of deviation from normality and an Auto-Associative Neural Network (AANN). Both of these techniques are trained by adopting the FRF data for normal and damage condition. The AANN is a method which has not yet been widely used in the condition monitoring of composite materials of blades. This paper is trying to introduce a new scheme for damage detection, localisation and severity assessment by adopting simple measurements such as FRFs and exploiting multilayer neural networks and outlier novelty detection.

  3. Usage of Probabilistic and General Regression Neural Network for Early Detection and Prevention of Oral Cancer

    PubMed Central

    Sharma, Neha; Om, Hari

    2015-01-01

    In India, the oral cancers are usually presented in advanced stage of malignancy. It is critical to ascertain the diagnosis in order to initiate most advantageous treatment of the suspicious lesions. The main hurdle in appropriate treatment and control of oral cancer is identification and risk assessment of early disease in the community in a cost-effective fashion. The objective of this research is to design a data mining model using probabilistic neural network and general regression neural network (PNN/GRNN) for early detection and prevention of oral malignancy. The model is built using the oral cancer database which has 35 attributes and 1025 records. All the attributes pertaining to clinical symptoms and history are considered to classify malignant and non-malignant cases. Subsequently, the model attempts to predict particular type of cancer, its stage and extent with the help of attributes pertaining to symptoms, gross examination and investigations. Also, the model envisages anticipating the survivability of a patient on the basis of treatment and follow-up details. Finally, the performance of the PNN/GRNN model is compared with that of other classification models. The classification accuracy of PNN/GRNN model is 80% and hence is better for early detection and prevention of the oral cancer. PMID:26171415

  4. Glutathione prevents ethanol induced gastric mucosal damage and depletion of sulfhydryl compounds in humans.

    PubMed Central

    Loguercio, C; Taranto, D; Beneduce, F; del Vecchio Blanco, C; de Vincentiis, A; Nardi, G; Romano, M

    1993-01-01

    Whether parenteral administration of reduced glutathione prevented ethanol induced damage to and depletion of sulfhydryl compounds in the human gastric mucosa was investigated. Ten healthy volunteers underwent endoscopy on three separate occasions. Gastric mucosal damage was induced by spraying 80% ethanol on to the gastric mucosa through the biopsy channel of the endoscope. The gastric mucosal score, total sulfhydryls, glutathione, and cysteine were evaluated in basal conditions and after ethanol administration with and without pretreatment with parenteral glutathione. Glutathione significantly decreased the extent of ethanol induced macroscopic injury to the mucosa of the gastric body and antrum. Glutathione's protective effect is associated with appreciable inhibition of ethanol induced depletion of gastric sulfhydryl compounds. This is the first report of protection against ethanol induced gastric mucosal damage by a sulfhydryl containing agent in humans. PMID:8432465

  5. Polyphenols in Exercise Performance and Prevention of Exercise-Induced Muscle Damage

    PubMed Central

    Hrelia, Silvana

    2013-01-01

    Although moderate physical exercise is considered an essential component of a healthy lifestyle that leads the organism to adapt itself to different stresses, exercise, especially when exhaustive, is also known to induce oxidative stress, inflammation, and muscle damage. Many efforts have been carried out to identify dietary strategies or micronutrients able to prevent or at least attenuate the exercise-induced muscle damage and stress. Unfortunately most studies have failed to show protection, and at the present time data supporting the protective effect of micronutrients, as antioxidant vitamins, are weak and trivial. This review focuses on those polyphenols, present in the plant kingdom, that have been recently suggested to exert some positive effects on exercise-induced muscle damage and oxidative stress. In the last decade flavonoids as quercetin, catechins, and other polyphenols as resveratrol have caught the scientists attention. However, at the present time drawing a clear and definitive conclusion seems to be untimely. PMID:23983900

  6. Hemopexin Prevents Endothelial Damage and Liver Congestion in a Mouse Model of Heme Overload

    PubMed Central

    Vinchi, Francesca; Gastaldi, Stefania; Silengo, Lorenzo; Altruda, Fiorella; Tolosano, Emanuela

    2008-01-01

    Intravascular hemolysis results in the release of massive amounts of hemoglobin and heme into plasma, where they are rapidly bound by haptoglobin and hemopexin, respectively. Data from haptoglobin and hemopexin knockout mice have shown that both proteins protect from renal damage after phenylhydrazine-induced hemolysis, whereas double-mutant mice were especially prone to liver damage. However, the specific role of hemopexin remains elusive because of the difficulty in discriminating between hemoglobin and heme recovery. To study the specific role of hemopexin in intravascular hemolysis, we established a mouse model of heme overload. Under these conditions, both endothelial activation and vascular permeability were significantly higher in hemopexin-null mice compared with wild-type controls. Vascular permeability was particularly altered in the liver, where congestion in the centrolobular area was believed to be associated with oxidative stress and inflammation. Liver damage in hemopexin- null mice may be prevented by induction of heme oxygenase-1 before heme overload. Furthermore, heme-treated hemopexin-null mice exhibited hyperbilirubinemia, prolonged heme oxygenase-1 expression, excessive heme metabolism, and lack of H-ferritin induction in the liver compared with heme-treated wild-type controls. Moreover, these mutant mice metabolize an excess of heme in the kidney. These studies highlight the importance of hemopexin in heme detoxification, thus suggesting that drugs mimicking hemopexin activity might be useful to prevent endothelial damage in patients suffering from hemolytic disorders. PMID:18556779

  7. A systematic approach for the prevention and treatment of formation damage caused by asphaltene deposition

    SciTech Connect

    Leontaritis, K.J.; Amaefule, J.O.; Charles, R.E. )

    1994-08-01

    Asphaltene plugging is a known cause of near-wellbore formation damage. Deposited asphaltenes can reduce effective hydrocarbon mobility by (1) blocking the pore throats; (2) adsorbing onto the rock, thereby altering the formation wettability from water-wet to oil-wet; and (3) increasing hydrocarbon viscosity by nucleating water-in-oil emulsions. Asphaltene flocculation and deposition can be avoided in some, but not all, cases. Some formation damage resulting from asphaltene plugging is permanent and hence must be prevented rather than treated. Prevention of asphaltene-induced formation damage should be started in the early stages of drilling and well completion, once the oil is known to be asphaltenic. This paper presents a systematic approach to successful diagnosis, prevention, and mitigation of asphaltene problems during recovery of asphaltenic oils. A mechanism of asphaltene flocculation and deposition is proposed and analyzed, and the previously defined concept of asphaltene deposition envelope is further refined. Diagnostic technology is presented that can test the compatibility of drilling and completion fluids with any asphaltenic oil. Important issues that need to be considered in the design of treatments for asphaltene removal are discussed. Finally, the paper presents a methodology for restoring unfavorable wettability changes caused by asphaltene deposition.

  8. R-spondin3 prevents mesenteric ischemia/reperfusion-induced tissue damage by tightening endothelium and preventing vascular leakage.

    PubMed

    Kannan, Lakshmi; Kis-Toth, Katalin; Yoshiya, Kazuhisa; Thai, To-Ha; Sehrawat, Seema; Mayadas, Tanya N; Dalle Lucca, Jurandir J; Tsokos, George C

    2013-08-27

    Inflammation and vascular injury triggered by ischemia/reperfusion (I/R) represent a leading cause of morbidity and mortality in a number of clinical settings. Wnt and its homolog partners R-spondins, in addition to regulating embryonic development have recently been demonstrated to serve as wound-healing agents in inflammation-associated conditions. Here we ask whether R-spondins could prevent inflammation-associated tissue damage in ischemic disorders and thus investigate the role of R-spondin3 (R-spo3) in a mouse model of mesenteric I/R. We demonstrate that R-spo3 ameliorates mesenteric I/R-induced local intestinal as well as remote lung damage by suppressing local and systemic cytokine response and deposition of IgM and complement in intestinal tissues. We also show that decreased inflammatory response is accompanied by tightening of endothelial cell junctions and reduction in vascular leakage. We conclude that R-spo3 stabilizes endothelial junctions and inhibits vascular leakage during I/R and thereby mitigates the inflammatory events and associated tissue damage. Our findings uniquely demonstrate a protective effect of R-spo3 in I/R-related tissue injury and suggest a mechanism by which it may have these effects. PMID:23942120

  9. Prevention of neural tube defects in the UK: a missed opportunity

    PubMed Central

    Morris, JK; Rankin, J; Draper, ES; Kurinczuk, JJ; Springett, A; Tucker, D; Wellesley, D; Wreyford, B; Wald, NJ

    2016-01-01

    Objective In 1991, the Medical Research Council (MRC) Vitamin Study demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). We aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in the UK from 1998 as it had been in the USA. Design Estimates of NTD prevalence, the preventive effect of folic acid and the proportion of women taking folic acid supplements before pregnancy were used to predict the number of NTD pregnancies that would have been prevented if folic acid fortification had been implemented. Setting Eight congenital anomaly registers in England and Wales. Main outcome measures The prevalence of pregnancies with an NTD in the UK and the number of these pregnancies that would have been prevented if folic acid fortification had been implemented. Results From 1991 to 2012, the prevalence of NTD pregnancies was 1.28 (95% CI 1.24 to 1.31) per 1000 total births (19% live births, 81% terminations and 0.5% stillbirths and fetal deaths ≥20 weeks’ gestation). If the USA levels of folic acid fortification from 1998 onwards had been adopted in the UK, an estimated 2014 fewer NTD pregnancies would have occurred. Conclusions Failure to implement folic acid fortification in the UK has caused, and continues to cause, avoidable terminations of pregnancy, stillbirths, neonatal deaths and permanent serious disability in surviving children. PMID:26681697

  10. Effectiveness of Disaster-prevention Technologies against Quake-induced Damage of MR Scanners during the Great East Japan Earthquake.

    PubMed

    Yamaguchi-Sekino, Sachiko; Machida, Yoshio; Tsuchihashi, Toshio; Isoda, Haruo; Noguchi, Takashi; Nakai, Toshiharu

    2016-04-11

    In the present study, we have performed a statistical analysis to investigate damages in magnetic resonance (MR) scanners caused by the Great East Japan Earthquake (GEJE, magnitude 9.0) and evaluated whether these disaster-prevention technologies contributed to the reduction of damages in the GEJE or not. It was confirmed that the extent of damage was significantly different between seismic scale (SS) 5 and SS over 6. Our survey study demonstrated that anchoring of MR facilities reduced damages due to quakes and demonstrated that anchoring is an efficient method for quake-induced damage prevention. The odds ratio revealed that base isolation was very useful to prevent damages in MR scanners. PMID:26597429

  11. Efficacy and safety of combination therapy for preventing bone damage in rheumatoid arthritis.

    PubMed

    Iannone, Florenzo; Lopalco, Giuseppe; Cantarini, Luca; Galeazzi, Mauro; Lapadula, Giovanni

    2016-01-01

    The main outcomes of the therapies for rheumatoid arthritis (RA) must be preventing, or at least lessening, the development of structural damage. Biological disease-modifying anti-rheumatic drugs (bDMARDs), targeting tumour necrosis factor-α (TNF-α) or other key steps (IL-1, IL-6, T cells, B cells) in the pathogenesis of RA, have given clues to be effective and safe as treatments for RA, being capable of improving disease activity, ameliorating functional ability and halting joint damage. A large body of evidence, stemming from randomized clinical trials, observational studies, and registries, has shown that the beneficial effects of the bDMARDs become optimal when combined with synthetic (s)-DMARDs, mainly methotrexate (MTX). Despite combination therapy is advocated by the international guidelines for the management of RA, data from the daily standard of care indicate that almost one third of RA patients are treated with bDMARDs as monotherapy. Many reasons may be taken into account to explain this gap from official recommendations, among which the fact that in real-life settings, the assessment of clinical outcomes is exclusively based on clinical indices, disregarding the evolution of bone damage. Furthermore, some bDMARDs have been launched in the market with the official approval to be used as monotherapy. But even for the latter, there is no conclusive proof that monotherapy regimen is comparable to co-therapy with MTX in preventing articular damage. In conclusion, the most recent published data show that combination therapy with bDMARDs and MTX represents the best therapeutic option for the treatment of RA since it can stop or at least slow the progression of disabling structural damage. PMID:26581205

  12. Concurrent Transient Activation of Wnt/{beta}-Catenin Pathway Prevents Radiation Damage to Salivary Glands

    SciTech Connect

    Hai Bo; Yang Zhenhua; Shangguan Lei; Zhao Yanqiu; Boyer, Arthur; Liu, Fei

    2012-05-01

    Purpose: Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/{beta}-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials: Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after, or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results: Radiation damage did not significantly affect activity of Wnt/{beta}-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/{beta}-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion: These results suggest that concurrent transient activation of the Wnt/{beta}-catenin pathway could prevent radiation-induced salivary gland dysfunction.

  13. Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia.

    PubMed

    Zugno, A I; Chipindo, H L; Volpato, A M; Budni, J; Steckert, A V; de Oliveira, M B; Heylmann, A S; da Rosa Silveira, F; Mastella, G A; Maravai, S G; Wessler, P G; Binatti, A R; Panizzutti, B; Schuck, P F; Quevedo, J; Gama, C S

    2014-02-14

    Supplementation with omega-3 has been identified as an adjunctive alternative for the treatment of psychiatric disorders, in order to minimize symptoms. Considering the lack of understanding concerning the pathophysiology of schizophrenia, the present study hypothesized that omega 3 prevents the onset of symptoms similar to schizophrenia in young Wistar rats submitted to ketamine treatment. Moreover, the role of oxidative stress in this model was assessed. Omega-3 (0.8g/kg) or vehicle was given by orogastric gavage once daily. Both treatments were performed during 21days, starting at the 30th day of life in young rats. After 14days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25mg/kg ip daily) was started and maintained until the last day of the experiment. We evaluated the pre-pulse inhibition of the startle reflex, activity of antioxidant systems and damage to proteins and lipids. Our results demonstrate that supplementation of omega-3 prevented: decreased inhibition of startle reflex, damage to lipids in the hippocampus and striatum and damage to proteins in the prefrontal cortex. Furthermore, these changes are associated with decreased GPx in brain tissues evaluated. Together, our results suggest the prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia. PMID:24316471

  14. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention.

    PubMed

    Greenberg, James A; Bell, Stacey J; Guan, Yong; Yu, Yan-Hong

    2011-01-01

    Folate (vitamin B(9)) is an essential nutrient that is required for DNA replication and as a substrate for a range of enzymatic reactions involved in amino acid synthesis and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus. Folate deficiency has been associated with abnormalities in both mothers (anemia, peripheral neuropathy) and fetuses (congenital abnormalities). This article reviews the metabolism of folic acid, the appropriate use of folic acid supplementation in pregnancy, and the potential benefits of folic acid, as well as the possible supplementation of l-methylfolate for the prevention of pregnancy-related complications other than neural tube defects. PMID:22102928

  15. Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia

    PubMed Central

    Vodret, Simone; Bortolussi, Giulia; Schreuder, Andrea B.; Jašprová, Jana; Vitek, Libor; Verkade, Henkjan J.; Muro, Andrés F.

    2015-01-01

    Therapies to prevent severe neonatal unconjugated hyperbilirubinemia and kernicterus are phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated bilirubin not bound to albumin (free bilirubin, Bf). Human serum albumin (HSA) administration was suggested to increase plasma bilirubin-binding capacity. However, its clinical use is infrequent due to difficulties to address its potential preventive and curative benefits, and to the absence of reliable markers to monitor bilirubin neurotoxicity risk. We used a genetic mouse model of unconjugated hyperbilirubinemia showing severe neurological impairment and neonatal lethality. We treated mutant pups with repeated HSA administration since birth, without phototherapy application. Daily intraperitoneal HSA administration completely rescued neurological damage and lethality, depending on dosage and administration frequency. Albumin infusion increased plasma bilirubin-binding capacity, mobilizing bilirubin from tissues to plasma. This resulted in reduced plasma Bf, forebrain and cerebellum bilirubin levels. We showed that, in our experimental model, Bf is the best marker to determine the risk of developing neurological damage. These results support the potential use of albumin administration in severe acute hyperbilirubinemia conditions to prevent or treat bilirubin neurotoxicity in situations in which exchange transfusion may be required. PMID:26541892

  16. Cranberry flavonoids prevent toxic rat liver mitochondrial damage in vivo and scavenge free radicals in vitro.

    PubMed

    Lapshina, Elena A; Zamaraeva, Maria; Cheshchevik, Vitali T; Olchowik-Grabarek, Ewa; Sekowski, Szymon; Zukowska, Izabela; Golovach, Nina G; Burd, Vasili N; Zavodnik, Ilya B

    2015-06-01

    The present study was undertaken for further elucidation of the mechanisms of flavonoid biological activity, focusing on the antioxidative and protective effects of cranberry flavonoids in free radical-generating systems and those on mitochondrial ultrastructure during carbon tetrachloride-induced rat intoxication. Treatment of rats with cranberry flavonoids (7 mg/kg) during chronic carbon tetrachloride-induced intoxication led to prevention of mitochondrial damage, including fragmentation, rupture and local loss of the outer mitochondrial membrane. In radical-generating systems, cranberry flavonoids effectively scavenged nitric oxide (IC50  = 4.4 ± 0.4 µg/ml), superoxide anion radicals (IC50  = 2.8 ± 0.3 µg/ml) and hydroxyl radicals (IC50  = 53 ± 4 µg/ml). The IC50 for reduction of 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH) was 2.2 ± 0.3 µg/ml. Flavonoids prevented to some extent lipid peroxidation in liposomal membranes and glutathione oxidation in erythrocytes treated with UV irradiation or organic hydroperoxides as well as decreased the rigidity of the outer leaflet of the liposomal membranes. The hepatoprotective potential of cranberry flavonoids could be due to specific prevention of rat liver mitochondrial damage. The mitochondria-addressed effects of flavonoids might be related both to radical-scavenging properties and modulation of various mitochondrial events. PMID:25962994

  17. DNA Damage in Mammalian Neural Stem Cells Leads to Astrocytic Differentiation Mediated by BMP2 Signaling through JAK-STAT

    PubMed Central

    Schneider, Leonid; Pellegatta, Serena; Favaro, Rebecca; Pisati, Federica; Roncaglia, Paola; Testa, Giuseppe; Nicolis, Silvia K.; Finocchiaro, Gaetano; d’Adda di Fagagna, Fabrizio

    2013-01-01

    Summary The consequences of DNA damage generation in mammalian somatic stem cells, including neural stem cells (NSCs), are poorly understood despite their potential relevance for tissue homeostasis. Here, we show that, following ionizing radiation-induced DNA damage, NSCs enter irreversible proliferative arrest with features of cellular senescence. This is characterized by increased cytokine secretion, loss of stem cell markers, and astrocytic differentiation. We demonstrate that BMP2 is necessary to induce expression of the astrocyte marker GFAP in irradiated NSCs via a noncanonical signaling pathway engaging JAK-STAT. This is promoted by ATM and antagonized by p53. Using a SOX2-Cre reporter mouse model for cell-lineage tracing, we demonstrate irradiation-induced NSC differentiation in vivo. Furthermore, glioblastoma assays reveal that irradiation therapy affects the tumorigenic potential of cancer stem cells by ablating self-renewal and inducing astroglial differentiation. PMID:24052948

  18. Prevention of cellular oxidative damage by an aqueous extract of Anoectochilus formosanus.

    PubMed

    Wang, Leng-Fang; Lin, Chun-Mao; Shih, Chwen-Ming; Chen, Hui-Ju; Su, Borcherng; Tseng, Cheng-Chuang; Gau, Bao-Bih; Cheng, Kur-Ta

    2005-05-01

    Anoectochilus formosanus (AF) is a popular folk medicine in Taiwan whose pharmacological effects have been characterized. In this work we investigated the antioxidant properties of an aqueous extract prepared from AF. The AF extract was capable of scavenging H2O2 in a dose-dependent manner. We induced oxidative stress in HL-60 cells, either by the addition of hydrogen peroxide (H2O2) or by the xanthine/xanthine oxidase reaction. Apoptosis caused by oxidative damage was displayed by DNA fragmentation on gel electrophoresis, and the apoptotic fraction was quantified with flow cytometry. The cell damage induced by oxidative stress was prevented by the plant extract in a concentration-dependent manner. Furthermore, the proteolytic cleavage of poly(ADP-ribose) polymerase during the apoptotic process was also inhibited by AF extract. Our results provide the basis for determining an AF extract to be an antioxidant. PMID:15965084

  19. MAPK15 upregulation promotes cell proliferation and prevents DNA damage in male germ cell tumors

    PubMed Central

    Ilardi, Gennaro; Acunzo, Mario; Nigita, Giovanni; Sasdelli, Federica; Celetti, Angela; Strambi, Angela; Staibano, Stefania; Croce, Carlo Maria; Chiariello, Mario

    2016-01-01

    Germ cell tumors (GCT) are the most common malignancies in males between 15 and 35 years of age. Despite the high cure rate, achieved through chemotherapy and/or surgery, the molecular basis of GCT etiology is still largely obscure. Here, we show a positive correlation between MAPK15 (ERK8; ERK7) expression and specific GCT subtypes, with the highest levels found in the aggressive embryonal carcinomas (EC). Indeed, in corresponding cellular models for EC, MAPK15 enhanced tumorigenicity in vivo and promoted cell proliferation in vitro, supporting a role for this kinase in human GCT. At molecular level, we demonstrated that endogenous MAPK15 is necessary to sustain cell cycle progression of EC cells, by limiting p53 activation and preventing the triggering of p53-dependent mechanisms resulting in cell cycle arrest. To understand MAPK15-dependent mechanisms impinging on p53 activation, we demonstrate that this kinase efficiently protects cells from DNA damage. Moreover, we show that the ability of MAPK15 to control the autophagic process is necessary for basal management of DNA damage and for tumor formation controlled by the kinase. In conclusion, our findings suggest that MAPK15 overexpression may contribute to the malignant transformation of germ cells by controlling a “stress support” autophagic pathway, able to prevent DNA damage and the consequent activation of the p53 tumor suppressor. Moreover, in light of these results, MAPK15-specific inhibitors might represent new tools to enhance the therapeutic index of cytotoxic therapy in GCT treatment, and to increase the sensitivity to DNA-damaging drugs in other chemotherapy-resistant human tumors. PMID:26988910

  20. MAPK15 upregulation promotes cell proliferation and prevents DNA damage in male germ cell tumors.

    PubMed

    Rossi, Matteo; Colecchia, David; Ilardi, Gennaro; Acunzo, Mario; Nigita, Giovanni; Sasdelli, Federica; Celetti, Angela; Strambi, Angela; Staibano, Stefania; Croce, Carlo Maria; Chiariello, Mario

    2016-04-12

    Germ cell tumors (GCT) are the most common malignancies in males between 15 and 35 years of age. Despite the high cure rate, achieved through chemotherapy and/or surgery, the molecular basis of GCT etiology is still largely obscure. Here, we show a positive correlation between MAPK15 (ERK8; ERK7) expression and specific GCT subtypes, with the highest levels found in the aggressive embryonal carcinomas (EC). Indeed, in corresponding cellular models for EC, MAPK15 enhanced tumorigenicity in vivo and promoted cell proliferation in vitro, supporting a role for this kinase in human GCT. At molecular level, we demonstrated that endogenous MAPK15 is necessary to sustain cell cycle progression of EC cells, by limiting p53 activation and preventing the triggering of p53-dependent mechanisms resulting in cell cycle arrest.To understand MAPK15-dependent mechanisms impinging on p53 activation, we demonstrate that this kinase efficiently protects cells from DNA damage. Moreover, we show that the ability of MAPK15 to control the autophagic process is necessary for basal management of DNA damage and for tumor formation controlled by the kinase.In conclusion, our findings suggest that MAPK15 overexpression may contribute to the malignant transformation of germ cells by controlling a "stress support" autophagic pathway, able to prevent DNA damage and the consequent activation of the p53 tumor suppressor. Moreover, in light of these results, MAPK15-specific inhibitors might represent new tools to enhance the therapeutic index of cytotoxic therapy in GCT treatment, and to increase the sensitivity to DNA-damaging drugs in other chemotherapy-resistant human tumors. PMID:26988910

  1. Multiple organ damage caused by tumor necrosis factor and prevented by prior neutrophil depletion

    SciTech Connect

    Mallick, A.A.; Ishizaka, A.; Stephens, K.E.; Hatherill, J.R.; Tazelaar, H.D.; Raffin, T.A. )

    1989-05-01

    The effect of TNF on nonpulmonary multiple organ damage (MOD) was studied. Since polymorphonuclear leukocytes (PMN) are thought to play an important role in septic or TNF-induced MOD, we investigated both neutrophil sufficient (PMN+) and neutropenic (PMN-) guinea pigs. Sepsis was induced by Escherichia coli administration (2 x 10(9)/kg) or recombinant human TNF (1.4 x 10(6) U/kg) was infused into PMN+ and PMN- guinea pigs. During necropsy, the PMN+/TNF and PMN+/E coli animals exhibited marked damage in the adrenal glands, kidneys and liver as evidenced by hemorrhage, congestion, and PMN sequestration on histopathologic examination. There was also increased tissue albumin accumulation in the adrenal glands, kidneys, spleen, heart, and liver as demonstrated by {sup 125}I-labeled albumin determinations. In contrast, the PMN-/TNF group did not reveal histopathologic damage in any organ system and there was no abnormal organ accumulation of {sup 125}I-albumin. However, in PMN-/E coli animals, marked histopathologic damage in the adrenal glands and liver was evident. Furthermore, there were marked accumulations of {sup 125}I-albumin in the adrenals, heart, kidneys, liver, and spleen. Moreover, the PMN-/E coli guinea pigs had a much greater accumulation (p less than 0.01) of {sup 125}I-albumin in the kidneys than any other group including the PMN+/E coli group. Thus, nonpulmonary MOD in guinea pigs is caused by TNF administration and can be prevented by PMN depletion. However, while E coli administration also caused marked nonpulmonary MOD in neutrophil sufficient guinea pigs, equivalent or greater damage was produced in neutropenic animals. This suggests that while TNF-induced MOD may be primarily mediated by PMN, E coli-induced MOD seems to be mediated by more than PMN.

  2. The Ets protein Pointed prevents both premature differentiation and dedifferentiation of Drosophila intermediate neural progenitors.

    PubMed

    Xie, Yonggang; Li, Xiaosu; Deng, Xiaobing; Hou, Yanjun; O'Hara, Krysten; Urso, Andreacarola; Peng, Ying; Chen, Li; Zhu, Sijun

    2016-09-01

    Intermediate neural progenitors (INPs) need to avoid both dedifferentiation and differentiation during neurogenesis, but the underlying mechanisms are not well understood. In Drosophila, the Ets protein Pointed P1 (PntP1) is required to generate INPs from type II neuroblasts. Here, we investigated how PntP1 promotes INP generation. By generating pntP1-specific mutants and using RNAi knockdown, we show that the loss of PntP1 leads to both an increase in type II neuroblast number and the elimination of INPs. The elimination of INPs results from the premature differentiation of INPs due to ectopic Prospero expression in newly generated immature INPs (imINPs), whereas the increase in type II neuroblasts results from the dedifferentiation of imINPs due to loss of Earmuff at later stages of imINP development. Furthermore, reducing Buttonhead enhances the loss of INPs in pntP1 mutants, suggesting that PntP1 and Buttonhead act cooperatively to prevent premature INP differentiation. Our results demonstrate that PntP1 prevents both the premature differentiation and the dedifferentiation of INPs by regulating the expression of distinct target genes at different stages of imINP development. PMID:27510969

  3. Gain control through divisive inhibition prevents abrupt transition to chaos in a neural mass model

    NASA Astrophysics Data System (ADS)

    Papasavvas, Christoforos A.; Wang, Yujiang; Trevelyan, Andrew J.; Kaiser, Marcus

    2015-09-01

    Experimental results suggest that there are two distinct mechanisms of inhibition in cortical neuronal networks: subtractive and divisive inhibition. They modulate the input-output function of their target neurons either by increasing the input that is needed to reach maximum output or by reducing the gain and the value of maximum output itself, respectively. However, the role of these mechanisms on the dynamics of the network is poorly understood. We introduce a novel population model and numerically investigate the influence of divisive inhibition on network dynamics. Specifically, we focus on the transitions from a state of regular oscillations to a state of chaotic dynamics via period-doubling bifurcations. The model with divisive inhibition exhibits a universal transition rate to chaos (Feigenbaum behavior). In contrast, in an equivalent model without divisive inhibition, transition rates to chaos are not bounded by the universal constant (non-Feigenbaum behavior). This non-Feigenbaum behavior, when only subtractive inhibition is present, is linked to the interaction of bifurcation curves in the parameter space. Indeed, searching the parameter space showed that such interactions are impossible when divisive inhibition is included. Therefore, divisive inhibition prevents non-Feigenbaum behavior and, consequently, any abrupt transition to chaos. The results suggest that the divisive inhibition in neuronal networks could play a crucial role in keeping the states of order and chaos well separated and in preventing the onset of pathological neural dynamics.

  4. Gain control through divisive inhibition prevents abrupt transition to chaos in a neural mass model

    PubMed Central

    Papasavvas, Christoforos A.; Wang, Yujiang; Trevelyan, Andrew J.; Kaiser, Marcus

    2016-01-01

    Experimental results suggest that there are two distinct mechanisms of inhibition in cortical neuronal networks: subtractive and divisive inhibition. They modulate the input-output function of their target neurons either by increasing the input that is needed to reach maximum output or by reducing the gain and the value of maximum output itself, respectively. However, the role of these mechanisms on the dynamics of the network is poorly understood. We introduce a novel population model and numerically investigate the influence of divisive inhibition on network dynamics. Specifically, we focus on the transitions from a state of regular oscillations to a state of chaotic dynamics via period-doubling bifurcations. The model with divisive inhibition exhibits a universal transition rate to chaos (Feigenbaum behavior). In contrast, in an equivalent model without divisive inhibition, transition rates to chaos are not bounded by the universal constant (non-Feigenbaum behavior). This non-Feigenbaum behavior, when only subtractive inhibition is present, is linked to the interaction of bifurcation curves in the parameter space. Indeed, searching the parameter space showed that such interactions are impossible when divisive inhibition is included. Therefore, divisive inhibition prevents non-Feigenbaum behavior and, consequently, any abrupt transition to chaos. The results suggest that the divisive inhibition in neuronal networks could play a crucial role in keeping the states of order and chaos well separated and in preventing the onset of pathological neural dynamics. PMID:26465514

  5. Preventive effects of Spirulina platensis on skeletal muscle damage under exercise-induced oxidative stress.

    PubMed

    Lu, Hsueh-Kuan; Hsieh, Chin-Cheng; Hsu, Jen-Jung; Yang, Yuh-Kuan; Chou, Hong-Nong

    2006-09-01

    The effects of spirulina supplementation on preventing skeletal muscle damage on untrained human beings were examined. Sixteen students volunteered to take Spirulina platensis in addition to their normal diet for 3-weeks. Blood samples were taken after finishing the Bruce incremental treadmill exercise before and after treatment. The results showed that plasma concentrations of malondialdehyde (MDA) were significantly decreased after supplementation with spirulina (P < 0.05). The activity of blood superoxide dismutase (SOD) was significantly raised after supplementation with spirulina or soy protein (P < 0.05). Both of the blood glutathione peroxidaes (GPx) and lactate dehydrogenase (LDH) levels were significantly different between spirulina and soy protein supplementation by an ANCOVA analysis (P < 0.05). In addition, the lactate (LA) concentration was higher and the time to exhaustion (TE) was significantly extended in the spirulina trail (P < 0.05). These results suggest that ingestion of S. platensis showed preventive effect of the skeletal muscle damage and that probably led to postponement of the time of exhaustion during the all-out exercise. PMID:16944194

  6. Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response

    SciTech Connect

    Zheng, Yi; Tao, Shasha; Lian, Fangru; Chau, Binh T.; Chen, Jie; Sun, Guifan; Fang, Deyu; Lantz, R. Clark; Zhang, Donna D.

    2012-12-15

    Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted in pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure. -- Highlights: ► Exposed to arsenic particles and/or SF have elevated Nrf2 and its target genes. ► Sulforaphane prevents pathological alterations, oxidative damage and cell death. ► Sulforaphane alleviates infiltration of inflammatory cells into the lungs. ► Sulforaphane suppresses arsenic-induced proinflammatory cytokine production.

  7. Analysis of thermal damage in vocal cords for the prevention of collateral laser treatment effects

    NASA Astrophysics Data System (ADS)

    Fanjul Vélez, Félix; Luis Arce-Diego, José; del Barrio Fernández, Ángela; Borragán Torre, Alfonso

    2007-05-01

    The importance of vocal cords for the interaction with the world around is obviously known. Vocal cords disorders can be divided mainly into three categories: difficulty of movement of one or both vocal folds, lesion formation on them, and difficulty or lack of mucosal wave movement. In this last case, a laser heating treatment can be useful in order to improve tissue vibration. However, thermal damage should be considered to adjust laser parameters and so to prevent irreversible harmful effects to the patient. in this work, an analysis of thermal damage in vocal folds is proposed. Firstly thermo-optical laser-tissue interaction is studied, by means of a RTT (Radiation Transfer Theory) model solved with a Monte Carlo approach for the optical propagation of radiation, and a bio-heat equation, with a finite difference numerical method based solution, taking into account blood perfusion and boundary effects, for the thermal distribution. The spatial-temporal temperature distributions are obtained for two widely used lasers, Nd:YAG (1064 nm) and KTP (532 nm). From these data, an Arrhenius thermal damage analysis allows a prediction of possible laser treatment harmful effects on vocal cords that could cause scar formation or tissue burn. Different source powers and exposition times are considered, in such a way that an approximation of adequate wavelength, power and duration is achieved, in order to implement an efficient and safe laser treatment.

  8. Microcapsule-Type Organogel-Based Self-Healing System Having Secondary Damage Preventing Capability.

    PubMed

    Yang, Hye-In; Kim, Dong-Min; Yu, Hwan-Chul; Chung, Chan-Moon

    2016-05-01

    We have developed a novel microcapsule-type organogel-based self-healing system in which secondary damage does not occur in the healed region. A mixture of an organogelator, poor and good solvents for the gelator is used as the healing agent; when the good solvent evaporates from this agent, a viscoelastic organogel forms. The healing agent is microencapsulated with urea-formaldehyde polymer, and the resultant microcapsules are integrated into a polymer coating to prepare self-healing coatings. When the coatings are scratched, they self-heal, as demonstrated by means of corrosion testing, electrochemical testing, optical microscopy, and scanning electron microscopy (SEM). After the healed coatings are subjected to vigorous vibration, it is demonstrated that no secondary damage occurs in the healed region. The secondary damage preventing capability of the self-healing coating is attributable to the viscoelasticity of the organogel. The result can give insight into the development of a "permanent" self-healing system. PMID:27070306

  9. Neural network based system for damage identification and location in structural and mechanical systems

    SciTech Connect

    Farrar, C.R.; Doebling, S.W.; Prime, M.B.; Cornwell, P.; Kam, M.; Straser, E.G.; Hoerst, B.C.

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Recent advances in wireless, remotely monitored data acquisition systems coupled with the development of vibration-based damage detection algorithms make the possibility of self- or remotely-monitored structures and mechanical systems appear to be within the capabilities of current technology. However, before such a system can be relied upon to perform this monitoring, the variability of the vibration properties that are the basis for the damage detection algorithm must be understood and quantified. This understanding is necessary so that the artificial intelligence/expert system that is employed to discriminate when changes in modal properties are indicative of damage will not yield false indications of damage. To this end, this project has focused on developing statistical methods for quantifying variability in identified vibration proper ties of structural and mechanical systems.

  10. 3,3'-Dihydroxyisorenieratene and isorenieratene prevent UV-induced DNA damage in human skin fibroblasts.

    PubMed

    Wagener, Sarah; Völker, Tanja; De Spirt, Silke; Ernst, Hansgeorg; Stahl, Wilhelm

    2012-08-01

    Skin cancer is among the most frequent neoplastic malignancies and exposure to UV irradiation is a major risk factor. In addition to topical sunscreens, photoprotection by dietary antioxidants such as carotenoids or polyphenols has been suggested as a means of prevention. Isorenieratene (IR) and dihydroxyisorenieratene (DHIR) are aromatic carotenoids with particular antioxidant properties produced by Brevibacterium linens. The aim of this study was to investigate the photoprotective and antioxidant activities of DHIR and IR in comparison to the nonaromatic carotenoid lutein in human dermal fibroblasts. Incubation of the cells with DHIR and IR significantly decreased the UV-induced formation of cyclobutane pyrimidine dimers and formation of DNA strand breaks. Lipid oxidation was lowered as determined by the formation of malondialdehyde as a biomarker. Both aromatic carotenoids also prevented oxidatively generated damage to DNA as demonstrated by a decrease in DNA strand breaks associated with the formation of oxidized DNA bases. These data highlight the multifunctional photoprotective properties of aromatic carotenoids, which may be suitable natural compounds for the prevention of skin cancer. PMID:22634149

  11. Experimental study on asphaltene adsorption onto formation rock: An approach to asphaltene formation damage prevention

    SciTech Connect

    Piro, G.; Barberis Canonica, L.; Galbariggi, G.; Bertero, L.; Carniani, C.

    1995-12-31

    In this paper, through a comparative study on Static vs Dynamic adsorption of asphaltene onto formation rock, it is reported how, for the particular asphaltene/formation rock system here considered, the Dynamic asphaltene adsorption onto formation rock is a continuous phenomenon by which the quantity of adsorbed asphaltene increases continuously. In the authors` opinion this rather remarkable adsorption behavior may contribute to asphaltene formation damage. In the hypothesis that prevention may represent a more economical approach than removal, in this work is also reported a possible prevention approach based on formation rock treatment by means of specific chemicals more apt than asphaltenes to be adsorbed onto rock. As preliminary demonstration, with the aim at assessing qualitatively the potential of their approach, the authors have pre-treated the rock by means of commercially available asphaltene dispersant and flocculation inhibitors. Albeit the chosen additives are not commercialized on the base of their specific adsorption feature, a prevention effect has been effectively found. Experimental set ups and procedures used as a base for a test able to rank chemicals with respect to their asphaltene adsorption inhibitive effects are also reported.

  12. Asphaltene adsorption onto formation rock: An approach to asphaltene formation damage prevention

    SciTech Connect

    Piro, G.; Canonico, L.B.; Galbariggi, G.; Bertero, L.; Carniani, C.

    1996-08-01

    In this paper, through a comparative study on static vs. dynamic adsorption of asphaltene onto formation rock, the authors report how, for the particular asphaltene/formation rock system considered, the dynamic asphaltene adsorption onto formation rock is a continuous phenomenon by which the quantity of adsorbed asphaltene increases continuously. In their opinion, this rather remarkable adsorption behavior may contribute to asphaltene formation damage. In the hypothesis that prevention may represent a more economical approach than removal, they also report a possible prevention approach based on formation rock treatment by means of specific chemicals more apt than asphaltenes to be adsorbed onto rock. As a preliminary demonstration, with the aim of assessing qualitatively the potential of their approach, they have pretreated the rock with commercially available asphaltene dispersant and flocculation inhibitors. Although the chosen additives are not commercialized on the basis of their specific adsorption feature, a modest prevention effect has been found. Experimental set-ups and procedures used as a base for a test to rank chemicals with respect to their asphaltene adsorption inhibitive effects are also reported.

  13. Preventing Damaging Pressure Gradients at the Walls of an Inflatable Space System

    NASA Technical Reports Server (NTRS)

    Scialdone, John J.

    2000-01-01

    An inflatable structural system to deploy a space system such as a solar shield, an antenna or another similar instrument, requires a stiffening element after it is extended by the inflated gas pressure. The stiffening element has to be packaged in a folded configuration before the deployment. It must be relatively small, lightweight, non-damaging to the inflated system, and be able to become stiff in a short time. One stiffening method is to use a flexible material inserted in the deployable system, which, upon a temperature curing, can become stiff and is capable to support the entire structure. There are two conditions during the space operations when the inflated volume could be damaged: during the transonic region of the launch phase and when the curing of the rigidizing element occurs. In both cases, an excess of pressure within the volume containing the rigid element could burst the walls of the low-pressure gas inflated portion of the system. This paper investigates those two conditions and indicates the vents, which will prevent those damaging overpressures. Vent openings at the non-inflated volumes have been calculated for the conditions existing during the launch. Those vents allow the initially folded volume to exhaust the trapped atmospheric gas at approximately the same rate as the ambient pressure drops. That will prevent pressure gradients across the container walls which otherwise could be as high as 14.7 psi. The other condition occurring during the curing of the stiffening element has been investigated. This has required the testing of the element to obtain the gas generation during the curing and the transformation from a pliable material to a rigid one. The tested material is a composite graphite/epoxy weave. The outgassing of the uncured sample at 121C was carried with the Cahn Microbalance and with other outgassing facilities including the micro-CVCM ASTM E-595 facility. The tests provided the mass of gas evolved during the test. That data

  14. Preventing Damaging Pressure Gradients at the Walls of an Inflatable Space System

    NASA Technical Reports Server (NTRS)

    Scialdone, John J.; Powers, Edward I. (Technical Monitor)

    2000-01-01

    An inflatable structural system to deploy a space system such as a solar shield, an antenna or another similar instrument requires a stiffening element after it is extended by the inflated gas pressure. The stiffening element has to be packaged in folded configuration before the deployment. It must be relatively small, lightweight, non-damaging to the inflated system and be able to become stiff in a short time. One stiffening method is to use a flexible material inserted in the deployable system, which, upon a temperature curing, can become stiff and is capable of supporting the entire structure. There are two conditions during the space operations when the inflated volume could be damaged: during the transonic region of the launch phase and when the curing of the rigidizing element occurs. In both cases, an excess of pressure within the volume containing the rigid element could burst the walls of the low-pressure gas inflated portion of the system. This paper investigates those two conditions and indicates the vents, which will prevent those damaging overpressures. Vent openings at the non-inflated volumes have been calculated for the conditions existing during the launch. Those vents allow the initially folded volume to exhaust the trapped atmospheric gas at approximately the same rate as the ambient pressure drops. That will prevent pressure gradients across the container walls which otherwise could be as high as 14.7 psi. The other condition occurring during the curing of the stiffening element has been investigated. This has required the testing of the element to obtain the gas generation during the curing and the transformation from a pliable material to a rigid on The tested material is a composite graphite/epoxy weave. The outgassing of the uncured sample at 121 deg Celcius was carried with the Cahn Microbalance and with other outgassing facilities including the micro-CVCM ASTM E-595 facility. The test provided the mass of gas evolved during the test. That

  15. Long Term Maintenance of Neural Tube Defects Prevention in a High Prevalence State

    PubMed Central

    Collins, Julianne S.; Atkinson, Kristy K.; Dean, Jane H.; Best, Robert G.; Stevenson, Roger E.

    2011-01-01

    Objective To assess the efficacy of folic acid (FA) supplementation and fortification in preventing neural tube defects (NTDs) in a high prevalence region of the US. Study design Active and passive surveillance methods were used to identify all fetuses/infants affected by an NTD in South Carolina. Prevalence rates were compared with FA intake to determine the effects of increased intake on NTD occurrence and recurrence. Results From 1992–2009, 916 NTD cases occurred in South Carolina with isolated defects comprising 79% of cases. The NTD rate decreased 58% during this period. There was one NTD-affected pregnancy among 418 subsequent pregnancies (0.2%) in mothers with previous NTD-affected pregnancies who consumed periconceptional FA supplements and four NTDs among 66 pregnancies (6.1%) in which the mother did not take FA supplements. Folic acid supplementation increased from 8% to 35% from 1992–2007 and knowledge of the protective benefits of FA increased from 8% to 65% in women of childbearing age. Conclusions Increased periconceptional intake of FA appeared to reduce NTDs in a high prevalence region. The rate of spina bifida and anencephaly in South Carolina is now essentially the same (0.69 cases per 1000 live births and fetal deaths) as the 1998–2005 US rate (0.69). PMID:21345450

  16. Orally administered melatonin prevents lipopolysaccharide-induced neural tube defects in mice.

    PubMed

    Fu, Lin; Yu, Zhen; Chen, Yuan-Hua; Xia, Mi-Zhen; Wang, Hua; Zhang, Cheng; Tao, Fang-Biao; Xu, De-Xiang

    2014-01-01

    Lipopolysaccharide (LPS) has been associated with adverse pregnant outcomes, including fetal demise, intra-uterine growth restriction (IUGR), neural tube defects (NTDs) and preterm delivery in rodent animals. Previous studies demonstrated that melatonin protected against LPS-induced fetal demise, IUGR and preterm delivery. The aim of the present study was to investigate the effects of melatonin on LPS-induced NTDs. All pregnant mice except controls were intraperitoneally injected with LPS (25 µg/kg) daily from gestational day (GD)8 to GD12. Some pregnant mice were orally administered with melatonin (MT, 50 mg/kg) before each LPS injection. A five-day LPS injection resulted in 27.5% of fetuses with anencephaly, exencephaly or encephalomeningocele. Additional experiment showed that maternal LPS exposure significantly down-regulated placental proton-coupled folate transporter (pcft) and disturbed folate transport from maternal circulation through the placentas into the fetus. Interestingly, melatonin significantly attenuated LPS-induced down-regulation of placental pcft. Moreover, melatonin markedly improved the transport of folate from maternal circulation through the placentas into the fetus. Correspondingly, orally administered melatonin reduced the incidence of LPS-induced anencephaly, exencephaly or encephalomeningocele. Taken together, these results suggest that orally administered melatonin prevents LPS-induced NTDs through alleviating LPS-induced disturbance of folate transport from maternal circulation through the placenta into the fetus. PMID:25420102

  17. Neural network technology as a pollution prevention tool in the electric utility industry

    SciTech Connect

    Johnson, M.L.

    1998-07-01

    This paper documents efforts by the Lower Colorado River Authority (LCRA) to pilot test the use of neural network technology as a pollution prevention tool for reducing stack emissions from a natural gas-fired power generating facility. The project was funded in part by a grant from the US Environmental Protection Agency (EPA), Region VI. combustion control is quickly becoming an emerging alternative for reducing utility plant emissions without installing costly end of pipe controls. The LCRA estimates that the technology has the potential to improve the thermal efficiency of a large utility boiler by more than 1 percent. preliminary calculations indicate that a 1% improvement in thermal efficiency at the 430 MW gas-fired utility boiler could results in an estimated energy savings of 142, 140 mmBtus and carbon dioxide (CO{sub 2}) reductions of 8,774 tons per year. This paper describes the process that were undertaken to identify and implement the pilot project at LCRA's Thomas C. Ferguson Power Plant, located in Marble Falls, Texas, Activities performed and documented include lessons learned, equipment selection, data acquisition, model evaluation and projected emission reductions.

  18. Resistant starch: a functional food that prevents DNA damage and chemical carcinogenesis.

    PubMed

    Navarro, S D; Mauro, M O; Pesarini, J R; Ogo, F M; Oliveira, R J

    2015-01-01

    Resistant starch is formed from starch and its degradation products and is not digested or absorbed in the intestine; thus, it is characterized as a fiber. Because fiber intake is associated with the prevention of DNA damage and cancer, the potential antigenotoxic, antimutagenic, and anticarcinogenic capabilities of resistant starch from green banana flour were evaluated. Animals were treated with 1,2-dimethylhydrazine and their diet was supplemented with 10% green banana flour according to the following resistant starch protocols: pretreatment, simultaneous treatment, post-treatment, and pre + continuous treatment. The results demonstrated that resistant starch is not genotoxic, mutagenic, or carcinogenic. The results suggest that resistant starch acts through desmutagenesis and bio-antimutagenesis, as well as by reducing aberrant crypt foci, thereby improving disease prognosis. These findings imply that green banana flour has therapeutic properties that should be explored for human dietary applications. PMID:25867310

  19. Evaluation of antioxidant activity and preventing DNA damage effect of pomegranate extracts by chemiluminescence method.

    PubMed

    Guo, Shanshan; Deng, Qianchun; Xiao, Junsong; Xie, Bijun; Sun, Zhida

    2007-04-18

    The antioxidant activities of three parts (peel, juice, and seed) and extracts of three pomegranate varieties in China were investigated by using a chemiluminescence (CL) method in vitro. The scavenging ability of pomegranate extracts (PEs) on superoxide anion, hydroxide radical, and hydrogen peroxide was determined by the pyrogallol-luminol system, the CuSO4-Phen-Vc-H2O2 system, and the luminol-H2O2 system, respectively. DNA damage preventing the effect of PE was determined by the CuSO4-Phen-Vc-H2O2-DNA CL system. The results showed that the peel extract of red pomegranate had the best effect on the scavenging ability of superoxide anion because its IC50 value (4.01 +/- 0.09 microg/mL) was the lowest in all PEs. The seed extract of white pomegranate could scavenge hydroxide radical most effectively of the nine extracts (the IC50 value was 1.69 +/- 0.03 microg/mL). The peel extract of white pomegranate had the best scavenging ability on hydrogen peroxide, which had the lowest IC50 value (0.032 +/- 0.003 microg/mL) in the nine extracts. The seed extract of white pomegranate (the IC50 value was 3.67 +/- 0.03 microg/mL) was the most powerful on the DNA damage-preventing effect in all of the PEs. Also, the statistical analysis indicated that there were significant differences (at P < 0.05) among the extracts of the different varieties and parts in each system. PMID:17381116

  20. Ultraviolet radiation, aging and the skin: prevention of damage by topical cAMP manipulation

    PubMed Central

    Amaro-Ortiz, Alexandra; Yan, Betty; D’Orazio, John A.

    2015-01-01

    Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of “realized” solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii) plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations. PMID:24838074

  1. Superoxide dismutase derivative prevents oxidative damage in liver and kidney of rats induced by exhausting exercise.

    PubMed

    Radák, Z; Asano, K; Inoue, M; Kizaki, T; Oh-Ishi, S; Suzuki, K; Taniguchi, N; Ohno, H

    1996-01-01

    To prevent oxidative tissue damage induced by strenuous exercise in the liver and kidney superoxide dismutase derivative (SM-SOD), which circulated bound to albumin with a half-life of 6 h, was injected intraperitoneally into rats. Exhausting treadmill running caused a significant increase in the activities of xanthine oxidase (XO), and glutathione peroxidase (GPX) in addition to concentrations of thiobarbituric acid-reactive substances (TBARS) in hepatic tissue immediately after running. There was a definite increase in the immunoreactive content of mitochondrial superoxide dismutase (Mn-SOD) 1 day after the running. Meanwhile, the TBARS concentration in the kidney was markedly elevated 3 days after running. The activities of GPX, and catalase in the kidney increased significantly immediately and on days 1 and 3 following the test. The immunoreactive content of Mn-SOD also increased 1 day after running. The exercise induced no significant changes in immunoreactive Cu, Zn-SOD content in either tissue. The administration of SM-SOD provided effective protection against lipid peroxidation, and significantly attenuated the alterations in XO and all the anti-oxidant enzymes, measured. In summary, the present data would suggest that exhausting exercise may induce XO-derived oxidative damage in the liver, while the increase in lipid peroxidation in the kidney might be the result of washout-dependent accumulation of peroxidised metabolites. We found that the administration of SM-SOD provided excellent protection against exercise-induced oxidative stress in both liver and kidney. PMID:8820884

  2. Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

    PubMed Central

    Czeizel, Andrew E.; Dudás, Istvan; Vereczkey, Attila; Bánhidy, Ferenc

    2013-01-01

    Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”. PMID:24284617

  3. MAPPING TOXICANT-INDUCED NERVOUS SYSTEM DAMAGE WITH A CUPRIC SILVER STAIN: A QUANTITATIVE ANALYSIS OF NEURAL DEGENERATION INDUCED BY 3,4-METHYLENEDIOXYMETHAMPETHAMINE (MDMA)

    EPA Science Inventory

    The purpose of structural assessments in neurotoxicology is to provide a convincing picture of the location and extent of damage to the nervous system. ilver stains that selectively reveal neural degeneration hold particular promise in this regard. n this chapter we describe resu...

  4. Oxidative DNA damage preventive activity and antioxidant potential of plants used in Unani system of medicine

    PubMed Central

    2010-01-01

    Background There is increasing recognition that many of today's diseases are due to the "oxidative stress" that results from an imbalance between the formation and neutralization of reactive molecules such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can be removed with antioxidants. The main objective of the present study was to evaluate the antioxidant activity of plants routinely used in the Unani system of medicine. Several plants were screened for radical scavenging activity, and the ten that showed promising results were selected for further evaluation. Methods Methanol (50%) extracts were prepared from ten Unani plants, namely Cleome icosandra, Rosa damascena, Cyperus scariosus, Gardenia gummifera, Abies pindrow, Valeriana wallichii, Holarrhena antidysenterica, Anacyclus pyrethrum, Asphodelus tenuifolius and Cyperus scariosus, and were used to determine their total phenolic, flavonoid and ascorbic acid contents, in vitro scavenging of DPPH·, ABTS·+, NO, ·OH, O2.- and ONOO-, and capacity to prevent oxidative DNA damage. Cytotoxic activity was also determined against the U937 cell line. Results IC50 values for scavenging DPPH·, ABTS·+, NO, ·OH, O2.- and ONOO- were in the ranges 0.007 ± 0.0001 - 2.006 ± 0.002 mg/ml, 2.54 ± 0.04 - 156.94 ± 5.28 μg/ml, 152.23 ± 3.51 - 286.59 ± 3.89 μg/ml, 18.23 ± 0.03 - 50.13 ± 0.04 μg/ml, 28.85 ± 0.23 - 537.87 ± 93 μg/ml and 0.532 ± 0.015 - 3.39 ± 0.032 mg/ml, respectively. The total phenolic, flavonoid and ascorbic acid contents were in the ranges 62.89 ± 0.43 - 166.13 ± 0.56 mg gallic acid equivalent (GAE)/g extract, 38.89 ± 0.52 - 172.23 ± 0.08 mg quercetin equivalent (QEE)/g extract and 0.14 ± 0.09 - 0.98 ± 0.21 mg AA/g extract. The activities of the different plant extracts against oxidative DNA damage were in the range 0.13-1.60 μg/ml. Of the ten selected plant extracts studied here, seven - C. icosandra, R. damascena, C. scariosus, G. gummifera, A. pindrow, V

  5. Neural Hyperactivity of the Central Auditory System in Response to Peripheral Damage

    PubMed Central

    Zhao, Yi; Song, Qiang; Li, Xinyi; Li, Chunyan

    2016-01-01

    It is increasingly appreciated that cochlear pathology is accompanied by adaptive responses in the central auditory system. The cause of cochlear pathology varies widely, and it seems that few commonalities can be drawn. In fact, despite intricate internal neuroplasticity and diverse external symptoms, several classical injury models provide a feasible path to locate responses to different peripheral cochlear lesions. In these cases, hair cell damage may lead to considerable hyperactivity in the central auditory pathways, mediated by a reduction in inhibition, which may underlie some clinical symptoms associated with hearing loss, such as tinnitus. Homeostatic plasticity, the most discussed and acknowledged mechanism in recent years, is most likely responsible for excited central activity following cochlear damage. PMID:26881094

  6. Use of Family History Information for Neural Tube Defect Prevention: Integration into State-Based Recurrence Prevention Programs

    ERIC Educational Resources Information Center

    Green, Ridgely Fisk; Ehrhardt, Joan; Ruttenber, Margaret F.; Olney, Richard S.

    2011-01-01

    A family history of neural tube defects (NTDs) can increase the risk of a pregnancy affected by an NTD. Periconceptional folic acid use decreases this risk. Purpose: Our objective was to determine whether second-degree relatives of NTD-affected children showed differences in folic acid use compared with the general population and to provide them…

  7. Dividing the self: distinct neural substrates of task-based and automatic self-prioritization after brain damage.

    PubMed

    Sui, Jie; Chechlacz, Magdalena; Humphreys, Glyn W

    2012-02-01

    Facial self-awareness is a basic human ability dependent on a distributed bilateral neural network and revealed through prioritized processing of our own over other faces. Using non-prosopagnosic patients we show, for the first time, that facial self-awareness can be fractionated into different component processes. Patients performed two face perception tasks. In a face orientation task, they judged whether their own or others' faces were oriented to the left or right. In the 'cross' experiment, they judged which horizontal or vertical element in a cross was relatively longer while ignoring a task-irrelevant face presented as background. The data indicate that impairments to a distinct task-based prioritization process (when faces had to be attended) were present after brain damage to right superior frontal gyrus, bilateral precuneus, and left middle temporal gyrus. In contrast, impairments to automatic prioritization processes (when faces had to be ignored) were associated only with left hemisphere damage (the cingulate gyrus, superior parietal lobe, and superior temporal gyrus). In addition, both automatic and task-based self-prioritizations were affected by damage to left supramarginal and angular gyrus. The results for the gray matter analyses also extended to the adjacent white matter fiber tracts including the inferior occipital-frontal fasciculus, cingulum, and optic radiation. The data provide the first empirical evidence for separate functional roles of the left and right hemispheres in different aspects of self-face perception and suggest distinct functional processes respectively for paying attention to and for ignoring self-related information. PMID:22115024

  8. Prevention and repair of protein damage by the Maillard reaction in vivo.

    PubMed

    Monnier, Vincent M; Sell, David R

    2006-01-01

    The aging human extracellular matrix (ECM) and tissues rich in long-lived proteins undergo extensive changes with age that include increased stiffening, loss of elasticity, insolubilization, and decreased proteolytic digestibility. Most if not all these changes can be duplicated by the Maillard reaction in vitro, that is, the incubation of the proteins with reducing sugars and oxoaldehydes. These carbonyls eventually form advanced glycation end products (AGEs) and crosslinks that impair proteolytic digestibility and alter protein conformation. To date, close to 20 AGEs have been found in the human skin, of which ornithine is the single major result of damage to arginine residues, and glucosepane the single major crosslink. Although redox active metals and oxoaldehydes appear to play an important role in protein damage in experimental diabetes, their role in diabetic humans is still poorly understood. Evidence for the existence of deglycating enzymes has been found in vertebrates, bacteria, and fungi. However, only the vertebrate enzymes can deglycate larger, intracellular proteins via an ATP-dependent mechanism. Protein engineering will thus be needed to adapt Amadoriase enzymes toward deglycation of ECM proteins for purpose of probing the role of advanced glycation in animal models of diabetes and age-related diseases. The blocking of the reactivity of the glucosepane precursor using potent nucleophiles may be useful in preventing age-related changes in ECM proteins. However, there currently is no evidence in support of the proposed ability of so-called "AGE breakers" to cleave existing crosslinks of the Maillard reaction in vivo, and other mechanisms of action should be sought for this class of compounds. PMID:16706654

  9. Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol.

    PubMed

    Cogram, Patricia; Hynes, Andrew; Dunlevy, Louisa P E; Greene, Nicholas D E; Copp, Andrew J

    2004-01-01

    A proportion of neural tube defects (NTDs) can be prevented by maternal folic acid supplementation, although some cases are unresponsive. The curly tail mutant mouse provides a model of folate-resistant NTDs, in which defects can be prevented by inositol therapy in early pregnancy. Hence, inositol represents a possible novel adjunct therapy to prevent human NTDs. The present study investigated the molecular mechanism by which inositol prevents mouse NTDs. Activation of protein kinase C (PKC) is known to be essential, and we examined neurulation-stage embryos for PKC expression and applied PKC inhibitors to curly tail embryos developing in culture. Although all known PKC isoforms were detected in the closing neural tube, use of chemical PKC inhibitors identified a particular requirement for 'conventional' PKC isoforms. Peptide inhibitors offer selective inhibition of individual PKCs, and we demonstrated isoform-specific inhibition of PKC in embryonic cell cultures. Application of peptide inhibitors to neurulation-stage embryos revealed an absolute dependence on the activity of PKCbetaI and gamma for prevention of NTDs by inositol, and partial dependence on PKCzeta, whereas other PKCs (alpha, betaII delta, and epsilon) were dispensable. To investigate the cellular action of inositol and PKCs in NTD prevention, we examined cell proliferation in curly tail embryos. Defective proliferation of hindgut cells is a key component of the pathogenic sequence leading to NTDs in curly tail. Hindgut cell proliferation was stimulated specifically by inositol, an effect that required activation of PKCbetaI. Our findings reveal an essential role of specific PKC isoforms in mediating the prevention of mouse NTDs by inositol. PMID:14613966

  10. Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy.

    PubMed

    Rey-Funes, Manuel; Larrayoz, Ignacio M; Fernández, Juan C; Contartese, Daniela S; Rolón, Federico; Inserra, Pablo I F; Martínez-Murillo, Ricardo; López-Costa, Juan J; Dorfman, Verónica B; Martínez, Alfredo; Loidl, César F

    2016-06-01

    Perinatal asphyxia induces retinal lesions, generating ischemic proliferative retinopathy, which may result in blindness. Previously, we showed that the nitrergic system was involved in the physiopathology of perinatal asphyxia. Here we analyze the application of methylene blue, a well-known soluble guanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy. Male rats (n = 28 per group) were treated in different ways: 1) control group comprised born-to-term animals; 2) methylene blue group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) group comprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4) methylene blue-PA group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery, and then the pups were subjected to PA as above. For molecular studies, mRNA was obtained at different times after asphyxia, and tissue was collected at 30 days for morphological and biochemical analysis. Perinatal asphyxia produced significant gliosis, angiogenesis, and thickening of the inner retina. Methylene blue treatment reduced these parameters. Perinatal asphyxia resulted in a significant elevation of the nitrergic system as shown by NO synthase (NOS) activity assays, Western blotting, and (immuno)histochemistry for the neuronal isoform of NOS and NADPH-diaphorase activity. All these parameters were also normalized by the treatment. In addition, methylene blue induced the upregulation of the anti-angiogenic peptide, pigment epithelium-derived factor. Application of methylene blue reduced morphological and biochemical parameters of retinopathy. This finding suggests the use of methylene blue as a new treatment to prevent or decrease retinal damage in the context of ischemic proliferative retinopathy. PMID:26984891

  11. 36 CFR 223.113 - Modification of contracts to prevent environmental damage or to conform to forest plans.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false Modification of contracts to prevent environmental damage or to conform to forest plans. 223.113 Section 223.113 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST...

  12. 36 CFR 223.113 - Modification of contracts to prevent environmental damage or to conform to forest plans.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Modification of contracts to prevent environmental damage or to conform to forest plans. 223.113 Section 223.113 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST...

  13. 36 CFR 223.113 - Modification of contracts to prevent environmental damage or to conform to forest plans.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 2 2014-07-01 2014-07-01 false Modification of contracts to prevent environmental damage or to conform to forest plans. 223.113 Section 223.113 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST...

  14. 36 CFR 223.113 - Modification of contracts to prevent environmental damage or to conform to forest plans.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 2 2013-07-01 2013-07-01 false Modification of contracts to prevent environmental damage or to conform to forest plans. 223.113 Section 223.113 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST...

  15. 36 CFR 223.113 - Modification of contracts to prevent environmental damage or to conform to forest plans.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Modification of contracts to prevent environmental damage or to conform to forest plans. 223.113 Section 223.113 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST...

  16. Dihydrolipoic acid inhibits tetrachlorohydroquinone-induced tumor promotion through prevention of oxidative damage.

    PubMed

    Wang, Ying-Jan; Yang, Ming-Chen; Pan, Ming-Hsiung

    2008-12-01

    alpha-Lipoic acid (LA) has been intensely investigated as a therapeutic agent for several diseases, including hepatic disorder and diabetic polyneuropathy. However, the effects of LA or its reduced form, dihydrolipoic acid (DHLA), on cancer chemoprevention has seldom been studied. Tetrachlorohydroquinone (TCHQ) is a toxic metabolite of pentachlorophenol (PCP) that was proven to be a tumor promoter in our previous study. We recently reported that DHLA can inhibit DMBA/TPA-induced skin tumor formation through its anti-inflammatory and anti-oxidizing functions. In the present study, we further examined the effects of DHLA on DMBA/TCHQ-induced skin tumor formation and the possible mechanisms. We found that DHLA significantly inhibited tumor incidence and tumor multiplicity in DMBA/TCHQ-induced skin tumor formation. Administration of DHLA prevented ROS generation, cytotoxicity, genotoxicity and apoptotic cell death in cells treated with TCHQ. In addition, activation of JNK and p38 MAPK may be involved in TCHQ-mediated apoptosis. Nonetheless, the detailed mechanisms of DHLA in attenuating TCHQ-induced skin tumor promotion are still unclear and need to be further investigated. We conclude that DHLA may be a useful protective agent against TCHQ-induced toxicity in epithelial cells, and for reversing TCHQ-induced damage in mouse skin. PMID:18951944

  17. In vitro PAMAM, phosphorus and viologen-phosphorus dendrimers prevent rotenone-induced cell damage.

    PubMed

    Milowska, Katarzyna; Szwed, Aleksandra; Zablocka, Maria; Caminade, Anne-Marie; Majoral, Jean-Pierre; Mignani, Serge; Gabryelak, Teresa; Bryszewska, Maria

    2014-10-20

    We have investigated whether polyamidoamine (PAMAM), phosphorus (pd) and viologen-phosphorus (vpd) dendrimers can prevent damage to embryonic mouse hippocampal cells (mHippoE-18) caused by rotenone, which is used as a pesticide, insecticide, and as a nonselective piscicide, that works by interfering with the electron transport chain in mitochondria. Several basic aspects, such as cell viability, production of reactive oxygen species and changes in mitochondrial transmembrane potential, were analyzed. mHippoE-18 cells were treated with these structurally different dendrimers at 0.1μM. A 1h incubation with dendrimers was followed by the addition of rotenone at 1μM, and a further 24h incubation. PAMAM, phosphorus and viologen-phosphorus dendrimers all increased cell viability (reduced cell death-data need to be compared with untreated controls). A lower level of reactive oxygen species and a favorable effect on mitochondrial system were found with PAMAM and viologen-phosphorus dendrimers. These results indicate reduced toxicity in the presence of dendrimers. PMID:25108046

  18. Prevention of ultraviolet damage to the dermis of hairless mice by sunscreens

    SciTech Connect

    Kligman, L.H.; Akin, F.J.; Kligman, A.M.

    1982-02-01

    To assess the ability of sunscreens to protect connective tissue from actinic damage, hairless mice were irradiated with Westinghouse FS20 sunlamps thrice weekly for 30 weeks. Each exposure, consisting mainly of UV-B and the less energetic UV-A, was approximately 6 human minimal erythema doses under these lights. One group of animals received irradiation only. The other 2 groups were treated, prior to irradiation, with sunscreens of either low or high sun protection factors (SPF 2 and SPF 15, respectively). Skin biopsies were taken at 10-week intervals and were stained with various histochemical stains to reveal changes in the dermis. The unprotected, irradiated animals showed a great increase in the following: reticulin fibers, elastic fibers to the extent of elastosis, neutral and acid mucopolysaccharides and melanin production. The SPF 15 sunscreen completely prevented these changes. The SPF 2 sunscreen was less effective. These effects were substantiated by ultrastructural examination of the tissues by electron microscopy. A surprising histologic finding was the repair capability of the dermis in the post-irradiation period.

  19. Toward sensitive graphene nanoribbon-nanopore devices by preventing electron beam-induced damage.

    PubMed

    Puster, Matthew; Rodríguez-Manzo, Julio A; Balan, Adrian; Drndić, Marija

    2013-12-23

    Graphene-based nanopore devices are promising candidates for next-generation DNA sequencing. Here we fabricated graphene nanoribbon-nanopore (GNR-NP) sensors for DNA detection. Nanopores with diameters in the range 2-10 nm were formed at the edge or in the center of graphene nanoribbons (GNRs), with widths between 20 and 250 nm and lengths of 600 nm, on 40 nm thick silicon nitride (SiN(x)) membranes. GNR conductance was monitored in situ during electron irradiation-induced nanopore formation inside a transmission electron microscope (TEM) operating at 200 kV. We show that GNR resistance increases linearly with electron dose and that GNR conductance and mobility decrease by a factor of 10 or more when GNRs are imaged at relatively high magnification with a broad beam prior to making a nanopore. By operating the TEM in scanning TEM (STEM) mode, in which the position of the converged electron beam can be controlled with high spatial precision via automated feedback, we were able to prevent electron beam-induced damage and make nanopores in highly conducting GNR sensors. This method minimizes the exposure of the GNRs to the beam before and during nanopore formation. The resulting GNRs with unchanged resistances after nanopore formation can sustain microampere currents at low voltages (∼50 mV) in buffered electrolyte solution and exhibit high sensitivity, with a large relative change of resistance upon changes of gate voltage, similar to pristine GNRs without nanopores. PMID:24224888

  20. [Effective interventions to prevent health damage related to ultraviolet exposure: a review of the literature].

    PubMed

    Nguyen Thanh, Viêt; Clément, Juliette; Haroutunian, Laetitia; Léon, Christophe; Arwidson, Pierre

    2015-01-01

    The purpose of this paper is to review the current scientific knowledge on health promotion interventions designed to prevent health damage caused by natural ultraviolet (UV) exposure. The current state of knowledge in this area was assessed using a specific method including a review of literature reviews and a classification of health promotion interventions identified using scientific databases. We found a large number of promising programmes. Briefly, some interventions based on environmental changes and provision of shade were considered to be promising. Health education programmes delivered at school have been proven to be effective in various settings, from nursery school to college. Some parentbased interventions designed to promote children's sun protection behaviours have been shown to be relevant. Appearance-based actions, using for instance photoaging information, may be effective. Finally, some multi-component interventions in community settings appear to be promising. These findings present a number of limitations due to the marked diversity of outcome measures and the general quality of the documents reviewed. Furthermore, most interventions are poorly described in the reviews. The present study should therefore be considered to be a first step that needs to be completed by a more detailed description of the promising interventions and of their transposition to the French context. PMID:26751922

  1. Electrode array-eluted dexamethasone protects against electrode insertion trauma induced hearing and hair cell losses, damage to neural elements, increases in impedance and fibrosis: A dose response study.

    PubMed

    Bas, Esperanza; Bohorquez, Jorge; Goncalves, Stefania; Perez, Enrique; Dinh, Christine T; Garnham, Carolyn; Hessler, Roland; Eshraghi, Adrien A; Van De Water, Thomas R

    2016-07-01

    We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT-induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10%, 1%, 0.1%, or 0% levels of micronized DXMb. These four types of electrode arrays were implanted into the scala tympani via basal turn cochleostomies and left in place for 3 months. Hearing thresholds were determined by ABR and CAP recordings in response to a series of defined pure tone stimuli (i.e. 16-0.5 kHz). Changes in impedance were measured between the implant electrode and a reference electrode. Hair cell counts and neural element integrity were determined by confocal microscopy analyses of stained organ of Corti whole mounts obtained from 90 day post-implantation animals. Fibrosis was measured in Masson trichrome stained cross-sections through the organ of Corti. The results showed that either 10% or 1.0% DXMb eluting electrode arrays protected; hearing thresholds, hair cells, and neural elements against EIT-induced losses and damage. Electrode arrays with 0.1% DXMb only partial protected against EIT-induced hearing loss and damage to the cochlea. Protection of hearing thresholds and organ of Corti sensory elements by electrode-eluted DXMb was still apparent at 3 months post-EIT. All three concentrations of DXMb in the electrode arrays prevented EIT-induced increases in impedance. EIT-initiated fibrosis was significantly reduced within the implanted cochlea of the two DXMb concentrations tested. In conclusion, DXMb eluting electrodes protected the cochlea against long term increases in hearing thresholds, loss of hair cells, damage to neural elements and

  2. Autophagy regulates intracerebral hemorrhage induced neural damage via apoptosis and NF-κB pathway.

    PubMed

    Shen, Xi; Ma, Lu; Dong, Wenwen; Wu, Qiong; Gao, Yuan; Luo, Chengliang; Zhang, Mingyang; Chen, Xiping; Tao, Luyang

    2016-06-01

    Autophagy can be a pro-survival or a pro-death mechanism depending on the context. The role of autophagy in intracerebral hemorrhage (ICH) remains elusive. In this study, in vivo and in vitro experiments have been carried out to investigate the role of autophagy after ICH. Collagenase-induced ICH model in mouse was made for in vivo experiments. Primary cortical neurons cultures were exposed to hemin to mimic ICH in vitro. 3-Methyladenine (3-MA) and rapamycin (RAP) were administrated both in vivo and in vitro. We first measured brain water content and cell death after ICH in model. Expression of LC3, p62/SQSTM1 (p62), Beclin1, Caspase3 and Bcl-2, which have been found related to autophagy and apoptosis, were assessed both in vivo and in vitro. Furthermore, NF-κB was detected to explore the potential mechanisms. We found brain edema in ICH model in mouse and the number of Propidium Iodide (PI)-positive cells both in vivo and in vitro were decreased by 3-MA pretreated. Simultaneously, both in vivo and in vitro, 3-MA significantly decreased the expression of LC3-II and Beclin-1, and maintained p62 at high level after ICH. Furthermore, pretreatment with 3-MA downregulated the level of cleaved caspase-3 but upregulated the Bcl-2 level. Conversely, RAP pretreatment reversed all these results above. These data indicated that autophagy activation may deprave ICH induced brain injury in ICH model and neuro-damage may be related to regulating of NF-κB pathway and thereby promote inflammation and apoptosis, thus might provide novel therapeutic interventions for ICH. PMID:26964766

  3. PE859, a Novel Tau Aggregation Inhibitor, Reduces Aggregated Tau and Prevents Onset and Progression of Neural Dysfunction In Vivo

    PubMed Central

    Okuda, Michiaki; Hijikuro, Ichiro; Fujita, Yuki; Wu, Xiaofeng; Nakayama, Shinichi; Sakata, Yoko; Noguchi, Yuji; Ogo, Makoto; Akasofu, Shigeru; Ito, Yoshimasa; Soeda, Yoshiyuki; Tsuchiya, Nobuhiko; Tanaka, Naoki; Takahashi, Takashi; Sugimoto, Hachiro

    2015-01-01

    In tauopathies, a neural microtubule-associated protein tau (MAPT) is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies. PMID:25659102

  4. Intranasal delivery of obidoxime to the brain prevents mortality and CNS damage from organophosphate poisoning.

    PubMed

    Krishnan, Jishnu K S; Arun, Peethambaran; Appu, Abhilash P; Vijayakumar, Nivetha; Figueiredo, Taíza H; Braga, Maria F M; Baskota, Sudikshya; Olsen, Cara H; Farkas, Natalia; Dagata, John; Frey, William H; Moffett, John R; Namboodiri, Aryan M A

    2016-03-01

    Intranasal delivery is an emerging method for bypassing the blood brain barrier (BBB) and targeting therapeutics to the CNS. Oximes are used to counteract the effects of organophosphate poisoning, but they do not readily cross the BBB. Therefore, they cannot effectively counteract the central neuropathologies caused by cholinergic over-activation when administered peripherally. For these reasons we examined intranasal administration of oximes in an animal model of severe organophosphate poisoning to determine their effectiveness in reducing mortality and seizure-induced neuronal degeneration. Using the paraoxon model of organophosphate poisoning, we administered the standard treatment (intramuscular pralidoxime plus atropine sulphate) to all animals and then compared the effectiveness of intranasal application of obidoxime (OBD) to saline in the control groups. Intranasally administered OBD was effective in partially reducing paraoxon-induced acetylcholinesterase inhibition in the brain and substantially reduced seizure severity and duration. Further, intranasal OBD completely prevented mortality, which was 41% in the animals given standard treatment plus intranasal saline. Fluoro-Jade-B staining revealed extensive neuronal degeneration in the surviving saline-treated animals 24h after paraoxon administration, whereas no detectable degenerating neurons were observed in any of the animals given intranasal OBD 30min before or 5min after paraoxon administration. These findings demonstrate that intranasally administered oximes bypass the BBB more effectively than those administered peripherally and provide an effective method for protecting the brain from organophosphates. The addition of intranasally administered oximes to the current treatment regimen for organophosphate poisoning would improve efficacy, reducing both brain damage and mortality. PMID:26751814

  5. Heme oxygenase-1 induction prevents neuronal damage triggered during mitochondrial inhibition: role of CO and bilirubin.

    PubMed

    Orozco-Ibarra, Marisol; Estrada-Sánchez, Ana María; Massieu, Lourdes; Pedraza-Chaverrí, José

    2009-06-01

    Heme oxygenase (HO) catalyzes the breakdown of heme to iron, carbon monoxide (CO), and biliverdin, the latter being further reduced to bilirubin (BR). A protective role of the inducible isoform, HO-1, has been described in pathological conditions associated with reactive oxygen species (ROS) and oxidative damage. The aim of this study was to investigate the role of HO-1 in the neurotoxicity induced by the mitochondrial toxin 3-nitropropionic acid (3-NP) in primary cultures of cerebellar granule neurons (CGNs). Toxicity of 3-NP is associated with ROS production, and this metabolic toxin has been used to mimic pathological conditions such as Huntington's disease. We found that cell death caused by 3-NP exposure was exacerbated by inhibition of HO with tin mesoporphyrin (SnMP). In addition, HO-1 up-regulation induced by the exposure to cobalt protoporphyrin (CoPP) before the incubation with 3-NP, prevented the cell death and the increase in ROS induced by 3-NP. Interestingly, addition of SnMP to CoPP-pretreated CGNs exposed to 3-NP, abolished the protective effect of CoPP suggesting that HO activity was responsible for this protective effect. This was additionally supported by the fact that CORM-2, a CO-releasing molecule, and BR, were able to protect against cell death and the increase in ROS induced by 3-NP. Our data clearly show that HO-1 elicits in CGNs a neuroprotective action against the neurotoxicity of 3-NP and that CO and BR may be involved, at least in part, in this protective effect. The present results increase our knowledge about the role of HO-1 in neuropathological conditions. PMID:19063990

  6. A fiber laser welding of plastics assisted by transparent solid heat sink to prevent the surface thermal damages

    NASA Astrophysics Data System (ADS)

    Kurosaki, Yasuo; Satoh, Kimitoshi

    This paper deals with an innovative fiber laser welding method for engineering plastics assisted by a solid heat sink transparent to the laser beam for preventing any thermal damage on the surface. The features of this fiber laser welding procedure are (1) to place a solid heat sink transparent to the fiber laser beam in contact with an irradiated plastics to cool the surface during welding process, (2) to use no pigmentation or dye for radiation absorption enhancement, (3) to sustain thermal damage on the surface, and (4) to avoid the emission of harmful gas due to decomposition of plastics.

  7. Vigabatrin and carbamazepine have different efficacies in the prevention of status epilepticus induced neuronal damage in the hippocampus and amygdala.

    PubMed

    Pitkänen, A; Tuunanen, J; Halonen, T

    1996-05-01

    The present study compares the efficacy of carbamazepine (20 mg/kg/day) and vigabatrin (250 mg/kg/day) in preventing hippocampal and amygdaloid damage in the perforant pathway stimulation model of status epilepticus in the rat. One group of rats received a combination of the drugs. Drug treatments were started one week before the stimulation and continued for two weeks thereafter. Gallyas silver impregnation and somatostatin immunohistochemistry were used to detect neuronal damage. All drug treatments were equally effective in decreasing the number and severity of seizures during electrical stimulation. In the vigabatrin group, the damage to the hilar somatostatin-immunoreactive (SOM-ir) neurons and hippocampal CA3c pyramidal cells was less severe than in the vehicle (SOM-ir, P < 0.01; CA3c, P < 0.05) and carbamazepine (SOM-ir, P < 0.01; CA3c, P < 0.05) groups. In the carbamazepine and combination groups, the severity of neuronal damage in the hippocampus did not differ from that in vehicle-treated animals. The amygdaloid neurons were not protected by any of the treatments. Our results show that even though vigabatrin and carbamazepine treatments had similar anticonvulsant efficacy during the perforant pathway stimulation, only vigabatrin but not carbamazepine decreased seizure-induced neuronal damage. Vigabatrin decreased neuronal damage in the hippocampus but not in the amygdala. These results demonstrate that different brain regions and neuronal networks may be protected unequally by different anticonvulsants. PMID:8800633

  8. Insights into prevention of human neural tube defects by folic acid arising from consideration of mouse mutants.

    PubMed

    Harris, Muriel J

    2009-04-01

    Almost 30 years after the initial study by Richard W. Smithells and coworkers, it is still unknown how maternal periconceptional folic acid supplementation prevents human neural tube defects (NTDs). In this article, questions about human NTD prevention are considered in relation to three groups of mouse models: NTD mutants that respond to folate, NTD mutants and strains that do not respond to folate, and mutants involving folate-pathway genes. Of the 200 mouse NTD mutants, only a few have been tested with folate; half respond and half do not. Among responsive mutants, folic acid supplementation reduces exencephaly and/or spina bifida aperta frequency in the Sp(2H), Sp, Cd, Cited2, Cart1, and Gcn5 mutants. Prevention ranges from 35 to 85%. The responsive Sp(2H) (Pax3) mutant has abnormal folate metabolism, but the responsive Cited2 mutant does not. Neither folic nor folinic acid reduces NTD frequency in Axd, Grhl3, Fkbp8, Map3k4, or Nog mutants or in the curly tail or SELH/Bc strains. Spina bifida frequency is reduced in Axd by methionine and in curly tail by inositol. Exencephaly frequency is reduced in SELH/Bc by an alternative commercial ration. Mutations in folate-pathway genes do not cause NTDs, except for 30% exencephaly in folate-treated Folr1. Among folate-pathway mutants, neural tube closure is normal in Cbs, Folr2, Mthfd1, Mthfd2, Mthfr, and Shmt1 mutants. Embryos die by midgestation in Folr1, Mtr, Mtrr, and RFC1 mutants. The mouse models point to genetic heterogeneity in the ability to respond to folic acid and also to heterogeneity in genetic cause of NTDs that can be prevented by folic acid. PMID:19117321

  9. Updated estimates of neural tube defects prevented by mandatory folic Acid fortification - United States, 1995-2011.

    PubMed

    Williams, Jennifer; Mai, Cara T; Mulinare, Joe; Isenburg, Jennifer; Flood, Timothy J; Ethen, Mary; Frohnert, Barbara; Kirby, Russell S

    2015-01-16

    In 1992, the U.S. Public Health Service recommended that all women capable of becoming pregnant consume 400 µg of folic acid daily to prevent neural tube defects (NTDs). NTDs are major birth defects of the brain and spine that occur early in pregnancy as a result of improper closure of the embryonic neural tube, which can lead to death or varying degrees of disability. The two most common NTDs are anencephaly and spina bifida. Beginning in 1998, the United States mandated fortification of enriched cereal grain products with 140 µg of folic acid per 100 g. Immediately after mandatory fortification, the birth prevalence of NTD cases declined. Fortification was estimated to avert approximately 1,000 NTD-affected pregnancies annually. To provide updated estimates of the birth prevalence of NTDs in the period after introduction of mandatory folic acid fortification (i.e., the post-fortification period), data from 19 population-based birth defects surveillance programs in the United States, covering the years 1999-2011, were examined. After the initial decrease, NTD birth prevalence during the post-fortification period has remained relatively stable. The number of births occurring annually without NTDs that would otherwise have been affected is approximately 1,326 (95% confidence interval = 1,122-1,531). Mandatory folic acid fortification remains an effective public health intervention. There remain opportunities for prevention among women with lower folic acid intakes, especially among Hispanic women, to further reduce the prevalence of NTDs in the United States. PMID:25590678

  10. Non-steroidal anti-inflammatory drug, nabumetone, prevents indometacin-induced gastric damage via inhibition of neutrophil functions.

    PubMed

    Ishiwata, Yoshiro; Okamoto, Masayuki; Yokochi, Shoji; Hashimoto, Hiroyuki; Nakamura, Takashi; Miyachi, Atsushi; Naito, Yuji; Yoshikawa, Toshikazu

    2003-02-01

    Nabumetone is a non-steroidal anti-inflammatory drug (NSAID). It works as a prodrug and is extensively metabolized to an active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). It is well known that neutrophil infiltration and activation are critical in the pathogenesis of NSAID-induced gastric injury, and nabumetone shows less incidence of gastrointestinal irritancy. We examined the effects of nabumetone on neutrophil activation and on indometacin-induced gastric damage. In the indometacin-induced gastric mucosal injury, rats were treated with indometacin and then nabumetone or 6MNA was orally administered. Nabumetone prevented gastric damage accompanied by the reduction of neutrophil infiltration into gastric mucosa, but such an effect was not observed with 6MNA. Nabumetone reduced the formyl methionyl leucyl phenylalanine (fMLP)-induced respiratory burst of human neutrophils to 30% of the control level in-vitro, but 6MNA did not. In addition, nabumetone prevented the fMLP-induced migration of neutrophils. Nabumetone did not inhibit O2- generation in the xanthine-xanthine oxidase system. These results suggest that nabumetone prevents gastric damage induced by the active metabolite, 6MNA, via the suppression of neutrophil activation in gastric mucosa. PMID:12635655

  11. Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice.

    PubMed

    Yi, Ruo-Kun; Song, Jia-Le; Lim, Yaung-Iee; Kim, Yong-Kyu; Park, Kun-Young

    2015-03-01

    This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-α, IL-1β, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage. PMID:25866750

  12. Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice

    PubMed Central

    Yi, Ruo-Kun; Song, Jia-Le; Lim, Yaung-Iee; Kim, Yong-Kyu; Park, Kun-Young

    2015-01-01

    This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-α, IL-1β, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage. PMID:25866750

  13. Folic Acid Protected Neural Cells Against Aluminum-Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation.

    PubMed

    Zhu, Mingming; Li, Bingfei; Ma, Xiao; Huang, Cong; Wu, Rui; Zhu, Weiwei; Li, Xiaoting; Liang, Zhaofeng; Deng, Feifei; Zhu, Jianyun; Xie, Wei; Yang, Xue; Jiang, Ye; Wang, Shijia; Wu, Jieshu; Geng, Shanshan; Xie, Chunfeng; Zhong, Caiyun; Liu, Haiyan

    2016-08-01

    Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway. PMID:27113042

  14. Mitochondria-targeted Ogg1 and Aconitase-2 Prevent Oxidant-induced Mitochondrial DNA Damage in Alveolar Epithelial Cells*

    PubMed Central

    Kim, Seok-Jo; Cheresh, Paul; Williams, David; Cheng, Yuan; Ridge, Karen; Schumacker, Paul T.; Weitzman, Sigmund; Bohr, Vilhelm A.; Kamp, David W.

    2014-01-01

    Mitochondria-targeted human 8-oxoguanine DNA glycosylase (mt-hOgg1) and aconitase-2 (Aco-2) each reduce oxidant-induced alveolar epithelial cell (AEC) apoptosis, but it is unclear whether protection occurs by preventing AEC mitochondrial DNA (mtDNA) damage. Using quantitative PCR-based measurements of mitochondrial and nuclear DNA damage, mtDNA damage was preferentially noted in AEC after exposure to oxidative stress (e.g. amosite asbestos (5–25 μg/cm2) or H2O2 (100–250 μm)) for 24 h. Overexpression of wild-type mt-hOgg1 or mt-long α/β 317–323 hOgg1 mutant incapable of DNA repair (mt-hOgg1-Mut) each blocked A549 cell oxidant-induced mtDNA damage, mitochondrial p53 translocation, and intrinsic apoptosis as assessed by DNA fragmentation and cleaved caspase-9. In contrast, compared with controls, knockdown of Ogg1 (using Ogg1 shRNA in A549 cells or primary alveolar type 2 cells from ogg1−/− mice) augmented mtDNA lesions and intrinsic apoptosis at base line, and these effects were increased further after exposure to oxidative stress. Notably, overexpression of Aco-2 reduced oxidant-induced mtDNA lesions, mitochondrial p53 translocation, and apoptosis, whereas siRNA for Aco-2 (siAco-2) enhanced mtDNA damage, mitochondrial p53 translocation, and apoptosis. Finally, siAco-2 attenuated the protective effects of mt-hOgg1-Mut but not wild-type mt-hOgg1 against oxidant-induced mtDNA damage and apoptosis. Collectively, these data demonstrate a novel role for mt-hOgg1 and Aco-2 in preserving AEC mtDNA integrity, thereby preventing oxidant-induced mitochondrial dysfunction, p53 mitochondrial translocation, and intrinsic apoptosis. Furthermore, mt-hOgg1 chaperoning of Aco-2 in preventing oxidant-mediated mtDNA damage and apoptosis may afford an innovative target for the molecular events underlying oxidant-induced toxicity. PMID:24429287

  15. Blood flow restriction prevents muscle damage but not protein synthesis signaling following eccentric contractions.

    PubMed

    Sudo, Mizuki; Ando, Soichi; Poole, David C; Kano, Yutaka

    2015-07-01

    There is a growing body of evidence to suggest that resistance training exercise combined with blood flow restriction (BFR) increases muscle size and strength in humans. Eccentric contraction (ECC) frequently induces severe muscle damage. However, it is not known whether and to what extent muscle damage occurs following ECC + BFR due to the difficulty of conducting definitive invasive studies. The purpose of this study was to examine muscle fiber damage following ECC + BFR at the cellular level. High-intensity ECC was purposefully selected to maximize the opportunity for muscle damage and hypertrophic signaling in our novel in vivo animal model. Male Wistar rats were assigned randomly to the following groups: ECC and ECC + BFR at varying levels of occlusion pressure (140, 160, and 200 Torr). In all conditions, electrical stimulation was applied to the dorsiflexor muscles simultaneously with electromotor-induced plantar flexion. We observed severe histochemical muscle fiber damage (area of damaged fibers/total fiber area analyzed) following ECC (26.4 ± 4.0%). Surprisingly, however, muscle damage was negligible following ECC + BFR140 (2.6 ± 1.2%), ECC+BFR160 (3.0 ± 0.5%), and ECC + BFR200 (0.2 ± 0.1%). Ribosomal S6 kinase 1 (S6K1) phosphorylation, a downstream target of rapamycin (mTOR)-phosphorylation kinase, increased following ECC + BFR200 as well as ECC. In contrast, S6K1 phosphorylation was not altered by BFR alone. The present findings suggest that ECC combined with BFR, even at high exercise intensities, may enhance muscle protein synthesis without appreciable muscle fiber damage. PMID:26149281

  16. Use of grafting to prevent Hypsipyla grandella (Zeller) (Lepidoptera: Pyralidae) damage to new world Meliaceae species.

    PubMed

    Perez, Julian; Eigenbrode, Sanford D; Hilje, Luko; Tripepi, Robert R; Aguilar, Maria E; Mesen, Francisco

    2010-01-01

    The susceptible species Cedrela odorata and Swietenia macrophylla to attack by Hypsipyla grandella (Zeller) larvae were grafted onto the resistant species Khaya senegalensis and Toona ciliata. Six-month-old grafted plants were then compared to their reciprocal grafts and to both intact (non-grafted) and autografted plants for damage due to H. grandella larvae and for their effects on larval performance. Two experiments were conducted: one in which the apical bud of the main plant shoot was inoculated with H. grandella eggs, and the other in which the bud was inoculated with third instars. Damage in each experiment was assessed by the number of frass piles, number and length of tunnels, number of damaged leaves, and damage to the apical bud. Larval performance was evaluated in terms of time to reach pupation and pupal weight and length. In both experiments, plant damage differed significantly among treatments (P < 0.03). Resistant rootstocks conferred resistance to susceptible scions. In both experiments, grafting by itself, regardless of the rootstock and scion combination, also reduced damage caused by H. grandella larvae. Scions of autografted susceptible species had similar resistance to susceptible scions grafted on resistant rootstocks. Few larvae reached pupation, and their pupal weight and length were similar. PMID:20878001

  17. Pre-treatment with LCZ696, an orally active angiotensin receptor neprilysin inhibitor, prevents ischemic brain damage.

    PubMed

    Bai, Hui-Yu; Mogi, Masaki; Nakaoka, Hirotomo; Kan-No, Harumi; Tsukuda, Kana; Chisaka, Toshiyuki; Wang, Xiao-Li; Kukida, Masayoshi; Shan, Bao-Shuai; Yamauchi, Toshifumi; Higaki, Akinori; Iwanami, Jun; Horiuchi, Masatsugu

    2015-09-01

    Angiotensin II receptor blockers (ARBs) are known to prevent ischemic brain damage after stroke. Natriuretic peptides, which are increased by a neprilysin inhibitor, are also reported to protect against brain damage. Therefore, we investigated the possible protective effect of valsartan (VAL) compared with LCZ696 (VAL+ neprilysin inhibitor; 1:1) after middle cerebral artery (MCA) occlusion. Eight-week-old male C57BL/6J mice were treated with VAL (3mg/kg per day) or LCZ696 (6mg/kg per day) for 2 weeks before MCA occlusion. Blood pressure and heart rate were measured by telemetry. Cerebral blood flow (CBF) was determined by laser-Doppler flowmetry. Ischemic area was evaluated by triphenytetrasodium chloride staining, and oxidative stress was determined by dihydroethidium staining. Blood pressure and heart rate were not significantly different before and after treatment. Pre-treatment with LCZ696 or VAL reduced the ischemic area, and this effect of LCZ696 was more marked than that of VAL pre-treatment. The decrease in CBF in the peripheral region of the ischemic area was significantly attenuated by pre-treatment with LCZ696 or VAL, without any significant effect on CBF in the core region. VAL or LCZ696 pre-treatment significantly decreased the increase of superoxide anion production in the cortex on the ischemic side. However, no significant difference in CBF and superoxide anion production was observed between VAL and LCZ696 pre-treatment. The preventive effect of LCZ696 on ischemic brain damage after stroke was more marked than that of VAL. LCZ696 could be used as a new approach to prevent brain damage after stroke. (246 words). PMID:26057694

  18. Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress

    PubMed Central

    Simoneau, Antoine; Ricard, Étienne; Weber, Sandra; Hammond-Martel, Ian; Wong, Lai Hong; Sellam, Adnane; Giaever, Guri; Nislow, Corey; Raymond, Martine; Wurtele, Hugo

    2016-01-01

    The Saccharomyces cerevisiae genome encodes five sirtuins (Sir2 and Hst1–4), which constitute a conserved family of NAD-dependent histone deacetylases. Cells lacking any individual sirtuin display mild growth and gene silencing defects. However, hst3Δ hst4Δ double mutants are exquisitely sensitive to genotoxins, and hst3Δ hst4Δ sir2Δ mutants are inviable. Our published data also indicate that pharmacological inhibition of sirtuins prevents growth of several fungal pathogens, although the biological basis is unclear. Here, we present genome-wide fitness assays conducted with nicotinamide (NAM), a pan-sirtuin inhibitor. Our data indicate that NAM treatment causes yeast to solicit specific DNA damage response pathways for survival, and that NAM-induced growth defects are mainly attributable to inhibition of Hst3 and Hst4 and consequent elevation of histone H3 lysine 56 acetylation (H3K56ac). Our results further reveal that in the presence of constitutive H3K56ac, the Slx4 scaffolding protein and PP4 phosphatase complex play essential roles in preventing hyperactivation of the DNA damage-response kinase Rad53 in response to spontaneous DNA damage caused by reactive oxygen species. Overall, our data support the concept that chromosome-wide histone deacetylation by sirtuins is critical to mitigate growth defects caused by endogenous genotoxins. PMID:26748095

  19. Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress.

    PubMed

    Simoneau, Antoine; Ricard, Étienne; Weber, Sandra; Hammond-Martel, Ian; Wong, Lai Hong; Sellam, Adnane; Giaever, Guri; Nislow, Corey; Raymond, Martine; Wurtele, Hugo

    2016-04-01

    The Saccharomyces cerevisiae genome encodes five sirtuins (Sir2 and Hst1-4), which constitute a conserved family of NAD-dependent histone deacetylases. Cells lacking any individual sirtuin display mild growth and gene silencing defects. However, hst3Δ hst4Δ double mutants are exquisitely sensitive to genotoxins, and hst3Δ hst4Δ sir2Δmutants are inviable. Our published data also indicate that pharmacological inhibition of sirtuins prevents growth of several fungal pathogens, although the biological basis is unclear. Here, we present genome-wide fitness assays conducted with nicotinamide (NAM), a pan-sirtuin inhibitor. Our data indicate that NAM treatment causes yeast to solicit specific DNA damage response pathways for survival, and that NAM-induced growth defects are mainly attributable to inhibition of Hst3 and Hst4 and consequent elevation of histone H3 lysine 56 acetylation (H3K56ac). Our results further reveal that in the presence of constitutive H3K56ac, the Slx4 scaffolding protein and PP4 phosphatase complex play essential roles in preventing hyperactivation of the DNA damage-response kinase Rad53 in response to spontaneous DNA damage caused by reactive oxygen species. Overall, our data support the concept that chromosome-wide histone deacetylation by sirtuins is critical to mitigate growth defects caused by endogenous genotoxins. PMID:26748095

  20. Melatonin's role in preventing toxin-related and sepsis-mediated hepatic damage: A review.

    PubMed

    Esteban-Zubero, Eduardo; Alatorre-Jiménez, Moisés Alejandro; López-Pingarrón, Laura; Reyes-Gonzales, Marcos César; Almeida-Souza, Priscilla; Cantín-Golet, Amparo; Ruiz-Ruiz, Francisco José; Tan, Dun-Xian; García, José Joaquín; Reiter, Russel J

    2016-03-01

    The liver is a central organ in detoxifying molecules and would otherwise cause molecular damage throughout the organism. Numerous toxic agents including aflatoxin, heavy metals, nicotine, carbon tetrachloride, thioacetamide, and toxins derived during septic processes, generate reactive oxygen species followed by molecular damage to lipids, proteins and DNA, which culminates in hepatic cell death. As a result, the identification of protective agents capable of ameliorating the damage at the cellular level is an urgent need. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other organs and many studies confirm its benefits against oxidative stress including lipid peroxidation, protein mutilation and molecular degeneration in various organs, including the liver. Recent studies confirm the benefits of melatonin in reducing the cellular damage generated as a result of the metabolism of toxic agents. These protective effects are apparent when melatonin is given as a sole therapy or in conjunction with other potentially protective agents. This review summarizes the published reports that document melatonin's ability to protect hepatocytes from molecular damage due to a wide variety of substances (aflatoxin, heavy metals, nicotine, carbon tetrachloride, chemotherapeutics, and endotoxins involved in the septic process), and explains the potential mechanisms by which melatonin provides these benefits. Melatonin is an endogenously-produced molecule which has a very high safety profile that should find utility as a protective molecule against a host of agents that are known to cause molecular mutilation at the level of the liver. PMID:26808084

  1. Prevention of UVB Radiation-induced Epidermal Damage by Expression of Heat Shock Protein 70*

    PubMed Central

    Matsuda, Minoru; Hoshino, Tatsuya; Yamashita, Yasuhiro; Tanaka, Ken-ichiro; Maji, Daisuke; Sato, Keizo; Adachi, Hiroaki; Sobue, Gen; Ihn, Hironobu; Funasaka, Yoko; Mizushima, Tohru

    2010-01-01

    Irradiation with UV light, especially UVB, causes epidermal damage via the induction of apoptosis, inflammatory responses, and DNA damage. Various stressors, including UV light, induce heat shock proteins (HSPs) and the induction, particularly that of HSP70, provides cellular resistance to such stressors. The anti-inflammatory activity of HSP70, such as its inhibition of nuclear factor kappa B (NF-κB), was recently revealed. These in vitro results suggest that HSP70 protects against UVB-induced epidermal damage. Here we tested this idea by using transgenic mice expressing HSP70 and cultured keratinocytes. Irradiation of wild-type mice with UVB caused epidermal damage such as induction of apoptosis, which was suppressed in transgenic mice expressing HSP70. UVB-induced apoptosis in cultured keratinocytes was suppressed by overexpression of HSP70. Irradiation of wild-type mice with UVB decreased the cutaneous level of IκB-α (an inhibitor of NF-κB) and increased the infiltration of leukocytes and levels of pro-inflammatory cytokines and chemokines in the epidermis. These inflammatory responses were suppressed in transgenic mice expressing HSP70. In vitro, the overexpression of HSP70 suppressed the expression of pro-inflammatory cytokines and chemokines and increased the level of IκB-α in keratinocytes irradiated with UVB. UVB induced an increase in cutaneous levels of cyclobutane pyrimidine dimers and 8-hydroxy-2′-deoxyguanosine, both of which were suppressed in transgenic mice expressing HSP70. This study provides genetic evidence that HSP70 protects the epidermis from UVB-induced radiation damage. The findings here also suggest that the protective action of HSP70 is mediated by anti-apoptotic, anti-inflammatory, and anti-DNA damage effects. PMID:20018843

  2. Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by Soman. (Reannouncement with new availability information)

    SciTech Connect

    Sparenborg, S.; Brennecke, L.H.; Jaax, N.K.; Braitman, D.J.

    1992-12-31

    The involvement of the NMDA receptor in the neurotoxicity induced by soman, an organophosphorus compound which irreversibly inhibits cholinesterase, was studied in guinea pigs. The drug MK-801 (0.5, 1 or 5 mg/kg, i.p.) was given as a pretreatment before a convulsant dose of soman or as a post treatment (30, 100 or 300 micron g/kg, i.m.) 5 min after the development of soman-induced status epilepticus. Pyridostigmine, atropine and pralidoxime chloride were also given to each subject to counteract the lethality of soman. All subjects that were challenged with soman and given the vehicle for MK-801 (saline) exhibited severe convulsions and electrographic seizure activity. Neuronal necrosis was found in the hippocampus, amygdala, thalamus and the pyriform and cerebral cortices of those subjects surviving for 48 hr. Pretreatment with 0.5 or 1 mg/kg doses of MK-801 did not prevent nor delay the onset of seizure activity but did diminish its intensity and led to its early arrest. At the largest dose (5 mg/kg), MK-801 completely prevented the development of seizure activity and brain damage. Post treatment with MK-801 prevented, arrested or reduced seizure activity, convulsions and neuronal necrosis in a dose-dependent manner. The NMDA receptor may play a more critical role in the spread and maintenance, rather than the initiation of cholinergically-induced seizure activity....Seizure-related brain damage, Organophosphorus compound, Nerve agent, Cholinesterase inhibition, Excitotoxicity, Guinea pig.

  3. Comparison of L-thyroxine and a saturated solution of potassium iodide in preventing damage to the thyroid following iodine-131-labeled antibody injection

    SciTech Connect

    Abdel-Nabi, H.; Waldman, W.J.; Hinkle, G.H.; Miller, E.A.; Trembath, L.; Olsen, J.O.; Martin, E.W. Jr.

    1987-01-01

    Following injection of radioiodinated antibodies in diagnostic amounts, there is variable uptake of radioiodine by the thyroid. Unless preventive steps are taken, radiation damage to the gland may occur. We have evaluated the role of L-thyroxine and a saturated solution of potassium iodide (SSKI) in preventing radiation damage to the thyroid glands of Sprague-Dawley adult male rats by measuring DNA strand breakage by the nucleoid sedimentation gradient method. Pretreatment with SSKI reduced DNA damage and also reduced /sup 131/I accumulation in the thyroid. Pretreatment with L-thyroxine also reduced DNA damage without significantly reducing /sup 131/I accumulation in the thyroid. The possible mechanisms of action of L-thyroxine and SSKI in preventing radiation damage to the thyroid are addressed.

  4. Evaluation of the protective effect of Ilex paraguariensis and Camellia sinensis extracts on the prevention of oxidative damage caused by ultraviolet radiation.

    PubMed

    Barg, Marlon; Rezin, Gislaine T; Leffa, Daniela D; Balbinot, Fernanda; Gomes, Lara M; Carvalho-Silva, Milena; Vuolo, Francieli; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio L; Andrade, Vanessa M

    2014-01-01

    We evaluated the effects green and mate teas on oxidative and DNA damages in rats exposed to ultraviolet radiation. Were utilized 70 adult male Wistar rats that received daily oral or topic green or mate tea treatment during exposed to radiation by seven days. After, animals were killed by decapitation. Thiobarbituric acid-reactive species levels, protein oxidative damage were evaluated in skin and DNA damage in blood. Our results show that the rats exposed to ultraviolet radiation presented DNA damage in blood and increased protein carbonylation and lipid peroxidation in skin. Oral and topic treatment with green tea and mate tea prevented lipid peroxidation, both treatments with mate tea also prevented DNA damage. However, only topic treatment with green tea and mate tea prevented increases in protein carbonylation. Our findings contribute to elucidate the beneficial effects of green tea and mate tea, here in demonstrated by the antioxidant and antigenotoxic properties presented by these teas. PMID:24361697

  5. Mushroom-derived preparations in the prevention of H2O2-induced oxidative damage to cellular DNA.

    PubMed

    Shi, Yu-ling; James, Anthony E; Benzie, Iris F F; Buswell, John A

    2002-01-01

    Aqueous extracts of the sporophores of eight mushroom species were assessed for their ability to prevent H2O2-induced oxidative damage to cellular DNA using the single-cell gel electrophoresis ("Comet") assay. The highest genoprotective effects were obtained with cold (20 degrees C) and hot (100 degrees C) water extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies, respectively. No protective effects were observed with Mushroom Derived Preparations (MDPs) from Flammulina velutipes, Auricularia auricula, Hypsizygus marmoreus, Lentinula edodes, Pleurotus sajor-caju, and Volvariella volvacea. These findings indicate that some edible mushrooms represent a valuable source of biologically active compounds with potential for protecting cellular DNA from oxidative damage. PMID:11835288

  6. Preventive role of lens antioxidant defense mechanism against riboflavin-mediated sunlight damaging of lens crystallins.

    PubMed

    Anbaraki, Afrooz; Khoshaman, Kazem; Ghasemi, Younes; Yousefi, Reza

    2016-10-01

    The main components of sunlight reaching the eye lens are UVA and visible light exerting their photo-damaging effects indirectly by the aid of endogenous photosensitizer molecules such as riboflavin (RF). In this study, lens proteins solutions were incubated with RF and exposed to the sunlight. Then, gel mobility shift analysis and different spectroscopic assessments were applied to examine the structural damaging effects of solar radiation on these proteins. Exposure of lens proteins to direct sunlight, in the presence of RF, leads to marked structural crosslinking, oligomerization and proteolytic instability. These structural damages were also accompanied with reduction in the emission fluorescence of Trp and Tyr and appearance of a new absorption peak between 300 and 400nm which can be related to formation of new chromophores. Also, photo-oxidation of lens crystallins increases their oligomeric size distribution as examined by dynamic light scattering analysis. The above mentioned structural insults, as potential sources of sunlight-induced senile cataract and blindness, were significantly attenuated in the presence of ascorbic acid and glutathione which are two important components of lens antioxidant defense system. Therefore, the powerful antioxidant defense mechanism of eye lens is an important barrier against molecular photo-damaging effects of solar radiations during the life span. PMID:27316765

  7. Dispersal of NOW and Prediction and Prevention of NOW Damage in Almonds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The current proceedings reports the results of experiments in 2007 examining: 1) use of pheromone and egg traps for in-season prediction of navel orangeworm damage to almonds; 2) movement of navel orangeworm females in and between adjacent blocks under mating disruption and conventional control, and...

  8. Iron-sulfur cluster damage by the superoxide radical in neural tissues of the SOD1(G93A) ALS rat model.

    PubMed

    Popović-Bijelić, Ana; Mojović, Miloš; Stamenković, Stefan; Jovanović, Miloš; Selaković, Vesna; Andjus, Pavle; Bačić, Goran

    2016-07-01

    Extensive clinical investigations, in hand with biochemical and biophysical research, have associated brain iron accumulation with the pathogenesis of the amyotrophic lateral sclerosis (ALS) disease. The origin of iron is still not identified, but it is proposed that it forms redox active complexes that can participate in the Fenton reaction generating the toxic hydroxyl radical. In this paper, the state of iron in the neural tissues isolated from SOD1(G93A) transgenic rats was investigated using low temperature EPR spectroscopy and is compared with that of nontransgenic (NTg) littermates. The results showed that iron in neural tissues is present as high- and low-spin, heme and non-heme iron. It appears that the SOD1(G93A) rat neural tissues were most likely exposed in vivo to higher amounts of reactive oxygen species when compared to the corresponding NTg tissues, as they showed increased oxidized [3Fe-4S](1+) cluster content relative to [4Fe-4S](1+). Also, the activity of cytochrome c oxidase (CcO) was found to be reduced in these tissues, which may be associated with the observed uncoupling of heme a3 Fe and CuB in the O2-reduction site of the enzyme. Furthermore, the SOD1(G93A) rat spinal cords and brainstems contained more manganese, presumably from MnSOD, than those of NTg rats. The addition of potassium superoxide to all neural tissues ex vivo, led to the [4Fe-4S]→[3Fe-4S] cluster conversion and concurrent release of Fe. These results suggest that the superoxide anion may be the cause of the observed oxidative damage to SOD1(G93A) rat neural tissues and that the iron-sulfur clusters may be the source of poorly liganded redox active iron implicated in ALS pathogenesis. Low temperature EPR spectroscopy appears to be a valuable tool in assessing the role of metals in neurodegenerative diseases. PMID:27130034

  9. A novel use of neural network model to determine the effects of multibiomarker on early health damage among Chinese steel workers.

    PubMed

    Shi, Xiu-Quan; Yang, Xiao-Bo; Wang, Zhong-Xu; Qiu, Li; Wu, Tang-Chun; Wang, Zeng-Zhen

    2011-02-01

    Coke-oven workers are exposed to many kinds of pollutants that can cause health damage even lead to carcinogenesis. Therefore, it is critical to identify biomarkers that predict early health damage in these exposed individuals in molecular epidemiological studies. We applied an artificial neural network (ANN) model to the identification of such predictors in a study of coke-oven workers. The study included 330 steel-factory workers who were exposed to different levels of polycyclic aromatic hydrocarbons (PAHs) in the workplace and their levels of early health damage were determined by cytokinesis-block micronuclei (CMN), heat shock protein 70 (Hsp70) expression, benzo(a)pyrene diolepoxide-albumin adduct (BPDE-AA), and olive tail moment (OTM). The ANN model was built to predict the early health damage index, and the receiver operating characteristic (ROC) curve was used to illustrate the judged criteria and the ANN model. Trend Chi-square modeling was also performed. We found that there were 55 subjects with early health damage among 330 workers based on the multibiomarker criteria using the 95 percentile of the control group as the cut-off value, while there were 22-35 positive subjects if screening by any single biomarker. The Cochran-Armitage trend test for these findings were statistically significant (Z = 3.21, P = 0.0013). Six variables were selected to simulate the ANN model. The area under ROC (AUROC) was 0.726 ± 0.037 (P < 0.001), and the predictors included workplace, cholesterol, waistline, and others. Therefore, collective using CMN frequency, Hsp70 level, BPDE-AA level, and OTM with equal weights to make an initial screening test for early health damage in coke-oven workers is feasible and superior to any single biomarker. The determinants of the effects of multibiomarker on early health damage screening can be identified by the ANN model and ROC curve method. PMID:19621472

  10. Pasta containing tartary buckwheat sprouts prevents DNA damage in spontaneously hypertensive rats.

    PubMed

    Meschini, Roberta; Filippi, Silvia; Molinari, Romina; Costantini, Lara; Bonafaccia, Giovanni; Merendino, Nicolò

    2015-01-01

    Recent studies have shown that DNA damage occurs more often in hypertensive patients than non-hypertensive individuals. Here, we analyzed the in vivo effect of pasta containing 30% of tartary buckwheat sprouts (TBSP) on spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKY) to elucidate if TBSP could have an anti-genotoxic effect in hypertensive animal models. Both SHRs and WKY rats were divided into two groups and fed for six weeks with 5 g of TBSP and durum wheat flour commercial pasta, respectively. Our results showed that a diet rich in TBSP has anti-genotoxic effect. Indeed, SHRs fed with TBSP exhibited a significant decrease in DNA damage (38%) and more efficient DNA repair (84%) compared to SHRs fed with commercial pasta. PMID:26068704

  11. Formation damage prevention through the control of paraffin and asphaltene deposition

    SciTech Connect

    Newberry, M.E.; Barker, K.M.

    1985-03-01

    Formation damage caused by the precipitation and deposition of paraffin or asphaltene particles has been a recurrent problem in the production of crude oil. A number of well established oilfield operations have been found to aggravate these organic deposition problems. Laboratory testing of crudes and chemical additives has led to a number of solutions to these problems. Case history information on testing, chemical application, and subsequent field results are presented.

  12. Arabidopsis Peptide Methionine Sulfoxide Reductase2 Prevents Cellular Oxidative Damage in Long NightsW⃞

    PubMed Central

    Bechtold, Ulrike; Murphy, Denis J.; Mullineaux, Philip M.

    2004-01-01

    Peptide methionine sulfoxide reductase (PMSR) is a ubiquitous enzyme that repairs oxidatively damaged proteins. In Arabidopsis (Arabidopsis thaliana), a null mutation in PMSR2 (pmsr2-1), encoding a cytosolic isoform of the enzyme, exhibited reduced growth in short-day conditions. In wild-type plants, a diurnally regulated peak of total PMSR activity occurred at the end of the 16-h dark period that was absent in pmsr2-1 plants. This PMSR activity peak in the wild-type plant coincided with increased oxidative stress late in the dark period in the mutant. In pmsr2-1, the inability to repair proteins resulted in higher levels of their turnover, which in turn placed an increased burden on cellular metabolism. This caused increased respiration rates, leading to the observed higher levels of oxidative stress. In wild-type plants, the repair of damaged proteins by PMSR2 at the end of the night in a short-day diurnal cycle alleviates this potential burden on metabolism. Although PMSR2 is not absolutely required for viability of plants, the observation of increased damage to proteins in these long nights suggests the timing of expression of PMSR2 is an important adaptation for conservation of their resources. PMID:15031406

  13. SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells.

    PubMed

    Eroglu, Elif; Burkard, Thomas R; Jiang, Yanrui; Saini, Nidhi; Homem, Catarina C F; Reichert, Heinrich; Knoblich, Juergen A

    2014-03-13

    Members of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in human cancer, but how they suppress tumorigenesis is currently unclear. Here, we use Drosophila neuroblasts to demonstrate that the SWI/SNF component Osa (ARID1) prevents tumorigenesis by ensuring correct lineage progression in stem cell lineages. We show that Osa induces a transcriptional program in the transit-amplifying population that initiates temporal patterning, limits self-renewal, and prevents dedifferentiation. We identify the Prdm protein Hamlet as a key component of this program. Hamlet is directly induced by Osa and regulates the progression of progenitors through distinct transcriptional states to limit the number of transit-amplifying divisions. Our data provide a mechanistic explanation for the widespread tumor suppressor activity of SWI/SNF. Because the Hamlet homologs Evi1 and Prdm16 are frequently mutated in cancer, this mechanism could well be conserved in human stem cell lineages. PAPERCLIP: PMID:24630726

  14. The Parkinsonism-associated protein DJ-1/Park7 prevents glycation damage in human keratinocyte.

    PubMed

    Advedissian, Tamara; Deshayes, Frédérique; Poirier, Françoise; Viguier, Mireille; Richarme, Gilbert

    2016-04-22

    Reducing sugars and dicarbonyls form covalent adducts with proteins through a nonenzymatic process known as glycation, which inactivates proteins, is increased in diabetic patients and is associated with diabetic complications, including retinopathy, cataracts, nephropathy, neuropathy, cardiomyopathy and skin defects. We recently characterized DJ-1/Park7 as a protein deglycase that repairs proteins from glycation by glyoxal and methylglyoxal, two major glycating agents which are responsible for up to 65% of glycation events. In this study, we investigated the ability of DJ-1 to prevent protein glycation in keratinocytes. Glycation of collagen and keratinocyte proteins was tested by measuring ultraviolet absorption and fluorescence emission. Protein glycation in HaCaT keratinocytes was investigated by immunodetection with anti-advanced glycation endproduct antibodies, after DJ-1 depletion or overexpression. In vitro, DJ-1 prevented glycation of collagen and keratinocyte protein extracts. In cell culture, DJ-1 depletion by small interfering RNAs resulted in a 3-fold increase in protein glycation levels. Moreover, protein glycation levels were decreased several-fold in cells overexpressing DJ-1 after addition of the Nrf2 inducer sulforaphane or after transfection with a DJ-1 plasmid. Thus, the DJ-1 deglycase plays a major role in preventing protein glycation in eukaryotic cells and might be important for preventing skin glycation. PMID:26995087

  15. Biocompatible films with tailored spectral response for prevention of DNA damage in skin cells.

    PubMed

    Núñez-Lozano, Rebeca; Pimentel, Belén; Castro-Smirnov, José R; Calvo, Mauricio E; Míguez, Hernán; de la Cueva-Méndez, Guillermo

    2015-09-16

    A hybrid nanostructured organic-in-organic biocompatible film capable of efficiently blocking a preselected range of ultraviolet light is designed to match the genotoxic action spectrum of human epithelial cells. This stack protects cultured human skin cells from UV-induced DNA lesions. As the shielding mechanism relies exclusively on reflection, the secondary effects due to absorption harmful radiation are prevented. PMID:26149339

  16. Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning.

    PubMed

    Nokia, Miriam S; Mikkonen, Jarno E; Penttonen, Markku; Wikgren, Jan

    2012-01-01

    Oscillations in hippocampal local-field potentials (LFPs) reflect the crucial involvement of the hippocampus in memory trace formation: theta (4-8 Hz) oscillations and ripples (~200 Hz) occurring during sharp waves are thought to mediate encoding and consolidation, respectively. During sharp wave-ripple complexes (SPW-Rs), hippocampal cell firing closely follows the pattern that took place during the initial experience, most likely reflecting replay of that event. Disrupting hippocampal ripples using electrical stimulation either during training in awake animals or during sleep after training retards spatial learning. Here, adult rabbits were trained in trace eyeblink conditioning, a hippocampus-dependent associative learning task. A bright light was presented to the animals during the inter-trial interval (ITI), when awake, either during SPW-Rs or irrespective of their neural state. Learning was particularly poor when the light was presented following SPW-Rs. While the light did not disrupt the ripple itself, it elicited a theta-band oscillation, a state that does not usually coincide with SPW-Rs. Thus, it seems that consolidation depends on neuronal activity within and beyond the hippocampus taking place immediately after, but by no means limited to, hippocampal SPW-Rs. PMID:23316148

  17. The function of cux1 in oxidative dna damage repair is needed to prevent premature senescence of mouse embryo fibroblasts

    PubMed Central

    Ramdzan, Zubaidah M.; Pal, Ranjana; Kaur, Simran; Leduy, Lam; Bérubé, Ginette; Davoudi, Sayeh; Vadnais, Charles; Nepveu, Alain

    2015-01-01

    Despite having long telomeres, mouse embryo fibroblasts (MEFs) senesce more rapidly than human diploid fibroblasts because of the accumulation of oxidative DNA damage. The CUX1 homeodomain protein was recently found to prevent senescence in RAS-driven cancer cells that produce elevated levels of reactive-oxygen species. Here we show that Cux1−/− MEFs are unable to proliferate in atmospheric (20%) oxygen although they can proliferate normally in physiological (3%) oxygen levels. CUX1 contains three domains called Cut repeats. Structure/function analysis established that a single Cut repeat domain can stimulate the DNA binding, Schiff-base formation, glycosylase and AP-lyase activities of 8-oxoguanine DNA glycosylase 1, OGG1. Strikingly and in contrast to previous reports, OGG1 exhibits efficient AP-lyase activity in the presence of a Cut repeat. Repair of oxidative DNA damage and proliferation in 20% oxygen were both rescued in Cux1−/− MEFs by ectopic expression of CUX1 or of a recombinant Cut repeat protein that stimulates OGG1 but is devoid of transcription activation potential. These findings reinforce the causal link between oxidative DNA damage and cellular senescence and suggest that the role of CUX1 as an accessory factor in DNA repair will be critical in physiological situations that generate higher levels of reactive oxygen species. PMID:25682875

  18. Date (Phoenix dactylifera) Polyphenolics and Other Bioactive Compounds: A Traditional Islamic Remedy’s Potential in Prevention of Cell Damage, Cancer Therapeutics and Beyond

    PubMed Central

    Yasin, Bibi R.; El-Fawal, Hassan A. N.; Mousa, Shaker A.

    2015-01-01

    This review analyzes current studies of the therapeutic effects of Phoenix dactylifera, or date palm fruit, on the physiologic system. Specifically, we sought to summarize the effects of its application in preventing cell damage, improving cancer therapeutics and reducing damage caused by conventional chemotherapy. Phoenix dactylifera exhibits potent anti-oxidative properties both in vitro and in vivo. This allows the fruit to prevent depletion of intrinsic protection from oxidative cell damage and assist these defense systems in reducing cell damage. Macroscopically, this mechanism may be relevant to the prevention of various adverse drug events common to chemotherapy including hepatotoxicity, nephrotoxicity, gastrotoxicity, and peripheral neuropathy. While such effects have only been studied in small animal systems, research suggests a potential application to more complex mammalian systems and perhaps a solution to some problems of chemotherapy in hepato-compromised and nephro-compromised patients. PMID:26694370

  19. Metformin Prevents Cisplatin-Induced Cognitive Impairment and Brain Damage in Mice

    PubMed Central

    Zhou, Wenjun; Kavelaars, Annemieke; Heijnen, Cobi J.

    2016-01-01

    Rationale Chemotherapy-induced cognitive impairment, also known as ‘chemobrain’, is now widely recognized as a frequent adverse side effect of cancer treatment that often persists into survivorship. There are no drugs available to prevent or treat chemotherapy-induced cognitive deficits. The aim of this study was to establish a mouse model of cisplatin-induced cognitive deficits and to determine the potential preventive effects of the anti-diabetic drug metformin. Results Treatment of C57/BL6J mice with cisplatin (cumulative dose 34.5mg/kg) impaired performance in the novel object and place recognition task as well as in the social discrimination task indicating cognitive deficits. Co-administration of metformin prevented these cisplatin-induced cognitive impairments. At the structural level, we demonstrate that cisplatin reduces coherency of white matter fibers in the cingulate cortex. Moreover, the number of dendritic spines and neuronal arborizations as quantified on Golgi-stained brains was reduced after cisplatin treatment. Co-administration of metformin prevented all of these structural abnormalities in cisplatin-treated mice. In contrast to what has been reported in other models of chemobrain, we do not have evidence for persistent microglial or astrocyte activation in the brains of cisplatin-treated mice. Finally, we show that co-administration of metformin also protects against cisplatin-induced peripheral neuropathy. Conclusion In summary, we show here for the first time that treatment of mice with cisplatin induces cognitive deficits that are associated with structural abnormalities in the brain. Moreover, we present the first evidence that the widely used and safe anti-diabetic drug metformin protects against these deleterious effects of cancer treatment. In view of the ongoing clinical trials to examine the potential efficacy of metformin as add-on therapy in patients treated for cancer, these findings should allow rapid clinical translation. PMID

  20. Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy

    PubMed Central

    Scheibye-Knudsen, Morten; Ramamoorthy, Mahesh; Sykora, Peter; Maynard, Scott; Lin, Ping-Chang; Minor, Robin K.; Wilson III, David M.; Cooper, Marcus; Spencer, Richard; de Cabo, Rafael; Croteau, Deborah L.

    2012-01-01

    Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized by neurodegeneration, cachexia, and accelerated aging. 80% of the cases are caused by mutations in the CS complementation group B (CSB) gene known to be involved in DNA repair and transcription. Recent evidence indicates that CSB is present in mitochondria, where it associates with mitochondrial DNA (mtDNA). We report an increase in metabolism in the CSBm/m mouse model and CSB-deficient cells. Mitochondrial content is increased in CSB-deficient cells, whereas autophagy is down-regulated, presumably as a result of defects in the recruitment of P62 and mitochondrial ubiquitination. CSB-deficient cells show increased free radical production and an accumulation of damaged mitochondria. Accordingly, treatment with the autophagic stimulators lithium chloride or rapamycin reverses the bioenergetic phenotype of CSB-deficient cells. Our data imply that CSB acts as an mtDNA damage sensor, inducing mitochondrial autophagy in response to stress, and that pharmacological modulators of autophagy are potential treatment options for this accelerated aging phenotype. PMID:22473955

  1. Basics of voice dysfunction--etiology and prevention of voice damage.

    PubMed

    Sepić, Tatjana; Pankas, Josipa; Grubesić, Aron; Tićac, Robert; Starcević, Radan

    2011-09-01

    Voice is one of the most important means of communication and as such should be taken care of. The etiology of voice disorders is diverse. Due to the development of the society we live in, way of life, environmental factors, and exposure to pharmacological agents as well as demands we make towards our voice, there is a substantial growth in the number of people with voice disorders. We tasked ourselves to find out if it is possible to enlighten people on the importance of voice, to motivate them to take care of it, to notice the changes in its quality and eventually ask for help. We assessed in which measure do we understand the importance of a healthy voice, and do we know which is the most important factor that adds to its decline. For a long number of years voice therapists and other experts in the voice disorder field have been discussing the optimal voice impostation as well as vocal exercises and methods behind voice recovery. They have all come to the same conclusion that phonation is dependant on the sort of the voice disorder and the patient motivation. We wanted to go one step further and investigate, dependence of voice quality and the damage etiology (organic - functional), which are the predominant causes, what are the factors that account for the damage and how the disorder motivates the patient and therefore influences the rehabilitation success rate. PMID:22220413

  2. Fungal Ku prevents permanent cell cycle arrest by suppressing DNA damage signaling at telomeres

    PubMed Central

    de Sena-Tomás, Carmen; Yu, Eun Young; Calzada, Arturo; Holloman, William K.; Lue, Neal F.; Pérez-Martín, José

    2015-01-01

    The Ku heterodimer serves in the initial step in repairing DNA double-strand breaks by the non-homologous end-joining pathway. Besides this key function, Ku also plays a role in other cellular processes including telomere maintenance. Inactivation of Ku can lead to DNA repair defects and telomere aberrations. In model organisms where Ku has been studied, inactivation can lead to DNA repair defects and telomere aberrations. In general Ku deficient mutants are viable, but a notable exception to this is human where Ku has been found to be essential. Here we report that similar to the situation in human Ku is required for cell proliferation in the fungus Ustilago maydis. Using conditional strains for Ku expression, we found that cells arrest permanently in G2 phase when Ku expression is turned off. Arrest results from cell cycle checkpoint activation due to persistent signaling via the DNA damage response (DDR). Our results point to the telomeres as the most likely source of the DNA damage signal. Inactivation of the DDR makes the Ku complex dispensable for proliferation in this organism. Our findings suggest that in U. maydis, unprotected telomeres arising from Ku depletion are the source of the signal that activates the DDR leading to cell cycle arrest. PMID:25653166

  3. Fungal Ku prevents permanent cell cycle arrest by suppressing DNA damage signaling at telomeres.

    PubMed

    de Sena-Tomás, Carmen; Yu, Eun Young; Calzada, Arturo; Holloman, William K; Lue, Neal F; Pérez-Martín, José

    2015-02-27

    The Ku heterodimer serves in the initial step in repairing DNA double-strand breaks by the non-homologous end-joining pathway. Besides this key function, Ku also plays a role in other cellular processes including telomere maintenance. Inactivation of Ku can lead to DNA repair defects and telomere aberrations. In model organisms where Ku has been studied, inactivation can lead to DNA repair defects and telomere aberrations. In general Ku deficient mutants are viable, but a notable exception to this is human where Ku has been found to be essential. Here we report that similar to the situation in human Ku is required for cell proliferation in the fungus Ustilago maydis. Using conditional strains for Ku expression, we found that cells arrest permanently in G2 phase when Ku expression is turned off. Arrest results from cell cycle checkpoint activation due to persistent signaling via the DNA damage response (DDR). Our results point to the telomeres as the most likely source of the DNA damage signal. Inactivation of the DDR makes the Ku complex dispensable for proliferation in this organism. Our findings suggest that in U. maydis, unprotected telomeres arising from Ku depletion are the source of the signal that activates the DDR leading to cell cycle arrest. PMID:25653166

  4. Dividing the Self: Distinct Neural Substrates of Task-Based and Automatic Self-Prioritization after Brain Damage

    ERIC Educational Resources Information Center

    Sui, Jie; Chechlacz, Magdalena; Humphreys, Glyn W.

    2012-01-01

    Facial self-awareness is a basic human ability dependent on a distributed bilateral neural network and revealed through prioritized processing of our own over other faces. Using non-prosopagnosic patients we show, for the first time, that facial self-awareness can be fractionated into different component processes. Patients performed two face…

  5. Mitochondrial ATP-sensitive potassium channel opening inhibits isoproterenol-induced cardiac hypertrophy by preventing oxidative damage.

    PubMed

    Lemos Caldas, Francisco Rodrigo; Rocha Leite, Iago Mateus; Tavarez Filgueiras, Ana Beatriz; de Figueiredo Júnior, Isaias Lima; Gomes Marques de Sousa, Tereza Amália; Martins, Pamela Reis; Kowaltowski, Alicia Juliana; Fernandes Facundo, Heberty di Tarso

    2015-04-01

    Cardiac hypertrophy is a chronic complex disease that occurs in response to hemodynamic load and is accompanied by oxidative stress and mitochondrial dysfunction. Mitochondrial ATP-sensitive K channels (mitoKATPs) have previously been shown to prevent oxidative cardiac damage under conditions of ischemia/reperfusion. However, the effect of these channels on cardiac hypertrophy has not been tested to date. In this study, we show that treatment of Swiss mice with isoproterenol (30 mg·kg·d) induces cardiac hypertrophy while significantly decreasing the levels of reduced protein thiols, glutathione, catalase, and superoxide dismutase activity, indicative of a condition of oxidative imbalance. Treatment with diazoxide (a mitoKATP opener, 5 mg·kg·d) normalized the levels of protein thiols and reduced glutathione, rescued superoxide dismutase activity, and significantly prevented cardiac hypertrophy. The protective effects of diazoxide were mitigated by the mitoKATP blockers 5-hydroxydecanoate (5 mg·kg·d) and glibenclamide (3 mg·kg·d), demonstrating that they were related to activation of the channel. Taken together, our results establish that mitoKATP activation promotes very robust prevention of cardiac hypertrophy and associated oxidative imbalance and suggest that these channels can be important drug targets for the pharmacological control of cardiac hypertrophy. PMID:25850726

  6. Prevention of acetaminophen induced hepatorenal damage in mice with rhizomes of Glycyrrhiza glabra A histophysiological study.

    PubMed

    Sharma, Anjali; Rathore, H S

    2011-01-01

    Protective role of Gycyrrhiza glabra rhizomes (roots) at three dose levels (100, 75, & 50 mg/kg/bw) against sublethaldose (300 mg/kg/bw) of acetaminophen (paracetamol) induced hepatorenal damage has been assessed in mice. Parameters of study were glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), billirubin, alkaline phosphatase (ALP) as liver function tests, creatinine and urea as kidney function tests and histology for pathology. G.glabra could antagonize acetaminophen induced both,hepato and nephrotoxicity in dose dependent manner. No protection provided by a single dose of G.glabra (1.5 gm/kg/bw) against lethal dose of acetaminophen (1gm/kg/bw). Probable protective role is discussed. PMID:22557431

  7. On the inlet vortex system. [preventing jet engine damage caused by debris pick-up

    NASA Technical Reports Server (NTRS)

    Bissinger, N. C.; Braun, G. W.

    1974-01-01

    The flow field of a jet engine with an inlet vortex, which can pick up heavy debris from the ground and damage the engine, was simulated in a small water tunnel by means of the hydrogen bubble technique. It was found that the known engine inlet vortex is accompained by a vortex system, consisting of two inlet vortices (the ground based and the trailing one), secondary vortices, and ground vortices. Simulation of the ground effect by an inlet image proved that the inlet vortex feeds on free stream vorticity and can exist without the presence of a ground boundary layer. The structural form of the inlet vortex system was explained by a simple potential flow model, which showed the number, location, and the importance of the stagnation points. A retractable horizontal screen or an up-tilt of the engine is suggested as countermeasure against debris ingestion.

  8. Inhaled NO prevents hyperoxia-induced white matter damage in neonatal rats.

    PubMed

    Pham, Hoa; Vottier, Gaelle; Pansiot, Julien; Duong-Quy, Sy; Bollen, Bieke; Dalous, Jérémie; Gallego, Jorge; Mercier, Jean-Christophe; Dinh-Xuan, Anh Tuan; Bonnin, Philippe; Charriaut-Marlangue, Christiane; Baud, Olivier

    2014-02-01

    White matter damage (WMD) and bronchopulmonary dysplasia (BPD) are the two main complications occurring in very preterm infants. Inhaled nitric oxide (iNO) has been proposed to promote alveolarization in the developing lung, and we have reported that iNO promotes myelination and induces neuroprotection in neonatal rats with excitotoxic brain damage. Our hypothesis is that, in addition to its pulmonary effects, iNO may be neuroprotective in rat pups exposed to hyperoxia. To test this hypothesis, we exposed rat pups to hyperoxia, and we assessed the impact of iNO on WMD and BPD. Rat pups were exposed to either hyperoxia (80% FiO2) or to normoxia for 8 days. Both groups received iNO (5 ppm) or air. We assessed the neurological and pulmonary effects of iNO in hyperoxia-injured rat pups using histological, molecular and behavioral approaches. iNO significantly attenuated the severity of hyperoxia-induced WMD induced in neonatal rats. Specifically, iNO decreased white matter inflammation, cell death, and enhanced the density of proliferating oligodendrocytes and oligodendroglial maturation. Furthermore, iNO triggered an early upregulation of P27kip1 and brain-derived growth factor (BDNF). Whereas hyperoxia disrupted early associative abilities, iNO treatment maintained learning scores to a level similar to that of control pups. In contrast to its marked neuroprotective effects, iNO induced only small and transient improvements of BPD. These findings suggest that iNO exposure at low doses is specifically neuroprotective in an animal model combining injuries of the developing lung and brain that mimicked BPD and WMD in preterm infants. PMID:24322053

  9. GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons.

    PubMed

    Pelsman, Alejandra; Hoyo-Vadillo, Carlos; Gudasheva, Tatiana A; Seredenin, Sergei B; Ostrovskaya, Rita U; Busciglio, Jorge

    2003-05-01

    The neuroprotective activity of a novel N-acylprolyl-containing dipeptide analog of the nootropic 2-oxo-1-pyrrolidine acetamide (Piracetam) designated as GVS-111 (DVD-111/Noopept) was tested in two in vitro models of neuronal degeneration mediated by oxidative stress: normal human cortical neurons treated with H(2)O(2), and Down's syndrome (DS) cortical neurons. Incubation of normal cortical neurons with 50 microM H(2)O(2) for 1h resulted in morphological and structural changes consistent with neuronal apoptosis and in the degeneration of more than 60% of the neurons present in the culture. GVS-111 significantly increased neuronal survival after H(2)O(2)-treatment displaying a dose-dependent neuroprotective activity from 10nM to 100 microM, and an IC(50) value of 1.21+/-0.07 microM. GVS-111 inhibited the accumulation of intracellular free radicals and lipid peroxidation damage in neurons treated with H(2)O(2) or FeSO(4), suggesting an antioxidant mechanism of action. GVS-111 exhibited significantly higher neuroprotection compared to the standard cognition enhancer Piracetam, or to the antioxidants Vitamin E, propyl gallate and N-tert-butyl-2-sulpho-phenylnitrone (s-PBN). In DS cortical cultures, chronic treatment with GVS-111 significantly reduced the appearance of degenerative changes and enhanced neuronal survival. The results suggest that the neuroprotective effect of GVS-111 against oxidative damage and its potential nootropic activity may present a valuable therapeutic combination for the treatment of mental retardation and chronic neurodegenerative disorders. PMID:12711349

  10. Sulforaphane prevents microcystin-LR-induced oxidative damage and apoptosis in BALB/c mice

    SciTech Connect

    Sun Xiaoyun; Mi Lixin; Liu Jin; Song Lirong; Chung Funglung; Gan Nanqin

    2011-08-15

    Microcystins (MCs), the products of blooming algae Microcystis, are waterborne environmental toxins that have been implicated in the development of liver cancer, necrosis, and even fatal intrahepatic bleeding. Alternative protective approaches in addition to complete removal of MCs in drinking water are urgently needed. In our previous work, we found that sulforaphane (SFN) protects against microcystin-LR (MC-LR)-induced cytotoxicity by activating the NF-E2-related factor 2 (Nrf2)-mediated defensive response in human hepatoma (HepG2) and NIH 3T3 cells. The purpose of this study was to investigate and confirm efficacy the SFN-induced multi-mechanistic defense system against MC-induced hepatotoxicity in an animal model. We report that SFN protected against MC-LR-induced liver damage and animal death at a nontoxic and physiologically relevant dose in BALB/c mice. The protection by SFN included activities of anti-cytochrome P450 induction, anti-oxidation, anti-inflammation, and anti-apoptosis. Our results suggest that SFN may protect mice against MC-induced hepatotoxicity. This raises the possibility of a similar protective effect in human populations, particularly in developing countries where freshwaters are polluted by blooming algae. - Graphical abstract: Display Omitted Research Highlights: > SFN protected against MC-LR-induced liver damage and animal death in BALB/c mice. > The dose of SFN is at a nontoxic and physiologically relevant dose. > The protection included activities of anti-oxidation, anti-inflammation, and anti-apoptosis. > SFN may protect mice against MC-induced hepatotoxicity.

  11. Use of Hydrodissection to Prevent Nerve and Muscular Damage during Radiofrequency Ablation of Kidney Tumors

    PubMed Central

    Lee, S. Justin; Choyke, Lynda T.; Locklin, Julia K.; Wood, Bradford J.

    2008-01-01

    Muscular complications are uncommon but have been reported after radiofrequency (RF) ablation of renal tumors. Ablation of renal lesions near the psoas muscle may result in paresthesia in the distribution of the genitofemoral nerve. The present report describes a case of sensory and muscular dysfunction after RF ablation of a renal lesion lying on top of the psoas muscle that was treated without hydrodissection. To prevent this complication, hydrodissection was effectively used in two other patients during RF ablation of lesions abutting or in close proximity to the psoas muscle. PMID:17185695

  12. The approach of the PREFER project to wildfire prevention and damage assessment in the Mediterranean area

    NASA Astrophysics Data System (ADS)

    Laneve, Giovanni; Fusilli, Lorenzo; Tampellini, Maria Lucia; Vimercati, Marco; Hirn, Barbara; Sebastian-Lopez, Ana; Diagourtas, Dimitri; Eftychidis, Georgios; Clandillon, Stephen; Caspard, Mathilde; Oliveira, Sandra; Lourenco, Luciano

    2015-04-01

    PREFER is a Copernicus Emergency project funded from the 2012 FP7 Space Work Programme, and it is aimed at developing products and services that will contribute to improve the European capacity to respond to the preparedness, prevention, and recovery management steps in the case of forest fire emergency cycle, with focus on the Mediterranean area. It is well known from the most recent reports on state of Europe's forests that the Mediterranean area is particularly affected by uncontrolled forest fires, with a number of negative consequences on ecosystems, such as desertification and soil erosion, and on the local economy. Most likely, the current risks of forest fires will be exacerbated by climate change. In particular, the climate of Southern Europe and the Mediterranean basin is projected to warm at a rate exceeding the global average. Wild fires will therefore remain the most serious threat to Southern European forests. In this situation, the need to collect better information and more knowledge concerning future risks of forest fires and fire prevention in the Mediterranean area is widely recognized to be a major urgent one. As part of the Copernicus programme (i.e. the European Earth Observation Programme), PREFER is based on advanced geo-information products using in particular the earth observation data acquired and developed in the frame of Copernicus. The objective of the PREFER project, started at the end of 2012, 8 partners (from Italy, Portugal, Spain, France and Greece) involved and three years schedule, is the design, development and demonstration of a pre-operational "end-to-end" information service, fully exploiting satellite sensors data and able to support prevention/ preparedness and recovery phases of the Forest Fires emergency cycle in the EU Mediterranean Region. The PREFER information is as general as to be usable in the different countries of the Mediterranean Region, and acts in full complement to already existing services, such as the EC

  13. [Exercise training in hypoxia prevents hypoxia induced mitochondrial DNA oxidative damage in skeletal muscle].

    PubMed

    Bo, Hai; Li, Ling; Duan, Fu-Qiang; Zhu, Jiang

    2014-10-25

    This study was undertaken to investigate the effect of exercise training on mitochondrial DNA (mtDNA) oxidative damage and 8-oxoguanine DNA glycosylase-1 (OGG1) expression in skeletal muscle of rats under continuous exposure to hypoxia. Male Sprague-Dawley rats were randomly divided into 4 groups (n = 8): normoxia control group (NC), normoxia training group (NT), hypoxia control group (HC), and hypoxia training group (HT). The hypoxia-treated animals were housed in normobaric hypoxic tent containing 11.3% oxygen for consecutive 4 weeks. The exercise-trained animals were exercised on a motor-driven rodent treadmill at a speed of 15 m/min, 5% grade for 60 min/day, 5 days per week for 4 weeks. The results showed that, compared with NC group, hypoxia attenuated complex I, II, IV and ATP synthase activities of the electron transport chain, and the level of mitochondrial membrane potential in HC group (P < 0.05 or P < 0.01). Moreover, hypoxia decreased mitochondrial OGG1, MnSOD, and GPx activities (P < 0.05 or P < 0.01), whereas elevated reactive oxygen species (ROS) generation and the level of 8-oxo-deoxyguanosine (8-oxodG) in mtDNA (P < 0.01). Furthermore, hypoxia attenuated muscle and mitochondrial [NAD⁺]/ [NADH] ratio, and SIRT3 protein expression (P < 0.05 or P < 0.01). Compared with HC group, exercise training in hypoxia elevated complex I, II, IV and ATP synthase activities, and the level of mitochondrial membrane potential in HT group (P < 0.05 or P < 0.01). Moreover, exercise training in hypoxia increased MnSOD and GPx activities and mitochondrial OGG1 level (P < 0.01), whereas decreased ROS generation and the level of 8-oxodG in mtDNA (P < 0.01). Furthermore, exercise training in hypoxia increased muscle and mitochondrial [NAD⁺]/[NADH] ratio, as well as SIRT3 protein expression (P < 0.05 or P < 0.01). These findings suggest that exercise training in hypoxia can decrease hypoxia-induced mtDNA oxidative damage in the skeletal muscle through up

  14. Controlling Hypertension to Prevent Target Organ Damage: Perspectives from the World Hypertension League President.

    PubMed

    Lackland, Daniel T

    2016-01-01

    The evidence from epidemiological and observational studies over the past five decades consistently identify a significant association of blood pressure level and disease risks for both sexes, all races and cultures, as well as all age groups. The evidence is strong such that clinical guidelines and intervention programs focus on blood pressure management and lower blood pressure levels for primary and secondary stroke prevention supported and promoted by numerous organizations including the World Hypertension League. These comprehensive components of population risk reduction are ideal models for the clinical medicine and population health partnership, and timely for global implementation. The accelerated decline in blood pressure-related outcomes (eg, stroke mortality), which began in the 1970s in the US and Western countries, included models for aggressive detection, treatment and control strategies for hypertension. These strategies can be implemented on a global scale to respond to the global risks from blood pressure, which is developing in the most vulnerable populations. PMID:27440963

  15. GST activity and membrane lipid saturation prevents mesotrione-induced cellular damage in Pantoea ananatis.

    PubMed

    Prione, Lilian P; Olchanheski, Luiz R; Tullio, Leandro D; Santo, Bruno C E; Reche, Péricles M; Martins, Paula F; Carvalho, Giselle; Demiate, Ivo M; Pileggi, Sônia A V; Dourado, Manuella N; Prestes, Rosilene A; Sadowsky, Michael J; Azevedo, Ricardo A; Pileggi, Marcos

    2016-12-01

    Callisto(®), containing the active ingredient mesotrione (2-[4-methylsulfonyl-2-nitrobenzoyl]1,3-cyclohenanedione), is a selective herbicide that controls weeds in corn crops and is a potential environmental contaminant. The objective of this work was to evaluate enzymatic and structural changes in Pantoea ananatis, a strain isolated from water, in response to exposure to this herbicide. Despite degradation of mesotrione, probably due a glutathione-S-transferase (GST) pathway in Pantoea ananatis, this herbicide induced oxidative stress by increasing hydrogen peroxide production. Thiol fragments, eventually produced after mesotrione degradation, could be involved in increased GST activity. Nevertheless, there was no peroxidation damage related to this production, as malondialdehyde (MDA) synthesis, which is due to lipid peroxidation, was highest in the controls, followed by the mesotrione- and Callisto(®)-treated cultures at log growth phase. Therefore, P. ananatis can tolerate and grow in the presence of the herbicide, probably due an efficient control of oxidative stress by a polymorphic catalase system. MDA rates depend on lipid saturation due to a pattern change to a higher level of saturation. These changes are likely related to the formation of GST-mesotrione conjugates and mesotrione degradation-specific metabolites and to the presence of cytotoxic adjuvants. These features may shift lipid membrane saturation, possibly providing a protective effect to bacteria through an increase in membrane impermeability. This response system in P. ananatis provides a novel model for bacterial herbicide tolerance and adaptation in the environment. PMID:27620734

  16. Safety apparatus for nuclear reactor to prevent structural damage from overheating by core debris

    DOEpatents

    Gabor, John D.; Cassulo, John C.; Pedersen, Dean R.; Baker Jr., Louis

    1986-07-01

    The invention teaches safety apparatus that can be included in a nuclear reactor, either when newly fabricated or as a retrofit add-on, that will minimize proliferation of structural damage to the reactor in the event the reactor is experiencing an overheating malfunction whereby radioactive nuclear debris might break away from and be discharged from the reactor core. The invention provides a porous bed or sublayer on the lower surface of the reactor containment vessel so that the debris falls on and piles up on the bed. Vapor release elements upstand from the bed in some laterally spaced array. Thus should the high heat flux of the debris interior vaporize the coolant at that location, the vaporized coolant can be vented downwardly to and laterally through the bed to the vapor release elements and in turn via the release elements upwardly through the debris. This minimizes the pressure buildup in the debris and allows for continuing infiltration of the liquid coolant into the debris interior.

  17. Safety apparatus for nuclear reactor to prevent structural damage from overheating by core debris

    DOEpatents

    Gabor, J.D.; Cassulo, J.C.; Pedersen, D.R.; Baker, L. Jr.

    The invention teaches safety apparatus that can be included in a nuclear reactor, either when newly fabricated or as a retrofit add-on, that will minimize proliferation of structural damage to the reactor in the event the reactor is experiencing an overheating malfunction whereby radioactive nuclear debris might break away from and can be discharged from the reactor core. The invention provides a porous bed of sublayer on the lower surface of the reactor containment vessel so that the debris falls on and piles up on the bed. Vapor release elements upstand from the bed in some laterally spaced array. Thus should the high heat flux of the debris interior vaporize the coolant at that location, the vaporized coolant can be vented downwardly to and laterally through the bed to the vapor release elements and in turn via the release elements upwardly through the debris. This minimizes the pressure buildup in the debris and allows for continuing infiltration of the liquid coolant into the debris interior.

  18. Safety apparatus for nuclear reactor to prevent structural damage from overheating by core debris

    DOEpatents

    Gabor, John D.; Cassulo, John C.; Pedersen, Dean R.; Baker, Jr., Louis

    1986-01-01

    The invention teaches safety apparatus that can be included in a nuclear reactor, either when newly fabricated or as a retrofit add-on, that will minimize proliferation of structural damage to the reactor in the event the reactor is experiencing an overheating malfunction whereby radioactive nuclear debris might break away from and be discharged from the reactor core. The invention provides a porous bed or sublayer on the lower surface of the reactor containment vessel so that the debris falls on and piles up on the bed. Vapor release elements upstand from the bed in some laterally spaced array. Thus should the high heat flux of the debris interior vaporize the coolant at that location, the vaporized coolant can be vented downwardly to and laterally through the bed to the vapor release elements and in turn via the release elements upwardly through the debris. This minimizes the pressure buildup in the debris and allows for continuing infiltration of the liquid coolant into the debris interior.

  19. Hexavalent chromium damages chamomile plants by alteration of antioxidants and its uptake is prevented by calcium.

    PubMed

    Kováčik, Jozef; Babula, Petr; Hedbavny, Josef; Klejdus, Bořivoj

    2014-05-30

    Toxicity of low (3μM) and high (60 and 120μM) concentrations of hexavalent chromium/Cr(VI) in chamomile plants was studied. Fluorescence staining confirmed reduction of Cr(VI) to Cr(III). Cr was mainly accumulated in the roots with translocation factor <0.007. Notwithstanding this, both shoots and roots revealed increase in oxidative stress and depletion of glutathione, total thiols, ascorbic acid and activities of glutathione reductase and partially ascorbate peroxidase mainly at 120μM Cr. Though some protective mechanisms were detected (elevation of nitric oxide, enhancement of GPX activity and increase in phenols and lignin), this was not sufficient to counteract the oxidative damage. Consequently, soluble proteins, tissue water content and biomass production were considerably depleted. Surprising increase in some mineral nutrients in roots (Ca, Fe, Zn and Cu) was also detected. Subsequent experiment confirmed that exogenous calcium suppressed oxidative symptoms and Cr uptake but growth of chamomile seedlings was not improved. Alteration of naturally present reductants could be a reason for Cr(III) signal detected using specific fluorescence reagent: in vitro assay confirmed disappearance of ascorbic acid in equimolar mixture with dichromate (>96% at pH 4 and 7) while such response of glutathione was substantially less visible. PMID:24727012

  20. Acrocomia aculeata prevents toxicogenetic damage caused by the antitumor agent cyclophosphamide.

    PubMed

    Magosso, M F; Carvalho, P C; Shneider, B U C; Pessatto, L R; Pesarini, J R; Silva, P V B; Correa, W A; Kassuya, C A L; Muzzi, R M; Oliveira, R J

    2016-01-01

    Acrocomia aculeata is a plant rich in antioxidant compounds. Studies suggest that this plant has anti-inflammatory, antidiabetic, and diuretic potential. We assessed the antigenotoxic, antimutagenic, immunomodulation, and apoptotic potentials of A. aculeata alone and in combination with an antitumor agent, cyclophosphamide. Swiss male mice (N = 140) were used. The animals were divided into 14 experimental groups as follows: a negative group, a positive group (100 mg/kg cyclophosphamide), groups that only received the oil extracted from the almond (AO) and from the pulp (PO) of A. aculeata at doses of 3, 15, and 30 mg/kg, and the associated treatment groups (oils combined with cyclophosphamide) involving pretreatment, simultaneous, and post-treatment protocols. Data suggest that both oils were chemopreventive at all doses, based on the tested protocols. The highest damage reduction percentages, observed for AO and PO were 88.19 and 90.03%, respectively, for the comet assay and 69.73 and 70.93%, respectively, for the micronucleus assay. Both AO and PO demonstrated immunomodulatory activity. The oils reduced the capacity of cyclophosphamide to trigger apoptosis in the liver, spleen, and kidney cells. These results suggest that A. aculeate AO and PO can be classified as a functional food and also enrich other functional foods and nutraceuticals with chemopreventive features. However, they are not appropriate sources for chemotherapeutic adjuvants, in particular for those used in combination with cyclophosphamide. PMID:27173316

  1. Pumping bottom water to prevent Korean red tide damage caused by Cochlodinium polykrikoides Margalef.

    PubMed

    Cho, Eun Seob; Moon, Seong Yong; Shu, Young Sang; Hwang, Jae Dong; Youn, Seok Hyun

    2015-09-01

    Cochlodinium polykrikoides Margalef produces annual massive blooms in Korean coastal waters which cause great damage to aquaculture and fisheries. Although various methods have been developed to remove the red tide of C. polykrikoides, release of yellow loess has been regarded as the most desirable technique for mitigation for over 10 years. Each August, strong irradiation generates water column stratification separating warm surface from colder bottom waters. Water from a distance of 0 (St. 1), 5 (St. 2), 10 (St. 3), and 15 m (St. 4) was pumped by running a pump for 0, 10, 30 and 90 min and characterized water temperature, salinity collected, suspended solids, Chl-a, and phytoplankton including C. polykrikoides. After running for 30 min, was temperature and salinity in surface water was similar to those of bottom water, and water column stratification completely reversed after 90 min. Likewise, suspended solids, Chl-a, and total phytoplankton cell density decreased after 30 min, but C. polykrikoides did not show strong removal because of low cell density during sampling. However, the number of C. polykrikoides was significantly diluted (80%) after 90 min. These results suggested that pumping device was as an environmentally-friendly method convenient to be install in fish cages and effective to remove C. polykrikoides stratified water column conditions. PMID:26521549

  2. Role of DNA damage response pathways in preventing carcinogenesis caused by intrinsic replication stress.

    PubMed

    Wallace, M D; Southard, T L; Schimenti, K J; Schimenti, J C

    2014-07-10

    Defective DNA replication can result in genomic instability, cancer and developmental defects. To understand the roles of DNA damage response (DDR) genes on carcinogenesis in mutants defective for core DNA replication components, we utilized the Mcm4(Chaos3/Chaos3) ('Chaos3') mouse model that, by virtue of an amino-acid alteration in MCM4 that destabilizes the MCM2-7 DNA replicative helicase, has fewer dormant replication origins and an increased number of stalled replication forks. This leads to genomic instability and cancer in most Chaos3 mice. We found that animals doubly mutant for Chaos3 and components of the ataxia telangiectasia-mutated (ATM) double-strand break response pathway (Atm, p21/Cdkn1a and Chk2/Chek2) had decreased tumor latency and/or increased tumor susceptibility. Tumor latency and susceptibility differed between genetic backgrounds and genders, with females demonstrating an overall greater cancer susceptibility to Atm and p21 deficiency than males. Atm deficiency was semilethal in the Chaos3 background and impaired embryonic fibroblast proliferation, suggesting that ATM drug inhibitors might be useful against tumors with DNA replication defects. Hypomorphism for the 9-1-1 component Hus1 did not affect tumor latency or susceptibility in Chaos3 animals, and tumors in these mice did not exhibit impaired ATR pathway signaling. These and other data indicate that under conditions of systemic replication stress, the ATM pathway is particularly important both for cancer suppression and viability during development. PMID:23975433

  3. Role of Bacillus subtilis Error Prevention Oxidized Guanine System in Counteracting Hexavalent Chromium-Promoted Oxidative DNA Damage

    PubMed Central

    Santos-Escobar, Fernando; Gutiérrez-Corona, J. Félix

    2014-01-01

    Chromium pollution is potentially detrimental to bacterial soil communities, compromising carbon and nitrogen cycles that are essential for life on earth. It has been proposed that intracellular reduction of hexavalent chromium [Cr(VI)] to trivalent chromium [Cr(III)] may cause bacterial death by a mechanism that involves reactive oxygen species (ROS)-induced DNA damage; the molecular basis of the phenomenon was investigated in this work. Here, we report that Bacillus subtilis cells lacking a functional error prevention oxidized guanine (GO) system were significantly more sensitive to Cr(VI) treatment than cells of the wild-type (WT) strain, suggesting that oxidative damage to DNA is involved in the deleterious effects of the oxyanion. In agreement with this suggestion, Cr(VI) dramatically increased the ROS concentration and induced mutagenesis in a GO-deficient B. subtilis strain. Alkaline gel electrophoresis (AGE) analysis of chromosomal DNA of WT and ΔGO mutant strains subjected to Cr(VI) treatment revealed that the DNA of the ΔGO strain was more susceptible to DNA glycosylase Fpg attack, suggesting that chromium genotoxicity is associated with 7,8-dihydro-8-oxodeoxyguanosine (8-oxo-G) lesions. In support of this notion, specific monoclonal antibodies detected the accumulation of 8-oxo-G lesions in the chromosomes of B. subtilis cells subjected to Cr(VI) treatment. We conclude that Cr(VI) promotes mutagenesis and cell death in B. subtilis by a mechanism that involves radical oxygen attack of DNA, generating 8-oxo-G, and that such effects are counteracted by the prevention and repair GO system. PMID:24973075

  4. Antioxidant properties of xanthones from Calophyllum brasiliense: prevention of oxidative damage induced by FeSO4

    PubMed Central

    2013-01-01

    Background Reactive oxygen species (ROS) are important mediators in a number of degenerative diseases. Oxidative stress refers to the imbalance between the production of ROS and the ability to scavenge these species through endogenous antioxidant systems. Since antioxidants can inhibit oxidative processes, it becomes relevant to describe natural compounds with antioxidant properties which may be designed as therapies to decrease oxidative damage and stimulate endogenous cytoprotective systems. The present study tested the protective effect of two xanthones isolated from the heartwood of Calophyllum brasilienses against FeSO4-induced toxicity. Methods Through combinatory chemistry assays, we evaluated the superoxide (O2●—), hydroxyl radical (OH●), hydrogen peroxide (H2O2) and peroxynitrite (ONOO—) scavenging capacity of jacareubin (xanthone III) and 2-(3,3-dimethylallyl)-1,3,5,6-tetrahydroxyxanthone (xanthone V). The effect of these xanthones on murine DNA and bovine serum albumin degradation induced by an OH• generator system was also evaluated. Additionally, we investigated the effect of these xanthones on ROS production, lipid peroxidation and glutathione reductase (GR) activity in FeSO4-exposed brain, liver and lung rat homogenates. Results Xanthone V exhibited a better scavenging capacity for O2●—, ONOO- and OH● than xanthone III, although both xanthones were unable to trap H2O2. Additionally, xanthones III and V prevented the albumin and DNA degradation induced by the OH● generator system. Lipid peroxidation and ROS production evoked by FeSO4 were decreased by both xanthones in all tissues tested. Xanthones III and V also prevented the GR activity depletion induced by pro-oxidant activity only in the brain. Conclusions Altogether, the collected evidence suggests that xanthones can play a role as potential agents to attenuate the oxidative damage produced by different pro-oxidants. PMID:24119308

  5. Role of Bacillus subtilis error prevention oxidized guanine system in counteracting hexavalent chromium-promoted oxidative DNA damage.

    PubMed

    Santos-Escobar, Fernando; Gutiérrez-Corona, J Félix; Pedraza-Reyes, Mario

    2014-09-01

    Chromium pollution is potentially detrimental to bacterial soil communities, compromising carbon and nitrogen cycles that are essential for life on earth. It has been proposed that intracellular reduction of hexavalent chromium [Cr(VI)] to trivalent chromium [Cr(III)] may cause bacterial death by a mechanism that involves reactive oxygen species (ROS)-induced DNA damage; the molecular basis of the phenomenon was investigated in this work. Here, we report that Bacillus subtilis cells lacking a functional error prevention oxidized guanine (GO) system were significantly more sensitive to Cr(VI) treatment than cells of the wild-type (WT) strain, suggesting that oxidative damage to DNA is involved in the deleterious effects of the oxyanion. In agreement with this suggestion, Cr(VI) dramatically increased the ROS concentration and induced mutagenesis in a GO-deficient B. subtilis strain. Alkaline gel electrophoresis (AGE) analysis of chromosomal DNA of WT and ΔGO mutant strains subjected to Cr(VI) treatment revealed that the DNA of the ΔGO strain was more susceptible to DNA glycosylase Fpg attack, suggesting that chromium genotoxicity is associated with 7,8-dihydro-8-oxodeoxyguanosine (8-oxo-G) lesions. In support of this notion, specific monoclonal antibodies detected the accumulation of 8-oxo-G lesions in the chromosomes of B. subtilis cells subjected to Cr(VI) treatment. We conclude that Cr(VI) promotes mutagenesis and cell death in B. subtilis by a mechanism that involves radical oxygen attack of DNA, generating 8-oxo-G, and that such effects are counteracted by the prevention and repair GO system. PMID:24973075

  6. Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease▿

    PubMed Central

    Waghabi, Mariana C.; de Souza, Elen M.; de Oliveira, Gabriel M.; Keramidas, Michelle; Feige, Jean-Jacques; Araújo-Jorge, Tania C.; Bailly, Sabine

    2009-01-01

    Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor β (TGF-β) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-β signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 104 trypomastigotes of T. cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-β signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration. PMID:19738024

  7. Eugenia jambolana pretreatment prevents isoproterenol-induced myocardial damage in rats: evidence from biochemical, molecular, and histopathological studies.

    PubMed

    Shukla, Santosh Kumar; Sharma, Suman Bala; Singh, Usha Rani; Ahmad, Sayeed; Maheshwari, Ankur; Misro, Manmohan; Dwivedi, Shridhar

    2014-02-01

    Preventive effects of hydroalcoholic extract of fruit pulp of Eugenia jambolana (HEEJ) on isoproterenol (ISP)-induced myocardial damage in rats were evaluated. Rats were pre-treated with HEEJ (100, 200, and 400 mg/kg) daily for 30 days. ISP (85 mg/kg bw) was administered on the 28th and 29th days at an interval of 24 h. Ischemic control group exhibited significant increases in oxidative stress parameters, markers of inflammation, cardiac damage markers, and apoptotic markers. Oral pre-treatment with HEEJ (100, 200, and 400 mg/kg bw) provided cardioprotective activity by decreasing levels of malondialdehyde, cardiac markers (serum glutamate oxaloacetate transaminase, creatine kinase-myocardial band, cardiac troponin I), and markers of inflammation (interleukin-6, C-reactive protein, and tumor necrosis factor alpha); and increased levels of superoxide dismutase and reduced glutathione. HEEJ (400 mg/kg bw) was found to exert significantly greater effects in comparison to HEEJ (100 and 200 mg/kg bw). Apoptotic marker Bcl-2 was increased, while Bax was decreased in pre-treated rats, which was further confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The present study provides evidence that pre-treatment with HEEJ attenuates oxidative stress, apoptosis and improves cardiac architecture in ISP-induced rats and, hence, is cardioprotective. PMID:24325453

  8. Eugenia jambolana Pretreatment Prevents Isoproterenol-Induced Myocardial Damage in Rats: Evidence from Biochemical, Molecular, and Histopathological Studies

    PubMed Central

    Shukla, Santosh Kumar; Singh, Usha Rani; Ahmad, Sayeed; Maheshwari, Ankur; Misro, Manmohan; Dwivedi, Shridhar

    2014-01-01

    Abstract Preventive effects of hydroalcoholic extract of fruit pulp of Eugenia jambolana (HEEJ) on isoproterenol (ISP)-induced myocardial damage in rats were evaluated. Rats were pre-treated with HEEJ (100, 200, and 400 mg/kg) daily for 30 days. ISP (85 mg/kg bw) was administered on the 28th and 29th days at an interval of 24 h. Ischemic control group exhibited significant increases in oxidative stress parameters, markers of inflammation, cardiac damage markers, and apoptotic markers. Oral pre-treatment with HEEJ (100, 200, and 400 mg/kg bw) provided cardioprotective activity by decreasing levels of malondialdehyde, cardiac markers (serum glutamate oxaloacetate transaminase, creatine kinase-myocardial band, cardiac troponin I), and markers of inflammation (interleukin-6, C-reactive protein, and tumor necrosis factor alpha); and increased levels of superoxide dismutase and reduced glutathione. HEEJ (400 mg/kg bw) was found to exert significantly greater effects in comparison to HEEJ (100 and 200 mg/kg bw). Apoptotic marker Bcl-2 was increased, while Bax was decreased in pre-treated rats, which was further confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The present study provides evidence that pre-treatment with HEEJ attenuates oxidative stress, apoptosis and improves cardiac architecture in ISP-induced rats and, hence, is cardioprotective. PMID:24325453

  9. Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia.

    PubMed

    Schuch, Clarissa Pedrini; Diaz, Ramiro; Deckmann, Iohanna; Rojas, Joseane Jiménez; Deniz, Bruna Ferrary; Pereira, Lenir Orlandi

    2016-03-23

    Our previous results demonstrated improved cognition in adolescent rats housed in environmental enrichment (EE) that underwent neonatal hypoxia-ischemia (HI). The aim of this study was to investigate the effects of early EE on neurobehavioral development and brain damage in rats submitted to neonatal HI. Wistar rats were submitted to the HI procedure on the 7th postnatal day (PND) and housed in an enriched environment (8th-20th PND). The maturation of physical characteristics and the neurological reflexes were evaluated and the volume of striatum, corpus callosum and neocortex was measured. Data analysis demonstrated a clear effect of EE on neurobehavioral development; also, daily performance was improved in enriched rats on righting, negative geotaxis and cliff aversion reflex. HI caused a transient motor deficit on gait latency. Brain atrophy was found in HI animals and this damage was partially prevented by the EE. In conclusion, early EE stimulated neurobehavioral development in neonate rats and also protects the neocortex and the corpus callosum from atrophy following HI. These findings reinforce the potential of EE as a strategy for rehabilitation following neonatal HI and provide scientific support to the use of this therapeutic strategy in the treatment of neonatal brain injuries in humans. PMID:26872850

  10. Prevention of UV-induced skin damages by 11,14,17-eicosatrienoic acid in hairless mice in vivo.

    PubMed

    Jin, Xing-Ji; Kim, Eun Ju; Oh, In Kyung; Kim, Yeon Kyung; Park, Chi-Hyun; Chung, Jin Ho

    2010-06-01

    Polyunsaturated fatty acids (PUFAs) are known to play important roles in various physiological and pathological processes. Recent studies have shown that some omega-3 (omega-3) PUFAs, such as eicosapentaenoic acid (EPA) and dodecahexaenoic acid (DHA), have protective effects on acute and chronic UV-induced changes. However, the effects of other omega-3 PUFAs including 11,14,17-eicosatrienoic acid (20:3) (ETA) on UV-induced skin damages are poorly understood. In this study, we investigated the cutaneous photoprotective effects of ETA in hairless mice in vivo. Female HR-1 hairless mice were topically treated with vehicle (ethanol:polyethylene glycol=30:70) only, 0.1% ETA, or 1% ETA once a day for 3 successive days after one time UV irradiation (200 mJ/cm(2)) on dorsal skins. Skin biopsy was carried out on the fourth day (72 hr after UV irradiation). We found that topical treatment with ETA attenuated UV-induced epidermal and dermal thickness and infiltration of inflammatory cells, and impairment of skin barrier function. In addition, ETA suppressed the expression of IL-1beta, COX-2, and MMP-13 induced by UV irradiation. Our results show that the topical application of ETA protects against UV-induced skin damage in hairless mice and suggest that ETA can be a potential agent for preventing and/or treating UV-induced inflammation and photoaging. PMID:20514317

  11. Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis

    NASA Astrophysics Data System (ADS)

    Caputo, Fanny; de Nicola, Milena; Sienkiewicz, Andrzej; Giovanetti, Anna; Bejarano, Ignacio; Licoccia, Silvia; Traversa, Enrico; Ghibelli, Lina

    2015-09-01

    Efficient inorganic UV shields, mostly based on refracting TiO2 particles, have dramatically changed the sun exposure habits. Unfortunately, health concerns have emerged from the pro-oxidant photocatalytic effect of UV-irradiated TiO2, which mediates toxic effects on cells. Therefore, improvements in cosmetic solar shield technology are a strong priority. CeO2 nanoparticles are not only UV refractors but also potent biological antioxidants due to the surface 3+/4+ valency switch, which confers anti-inflammatory, anti-ageing and therapeutic properties. Herein, UV irradiation protocols were set up, allowing selective study of the extra-shielding effects of CeO2vs. TiO2 nanoparticles on reporter cells. TiO2 irradiated with UV (especially UVA) exerted strong photocatalytic effects, superimposing their pro-oxidant, cell-damaging and mutagenic action when induced by UV, thereby worsening the UV toxicity. On the contrary, irradiated CeO2 nanoparticles, via their Ce3+/Ce4+ redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer. Interestingly, CeO2 nanoparticles also protect cells from the damage induced by irradiated TiO2, suggesting that these two particles may also complement their effects in solar lotions. CeO2 nanoparticles, which intrinsically couple UV shielding with biological and genetic protection, appear to be ideal candidates for next-generation sun shields.

  12. The Insect Peptide Coprisin Prevents Clostridium difficile-Mediated Acute Inflammation and Mucosal Damage through Selective Antimicrobial Activity▿

    PubMed Central

    Kang, Jin Ku; Hwang, Jae Sam; Nam, Hyo Jung; Ahn, Keun Jae; Seok, Heon; Kim, Sung-Kuk; Yun, Eun Young; Pothoulakis, Charalabos; Lamont, John Thomas; Kim, Ho

    2011-01-01

    Clostridium difficile-associated diarrhea and pseudomembranous colitis are typically treated with vancomycin or metronidazole, but recent increases in relapse incidence and the emergence of drug-resistant strains of C. difficile indicate the need for new antibiotics. We previously isolated coprisin, an antibacterial peptide from Copris tripartitus, a Korean dung beetle, and identified a nine-amino-acid peptide in the α-helical region of it (LLCIALRKK) that had antimicrobial activity (J.-S. Hwang et al., Int. J. Pept., 2009, doi:10.1155/2009/136284). Here, we examined whether treatment with a coprisin analogue (a disulfide dimer of the nine peptides) prevented inflammation and mucosal damage in a mouse model of acute gut inflammation established by administration of antibiotics followed by C. difficile infection. In this model, coprisin treatment significantly ameliorated body weight decreases, improved the survival rate, and decreased mucosal damage and proinflammatory cytokine production. In contrast, the coprisin analogue had no apparent antibiotic activity against commensal bacteria, including Lactobacillus and Bifidobacterium, which are known to inhibit the colonization of C. difficile. The exposure of C. difficile to the coprisin analogue caused a marked increase in nuclear propidium iodide (PI) staining, indicating membrane damage; the staining levels were similar to those seen with bacteria treated with a positive control for membrane disruption (EDTA). In contrast, coprisin analogue treatment did not trigger increases in the nuclear PI staining of Bifidobacterium thermophilum. This observation suggests that the antibiotic activity of the coprisin analogue may occur through specific membrane disruption of C. difficile. Thus, these results indicate that the coprisin analogue may prove useful as a therapeutic agent for C. difficile infection-associated inflammatory diarrhea and pseudomembranous colitis. PMID:21807975

  13. THEOS-2 Orbit Design: Formation Flying in Equatorial Orbit and Damage Prevention Technique for the South Atlantic Magnetic Anomaly (SAMA)

    NASA Astrophysics Data System (ADS)

    Pimnoo, Ammarin

    2016-07-01

    Geo-Informatics and Space Technology Development Agency (GISTDA) has initiative THEOS-2 project after the THEOS-1 has been operated for more than 7 years which is over the lifetime already. THEOS-2 project requires not only the development of earth observation satellite(s), but also the development of the area-based decision making solution platform comprising of data, application systems, data processing and production system, IT infrastructure improvement and capacity building through development of satellites, engineering model, and infrastructures capable of supporting research in related fields. The developing satellites in THEOS-2 project are THAICHOTE-2 and THAICHOTE-3. This paper focuses the orbit design of THAICHOTE-2 & 3. It discusses the satellite orbit design for the second and third EOS of Thailand. In this paper, both THAICHOTE will be simulated in an equatorial orbit as a formation flying which will be compared the productive to THAICHOTE-1 (THEOS-1). We also consider a serious issue in equatorial orbit design, namely the issue of the geomagnetic field in the area of the eastern coast of South America, called the South Atlantic Magnetic Anomaly (SAMA). The high-energy particles of SAMA comprise a radiation environment which can travel through THAICHOTE-2 & 3 material and deposit kinetic energy. This process causes atomic displacement or leaves a stream of charged atoms in the incident particles' wake. It can cause damage to the satellite including reduction of power generated by solar arrays, failure of sensitive electronics, increased background noise in sensors, and exposure of the satellite devices to radiation. This paper demonstrates the loss of ionizing radiation damage and presents a technique to prevent damage from high-energy particles in the SAMA.

  14. Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis.

    PubMed

    Caputo, Fanny; De Nicola, Milena; Sienkiewicz, Andrzej; Giovanetti, Anna; Bejarano, Ignacio; Licoccia, Silvia; Traversa, Enrico; Ghibelli, Lina

    2015-10-14

    Efficient inorganic UV shields, mostly based on refracting TiO2 particles, have dramatically changed the sun exposure habits. Unfortunately, health concerns have emerged from the pro-oxidant photocatalytic effect of UV-irradiated TiO2, which mediates toxic effects on cells. Therefore, improvements in cosmetic solar shield technology are a strong priority. CeO2 nanoparticles are not only UV refractors but also potent biological antioxidants due to the surface 3+/4+ valency switch, which confers anti-inflammatory, anti-ageing and therapeutic properties. Herein, UV irradiation protocols were set up, allowing selective study of the extra-shielding effects of CeO2vs. TiO2 nanoparticles on reporter cells. TiO2 irradiated with UV (especially UVA) exerted strong photocatalytic effects, superimposing their pro-oxidant, cell-damaging and mutagenic action when induced by UV, thereby worsening the UV toxicity. On the contrary, irradiated CeO2 nanoparticles, via their Ce(3+)/Ce(4+) redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer. Interestingly, CeO2 nanoparticles also protect cells from the damage induced by irradiated TiO2, suggesting that these two particles may also complement their effects in solar lotions. CeO2 nanoparticles, which intrinsically couple UV shielding with biological and genetic protection, appear to be ideal candidates for next-generation sun shields. PMID:26349675

  15. Prevention of neonatal oxygen-induced brain damage by reduction of intrinsic apoptosis

    PubMed Central

    Sifringer, M; Bendix, I; Börner, C; Endesfelder, S; von Haefen, C; Kalb, A; Holifanjaniaina, S; Prager, S; Schlager, G W; Keller, M; Jacotot, E; Felderhoff-Mueser, U

    2012-01-01

    Within the last decade, it became clear that oxygen contributes to the pathogenesis of neonatal brain damage, leading to neurocognitive impairment of prematurely born infants in later life. Recently, we have identified a critical role for receptor-mediated neuronal apoptosis in the immature rodent brain. However, the contribution of the intrinsic apoptotic pathway accompanied by activation of caspase-2 under hyperoxic conditions in the neonatal brain still remains elusive. Inhibition of caspases appears a promising strategy for neuroprotection. In order to assess the influence of specific caspases on the developing brain, we applied a recently developed pentapeptide-based group II caspase inhibitor (5-(2,6-difluoro-phenoxy)-3(R,S)-(2(S)-(2(S)-(3-methoxycarbonyl-2(S)-(3-methyl-2(S)-((quinoline-2-carbonyl)-amino)-butyrylamino)propionylamino)3-methylbutyrylamino)propionylamino)-4-oxo-pentanoic acid methyl ester; TRP601). Here, we report that elevated oxygen (hyperoxia) triggers a marked increase in active caspase-2 expression, resulting in an initiation of the intrinsic apoptotic pathway with upregulation of key proteins, namely, cytochrome c, apoptosis protease-activating factor-1, and the caspase-independent protein apoptosis-inducing factor, whereas BH3-interacting domain death agonist and the anti-apoptotic protein B-cell lymphoma-2 are downregulated. These results coincide with an upregulation of caspase-3 activity and marked neurodegeneration. However, single treatment with TRP601 at the beginning of hyperoxia reversed the detrimental effects in this model. Hyperoxia-mediated neurodegeneration is supported by intrinsic apoptosis, suggesting that the development of highly selective caspase inhibitors will represent a potential useful therapeutic strategy in prematurely born infants. PMID:22237207

  16. Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan.

    PubMed

    Xu, Xiaofeng; Zhang, Bin; Lu, Kaili; Deng, Jiangshan; Zhao, Fei; Zhao, Bing-Qiao; Zhao, Yuwu

    2016-07-01

    Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD. PMID:26887382

  17. Oxidative DNA damage preventive activity and antioxidant potential of Stevia rebaudiana (Bertoni) Bertoni, a natural sweetener.

    PubMed

    Ghanta, Srijani; Banerjee, Anindita; Poddar, Avijit; Chattopadhyay, Sharmila

    2007-12-26

    At 0.1 mg/mL, the ethyl acetate extract (EAE) of the crude 85% methanolic extract (CAE) of Stevia rebaudiana leaves exhibited preventive activity against DNA strand scission by *OH generated in Fenton's reaction on pBluescript II SK (-) DNA. Its efficacy is better than that of quercetin. The radical scavenging capacity of CAE was evaluated by the DPPH test (IC50=47.66+/-1.04 microg/mL). EAE was derived from CAE scavenged DPPH (IC50=9.26+/-0.04 microg/mL), ABTS+ (IC50=3.04+/-0.22 microg/mL) and *OH (IC50=3.08+/-0.19 microg/mL). Additionally, inhibition of lipid peroxidation induced with 25 mM FeSO 4 on rat liver homogenate as a lipid source was noted with CAE (IC50=2.1+/-1.07 mg/mL). The total polyphenols and total flavonoids of EAE were 0.86 mg gallic acid equivalents/mg and 0.83 mg of quercetin equivalents/mg, respectively. Flavonoids, isolated from EAE, were characterized as quercetin-3-O-arabinoside, quercitrin, apigenin, apigenin-4-O-glucoside, luteolin, and kaempferol-3-O-rhamnoside by LC-MS and NMR analysis. These results indicate that Stevia rebaudiana may be useful as a potential source of natural antioxidants. PMID:18038982

  18. Nested Neural Networks

    NASA Technical Reports Server (NTRS)

    Baram, Yoram

    1992-01-01

    Report presents analysis of nested neural networks, consisting of interconnected subnetworks. Analysis based on simplified mathematical models more appropriate for artificial electronic neural networks, partly applicable to biological neural networks. Nested structure allows for retrieval of individual subpatterns. Requires fewer wires and connection devices than fully connected networks, and allows for local reconstruction of damaged subnetworks without rewiring entire network.

  19. Galectin-1 Prevents Infection and Damage Induced by Trypanosoma cruzi on Cardiac Cells

    PubMed Central

    Benatar, Alejandro F.; García, Gabriela A.; Bua, Jacqeline; Cerliani, Juan P.; Postan, Miriam; Tasso, Laura M.; Scaglione, Jorge; Stupirski, Juan C.; Toscano, Marta A.

    2015-01-01

    Background Chronic Chagas cardiomyopathy caused by Trypanosoma cruzi is the result of a pathologic process starting during the acute phase of parasite infection. Among different factors, the specific recognition of glycan structures by glycan-binding proteins from the parasite or from the mammalian host cells may play a critical role in the evolution of the infection. Methodology and Principal Findings Here we investigated the contribution of galectin–1 (Gal–1), an endogenous glycan-binding protein abundantly expressed in human and mouse heart, to the pathophysiology of T. cruzi infection, particularly in the context of cardiac pathology. We found that exposure of HL–1 cardiac cells to Gal–1 reduced the percentage of infection by two different T. cruzi strains, Tulahuén (TcVI) and Brazil (TcI). In addition, Gal–1 prevented exposure of phosphatidylserine and early events in the apoptotic program by parasite infection on HL–1 cells. These effects were not mediated by direct interaction with the parasite surface, suggesting that Gal–1 may act through binding to host cells. Moreover, we also observed that T. cruzi infection altered the glycophenotype of cardiac cells, reducing binding of exogenous Gal–1 to the cell surface. Consistent with these data, Gal–1 deficient (Lgals1-/-) mice showed increased parasitemia, reduced signs of inflammation in heart and skeletal muscle tissues, and lower survival rates as compared to wild-type (WT) mice in response to intraperitoneal infection with T. cruzi Tulahuén strain. Conclusion/Significance Our results indicate that Gal–1 modulates T. cruzi infection of cardiac cells, highlighting the relevance of galectins and their ligands as regulators of host-parasite interactions. PMID:26451839

  20. Post-Natal Inhibition of NF-κB Activation Prevents Renal Damage Caused by Prenatal LPS Exposure

    PubMed Central

    Sun, Xiongshan; Wang, Fangjie; Ji, Yan; Huang, Pei; Deng, Yafei; Zhang, Qi; Han, Qi; Yi, Ping; Namaka, Michael; Liu, Ya; Li, Xiaohui

    2016-01-01

    Prenatal exposure to an inflammatory stimulus has been shown to cause renal damage in offspring. Our present study explored the role of intra-renal NF-κB activation in the development of progressive renal fibrosis in offspring that underwent prenatal exposure to an inflammatory stimulus. Time-dated pregnant rats were treated with saline (control group) or 0.79 mg/kg lipopolysaccharide (LPS) through intra-peritoneal injection on gestational day 8, 10 and 12. At the age of 7 weeks, offspring from control or LPS group were treated with either tap water (Con+Ve or LPS+Ve group) or pyrollidine dithiocarbamate (PDTC, 120mg/L), a NF-κB inhibitor, via drinking water starting (Con+PDTC or LPS+PDTC group), respectively, till the age of 20 or 68 weeks. The gross structure of kidney was assessed by hematoxylin-eosin, periodic acid–Schiff staining and Sirius red staining. The expression levels of TNF-α, IL-6, α-smooth muscle actin (α-SMA) and renin-angiotensin system (RAS) genes were determined by real time polymerase chain reaction and/or immunohistochemical staining. Our data showed that post-natal persistent PDTC administration efficiently repressed intra-renal NF-κB activation, TNF-α and IL-6 expression. Post-natal PDTC also prevented intra-renal glycogen deposition and collagenous fiber generation as evident by the reduced expression of collagen III and interstitial α-SMA in offspring of prenatal LPS exposure. Furthermore, post-natal PDTC administration reversed the intra-renal renin-angiotensin system (RAS) over-activity in offspring of prenatal LPS exposure. In conclusion, prenatal inflammatory exposure results in offspring’s intra-renal NF-κB activation along with inflammation which cross-talked with excessive RAS activation that caused exacerbation of renal fibrosis and dysfunction in the offspring. Thus, early life prevention of NF-κB activation may be a potential preventive strategy for chronic renal inflammation and progressive renal damage. PMID

  1. Post-Natal Inhibition of NF-κB Activation Prevents Renal Damage Caused by Prenatal LPS Exposure.

    PubMed

    Guo, Wei; Guan, Xiao; Pan, Xiaodong; Sun, Xiongshan; Wang, Fangjie; Ji, Yan; Huang, Pei; Deng, Yafei; Zhang, Qi; Han, Qi; Yi, Ping; Namaka, Michael; Liu, Ya; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Prenatal exposure to an inflammatory stimulus has been shown to cause renal damage in offspring. Our present study explored the role of intra-renal NF-κB activation in the development of progressive renal fibrosis in offspring that underwent prenatal exposure to an inflammatory stimulus. Time-dated pregnant rats were treated with saline (control group) or 0.79 mg/kg lipopolysaccharide (LPS) through intra-peritoneal injection on gestational day 8, 10 and 12. At the age of 7 weeks, offspring from control or LPS group were treated with either tap water (Con+Ve or LPS+Ve group) or pyrollidine dithiocarbamate (PDTC, 120mg/L), a NF-κB inhibitor, via drinking water starting (Con+PDTC or LPS+PDTC group), respectively, till the age of 20 or 68 weeks. The gross structure of kidney was assessed by hematoxylin-eosin, periodic acid-Schiff staining and Sirius red staining. The expression levels of TNF-α, IL-6, α-smooth muscle actin (α-SMA) and renin-angiotensin system (RAS) genes were determined by real time polymerase chain reaction and/or immunohistochemical staining. Our data showed that post-natal persistent PDTC administration efficiently repressed intra-renal NF-κB activation, TNF-α and IL-6 expression. Post-natal PDTC also prevented intra-renal glycogen deposition and collagenous fiber generation as evident by the reduced expression of collagen III and interstitial α-SMA in offspring of prenatal LPS exposure. Furthermore, post-natal PDTC administration reversed the intra-renal renin-angiotensin system (RAS) over-activity in offspring of prenatal LPS exposure. In conclusion, prenatal inflammatory exposure results in offspring's intra-renal NF-κB activation along with inflammation which cross-talked with excessive RAS activation that caused exacerbation of renal fibrosis and dysfunction in the offspring. Thus, early life prevention of NF-κB activation may be a potential preventive strategy for chronic renal inflammation and progressive renal damage. PMID:27073902

  2. Prevention

    MedlinePlus

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

  3. Diabetes and obesity-related genes and the risk of neural tube defects in the national birth defects prevention study.

    PubMed

    Lupo, Philip J; Canfield, Mark A; Chapa, Claudia; Lu, Wei; Agopian, A J; Mitchell, Laura E; Shaw, Gary M; Waller, D Kim; Olshan, Andrew F; Finnell, Richard H; Zhu, Huiping

    2012-12-15

    Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999-2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy. PMID:23132673

  4. Prevention of neural tube defects by the fortification of flour with folic acid: a population-based retrospective study in Brazil

    PubMed Central

    Lecca, Roberto Carlos Reyes; Cortez-Escalante, Juan Jose; Sanchez, Mauro Niskier; Rodrigues, Humberto Gabriel

    2016-01-01

    Abstract Objective To determine if the fortification of wheat and maize flours with iron and folic acid – which became mandatory in Brazil from June 2004 – is effective in the prevention of neural tube defects. Methods Using data from national information systems on births in central, south-eastern and southern Brazil, we determined the prevalence of neural tube defects among live births and stillbirths in a pre-fortification period – i.e. 2001–2004 – and in a post-fortification period – i.e. 2005–2014. We distinguished between anencephaly, encephalocele, meningocele, myelomeningocele and other forms of spina bifida. Findings There were 8554 neural tube defects for 17 925 729 live births notified between 2001 and 2014. For the same period, 2673 neural tube defects were reported for 194 858 stillbirths. The overall prevalence of neural tube defects fell from 0.79 per 1000 pre-fortification to 0.55 per 1000 post-fortification (prevalence ratio, PR: 1.43; 95% confidence interval, CI: 1.38–1.50). For stillbirths, prevalence fell from 17.74 per 1000 stillbirths pre-fortification to 11.70 per 1000 stillbirths post-fortification. The corresponding values among live births were 0.57 and 0.44, respectively. Conclusion The introduction of the mandatory fortification of flour with iron and folic acid in Brazil was followed by a significant reduction in the prevalence of neural tube defects in our study area. PMID:26769993

  5. A novel eye drop of alpha tocopherol to prevent ocular oxidant damage: improve the stability and ocular efficacy.

    PubMed

    Xin, Jiayu; Tang, Jingling; Bu, Meng; Sun, Yanhui; Wang, Xinyu; Wu, Linhua; Liu, Hongzhuo

    2016-04-01

    The aim of this study was to design novel mixed micelles as an ophthalmic delivery system for alpha-tocopherol (TOC) to prevent its degradation and improve ocular efficacy. The nonionic polymers, Polyoxyl 15 Hydroxystearate (Solutol® HS15) and Pluronic® F127, were discovered to be the most effective agents for retaining the activity and solubilization of TOC, respectively. Prepared by a thin-film hydration method, HS15/Pluronic® F127 yielded good encapsulation percentages of TOC, with a 27.7% drug loading efficiency. Incorporation of cetalkonium chloride (CKC) into HS15/Pluronic® F127 mixed micelles made the zeta potential of the micelles +17 mV, potentially prolonging the residence time of formulations on ocular surfaces. The optimized micelle preparation remained stable when diluted in a synthetic tear solution. It is known that the antioxidant ability of TOC in typical formulations reduces to around 85% of its initial value after 1 month when stored at 4 or 25 °C under an air atmosphere, which limits ophthalmic applications to less than 1 month. However, encapsulated TOC in investigated micelles remained stable for at least 6 months when sealed with N2. Finally, the cationic micelles were well tolerated after multiple administrations in rabbits, and they improved ocular accumulation of TOC. Taken together, these data suggest that the optimized micelle preparations described in this study may be suitable drug carriers for the treatment of ocular oxidant damage. PMID:26340610

  6. Ammonia-induced oxidative damage in neurons is prevented by resveratrol and lipoic acid with participation of heme oxygenase 1.

    PubMed

    Bobermin, Larissa Daniele; Wartchow, Krista Minéia; Flores, Marianne Pires; Leite, Marina Concli; Quincozes-Santos, André; Gonçalves, Carlos-Alberto

    2015-07-01

    Ammonia is a metabolite that, at high concentrations, is implicated in neurological disorders, such as hepatic encephalopathy (HE), which is associated with acute or chronic liver failure. Astrocytes are considered the primary target of ammonia toxicity in the central nervous system (CNS) because glutamine synthetase (GS), responsible for ammonia metabolism in CNS, is an astrocytic enzyme. Thus, neuronal dysfunction has been associated as secondary to astrocytic impairment. However, we demonstrated that ammonia can induce direct effects on neuronal cells. The cell viability was decreased by ammonia in SH-SY5Y cells and cerebellar granule neurons. In addition, ammonia induced increased reactive oxygen species (ROS) production and decreased GSH intracellular content, the main antioxidant in CNS. As ammonia neurotoxicity is strongly associated with oxidative stress, we also investigated the potential neuroprotective roles of the antioxidants, resveratrol (RSV) and lipoic acid (LA), against ammonia toxicity in cerebellar granule neurons. RSV and LA were able to prevent the oxidative damage induced by ammonia, maintaining the levels of ROS production and GSH close to basal values. Both antioxidants also decreased ROS production and increased GSH content under basal conditions (in the absence of ammonia). Moreover, we showed that heme oxygenase 1 (HO1), a protein associated with protection against stress conditions, is involved in the beneficial effects of RSV and LA in cerebellar granule neurons. Thus, this study reinforces the neuroprotective effects of RSV and LA. Although more studies in vivo are required, RSV and LA could represent interesting therapeutic strategies for the management of HE. PMID:26003724

  7. Astragaloside IV possesses antiarthritic effect by preventing interleukin 1β-induced joint inflammation and cartilage damage.

    PubMed

    Wang, Bin; Chen, Min-Zhu

    2014-06-01

    The saponin astragaloside IV (AST) is one of major active components purified from Astragalus membranaceus (Fisch) Bge, which has been used in traditional Chinese medicine to treat immune disorders including rheumatoid arthritis (RA). The effects of AST on the suppression of experimental arthritis and its possible mechanisms are unknown. We measured the paw swelling of ankle joints, splenocyte proliferation, interleukin 1β (IL-1β), tumor necrosis factor α (TNFα) and nitric oxide (NO) formation by macrophages in rat adjuvant-induced arthritis (AIA). Intraarticular injection of IL-1β to rat knee joint for inducing the edema and in vitro IL-1β-stimulated cartilage impairment were examined. The results showed that oral treatment of AST (100 mg/kg/day) suppressed the joint inflammation and inhibited IL-1β, TNFα and NO production in macrophages from AIA rats. Macrophages were one of AST targeted cells, and mediated the reduced splenocyte proliferation in AIA rats. In addition, AST reduced the swelling induced by intraarticular injection of IL-1β, and protected against IL-1β-induced damage of cartilage proteoglycan synthesis and chondrocyte proliferation. We conclude that AST possesses antiarthritic effect and prevents IL-1β-induced joint inflammation and cartilage destruction. These findings suggest that AST may be used for the treatment of RA and other inflammatory joint diseases. PMID:24469603

  8. Inhibition of the phospholipase A2 activity of peroxiredoxin 6 prevents lung damage with exposure to hyperoxia

    PubMed Central

    Benipal, Bavneet; Feinstein, Sheldon I.; Chatterjee, Shampa; Dodia, Chandra; Fisher, Aron B.

    2015-01-01

    Lung injury associated with hyperoxia reflects in part the secondary effects of pulmonary inflammation and the associated production of reactive oxygen species due to activation of NADPH oxidase, type 2 (NOX2). Activation of NOX2 requires the phospholipase A2 (PLA2) activity of peroxiredoxin 6 (Prdx6). Therefore, we evaluated whether blocking Prdx6 PLA2 activity using the inhibitor MJ33 would be protective in a mouse model of acute lung injury resulting from hyperoxic exposure. Mice were treated with an intraperitoneal injection of MJ33 (2.5 nmol/g body weight) at the start of exposure (zero time) and at 48 h during continuous exposure to 100% O2 for 80 h. Treatment with MJ33 reduced the number of neutrophils and the protein content in the fluid obtained by bronchoalveolar lavage, inhibited the increase in lipid peroxidation products in lung tissue, decreased the number of apoptotic cells in the lung, and decreased the perivascular edema associated with the 80 h exposure to hyperoxia. Thus, blocking Prdx6 PLA2 activity by MJ33 significantly protected lungs against damage from hyperoxia, presumably by preventing the activation of NOX2 and the amplification of lung injury associated with inflammation. These findings demonstrate that MJ33, a potent inhibitor of Prdx6 PLA2 activity, can protect mouse lungs against the manifestations of acute lung injury due to oxidative stress. PMID:25637741

  9. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines.

    PubMed

    Cordero, Amy M; Crider, Krista S; Rogers, Lisa M; Cannon, Michael J; Berry, R J

    2015-04-24

    Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 µg of folic acid daily for NTD prevention. Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings and is a highly cost-effective intervention. PMID:25905896

  10. Transcriptional profiling of radiation damage and preventive treatments in a 3-dimensional (3D) human cell culture model of oral mucositis

    PubMed Central

    Lambros, Maria P.; DeSalvo, Michael K.; Moreno, Jonathan; Mulamalla, Hari Chandana; Kondapalli, Lavanya

    2015-01-01

    Cancer patients who receive radiation are often afflicted by oral mucositis, a debilitating disease, characterized by mouth sores and difficulty in swallowing. Oftentimes, cancer patients afflicted with mucositis must stop life-saving therapies. Thus it is very important to prevent mucositis before it develops. Using a validated organotypic model of human oral mucosa, a 3-dimensional cell culture model of human oral keratinocytes, it has been shown that a mixture (NAC–QYD) of N-acetyl cysteine (NAC) and a traditional Chinese medicine, Qingre Liyan decoction (QYD), prevented radiation damage (Lambros et al., 2014). Here we provide detailed methods and analysis of microarray data for non-irradiated and irradiated human oral mucosal tissue with and without pretreatment with NAC, QYD and NAC-QYD. The microarray data been deposited in Gene Expression Omnibus (GEO): GSE62397. These data can be used to further elucidate the mechanisms of irradiation damage in oral mucosa and its prevention. PMID:26697327

  11. Transcriptional profiling of radiation damage and preventive treatments in a 3-dimensional (3D) human cell culture model of oral mucositis.

    PubMed

    Lambros, Maria P; DeSalvo, Michael K; Moreno, Jonathan; Mulamalla, Hari Chandana; Kondapalli, Lavanya

    2015-12-01

    Cancer patients who receive radiation are often afflicted by oral mucositis, a debilitating disease, characterized by mouth sores and difficulty in swallowing. Oftentimes, cancer patients afflicted with mucositis must stop life-saving therapies. Thus it is very important to prevent mucositis before it develops. Using a validated organotypic model of human oral mucosa, a 3-dimensional cell culture model of human oral keratinocytes, it has been shown that a mixture (NAC-QYD) of N-acetyl cysteine (NAC) and a traditional Chinese medicine, Qingre Liyan decoction (QYD), prevented radiation damage (Lambros et al., 2014). Here we provide detailed methods and analysis of microarray data for non-irradiated and irradiated human oral mucosal tissue with and without pretreatment with NAC, QYD and NAC-QYD. The microarray data been deposited in Gene Expression Omnibus (GEO): GSE62397. These data can be used to further elucidate the mechanisms of irradiation damage in oral mucosa and its prevention. PMID:26697327

  12. Prevention

    MedlinePlus

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

  13. Pycnogenol prevents potassium dichromate K2Cr2O7-induced oxidative damage and nephrotoxicity in rats.

    PubMed

    Parveen, Kehkashan; Khan, Mohd Rashid; Siddiqui, Waseem A

    2009-10-30

    Environmental and occupational exposure to chromium compounds, especially hexavalent chromium [Cr(VI)], is widely recognized as a potential nephrotoxic in humans and animals. Its toxicity is associated with overproduction of free radicals, which induces oxidative damage. Recent evidence indicates that Pycnogenol (PYC), French maritime pine bark extract, exhibits antioxidant potential and protects against various oxidative stressors. The aim of the present study was to examine the modulating impacts of PYC on potassium dichromate K2Cr2O7-induced oxidative damage and nephrotoxicity in rats. Male Wistar rats were divided into four groups. The first group was control, the second group was control plus pre-treated with PYC (10 mg/kg, body weight; in saline; intraperitoneally; once daily for 3 weeks) as drug control and the third group was saline pre-treated plus treated with a single injection of K2Cr2O7 (15 mg/kg, body weight; in saline; intraperitoneally) as toxicant group. The fourth group was PYC pre-treated plus K2Cr2O7 injected. Forty-eight hours after K2Cr2O7-treatment, blood was drawn for estimation of renal injury markers in serum. Rats were then sacrificed, and their kidneys were dissected for biochemical and histopathological assays. K2Cr2O7-treated rats showed significant increases in markers of renal injury in serum, including blood urea nitrogen (BUN), serum creatinine (Scr), and alkaline phosphatase (ALP), which were significantly (P < 0.05) decreased by PYC pre-treatment. Moreover, prophylactic pre-treatment of rats with PYC significantly (P < 0.05) ameliorated increased thiobarbituric reactive substances (TBARS), malonaldehyde (MDA) and protein carbonyl (PC), and decreased levels of glutathione (GSH) and catalase activity in the kidney homogenate of K2Cr2O7-treated rats. These results were also supported and confirmed with histopathological findings. The study suggests that PYC is effective in preventing K2Cr2O7-induced oxidative mediated nephrotoxicity

  14. Ghrelin Prevents Cisplatin-Induced Testicular Damage by Facilitating Repair of DNA Double Strand Breaks Through Activation of p53 in Mice.

    PubMed

    Garcia, Jose M; Chen, Ji-an; Guillory, Bobby; Donehower, Lawrence A; Smith, Roy G; Lamb, Dolores J

    2015-07-01

    Cisplatin administration induces DNA damage resulting in germ cell apoptosis and subsequent testicular atrophy. Although 50 percent of male cancer patients receiving cisplatin-based chemotherapy develop long-term secondary infertility, medical treatment to prevent spermatogenic failure after chemotherapy is not available. Under normal conditions, testicular p53 promotes cell cycle arrest, which allows time for DNA repair and reshuffling during meiosis. However, its role in the setting of cisplatin-induced infertility has not been studied. Ghrelin administration ameliorates the spermatogenic failure that follows cisplatin administration in mice, but the mechanisms mediating these effects have not been well established. The aim of the current study was to characterize the mechanisms of ghrelin and p53 action in the testis after cisplatin-induced testicular damage. Here we show that cisplatin induces germ cell damage through inhibition of p53-dependent DNA repair mechanisms involving gamma-H2AX and ataxia telangiectasia mutated protein kinase. As a result, testicular weight and sperm count and motility were decreased with an associated increase in sperm DNA damage. Ghrelin administration prevented these sequelae by restoring the normal expression of gamma-H2AX, ataxia telangiectasia mutated, and p53, which in turn allows repair of DNA double stranded breaks. In conclusion, these findings indicate that ghrelin has the potential to prevent or diminish infertility caused by cisplatin and other chemotherapeutic agents by restoring p53-dependent DNA repair mechanisms. PMID:26019260

  15. Ghrelin Prevents Cisplatin-Induced Testicular Damage by Facilitating Repair of DNA Double Strand Breaks Through Activation of p53 in Mice1

    PubMed Central

    Garcia, Jose M.; Chen, Ji-an; Guillory, Bobby; Donehower, Lawrence A.; Smith, Roy G.; Lamb, Dolores J.

    2015-01-01

    Cisplatin administration induces DNA damage resulting in germ cell apoptosis and subsequent testicular atrophy. Although 50 percent of male cancer patients receiving cisplatin-based chemotherapy develop long-term secondary infertility, medical treatment to prevent spermatogenic failure after chemotherapy is not available. Under normal conditions, testicular p53 promotes cell cycle arrest, which allows time for DNA repair and reshuffling during meiosis. However, its role in the setting of cisplatin-induced infertility has not been studied. Ghrelin administration ameliorates the spermatogenic failure that follows cisplatin administration in mice, but the mechanisms mediating these effects have not been well established. The aim of the current study was to characterize the mechanisms of ghrelin and p53 action in the testis after cisplatin-induced testicular damage. Here we show that cisplatin induces germ cell damage through inhibition of p53-dependent DNA repair mechanisms involving gamma-H2AX and ataxia telangiectasia mutated protein kinase. As a result, testicular weight and sperm count and motility were decreased with an associated increase in sperm DNA damage. Ghrelin administration prevented these sequelae by restoring the normal expression of gamma-H2AX, ataxia telangiectasia mutated, and p53, which in turn allows repair of DNA double stranded breaks. In conclusion, these findings indicate that ghrelin has the potential to prevent or diminish infertility caused by cisplatin and other chemotherapeutic agents by restoring p53-dependent DNA repair mechanisms. PMID:26019260

  16. Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage

    PubMed Central

    Louboutin, Jean-Pierre; Chekmasova, Alena; Marusich, Elena; Agrawal, Lokesh; Strayer, David S.

    2011-01-01

    Chemokines may play a role in leukocyte migration across the blood-brain barrier (BBB) during neuroinflammation and other neuropathological processes, such as epilepsy. We investigated the role of the chemokine receptor CCR5 in seizures. We used a rat model based on intraperitoneal kainic acid (KA) administration. Four months before KA injection, adult rats were given femoral intramarrow inoculations of SV (RNAiR5-RevM10.AU1), which carries an interfering RNA (RNAi) against CCR5, plus a marker epitope (AU1), or its monofunctional RNAi-carrying homologue, SV(RNAiR5). This treatment lowered expression of CCR5 in circulating cells. In control rats, seizures induced elevated expression of CCR5 ligands MIP-1α and RANTES in the microvasculature, increased BBB leakage and CCR5+ cells, as well as neuronal loss, inflammation, and gliosis in the hippocampi. Animals given either the bifunctional or the monofunctional vector were largely protected from KA-induced seizures, neuroinflammation, BBB damage, and neuron loss. Brain CCR5 mRNA was reduced. Rats receiving RNAiR5-bearing vectors showed far greater repair responses: increased neuronal proliferation, and decreased production of MIP-1α and RANTES. Controls received unrelated SV(BUGT) vectors. Decrease in CCR5 in circulating cells strongly protected from excitotoxin-induced seizures, BBB leakage, CNS injury, and inflammation, and facilitated neurogenic repair.—Louboutin, J.-P., Chekmasova, A., Marusich, E., Agrawal, L., Strayer, D. S. Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage. PMID:20940264

  17. Analysis of the Thermal Comfort and Impact Properties of the Neoprene-Spacer Fabric Structure for Preventing the Joint Damages

    PubMed Central

    Ghorbani, Ehsan; Hasani, Hossein; Rafeian, Homa; Hashemibeni, Batool

    2013-01-01

    Background: Frequent moves at the joint, plus external factors such as trauma, aging, and etc., are all reasons for joint damages. In order to protect and care of joints, the orthopedic textiles are used. To protect the joints, these textiles keep muscles warm to prevent shock. To produce orthopedic textiles, Neoprene foams have been traditionally used. These foams are flexible and resist impact, but are not comfortable enough and might cause problems for the consumer. This study introduces a new structure consisting of perforated Neoprene foam attached to the spacer fabric and also compares the properties of thermal and moisture comfort and impact properties of this structure in comparison with Neoprene foam. Methods: In order to measure the factors related to the samples lateral pressure behavior, a tensile tester was used. A uniform pressure is applied to the samples and a force – displacement curve is obtained. The test continues until the maximum compression force is reached to 50 N. The area under the curve is much greater; more energy is absorbed during the impact. In order to investigate the dynamic heat and moisture transfer of fabrics, an experimental apparatus was developed. This device made the simulation of sweating of human body possible and consisted of a controlled environmental chamber, sweating guarded hot plate, and data acquisition system. Results: The findings show that the Neoprene-spacer fabric structure represents higher toughness values compared to other samples (P ≤ 0.001). Neoprene-spacer fabric structure (A3) has higher rate of moisture transport than conventional Neoprene foam; because of undesirable comfort characteristics in Neoprene. Conclusions: Results of the tests indicate full advantage of the new structure compared with the Neoprene foam for use in orthopedic textiles (P ≤ 0.001). PMID:24049594

  18. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    PubMed Central

    Jiao, Yu; Palmgren, Björn; Novozhilova, Ekaterina; Englund Johansson, Ulrica; Spieles-Engemann, Anne L.; Kale, Ajay; Stupp, Samuel I.; Olivius, Petri

    2014-01-01

    Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN). PMID:25243135

  19. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of neural tube defects, with a concurrent assessment of other potential benefits or adverse effects. The evaluation was based on a systematic review of the published ...

  20. Brca1 is required for embryonic development of the mouse cerebral cortex to normal size by preventing apoptosis of early neural progenitors.

    PubMed

    Pulvers, Jeremy N; Huttner, Wieland B

    2009-06-01

    The extent of apoptosis of neural progenitors is known to influence the size of the cerebral cortex. Mouse embryos lacking Brca1, the ortholog of the human breast cancer susceptibility gene BRCA1, show apoptosis in the neural tube, but the consequences of this for brain development have not been studied. Here we investigated the role of Brca1 during mouse embryonic cortical development by deleting floxed Brca1 using Emx1-Cre, which leads to conditional gene ablation specifically in the dorsal telencephalon after embryonic day (E) 9.5. The postnatal Brca1-ablated cerebral cortex was substantially reduced in size with regard to both cortical thickness and surface area. Remarkably, although the thickness of the cortical layers (except for the upper-most layer) was decreased, cortical layering as such was essentially unperturbed. High levels of apoptosis were found at E11.5 and E13.5, but dropped to near-control levels by E16.5. The apoptosis at the early stage of neurogenesis occurred in both BrdU pulse-labeled neural progenitors and the neurons derived therefrom. No changes were observed in the mitotic index of apical (neuroepithelial, radial glial) progenitors and basal (intermediate) progenitors, indicating that Brca1 ablation did not affect cell cycle progression. Brca1 ablation did, however, result in the nuclear translocation of p53 in neural progenitors, suggesting that their apoptosis involved activation of the p53 pathway. Our results show that Brca1 is required for the cerebral cortex to develop to normal size by preventing the apoptosis of early cortical progenitors and their immediate progeny. PMID:19403657

  1. Nanopharmaceutical approach using pelargonidin towards enhancement of efficacy for prevention of alloxan-induced DNA damage in L6 cells via activation of PARP and p53.

    PubMed

    Samadder, Asmita; Abraham, Suresh K; Khuda-Bukhsh, Anisur Rahman

    2016-04-01

    Alloxan is an environmental food contaminant that causes DNA damage in living cells and induces hyperglycemia. Pelargonidin (PG), an active ingredient found in extract of various fruits and vegetables, has been nanoencapsulated (NPG) with poly-lactide-co-glycolide (PLGA) and tested for efficacy in prevention of alloxan (ALX)-induced DNA damage in L6 cells in vitro. Glucose uptake, reactive oxygen species (ROS) generation, glucose transporter 4, glucokinase levels and mechanism of activation of DNA repair proteins (PARP and p53) have been studied in ALX-induced L6 cells. Drug-DNA interaction has been analyzed using calf thymus DNA as target through circular dichroism and melting temperature profile. NPGs were physico-chemically characterized by standard protocols using dynamic light scattering and transmission electron microscopy. Pre-treatment with both PG and/or NPG was effective in reducing ALX-induced oxidative stress and showed favourable effects for protection against DNA damage by activating DNA repair cascades. Results suggested ∼10-fold increase in efficacy of NPG than PG in prevention of alloxan-induced oxidative stress and DNA damage. PMID:26943895

  2. Neural induction, neural fate stabilization, and neural stem cells.

    PubMed

    Moody, Sally A; Je, Hyun-Soo

    2002-04-28

    The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural-fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies. PMID:12805974

  3. Oxidative DNA Damage in Kidneys and Heart of Hypertensive Mice Is Prevented by Blocking Angiotensin II and Aldosterone Receptors

    PubMed Central

    Brand, Susanne; Amann, Kerstin; Mandel, Philipp; Zimnol, Anna; Schupp, Nicole

    2014-01-01

    Introduction Recently, we could show that angiotensin II, the reactive peptide of the blood pressure-regulating renin-angiotensin-aldosterone-system, causes the formation of reactive oxygen species and DNA damage in kidneys and hearts of hypertensive mice. To further investigate on the one hand the mechanism of DNA damage caused by angiotensin II, and on the other hand possible intervention strategies against end-organ damage, the effects of substances interfering with the renin-angiotensin-aldosterone-system on angiotensin II-induced genomic damage were studied. Methods In C57BL/6-mice, hypertension was induced by infusion of 600 ng/kg • min angiotensin II. The animals were additionally treated with the angiotensin II type 1 receptor blocker candesartan, the mineralocorticoid receptor blocker eplerenone and the antioxidant tempol. DNA damage and the activation of transcription factors were studied by immunohistochemistry and protein expression analysis. Results Administration of angiotensin II led to a significant increase of blood pressure, decreased only by candesartan. In kidneys and hearts of angiotensin II-treated animals, significant oxidative stress could be detected (1.5-fold over control). The redox-sensitive transcription factors Nrf2 and NF-κB were activated in the kidney by angiotensin II-treatment (4- and 3-fold over control, respectively) and reduced by all interventions. In kidneys and hearts an increase of DNA damage (3- and 2-fold over control, respectively) and of DNA repair (3-fold over control) was found. These effects were ameliorated by all interventions in both organs. Consistently, candesartan and tempol were more effective than eplerenone. Conclusion Angiotensin II-induced DNA damage is caused by angiotensin II type 1 receptor-mediated formation of oxidative stress in vivo. The angiotensin II-mediated physiological increase of aldosterone adds to the DNA-damaging effects. Blocking angiotensin II and mineralocorticoid receptors therefore

  4. Hypervelocity Impacts on ISS Handrails and Evaluation of Alternative Materials to Prevent Extravehicular Mobility Unit (EMU) Glove Damage During EVA

    NASA Technical Reports Server (NTRS)

    Ryan, Shannon; Christiansen, Eruc; Davis, B. Alan; Ordonez, Erick

    2009-01-01

    During post-flight processing of STS-116, damage to crewmember Robert Curbeam's Phase VI Glove Thermal Micrometeoroid Garment was discovered. This damage consisted of: loss of RTV-157 palm pads on the thumb area on the right glove, a 0.75 inch cut in the Vectran adjacent to the seam and thumb pad (single event cut), constituting the worst glove damage ever recorded for the U.S. space program. The underlying bladder and restraint were found not be damaged by this event. Evaluation of glove damage found that the outer Vectran fibers were sliced as a result of contact with a sharp edge or pinch point rather than general wear or abrasion (commonly observed on the RTV pads). Damage to gloves was also noted on STS-118 and STS-120. One potential source of EMU glove damages are sharp crater lips on external handrails, generated by micrometeoroid and orbital debris (MMOD) impacts. In this paper, the results of a hypervelocity impact (HVI) test program on representative and actual ISS handrails are presented. These tests were performed in order to characterize impact damage profiles on ISS handrails and evaluate alternatives for limiting risk to future missions. It was determined that both penetrating and non-penetrating MMOD impacts on aluminum and steel ISS handrails are capable of generating protruding crater profiles which exceed the heights required for EMU glove abrasion risk by an order of magnitude. Testing demonstrated that flexible overwraps attached to the outside of existing handrails are capable of limiting contact between hazardous crater formations and crewmember gloves during extravehicular activity (EVA). Additionally, replacing metallic handrails with high strength, low ductility, fiber reinforced composite materials would limit the formation of protruding crater lips on new ISS modules.

  5. Hydrogen sulfide prevents ethanol-induced gastric damage in mice: role of ATP-sensitive potassium channels and capsaicin-sensitive primary afferent neurons.

    PubMed

    Medeiros, Jand Venes R; Bezerra, Víctor H; Gomes, Antoniella S; Barbosa, André Luiz R; Lima-Júnior, Roberto César P; Soares, Pedro Marcos G; Brito, Gerly Anne C; Ribeiro, Ronaldo A; Cunha, Fernando Q; Souza, Marcellus H L P

    2009-09-01

    The aim of this study was to evaluate the protective effect of hydrogen sulfide (H(2)S) on ethanol-induced gastric lesions in mice and the influence of ATP-sensitive potassium (K(ATP)) channels, capsaicin-sensitive sensory afferent neurons, and transient receptor potential vanilloid (TRPV) 1 receptors on such an effect. Saline and L-cysteine alone or with propargylglycine, sodium hydrogen sulfide (NaHS), or Lawesson's reagent were administrated for testing purposes. For other experiments, mice were pretreated with glibenclamide, neurotoxic doses of capsaicin, or capsazepine. Afterward, mice received L-cysteine, NaHS, or Lawesson's reagent. After 30 min, 50% ethanol was administrated by gavage. After 1 h, mice were sacrificed, and gastric damage was evaluated by macroscopic and microscopic analyses. L-cysteine, NaHS, and Lawesson's reagent treatment prevented ethanol-induced macroscopic and microscopic gastric damage in a dose-dependent manner. Administration of propargylglycine, an inhibitor of endogenous H(2)S synthesis, reversed gastric protection induced by L-cysteine. Glibenclamide reversed L-cysteine, NaHS, or Lawesson's reagent gastroprotective effects against ethanol-induced macroscopic damage in a dose-dependent manner. Chemical ablation of sensory afferent neurons by capsaicin reversed gastroprotective effects of L-cysteine or H(2)S donors (NaHS or Lawesson's reagent) in ethanol-induced macroscopic gastric damage. Likewise, in the presence of the TRPV1 antagonist capsazepine, the gastroprotective effects of L-cysteine, NaHS, or Lawesson's reagent were also abolished. Our results suggest that H(2)S prevents ethanol-induced gastric damage. Although there are many mechanisms through which this effect can occur, our data support the hypothesis that the activation of K(ATP) channels and afferent neurons/TRPV1 receptors is of primary importance. PMID:19491326

  6. Using prophylactic antioxidants to prevent noise-induced hearing damage in young adults: a protocol for a double-blind, randomized controlled trial

    PubMed Central

    2014-01-01

    Background During leisure activities young people are often exposed to excessive noise levels resulting in an increase of noise-induced symptoms such as hearing loss, tinnitus and hyperacusis. Noise-induced tinnitus is often perceived after loud music exposure and provides an important marker for overexposure as a temporary threshold shift that is often not experienced by the individual itself. As oxidative stress plays an important role in the pathogenesis of noise-induced hearing loss, the use of antioxidants to prevent hearing damage has recently become the subject of research. Methods This study proposes a randomized, double-blind, placebo-controlled crossover trial to assess the effects of a prophylactic combination of N-acetylcysteine (600 mg) and magnesium (200 mg) prior to leisure noise exposure in young adults. The primary outcome measure is the tinnitus loudness scored by a visual analogue scale (VAS). Secondary outcome measures are the differences in audiological measurements for the antioxidant treatments compared to placebo intake. Audiological testing comprising of pure tone audiometry including frequencies up to 16 kHz, distortion product otoacoustic emissions, transient-evoked otoacoustic emissions and speech-in-noise testing will be performed prior to and within 7 hours after noise exposure. By use of a mixed effects statistical model, the effects of antioxidants compared to placebo intake will be assessed. Discussion As adolescents and young adults often do not use hearing protection while being exposed to loud music, the use of preventive antioxidant intake may provide a useful and harmless way to prevent noise-induced hearing damage in this population. Furthermore, when exposed to hazardous noise levels the protection provided by hearing protectors might not be sufficient to prevent hearing damage and antioxidants may provide additive otoprotective effects. Previous research mainly focused on occupational noise exposure. The present study

  7. Evaluation of reactive oxygen species scavenging activities and DNA damage prevention effect of Pleioblastus kongosanensis f. aureostriatus leaf extract by chemiluminescence assay.

    PubMed

    Ni, Qinxue; Xu, Guangzhi; Gao, Qianxin; Yang, Dongdong; Zhang, Youzuo

    2013-11-01

    Reactive oxygen species scavenging effect of Pleioblastus kongosanensis f. aureostriatus leaf extract against O2(-), OH and H2O2 were investigated by chemiluminescence methods in vitro. Bamboo grass leaves were extracted with 70% ethanol solution and sequentially partitioned with solvents in an order of increasing polarity. Among fractions of different polarity, BuOH and EtOAc fractions showed powerful scavenging activities than others, and showed better scavenging ability on OH than that of O2(-)and H2O2, with IC50 of 0.55 μg/mL and 0.60 μg/mL, respectively. Both OH-induced DNA damage model by chemiluminescence assay and plasmid pUC18 double-strand break model by agarose gel electrophoresis showed that BuOH and EtOAc fractions had remarkable concentration-dependent prevention effect on the OH-induced damage of DNA attribute to their good scavenging effects on ROS. Results from the compositional analysis of different fractions indicate that the flavonoids in the Pleioblastus kongosanensis f. aureostriatus leaf may be responsible for its ROS scavenging activity and DNA damage prevention ability. PMID:24103782

  8. Long term effects of periconceptional multivitamin supplements for prevention of neural tube defects: a seven to 10 year follow up.

    PubMed Central

    Holmes-Siedle, M; Dennis, J; Lindenbaum, R H; Galliard, A

    1992-01-01

    Periconceptional supplementation with Pregnavite Forte F was offered to women who presented consecutively to the Oxford genetic counselling service in the early 1980s who had previously had one or more pregnancies complicated by a neural tube defect. The first 100 children born alive to these women are the subject of this study. Birth weight, gestation, and congenital abnormalities were recorded. At age 2-5 years all 96 children remaining in the United Kingdom were assessed clinically and developmentally and behavioural information was obtained by questionnaire. At age 7-10 years, follow up of 91 children by telephone and postal questionnaire yielded further information about growth, general health, vision, hearing, and educational and behavioural status. Entry criteria excluded single mothers but the social class distribution of the sample was otherwise representative of the Oxfordshire population. There were no recurrences of neural tube defects. One child had radiological evidence of spina bifida occulta affecting only the fifth lumbar vertebra. One had an autosomal recessive disorder. Eight had random minor congenital anomalies. Birth weight for gestational age was significantly greater than for the local population and at age 7-10 years the girls were considerably taller than expected. Health, auditory, visual, and developmental status were no different from the general population. None of the children had special educational needs. None showed a major behaviour disorder but worries, fussiness, and fearfulness were highly significantly over represented. PMID:1489221

  9. [Prevention and control of air pollution needs to strengthen further study on health damage caused by air pollution].

    PubMed

    Wu, T C

    2016-08-01

    Heath issues caused by air pollution such as particulate matter (PM) are much concerned and focused among air, water and soil pollutions because human breathe air for whole life span. Present comments will review physical and chemical characteristics of PM2.5 and PM10; Dose-response associations of PM10, PM2.5 and their components with mortality and risk of cardiopulmonary diseases, early health damages such as the decrease of lung functions and heart rate variability, DNA damage; And the roles of genetic variations and epigenetic changes in lung functions and heart rate variability, DNA damage related to PMs and their components. This comments list some limitations and perspectives about the associations of air pollution with health. PMID:27539517

  10. Antioxidant Formulae, Shengmai San, and LingGuiZhuGanTang, Prevent MPTP Induced Brain Dysfunction and Oxidative Damage in Mice

    PubMed Central

    Giridharan, Vijayasree Vayalanellore; Thandavarayan, Rajarajan Amirthalingam; Konishi, Tetsuya

    2015-01-01

    The present study was designed to evaluate the preventive effect of antioxidative traditional oriental medicine formulae, Shengmai San (SMS) and LingGuiZhuGanTang (LGZGT), against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (i.p 30 mg·kg−1 for 5 consecutive days) induced neurotoxicity. In in vitro antioxidant assays measured with Trolox and butyl hydroxyl toluene as reference antioxidant revealed that SMS has higher scavenging potential against hydroxyl radical than superoxide anion radical, but LGZGT was the reverse. The neuroprotective effect of SMS and LGZGT against MPTP was evaluated in mice by behavioral, biochemical, and immunohistochemical studies. In the behavioral study, both SMS and LGZGT significantly reversed the locomotive impairment induced by MPTP. Simultaneously, both formulae significantly prevented the MPTP induced dopaminergic neuron loss assessed by tyrosine hydroxylase in the midbrain. Both SMS and LGZGT significantly attenuated the elevated lipid peroxidation and protein carbonyls levels by MPTP. The DNA damage induced by MPTP was also prevented by both formulae. Although a little difference in the protective functions was observed between the two formulae, such as in DNA damage and behavioral studies, the results indicate that both SMS and LGZGT with antioxidant property act as a good candidate applicable for the antioxidant based complementary therapies of neurodegenerative diseases. PMID:26612995

  11. Prevention of DNA damage by L-carnitine induced by metabolites accumulated in maple syrup urine disease in human peripheral leukocytes in vitro.

    PubMed

    Mescka, Caroline Paula; Wayhs, Carlos Alberto Yasin; Guerreiro, Gilian; Manfredini, Vanusa; Dutra-Filho, Carlos Severo; Vargas, Carmen Regla

    2014-09-15

    Maple syrup urine disease (MSUD) is an inherited aminoacidopathy caused by a deficiency in branched-chain α-keto acid dehydrogenase complex activity that leads to the accumulation of the branched-chain amino acids (BCAAs) leucine (Leu), isoleucine, and valine and their respective α-keto-acids, α-ketoisocaproic acid (KIC), α keto-β-methylvaleric acid, and α-ketoisovaleric acid. The major clinical features presented by MSUD patients include ketoacidosis, failure to thrive, poor feeding, apnea, ataxia, seizures, coma, psychomotor delay, and mental retardation; however, the pathophysiology of this disease is poorly understood. MSUD treatment consists of a low protein diet supplemented with a mixture containing micronutrients and essential amino acids but excluding BCAAs. Studies have shown that oxidative stress may be involved in the neuropathology of MSUD, with the existence of lipid and protein oxidative damage in affected patients. In recent years, studies have demonstrated the antioxidant role of L-carnitine (L-Car), which plays a central function in cellular energy metabolism and for which MSUD patients have a deficiency. In this work, we investigated the in vitro effect of Leu and KIC in the presence or absence of L-Car on DNA damage in peripheral whole blood leukocytes using the alkaline comet assay with silver staining and visual scoring. Leu and KIC resulted in a DNA damage index that was significantly higher than that of the control group, and L-Car was able to significantly prevent this damage, mainly that due to KIC. PMID:25046137

  12. Loss of Nek11 Prevents G2/M Arrest and Promotes Cell Death in HCT116 Colorectal Cancer Cells Exposed to Therapeutic DNA Damaging Agents

    PubMed Central

    Sabir, Sarah R.; Sahota, Navdeep K.; Jones, George D. D.; Fry, Andrew M.

    2015-01-01

    The Nek11 kinase is a potential mediator of the DNA damage response whose expression is upregulated in early stage colorectal cancers (CRCs). Here, using RNAi-mediated depletion, we examined the role of Nek11 in HCT116 WT and p53-null CRC cells exposed to ionizing radiation (IR) or the chemotherapeutic drug, irinotecan. We demonstrate that depletion of Nek11 prevents the G2/M arrest induced by these genotoxic agents and promotes p53-dependent apoptosis both in the presence and absence of DNA damage. Interestingly, Nek11 depletion also led to long-term loss of cell viability that was independent of p53 and exacerbated following IR exposure. CRC cells express four splice variants of Nek11 (L/S/C/D). These are predominantly cytoplasmic, but undergo nucleocytoplasmic shuttling mediated through adjacent nuclear import and export signals in the C-terminal non-catalytic domain. In HCT116 cells, Nek11S in particular has an important role in the DNA damage response. These data provide strong evidence that Nek11 contributes to the response of CRC cells to genotoxic agents and is essential for survival either with or without exposure to DNA damage. PMID:26501353

  13. [The concept of loss of chance: A major evolution in the definition of damage or how to prevent litigation for loss of chance?].

    PubMed

    Nguyen, T-D

    2016-07-01

    The concept of medical error in responsibility litigation was based until the past last years on a necessary direct and definite causal link between fault and injury. In France, since the 1960s and increasingly during the last decade, the idea of loss of chance arose, considered as a new and genuine prejudice (practically, a fixable damage); it became the subject of several legal precedents from the Cour de cassation and the Conseil d'État. Thus, plaintiffs may currently demand a compensation for a loss of chance even though a doubt exists on the causal link between the fault and the observed damage. The most frequent litigation circumstances implying a loss of chance are lack of information, lack or delay in diagnosis, delay in action, and default in medical assessment. Based on practical cases, the author presents the most propitious situations where litigation for loss of chance may occur and discusses possible preventive measures. PMID:27342945

  14. Periodic health examination, 1994 update: 3. Primary and secondary prevention of neural tube defects. Canadian Task Force on the Periodic Health Examination.

    PubMed Central

    1994-01-01

    OBJECTIVE: To make recommendations on nutritional interventions and screening manoeuvres to prevent the birth of infants with neural tube defects (NTDs). OPTIONS: Folic acid consumption through diet or supplementation in women at low risk and at high risk of having a fetus with an NTD, and maternal serum alpha-fetoprotein (MSAFP) screening in low-risk pregnancies. OUTCOMES: A reduction in the incidence rate of NTDs and potentially harmful effects of false-positive results of screening tests (i.e., abortion of a normal fetus). EVIDENCE: A MEDLINE search with the use of medical subject headings "neural tube defects," "prenatal diagnosis" and "prevention and control" identified 103 original articles published between January 1979 and March 1993. Two reviewers extracted the data by applying the rules of evidence developed by the Canadian Task Force on the Periodic Health Examination. VALUES: The task force's evidence-based methods and values were used; high value was placed on prevention of NTDs and on limitation of the harmful effects of a pregnancy involving a fetus with an NTD. BENEFITS, HARMS AND COSTS: Evidence suggests that folic acid supplementation can decrease the incidence rate of NTDs in low-risk pregnancies by 40% to 60% with no adverse effects. MSAFP screening between the 16th and 18th weeks of gestation can reach a sensitivity of 83% and a specificity of 98% when it is used as part of an organized program. The effect of screening on the incidence rate of NTDs depends on whether affected fetuses are aborted. RECOMMENDATIONS: All women of childbearing age should be advised to increase their consumption of folic acid through diet or supplementation to 0.4 mg/d beginning 1 month before pregnancy and ending at the start of the second trimester. MSAFP screening is recommended in low-risk pregnancies only when it is part of a screening program that includes access to all necessary diagnostic services. High-risk women should be referred to genetic counselling

  15. MDM2-regulated degradation of HIPK2 prevents p53Ser46 phosphorylation and DNA damage-induced apoptosis.

    PubMed

    Rinaldo, Cinzia; Prodosmo, Andrea; Mancini, Francesca; Iacovelli, Stefano; Sacchi, Ada; Moretti, Fabiola; Soddu, Silvia

    2007-03-01

    In response to DNA damage, p53 induces either cell-cycle arrest or apoptosis by differential transcription of several target genes and through transcription-independent apoptotic functions. p53 phosphorylation at Ser46 by HIPK2 is one determinant of the outcome because it takes place only upon severe, nonrepairable DNA damage that irreversibly drives cells to apoptosis. Here, we show that p53 represses its proapoptotic activator HIPK2 via MDM2-mediated degradation, whereas a degradation-resistant HIPK2 mutant has increased apoptotic activity. Upon cytostatic, nonsevere DNA damage, inhibition of HIPK2 degradation is sufficient to induce p53Ser46 phosphorylation and apoptosis, converting growth-arresting stimuli to apoptotic ones. These findings establish HIPK2 as an MDM2 target and support a model in which, upon nonsevere DNA damage, p53 represses its own phosphorylation at Ser46 due to HIPK2 degradation, supporting the notion that the cell-cycle-arresting functions of p53 include active inhibition of the apoptotic ones. PMID:17349959

  16. Protein formulation and lyophilization cycle design: prevention of damage due to freeze-concentration induced phase separation.

    PubMed

    Heller, M C; Carpenter, J F; Randolph, T W

    1999-04-20

    Hemoglobin has been previously shown to unfold during freeze drying when lyophilized from formulations that undergo freeze-concentration induced phase separation (Heller et al. 1997. Biotechnol Prog 13:590-596). In this report, we show that such damage may be avoided using kinetic strategies to arrest the phase separation. By rapidly cooling samples during liquid nitrogen spray-freeze drying, the time that the formulation spends in temperature regimes (ca. -3 to -23 degrees C) in which phase separation is both thermodynamically favorable and kinetically realizable is minimized. Increased protein damage with decreasing cooling rates and/or longer annealing periods at -7 degrees C is observed by FTIR spectroscopy. Phase separation and concomitant protein damage may also be avoided by addition of mannitol at concentrations sufficient to cause crystallization. Mannitol crystals segregate the freeze concentrated solution into microscopic domains that block propagation and nucleation of phase separating events. Addition of noncrystallizing sugars, such as sucrose and trehalose, or nonionic surfactants, such as Tween 80 and Triton X-100, has little protective effect against phase separation induced damage during freezing drying. PMID:10099593

  17. Failure of the inhibition of rat gastric mucosal 5-lipoxygenase by novel acetohydroxamic acids to prevent ethanol-induced damage.

    PubMed

    Boughton-Smith, N K; Whittle, B J

    1988-09-01

    1. The role of leukotriene B4 (LTB4) and LTC4 as mediators of gastric mucosal damage following ethanol challenge in vivo has been investigated using two selective 5-lipoxygenase inhibitors, BW A4C and BW A137C. 2. Oral administration of ethanol to rats in vivo, induced macroscopic damage to the gastric mucosa and markedly increased the formation of the 5-lipoxygenase products, LTB4 and LTC4, from the mucosa ex vivo. 3. Pretreatment with the acetohydroxamic acids BW A4C and BW A137C (5-50 mg kg-1 p.o.) dose-dependently reduced ethanol-stimulated LTB4 and LTC4 formation by the gastric mucosa, with an ID50 of approximately 5 mg kg-1 p.o. 4. A single oral dose of BW A4C (20 mg kg-1) induced near-maximal inhibition of mucosal LTB4 formation within 30 min, which was well maintained for 5 h, whereas BW A137C (20 mg kg-1 p.o.) induced maximal inhibition between 30 and 60 min after administration, which then diminished over the subsequent 5 h. 5. The mucosal formation of the cyclo-oxygenase product, 6-keto-prostaglandin F1 alpha, which was unaltered following ethanol challenge, was not inhibited by the acetohydroxamic acids. Likewise, the small increase in mucosal thromboxane B2 formation following challenge was not inhibited by BW A4C. 6. Neither BW A4C nor BW A137C, at doses that almost completely inhibited the mucosal synthesis of LTB4 or LTC4, reduced the macroscopic gastric mucosal damage induced by ethanol. 7. Pretreatment with the lipoxygenase inhibitor BW 755C (5-50 mg kg-1 p.o.) did reduce mucosal damage, but there was a dissociation between the degree of protection and the inhibition of leukotriene biosynthesis. 8. Oral administration of high doses of either BW A4C or BW A137C (300mgkg-1) did not induce macroscopic gastric damage over a 3 h period. 9. These findings suggest that the leukotrienes, LTB4 and LTC4 are not the primary mediators of ethanol-induced acute mucosal damage, but do not exclude their role in more chronic gastric damage and inflammation. PMID

  18. Formate supplementation enhances folate-dependent nucleotide biosynthesis and prevents spina bifida in a mouse model of folic acid-resistant neural tube defects.

    PubMed

    Sudiwala, Sonia; De Castro, Sandra C P; Leung, Kit-Yi; Brosnan, John T; Brosnan, Margaret E; Mills, Kevin; Copp, Andrew J; Greene, Nicholas D E

    2016-07-01

    The curly tail mouse provides a model for neural tube defects (spina bifida and exencephaly) that are resistant to prevention by folic acid. The major ct gene, responsible for spina bifida, corresponds to a hypomorphic allele of grainyhead-like 3 (Grhl3) but the frequency of NTDs is strongly influenced by modifiers in the genetic background. Moreover, exencephaly in the curly tail strain is not prevented by reinstatement of Grhl3 expression. In the current study we found that expression of Mthfd1L, encoding a key component of mitochondrial folate one-carbon metabolism (FOCM), is significantly reduced in ct/ct embryos compared to a partially congenic wild-type strain. This expression change is not attributable to regulation by Grhl3 or the genetic background at the Mthfd1L locus. Mitochondrial FOCM provides one-carbon units as formate for FOCM reactions in the cytosol. We found that maternal supplementation with formate prevented NTDs in curly tail embryos and also resulted in increased litter size. Analysis of the folate profile of neurulation-stage embryos showed that formate supplementation resulted in an increased proportion of formyl-THF and THF but a reduction in proportion of 5-methyl THF. In contrast, THF decreased and 5-methyl THF was relatively more abundant in the liver of supplemented dams than in controls. In embryos cultured through the period of spinal neurulation, incorporation of labelled thymidine and adenine into genomic DNA was suppressed by supplemental formate, suggesting that de novo folate-dependent biosynthesis of nucleotides (thymidylate and purines) was enhanced. We hypothesise that reduced Mthfd1L expression may contribute to susceptibility to NTDs in the curly tail strain and that formate acts as a one-carbon donor to prevent NTDs. PMID:26924399

  19. Disruption of the ECM33 gene in Candida albicans prevents biofilm formation, engineered human oral mucosa tissue damage and gingival cell necrosis/apoptosis.

    PubMed

    Rouabhia, Mahmoud; Semlali, Abdelhabib; Chandra, Jyotsna; Mukherjee, Pranab; Chmielewski, Witold; Ghannoum, Mahmoud A

    2012-01-01

    In this study we demonstrated that ΔCaecm33 double mutant showed reduced biofilm formation and causes less damage to gingival mucosa tissues. This was confirmed by the reduced level of necrotic cells and Bax/Bcl2 gene expression as apoptotic markers. In contrast, parental and Caecm33 mutant strains decreased basement membrane protein production (laminin 5 and type IV collagen). We thus propose that ECM33 gene/protein represents a novel target for the prevention and treatment of infections caused by Candida. PMID:22665950

  20. Cell-Surface and Secreted Isoforms of CSF-1 Exert Opposing Roles in Macrophage-Mediated Neural Damage in Cx32-Deficient Mice

    PubMed Central

    Basu, Ranu; Stanley, E. Richard

    2016-01-01

    Previous studies in myelin-mutant mouse models of the inherited and incurable nerve disorder, Charcot-Marie-Tooth (CMT) neuropathy, have demonstrated that low-grade secondary inflammation implicating phagocytosing macrophages amplifies demyelination, Schwann cell dedifferentiation and perturbation of axons. The cytokine colony stimulating factor-1 (CSF-1) acts as an important regulator of these macrophage-related disease mechanisms, as genetic and pharmacologic approaches to block the CSF-1/CSF-1R signaling result in a significant alleviation of pathological alterations in mutant peripheral nerves. In mouse models of CMT1A and CMT1X, as well as in human biopsies, CSF-1 is predominantly expressed by endoneurial fibroblasts, which are closely associated with macrophages, suggesting local stimulatory mechanisms. Here we investigated the impact of cell-surface and secreted isoforms of CSF-1 on macrophage-related disease in connexin32-deficient (Cx32def) mice, a mouse model of CMT1X. Our present observations suggest that the secreted proteoglycan isoform (spCSF-1) is predominantly expressed by fibroblasts, whereas the membrane-spanning cell-surface isoform (csCSF-1) is expressed by macrophages. Using crossbreeding approaches to selectively restore or overexpress distinct isoforms in CSF-1-deficient (osteopetrotic) Cx32def mice, we demonstrate that both isoforms equally regulate macrophage numbers dose-dependently. However, spCSF-1 mediates macrophage activation and macrophage-related neural damage, whereas csCSF-1 inhibits macrophage activation and attenuates neuropathy. These results further corroborate the important role of secondary inflammation in mouse models of CMT1 and might identify specific targets for therapeutic approaches to modulate innate immune reactions. SIGNIFICANCE STATEMENT Mouse models of Charcot-Marie-Tooth neuropathy have indicated that low-grade secondary inflammation involving phagocytosing macrophages amplifies demyelination, Schwann cell

  1. Protection from palmitate-induced mitochondrial DNA damage prevents from mitochondrial oxidative stress, mitochondrial dysfunction, apoptosis, and impaired insulin signaling in rat L6 skeletal muscle cells.

    PubMed

    Yuzefovych, Larysa V; Solodushko, Viktoriya A; Wilson, Glenn L; Rachek, Lyudmila I

    2012-01-01

    Saturated free fatty acids have been implicated in the increase of oxidative stress, mitochondrial dysfunction, apoptosis, and insulin resistance seen in type 2 diabetes. The purpose of this study was to determine whether palmitate-induced mitochondrial DNA (mtDNA) damage contributed to increased oxidative stress, mitochondrial dysfunction, apoptosis, impaired insulin signaling, and reduced glucose uptake in skeletal muscle cells. Adenoviral vectors were used to deliver the DNA repair enzyme human 8-oxoguanine DNA glycosylase/(apurinic/apyrimidinic) lyase (hOGG1) to mitochondria in L6 myotubes. After palmitate exposure, we evaluated mtDNA damage, mitochondrial function, production of mitochondrial reactive oxygen species, apoptosis, insulin signaling pathways, and glucose uptake. Protection of mtDNA from palmitate-induced damage by overexpression of hOGG1 targeted to mitochondria significantly diminished palmitate-induced mitochondrial superoxide production, restored the decline in ATP levels, reduced activation of c-Jun N-terminal kinase (JNK) kinase, prevented cells from entering apoptosis, increased insulin-stimulated phosphorylation of serine-threonine kinase (Akt) (Ser473) and tyrosine phosphorylation of insulin receptor substrate-1, and thereby enhanced glucose transporter 4 translocation to plasma membrane, and restored insulin signaling. Addition of a specific inhibitor of JNK mimicked the effect of mitochondrial overexpression of hOGG1 and partially restored insulin sensitivity, thus confirming the involvement of mtDNA damage and subsequent increase of oxidative stress and JNK activation in insulin signaling in L6 myotubes. Our results are the first to report that mtDNA damage is the proximal cause in palmitate-induced mitochondrial dysfunction and impaired insulin signaling and provide strong evidence that targeting DNA repair enzymes into mitochondria in skeletal muscles could be a potential therapeutic treatment for insulin resistance. PMID:22128025

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

    PubMed Central

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

    2013-01-01

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

  3. Polyphenols isolated from Broussonetia kazinoki prevent cytokine-induced β-cell damage and the development of type 1 diabetes

    PubMed Central

    Bae, Ui-Jin; Jang, Hyun-Young; Lim, Jung Min; Hua, Li; Ryu, Jae-Ha; Park, Byung-Hyun

    2015-01-01

    The axis of nuclear factor κB (NF-κB)-inducible NO synthase (iNOS)-nitric oxide plays a key role in cytokine- and streptozotocin-mediated pancreatic β-cell damage. In this study, we investigated the effects of kazinol C and isokazinol D isolated from Broussonetia kazinoki on the β-cell viability and function. RINm5F cells and primary islets were used for in vitro and ex vivo cytokine toxicity experiments, respectively. For type 1 diabetes induction, mice were injected with multiple low-dose streptozotocin (MLDS). Cytokine-induced toxicity was completely abolished in both RINm5F cells and islets that were pretreated with either kazinol C or isokazinol D. Both kazinols inhibited the NF-κB signaling pathway, thereby inhibiting cytokine-mediated iNOS induction, nitric oxide production, apoptotic cell death and defects in insulin secretion. Moreover, the occurrence of diabetes in MLDS-treated mice was efficiently attenuated in kazinol-pretreated mice. Immunohistochemical analysis revealed that the numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic cells and nuclear p65-positive cells were significantly decreased in kazinol-pretreated mice. Our results suggest that kazinol C and isokazinol D block the NF-κB pathway, thus reducing the extent of β-cell damage. Therefore, kazinol C and isokazinol D may have therapeutic value in delaying pancreatic β-cell damage in type 1 diabetes. PMID:25907110

  4. Vitamin C Compound Mixtures Prevent Ozone-Induced Oxidative Damage in Human Keratinocytes as Initial Assessment of Pollution Protection

    PubMed Central

    Valacchi, Giuseppe; Sticozzi, Claudia; Belmonte, Giuseppe; Cervellati, Franco; Demaude, Julien; Chen, Nannan; Krol, Yevgeniy; Oresajo, Christian

    2015-01-01

    Introduction One of the main functions of cutaneous tissues is to protect our body from the outdoor insults. Ozone (O3) is among the most toxic stressors to which we are continuously exposed and because of its critical location, the skin is one of the most susceptible tissues to the oxidative damaging effect of O3. O3 is not able to penetrate the skin, and although it is not a radical per se, the damage is mainly a consequence of its ability to induce oxidative stress via the formation of lipid peroxidation products. Aim of Study In this study we investigated the protective effect of defined “antioxidant” mixtures against O3 induced oxidative stress damage in human keratinocytes and understand their underlying mechanism of action. Results Results showed that the mixtures tested were able to protect human keratinocytes from O3-induced cytotoxicity, inhibition of cellular proliferation, decrease the formation of HNE protein adducts, ROS, and carbonyls levels. Furthermore, we have observed the decreased activation of the redox sensitive transcription factor NF-kB, which is involved in transcribing pro-inflammatory cytokines and therefore constitutes one of the main players associated with O3 induced skin inflammation. Cells exposed to O3 demonstrated a dose dependent increase in p65 subunit nuclear expression as a marker of NF-kB activation, while pre-treatment with the mixtures abolished NF-kB nuclear translocation. In addition, a significant activation of Nrf2 in keratinocytes treated with the mixtures was also observed. Conclusion Overall this study was able to demonstrate a protective effect of the tested compounds versus O3-induced cell damage in human keratinocytes. Pre-treatment with the tested compounds significantly reduced the oxidative damage induced by O3 exposure and this protective effect was correlated to the abolishment of NF-kB nuclear translocation, as well as activation of Nrf2 nuclear translocation activating the downstream defence enzymes

  5. Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity

    PubMed Central

    Guescini, Michele; Calcabrini, Cinzia; Vallorani, Luciana; Diaz, Anna Rita; Canonico, Barbara; Luchetti, Francesca; Papa, Stefano; Battistelli, Michela; Falcieri, Elisabetta; Romanello, Vanina; Sandri, Marco; Stocchi, Vilberto; Ciacci, Caterina

    2016-01-01

    Creatine (Cr) is a nutritional supplement promoting a number of health benefits. Indeed Cr has been shown to be beneficial in disease-induced muscle atrophy, improve rehabilitation, and afford mild antioxidant activity. The beneficial effects are likely to derive from pleiotropic interactions. In accord with this notion, we previously demonstrated that multiple pleiotropic effects, including preservation of mitochondrial damage, account for the capacity of Cr to prevent the differentiation arrest caused by oxidative stress in C2C12 myoblasts. Given the importance of mitochondria in supporting the myogenic process, here we further explored the protective effects of Cr on the structure, function, and networking of these organelles in C2C12 cells differentiating under oxidative stressing conditions; the effects on the energy sensor AMPK, on PGC-1α, which is involved in mitochondrial biogenesis and its downstream effector Tfam were also investigated. Our results indicate that damage to mitochondria is crucial in the differentiation imbalance caused by oxidative stress and that the Cr-prevention of these injuries is invariably associated with the recovery of the normal myogenic capacity. We also found that Cr activates AMPK and induces an upregulation of PGC-1α expression, two events which are likely to contribute to the protection of mitochondrial quality and function. PMID:27610211

  6. Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity.

    PubMed

    Barbieri, Elena; Guescini, Michele; Calcabrini, Cinzia; Vallorani, Luciana; Diaz, Anna Rita; Fimognari, Carmela; Canonico, Barbara; Luchetti, Francesca; Papa, Stefano; Battistelli, Michela; Falcieri, Elisabetta; Romanello, Vanina; Sandri, Marco; Stocchi, Vilberto; Ciacci, Caterina; Sestili, Piero

    2016-01-01

    Creatine (Cr) is a nutritional supplement promoting a number of health benefits. Indeed Cr has been shown to be beneficial in disease-induced muscle atrophy, improve rehabilitation, and afford mild antioxidant activity. The beneficial effects are likely to derive from pleiotropic interactions. In accord with this notion, we previously demonstrated that multiple pleiotropic effects, including preservation of mitochondrial damage, account for the capacity of Cr to prevent the differentiation arrest caused by oxidative stress in C2C12 myoblasts. Given the importance of mitochondria in supporting the myogenic process, here we further explored the protective effects of Cr on the structure, function, and networking of these organelles in C2C12 cells differentiating under oxidative stressing conditions; the effects on the energy sensor AMPK, on PGC-1α, which is involved in mitochondrial biogenesis and its downstream effector Tfam were also investigated. Our results indicate that damage to mitochondria is crucial in the differentiation imbalance caused by oxidative stress and that the Cr-prevention of these injuries is invariably associated with the recovery of the normal myogenic capacity. We also found that Cr activates AMPK and induces an upregulation of PGC-1α expression, two events which are likely to contribute to the protection of mitochondrial quality and function. PMID:27610211

  7. Protein kinase C α inhibition prevents peritoneal damage in a mouse model of chronic peritoneal exposure to high-glucose dialysate.

    PubMed

    Wang, Le; Balzer, Michael S; Rong, Song; Menne, Jan; von Vietinghoff, Sibylle; Dong, Lei; Gueler, Faikah; Jang, Mi-Sun; Xu, Gang; Timrott, Kai; Tkachuk, Sergey; Hiss, Marcus; Haller, Hermann; Shushakova, Nelli

    2016-06-01

    Chronic exposure to commercial glucose-based peritoneal dialysis fluids during peritoneal dialysis induces peritoneal membrane damage leading to ultrafiltration failure. In this study the role of protein kinase C (PKC) α in peritoneal membrane damage was investigated in a mouse model of peritoneal dialysis. We used 2 different approaches: blockade of biological activity of PKCα by intraperitoneal application of the conventional PKC inhibitor Go6976 in C57BL/6 wild-type mice and PKCα-deficient mice on a 129/Sv genetic background. Daily administration of peritoneal dialysis fluid for 5 weeks induced peritoneal upregulation and activation of PKCα accompanied by epithelial-to-mesenchymal transition of peritoneal mesothelial cells, peritoneal membrane fibrosis, neoangiogenesis, and macrophage and T cell infiltration, paralleled by reduced ultrafiltration capacity. All pathological changes were prevented by PKCα blockade or deficiency. Moreover, treatment with Go6976 and PKCα deficiency resulted in strong reduction of proinflammatory, profibrotic, and proangiogenic mediators. In cell culture experiments, both treatment with Go6976 and PKCα deficiency prevented peritoneal dialysis fluid-induced release of MCP-1 from mouse peritoneal mesothelial cells and ameliorated transforming growth factor-β1-induced epithelial-to-mesenchymal transition and peritoneal dialysis fluid-induced MCP-1 release in human peritoneal mesothelial cells. Thus, PKCα plays a crucial role in the pathophysiology of peritoneal membrane dysfunction induced by peritoneal dialysis fluids, and we suggest that its therapeutic inhibition might be a valuable treatment option for peritoneal dialysis patients. PMID:27142955

  8. A Potential Nanofiber Membrane Device for Filling Surgical Residual Cavity to Prevent Glioma Recurrence and Improve Local Neural Tissue Reconstruction

    PubMed Central

    Huang, Daoxiang; Lin, Chao; Wen, Xuejun; Gu, Shuying; Zhao, Peng

    2016-01-01

    This study aims to develop a novel device with nanofiber membrane capable of sustained release of temozolomide (TMZ) and neuron growth factor (NGF). An improved bio-availability of TMZ and NGF in surroundings proximal to the device was expected to be attained for a prolonged period of time. The device was developed by integrating TMZ-doped polycaprolactone (PCL) nanofiber (TP) membrane and NGF-coated PCL (NGFP) membrane using sodium alginate hydrogel. TP was prepared by direct electrospinning of TMZ/PCL. NGFP membrane was developed by layer-by-layer assembling technology. The incorporation of TMZ-doped nanofiber and NGFP nanofiber in the device was confirmed by scanning electron microscopy. The number of NGF layer in NGF-coated PCL membrane could be readily measured with energy spectrum analysis. The in vitro release study showed that TP-NGFP-TP membrane could efficiently liberate TMZ to inhibit the growth of C6 glioma cells, and sufficient NGF to induce the differentiation of PC12 neuron cells over four weeks. Such TP-NGFP-TP membrane device can be employed as a tampon to fill up surgical residual cavity and afford residual glioma removal, structural support, hemostasis, and local neural tissue reconstruction in the surgical treatment of glioma. The study opens a horizon to develop multifunctional biomaterial device for maximized glioma treatment efficacy. PMID:27548322

  9. The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors.

    PubMed

    Schwamborn, Jens C; Berezikov, Eugene; Knoblich, Juergen A

    2009-03-01

    In the mouse neocortex, neural progenitor cells generate both differentiating neurons and daughter cells that maintain progenitor fate. Here, we show that the TRIM-NHL protein TRIM32 regulates protein degradation and microRNA activity to control the balance between those two daughter cell types. In both horizontally and vertically dividing progenitors, TRIM32 becomes polarized in mitosis and is concentrated in one of the two daughter cells. TRIM32 overexpression induces neuronal differentiation while inhibition of TRIM32 causes both daughter cells to retain progenitor cell fate. TRIM32 ubiquitinates and degrades the transcription factor c-Myc but also binds Argonaute-1 and thereby increases the activity of specific microRNAs. We show that Let-7 is one of the TRIM32 targets and is required and sufficient for neuronal differentiation. TRIM32 is the mouse ortholog of Drosophila Brat and Mei-P26 and might be part of a protein family that regulates the balance between differentiation and proliferation in stem cell lineages. PMID:19269368

  10. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region

    PubMed Central

    Wang, Haochen; De Steur, Hans; Chen, Gong; Zhang, Xiaotian; Pei, Lijun; Gellynck, Xavier; Zheng, Xiaoying

    2016-01-01

    Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207–0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China. PMID:27005659

  11. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region.

    PubMed

    Wang, Haochen; De Steur, Hans; Chen, Gong; Zhang, Xiaotian; Pei, Lijun; Gellynck, Xavier; Zheng, Xiaoying

    2016-03-01

    Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207-0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China. PMID:27005659

  12. A Potential Nanofiber Membrane Device for Filling Surgical Residual Cavity to Prevent Glioma Recurrence and Improve Local Neural Tissue Reconstruction.

    PubMed

    Huang, Daoxiang; Lin, Chao; Wen, Xuejun; Gu, Shuying; Zhao, Peng

    2016-01-01

    This study aims to develop a novel device with nanofiber membrane capable of sustained release of temozolomide (TMZ) and neuron growth factor (NGF). An improved bio-availability of TMZ and NGF in surroundings proximal to the device was expected to be attained for a prolonged period of time. The device was developed by integrating TMZ-doped polycaprolactone (PCL) nanofiber (TP) membrane and NGF-coated PCL (NGFP) membrane using sodium alginate hydrogel. TP was prepared by direct electrospinning of TMZ/PCL. NGFP membrane was developed by layer-by-layer assembling technology. The incorporation of TMZ-doped nanofiber and NGFP nanofiber in the device was confirmed by scanning electron microscopy. The number of NGF layer in NGF-coated PCL membrane could be readily measured with energy spectrum analysis. The in vitro release study showed that TP-NGFP-TP membrane could efficiently liberate TMZ to inhibit the growth of C6 glioma cells, and sufficient NGF to induce the differentiation of PC12 neuron cells over four weeks. Such TP-NGFP-TP membrane device can be employed as a tampon to fill up surgical residual cavity and afford residual glioma removal, structural support, hemostasis, and local neural tissue reconstruction in the surgical treatment of glioma. The study opens a horizon to develop multifunctional biomaterial device for maximized glioma treatment efficacy. PMID:27548322

  13. Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex.

    PubMed

    Zhu, Ben-Zhan; Mao, Li; Fan, Rui-Mei; Zhu, Jun-Ge; Zhang, Ying-Nan; Wang, Jing; Kalyanaraman, Balaraman; Frei, Balz

    2011-01-14

    Ergothioneine (2-mercaptohistidine trimethylbetaine) is a naturally occurring amino acid analogue found in up to millimolar concentrations in several tissues and biological fluids. However, the biological functions of ergothioneine remain incompletely understood. In this study, we investigated the role of ergothioneine in copper-induced oxidative damage to DNA and protein, using two copper-containing systems: Cu(II) with ascorbate and Cu(II) with H(2)O(2) [0.1 mM Cu(II), 1 mM ascorbate, and 1 mM H(2)O(2)]. Oxidative damage to DNA and bovine serum albumin was measured as strand breakage and protein carbonyl formation, respectively. Ergothioneine (0.1-1.0 mM) provided strong, dose-dependent protection against oxidation of DNA and protein in both copper-containing systems. In contrast, only limited protection was observed with the purported hydroxyl radical scavengers, dimethyl sulfoxide and mannitol, even at concentrations as high as 100 mM. Ergothioneine also significantly inhibited copper-catalyzed oxidation of ascorbate and competed effectively with histidine and 1,10-phenanthroline for binding of cuprous copper, but not cupric copper, as demonstrated by UV-visible and low-temperature electron spin resonance techniques. We conclude that ergothioneine is a potent, natural sulfur-containing antioxidant that prevents copper-dependent oxidative damage to biological macromolecules by forming a redox-inactive ergothioneine-copper complex. PMID:21047085

  14. Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy

    PubMed Central

    Dungl, Daniela A.; Maginn, Elaina N.; Stronach, Euan A.

    2015-01-01

    Platinum-based chemotherapy is the cornerstone of ovarian cancer treatment, and its efficacy is dependent on the generation of DNA damage, with subsequent induction of apoptosis. Inappropriate or aberrant activation of the DNA damage response network is associated with resistance to platinum, and defects in DNA repair pathways play critical roles in determining patient response to chemotherapy. In ovarian cancer, tumor cell defects in homologous recombination – a repair pathway activated in response to double-strand DNA breaks (DSB) – are most commonly associated with platinum-sensitive disease. However, despite initial sensitivity, the emergence of resistance is frequent. Here, we review strategies for directly interfering with DNA repair pathways, with particular focus on direct inhibition of non-homologous end joining (NHEJ), another DSB repair pathway. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a core component of NHEJ and it has shown considerable promise as a chemosensitization target in numerous cancer types, including ovarian cancer where it functions to promote platinum-induced survival signaling, via AKT activation. The development of pharmacological inhibitors of DNA-PKcs is on-going, and clinic-ready agents offer real hope to patients with chemoresistant disease. PMID:26579492

  15. Dexamethasone prevents vascular damage in early-stage non-freezing cold injury of the sciatic nerve

    PubMed Central

    Li, Hao; Zhang, Lei; Xu, Min

    2016-01-01

    Non-freezing cold injury is a prevalent cause of peripheral nerve damage, but its pathogenic mechanism is poorly understood, and treatment remains inadequate. Glucocorticoids have anti-inflammatory and lipid peroxidation-inhibiting properties. We therefore examined whether dexamethasone, a synthetic glucocorticoid compound, would alleviate early-stage non-freezing cold injury of the sciatic nerve. We established Wistar rat models of non-freezing cold injury by exposing the left sciatic nerve to cold (3–5°C) for 2 hours, then administered dexamethasone (3 mg/kg intraperitoneally) to half of the models. One day after injury, the concentration of Evans blue tracer in the injured sciatic nerve of rats that received dexamethasone was notably lower than that in the injured sciatic nerve of rats that did not receive dexamethasone; neither Evans blue dye nor capillary stenosis was observed in the endoneurium, but myelinated nerve fibers were markedly degenerated in the injured sciatic nerve of animals that received dexamethasone. After dexamethasone administration, however, endoneurial vasculopathy was markedly improved, although damage to the myelinated nerve fiber was not alleviated. These findings suggest that dexamethasone protects the blood-nerve barrier, but its benefit in non-freezing cold injury is limited to the vascular system. PMID:26981107

  16. Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-κB Pathways

    PubMed Central

    Kim, Sung Hwan; Lee, In Chul; Ko, Je Won; Moon, Changjong; Kim, Sung Ho; Shin, In Sik; Seo, Young Won; Kim, Hyoung Chin; Kim, Jong Choon

    2015-01-01

    This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2’-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-κB, COX-2, iNOS, TNF-α, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-κB, COX-2, iNOS, TNF-α, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-κB and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder. PMID:25767687

  17. Assessment of Free Radical Scavenging Potential and Oxidative DNA Damage Preventive Activity of Trachyspermum ammi L. (Carom) and Foeniculum vulgare Mill. (Fennel) Seed Extracts

    PubMed Central

    2014-01-01

    Oxidation of biomolecules such as carbohydrates, proteins, lipids, and nucleic acids results in generation of free radicals in an organism which is the major cause of onset of various degenerative diseases. Antioxidants scavenge these free radicals, thereby protecting the cell from damage. The present study was designed to examine the free radical scavenging potential and oxidative DNA damage preventive activity of traditionally used spices Trachyspermum ammi L. (carom) and Foeniculum vulgare Mill. (fennel). The aqueous, methanolic, and acetonic extracts of T. ammi and F. vulgare seeds were prepared using soxhlet extraction assembly and subjected to qualitative and quantitative estimation of phytochemical constituents. Free radical scavenging potential was investigated using standard methods, namely, DPPH radical scavenging assay and ferric reducing antioxidant power assay along with the protection against oxidative DNA damage. The results stated that acetonic seed extracts (AAcSE and FAcSE) of both the spices possessed comparatively high amount of total phenolics whereas methanolic seed extracts (AMSE and FMSE) were found to have highest amount of total flavonoids. At 1 mg/mL concentration, highest DPPH radical scavenging activity was shown by FMSE (96.2%), AAcSE was recorded with highest FRAP value (2270.27 ± 0.005 μmol/L), and all the seed extracts have been shown to mitigate the damage induced by Fenton reaction on calf thymus DNA. Therefore, the study suggests that T. ammi and F. vulgare seed extracts could contribute as a highly significant bioresource of antioxidants to be used in our day-to-day life and in food and pharmaceutical industry. PMID:25143939

  18. Genetic engineering of AtAOX1a in Saccharomyces cerevisiae prevents oxidative damage and maintains redox homeostasis.

    PubMed

    Vishwakarma, Abhaypratap; Dalal, Ahan; Tetali, Sarada Devi; Kirti, Pulugurtha Bharadwaja; Padmasree, Kollipara

    2016-02-01

    This study aimed to validate the physiological importance of Arabidopsis thaliana alternative oxidase 1a (AtAOX1a) in alleviating oxidative stress using Saccharomyces cerevisiae as a model organism. The AOX1a transformant (pYES2AtAOX1a) showed cyanide resistant and salicylhydroxamic acid (SHAM)-sensitive respiration, indicating functional expression of AtAOX1a in S. cerevisiae. After exposure to oxidative stress, pYES2AtAOX1a showed better survival and a decrease in reactive oxygen species (ROS) when compared to S. cerevisiae with empty vector (pYES2). Furthermore, pYES2AtAOX1a sustained growth by regulating GPX2 and/or TSA2, and cellular NAD (+)/NADH ratio. Thus, the expression of AtAOX1a in S. cerevisiae enhances its respiratory tolerance which, in turn, maintains cellular redox homeostasis and protects from oxidative damage. PMID:27239435

  19. β-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage and squamous metaplasia in ferrets

    PubMed Central

    Liu, Chun; Bronson, Roderick T.; Russell, Robert M.; Wang, Xiang-Dong

    2011-01-01

    In epidemiologic studies, high intake of β-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of β-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which β-cryptoxanthin might affect lung carcinogenesis. We evaluated the effects of β-cryptoxanthin supplementation on cigarette smoke-induced squamous metaplasia, inflammation, and changes in protein levels of pro-inflammatory cytokine [tumor necrosis factor alpha (TNFα)] and transcription factors [nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1)], as well as on smoke-induced oxidative DNA damage [8-hydroxy-2′-deoxyguanosine (8-OHdG)] in the lung tissue of ferrets. Thirty six male ferrets were assigned to cigarette smoke exposure or no exposure and to low-dose, or high-dose β-cryptoxanthin, or no dose (2 × 3 factorial design) for 3 months. β-Cryptoxanthin supplementation dose-dependently increased plasma and lung β-cryptoxanthin levels in ferrets, whereas cigarette smoke exposure lowered plasma and lung β-cryptoxanthin levels. β-Cryptoxanthin at both doses significantly decreased smoke-induced lung squamous metaplasia and inflammation. β-Cryptoxanthin also substantially reduced smoke-elevated TNFα levels in alveolar, bronchial, bronchiolar and bronchial serous/mucous gland epithelial cells and in lung macrophages. Moreover, β-cryptoxanthin decreased smoke-induced activation of NF-κB, expression of AP-1 and levels of 8-OHdG. The beneficial effects of β-cryptoxanthin were stronger for high-dose β-cryptoxanthin than for low-dose β-cryptoxanthin. Data from this study indicate that β-cryptoxanthin provides a beneficial effect against cigarette smoke-induced inflammation, oxidative DNA damage and squamous metaplasia in the lungs. PMID:21421799

  20. Oxidative damage to specific proteins in replicative and chronological-aged Saccharomyces cerevisiae: common targets and prevention by calorie restriction.

    PubMed

    Reverter-Branchat, Gemma; Cabiscol, Elisa; Tamarit, Jordi; Ros, Joaquim

    2004-07-23

    Oxidative modifications of cellular components have been described as one of the main contributions to aged phenotype. In Saccharomyces cerevisiae, two distinct life spans can be considered, replicative and chronological. The relationship between both aging models is still not clear despite suggestions that these phenomena may be related. In this work, we show that replicative and chronological-aged yeast cells are affected by an oxidative stress situation demonstrated by increased protein carbonylation when compared with young cells. The data on the identification of these oxidatively modified proteins gives clues to better understand cellular dysfunction that occurs during aging. Strikingly, although in both aging models metabolic differences are important, major targets are almost the same. Common targets include stress resistance proteins (Hsp60 and Hsp70) and enzymes involved in glucose metabolism such as enolase, glyceraldehydes-3-P dehydrogenase, fructose-1,6-biphosphate aldolase, pyruvate decarboxylase, and alcohol dehydrogenase. In both aging models, calorie restriction results in decreased damage to these proteins. In addition, chronological-aged cells grown under glucose restriction displayed lowered levels of lipid peroxidation product lipofuscin. Intracellular iron concentration is kept almost unchanged, whereas in non-restricted cells, the values increase up 4-5 times. The pro-oxidant effects of such increased iron concentration would account for the damage observed. Also, calorie-restricted cells show undamaged catalase, which clearly appears carbonylated in cells grown at a high glucose concentration. These results may explain lengthening of the viability of chronological-aged cells and could have an important role in replicative life span extension by calorie restriction. PMID:15166233

  1. β-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage, and squamous metaplasia in ferrets.

    PubMed

    Liu, Chun; Bronson, Roderick T; Russell, Robert M; Wang, Xiang-Dong

    2011-08-01

    In epidemiologic studies, high intake of β-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of β-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which β-cryptoxanthin might affect lung carcinogenesis. We evaluated the effects of β-cryptoxanthin supplementation on cigarette smoke-induced squamous metaplasia, inflammation, and changes in protein levels of proinflammatory cytokine [tumor necrosis factor alpha (TNFα)] and transcription factors [nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1)], as well as on smoke-induced oxidative DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)] in the lung tissue of ferrets. Thirty-six male ferrets were assigned to cigarette smoke exposure or no exposure and to low-dose, or high-dose β-cryptoxanthin, or no dose (2 × 3 factorial design) for 3 months. β-Cryptoxanthin supplementation dose-dependently increased plasma and lung β-cryptoxanthin levels in ferrets, whereas cigarette smoke exposure lowered plasma and lung β-cryptoxanthin levels. β-Cryptoxanthin at both doses significantly decreased smoke-induced lung squamous metaplasia and inflammation. β-Cryptoxanthin also substantially reduced smoke-elevated TNFα levels in alveolar, bronchial, bronchiolar, and bronchial serous/mucous gland epithelial cells and in lung macrophages. Moreover, β-cryptoxanthin decreased smoke-induced activation of NF-κB, expression of AP-1 and levels of 8-OHdG. The beneficial effects of β-cryptoxanthin were stronger for high-dose β-cryptoxanthin than for low-dose β-cryptoxanthin. Data from this study indicate that β-cryptoxanthin provides a beneficial effect against cigarette smoke-induced inflammation, oxidative DNA damage and squamous metaplasia in the lungs. PMID:21421799

  2. Aflibercept, bevacizumab and ranibizumab prevent glucose-induced damage in human retinal pericytes in vitro, through a PLA2/COX-2/VEGF-A pathway.

    PubMed

    Giurdanella, Giovanni; Anfuso, Carmelina Daniela; Olivieri, Melania; Lupo, Gabriella; Caporarello, Nunzia; Eandi, Chiara M; Drago, Filippo; Bucolo, Claudio; Salomone, Salvatore

    2015-08-01

    Diabetic retinopathy, a major cause of vision loss, is currently treated with anti-VEGF agents. Here we tested two hypotheses: (i) high glucose damages retinal pericytes, the cell layer surrounding endothelial cells, via VEGF induction, which may be counteracted by anti-VEGFs and (ii) activation of PLA2/COX-2 pathway by high glucose might be upstream and/or downstream of VEGF in perycites, as previously observed in endothelial cells. Human retinal pericytes were treated with high glucose (25mM) for 48h and/or anti-VEGFs (40μg/ml aflibercept, 25μg/ml bevacizumab, 10μg/ml ranibizumab). All anti-VEGFs significantly prevented high glucose-induced cell damage (assessed by LDH release) and improved cell viability (assessed by MTT and Evans blue). High glucose-induced VEGF-A expression, as detected both at mRNA (qPCR) and protein (ELISA) level, while receptor (VEGFR1 and VEGFR2) expression, detected in control condition, was unaffected by treatments. High glucose induced also activation of PLA2/COX-2 pathway, as revealed by increased phosphorylation of cPLA2, COX-2 expression and PGE2 release. Treatment with cPLA2 (50μM AACOCF3) and COX-2 (5μM NS-392) inhibitors prevented both cell damage and VEGF-A induced by high glucose. Finally, challenge with exogenous VEGF-A (10ng/ml) induced VEGF-A expression, while anti-VEGFs reduced VEGF-A expression induced by either high glucose or exogenous VEGF-A. These data indicate that high glucose directly damages pericytes through activation of PLA2/COX-2/VEGF-A pathway. Furthermore, a kind of feed-forward loop between cPLA2/COX-2/PG axis and VEGF appears to operate in this system. Thus, anti-VEGFs afford protection of pericytes from high glucose by inhibiting this loop. PMID:26056075

  3. Early MEK1/2 Inhibition after Global Cerebral Ischemia in Rats Reduces Brain Damage and Improves Outcome by Preventing Delayed Vasoconstrictor Receptor Upregulation

    PubMed Central

    Johansson, Sara Ellinor; Larsen, Stine Schmidt; Povlsen, Gro Klitgaard; Edvinsson, Lars

    2014-01-01

    Background Global cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby improve functional outcome after global cerebral ischemia. Incomplete global cerebral ischemia was induced in Wistar rats and the time-course of enhanced contractile responses and the effect of U0126 in cerebral arteries were studied by wire myography and the neuronal cell death by TUNEL. The expression of ETB and 5-HT1B receptors was determined by immunofluorescence. Results Enhanced vasoconstriction peaked in fore- and midbrain arteries 3 days after ischemia. Neuronal cell death appeared initially in the hippocampus 3 days after ischemia and gradually increased until 7 days post-ischemia. Treatment with U0126 normalised cerebrovascular ETB and 5-HT1B receptor expression and contractile function, reduced hippocampal cell death and improved survival rate compared to vehicle treated animals. Conclusions Excessive cerebrovascular expression of contractile ETB and 5-HT1B receptors is a delayed response to global cerebral ischemia peaking 3 days after the insult, which likely contributes to the development of delayed neuronal damage. The enhanced cerebrovascular contractility can be

  4. NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea

    PubMed Central

    Honkura, Yohei; Matsuo, Hirotaka; Murakami, Shohei; Sakiyama, Masayuki; Mizutari, Kunio; Shiotani, Akihiro; Yamamoto, Masayuki; Morita, Ichiro; Shinomiya, Nariyoshi; Kawase, Tetsuaki; Katori, Yukio; Motohashi, Hozumi

    2016-01-01

    Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2–/– mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2–/– mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2–/– mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention. PMID:26776972

  5. NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea.

    PubMed

    Honkura, Yohei; Matsuo, Hirotaka; Murakami, Shohei; Sakiyama, Masayuki; Mizutari, Kunio; Shiotani, Akihiro; Yamamoto, Masayuki; Morita, Ichiro; Shinomiya, Nariyoshi; Kawase, Tetsuaki; Katori, Yukio; Motohashi, Hozumi

    2016-01-01

    Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2(-/-) mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2(-/-) mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2(-/-) mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention. PMID:26776972

  6. Prevention of DNA damage in spores and in vitro by small, acid-soluble proteins from Bacillus species.

    PubMed Central

    Fairhead, H; Setlow, B; Setlow, P

    1993-01-01

    The DNA in dormant spores of Bacillus species is saturated with a group of nonspecific DNA-binding proteins, termed alpha/beta-type small, acid-soluble spore proteins (SASP). These proteins alter DNA structure in vivo and in vitro, providing spore resistance to UV light. In addition, heat treatments (e.g., 85 degrees C for 30 min) which give little killing of wild-type spores of B. subtilis kill > 99% of spores which lack most alpha/beta-type SASP (termed alpha - beta - spores). Similar large differences in survival of wild-type and alpha - beta - spores were found at 90, 80, 65, 22, and 10 degrees C. After heat treatment (85 degrees C for 30 min) or prolonged storage (22 degrees C for 6 months) that gave > 99% killing of alpha - beta - spores, 10 to 20% of the survivors contained auxotrophic or asporogenous mutations. However, alpha - beta - spores heated for 30 min at 85 degrees C released no more dipicolinic acid than similarly heated wild-type spores (< 20% of the total dipicolinic acid) and triggered germination normally. In contrast, after a heat treatment (93 degrees C for 30 min) that gave > or = 99% killing of wild-type spores, < 1% of the survivors had acquired new obvious mutations, > 85% of the spore's dipicolinic acid had been released, and < 1% of the surviving spores could initiate spore germination. Analysis of DNA extracted from heated (85 degrees C, 30 min) and unheated wild-type spores and unheated alpha - beta - spores revealed very few single-strand breaks (< 1 per 20 kb) in the DNA. In contrast, the DNA from heated alpha- beta- spores had more than 10 single-strand breaks per 20 kb. These data suggest that binding of alpha/beta-type SASP to spore DNA in vivo greatly reduces DNA damage caused by heating, increasing spore heat resistance and long-term survival. While the precise nature of the initial DNA damage after heating of alpha- beta- spores that results in the single-strand breaks is not clear, a likely possibility is DNA depurination. A

  7. N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction

    PubMed Central

    Visalli, Valeria; Muscoli, Carolina; Sacco, Iolanda; Sculco, Francesca; Palma, Ernesto; Costa, Nicola; Colica, Carmela; Rotiroti, Domenicantonio; Mollace, Vincenzo

    2007-01-01

    Background HIV envelope gp 120 glycoprotein is released during active HIV infection of brain macrophages thereby generating inflammation and oxidative stress which contribute to the development of the AIDS-Dementia Complex (ADC). Gp120 has also been found capable to generate excitotoxic effect on brain tissue via enhancement of glutamatergic neurotransmission, leading to neuronal and astroglial damage, though the mechanism is still to be better understood. Here we investigated on the effect of N-acetylcysteine (NAC), on gp120-induced damage in human cultured astroglial cells and the possible contribution of gp120-related reacting oxygen species (ROS) in the imbalanced activity of glutamine synthase (GS), the enzyme that metabolizes glutamate into glutamine within astroglial cells playing a neuroprotective role in brain disorders. Results Incubation of Lipari human cultured astroglial cells with gp 120 (0.1–10 nM) produced a significant reduction of astroglial cell viability and apoptosis as evaluated by TUNEL reaction and flow cytometric analysis (FACS). This effect was accompanied by lipid peroxidation as detected by means of malondialdehyde assay (MDA). In addition, gp 120 reduced both glutamine concentration in astroglial cell supernatants and GS expression as detected by immunocytochemistry and western blotting analysis. Pre-treatment of cells with NAC (0.5–5 mM), dose-dependently antagonised astroglial apoptotic cell death induced by gp 120, an effect accompanied by significant attenuation of MDA accumulation. Furthermore, both effects were closely associated with a significant recovery of glutamine levels in cell supernatants and by GS expression, thus suggesting that overproduction of free radicals might contribute in gp 120-related dysfunction of GS in astroglial cells. Conclusion In conclusion, the present experiments demonstrate that gp 120 is toxic to astroglial cells, an effect accompanied by lipid peroxidation and by altered glutamine release. All

  8. Moringa oleifera leaf extract prevents isoproterenol-induced myocardial damage in rats: evidence for an antioxidant, antiperoxidative, and cardioprotective intervention.

    PubMed

    Nandave, Mukesh; Ojha, Shreesh Kumar; Joshi, Sujata; Kumari, Santosh; Arya, Dharamvir Singh

    2009-02-01

    The present study evaluated cardioprotective effect of lyophilized hydroalcoholic extract of Moringa oleifera in the isoproterenol (ISP)-induced model of myocardial infarction. Wistar albino male rats were divided into three groups and orally fed saline once daily alone (sham) or with ISP (ISP control) or ISP with M. oleifera (200 mg/kg), respectively, for 1 month. On days 29 and 30 of administration, rats of the ISP control and M. oleifera-ISP groups were administered ISP (85 mg/kg, s.c.) at an interval of 24 hours. On day 31, hemodynamic parameters (mean arterial pressure [MAP], heart rate [HR], left ventricular end-diastolic pressure [LVEDP], and left ventricular peak positive [(+) LV dP/dt] and negative [(-) LV dP/dt] pressures were recorded. At the end of the experiment, the animals were sacrificed, and hearts were excised and processed for biochemical, histopathological, and ultrastructural studies. Chronic treatment with M. oleifera demonstrated mitigating effects on ISP-induced hemodynamic [HR, (+) LV dP/dt, (-) LV dP/dt, and LVEDP] perturbations. Chronic M. oleifera treatment resulted in significant favorable modulation of the biochemical enzymes (superoxide dismutase, catalase, glutathione peroxidase, lactate dehydrogenase, and creatine kinase-MB) but failed to demonstrate any significant effect on reduced glutathione compared to the ISP control group. Moringa treatment significantly prevented the rise in lipid peroxidation in myocardial tissue. Furthermore, M. oleifera also prevented the deleterious histopathological and ultrastructural perturbations caused by ISP. Based on the results of the present study, it can be concluded that M. oleifera extract possesses significant cardioprotective effect, which may be attributed to its antioxidant, antiperoxidative, and myocardial preservative properties. PMID:19298195

  9. Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4) Treated Rats

    PubMed Central

    Chowdhury, Mohammed Riaz Hasan; Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah

    2015-01-01

    Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (−)-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4) treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA), nitric oxide, advanced protein oxidation products level (APOP), and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level) and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats. PMID:26106435

  10. Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory response, but not apoptosis in mouse: The prevention of curcumin

    SciTech Connect

    Xu, Demei; Hu, Lihua; Su, Chuanyang; Xia, Xiaomin; Zhang, Pu; Fu, Juanli; Wang, Wenchao; Xu, Duo; Du, Hong; Hu, Qiuling; Song, Erqun; Song, Yang

    2014-10-15

    This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling. - Highlights: • TCBQ-intoxication significantly increased AST and ALT activities. • TCBQ-intoxication induced oxidative stress in mice liver. • TCBQ-intoxication induced inflammatory response in mice liver. • TCBQ-intoxication induced hepatotoxicity is independent of apoptosis. • Curcumin relieved TCBQ-induced liver damage remarkably.

  11. Ginkgo biloba Extract Prevents Female Mice from Ischemic Brain Damage and the Mechanism Is Independent of the HO1/Wnt Pathway.

    PubMed

    Tulsulkar, Jatin; Glueck, Bryan; Hinds, Terry D; Shah, Zahoor A

    2016-04-01

    It is well known that gender differences exist in experimental or clinical stroke with respect to brain damage and loss of functional outcome. We have previously reported neuroprotective properties of Ginkgo biloba/EGb 761® (EGb 761) in transient and permanent mouse models of brain ischemia using male mice, and the mechanism of action was attributed to the upregulation of the heme oxygenase 1 (HO1)/Wnt pathway. Here, we sought to investigate whether EGb 761's protective effect in ovariectomized female mice following stroke is also mediated by the HO1/Wnt pathway. Female mice were ovariectomized (OVX) to remove the protective effect of estrogen and were treated with EGb 761 for 7 days prior to inducing permanent middle cerebral artery occlusion (pMCAO) and allowed to survive for an additional 7 days. At day 8, animals were sacrificed, and the brains were harvested for infarct volume analysis, western blots, and immunohistochemistry. The OVX female mice treated with EGb 761 showed significantly lower infarct size as compared to Veh/OVX animals. EGb 761 treatment in female mice inhibited apoptosis by preventing caspase-3 cleavage and blocking the extrinsic apoptotic pathway. EGb 761 pretreatment significantly enhanced neurogenesis in OVX mice as compared to the Veh/OVX group and significantly upregulated androgen receptor expression with no changes in HO1/Wnt signaling. These results suggest that EGb 761 prevented brain damage in OVX female mice by improving grip strength and neurological deficits, and the mechanism of action is not through HO1/Wnt but via blocking the extrinsic apoptotic pathway. PMID:26573919

  12. N-Acetyl-Cysteine and l-Carnitine Prevent Meiotic Oocyte Damage Induced by Follicular Fluid From Infertile Women With Mild Endometriosis.

    PubMed

    Giorgi, Vanessa S I; Da Broi, Michele G; Paz, Claudia C P; Ferriani, Rui A; Navarro, Paula A

    2016-03-01

    This study evaluated the potential protective effect of the antioxidants, l-carnitine (LC) and N-acetyl-cysteine (NAC), in preventing meiotic oocyte damage induced by follicular fluid (FF) from infertile women with mild endometriosis (ME). We performed an experimental study. The FF samples were obtained from 22 infertile women undergoing stimulated cycles for intracytoplasmic sperm injection (11 with ME and 11 without endometriosis). Immature bovine oocytes were submitted to in vitro maturation (IVM) divided into 9 groups: no-FF (No-FF); with FF from control (CFF) or ME (EFF) groups; and with LC (C + LC and E + LC), NAC (C + NAC and E + NAC), or both antioxidants (C + 2Ao and E + 2Ao). After IVM, oocytes were immunostained for visualization of microtubules and chromatin by confocal microscopy. The percentage of meiotically normal metaphase II (MII) oocytes was significantly lower in the EFF group (51.35%) compared to No-FF (86.36%) and CFF (83.52%) groups. The E + NAC (62.22%), E + LC (80.61%), and E + 2Ao (61.40%) groups showed higher percentage of normal MII than EFF group. The E + LC group showed higher percentage of normal MII than E + NAC and E + 2Ao groups and a similar percentage to No-FF and CFF groups. Therefore, FF from infertile women with ME causes meiotic abnormalities in bovine oocytes, and, for the first time, we demonstrated that the use of NAC and LC prevents these damages. Our findings elucidate part of the pathogenic mechanisms involved in infertility associated with ME and open perspectives for further studies investigating whether the use of LC could improve the natural fertility and/or the results of in vitro fertilization of women with ME. PMID:26342050

  13. Reduced ultraviolet-induced DNA damage and apoptosis in human skin with topical application of a photolyase-containing DNA repair enzyme cream: clues to skin cancer prevention.

    PubMed

    Berardesca, Enzo; Bertona, Marco; Altabas, Karmela; Altabas, Velimir; Emanuele, Enzo

    2012-02-01

    The exposure of human skin to ultraviolet radiation (UVR) results in the formation of DNA photolesions that give rise to photoaging, mutations, cell death and the onset of carcinogenic events. Photolyase (EC 4.1.99.3) is a DNA repair enzyme that reverses damage caused by exposure to UVR. We sought to investigate whether addition of photolyase enhances the protection provided by a traditional sunscreen (SS), by reducing the in vivo formation of cyclobutane-type pyrimidine dimers (CPDs) and UVR-induced apoptosis in human skin. Ten volunteers (Fitzpatrick skin type II) were exposed to solar-simulated (ss) UVR at a three times minimal erythema dose for 4 consecutive days. Thirty minutes prior to each exposure, the test materials [vehicle, SS (sun protection factor 50) alone, and SS plus photolyase from Anacystis nidulans] were applied topically to three different sites. One additional site was left untreated and one received ssUVR only. Biopsy specimens were taken 72 h after the last irradiation. The amount of CPDs and the extent of apoptosis were measured by ELISA. Photolyase plus SS was superior to SS alone in reducing both the formation of CPDs and apoptotic cell death (both P<0.001). In conclusion, the addition of photolyase to a traditional SS contributes significantly to the prevention of UVR-induced DNA damage and apoptosis when applied topically to human skin. PMID:22086236

  14. Berberine Prevents Intestinal Mucosal Barrier Damage During Early Phase of Sepsis in Rat through the Toll-Like Receptors Signaling Pathway

    PubMed Central

    Li, Guo-xun; Wang, Xi-mo; Jiang, Tao; Gong, Jian-feng; Niu, Ling-ying

    2015-01-01

    Our previous study has shown berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway. In this study, we explored the regulatory effects of berberine on Toll-like receptors during the intestinal mucosal damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with berberine for 5 d before undergoing cecal ligation and puncture (CLP) to induce polymicrobial sepsis. The expression of Toll-like receptor 2 (TLR 2), TLR 4, TLR 9, the activity of nuclear factor-kappa B (NF-κB), the levels of selected cytokines and chemokines, percentage of cell death in intestinal epithelial cells, and mucosal permeability were investigated at 0, 2, 6, 12 and 24 h after CLP. Results showed that the tumor necrosis factor-α (TNF-α ) and interleukin-6 (IL-6) level were significantly lower in berberine-treated rats compared to the control animals. Conversely, the expression level of tight junction proteins, percentage of cell death in intestinal epithelial cells and the mucosal permeability were significantly higher in berberine-treated rats. The mRNA expression of TLR 2, TLR 4, and TLR 9 were significantly affected by berberine treatment. Our results indicate that pretreatment with berberine attenuates tissue injury and protects the intestinal mucosal barrier in early phase of sepsis and this may possibly have been mediated through the TLRs pathway. PMID:25605990

  15. Schisandrin B Prevents Doxorubicin Induced Cardiac Dysfunction by Modulation of DNA Damage, Oxidative Stress and Inflammation through Inhibition of MAPK/p53 Signaling

    PubMed Central

    Arumugam, Somasundaram; Suzuki, Kenji; Ko, Kam Ming; Krishnamurthy, Prasanna; Watanabe, Kenichi; Konishi, Tetsuya

    2015-01-01

    Doxorubicin (Dox) is a highly effective antineoplastic drug. However, Dox-induced apoptosis in cardiomyocytes leads to irreversible degenerative cardiomyopathy, which limits Dox clinical application. Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to protect against oxidative damage in liver, heart and brain tissues in rodents. In current study, we investigated possible protective effects of Sch B against Dox-induced cardiomyopathy in mice. Mice received a single injection of Dox (20 mg/kg IP). Five days after Dox administration, left ventricular (LV) performance was significantly depressed and was improved by Sch B treatment. Sch B prevented the Dox-induced increase in lipid peroxidation, nitrotyrosine formation, and metalloproteinase activation in the heart. In addition, the increased expression of phospho-p38 MAPK and phospho-MAPK activated mitogen kinase 2 levels by Dox were significantly suppressed by Sch B treatment. Sch B also attenuated Dox-induced higher expression of LV proinflammatory cytokines, cardiomyocyte DNA damage, myocardial apoptosis, caspase-3 positive cells and phopho-p53 levels in mice. Moreover, LV expression of NADPH oxidase subunits and reactive oxygen species were significantly less in Sch B treatment mice after Dox injection. These findings suggest that Sch B attenuates Dox-induced cardiotoxicity via antioxidative and anti-inflammatory effects. PMID:25742619

  16. Evidence for rapid inter- and intramolecular chlorine transfer reactions of histamine and carnosine chloramines: implications for the prevention of hypochlorous-acid-mediated damage.

    PubMed

    Pattison, David I; Davies, Michael J

    2006-07-01

    Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and Cl(-) by the heme enzyme myeloperoxidase, which is released from activated leukocytes. HOCl possesses potent antibacterial properties, but excessive production can lead to host tissue damage that is implicated in a wide range of human diseases (e.g., atherosclerosis). Histamine and carnosine have been proposed as protective agents against such damage. However, as recent studies have shown that histidine-containing compounds readily form imidazole chloramines that can rapidly chlorinate other targets, it was hypothesized that similar reactions may occur with histamine and carnosine, leading to propagation, rather than prevention, of HOCl-mediated damage. In this study, the reactions of HOCl with histamine, histidine, carnosine, and other compounds containing imidazole and free amine sites were examined. In all cases, rapid formation (k, 1.6 x 10(5) M(-)(1) s(-)(1)) of imidazole chloramines was observed, followed by chlorine transfer to yield more stable, primary chloramines (R-NHCl). The rates of most of these secondary reactions are dependent upon substrate concentrations, consistent with intermolecular mechanisms (k, 10(3)-10(4) M(-)(1) s(-)(1)). However, for carnosine, the imidazole chloramine transfer rates are independent of the concentration, indicative of intramolecular processes (k, 0.6 s(-)(1)). High-performance liquid chromatography studies show that in all cases the resultant R-NHCl species can slowly chlorinate N-alpha-acetyl-Tyr. Thus, the current data indicate that the chloramines formed on the imidazole and free amine groups of these compounds can oxidize other target molecules but with limited efficiency, suggesting that histamine and particularly carnosine may be able to limit HOCl-mediated oxidation in vivo. PMID:16800640

  17. 4(α-L-RHAMNOSYLOXY)-BENZYL ISOTHIOCYANATE, A BIOACTIVE PHYTOCHEMICAL THAT DEFENDS CEREBRAL TISSUE AND PREVENTS SEVERE DAMAGE INDUCED BY FOCAL ISCHEMIA/REPERFUSION.

    PubMed

    Galuppo, M; Giacoppo, S; Iori, R; De Nicola, G R; Milardi, D; Bramanti, P; Mazzon, E

    2015-01-01

    Natural compounds are a promising source to treat several pathologies. The present study shows the in vivo pharmacological beneficial effect of 4(α-L-rhamnosyloxy)-benzyl isothiocyanate (glucomoringin isothiocyanate; GMG-ITC) obtained from glucomoringin (GMG; 4(α;-L-rhamnosyloxy)- benzyl glucosinolate), purified from Moringa oleifera seeds and hydrolyzed by myrosinase enzyme (β-thioglucoside glucohydrolase; E.C. 3.2.1.147). Cerebral ischemia/reperfusion (CIR) was induced in rats according to a classic model of carotid artery occlusion for a time period of 1 h and the reperfusion time was prolonged for seven days. GMG-ITC (3.5 mg GMG/ml plus 30 μl enzyme/rat; one ml i.p./rat) was administered 15 min after the beginning of ischemia and daily. The results clearly show that GMG-ITC possesses the capability to counteract the CIR-induced damage reducing TNF-alpha release, IκB-alpha cytosolic degradation/NFκBp65 nuclear translocation, as well as several other direct or indirect markers of inflammation (phospho-ERK p42/44, p-selectin) and oxidative stress (inducible Nitric Oxide Synthase (iNOS), MMP-9). GMG-ITC was shown to exert neuroprotective properties in preventing CIR-induced damage and the related cascade of inflammatory and oxidative mediators that exacerbate the progression of this disease in an experimental rat model. Our results clearly show that the tested phytochemical GMG-ITC possesses the capability to counteract CIR-induced damage. PMID:26122222

  18. Application of citrate as a tricarboxylic acid (TCA) cycle intermediate, prevents diabetic-induced heart damages in mice

    PubMed Central

    Liang, Qianqian; Wang, Baoyu; Pang, Lingxia; Wang, Youpei; Zheng, Meiqin; Wang, Qing; Yan, Jingbin; Xu, Jinzhong

    2016-01-01

    Objective(s): Higher cellular reactive oxygen species (ROS) levels is important in reducing cellular energy charge (EC) by increasing the levels of key metabolic protein, and nitrosative modifications, and have been shown to damage the cardiac tissue of diabetic mice. However, the relation between energy production and heart function is unclear. Materials and Methods: Streptozotocin (STZ, 150 mg/kg body weight) was injected intraperitoneally once to mice that had been fasted overnight for induction of diabetes. After diabetic induction, mice received citrate (5 µg/kg) through intraperitoneal injection every other day for 5 weeks. The caspase-3, plasminogen activator inhibitor 1 (PAI1), protein kinase B (PKB), commonly known as AKT and phosphorylated-AKT (p-AKT) proteins were examined to elucidate inflammation and apoptosis in the heart. For histological analysis, heart samples were fixed with 10% formalin and stained with hematoxylin-eosin (HE) and Sirius red to assess pathological changes and fibrosis. The expression levels[AGA1] of marker proteins, tyrosine nitration, activity of ATP synthase and succinyl-CoA3-ketoacid coenzyme A transferase-1 (SCOT), and EC were measured. Results: Intraperitoneal injection of citrate significantly reduced caspase-3 and PAI-1 protein levels and increased p-AKT level on the 5th week; EC in the heart was found to be increased as well. Further, the expression level, activity, and tyrosine nitration of ATP synthase and SCOT were not affected after induction of diabetes. Conclusion: Results indicate that application of citrate, a tricarboxylic acid (TCA) cycle intermediate, might alleviate cardiac dysfunction by reducing cardiac inflammation, apoptosis, and increasing cardiac EC. PMID:27096063

  19. Recommendations on the use of folic acid supplementation to prevent the recurrence of neural tube defects. Clinical Teratology Committee, Canadian College of Medical Geneticists.

    PubMed Central

    Van Allen, M I; Fraser, F C; Dallaire, L; Allanson, J; McLeod, D R; Andermann, E; Friedman, J M

    1993-01-01

    OBJECTIVE: To prevent the recurrence of neural tube defects (NTDs) in families at increased risk of having offspring with NTDs with the use of periconceptional folic acid supplementation. OPTIONS: Genetic counselling and prenatal diagnosis of NTDs. OUTCOMES: NTDs cause stillbirth, neonatal death and severe disabilities. The cost for medical care and rehabilitation in the first 10 years of life of a child with spina bifida cystica was estimated to be $42,507 in 1987. EVIDENCE: The authors reviewed the medical literature, communicated with investigators from key studies, reviewed policy recommendations from other organizations and drew on their own expertise. A recent multicentre randomized controlled trial showed that among women at high risk of having a child with an NTD those who received 4 mg/d of folic acid had 72% fewer cases of NTD-affected offspring than nonsupplemented women. Two previous intervention studies also demonstrated that folic acid supplementation was effective in reducing the rate of NTD recurrence. Several retrospective studies support this conclusion. VALUES: Recommendations are the consensus of the Clinical Teratology Committee of the Canadian College of Medical Geneticists (CCMG) and have been approved by the CCMG Board. The committee believes that primary prevention of NTDs is preferable to treatment or to prenatal detection and abortion. BENEFITS, HARMS AND COSTS: Folic acid supplementation should result in fewer NTDs among infants in Canada and ancillary savings in medical costs. The recommended dosage of folic acid is not known to be associated with adverse effects. Higher dosages of folic acid may make vitamin B12 deficiency difficult to diagnose and may alter seizure frequency in patients with epilepsy due to drug interactions with anticonvulsants. RECOMMENDATIONS: A minimum dosage of folic acid of 0.8 mg/d, not to exceed 5.0 mg/d, is recommended along with a well-balanced, nutritious diet for all women who are at increased risk of

  20. [Blood vessel and nerve damage in total hip arthroplasty].

    PubMed

    Dietze, S; Perka, C; Baecker, H

    2014-01-01

    Blood vessel and nerve damage are uncommon complications in total hip arthroplasty (THA). With an incidence between 0.1 and 0.2 % in primary THA these complications are rare but can be serious with a high mortality risk. The individual risk is determined by multiple factors depending on the surgeon's skills, the number of previous surgeries and the approach itself. The anatomy of the defect is an essential risk factor. Some procedures, such as the use of screws for cup fixation are associated with a higher risk of vascular and neural damage. The acetabular quadrant system of the hip as described by Wasielewski et al. is a useful tool to visualize the neurovascular anatomy of the hip, to detect the safe zone and subsequently prevent complications. Sciatic nerve palsy after total hip replacement is the most common nerve damage followed by femoral nerve damage. Previous surgery, a posterior approach and excessive leg extension are the most common risk factors for nerve damage. In order to diagnose nerve palsy after orthopedic surgery an electromyogram can be of use to assess the extent and prognosis. This article focuses on vascular and neural complications after total hip arthroplasty and the options for diagnosis, treatment and prevention. PMID:24384891

  1. Suppression of Reactive Oxygen Species Accumulation in Chloroplasts Prevents Leaf Damage but Not Growth Arrest in Salt-Stressed Tobacco Plants

    PubMed Central

    Lodeyro, Anabella F.; Giró, Mariana; Poli, Hugo O.; Bettucci, Gabriel; Cortadi, Adriana; Ferri, Alejandro M.; Carrillo, Néstor

    2016-01-01

    Crop yield reduction due to salinity is a growing agronomical concern in many regions. Increased production of reactive oxygen species (ROS) in plant cells accompanies many abiotic stresses including salinity, acting as toxic and signaling molecules during plant stress responses. While ROS are generated in various cellular compartments, chloroplasts represent a main source in the light, and plastid ROS synthesis and/or elimination have been manipulated to improve stress tolerance. Transgenic tobacco plants expressing a plastid-targeted cyanobacterial flavodoxin, a flavoprotein that prevents ROS accumulation specifically in chloroplasts, displayed increased tolerance to many environmental stresses, including drought, excess irradiation, extreme temperatures and iron starvation. Surprisingly, flavodoxin expression failed to protect transgenic plants against NaCl toxicity. However, when high salt was directly applied to leaf discs, flavodoxin did increase tolerance, as reflected by preservation of chlorophylls, carotenoids and photosynthetic activities. Flavodoxin decreased salt-dependent ROS accumulation in leaf tissue from discs and whole plants, but this decline did not improve tolerance at the whole plant level. NaCl accumulation in roots, as well as increased osmotic pressure and salt-induced root damage, were not prevented by flavodoxin expression. The results indicate that ROS formed in chloroplasts have a marginal effect on plant responses during salt stress, and that sensitive targets are present in roots which are not protected by flavodoxin. PMID:27441560

  2. Suppression of Reactive Oxygen Species Accumulation in Chloroplasts Prevents Leaf Damage but Not Growth Arrest in Salt-Stressed Tobacco Plants.

    PubMed

    Lodeyro, Anabella F; Giró, Mariana; Poli, Hugo O; Bettucci, Gabriel; Cortadi, Adriana; Ferri, Alejandro M; Carrillo, Néstor

    2016-01-01

    Crop yield reduction due to salinity is a growing agronomical concern in many regions. Increased production of reactive oxygen species (ROS) in plant cells accompanies many abiotic stresses including salinity, acting as toxic and signaling molecules during plant stress responses. While ROS are generated in various cellular compartments, chloroplasts represent a main source in the light, and plastid ROS synthesis and/or elimination have been manipulated to improve stress tolerance. Transgenic tobacco plants expressing a plastid-targeted cyanobacterial flavodoxin, a flavoprotein that prevents ROS accumulation specifically in chloroplasts, displayed increased tolerance to many environmental stresses, including drought, excess irradiation, extreme temperatures and iron starvation. Surprisingly, flavodoxin expression failed to protect transgenic plants against NaCl toxicity. However, when high salt was directly applied to leaf discs, flavodoxin did increase tolerance, as reflected by preservation of chlorophylls, carotenoids and photosynthetic activities. Flavodoxin decreased salt-dependent ROS accumulation in leaf tissue from discs and whole plants, but this decline did not improve tolerance at the whole plant level. NaCl accumulation in roots, as well as increased osmotic pressure and salt-induced root damage, were not prevented by flavodoxin expression. The results indicate that ROS formed in chloroplasts have a marginal effect on plant responses during salt stress, and that sensitive targets are present in roots which are not protected by flavodoxin. PMID:27441560

  3. TSPO-ligands prevent oxidative damage and inflammatory response in C6 glioma cells by neurosteroid synthesis.

    PubMed

    Santoro, Anna; Mattace Raso, Giuseppina; Taliani, Sabrina; Da Pozzo, Eleonora; Simorini, Francesca; Costa, Barbara; Martini, Claudia; Laneri, Sonia; Sacchi, Antonia; Cosimelli, Barbara; Calignano, Antonio; Da Settimo, Federico; Meli, Rosaria

    2016-06-10

    Translocator protein 18kDa (TSPO) is predominantly located in the mitochondrial outer membrane, playing an important role in steroidogenesis, inflammation, cell survival and proliferation. Its expression in central nervous system, mainly in glial cells, has been found to be upregulated in neuropathology, and brain injury. In this study, we investigated the anti-oxidative and anti-inflammatory effects of a group of TSPO ligands from the N,N-dialkyl-2-phenylindol-3-ylglyoxylamide class (PIGAs), highlighting the involvement of neurosteroids in their pharmacological effects. To this aim we used a well-known in vitro model of neurosteroidogenesis: the astrocytic C6 glioma cell line, where TSPO expression and localization, as well as cell response to TSPO ligand treatment, have been established. All PIGAs reduced l-buthionine-(S,R)-sulfoximine (BSO)-driven cell cytotoxicity and lipid peroxidation. Moreover, an anti-inflammatory effect was observed due to the reduction of inducible nitric oxide synthase and cyclooxygenase-2 induction in LPS/IFNγ challenged cells. Both effects were blunted by aminoglutethimide (AMG), an inhibitor of pregnenolone synthesis, suggesting neurosteroids' involvement in PIGA protective mechanism. Finally, pregnenolone evaluation in PIGA exposed cells revealed an increase in its synthesis, which was prevented by AMG pre-treatment. These findings indicate that these TSPO ligands reduce oxidative stress and pro-inflammatory enzymes in glial cells through the de novo synthesis of neurosteroids, suggesting that these compounds could be potential new therapeutic tools for the treatment of inflammatory-based neuropathologies with beneficial effects possibly comparable to steroids, but potentially avoiding the negative side effects of long-term therapies with steroid hormones. PMID:27094781

  4. Testosterone and phosphodiesterase type-5 inhibitors: new strategy for preventing endothelial damage in internal and sexual medicine?

    PubMed Central

    Aversa, Antonio; Bruzziches, Roberto; Francomano, Davide; Natali, Marco; Lenzi, Andrea

    2009-01-01

    Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone (e.g. nitric oxide; NO), cell adhesion (e.g. endothelins, interleukins), and the homeostasis of clotting and fibrinolysis (e.g. plasminogen inhibitors, von Willebrand factor). The degeneration of endothelial integrity promotes adverse events (AEs) leading to increased atherogenesis and to the development of vascular systemic and penile end-organ disease. Testosterone (T) is an important player in the regulation of vascular tone through non-genomic actions exerted via blockade of extracellular-calcium entry or activation of potassium channels; also, adequate T concentrations are paramount for the regulation of phosphodiesterase type-5 (PDE5) expression and finally, for the actions exerted by hydrogen sulphide, a gas involved in the alternative pathway controlling vasodilator responses in penile tissue. It is known that an age-related decline of serum T is reported in approximately 20 to 30% of men whereas T deficiency is reported in up to 50% of men with metabolic syndrome or diabetes. A number of laboratory and human studies have shown the combination of T and other treatments for erectile dysfunction (ED), such as PDE5 inhibitors, to be more beneficial in patients with ED and hypogonadism, who fail monotherapy for sexual disturbances. The aim of this review is to show evidence on the role of T and PDE5 inhibitors, alone or in combination, as potential boosters of endothelial function in internal medicine diseases associated with reduced T or NO bioavailability, i.e. metabolic syndrome, obesity, diabetes, coronary artery disease, hyperhomocysteinemia, that share common risk factors with ED. Furthermore, the possibility of such a strategy to prevent endothelial dysfunction in men at increased cardiovascular risk is discussed. PMID:21789066

  5. Probiotic factors partially prevent changes to caspases 3 and 7 activation and transepithelial electrical resistance in a model of 5-fluorouracil-induced epithelial cell damage.

    PubMed

    Prisciandaro, Luca D; Geier, Mark S; Chua, Ann E; Butler, Ross N; Cummins, Adrian G; Sander, Guy R; Howarth, Gordon S

    2012-12-01

    The potential efficacy of a probiotic-based preventative strategy against intestinal mucositis has yet to be investigated in detail. We evaluated supernatants (SN) from Escherichia coli Nissle 1917 (EcN) and Lactobacillus rhamnosus GG (LGG) for their capacity to prevent 5-fluorouracil (5-FU)-induced damage to intestinal epithelial cells. A 5-day study was performed. IEC-6 cells were treated daily from days 0 to 3, with 1 mL of PBS (untreated control), de Man Rogosa Sharpe (MRS) broth, tryptone soy roth (TSB), LGG SN, or EcN SN. With the exception of the untreated control cells, all groups were treated with 5-FU (5 μM) for 24 h at day 3. Transepithelial electrical resistance (TEER) was determined on days 3, 4, and 5, while activation of caspases 3 and 7 was determined on days 4 and 5 to assess apoptosis. Pretreatment with LGG SN increased TEER (p < 0.05) compared to controls at day 3. 5-FU administration reduced TEER compared to untreated cells on days 4 and 5. Pretreatment with MRS, LGG SN, TSB, and EcN SN partially prevented the decrease in TEER induced by 5-FU on day 4, while EcN SN also improved TEER compared to its TSB vehicle control. These differences were also observed at day 5, along with significant improvements in TEER in cells treated with LGG and EcN SN compared to healthy controls. 5-FU increased caspase activity on days 4 and 5 compared to controls. At day 4, cells pretreated with MRS, TSB, LGG SN, or EcN SN all displayed reduced caspase activity compared to 5-FU controls, while both SN groups had significantly lower caspase activity than their respective vehicle controls. Caspase activity in cells pretreated with MRS, LGG SN, and EcN SN was also reduced at day 5, compared to 5-FU controls. We conclude that pretreatment with selected probiotic SN could prevent or inhibit enterocyte apoptosis and loss of intestinal barrier function induced by 5-FU, potentially forming the basis of a preventative treatment modality for mucositis. PMID:22526145

  6. 6-Gingerol-Rich Fraction from Zingiber officinale Prevents Hematotoxicity and Oxidative Damage in Kidney and Liver of Rats Exposed to Carbendazim.

    PubMed

    Salihu, Mariama; Ajayi, Babajide O; Adedara, Isaac A; Farombi, Ebenezer O

    2016-07-01

    Ginger (Zingiber officinale) is a globally marketed flavoring agent and cooking spice with a long history of human health benefits. The fungicide carbendazim (CBZ) is often detected in fruits and vegetables for human nutrition and has been reported to elicit toxic effects in different experimental animal models. The present study investigated the protective effects of 6-Gingerol-rich fraction (6-GRF) from ginger on hematotoxicity and hepatorenal damage in rats exposed to CBZ. CBZ was administered at a dose of 50 mg/kg alone or simultaneously administered with 6-GRF at 50, 100, and 200 mg/kg, whereas control rats received corn oil alone at 2 mL/kg for 14 days. Hematological examination showed that CBZ-mediated toxicity to the total white blood cell (WBC), neutrophils, lymphocytes, and platelets counts were normalized to the control values in rats cotreated with 6-GRF. Moreover, administration of CBZ significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase as well as glutathione level in the livers and kidneys of rats compared with control. However, the levels of hydrogen peroxide (H2O2) and malondialdehyde were markedly elevated in kidneys and livers of CBZ-treated rats compared with control. The significant elevation in the plasma indices of renal and hepatic dysfunction in CBZ-treated rats was confirmed by light microscopy. Coadministration of 6-GRF exhibited chemoprotection against CBZ-mediated hematotoxicity, augmented antioxidant status, and prevented oxidative damage in the kidney and liver of rats. PMID:26673969

  7. 3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter.

    PubMed

    Anneken, John H; Angoa-Pérez, Mariana; Kuhn, Donald M

    2015-04-01

    Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of 'bath salts' and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classified chemically as β-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neurochemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS. Unlike methamphetamine, the β-ketoamphetamines do not damage dopamine (DA) nerve endings. However, mephedrone has been shown to significantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA nerve endings. The β-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA nerve endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that β-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity. METH (a) enters DA nerve endings via the DAT, causes leakage of DA into the cytoplasm and then into the synapse via DAT-mediated reverse transport. Methylone (METHY) and mephedrone (MEPH; b), like METH, are substrates for the DAT but release

  8. Neural Tube Defects

    MedlinePlus

    ... The two most common neural tube defects are spina bifida and anencephaly. In spina bifida, the fetal spinal column doesn't close completely. There is usually nerve damage that causes at least some paralysis of the legs. In anencephaly, ... National Institute of Child Health and Human Development

  9. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-{kappa}B, p38 and JNK MAPK pathway

    SciTech Connect

    Ghosh, Jyotirmoy; Das, Joydeep; Manna, Prasenjit

    2009-10-01

    Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-{kappa}B (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-{kappa}B and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-{kappa}B activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-{kappa}B activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection

  10. Development of a national system for prevention and mitigation of earthquake damages to people and properties, and the reduction of costs related to earthquakes for the Italian Government

    NASA Astrophysics Data System (ADS)

    Console, R.; Greco, M.; Colangelo, A.; Cioè, A.; Trivigno, L.; Chiappini, M.; Ponzo, F.

    2015-12-01

    Recognizing that the Italian territory is prone to disasters in connection with seismic and hydro-geological risk, it has become necessary to define novel regulations and viable solutions aimed at conveying the economical resources of the Italian Government, too often utilized for the management of post-event situations, towards prevention activities. The work synthetically presents the project developed by the CGIAM together with the INGV, and open to collaboration with other Italian and International partners. This project is aimed at the development of a National System for prevention and mitigation of the earthquakes damages, through the definition of a model that achieves the mitigation of the building collapsing risk and the consequent reduction of casualties. Such a model is based on two main issues a) a correct evaluation of risk, defined as a reliable assessment of the hazard expected at a given site and of the vulnerability of civil and industrial buildings, b) setting up of novel strategies for the safety of buildings. The hazard assessment is pursued through the application of innovative multidisciplinary geophysical methodologies and the application of a physically based earthquake simulator. The structural vulnerability of buildings is estimated by means of simplified techniques based on few representative parameters (such as different structural typologies, dynamic soil-structure interaction, etc.) and, for detailed studies, standard protocols for model updating techniques. We analyze, through numerical and experimental approaches, new solutions for the use of innovative materials, and new techniques for the reduction of seismic vulnerability of structural, non-structural and accessorial elements, including low cost type. The project activities are initially implemented on a study area in Southern Italy (Calabria) selected because of its tectonic complexity. The results are expected to be applicable for other hazardous seismic areas of Italy.

  11. Improved estimates of separation distances to prevent unacceptable damage to nuclear power plant structures from hydrogen detonation for gaseous hydrogen storage. Technical report

    SciTech Connect

    Not Available

    1994-05-01

    This report provides new estimates of separation distances for nuclear power plant gaseous hydrogen storage facilities. Unacceptable damage to plant structures from hydrogen detonations will be prevented by having hydrogen storage facilities meet separation distance criteria recommended in this report. The revised standoff distances are based on improved calculations on hydrogen gas cloud detonations and structural analysis of reinforced concrete structures. Also, the results presented in this study do not depend upon equivalencing a hydrogen detonation to an equivalent TNT detonation. The static and stagnation pressures, wave velocity, and the shock wave impulse delivered to wall surfaces were computed for several different size hydrogen explosions. Separation distance equations were developed and were used to compute the minimum separation distance for six different wall cases and for seven detonating volumes (from 1.59 to 79.67 lbm of hydrogen). These improved calculation results were compared to previous calculations. The ratio between the separation distance predicted in this report versus that predicted for hydrogen detonation in previous calculations varies from 0 to approximately 4. Thus, the separation distances results from the previous calculations can be either overconservative or unconservative depending upon the set of hydrogen detonation parameters that are used. Consequently, it is concluded that the hydrogen-to-TNT detonation equivalency utilized in previous calculations should no longer be used.

  12. Device for preventing damage to a submarine cable at the point where it leaves an equipment casing during passage round the cable drum and over the davit

    SciTech Connect

    Guazzo, L.; Vives, J.P.

    1984-11-06

    A device for preventing damage to a submarine cable at the point where it leaves an equipment casing during passage round the cable drum and over the davit, and consisting of a chocking member on each side of the casing surrounding the cable from its outlet from the casing to a point of contact of the cable with the drum, said chocking member being in the form of a body of revolution about the cable axis of generally pear-shaped configuration when unstressed and having a swollen part at the casing end, said chocking member occupying all the space between the cable and the drum when the cable is wound on the drum, the swollen part of the chocking member when unstressed having a radius at least equal to the distance between the cable and the drum at the outlet from the casing. The chocking member may be a sleeve of a strong and flexible material; it may also consist of a stack of elementary chocking members.

  13. Pioglitazone significantly prevented decreased rate of neural differentiation of mouse embryonic stem cells which was reduced by Pex11β knock-down.

    PubMed

    Esmaeili, M; Ghaedi, K; Shoaraye Nejati, A; Nematollahi, M; Shiralyian, H; Nasr-Esfahani, M H

    2016-01-15

    Peroxisomes constitute special cellular organelles which display a variety of metabolic functions including fatty acid oxidation and free radical elimination. Abundance of these flexible organelles varies in response to different environmental stimuli. It has been demonstrated that PEX11β, a peroxisomal membrane elongation factor, is involved in the regulation of size, shape and number of peroxisomes. To investigate the role of PEX11β in neural differentiation of mouse embryonic stem cells (mESCs), we generated a stably transduced mESCs line that derives the expression of a short hairpin RNA against Pex11β gene following doxycycline (Dox) induction. Knock-down of Pex11β, during neural differentiation, significantly reduced the expression of neural progenitor cells and mature neuronal markers (p<0.05) indicating that decreased expression of PEX11β suppresses neuronal maturation. Additionally, mRNA levels of other peroxisome-related genes such as PMP70, Pex11α, Catalase, Pex19 and Pex5 were also significantly reduced by Pex11β knock-down (p<0.05). Interestingly, pretreatment of transduced mESCs with peroxisome proliferator-activated receptor γ agonist (pioglitazone (Pio)) ameliorated the inhibitory effects of Pex11β knock down on neural differentiation. Pio also significantly (p<0.05) increased the expression of neural progenitor and mature neuronal markers besides the expression of peroxisomal genes in transduced mESC. Results elucidated the importance of Pex11β expression in neural differentiation of mESCs, thereby highlighting the essential role of peroxisomes in mammalian neural differentiation. The observation that Pio recovered peroxisomal function and improved neural differentiation of Pex11β knocked-down mESCs, proposes a potential new pharmacological implication of Pio for neurogenesis in patients with peroxisomal defects. PMID:26562432

  14. Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

  15. Utility of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a systematic review and meta-analysis

    PubMed Central

    Shen, Yan-Wei; Zhang, Xiao-Man; Lv, Meng; Chen, Ling; Qin, Tian-Jie; Wang, Fan; Yang, Jiao; Liu, Pei-Jun; Yang, Jin

    2015-01-01

    Background Premature ovarian failure and infertility following chemotherapy are major concerns for premenopausal women with breast cancer. A potential ovarian function preservation strategy is administration of gonadotropin-releasing hormone (GnRH) agonists during adjuvant chemotherapy; however, studies of the clinical efficacy of GnRH agonists to protect chemotherapy-induced ovarian damage have shown mixed results. Objective This meta-analysis study was designed to estimate the efficacy of GnRH agonists administered concurrently with chemotherapy to prevent chemotherapy-induced ovarian damage in premenopausal women with breast cancer. Methods Electronic literature databases (PubMed, EMBASE, MEDLINE, Cochrane Library databases searching, China National Knowledge Infrastructure, Web of Science, and the Wanfang Data) were searched for relevant randomized controlled trials (RCTs) published until September 2015. Only RCTs that examined the effect of GnRH agonists for chemotherapy-induced ovarian failure in premenopausal women with breast cancer were selected. The rate of spontaneous resumption of menses and spontaneous pregnancy were collected. All data were analyzed by RevMan 5.3 (Cochrane Collaboration, Copenhagen, Denmark) and Stata 12.0 (StataCorp, College Station, TX, USA). Results Eleven RCTs with a total of 1,062 participants (GnRH agonists administered concurrently with chemotherapy, n=541; chemotherapy alone, n=521) were included in the meta-analysis. A significantly greater number of women treated with GnRH agonist experienced spontaneous resumption of menses after the adjuvant chemotherapy, yielding a pooled odds ratio of 2.57 (versus chemotherapy alone, 95% confidence interval (CI)=1.65, 4.01; P<0.0001). A subgroup analysis showed that addition of GnRH agonists significantly improved the resumption of menses rate in patients who were hormone-insensitive. However, the two treatment groups experienced similar spontaneous pregnancy (odds ratio =0.177; 95% CI=0

  16. The novel porcine Lactobacillus sobrius strain protects intestinal cells from enterotoxigenic Escherichia coli K88 infection and prevents membrane barrier damage.

    PubMed

    Roselli, Marianna; Finamore, Alberto; Britti, Maria Serena; Konstantinov, Sergey R; Smidt, Hauke; de Vos, Willem M; Mengheri, Elena

    2007-12-01

    Lactobacilli have a potential to overcome intestinal disorders; however, the exact mode of action is still largely unknown. In this study, we have used the intestinal porcine intestinal IPEC-1 epithelial cells as a model to investigate a possible protective activity of a new Lactobacillus species, the L. sobrius DSM 16698(T), against intestinal injury induced by enterotoxigenic Escherichia coli (ETEC) K88 infection and the underlying mechanisms. Treatment of infected cells with L. sobrius strongly reduced the pathogen adhesion. L. sobrius was also able to prevent the ETEC-induced membrane damage by inhibiting delocalization of zonula occludens (ZO)-1, reduction of occludin amount, rearrangement of F-actin, and dephosphorylation of occludin caused by ETEC. RT-PCR and ELISA experiments showed that L. sobrius counteracted the ETEC-induced increase of IL-8 and upregulated the IL-10 expression. The involvement of IL-8 in the deleterious effects of ETEC was proven by neutralization of IL-8 with a specific antibody. A crucial role of IL-10 was indicated by blockage of IL-10 production with neutralizing anti-IL-10 antibody that fully abrogated the L. sobrius protection. L. sobrius was also able to inhibit the internalization of ETEC, which was likely favored by the leaking barrier. The protective effects were not found with L. amylovorus DSM 20531(T) treatment, a strain derived from cattle waste but phylogenetically closely related to L. sobrius. Together, the data indicate that L. sobrius exerts protection against the harmful effects of ETEC by different mechanisms, including pathogen adhesion inhibition and maintenance of membrane barrier integrity through IL-10 regulation. PMID:18029488

  17. Hydrogen Sulfide Prevents Synaptic Plasticity from VD-Induced Damage via Akt/GSK-3β Pathway and Notch Signaling Pathway in Rats.

    PubMed

    Liu, Chunhua; Xu, Xiaxia; Gao, Jing; Zhang, Tao; Yang, Zhuo

    2016-08-01

    Our previous study has demonstrated that hydrogen sulfide (H2S) attenuates neuronal injury induced by vascular dementia (VD) in rats, but the mechanism is still poorly understood. In this study, we aimed to investigate whether the neuroprotection of H2S was associated with synaptic plasticity and try to interpret the potential underlying mechanisms. Adult male Wistar rats were suffered the ligation of bilateral common carotid arteries. At 24 h after surgery, rats were administered intraperitoneally with sodium hydrosulfide (NaHS, 5.6 mg·kg(-1)·day(-1)), a H2S donor, for 3 weeks in the VD+NaHS group and treated intraperitoneally with saline in the VD group respectively. Our results demonstrated that NaHS significantly decreased the level of glutamate. It obviously ameliorated cognitive flexibility as well as the spatial learning and memory abilities by Morris water maze. Moreover, NaHS significantly improved the long-term depression (LTD), and was able to elevate the expression of N-methyl-D-aspartate receptor subunit 2A, which plays a pivotal role in synaptic plasticity. Interestingly, NaHS decreased the phosphorylation of Akt, and it could maintain the activity of glycogen synthase kinase-3β (GSK-3β). Surprisingly, NaHS triggered the canonical Notch pathway by increasing expressions of Jagged-1 and Hes-1. These findings suggest that NaHS prevents synaptic plasticity from VD-induced damage partly via Akt/GSK-3β pathway and Notch signaling pathway.Hydrogen sulfide modulated the ratio of NMDAR 2A/2B and improved the synaptic plasticity via Akt/GSK-3β pathway and Notch signaling pathway in VD rats. PMID:26208699

  18. Neural tube defects.

    PubMed

    Greene, Nicholas D E; Copp, Andrew J

    2014-01-01

    Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies. PMID:25032496

  19. Neural Tube Defects

    PubMed Central

    Greene, Nicholas D.E.; Copp, Andrew J.

    2015-01-01

    Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies. PMID:25032496

  20. Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway

    PubMed Central

    Wang, Qin; Chuikov, Sergei; Taitano, Sophina; Wu, Qi; Rastogi, Arjun; Tuck, Samuel J.; Corey, Joseph M.; Lundy, Steven K.; Mao-Draayer, Yang

    2015-01-01

    Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) is an oral formulation of the fumaric acid esters (FAE), containing the active metabolite dimethyl fumarate (DMF). Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood. In this study, we reported the potential neuroprotective effects of dimethyl fumarate (DMF) on mouse and rat neural stem/progenitor cells (NPCs) and neurons. We found that DMF increased the frequency of the multipotent neurospheres and the survival of NPCs following oxidative stress with hydrogen peroxide (H2O2) treatment. In addition, utilizing the reactive oxygen species (ROS) assay, we showed that DMF reduced ROS production induced by H2O2. DMF also decreased oxidative stress-induced apoptosis. Using motor neuron survival assay, DMF significantly promoted survival of motor neurons under oxidative stress. We further analyzed the expression of oxidative stress-induced genes in the NPC cultures and showed that DMF increased the expression of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) at both levels of RNA and protein. Furthermore, we demonstrated the involvement of Nrf2-ERK1/2 MAPK pathway in DMF-mediated neuroprotection. Finally, we utilized SuperArray gene screen technology to identify additional anti-oxidative stress genes (Gstp1, Sod2, Nqo1, Srxn1, Fth1). Our data suggests that analysis of anti-oxidative stress mechanisms may yield further insights into new targets for treatment of multiple sclerosis (MS). PMID:26090715

  1. Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway.

    PubMed

    Wang, Qin; Chuikov, Sergei; Taitano, Sophina; Wu, Qi; Rastogi, Arjun; Tuck, Samuel J; Corey, Joseph M; Lundy, Steven K; Mao-Draayer, Yang

    2015-01-01

    Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) is an oral formulation of the fumaric acid esters (FAE), containing the active metabolite dimethyl fumarate (DMF). Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood. In this study, we reported the potential neuroprotective effects of dimethyl fumarate (DMF) on mouse and rat neural stem/progenitor cells (NPCs) and neurons. We found that DMF increased the frequency of the multipotent neurospheres and the survival of NPCs following oxidative stress with hydrogen peroxide (H2O2) treatment. In addition, utilizing the reactive oxygen species (ROS) assay, we showed that DMF reduced ROS production induced by H2O2. DMF also decreased oxidative stress-induced apoptosis. Using motor neuron survival assay, DMF significantly promoted survival of motor neurons under oxidative stress. We further analyzed the expression of oxidative stress-induced genes in the NPC cultures and showed that DMF increased the expression of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) at both levels of RNA and protein. Furthermore, we demonstrated the involvement of Nrf2-ERK1/2 MAPK pathway in DMF-mediated neuroprotection. Finally, we utilized SuperArray gene screen technology to identify additional anti-oxidative stress genes (Gstp1, Sod2, Nqo1, Srxn1, Fth1). Our data suggests that analysis of anti-oxidative stress mechanisms may yield further insights into new targets for treatment of multiple sclerosis (MS). PMID:26090715

  2. Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage.

    PubMed

    Louboutin, Jean-Pierre; Chekmasova, Alena; Marusich, Elena; Agrawal, Lokesh; Strayer, David S

    2011-02-01

    Chemokines may play a role in leukocyte migration across the blood-brain barrier (BBB) during neuroinflammation and other neuropathological processes, such as epilepsy. We investigated the role of the chemokine receptor CCR5 in seizures. We used a rat model based on intraperitoneal kainic acid (KA) administration. Four months before KA injection, adult rats were given femoral intramarrow inoculations of SV (RNAiR5-RevM10.AU1), which carries an interfering RNA (RNAi) against CCR5, plus a marker epitope (AU1), or its monofunctional RNAi-carrying homologue, SV(RNAiR5). This treatment lowered expression of CCR5 in circulating cells. In control rats, seizures induced elevated expression of CCR5 ligands MIP-1α and RANTES in the microvasculature, increased BBB leakage and CCR5(+) cells, as well as neuronal loss, inflammation, and gliosis in the hippocampi. Animals given either the bifunctional or the monofunctional vector were largely protected from KA-induced seizures, neuroinflammation, BBB damage, and neuron loss. Brain CCR5 mRNA was reduced. Rats receiving RNAiR5-bearing vectors showed far greater repair responses: increased neuronal proliferation, and decreased production of MIP-1α and RANTES. Controls received unrelated SV(BUGT) vectors. Decrease in CCR5 in circulating cells strongly protected from excitotoxin-induced seizures, BBB leakage, CNS injury, and inflammation, and facilitated neurogenic repair. PMID:20940264

  3. Lubiprostone prevents nonsteroidal anti-inflammatory drug-induced small intestinal damage by suppressing the expression of inflammatory mediators via EP4 receptors.

    PubMed

    Hayashi, Shusaku; Kurata, Naoto; Yamaguchi, Aya; Amagase, Kikuko; Takeuchi, Koji

    2014-06-01

    Lubiprostone, a bicyclic fatty acid derived from prostaglandin E1, has been used to treat chronic constipation and irritable bowel syndrome, and its mechanism of action has been attributed to the stimulation of intestinal fluid secretion via the activation of the chloride channel protein 2/cystic fibrosis transmembrane regulator (ClC-2/CFTR) chloride channels. We examined the effects of lubiprostone on indomethacin-induced enteropathy and investigated the functional mechanisms involved, including its relationship with the EP4 receptor subtype. Male Sprague-Dawley rats were administered indomethacin (10 mg/kg p.o.) and killed 24 hours later to examine the hemorrhagic lesions that developed in the small intestine. Lubiprostone (0.01-1 mg/kg) was administered orally twice 30 minutes before and 9 h after the indomethacin treatment. Indomethacin markedly damaged the small intestine, accompanied by intestinal hypermotility, a decrease in mucus and fluid secretion, and an increase in enterobacterial invasion as well as the up-regulation of inducible nitric-oxide synthase (iNOS) and tumor necrosis factor α (TNFα) mRNAs. Lubiprostone significantly reduced the severity of these lesions, with the concomitant suppression of the functional changes. The effects of lubiprostone on the intestinal lesions and functional alterations were significantly abrogated by the coadministration of AE3-208 [4-(4-cyano-2-(2-(4-fluoronaphthalen-1-yl)propionylamino)phenyl)butyric acid], a selective EP4 antagonist, but not by CFTR(inh)-172, a CFTR inhibitor. These results suggest that lubiprostone may prevent indomethacin-induced enteropathy via an EP4 receptor-dependent mechanism. This effect may be functionally associated with the inhibition of intestinal hypermotility and increase in mucus/fluid secretion, resulting in the suppression of bacterial invasion and iNOS/TNFα expression, which are major pathogenic events in enteropathy. The direct activation of CFTR/ClC-2 chloride channels is not

  4. Curcumin prevents muscle damage by regulating NF-κB and Nrf2 pathways and improves performance: an in vivo model

    PubMed Central

    Sahin, Kazim; Pala, Ragip; Tuzcu, Mehmet; Ozdemir, Oguzhan; Orhan, Cemal; Sahin, Nurhan; Juturu, Vijaya

    2016-01-01

    potential to help prevent muscle damage by regulating the nuclear factor-κB and nuclear factor (erythroid-derived 2)-like 2 pathways and improve the performance and nutritional values of CW. PMID:27621662

  5. The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion.

    PubMed

    Ganesan, Shanthi; Keating, Aileen F

    2016-02-01

    Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide and destroys primordial and primary follicles potentially by DNA damage induction. The temporal pattern by which PM induces DNA damage and initiation of the ovarian response to DNA damage has not yet been well characterized. This study investigated DNA damage initiation, the DNA repair response, as well as induction of follicular demise using a neonatal rat ovarian culture system. Additionally, to delineate specific mechanisms involved in the ovarian response to PM exposure, utility was made of PKC delta (PKCδ) deficient mice as well as an ATM inhibitor (KU 55933; AI). Fisher 344 PND4 rat ovaries were cultured for 12, 24, 48 or 96h in medium containing DMSO ±60μM PM or KU 55933 (48h; 10nM). PM-induced activation of DNA damage repair genes was observed as early as 12h post-exposure. ATM, PARP1, E2F7, P73 and CASP3 abundance were increased but RAD51 and BCL2 protein decreased after 96h of PM exposure. PKCδ deficiency reduced numbers of all follicular stages, but did not have an additive impact on PM-induced ovotoxicity. ATM inhibition protected all follicle stages from PM-induced depletion. In conclusion, the ovarian DNA damage repair response is active post-PM exposure, supporting that DNA damage contributes to PM-induced ovotoxicity. PMID:26708502

  6. Damage Detection Using Holography and Interferometry

    NASA Technical Reports Server (NTRS)

    Decker, Arthur J.

    2003-01-01

    This paper reviews classical approaches to damage detection using laser holography and interferometry. The paper then details the modern uses of electronic holography and neural-net-processed characteristic patterns to detect structural damage. The design of the neural networks and the preparation of the training sets are discussed. The use of a technique to optimize the training sets, called folding, is explained. Then a training procedure is detailed that uses the holography-measured vibration modes of the undamaged structures to impart damage-detection sensitivity to the neural networks. The inspections of an optical strain gauge mounting plate and an International Space Station cold plate are presented as examples.

  7. Constitutive activation of the ATM/BRCA1 pathway prevents DNA damage-induced apoptosis in 5-azacytidine-resistant cell lines.

    PubMed

    Imanishi, Satoshi; Umezu, Tomohiro; Ohtsuki, Kazushige; Kobayashi, Chiaki; Ohyashiki, Kazuma; Ohyashiki, Junko H

    2014-06-01

    5-Azacytidine (AZA) exerts its anti-tumor effects by exerting cytotoxicity via its incorporation into RNA and DNA, which causes the reactivation of aberrantly silenced growth-regulatory genes by promoter demethylation, as well as DNA damage. AZA is used for patients with myelodysplastic syndrome and acute myeloid leukemia. However, some patients demonstrate resistance to AZA, the mechanisms of which are not fully elucidated. We therefore sought to better characterize the molecular mechanism of AZA resistance using an in vitro model of AZA resistance. We established AZA-resistant cell lines by exposing the human leukemia cell lines U937 and HL-60 to clinical concentrations of AZA, and characterized these cells. AZA-resistant cells showed a down-regulation of the DNMT3A protein, in correlation with their marked genome-wide DNA hypomethylation. Furthermore, genes involved in pyrimidine metabolism were down-regulated in both AZA-resistant cell lines; AZA sensitivity was restored by inhibition of CTP synthase. Of note is that the DNA damage response pathway is constitutively activated in the AZA-resistant cell lines, but not in the parental cell lines. Inhibition of the DNA damage response pathway canceled the AZA resistance, in association with an increase in apoptotic cells. We found that the molecular mechanism underlying AZA resistance involves pyrimidine metabolism and the DNA damage response through ATM kinase. This study therefore sheds light on the mechanisms underlying AZA resistance, and will enable better understanding of AZA resistance in patients undergoing AZA treatment. PMID:24680865

  8. Neural Networks for Flight Control

    NASA Technical Reports Server (NTRS)

    Jorgensen, Charles C.

    1996-01-01

    Neural networks are being developed at NASA Ames Research Center to permit real-time adaptive control of time varying nonlinear systems, enhance the fault-tolerance of mission hardware, and permit online system reconfiguration. In general, the problem of controlling time varying nonlinear systems with unknown structures has not been solved. Adaptive neural control techniques show considerable promise and are being applied to technical challenges including automated docking of spacecraft, dynamic balancing of the space station centrifuge, online reconfiguration of damaged aircraft, and reducing cost of new air and spacecraft designs. Our experiences have shown that neural network algorithms solved certain problems that conventional control methods have been unable to effectively address. These include damage mitigation in nonlinear reconfiguration flight control, early performance estimation of new aircraft designs, compensation for damaged planetary mission hardware by using redundant manipulator capability, and space sensor platform stabilization. This presentation explored these developments in the context of neural network control theory. The discussion began with an overview of why neural control has proven attractive for NASA application domains. The more important issues in control system development were then discussed with references to significant technical advances in the literature. Examples of how these methods have been applied were given, followed by projections of emerging application needs and directions.

  9. CDK5-mediated phosphorylation of p19INK4d avoids DNA damage-induced neurodegeneration in mouse hippocampus and prevents loss of cognitive functions.

    PubMed

    Ogara, María Florencia; Belluscio, Laura M; de la Fuente, Verónica; Berardino, Bruno G; Sonzogni, Silvina V; Byk, Laura; Marazita, Mariela; Cánepa, Eduardo T

    2014-07-01

    DNA damage, which perturbs genomic stability, has been linked to cognitive decline in the aging human brain, and mutations in DNA repair genes have neurological implications. Several studies have suggested that DNA damage is also increased in brain disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. However, the precise mechanisms connecting DNA damage with neurodegeneration remain poorly understood. CDK5, a critical enzyme in the development of the central nervous system, phosphorylates a number of synaptic proteins and regulates dendritic spine morphogenesis, synaptic plasticity and learning. In addition to these physiological roles, CDK5 has been involved in the neuronal death initiated by DNA damage. We hypothesized that p19INK4d, a member of the cell cycle inhibitor family INK4, is involved in a neuroprotective mechanism activated in response to DNA damage. We found that in response to genotoxic injury or increased levels of intracellular calcium, p19INK4d is transcriptionally induced and phosphorylated by CDK5 which provides it with greater stability in postmitotic neurons. p19INK4d expression improves DNA repair, decreases apoptosis and increases neuronal survival under conditions of genotoxic stress. Our in vivo experiments showed that decreased levels of p19INK4d rendered hippocampal neurons more sensitive to genotoxic insult resulting in the loss of cognitive abilities that rely on the integrity of this brain structure. We propose a feedback mechanism by which the neurotoxic effects of CDK5-p25 activated by genotoxic stress or abnormal intracellular calcium levels are counteracted by the induction and stabilization of p19INK4d protein reducing the adverse consequences on brain functions. PMID:24703879

  10. 3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter

    PubMed Central

    Anneken, John H.; Angoa-Pérez, Mariana; Kuhn, Donald M.

    2016-01-01

    Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of ‘bath salts’ and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classified chemically as β-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neurochemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS. Unlike methamphetamine, the β-ketoamphetamines do not damage dopamine (DA) nerve endings. However, mephedrone has been shown to significantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA nerve endings. The β-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA nerve endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that β-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity. PMID:25626880

  11. Low molecular weight guluronate prevents TNF-α-induced oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells.

    PubMed

    Dun, Yun-lou; Zhou, Xiao-lin; Guan, Hua-shi; Yu, Guang-li; Li, Chun-xia; Hu, Ting; Zhao, Xia; Cheng, Xiao-lei; He, Xiao-xi; Hao, Jie-jie

    2015-09-01

    Muscle wasting is associated with a variety of chronic or inflammatory disorders. Evidence suggests that inflammatory cytokines play a vital role in muscle inflammatory pathology and this may result in oxidative damage and mitochondrial dysfunction in skeletal muscle. In our study, we used microwave degradation to prepare a water-soluble low molecular weight guluronate (LMG) of 3000 Da from Fucus vesiculosus obtained from Canada, the Atlantic Ocean. We demonstrated the structural characteristics, using HPLC, FTIR and NMR of LMG and investigated its effects on oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells induced by tumor necrosis factor alpha (TNF-α), a cell inflammatory cytokine. The results indicated that LMG could alleviate mitochondrial reactive oxygen species (ROS) production, increase the activities of antioxidant enzymes (GSH and SOD), promote mitochondrial membrane potential (MMP) and upregulate the expression of mitochondrial respiratory chain protein in TNF-α-induced C2C12 cells. LMG supplement also increased the mitochondrial DNA copy number and mitochondrial biogenesis related genes in TNF-α-induced C2C12 cells. LMG may exert these protective effects through the nuclear factor kappa B (NF-κB) signaling pathway. These suggest that LMG is capable of protecting TNF-α-induced C2C12 cells against oxidative damage and mitochondrial dysfunction. PMID:26205038

  12. [Prevention of diabetic foot].

    PubMed

    Metelko, Zeljko; Brkljacić Crkvencić, Neva

    2013-10-01

    Diabetic foot (DF) is the most common chronic complication, which depends mostly on the duration and successful treatment of diabetes mellitus. Based on epidemiological studies, it is estimated that 25% of persons with diabetes mellitus (PwDM) will develop the problems with DF during lifetime, while 5% do 15% will be treated for foot or leg amputation. The treatment is prolonged and expensive, while the results are uncertain. The changes in DF are influenced by different factors usually connected with the duration and regulation of diabetes mellitus. The first problems with DF are the result of misbalance between nutritional, defensive and reparatory mechanisms on the one hand and the intensity of damaging factors against DF on the other hand. Diabetes mellitus is a state of chronic hyperglycemia, consisting of changes in carbohydrate, protein and fat metabolism. As a consequence of the long duration of diabetes mellitus, late complications can develop. Foot is in its structure very complex, combined with many large and small bones connected with ligaments, directed by many small and large muscles, interconnected with many small and large blood vessels and nerves. Every of these structures can be changed by nutritional, defensive and reparatory mechanisms with consequential DE Primary prevention of DF includes all measures involved in appropriate maintenance of nutrition, defense and reparatory mechanisms.First, it is necessary to identify the high-risk population for DF, in particular for macrovascular, microvascular and neural complications. The high-risk population of PwDM should be identified during regular examination and appropriate education should be performed. In this group, it is necessary to include more frequent and intensified empowerment for lifestyle changes, appropriate diet, regular exercise (including frequent breaks for short exercise during sedentary work), regular self control of body weight, quit smoking, and appropriate treatment of glycemia

  13. Endobronchial Ultrasound Bronchoscope Damage.

    PubMed

    Patil, Monali; Harris, Kassem; Krishnan, Amita; Alraiyes, Abdul H; Dhillon, Samjot S

    2016-07-01

    Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration is an effective, safe, and cost-effective diagnostic bronchoscopy technique for the work-up of mediastinal lymphadenopathy. Concern has been raised, however, about the high cost of convex-probe EBUS bronchoscope repairs. The damage is usually due to breakage of the insertion tube (the flexible part that is advanced into the airways), moisture invasion and damages to the working channel, image guide bundle, or umbilical cord. Understanding the root cause of EBUS scope damage is important for its prevention. We describe 2 unusual cases of EBUS scope damage. In the first case, the distal black rubber covering of the EBUS scope insertion tube was damaged due to friction with the edge of an endotracheal tube and in the second case, the EBUS scope insertion tube was angulating laterally instead of vertically during the flexion maneuver, probably due to scope manipulation while wedged tightly in a segmental bronchus. PMID:27077640

  14. Evolvable synthetic neural system

    NASA Technical Reports Server (NTRS)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  15. Prevention of UVA-Induced Oxidative Damage in Human Dermal Fibroblasts by New UV Filters, Assessed Using a Novel In Vitro Experimental System

    PubMed Central

    Emanuelli, Monica; Damiani, Elisabetta

    2014-01-01

    Background UVA rays present in sunlight are able to reach the dermal skin layer generating reactive oxygen species (ROS) responsible for oxidative damage, alterations in gene expression, DNA damage, leading to cell inflammation, photo-ageing/-carcinogenesis. Sunscreens contain UV filters as active ingredients that absorb/reflect/dissipate UV radiation: their efficiency depends on their spectral profile and photostability which should then be reflected in biological protection of underlying skin. Methods A set of new UV filters was synthesized, and the most photostable one was compared to BMDBM, a widely used UVA filter. Cultured human dermal fibroblasts were exposed to UVA radiation which was filtered by a base cream containing or not UV filters placed above cell culture wells. The endpoints measured were: cell viability (MTT assay), ROS generation (DCFH-DA assay), mitochondrial function (JC-1 assay), DNA integrity (Comet assay) and gene expression (MMP-1, COL1A1) by RT-qPCR. Results The new UV filter resulted more efficient than BMDBM in preserving cell viability, mitochondrial functionality and oxidative DNA damage, despite similar inhibition levels of intracellular ROS. Moreover, expression of genes involved in dermal photoageing were positively affected by the filtering action of the tested molecules. Conclusions The experimental model proposed was able to validate the efficacy of the new UV filter, taking into account important cellular events related to UV-induced intracellular oxidative stress, often underestimated in the assessments of these compounds. General Significance The model may be used to compare the actual biological protection of commercial sunscreens and suncare products aside from their SPF and UVA-PF values. PMID:24409282

  16. Prevention by eliprodil (SL 82.0715) of traumatic brain damage in the rat. Existence of a large (18 h) therapeutic window.

    PubMed

    Toulmond, S; Serrano, A; Benavides, J; Scatton, B

    1993-08-20

    The neuroprotective potential of eliprodil (SL 82.0715), an N-methyl-D-aspartate (NMDA) receptor antagonist acting at the polyamine modulatory site, in brain trauma was examined in a rat model of lateral fluid-percussion brain injury. The volume of the lesion was assessed histologically by measuring, at 7 days post-injury, the area of brain damage at 10 coronal planes. Eliprodil (10 mg/kg i.p.) when given 15 min, 6 h and 24 h after fluid percussion (1.6 atm) and then b.i.d. for the following 6 days, reduced by 60% the volume of cortical damage. A similar neuroprotection was obtained when the first administration of eliprodil was delayed by up to 12 h after the brain insult. Moreover, when the treatment with this compound was started at 18 h post-injury, cortical damage was still significantly reduced by 33%. Autoradiographic studies showed that eliprodil treatment (10 mg/kg, i.p.), initiated 15 min after the trauma, also caused a marked reduction of the loss of the neuronal marker omega 1-2 (central benzodiazepine) binding sites and of the increase in the glial/macrophage marker peripheral type benzodiazepine binding sites in the cerebral cortex. In contrast, dizocilpine (a blocker of the cationic channel coupled to the NMDA receptor) when administered 6 h and 24 h after fluid percussion and then b.i.d. for the following 6 days induced a non significant reduction of the volume of the lesion at the highest tolerated dose (0.6 mg/kg i.p.). These results demonstrate the neuroprotective activity of eliprodil in experimental brain trauma using neuropathology as an endpoint and indicate that there is a very large time window for therapeutic intervention, consistent with the delayed nature of the neuronal loss, in this condition. PMID:8402196

  17. How Diet Intervention via Modulation of DNA Damage Response through MicroRNAs May Have an Effect on Cancer Prevention and Aging, an in Silico Study.

    PubMed

    Carotenuto, Felicia; Albertini, Maria C; Coletti, Dario; Vilmercati, Alessandra; Campanella, Luigi; Darzynkiewicz, Zbigniew; Teodori, Laura

    2016-01-01

    The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in silico analysis by the DIANA-mirPathv3 software. The in silico analysis allowed us to identify pathways shared by different miRs involved in DD/DDR vis-à-vis the specific compounds. The results demonstrate that certain miRs (e.g., -146, -21) play a central role in the interplay among DD/DDR and the bioactive compounds. Furthermore, some specific pathways, such as "fatty acids biosynthesis/metabolism", "extracellular matrix-receptor interaction" and "signaling regulating the pluripotency of stem cells", appear to be targeted by most miRs affected by the studied compounds. Since DD/DDR and these pathways are strongly related to aging and carcinogenesis, the present in silico results of our study suggest that monitoring the induction of specific miRs may provide the means to assess the antiaging and chemopreventive properties of particular dietary compounds. PMID:27213347

  18. How Diet Intervention via Modulation of DNA Damage Response through MicroRNAs May Have an Effect on Cancer Prevention and Aging, an in Silico Study

    PubMed Central

    Carotenuto, Felicia; Albertini, Maria C.; Coletti, Dario; Vilmercati, Alessandra; Campanella, Luigi; Darzynkiewicz, Zbigniew; Teodori, Laura

    2016-01-01

    The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in silico analysis by the DIANA-mirPathv3 software. The in silico analysis allowed us to identify pathways shared by different miRs involved in DD/DDR vis-à-vis the specific compounds. The results demonstrate that certain miRs (e.g., -146, -21) play a central role in the interplay among DD/DDR and the bioactive compounds. Furthermore, some specific pathways, such as “fatty acids biosynthesis/metabolism”, “extracellular matrix-receptor interaction” and “signaling regulating the pluripotency of stem cells”, appear to be targeted by most miRs affected by the studied compounds. Since DD/DDR and these pathways are strongly related to aging and carcinogenesis, the present in silico results of our study suggest that monitoring the induction of specific miRs may provide the means to assess the antiaging and chemopreventive properties of particular dietary compounds. PMID:27213347

  19. Neural Networks

    SciTech Connect

    Smith, Patrick I.

    2003-09-23

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

  20. Neural Flight Control System

    NASA Technical Reports Server (NTRS)

    Gundy-Burlet, Karen

    2003-01-01

    The Neural Flight Control System (NFCS) was developed to address the need for control systems that can be produced and tested at lower cost, easily adapted to prototype vehicles and for flight systems that can accommodate damaged control surfaces or changes to aircraft stability and control characteristics resulting from failures or accidents. NFCS utilizes on a neural network-based flight control algorithm which automatically compensates for a broad spectrum of unanticipated damage or failures of an aircraft in flight. Pilot stick and rudder pedal inputs are fed into a reference model which produces pitch, roll and yaw rate commands. The reference model frequencies and gains can be set to provide handling quality characteristics suitable for the aircraft of interest. The rate commands are used in conjunction with estimates of the aircraft s stability and control (S&C) derivatives by a simplified Dynamic Inverse controller to produce virtual elevator, aileron and rudder commands. These virtual surface deflection commands are optimally distributed across the aircraft s available control surfaces using linear programming theory. Sensor data is compared with the reference model rate commands to produce an error signal. A Proportional/Integral (PI) error controller "winds up" on the error signal and adds an augmented command to the reference model output with the effect of zeroing the error signal. In order to provide more consistent handling qualities for the pilot, neural networks learn the behavior of the error controller and add in the augmented command before the integrator winds up. In the case of damage sufficient to affect the handling qualities of the aircraft, an Adaptive Critic is utilized to reduce the reference model frequencies and gains to stay within a flyable envelope of the aircraft.

  1. Craniofacial Birth Defects: The Role of Neural Crest Cells in the Etiology and Pathogenesis of Treacher Collins Syndrome and the Potential for Prevention

    PubMed Central

    Trainor, Paul A.

    2013-01-01

    Of all the babies born with birth defects, approximately one-third display anomalies of the head and face [Gorlin et al., 1990] including cleft lip, cleft palate, small or absent facial and skull bones and improperly formed nose, eyes, ears, and teeth. Craniofacial disorders are a primary cause of infant mortality and have serious lifetime functional, esthetic, and social consequences that are devastating to both children and parents alike. Comprehensive surgery, dental care, psychological counseling, and rehabilitation can help ameliorate-specific problems but at great cost over many years which dramatically affects national health care budgets. For example, the Center for Disease Control and Prevention estimates that the lifetime cost of treating the children born each year with cleft lip and/or cleft palate alone to be US$697 million. Treating craniofacial malformations, of which in excess of 700 distinct syndromes have been described, through comprehensive, well-coordinated and integrated strategies can provide satisfactory management of individual conditions, however, the results are often variable and rarely fully corrective. Therefore, better techniques for tissue repair and regeneration need to be developed and therapeutic avenues of prevention need to be explored in order to eliminate the devastating consequences of head and facial birth defects. To do this requires a thorough understanding of the normal events that control craniofacial development during embryogenesis. This review therefore focuses on recent advances in our understanding of the basic etiology and pathogenesis of a rare craniofacial disorder known as Treacher Collins syndrome and emerging prospects for prevention that may have broad application to congenital craniofacial birth defects. PMID:20734335

  2. Effectiveness of cinnamon (Cinnamomum zeylanicum) bark oil in the prevention of carbon tetrachloride-induced damages on the male reproductive system.

    PubMed

    Yüce, A; Türk, G; Çeribaşı, S; Güvenç, M; Çiftçi, M; Sönmez, M; Özer Kaya, Ş; Çay, M; Aksakal, M

    2014-04-01

    In this study, it was aimed to investigate the likelihood of detrimental effects of carbon tetrachloride (CCl4 ) on male reproductive system through oxidative stress mechanism and also protective effects of cinnamon bark oil (CBO). For this purpose, 28 healthy male Wistar rats were divided into four groups, seven rats in each. Group 1 received only olive oil daily; group 2 was treated with 100 mg kg(-1) CBO daily; group 3 was treated with only 0.25 ml kg(-1) CCl4 weekly; and group 4 received weekly CCl4 + daily CBO. All administrations were made by intragastric catheter and maintained for 10 weeks. Body and reproductive organ weights, sperm characteristics, testicular oxidative stress markers and testicular apoptosis were examined. CCl4 administration caused significant decreases in body and reproductive organ weights, testicular catalase (CAT) activity, sperm motility and concentration, and significant increases in lipid peroxidation (LPO) level, abnormal sperm rate and apoptotic index along with some histopathological damages compared with the control group. However, significant improvements were observed in absolute weights of testis and epididymis, all sperm quality parameters, LPO level, apoptotic index and testicular histopathological structure following the administration of CCl4 together with CBO when compared to group given CCl4 only. The findings of this study clearly suggest that CBO has protective effect against damages in male reproductive organs and cells induced by CCl4 . PMID:23410011

  3. Moringa oleifera Lam. seed extract prevents fat diet induced oxidative stress in mice and protects liver cell-nuclei from hydroxyl radical mediated damage.

    PubMed

    Das, Nilanjan; Ganguli, Debdutta; Dey, Sanjit

    2015-12-01

    High fat diet (HFD) prompts metabolic pattern inducing reactive oxygen species (ROS) production in mitochondria thereby triggering multitude of chronic disorders in human. Antioxidants from plant sources may be an imperative remedy against this disorder. However, it requires scientific validation. In this study, we explored if (i) Moringa oleifera seed extract (MoSE) can neutralize ROS generated in HFD fed mice; (ii) protect cell-nuclei damage developed by Fenton reaction in vitro. Swiss mice were fed with HFD to develop oxidative stress model (HFD group). Other groups were control, seed extract alone treated, and MoSE simultaneously (HS) treated. Treatment period was of 15 days. Antioxidant enzymes with tissue nitrite content (TNC) and lipid peroxidation (LPO) were estimated from liver homogenate. HS group showed significantly higher (P < 0.05) superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) activity, and ferric reducing antioxidant power (FRAP) compared to only HFD fed group. Further, TNC and LPO decreased significantly (P < 0.05) in HS group compared to HFD fed group. MoSE also protected hepatocytes nuclei from the hydroxyl radicals generated by Fenton reaction. MoSE was found to be polyphenol rich with potent reducing power, free radicals and hydroxyl radicals scavenging activity. Thus, MoSE exhibited robust antioxidant prospective to neutralize ROS developed in HFD fed mice and also protected the nuclei damage from hydroxyl radicals. Hence, it can be used as herbal medication against HFD induced ROS mediated disorders. PMID:26742324

  4. Role of permissive hypotension, hypertonic resuscitation and the global increased permeability syndrome in patients with severe hemorrhage: adjuncts to damage control resuscitation to prevent intra-abdominal hypertension.

    PubMed

    Duchesne, Juan C; Kaplan, Lewis J; Balogh, Zsolt J; Malbrain, Manu L N G

    2015-01-01

    Secondary intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are closely related to fluid resuscitation. IAH causes major deterioration of the cardiac function by affecting preload, contractility and afterload. The aim of this review is to discuss the different interactions between IAH, ACS and resuscitation, and to explore a new hypothesis with regard to damage control resuscitation, permissive hypotension and global increased permeability syndrome. Review of the relevant literature via PubMed search. The recognition of the association between the development of ACS and resuscitation urged the need for new approach in traumatic shock management. Over a decade after wide spread application of damage control surgery damage control resuscitation was developed. DCR differs from previous resuscitation approaches by attempting an earlier and more aggressive correction of coagulopathy, as well as metabolic derangements like acidosis and hypothermia, often referred to as the 'deadly triad' or the 'bloody vicious cycle'. Permissive hypotension involves keeping the blood pressure low enough to avoid exacerbating uncontrolled haemorrhage while maintaining perfusion to vital end organs. The potential detrimental mechanisms of early, aggressive crystalloid resuscitation have been described. Limitation of fluid intake by using colloids, hypertonic saline (HTS) or hyperoncotic albumin solutions have been associated with favourable effects. HTS allows not only for rapid restoration of circulating intravascular volume with less administered fluid, but also attenuates post-injury oedema at the microcirculatory level and may improve microvascular perfusion. Capillary leak represents the maladaptive, often excessive, and undesirable loss of fluid and electrolytes with or without protein into the interstitium that generates oedema. The global increased permeability syndrome (GIPS) has been articulated in patients with persistent systemic inflammation failing

  5. Neural repair in the adult brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury to the adult brain often results in substantial loss of neural tissue and subsequent permanent functional impairment. Over the last two decades, a number of approaches have been developed to harness the regenerative potential of neural stem cells and the existing fate plasticity of neural cells in the nervous system to prevent tissue loss or to enhance structural and functional regeneration upon injury. Here, we review recent advances of stem cell-associated neural repair in the adult brain, discuss current challenges and limitations, and suggest potential directions to foster the translation of experimental stem cell therapies into the clinic. PMID:26918167

  6. Calcitriol prevents peripheral RSC96 Schwann neural cells from high glucose & methylglyoxal-induced injury through restoration of CBS/H2S expression.

    PubMed

    Zhang, Hui; Zhuang, Xiao-dong; Meng, Fu-hui; Chen, Li; Dong, Xiao-bian; Liu, Guo-Hui; Li, Jian-hua; Dong, Qi; Xu, Ji-de; Yang, Chun-tao

    2016-01-01

    A meta-analysis has suggested that vitamin D deficiency is involved in diabetic peripheral neuropathy (DPN) and the levels of hydrogen sulfide (H2S) are also decreased in type 2 diabetes. The injection of vitamin D induces cystathionine-β-synthase (CBS) expression and H2S generation. However, it remains unclear whether the supplementation of vitamin D prevents DPN through improvement of CBS/H2S expression. In the present study, RSC96 cells, a rat Schwann cell line, were exposed to high glucose and methylglyoxal (HG&MG) to simulate diabetic peripheral nerve injury in vivo. Before the exposure to HG&MG, the cells were preconditioned with calcitriol (CCT), an active form of vitamin D, and then CCT-mediated neuroprotection was investigated in respect of cellular viability, superoxide anion (O2(-)) generation, inducible nitric oxide (NO) synthase (iNOS)/NO expression, mitochondrial membrane potential (MMP), as well as CBS expression and activity. It was found that both high glucose and MGO decreased cell viability and co-treatment with the two induced a more serious injury in RSC96 cells. Therefore, the exposure to HG&MG was used in the present study. The exposure to HG&MG markedly induced iNOS expression, NO and O2(-) generation, as well as MMP loss. In addition, the exposure to HG&MG depressed CBS expression and activity in RSC96 cells. However, the preconditioning with CCT significantly antagonized HG&MG-induced cell injury including the decreased viability, iNOS overexpression, NO and O2(-) accumulation, as well as MMP loss. CCT also partially restored the decreased CBS expression and activity triggered by HG&MG, while the inhibition of CBS with hydroxylamine attenuated CCT-mediated neuroprotection. Moreover, the exogenous donation of H2S produced similar cellular protective effects to CCT. The data indicate that the supplementation of vitamin D prevents HG&MG-induced peripheral nerve injury involving the restoration of endogenous H2S system, which may provide a

  7. Prevention of cardiac damage induced by formyl-leurosine, a potent cytostatic agent, by radio-detoxified endotoxin (Tolerin) in dogs

    SciTech Connect

    Bertok, L.; Juhasz-Nagy, A.; Sotonyi, P.

    1984-08-01

    Radio-detoxified endotoxin (Tolerin), produced by /sup 60/Co-gamma irradiation of Escherichia coli 089 endotoxin, can protect dogs against the acute cardiotoxic side-effects of formyl-leurosine, a semi-synthetic Vinca derivative with promising antineoplastic potency. Formyl-leurosine induces a rapid decrease in arterial blood pressure and diminishes the contractile force of the myocardium in the anaesthetized dog. These responses indicate a direct pharmacologic relaxant effect of the drug on the heart and vasculature smooth muscle. The early cardiovascular depression is of short duration and is unaffected by Tolerin. Tolerin can prevent, however, the secondary, more dangerous phase of circulatory depression that is associated with the severe cardiotoxic manifestations of the drug, as demonstrated by hemodynamic and morphologic (light and electronmicroscopic) patterns.

  8. The structural basis for the prevention of nonsteroidal antiinflammatory drug-induced gastrointestinal tract damage by the C-lobe of bovine colostrum lactoferrin.

    PubMed

    Mir, Rafia; Singh, Nagendra; Vikram, Gopalakrishnapillai; Kumar, Ramasamy Prem; Sinha, Mau; Bhushan, Asha; Kaur, Punit; Srinivasan, Alagiri; Sharma, Sujata; Singh, Tej P

    2009-12-16

    Nonsteroidal antiinflammatory drugs (NSAIDs), due to their good efficacy in the treatment of pain, inflammation, and fever, are among the most prescribed class of medicines in the world. The main drawback of NSAIDs is that they induce gastric complications such as peptic ulceration and injury to the intestine. Four NSAIDs, indomethacin, diclofenac, aspirin, and ibuprofen were selected to induce gastropathy in mouse models. It was found that the addition of C-terminal half of bovine lactoferrin (C-lobe) reversed the NSAID-induced injuries to the extent of 47-70% whereas the coadministration of C-lobe prevented it significantly. The C-lobe was prepared proteolytically using serine proteases. The binding studies of C-lobe with NSAIDs showed that these compounds bind to C-lobe with affinities ranging from 2.6 to 4.8 x 10(-4) M. The complexes of C-lobe were prepared with the above four NSAIDs. All four complexes were crystallized and their detailed three-dimensional structures were determined using x-ray crystallographic method. The structures showed that all the four NSAID molecules bound to C-lobe at the newly identified ligand binding site in C-lobe that is formed involving two alpha-helices, alpha10 and alpha11. The ligand binding site is separated from the well known iron binding site by the longest and the most stable beta-strand, betaj, in the structure. Similar results were also obtained with the full length lactoferrin molecule. This novel, to our knowledge, binding site in C-lobe of lactoferrin shows a good complementarity for the acidic and lipophilic compounds such as NSAIDs. We believe this indicates that C-lobe of lactoferrin can be exploited for the prevention of NSAID-induced gastropathy. PMID:20006955

  9. Preventive effect of Nile tilapia hydrolysate against oxidative damage of HepG2 cells and DNA mediated by H2O2 and AAPH.

    PubMed

    Yarnpakdee, Suthasinee; Benjakul, Soottawat; Kristinsson, Hordur G; Bakken, Hilma Eiðsdóttir

    2015-10-01

    Antioxidant activities of protein hydrolysate prepared from Nile tilapia protein isolate using Alcalase (HA), Alcalase followed by papain (HAPa) and their Sephadex G-25 fractions (FHA and FHAPa) were investigated in both chemical and cellular based models. Amongst all samples, FHAPa showed the highest chemical antioxidant activities, however it had no metal chelation activity. Cellular antioxidant ability of HA, HAPa and their fractions against H2O2 and AAPH induced oxidative damage of HepG2 cell and DNA were tested. When cells were pretreated with all hydrolysates or fractions at different concentrations (0.5-2 mg/mL) in the absence and presence of 50 μM Trolox, cell viability was in the range of 91.10-111.40 %. However, no difference in cell viability was observed among samples having various concentrations (P > 0.05). Cell reactive oxygen species (ROS) generation as mediated by H2O2 and AAPH decreased with treatment of hydrolysates or their fractions, especially in combination with 50 μM Trolox. FHAPa effectively inhibited H2O2 and peroxyl radical induced DNA scission in a dose dependent manner. Therefore, Nile tilapia protein hydrolysates could serve as a functional food ingredient. PMID:26396366

  10. Systematic analysis of time-dependent neural effects of soluble amyloid β oligomers in culture and in vivo: Prevention by scyllo-inositol.

    PubMed

    Jin, Ming; Selkoe, Dennis J

    2015-10-01

    Alzheimer's disease (AD) is currently being addressed by intensive investment in pre-clinical and clinical research on the amyloid hypothesis, but concern remains about the validity of the concept that soluble Aβ oligomers are principally responsible for initiating AD phenotypes. Here, we apply well-defined Aβ oligomers isolated from AD brains or made synthetically to document a systematic accrual of first subtle and then more profound changes in certain synaptic proteins in both primary neuronal cultures and behaving adult mice. Among the first (within hours) synaptic changes are selective decreases in surface levels of certain (e.g., GluA1) but not other (e.g., GluN2B) glutamate receptors and subtle microglial activation. After 4 days, numerous additional synaptic proteins are altered. Moreover, Aβ oligomers induce hyperphosphorylation of tau and subsequent neuritic dystrophy. All changes are prevented by scyllo-inositol in a dose- and stereoisomer-specific manner. Mechanistically, scyllo-inositol interferes quantitatively with the binding of Aβ oligomers to plasma membranes. These comprehensive analyses in culture and in vivo provide direct evidence that diffusible oligomers of human Aβ (without plaques) induce multiple phenotypic changes in healthy neurons, indicating their role as principal endogenous cytotoxins in AD. Our data recommend a re-examination of scyllo-inositol as an anti-oligomer therapeutic in humans with early AD. PMID:26054438

  11. Melatonin prevents cytosolic calcium overload, mitochondrial damage and cell death due to toxically high doses of dexamethasone-induced oxidative stress in human neuroblastoma SH-SY5Y cells.

    PubMed

    Suwanjang, Wilasinee; Abramov, Andrey Y; Charngkaew, Komgrid; Govitrapong, Piyarat; Chetsawang, Banthit

    2016-07-01

    Stressor exposure activates the hypothalamic-pituitary-adrenal (HPA) axis and causes elevations in the levels of glucocorticoids (GC) from the adrenal glands. Increasing evidence has demonstrated that prolonged exposure to high GC levels can lead to oxidative stress, calcium deregulation, mitochondrial dysfunction and apoptosis in a number of cell types. However, melatonin, via its antioxidant activity, exhibits a neuroprotective effect against oxidative stress-induced cell death. Therefore, in the present study, we explored the protective effect of melatonin in GC-induced toxicity in human neuroblastoma SH-SY5Y cells. Cellular treatment with the toxically high doses of the synthetic GC receptor agonist, dexamethasone (DEX) elicited marked decreases in the levels of glutathione and increases in ROS production, lipid peroxidation and cell death. DEX toxicity also induced increases in the levels of cytosolic calcium and mitochondrial fusion proteins (Mfn1 and Opa1) but decreases in the levels of mitochondrial fission proteins (Fis1 and Drp1). Mitochondrial damage was observed in large proportions of the DEX-treated cells. Pretreatment of the cells with melatonin substantially prevented the DEX-induced toxicity. These results suggest that melatonin might exert protective effects against oxidative stress, cytosolic calcium overload and mitochondrial damage in DEX-induced neurotoxicity. PMID:27155536

  12. Review of health hazards and prevention measures for response and recovery workers and volunteers after natural disasters, flooding, and water damage: mold and dampness.

    PubMed

    Johanning, Eckardt; Auger, Pierre; Morey, Philip R; Yang, Chin S; Olmsted, Ed

    2014-03-01

    Health problems and illnesses encountered by unprotected workers, first-responders, home-owners, and volunteers in recovery and restoration of moldy indoor environments after hurricanes, typhoons, tropical storms, and flooding damage are a growing concern for healthcare providers and disaster medicine throughout the world. Damp building materials, particularly cellulose-containing substrates, are prone to fungal (mold) and bacterial infestation. During remediation and demolition work, the airborne concentrations of such microbes and their by-products can rise significantly and result in an exposure risk. Symptoms reported by unprotected workers and volunteers may relate to reactions of the airways, skin, mucous membranes, or internal organs. Dampness-related fungi are primarily associated with allergies, respiratory symptoms or diseases such as dermatitis, rhinosinusitis, bronchitis, and asthma, as well as changes of the immunological system. Also, cognitive, endocrine, or rheumatological changes have been reported. Based on the consensus among experts at a recent scientific conference and a literature review, it is generally recommended to avoid and minimize unnecessary fungal exposure and use appropriate personal protective equipment (PPE) in disaster response and recovery work. Mycologists recommend addressing any moisture or water intrusion rapidly, since significant mold growth can occur within 48 h. Systematic source removal, cleaning with "soap and water," and "bulk removal" followed by high-efficiency particulate air vacuuming is recommended in most cases; use of "biocides" should be avoided in occupied areas. Public health agencies recommend use of adequate respiratory, skin, and eye protection. Workers can be protected against these diseases by use of dust control measures and appropriate personal protective equipment. At a minimum, a facial dust mask such as the National Institute for Occupational Safety and Health (NIOSH)-approved N95 respirator should

  13. Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP

    PubMed Central

    Mukherjee, Rajarshi; Mareninova, Olga A; Odinokova, Irina V; Huang, Wei; Murphy, John; Chvanov, Michael; Javed, Muhammad A; Wen, Li; Booth, David M; Cane, Matthew C; Awais, Muhammad; Gavillet, Bruno; Pruss, Rebecca M; Schaller, Sophie; Molkentin, Jeffery D; Tepikin, Alexei V; Petersen, Ole H; Pandol, Stephen J; Gukovsky, Ilya; Criddle, David N; Gukovskaya, Anna S; Sutton, Robert

    2016-01-01

    Objective Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. Design We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. Results MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. Conclusions This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease. PMID:26071131

  14. Phenylalanine Is Required to Promote Specific Developmental Responses and Prevents Cellular Damage in Response to Ultraviolet Light in Soybean (Glycine max) during the Seed-to-Seedling Transition

    PubMed Central

    Sullivan, Joe H.; Muhammad, DurreShahwar; Warpeha, Katherine M.

    2014-01-01

    UV-radiation elicits a suite of developmental (photomorphogenic) and protective responses in plants, but responses early post-germination have received little attention, particularly in intensively bred plants of economic importance. We examined germination, hypocotyl elongation, leaf pubescence and subcellular responses of germinating and/or etiolated soybean (Glycine max (L.) Merr.) seedlings in response to treatment with discrete wavelengths of UV-A or UV-B radiation. We demonstrate differential responses of germinating/young soybean seedlings to a range of UV wavelengths that indicate unique signal transduction mechanisms regulate UV-initiated responses. We have investigated how phenylalanine, a key substrate in the phenylpropanoid pathway, may be involved in these responses. Pubescence may be a key location for phenylalanine-derived protective compounds, as UV-B irradiation increased pubescence and accumulation of UV-absorbing compounds within primary leaf pubescence, visualized by microscopy and absorbance spectra. Mass spectrometry analysis of pubescence indicated that sinapic esters accumulate in the UV-irradiated hairs compared to unirradiated primary leaf tissue. Deleterious effects of some UV-B wavelengths on germination and seedling responses were reduced or entirely prevented by inclusion of phenylalanine in the growth media. Key effects of phenylalanine were not duplicated by tyrosine or tryptophan or sucrose, nor is the specificity of response due to the absorbance of phenylalanine itself. These results suggest that in the seed-to-seedling transition, phenylalanine may be a limiting factor in the development of initial mechanisms of UV protection in the developing leaf. PMID:25549094

  15. Haptoglobin binding to apolipoprotein A-I prevents damage from hydroxyl radicals on its stimulatory activity of the enzyme lecithin-cholesterol acyl-transferase.

    PubMed

    Salvatore, Alfonso; Cigliano, Luisa; Bucci, Enrico M; Corpillo, Davide; Velasco, Silvia; Carlucci, Alessandro; Pedone, Carlo; Abrescia, Paolo

    2007-10-01

    Apolipoprotein A-I (ApoA-I), a major component of HDL, binds haptoglobin, a plasma protein transporting to liver or macrophages free Hb for preventing hydroxyl radical production. This work aimed to assess whether haptoglobin protects ApoA-I against this radical. Human ApoA-I structure, as analyzed by electrophoresis and MS, was found severely altered by hydroxyl radicals in vitro. Lower alteration of ApoA-I was found when HDL was oxidized in the presence of haptoglobin. ApoA-I oxidation was limited also when the complex of haptoglobin with both high-density lipoprotein and Hb, immobilized on resin beads, was exposed to hydroxyl radicals. ApoA-I function to stimulate cholesterol esterification was assayed in vitro by using ApoA-I-containing liposomes. Decreased stimulation was observed when liposomes oxidized without haptoglobin were used. Conversely, after oxidative stress in the presence of haptoglobin (0.5 microM monomer), the liposome activity did not change. Plasma of carrageenan-treated mice was analyzed by ELISA for the levels of haptoglobin and ApoA-I, and used to isolate HDL for MS analysis. Hydroxyproline-containing fragments of ApoA-I were found associated with low levels of haptoglobin (18 microM monomer), whereas they were not detected when the haptoglobin level increased (34-70 microM monomer). Therefore haptoglobin, when circulating at enhanced levels with free Hb during the acute phase of inflammation, might protect ApoA-I structure and function against hydroxyl radicals. PMID:17824618

  16. Occurrence of sulfated fucose branches in fucosylated chondroitin sulfate are essential for the polysaccharide effect preventing muscle damage induced by toxins and crude venom from Bothrops jararacussu snake.

    PubMed

    Monteiro-Machado, Marcos; Tomaz, Marcelo A; Fonseca, Roberto J C; Strauch, Marcelo A; Cons, Bruno L; Borges, Paula A; Patrão-Neto, Fernando C; Tavares-Henriques, Matheus S; Teixeira-Cruz, Jhonatha M; Calil-Elias, Sabrina; Cintra, Adélia C O; Martinez, Ana Maria B; Mourão, Paulo A S; Melo, Paulo A

    2015-05-01

    Snake envenoming is an important public health problem around the world, particularly in tropics. Beyond deaths, morbidity induced by snake venoms, such as myotoxicity, is of pivotal consequence to population. Bothrops jararacussu is the main venomous snake in southeast region of Brazil, and particularly presents strong myotoxic effect. The only available therapy, antibothropic antivenom, poorly affects venom-induced myotoxicity. The aim of this study is to assess the ability of fucosylated chondroitin sulfate (fucCS), a glycosaminoglycan with anticoagulant and antithrombotic properties, and its derivatives to inhibit toxic activities of B. jararacussu crude venom and its isolated toxins, named bothropstoxins (BthTX-I and BthTX-II). The in vitro myotoxic activities induced by crude venom, by BthTX-I alone and by toxins together were abolished by fucCS. Carboxyl reduction (fucCS-CR) kept this ability whereas defucosilation (defucCS) abrogates myoprotection. We observed the same pattern in the response of these polysaccharides in antagonizing the increase in plasma creatine kinase (CK) levels, the reduction of skeletal muscle CK content and the rise of myeloperoxidase (MPO) activity induced by crude venom and isolated toxins. FucCS inhibited edematogenic activity and partially prevented the reduction of total leukocytes in blood when pre-incubated with crude venom. Furthermore, the venom procoagulant effect was completely antagonized by increasing concentrations of fucCS, although this polyanion could stop neither the tail bleeding nor the skin hemorrhage induced by Bothrops jararaca venom. The B. jararacussu phospholipase, hyaluronidase, proteolytic and collagenase activities were inhibited in vitro. The results suggest that fucCS could be able to interact with both toxins, and it is able to inhibit BthTX-II phospholipase activity. Light microscopy of extensor digitorum longus muscle (EDL) muscle showed myoprotection by fucCS, once necrotic areas, edema and

  17. Neural Engineering

    NASA Astrophysics Data System (ADS)

    He, Bin

    About the Series: Bioelectric Engineering presents state-of-the-art discussions on modern biomedical engineering with respect to applications of electrical engineering and information technology in biomedicine. This focus affirms Springer's commitment to publishing important reviews of the broadest interest to biomedical engineers, bioengineers, and their colleagues in affiliated disciplines. Recent volumes have covered modeling and imaging of bioelectric activity, neural engineering, biosignal processing, bionanotechnology, among other topics.

  18. DNA Damage and Repair in Vascular Disease.

    PubMed

    Uryga, Anna; Gray, Kelly; Bennett, Martin

    2016-01-01

    DNA damage affecting both genomic and mitochondrial DNA is present in a variety of both inherited and acquired vascular diseases. Multiple cell types show persistent DNA damage and a range of lesions. In turn, DNA damage activates a variety of DNA repair mechanisms, many of which are activated in vascular disease. Such DNA repair mechanisms either stall the cell cycle to allow repair to occur or trigger apoptosis or cell senescence to prevent propagation of damaged DNA. Recent evidence has indicated that DNA damage occurs early, is progressive, and is sufficient to impair function of cells composing the vascular wall. The consequences of persistent genomic and mitochondrial DNA damage, including inflammation, cell senescence, and apoptosis, are present in vascular disease. DNA damage can thus directly cause vascular disease, opening up new possibilities for both prevention and treatment. We review the evidence for and the causes, types, and consequences of DNA damage in vascular disease. PMID:26442438

  19. Molecular Signatures in the Prevention of Radiation Damage by the Synergistic Effect of N-Acetyl Cysteine and Qingre Liyan Decoction, a Traditional Chinese Medicine, Using a 3-Dimensional Cell Culture Model of Oral Mucositis

    PubMed Central

    Lambros, Maria P.; Kondapalli, Lavanya; Parsa, Cyrus; Mulamalla, Hari Chandana; Orlando, Robert; Pon, Doreen; Huang, Ying; Chow, Moses S. S.

    2015-01-01

    Qingre Liyan decoction (QYD), a Traditional Chinese medicine, and N-acetyl cysteine (NAC) have been used to prevent radiation induced mucositis. This work evaluates the protective mechanisms of QYD, NAC, and their combination (NAC-QYD) at the cellular and transcriptional level. A validated organotypic model of oral mucosal consisting of a three-dimensional (3D) cell tissue-culture of primary human keratinocytes exposed to X-ray irradiation was used. Six hours after the irradiation, the tissues were evaluated by hematoxylin and eosin (H and E) and a TUNEL assay to assess histopathology and apoptosis, respectively. Total RNA was extracted and used for microarray gene expression profiling. The tissue-cultures treated with NAC-QYD preserved their integrity and showed no apoptosis. Microarray results revealed that the NAC-QYD caused the upregulation of genes encoding metallothioneins, HMOX1, and other components of the Nrf2 pathway, which protects against oxidative stress. DNA repair genes (XCP, GADD45G, RAD9, and XRCC1), protective genes (EGFR and PPARD), and genes of the NFκB pathway were upregulated. Finally, tissue-cultures treated prophylactically with NAC-QYD showed significant downregulation of apoptosis, cytokines and chemokines genes, and constrained damage-associated molecular patterns (DAMPs). NAC-QYD treatment involves the protective effect of Nrf2, NFκB, and DNA repair factors. PMID:25705238

  20. Ginkgo Biloba Extract Attenuates Oxidative Stress and Apoptosis in Mouse Cochlear Neural Stem Cells.

    PubMed

    Wang, Congpin; Wang, Bin

    2016-05-01

    In the organ or Corti, oxidative stress could result in damage to the hearing, and neural stem cells (NSCs) hold great therapeutic potential in treating hearing loss. Ginkgo biloba extract (GBE) has been widely shown to exhibit anti-oxidative and anti-apoptotic effects in treatments of neural damage and disorder. Using hydrogen peroxide to induced oxidative stress as a model, we investigated the anti-oxidative role of GBE in isolated mouse cochlear NSCs. GBE treatment was found to significantly promote viability of NSCs, by markedly attenuating hydrogen peroxide induced oxidative stress. In addition, this anti-oxidative function of GBE was also able to prevent mitochondrial depolarization and subsequent apoptosis. Moreover, the anti-apoptotic role of GBE was mediated by antagonizing the intrinsic mitochondrial apoptotic pathway, where GBE could reverse the changes in key intrinsic apoptosis pathway factors including Bcl-2, Bax, and Caspase-3. Our data provided the first report on the beneficial role of GBE in protecting cochlear NSCs, by attenuating oxidative stress triggered intrinsic apoptosis, therefore supporting the potential therapeutic value of GBE in preventing oxidative stress-related hearing loss. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26799058

  1. Preventing stroke

    MedlinePlus

    Stroke - prevention; CVA - prevention; cerebral vascular accident - prevention; TIA - prevention, transient ischemic attack - prevention ... Clinical Cardiology; Council on Functional Genomics and ... Council on Hypertension. Guidelines for the primary prevention ...

  2. A Developmental Strategy To Prevent Lifelong Damage.

    ERIC Educational Resources Information Center

    Hamburg, David A.

    This report provides an overview of initiatives of the Carnegie Corporation, including its Task Force on Meeting the Needs of Young Children. This task force was established to promote healthy development and education in children ages 3 to 10, including an emphasis on primary education strategies for improvement in disadvantaged communities. The…

  3. Calcium-dependent neuroepithelial contractions expel damaged cells from the developing brain

    PubMed Central

    Herrgen, Leah; Voss, Oliver P.; Akerman, Colin J.

    2016-01-01

    Summary Both developing and adult organisms need efficient strategies for wound repair. In adult mammals, wounding triggers an inflammatory response that can exacerbate tissue injury and lead to scarring. In contrast, embryonic wounds heal quickly and with minimal inflammation, but how this is achieved remains incompletely understood. Using in vivo imaging in the developing brain of Xenopus laevis, we show that ATP release from damaged cells and subsequent activation of purinergic receptors induce long-range calcium waves in neural progenitor cells. Cytoskeletal reorganization, and activation of the actomyosin contractile machinery in a Rho kinase-dependent manner, then lead to rapid and pronounced apical-basal contractions of the neuroepithelium. These contractions drive the expulsion of damaged cells into the brain ventricle within seconds. Successful cell expulsion prevents the death of nearby cells and an exacerbation of the injury. Cell expulsion through neuroepithelial contraction represents a novel mechanism for rapid wound healing in the developing brain. PMID:25468753

  4. Calcium-dependent neuroepithelial contractions expel damaged cells from the developing brain.

    PubMed

    Herrgen, Leah; Voss, Oliver P; Akerman, Colin J

    2014-12-01

    Both developing and adult organisms need efficient strategies for wound repair. In adult mammals, wounding triggers an inflammatory response that can exacerbate tissue injury and lead to scarring. In contrast, embryonic wounds heal quickly and with minimal inflammation, but how this is achieved remains incompletely understood. Using in vivo imaging in the developing brain of Xenopus laevis, we show that ATP release from damaged cells and subsequent activation of purinergic receptors induce long-range calcium waves in neural progenitor cells. Cytoskeletal reorganization and activation of the actomyosin contractile machinery in a Rho kinase-dependent manner then lead to rapid and pronounced apical-basal contractions of the neuroepithelium. These contractions drive the expulsion of damaged cells into the brain ventricle within seconds. Successful cell expulsion prevents the death of nearby cells and an exacerbation of the injury. Cell expulsion through neuroepithelial contraction represents a mechanism for rapid wound healing in the developing brain. PMID:25468753

  5. Classification of HIV-1-mediated neuronal dendritic and synaptic damage using multiple criteria linear programming.

    PubMed

    Zheng, Jialin; Zhuang, Wei; Yan, Nian; Kou, Gang; Peng, Hui; McNally, Clancy; Erichsen, David; Cheloha, Abby; Herek, Shelley; Shi, Chris

    2004-01-01

    The ability to identify neuronal damage in the dendritic arbor during HIV-1-associated dementia (HAD) is crucial for designing specific therapies for the treatment of HAD. To study this process, we utilized a computer-based image analysis method to quantitatively assess HIV-1 viral protein gp120 and glutamate-mediated individual neuronal damage in cultured cortical neurons. Changes in the number of neurites, arbors, branch nodes, cell body area, and average arbor lengths were determined and a database was formed (http://dm.ist.unomaha. edu/database.htm). We further proposed a two-class model of multiple criteria linear programming (MCLP) to classify such HIV-1-mediated neuronal dendritic and synaptic damages. Given certain classes, including treatments with brain-derived neurotrophic factor (BDNF), glutamate, gp120 or non-treatment controls from our in vitro experimental systems, we used the two-class MCLP model to determine the data patterns between classes in order to gain insight about neuronal dendritic damages. This knowledge can be applied in principle to the design and study of specific therapies for the prevention or reversal of neuronal damage associated with HAD. Finally, the MCLP method was compared with a well-known artificial neural network algorithm to test for the relative potential of different data mining applications in HAD research. PMID:15365193

  6. Electronic Neural Networks

    NASA Technical Reports Server (NTRS)

    Thakoor, Anil

    1990-01-01

    Viewgraphs on electronic neural networks for space station are presented. Topics covered include: electronic neural networks; electronic implementations; VLSI/thin film hybrid hardware for neurocomputing; computations with analog parallel processing; features of neuroprocessors; applications of neuroprocessors; neural network hardware for terrain trafficability determination; a dedicated processor for path planning; neural network system interface; neural network for robotic control; error backpropagation algorithm for learning; resource allocation matrix; global optimization neuroprocessor; and electrically programmable read only thin-film synaptic array.

  7. Modifying Radiation Damage

    PubMed Central

    Kim, Kwanghee; McBride, William H.

    2011-01-01

    Radiation leaves a fairly characteristic footprint in biological materials, but this is rapidly all but obliterated by the canonical biological responses to the radiation damage. The innate immune recognition systems that sense “danger” through direct radiation damage and through associated collateral damage set in motion a chain of events that, in a tissue compromised by radiation, often unwittingly result in oscillating waves of molecular and cellular responses as tissues attempt to heal. Understanding “nature’s whispers” that inform on these processes will lead to novel forms of intervention targeted more precisely towards modifying them in an appropriate and timely fashion so as to improve the healing process and prevent or mitigate the development of acute and late effects of normal tissue radiation damage, whether it be accidental, as a result of a terrorist incident, or of therapeutic treatment of cancer. Here we attempt to discuss some of the non-free radical scavenging mechanisms that modify radiation responses and comment on where we see them within a conceptual framework of an evolving radiation-induced lesion. PMID:20583981

  8. Genetic, Epigenetic, and Environmental Contributions to Neural Tube Closure

    PubMed Central

    Wilde, Jonathan J.; Petersen, Juliette R.; Niswander, Lee

    2015-01-01

    The formation of the embryonic brain and spinal cord begins as the neural plate bends to form the neural folds, which meet and fuse to close the neural tube. The neural ectoderm and surrounding tissues also coordinate proliferation, differentiation, and patterning. This highly orchestrated process is susceptible to disruption, leading to neural tube defects (NTDs), a common birth defect. Here, we highlight genetic and epigenetic contributions to neural tube closure. We describe an online database we created as a resource for researchers, geneticists, and clinicians. Neural tube closure is sensitive to environmental influences, and we discuss disruptive causes, preventative measures, and possible mechanisms. New technologies will move beyond candidate genes in small cohort studies toward unbiased discoveries in sporadic NTD cases. This will uncover the genetic complexity of NTDs and critical gene-gene interactions. Animal models can reveal the causative nature of genetic variants, the genetic interrelationships, and the mechanisms underlying environmental influences. PMID:25292356

  9. Right Hemisphere Brain Damage

    MedlinePlus

    ... Language and Swallowing / Disorders and Diseases Right Hemisphere Brain Damage [ en Español ] What is right hemisphere brain ... right hemisphere brain damage ? What is right hemisphere brain damage? Right hemisphere brain damage (RHD) is damage ...

  10. DNA damage tolerance.

    PubMed

    Branzei, Dana; Psakhye, Ivan

    2016-06-01

    Accurate chromosomal DNA replication is fundamental for optimal cellular function and genome integrity. Replication perturbations activate DNA damage tolerance pathways, which are crucial to complete genome duplication as well as to prevent formation of deleterious double strand breaks. Cells use two general strategies to tolerate lesions: recombination to a homologous template, and trans-lesion synthesis with specialized polymerases. While key players of these processes have been outlined, much less is known on their choreography and regulation. Recent advances have uncovered principles by which DNA damage tolerance is regulated locally and temporally - in relation to replication timing and cell cycle stage -, and are beginning to elucidate the DNA dynamics that mediate lesion tolerance and influence chromosome structure during replication. PMID:27060551

  11. Hypertension and cerebrovascular damage.

    PubMed

    Veglio, Franco; Paglieri, Cristina; Rabbia, Franco; Bisbocci, Daniela; Bergui, Mauro; Cerrato, Paolo

    2009-08-01

    Hypertension is the most important modifiable factor for cerebrovascular disease. Stroke and dementia are growing health problems that have considerable social and economical consequences. Hypertension causes brain lesions by several mechanisms predisposing to lacunar infarctions, leucoaraiosis, and white matter changes as well as to intracerebral haemorrhages. These parenchymal damages determine evident or silent neurological alterations that often precede the onset of cognitive decline. It is important to recognize cerebrovascular disease and, above all, to correlate typical lesions to hypertension. Antihypertensive therapy has shown clinical benefits in primary and secondary prevention of stroke. These drugs represent important instruments against cerebrovascular disease but their effects on cognition are still matter of debate. Cerebral parenchymal and functional damages have to be considered together to make medical intervention more incisive. PMID:19100549

  12. Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation

    PubMed Central

    Sakai, Daisuke; Dixon, Jill; Achilleos, Annita; Dixon, Michael; Trainor, Paul A.

    2016-01-01

    Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype–phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1+/− mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies. PMID:26792133

  13. Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation.

    PubMed

    Sakai, Daisuke; Dixon, Jill; Achilleos, Annita; Dixon, Michael; Trainor, Paul A

    2016-01-01

    Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype-phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1(+/-) mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies. PMID:26792133

  14. Intelligent-based Structural Damage Detection Model

    SciTech Connect

    Lee, Eric Wai Ming; Yu, K.F.

    2010-05-21

    This paper presents the application of a novel Artificial Neural Network (ANN) model for the diagnosis of structural damage. The ANN model, denoted as the GRNNFA, is a hybrid model combining the General Regression Neural Network Model (GRNN) and the Fuzzy ART (FA) model. It not only retains the important features of the GRNN and FA models (i.e. fast and stable network training and incremental growth of network structure) but also facilitates the removal of the noise embedded in the training samples. Structural damage alters the stiffness distribution of the structure and so as to change the natural frequencies and mode shapes of the system. The measured modal parameter changes due to a particular damage are treated as patterns for that damage. The proposed GRNNFA model was trained to learn those patterns in order to detect the possible damage location of the structure. Simulated data is employed to verify and illustrate the procedures of the proposed ANN-based damage diagnosis methodology. The results of this study have demonstrated the feasibility of applying the GRNNFA model to structural damage diagnosis even when the training samples were noise contaminated.

  15. School Building Intrusions: Prevention Strategies.

    ERIC Educational Resources Information Center

    Gamble, Lanny R.; And Others

    1987-01-01

    Discusses the uses of building security systems to prevent loss from damage by vandalism in school buildings. Outlines types of systems, selection of systems, and current practices in securing schools. (MD)

  16. Optimal controller design for structural damage detection

    NASA Astrophysics Data System (ADS)

    Lew, Jiann-Shiun

    2005-03-01

    The virtual passive control technique has recently been applied to structural damage detection, where the virtual passive controller only uses the existing control devices, and no additional physical elements are attached to the tested structure. One important task is to design passive controllers that can enhance the sensitivity of the identified parameters, such as natural frequencies, to structural damage. This paper presents a novel study of an optimal controller design for structural damage detection. We apply not only passive controllers but also low-order and fixed-structure controllers, such as PID controllers. In the optimal control design, the performance of structural damage detection is based on the application of a neural network technique, which uses the pattern of the correlation between the natural frequency changes of the tested system and the damaged system.

  17. FGF signaling transforms non-neural ectoderm into neural crest.

    PubMed

    Yardley, Nathan; García-Castro, Martín I

    2012-12-15

    The neural crest arises at the border between the neural plate and the adjacent non-neural ectoderm. It has been suggested that both neural and non-neural ectoderm can contribute to the neural crest. Several studies have examined the molecular mechanisms that regulate neural crest induction in neuralized tissues or the neural plate border. Here, using the chick as a model system, we address the molecular mechanisms by which non-neural ectoderm generates neural crest. We report that in response to FGF the non-neural ectoderm can ectopically express several early neural crest markers (Pax7, Msx1, Dlx5, Sox9, FoxD3, Snail2, and Sox10). Importantly this response to FGF signaling can occur without inducing ectopic mesodermal tissues. Furthermore, the non-neural ectoderm responds to FGF by expressing the prospective neural marker Sox3, but it does not express definitive markers of neural or anterior neural (Sox2 and Otx2) tissues. These results suggest that the non-neural ectoderm can launch the neural crest program in the absence of mesoderm, without acquiring definitive neural character. Finally, we report that prior to the upregulation of these neural crest markers, the non-neural ectoderm upregulates both BMP and Wnt molecules in response to FGF. Our results provide the first effort to understand the molecular events leading to neural crest development via the non-neural ectoderm in amniotes and present a distinct response to FGF signaling. PMID:23000357

  18. Neural mechanisms and potential treatment of epilepsy and its complications

    PubMed Central

    Liu, Tao-Tao; He, Zhi-Gang; Tian, Xue-Bi; Xiang, Hong-Bing

    2014-01-01

    The factors underlying epilepsy are multifaceted, but recent research suggests that the brain’s neural circuits, which play a key role in controlling the balance between epileptic and antiepileptic factors, may lie at the heart of epilepsy. This article provides a comprehensive review of the neural mechanisms and potential treatment of intractable epilepsy from neural inflammatory responses, melanocortin circuits in brain and pedunculopontine tegmental nucleus. Further studies should be undertaken to elucidate the nature of neural circuits so that we may more effectively apply these new preventive and symptomatic therapies to the patient suffering from medically refractory seizures and its complications. PMID:25628775

  19. Mitochondrial DNA Damage and Diseases

    PubMed Central

    Singh, Gyanesh; Pachouri, U C; Khaidem, Devika Chanu; Kundu, Aman; Chopra, Chirag; Singh, Pushplata

    2015-01-01

    Various endogenous and environmental factors can cause mitochondrial DNA (mtDNA) damage.  One of the reasons for enhanced mtDNA damage could be its proximity to the source of oxidants, and lack of histone-like protective proteins. Moreover, mitochondria contain inadequate DNA repair pathways, and, diminished DNA repair capacity may be one of the factors responsible for high mutation frequency of the mtDNA. mtDNA damage might cause impaired mitochondrial function, and, unrepaired mtDNA damage has been frequently linked with several diseases. Exploration of mitochondrial perspective of diseases might lead to a better understanding of several diseases, and will certainly open new avenues for detection, cure, and prevention of ailments.

  20. Brain and language: evidence for neural multifunctionality.

    PubMed

    Cahana-Amitay, Dalia; Albert, Martin L

    2014-01-01

    This review paper presents converging evidence from studies of brain damage and longitudinal studies of language in aging which supports the following thesis: the neural basis of language can best be understood by the concept of neural multifunctionality. In this paper the term "neural multifunctionality" refers to incorporation of nonlinguistic functions into language models of the intact brain, reflecting a multifunctional perspective whereby a constant and dynamic interaction exists among neural networks subserving cognitive, affective, and praxic functions with neural networks specialized for lexical retrieval, sentence comprehension, and discourse processing, giving rise to language as we know it. By way of example, we consider effects of executive system functions on aspects of semantic processing among persons with and without aphasia, as well as the interaction of executive and language functions among older adults. We conclude by indicating how this multifunctional view of brain-language relations extends to the realm of language recovery from aphasia, where evidence of the influence of nonlinguistic factors on the reshaping of neural circuitry for aphasia rehabilitation is clearly emerging. PMID:25009368

  1. Neural Tube Defects

    MedlinePlus

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the first month ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In spina bifida, ...

  2. Morphological neural networks

    SciTech Connect

    Ritter, G.X.; Sussner, P.

    1996-12-31

    The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

  3. Robust Fault Detection of Wind Energy Conversion Systems Based on Dynamic Neural Networks

    PubMed Central

    Talebi, Nasser; Sadrnia, Mohammad Ali; Darabi, Ahmad

    2014-01-01

    Occurrence of faults in wind energy conversion systems (WECSs) is inevitable. In order to detect the occurred faults at the appropriate time, avoid heavy economic losses, ensure safe system operation, prevent damage to adjacent relevant systems, and facilitate timely repair of failed components; a fault detection system (FDS) is required. Recurrent neural networks (RNNs) have gained a noticeable position in FDSs and they have been widely used for modeling of complex dynamical systems. One method for designing an FDS is to prepare a dynamic neural model emulating the normal system behavior. By comparing the outputs of the real system and neural model, incidence of the faults can be identified. In this paper, by utilizing a comprehensive dynamic model which contains both mechanical and electrical components of the WECS, an FDS is suggested using dynamic RNNs. The presented FDS detects faults of the generator's angular velocity sensor, pitch angle sensors, and pitch actuators. Robustness of the FDS is achieved by employing an adaptive threshold. Simulation results show that the proposed scheme is capable to detect the faults shortly and it has very low false and missed alarms rate. PMID:24744774

  4. Robust fault detection of wind energy conversion systems based on dynamic neural networks.

    PubMed

    Talebi, Nasser; Sadrnia, Mohammad Ali; Darabi, Ahmad

    2014-01-01

    Occurrence of faults in wind energy conversion systems (WECSs) is inevitable. In order to detect the occurred faults at the appropriate time, avoid heavy economic losses, ensure safe system operation, prevent damage to adjacent relevant systems, and facilitate timely repair of failed components; a fault detection system (FDS) is required. Recurrent neural networks (RNNs) have gained a noticeable position in FDSs and they have been widely used for modeling of complex dynamical systems. One method for designing an FDS is to prepare a dynamic neural model emulating the normal system behavior. By comparing the outputs of the real system and neural model, incidence of the faults can be identified. In this paper, by utilizing a comprehensive dynamic model which contains both mechanical and electrical components of the WECS, an FDS is suggested using dynamic RNNs. The presented FDS detects faults of the generator's angular velocity sensor, pitch angle sensors, and pitch actuators. Robustness of the FDS is achieved by employing an adaptive threshold. Simulation results show that the proposed scheme is capable to detect the faults shortly and it has very low false and missed alarms rate. PMID:24744774

  5. Optical Neural Interfaces

    PubMed Central

    Warden, Melissa R.; Cardin, Jessica A.; Deisseroth, Karl

    2014-01-01

    Genetically encoded optical actuators and indicators have changed the landscape of neuroscience, enabling targetable control and readout of specific components of intact neural circuits in behaving animals. Here, we review the development of optical neural interfaces, focusing on hardware designed for optical control of neural activity, integrated optical control and electrical readout, and optical readout of population and single-cell neural activity in freely moving mammals. PMID:25014785

  6. Patterns in neural processing

    NASA Astrophysics Data System (ADS)

    Engineer, Sunu

    2012-03-01

    In this paper we propose a model for neural processing that addresses both the evolutionary and functional aspects of neural systems that are observed in nature, from the simplest neural collections to dense large scale associations such as human brains. We propose both an architecture and a process in which these components interact to create the emergent behavior that we define as the 'mind'.

  7. Neural crest induction by paraxial mesoderm in Xenopus embryos requires FGF signals.

    PubMed

    Monsoro-Burq, Anne-Hélène; Fletcher, Russell B; Harland, Richard M

    2003-07-01

    At the border of the neural plate, the induction of the neural crest can be achieved by interactions with the epidermis, or with the underlying mesoderm. Wnt signals are required for the inducing activity of the epidermis in chick and amphibian embryos. Here, we analyze the molecular mechanisms of neural crest induction by the mesoderm in Xenopus embryos. Using a recombination assay, we show that prospective paraxial mesoderm induces a panel of neural crest markers (Slug, FoxD3, Zic5 and Sox9), whereas the future axial mesoderm only induces a subset of these genes. This induction is blocked by a dominant negative (dn) form of FGFR1. However, neither dnFGFR4a nor inhibition of Wnt signaling prevents neural crest induction in this system. Among the FGFs, FGF8 is strongly expressed by the paraxial mesoderm. FGF8 is sufficient to induce the neural crest markers FoxD3, Sox9 and Zic5 transiently in the animal cap assay. In vivo, FGF8 injections also expand the Slug expression domain. This suggests that FGF8 can initiate neural crest formation and cooperates with other DLMZ-derived factors to maintain and complete neural crest induction. In contrast to Wnts, eFGF or bFGF, FGF8 elicits neural crest induction in the absence of mesoderm induction and without a requirement for BMP antagonists. In vivo, it is difficult to dissociate the roles of FGF and WNT factors in mesoderm induction and neural patterning. We show that, in most cases, effects on neural crest formation were parallel to altered mesoderm or neural development. However, neural and neural crest patterning can be dissociated experimentally using different dominant-negative manipulations: while Nfz8 blocks both posterior neural plate formation and neural crest formation, dnFGFR4a blocks neural patterning without blocking neural crest formation. These results suggest that different signal transduction mechanisms may be used in neural crest induction, and anteroposterior neural patterning. PMID:12783784

  8. Integrated Neural Flight and Propulsion Control System

    NASA Technical Reports Server (NTRS)

    Kaneshige, John; Gundy-Burlet, Karen; Norvig, Peter (Technical Monitor)

    2001-01-01

    This paper describes an integrated neural flight and propulsion control system. which uses a neural network based approach for applying alternate sources of control power in the presence of damage or failures. Under normal operating conditions, the system utilizes conventional flight control surfaces. Neural networks are used to provide consistent handling qualities across flight conditions and for different aircraft configurations. Under damage or failure conditions, the system may utilize unconventional flight control surface allocations, along with integrated propulsion control, when additional control power is necessary for achieving desired flight control performance. In this case, neural networks are used to adapt to changes in aircraft dynamics and control allocation schemes. Of significant importance here is the fact that this system can operate without emergency or backup flight control mode operations. An additional advantage is that this system can utilize, but does not require, fault detection and isolation information or explicit parameter identification. Piloted simulation studies were performed on a commercial transport aircraft simulator. Subjects included both NASA test pilots and commercial airline crews. Results demonstrate the potential for improving handing qualities and significantly increasing survivability rates under various simulated failure conditions.

  9. XSIP1 is essential for early neural gene expression and neural differentiation by suppression of BMP signaling.

    PubMed

    Nitta, Kazuhiro R; Tanegashima, Kousuke; Takahashi, Shuji; Asashima, Makoto

    2004-11-01

    Neural differentiation is induced by inhibition of BMP signaling. Secreted inhibitors of BMP such as Chordin from the Spemann organizer contribute to the initial step of neural induction. Xenopus Smad-interacting protein-1 gene (XSIP1) is expressed in neuroectoderm from the early gastrula stage through to the neurula stage. XSIP1 is able to inhibit BMP signaling and overexpression of XSIP1 induces neural differentiation. To clarify the function of XSIP1 in neural differentiation, we performed a loss-of-function study of XSIP1. Knockdown of XSIP1 inhibited SoxD expression and neural differentiation. These results indicate that XSIP1 is essential for neural induction. Furthermore, loss-of-function experiments showed that SoxD is essential for XSIP1 transcription and for neural differentiation. However, inhibition of XSIP1 translation prevented neural differentiation induced by SoxD; thus, SoxD was not sufficient to mediate neural differentiation. Expression of XSIP1 was also required for inhibition of BMP signaling. Together, these results suggest that XSIP1 and SoxD interdependently function to maintain neural differentiation. PMID:15464588

  10. [Nerve injury following implant placement: prevention, diagnosis and treatment modalities].

    PubMed

    Nazarian, Y; Eliav, E; Nahlieli, O

    2003-07-01

    Nerve injury is a well-known complication following oral and maxillofacial surgery. Direct trauma, inflammation and infection are postoperative neural disturbances main causes. The most inflicted nerves associated with endosseous implant placement are those innervating the mandible: the inferior alveolar nerve, the mental nerve and the lingual nerve. Evaluation of the nerve injury characteristics and severity as early as possible has always imposed a great challenge for clinicians. We demonstrate a reliable yet simple way of dealing with this kind of problem in conjunction with comparing preoperative and postoperative sensation of the chin, the tongue and the lower lip. On the other hand, it is considerably important to take preventive measures for such injuries by using appropriate radiographic images. If a nerve damage has occurred, best prognosis is to be expected by early and appropriate treatment. It is imperative to treat such injuries in four months following the injury, otherwise a permanent nerve damage may occur. Further investigation of nerve damage risks following implant placement should be performed in order to enable patient to decide whether having implants dependent rehabilitation or choosing an alternative. PMID:14515628

  11. EDITORIAL: Focus on the neural interface Focus on the neural interface

    NASA Astrophysics Data System (ADS)

    Durand, Dominique M.

    2009-10-01

    they can fail to record reliably neural signals for long periods of time. McConnell et al show that by measuring the impedance of the tissue, one can evaluate the extent of the tissue response to the presence of the electrode. Another problem with the neural interface is the mismatch of the mechanical properties between electrode and tissue. Basinger et al use finite element modeling to analyze this mismatch in retinal prostheses and guide the design of new implantable devices. Electrical stimulation has been the method of choice to activate externally the nervous system. However, Zhang et al show that a novel dual hybrid device integrating electrical and optical stimulation can provide an effective interface for simultaneous recording and stimulation. By interfacing an EMG recording system and a movement detection system, Johnson and Fuglevand develop a model capable of predicting muscle activity during movement that could be important for the development of motor prostheses. Sensory restoration is another unsolved problem in neural prostheses. By developing a novel interface between the dorsal root ganglia and electrodes arrays, Gaunt et al show that it is possible to recruit afferent fibers for sensory substitution. Finally, by interfacing directly with muscles, Jung and colleagues show that stimulation of muscles involved in locomotion following spinal cord damage in rats can provide an effective treatment modality for incomplete spinal cord injury. This series of articles clearly shows that the interface is indeed one of the keys to successful therapeutic neural devices. The next Neural Interfaces Conference will take place in Los Angeles, CA in June 2010 and one can expect to see new developments in neural engineering obtained by focusing on the neural interface.

  12. Modified bacterial cellulose tubes for regeneration of damaged peripheral nerves

    PubMed Central

    Cala, Jaroslaw; Grobelski, Bartlomiej; Sygut, Dominik; Jesionek-Kupnicka, Dorota; Kolodziejczyk, Marek; Bielecki, Stanislaw; Pasieka, Zbigniew

    2013-01-01

    Introduction The subject of the experiment was bacterial nanocellulose, a natural polymer produced by bacteria – Gluconacetobacter xylinus. Following a specific modification process a cartilage-like material for restoration of damaged tissues may be produced. The obtained implants with excellent biocompatibility, mouldability, biophysical and chemical properties perfectly fit the needs of reconstructive surgery. The goal of the experiment was to develop and analyze cellulosic guidance channels in vivo for the reconstruction of damaged peripheral nerves. Material and methods The experiments were conducted on Wistar rats, femoral nerve. Cellulose was produced according to a self-patented method. In the experimental group tubulization was applied, whereas in the control traditional end-to-end connection was used. Observation time was 30, 60, 90, and 180 days. Results evaluation included histological analysis and postoperative observation of motor recovery. Results The overgrowth of connective tissue and disorganisation of neural structures was evident in 86.67% of control specimens, while for cellulosic group it was only 35% (p = 0.0022). Tubulization prevented the excessive proliferation of connective tissue and isolated from penetration with scar tissue. Autocannibalism, being probably an evidence of neurotrophic factors amassment, was observed in cellulosic group but not in the control one. Motor recovery did not differ significantly (p > 0.05). Biocompatibility of implants was affirmed by very small level of tissue response and susceptibility to vascularisation. Conclusions Cellulosic neurotubes effectively prevent the formation of neuromas. They are of very good biocompatibility and allow the accumulation of neurotrophic factors inside, thus facilitating the process of nerve regeneration. PMID:23847677

  13. Neural crest development in fetal alcohol syndrome.

    PubMed

    Smith, Susan M; Garic, Ana; Flentke, George R; Berres, Mark E

    2014-09-01

    Fetal alcohol spectrum disorder (FASD) is a leading cause of neurodevelopmental disability. Some affected individuals possess distinctive craniofacial deficits, but many more lack overt facial changes. An understanding of the mechanisms underlying these deficits would inform their diagnostic utility. Our understanding of these mechanisms is challenged because ethanol lacks a single receptor when redirecting cellular activity. This review summarizes our current understanding of how ethanol alters neural crest development. Ample evidence shows that ethanol causes the "classic" fetal alcohol syndrome (FAS) face (short palpebral fissures, elongated upper lip, deficient philtrum) because it suppresses prechordal plate outgrowth, thereby reducing neuroectoderm and neural crest induction and causing holoprosencephaly. Prenatal alcohol exposure (PAE) at premigratory stages elicits a different facial appearance, indicating FASD may represent a spectrum of facial outcomes. PAE at this premigratory period initiates a calcium transient that activates CaMKII and destabilizes transcriptionally active β-catenin, thereby initiating apoptosis within neural crest populations. Contributing to neural crest vulnerability are their low antioxidant responses. Ethanol-treated neural crest produce reactive oxygen species and free radical scavengers attenuate their production and prevent apoptosis. Ethanol also significantly impairs neural crest migration, causing cytoskeletal rearrangements that destabilize focal adhesion formation; their directional migratory capacity is also lost. Genetic factors further modify vulnerability to ethanol-induced craniofacial dysmorphology and include genes important for neural crest development, including shh signaling, PDFGA, vangl2, and ribosomal biogenesis. Because facial and brain development are mechanistically and functionally linked, research into ethanol's effects on neural crest also informs our understanding of ethanol's CNS pathologies. PMID

  14. Neural Crest Development in Fetal Alcohol Syndrome

    PubMed Central

    Smith, Susan M.; Garic, Ana; Flentke, George R.; Berres, Mark E.

    2016-01-01

    Fetal alcohol spectrum disorder (FASD) is a leading cause of neurodevelopmental disability. Some affected individuals possess distinctive craniofacial deficits, but many more lack overt facial changes. An understanding of the mechanisms underlying these deficits would inform their diagnostic utility. Our understanding of these mechanisms is challenged because ethanol lacks a single receptor when redirecting cellular activity. This review summarizes our current understanding of how ethanol alters neural crest development. Ample evidence shows that ethanol causes the “classic” fetal alcohol syndrome (FAS) face (short palpebral fissures, elongated upper lip, deficient philtrum) because it suppresses prechordal plate outgrowth, thereby reducing neuroectoderm and neural crest induction and causing holoprosencephaly. Prenatal alcohol exposure (PAE) at premigratory stages elicits a different facial appearance, indicating FASD may represent a spectrum of facial outcomes. PAE at this premigratory period initiates a calcium transient that activates CaMKII and destabilizes transcriptionally active β-catenin, thereby initiating apoptosis within neural crest populations. Contributing to neural crest vulnerability are their low antioxidant responses. Ethanol-treated neural crest produce reactive oxygen species, and free radical scavengers attenuate their production and prevent apoptosis. Ethanol also significantly impairs neural crest migration, causing cytoskeletal rearrangements that destabilize focal adhesion formation; their directional migratory capacity is also lost. Genetic factors further modify vulnerability to ethanol-induced craniofacial dysmorphology, and include genes important for neural crest development including shh signaling, PDFGA, vangl2, and ribosomal biogenesis. Because facial and brain development are mechanistically and functionally linked, research into ethanol’s effects on neural crest also informs our understanding of ethanol’s CNS pathologies

  15. Evolvable Neural Software System

    NASA Technical Reports Server (NTRS)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  16. [A Handling Qualities Metric for Damaged Aircraft

    NASA Technical Reports Server (NTRS)

    Cogan, Bruce; Hayes, Peggy

    2009-01-01

    In recent flight tests of F-15 Intelligent Flight Control System (IFCS), software simulated aircraft control surface failures were inserted to evaluate the IFCS adaptive systems. The failure commanded the left stabilator to a fixed position. The adaptive system uses a neural network that is designed to change control law gains, in the event of damage (real or simulated), that allows the aircraft to fly as it had before the damage. The performance of the adaptive system was assessed in terms of its ability to re-establish good onboard model tracking and its ability to decouple roll and pitch response.

  17. Human amniotic fluid-derived mesenchymal cells from fetuses with a neural tube defect do not deposit collagen type i protein after TGF-β1 stimulation in vitro.

    PubMed

    Hosper, Nynke A; Bank, Ruud A; van den Berg, Paul P

    2014-03-01

    In spina bifida, the neural tube fails to close during the embryonic period. Exposure of the neural tube to the amniotic fluid during pregnancy causes additional neural damage. Intrauterine tissue engineering using a biomaterial seeded with stem cells might prevent this additional damage. For this purpose, autologous cells from the amniotic fluid are an attractive source. To close the defect, it is important that these cells deposit an extracellular matrix. However, it is not known if amniotic fluid mesenchymal cells (AFMCs) from a fetus with a neural tube defect (NTD) share the same characteristics as AFMCs from a healthy fetus. We found that cells derived from fetuses with a NTD, in contrast to healthy human amniotic fluid cells, did not deposit collagen type I. Furthermore, the NTD cells showed, compared with both healthy amniotic fluid cells and fetal fibroblasts, much lower mRNA expression levels of genes that are involved in collagen biosynthesis [procollagen C-endopeptidase enhancer proteins (PCOLCE), PCOLCE2, ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2), ADAMTS14]. This indicates that NTD-AFMCs have different characteristics compared with healthy AFMCs and might not be suitable for fetal therapy to close the defect in spina bifida patients. PMID:24171700

  18. Diagnosis and Prognosis of Bearing Failure in Rotating Machinery Using Acoustic Emission and Artificial Neural Network

    NASA Astrophysics Data System (ADS)

    Mahamad, Abd Kadir; Hiyama, Takashi; Ghazali, Mohd Imran

    Bearing failure is well-known as a common problem in industries. Therefore, timely diagnosis and prognosis (DAP) of bearing fault is very crucial in order to prevent sudden damages. This paper proposes the practical method of bearing fault DAP using acoustic emission (AE) technique assisted with artificial neural network (ANN). The bearings failure data is measured based on the AE in terms of decibel (dB) and Distress levels, which are used as input for ANN of a bearing fault DAP. For this purpose, an experimental rig is setup to collect data from target bearing by using Machine Health Checker (MHC) Memo assisted with MHC Analysis software. In this work, Elman network with training algorithm, Levenberg-Marquardt Back- propagation is used for ANN DAP. The obtained results indicates that the proposed methods are suitable to inform the remaining useful life time of a faulty bearing.

  19. Smart accelerometer. [vibration damage detection

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J., Jr. (Inventor)

    1994-01-01

    The invention discloses methods and apparatus for detecting vibrations from machines which indicate an impending malfunction for the purpose of preventing additional damage and allowing for an orderly shutdown or a change in mode of operation. The method and apparatus is especially suited for reliable operation in providing thruster control data concerning unstable vibration in an electrical environment which is typically noisy and in which unrecognized ground loops may exist.

  20. Exploring neural network technology

    SciTech Connect

    Naser, J.; Maulbetsch, J.

    1992-12-01

    EPRI is funding several projects to explore neural network technology, a form of artificial intelligence that some believe may mimic the way the human brain processes information. This research seeks to provide a better understanding of fundamental neural network characteristics and to identify promising utility industry applications. Results to date indicate that the unique attributes of neural networks could lead to improved monitoring, diagnostic, and control capabilities for a variety of complex utility operations. 2 figs.

  1. Fuzzy and neural control

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1992-01-01

    Fuzzy logic and neural networks provide new methods for designing control systems. Fuzzy logic controllers do not require a complete analytical model of a dynamic system and can provide knowledge-based heuristic controllers for ill-defined and complex systems. Neural networks can be used for learning control. In this chapter, we discuss hybrid methods using fuzzy logic and neural networks which can start with an approximate control knowledge base and refine it through reinforcement learning.

  2. Computing with Neural Synchrony

    PubMed Central

    Brette, Romain

    2012-01-01

    Neurons communicate primarily with spikes, but most theories of neural computation are based on firing rates. Yet, many experimental observations suggest that the temporal coordination of spikes plays a role in sensory processing. Among potential spike-based codes, synchrony appears as a good candidate because neural firing and plasticity are sensitive to fine input correlations. However, it is unclear what role synchrony may play in neural computation, and what functional advantage it may provide. With a theoretical approach, I show that the computational interest of neural synchrony appears when neurons have heterogeneous properties. In this context, the relationship between stimuli and neural synchrony is captured by the concept of synchrony receptive field, the set of stimuli which induce synchronous responses in a group of neurons. In a heterogeneous neural population, it appears that synchrony patterns represent structure or sensory invariants in stimuli, which can then be detected by postsynaptic neurons. The required neural circuitry can spontaneously emerge with spike-timing-dependent plasticity. Using examples in different sensory modalities, I show that this allows simple neural circuits to extract relevant information from realistic sensory stimuli, for example to identify a fluctuating odor in the presence of distractors. This theory of synchrony-based computation shows that relative spike timing may indeed have computational relevance, and suggests new types of neural network models for sensory processing with appealing computational properties. PMID:22719243

  3. A consensual neural network

    NASA Technical Reports Server (NTRS)

    Benediktsson, J. A.; Ersoy, O. K.; Swain, P. H.

    1991-01-01

    A neural network architecture called a consensual neural network (CNN) is proposed for the classification of data from multiple sources. Its relation to hierarchical and ensemble neural networks is discussed. CNN is based on the statistical consensus theory and uses nonlinearly transformed input data. The input data are transformed several times, and the different transformed data are applied as if they were independent inputs. The independent inputs are classified using stage neural networks and outputs from the stage networks are then weighted and combined to make a decision. Experimental results based on remote-sensing data and geographic data are given.

  4. What Are Neural Tube Defects?

    MedlinePlus

    ... NICHD Research Information Clinical Trials Resources and Publications Neural Tube Defects (NTDs): Condition Information Skip sharing on ... media links Share this: Page Content What are neural tube defects? Neural (pronounced NOOR-uhl ) tube defects ...

  5. The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

    PubMed Central

    Petroni, M; Sardina, F; Heil, C; Sahún-Roncero, M; Colicchia, V; Veschi, V; Albini, S; Fruci, D; Ricci, B; Soriani, A; Di Marcotullio, L; Screpanti, I; Gulino, A; Giannini, G

    2016-01-01

    The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions. PMID:26068589

  6. ALTERED THALAMOCORTICAL AXON MORPHOLOGY FOLLOWING NEONATAL PERIPHERAL NERVE DAMAGE: IMPLICATIONS FOR THE STUDY OF DEVELOPMENTAL NEUROTOXICITY

    EPA Science Inventory

    Toxicant effects on central connectivity have not been extensively characterized. Studies of developmental neurotoxicity have typically described malformations arising from damage to neuronal precursors. Toxicants may also affect later stages of neural development. In particular,...

  7. Genetics and development of neural tube defects.

    PubMed

    Copp, Andrew J; Greene, Nicholas D E

    2010-01-01

    Congenital defects of neural tube closure (neural tube defects; NTDs) are among the commonest and most severe disorders of the fetus and newborn. Disturbance of any of the sequential events of embryonic neurulation produce NTDs, with the phenotype (eg anencephaly, spina bifida) varying depending on the region of neural tube that remains open. While mutation of > 200 genes is known to cause NTDs in mice, the pattern of occurrence in humans suggests a multifactorial polygenic or oligogenic aetiology. This emphasizes the importance of gene-gene and gene-environment interactions in the origins of these defects. A number of cell biological functions are essential for neural tube closure, with defects of the cytoskeleton, cell cycle and molecular regulation of cell viability prominent among the mouse NTD mutants. Many transcriptional regulators and proteins that affect chromatin structure are also required for neural tube closure, although the downstream molecular pathways regulated by these proteins is unknown. Some key signalling pathways for NTDs have been identified: over-activation of sonic hedgehog signalling and loss of function in the planar cell polarity (non-canonical Wnt) pathway are potent causes of NTD, with requirements also for retinoid and inositol signalling. Folic acid supplementation is an effective method for primary prevention of a proportion of NTDs in both humans and mice, although the embryonic mechanism of folate action remains unclear. Folic acid-resistant cases can be prevented by inositol supplementation in mice, raising the possibility that this could lead to an additional preventive strategy for human NTDs in future. PMID:19918803

  8. Critical Branching Neural Networks

    ERIC Educational Resources Information Center

    Kello, Christopher T.

    2013-01-01

    It is now well-established that intrinsic variations in human neural and behavioral activity tend to exhibit scaling laws in their fluctuations and distributions. The meaning of these scaling laws is an ongoing matter of debate between isolable causes versus pervasive causes. A spiking neural network model is presented that self-tunes to critical…

  9. High-performance neural networks. [Neural computers

    SciTech Connect

    Dress, W.B.

    1987-06-01

    The new Forth hardware architectures offer an intermediate solution to high-performance neural networks while the theory and programming details of neural networks for synthetic intelligence are developed. This approach has been used successfully to determine the parameters and run the resulting network for a synthetic insect consisting of a 200-node ''brain'' with 1760 interconnections. Both the insect's environment and its sensor input have thus far been simulated. However, the frequency-coded nature of the Browning network allows easy replacement of the simulated sensors by real-world counterparts.

  10. Is neural Darwinism Darwinism?

    PubMed

    van Belle, T

    1997-01-01

    Neural Darwinism is a theory of cognition developed by Gerald Edelman along with George Reeke and Olaf Sporns at Rockefeller University. As its name suggests, neural Darwinism is modeled after biological Darwinism, and its authors assert that the two processes are strongly analogous. both operate on variation in a population, amplifying the more adaptive individuals. However, from a computational perspective, neural Darwinism is quite different from other models of natural selection, such as genetic algorithms. The individuals of neural Darwinism do not replicate, thus robbing the process of the capacity to explore new solutions over time and ultimately reducing it to a random search. Because neural Darwinism does not have the computational power of a truly Darwinian process, it is misleading to label it as such. to illustrate this disparity in adaptive power, one of Edelman's early computer experiments, Darwin I, is revisited, and it is shown that adding replication greatly improves the adaptive power of the system. PMID:9090158

  11. A real time neural net estimator of fatigue life

    NASA Technical Reports Server (NTRS)

    Troudet, T.; Merrill, W.

    1990-01-01

    A neural net architecture is proposed to estimate, in real-time, the fatigue life of mechanical components, as part of the Intelligent Control System for Reusable Rocket Engines. Arbitrary component loading values were used as input to train a two hidden-layer feedforward neural net to estimate component fatigue damage. The ability of the net to learn, based on a local strain approach, the mapping between load sequence and fatigue damage has been demonstrated for a uniaxial specimen. Because of its demonstrated performance, the neural computation may be extended to complex cases where the loads are biaxial or triaxial, and the geometry of the component is complex (e.g., turbopump blades). The generality of the approach is such that load/damage mappings can be directly extracted from experimental data without requiring any knowledge of the stress/strain profile of the component. In addition, the parallel network architecture allows real-time life calculations even for high frequency vibrations. Owing to its distributed nature, the neural implementation will be robust and reliable, enabling its use in hostile environments such as rocket engines. This neural net estimator of fatigue life is seen as the enabling technology to achieve component life prognosis, and therefore would be an important part of life extending control for reusable rocket engines.

  12. Neural constraints on learning.

    PubMed

    Sadtler, Patrick T; Quick, Kristin M; Golub, Matthew D; Chase, Steven M; Ryu, Stephen I; Tyler-Kabara, Elizabeth C; Yu, Byron M; Batista, Aaron P

    2014-08-28

    Learning, whether motor, sensory or cognitive, requires networks of neurons to generate new activity patterns. As some behaviours are easier to learn than others, we asked if some neural activity patterns are easier to generate than others. Here we investigate whether an existing network constrains the patterns that a subset of its neurons is capable of exhibiting, and if so, what principles define this constraint. We employed a closed-loop intracortical brain-computer interface learning paradigm in which Rhesus macaques (Macaca mulatta) controlled a computer cursor by modulating neural activity patterns in the primary motor cortex. Using the brain-computer interface paradigm, we could specify and alter how neural activity mapped to cursor velocity. At the start of each session, we observed the characteristic activity patterns of the recorded neural population. The activity of a neural population can be represented in a high-dimensional space (termed the neural space), wherein each dimension corresponds to the activity of one neuron. These characteristic activity patterns comprise a low-dimensional subspace (termed the intrinsic manifold) within the neural space. The intrinsic manifold presumably reflects constraints imposed by the underlying neural circuitry. Here we show that the animals could readily learn to proficiently control the cursor using neural activity patterns that were within the intrinsic manifold. However, animals were less able to learn to proficiently control the cursor using activity patterns that were outside of the intrinsic manifold. These results suggest that the existing structure of a network can shape learning. On a timescale of hours, it seems to be difficult to learn to generate neural activity patterns that are not consistent with the existing network structure. These findings offer a network-level explanation for the observation that we are more readily able to learn new skills when they are related to the skills that we already

  13. Synergy of endothelial and neural progenitor cells from adipose-derived stem cells to preserve neurovascular structures in rat hypoxic-ischemic brain injury

    PubMed Central

    Hsueh, Yuan-Yu; Chang, Ya-Ju; Huang, Chia-Wei; Handayani, Fitri; Chiang, Yi-Lun; Fan, Shih-Chen; Ho, Chien-Jung; Kuo, Yu-Min; Yang, Shang-Hsun; Chen, Yuh-Ling; Lin, Sheng-Che; Huang, Chao-Ching; Wu, Chia-Ching

    2015-01-01

    Perinatal cerebral hypoxic-ischemic (HI) injury damages the architecture of neurovascular units (NVUs) and results in neurological disorders. Here, we differentiated adipose-derived stem cells (ASCs) toward the progenitor of endothelial progenitor cells (EPCs) and neural precursor cells (NPCs) via microenvironmental induction and investigated the protective effect by transplanting ASCs, EPCs, NPCs, or a combination of EPCs and NPCs (E+N) into neonatal HI injured rat pups. The E+N combination produced significant reduction in brain damage and cell apoptosis and the most comprehensive restoration in NVUs regarding neuron number, normal astrocytes, and vessel density. Improvements in cognitive and motor functions were also achieved in injured rats with E+N therapy. Synergistic interactions to facilitate transmigration under in vitro hypoxic microenvironment were discovered with involvement of the neuropilin-1 (NRP1) signal in EPCs and the C-X-C chemokine receptor 4 (CXCR4) and fibroblast growth factor receptor 1 (FGFR1) signals in NPCs. Therefore, ASCs exhibit great potential for cell sources in endothelial and neural lineages to prevent brain from HI damage. PMID:26447335

  14. Synergy of endothelial and neural progenitor cells from adipose-derived stem cells to preserve neurovascular structures in rat hypoxic-ischemic brain injury.

    PubMed

    Hsueh, Yuan-Yu; Chang, Ya-Ju; Huang, Chia-Wei; Handayani, Fitri; Chiang, Yi-Lun; Fan, Shih-Chen; Ho, Chien-Jung; Kuo, Yu-Min; Yang, Shang-Hsun; Chen, Yuh-Ling; Lin, Sheng-Che; Huang, Chao-Ching; Wu, Chia-Ching

    2015-01-01

    Perinatal cerebral hypoxic-ischemic (HI) injury damages the architecture of neurovascular units (NVUs) and results in neurological disorders. Here, we differentiated adipose-derived stem cells (ASCs) toward the progenitor of endothelial progenitor cells (EPCs) and neural precursor cells (NPCs) via microenvironmental induction and investigated the protective effect by transplanting ASCs, EPCs, NPCs, or a combination of EPCs and NPCs (E+N) into neonatal HI injured rat pups. The E+N combination produced significant reduction in brain damage and cell apoptosis and the most comprehensive restoration in NVUs regarding neuron number, normal astrocytes, and vessel density. Improvements in cognitive and motor functions were also achieved in injured rats with E+N therapy. Synergistic interactions to facilitate transmigration under in vitro hypoxic microenvironment were discovered with involvement of the neuropilin-1 (NRP1) signal in EPCs and the C-X-C chemokine receptor 4 (CXCR4) and fibroblast growth factor receptor 1 (FGFR1) signals in NPCs. Therefore, ASCs exhibit great potential for cell sources in endothelial and neural lineages to prevent brain from HI damage. PMID:26447335

  15. Neural responses to macronutrients: hedonic and homeostatic mechanisms.

    PubMed

    Tulloch, Alastair J; Murray, Susan; Vaicekonyte, Regina; Avena, Nicole M

    2015-05-01

    The brain responds to macronutrients via intricate mechanisms. We review how the brain's neural systems implicated in homeostatic control of feeding and hedonic responses are influenced by the ingestion of specific types of food. We discuss how these neural systems are dysregulated in preclinical models of obesity. Findings from these studies can increase our understanding of overeating and, perhaps in some cases, the development of obesity. In addition, a greater understanding of the neural circuits affected by the consumption of specific macronutrients, and by obesity, might lead to new treatments and strategies for preventing unhealthy weight gain. PMID:25644095

  16. Role of the lesion scar in the response to damage and repair of the central nervous system.

    PubMed

    Kawano, Hitoshi; Kimura-Kuroda, Junko; Komuta, Yukari; Yoshioka, Nozomu; Li, Hong Peng; Kawamura, Koki; Li, Ying; Raisman, Geoffrey

    2012-07-01

    Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation. PMID:22362507

  17. Nanomedicine Approaches to Modulate Neural Stem Cells in Brain Repair.

    PubMed

    Santos, Tiago; Boto, Carlos; Saraiva, Cláudia M; Bernardino, Liliana; Ferreira, Lino

    2016-06-01

    We explore the concept of modulating neural stem cells and their niches for brain repair using nanotechnology-based approaches. These approaches include stimulating cell proliferation, recruitment, and differentiation to functionally recover damaged areas. Nanoscale-engineered materials potentially overcome limited crossing of the blood-brain barrier, deficient drug delivery, and cell targeting. PMID:26917252

  18. Preventing Suicide

    MedlinePlus

    ... The top three methods used in suicides include firearms (49.9%), suffocation (26.7%), and poisoning (15. ... Content source: National Center for Injury Prevention and Control, Division of Violence Prevention Page maintained by: Office ...

  19. Drowning Prevention

    MedlinePlus

    ... Listen Español Text Size Email Print Share Drowning Prevention: Information for Parents Page Content Article Body Drowning ... in very cold water for lengthy periods. Drowning Prevention: Know the Warning Signs These signs may signal ...

  20. Dynamics of neural cryptography

    SciTech Connect

    Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

    2007-05-15

    Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

  1. Hidden synaptic differences in a neural circuit underlie differential behavioral susceptibility to a neural injury

    PubMed Central

    Sakurai, Akira; Tamvacakis, Arianna N; Katz, Paul S

    2014-01-01

    Individuals vary in their responses to stroke and trauma, hampering predictions of outcomes. One reason might be that neural circuits contain hidden variability that becomes relevant only when those individuals are challenged by injury. We found that in the mollusc, Tritonia diomedea, subtle differences between animals within the neural circuit underlying swimming behavior had no behavioral relevance under normal conditions but caused differential vulnerability of the behavior to a particular brain lesion. The extent of motor impairment correlated with the site of spike initiation in a specific neuron in the neural circuit, which was determined by the strength of an inhibitory synapse onto this neuron. Artificially increasing or decreasing this inhibitory synaptic conductance with dynamic clamp correspondingly altered the extent of motor impairment by the lesion without affecting normal operation. The results suggest that neural circuit differences could serve as hidden phenotypes for predicting the behavioral outcome of neural damage. DOI: http://dx.doi.org/10.7554/eLife.02598.001 PMID:24920390

  2. Application of neural networks to health monitoring of bridge structures

    NASA Astrophysics Data System (ADS)

    Loh, Chin-Hsiung; Yeh, ShyChing

    2000-06-01

    A procedure based on the use of artificial neural networks for the identification of dynamic system is developed and applied to the bridge structure under earthquake excitation. This neural network-based approach is also applied for the detection of changes in the characteristics of structure- unknown system. Based on the vibration measurement from a linear/healthy system to train the neural network for identification purposes, then the trained network is fed comparable vibration measurements from the same structure under different episodes of response in order to monitor the nonlinearity of the system. The learning ability of the network is examined for the use of multiple inputs. The effects of the network parameters on learning and accuracy of predictions are discussed. Based on this study it is found that the configuration of neural network model is the same as NARMA model and has the potential for structural damage detection.

  3. Vibrational analysis using neural network classifier for motor fault detection

    NASA Astrophysics Data System (ADS)

    Su, Hua; Kim, Yeong Cheol; Lee, Yidong; Chong, Kil To

    2005-12-01

    Early detection and diagnosis of induction machine incipient faults are desirable for increasing machinery availability, reducing consequential damage, and improving operational efficiency. However, fault detection using analytical method is not always possible because it requires perfect knowledge of a process model. A neural network based expert system was proposed for diagnostic problems of the induction motors using vibration analysis. The short-time Fourier transform (STFT) was used to process the quasi-steady vibration signals, and the neural network was trained and tested using the vibration spectra. The efficiency of the developed neural network expert system was evaluated. The obtained results lead to a conclusion that neural network expert system can be developed based on vibration measurements acquired online from the machine.

  4. War damages and reconstruction of Peruca dam

    SciTech Connect

    Nonveiller, E.; Rupcic, J. |; Sever, Z.

    1999-04-01

    The paper describes the heavy damages caused by blasting in the Peruca rockfill dam in Croatia in January 1993. Complete collapse of the dam by overtopping was prevented through quick action of the dam owner by dumping clayey gravel on the lowest sections of the dam crest and opening the bottom outlet of the reservoir, thus efficiently lowering the water level. After the damages were sufficiently established and alternatives for restoration of the dam were evaluated, it was decided to construct a diaphragm wall through the damaged core in the central dam part as the impermeable dam element and to rebuild the central clay core at the dam abutments. Reconstruction works are described.

  5. Neural control of muscle

    NASA Technical Reports Server (NTRS)

    Max, S. R.; Markelonis, G. J.

    1983-01-01

    Cholinergic innervation regulates the physiological and biochemical properties of skeletal muscle. The mechanisms that appear to be involved in this regulation include soluble, neurally-derived polypeptides, transmitter-evoked muscle activity and the neurotransmitter, acetylcholine, itself. Despite extensive research, the interacting neural mechanisms that control such macromolecules as acetylcholinesterase, the acetylcholine receptor and glucose 6-phosphate dehydrogenase remain unclear. It may be that more simplified in vitro model systems coupled with recent dramatic advances in the molecular biology of neurally-regulated proteins will begin to allow researchers to unravel the mechanisms controlling the expression and maintenance of these macromolecules.

  6. Retinoic acid reduces solvent-induced neuropathy and promotes neural regeneration in mice.

    PubMed

    Palencia, Guadalupe; Hernández-Pedro, Norma; Saavedra-Perez, David; Peña-Curiel, Omar; Ortiz-Plata, Alma; Ordoñez, Graciela; Flores-Estrada, Diana; Sotelo, Julio; Arrieta, Oscar

    2014-08-01

    In humans, exposure to organic solvents (OS) is frequent in work activities or as a recreational inhalant, inducing severe neuropathy (secondary to demyelization of peripheral nerves). We have previously shown that all-trans retinoic acid (ATRA) increases local content of neural growth factor (NGF), improving peripheral neuropathy of diverse origins. In this study, we evaluated the effect of ATRA on OS-induced peripheral neuropathy in experimental mice. Two simultaneous experiments were performed. The first one aimed to evaluate ATRA for the prevention of damage induced by OS, the second to test ATRA as an OS-induced neuropathy treatment. Nociceptive threshold latency and NGF concentration in serum and in peripheral nerves were determined. Morphological changes and evidence of sciatic nerve regeneration were evaluated. Mice exposed to OS developed neuropathy and axonal degeneration. ATRA diminished the effects of OS inhalation on sensorial changes and nerve morphology. Treatment with ATRA reversed sensorial and nerve morphological changes of OS-induced neuropathy, and this was associated with increased contents of NGF. Similar to previous experiences on diabetic and toxic neuropathy, ATRA reduced and partially reversed the peripheral neuropathy caused by OS exposure. These favorable effects apparently are due to local production of NGF induced by neural regeneration in response to the administration of retinoic acid. PMID:24647975

  7. Generation of diverse neural cell types through direct conversion

    PubMed Central

    Petersen, Gayle F; Strappe, Padraig M

    2016-01-01

    A characteristic of neurological disorders is the loss of critical populations of cells that the body is unable to replace, thus there has been much interest in identifying methods of generating clinically relevant numbers of cells to replace those that have been damaged or lost. The process of neural direct conversion, in which cells of one lineage are converted into cells of a neural lineage without first inducing pluripotency, shows great potential, with evidence of the generation of a range of functional neural cell types both in vitro and in vivo, through viral and non-viral delivery of exogenous factors, as well as chemical induction methods. Induced neural cells have been proposed as an attractive alternative to neural cells derived from embryonic or induced pluripotent stem cells, with prospective roles in the investigation of neurological disorders, including neurodegenerative disease modelling, drug screening, and cellular replacement for regenerative medicine applications, however further investigations into improving the efficacy and safety of these methods need to be performed before neural direct conversion becomes a clinically viable option. In this review, we describe the generation of diverse neural cell types via direct conversion of somatic cells, with comparison against stem cell-based approaches, as well as discussion of their potential research and clinical applications. PMID:26981169

  8. Neural networks for aircraft control

    NASA Technical Reports Server (NTRS)

    Linse, Dennis

    1990-01-01

    Current research in Artificial Neural Networks indicates that networks offer some potential advantages in adaptation and fault tolerance. This research is directed at determining the possible applicability of neural networks to aircraft control. The first application will be to aircraft trim. Neural network node characteristics, network topology and operation, neural network learning and example histories using neighboring optimal control with a neural net are discussed.

  9. Geometric neural computing.

    PubMed

    Bayro-Corrochano, E J

    2001-01-01

    This paper shows the analysis and design of feedforward neural networks using the coordinate-free system of Clifford or geometric algebra. It is shown that real-, complex-, and quaternion-valued neural networks are simply particular cases of the geometric algebra multidimensional neural networks and that some of them can also be generated using support multivector machines (SMVMs). Particularly, the generation of radial basis function for neurocomputing in geometric algebra is easier using the SMVM, which allows one to find automatically the optimal parameters. The use of support vector machines in the geometric algebra framework expands its sphere of applicability for multidimensional learning. Interesting examples of nonlinear problems show the effect of the use of an adequate Clifford geometric algebra which alleviate the training of neural networks and that of SMVMs. PMID:18249926

  10. Weakly connected neural nets

    NASA Technical Reports Server (NTRS)

    Zak, Michail

    1990-01-01

    A new neural network architecture is proposed based upon effects of non-Lipschitzian dynamics. The network is fully connected, but these connections are active only during vanishingly short time periods. The advantages of this architecture are discussed.

  11. Damage assessment in ANCA-associated vasculitis.

    PubMed

    Bhamra, Kuljeet; Luqmani, Raashid

    2012-12-01

    Antineutrophil cytoplasm antibody associated vasculitis has been transformed from life-threatening conditions to chronic relapsing long-term diseases as a result of significant advances in immunosuppressive therapy. Although mortality still occurs, it is much less frequent, with an average 5-year survival of over 70 %. In the setting of chronic conditions, it becomes increasingly important to monitor the burden of disease in terms of both active inflammation requiring immunosuppression and chronic damage (scarring) from vasculitis and its treatment and associated comorbidity. The damage that accumulates in patients with vasculitis does not respond to immunosuppressive treatment. It is important to distinguish disease activity from disease damage to prevent unnecessary immunosuppression, but it is equally important to recognize damage for what it is, so that it can be addressed appropriately. Damage is an inevitable consequence of long-term vasculitis for over 80 % of patients, which should not surprise us given the severity of the original illness. There is potential value in measuring damage as a means of providing prognostic information. Using a quantified score such as the Vasculitis Damage Index (VDI) allows us to predict mortality. Patients with at least five items of damage on the VDI score have substantially worse mortality (7- to 11-fold worse risk), as compared with those with lesser amounts of damage. These findings should be taken into context when planning the management of patients with vasculitis, as well as in clinical trials of vasculitis. Disease damage is an important surrogate for long-term outcome in vasculitis, and studies should be designed to limit the amount of damage accumulating as a result of therapeutic intervention, rather than simply controlling disease activity, as is currently the aim in recent randomized controlled trials in vasculitis. Furthermore, careful cataloguing of damage, as well as disease activity items, provides much

  12. A Neural Basis for Developmental Topographic Disorientation

    PubMed Central

    Aminoff, Elissa M.; Kastner, Sabine; Behrmann, Marlene

    2015-01-01

    Developmental topographic disorientation (DTD) is a life-long condition in which affected individuals are severely impaired in navigating around their environment. Individuals with DTD have no apparent structural brain damage on conventional imaging and the neural mechanisms underlying DTD are currently unknown. Using functional and diffusion tensor imaging, we present a comprehensive neuroimaging study of an individual, J.N., with well defined DTD. J.N. has intact scene-selective responses in the parahippocampal place area (PPA), transverse occipital sulcus, and retrosplenial cortex (RSC), key regions associated with scene perception and navigation. However, detailed fMRI studies probing selective tuning properties of these regions, as well as functional connectivity, suggest that J.N.'s RSC has an atypical response profile and an atypical functional coupling to PPA compared with human controls. This deviant functional profile of RSC is not due to compromised structural connectivity. This comprehensive examination suggests that the RSC may play a key role in navigation-related processing and that an alteration of the RSC's functional properties may serve as the neural basis for DTD. SIGNIFICANCE STATEMENT Individuals with developmental topographic disorientation (DTD) have a life-long impairment in spatial navigation in the absence of brain damage, neurological conditions, or basic perceptual or memory deficits. Although progress has been made in identifying brain regions that subserve normal navigation, the neural basis of DTD is unknown. Using functional and structural neuroimaging and detailed statistical analyses, we investigated the brain regions typically involved in navigation and scene processing in a representative DTD individual, J.N. Although scene-selective regions were identified, closer scrutiny indicated that these areas, specifically the retrosplenial cortex (RSC), were functionally disrupted in J.N. This comprehensive examination of a

  13. Neural cryptography with feedback

    NASA Astrophysics Data System (ADS)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  14. Neural network applications

    NASA Technical Reports Server (NTRS)

    Padgett, Mary L.; Desai, Utpal; Roppel, T.A.; White, Charles R.

    1993-01-01

    A design procedure is suggested for neural networks which accommodates the inclusion of such knowledge-based systems techniques as fuzzy logic and pairwise comparisons. The use of these procedures in the design of applications combines qualitative and quantitative factors with empirical data to yield a model with justifiable design and parameter selection procedures. The procedure is especially relevant to areas of back-propagation neural network design which are highly responsive to the use of precisely recorded expert knowledge.

  15. Neural constraints on learning

    PubMed Central

    Sadtler, Patrick T.; Quick, Kristin M.; Golub, Matthew D.; Chase, Steven M.; Ryu, Stephen I.; Tyler-Kabara, Elizabeth C.; Yu, Byron M.; Batista, Aaron P.

    2014-01-01

    Motor, sensory, and cognitive learning require networks of neurons to generate new activity patterns. Because some behaviors are easier to learn than others1,2, we wondered if some neural activity patterns are easier to generate than others. We asked whether the existing network constrains the patterns that a subset of its neurons is capable of exhibiting, and if so, what principles define the constraint. We employed a closed-loop intracortical brain-computer interface (BCI) learning paradigm in which Rhesus monkeys controlled a computer cursor by modulating neural activity patterns in primary motor cortex. Using the BCI paradigm, we could specify and alter how neural activity mapped to cursor velocity. At the start of each session, we observed the characteristic activity patterns of the recorded neural population. These patterns comprise a low-dimensional space (termed the intrinsic manifold, or IM) within the high-dimensional neural firing rate space. They presumably reflect constraints imposed by the underlying neural circuitry. We found that the animals could readily learn to proficiently control the cursor using neural activity patterns that were within the IM. However, animals were less able to learn to proficiently control the cursor using activity patterns that were outside of the IM. This result suggests that the existing structure of a network can shape learning. On the timescale of hours, it appears to be difficult to learn to generate neural activity patterns that are not consistent with the existing network structure. These findings offer a network-level explanation for the observation that we are more readily able to learn new skills when they are related to the skills that we already possess3,4. PMID:25164754

  16. Core damage severity evaluation for pressurized water reactors by artificial intelligence methods

    NASA Astrophysics Data System (ADS)

    Mironidis, Anastasios Pantelis

    1998-12-01

    During the course of nuclear power evolution, accidents have occurred. However, in the western world, none of them had a severe impact on the public because of the design features of nuclear plants. In nuclear reactors, barriers constitute physical obstacles to uncontrolled fission product releases. These barriers are an important factor in safety analysis. During an accident, reactor safety systems become actuated to prevent the barriers from been breached. In addition, operators are required to take specified actions, meticulously depicted in emergency response procedures. In an accident, on-the-spot knowledge regarding the condition of the core is necessary. In order to make the right decisions toward mitigating the accident severity and its consequences, we need to know the status of the core [1, 3]. However, power plant instrumentation that can provide a direct indication of the status of the core during the time when core damage is a potential outcome, does not exist. Moreover, the information from instruments may have large uncertainty of various types. Thus, a very strong potential for misinterpreting incoming information exists. This research endeavor addresses the problem of evaluating the core damage severity of a Pressurized Water Reactor during a transient or an accident. An expert system has been constructed, that incorporates knowledge and reasoning of human experts. The expert system's inference engine receives incoming plant data that originate in the plethora of core-related instruments. Its knowledge base relies on several massive, multivariate fuzzy logic rule-sets, coupled with several artificial neural networks. These mathematical models have encoded information that defines possible core states, based on correlations of parameter values. The inference process classifies the core as intact, or as experiencing clad damage and/or core melting. If the system detects a form of core damage, a quantification procedure will provide a numerical

  17. Mitochondrial ferritin suppresses MPTP-induced cell damage by regulating iron metabolism and attenuating oxidative stress.

    PubMed

    You, Lin-Hao; Li, Zhen; Duan, Xiang-Lin; Zhao, Bao-Lu; Chang, Yan-Zhong; Shi, Zhen-Hua

    2016-07-01

    Our previous work showed that mitochondrial ferritin (MtFt) played an important role in preventing neuronal damage in 6-OHDA-induced Parkinson's disease (PD). However, the role of MtFt in a PD model induced by MPTP is not clear. Here, we found that methyl-4-phenyl-1, 2, 3, 6-tetra-pyridine (MPTP) significantly upregulated MtFt in the mouse hippocampus, substantia nigra (SN) and striatum. To explore the effect of MtFt upregulation on the MPTP-mediated injury to neural cells, MtFt-/- mice and MtFt-overexpressing cells were used to construct models of PD induced by MPTP. Our results showed that MPTP dramatically downregulated expression of transferrin receptor 1 (TfR1) and tyrosine hydroxylase and upregulated L-ferritin expression in the mouse striatum and SN. Interestingly, MPTP induced high levels of MtFt in these tissues, indicating that MtFt was involved in iron metabolism and influenced dopamine synthesis induced by MPTP. Meanwhile, the Bcl2/Bax ratio was decreased significantly by MPTP in the striatum and SN of MtFt knockout (MtFt-/-) mice compared with controls. Overexpression of MtFt increased TfR1 and decreased ferroportin 1 induced by 1-methyl-4-phenylpyridinium ions (MPP+). MtFt strongly inhibited mitochondrial damage through maintaining the mitochondrial membrane potential and protecting the integrity of the mitochondrial membrane. It also suppressed the increase of the labile iron pool, decreased production of reactive oxygen species and dramatically rescued the apoptosis induced by MPP+. In conclusion, this study demonstrates that MtFt plays an important role in preventing neuronal damage in the MPTP-induced parkinsonian phenotype by inhibiting cellular iron accumulation and subsequent oxidative stress. PMID:27017962

  18. Neural Networks Art: Solving Problems with Multiple Solutions and New Teaching Algorithm

    PubMed Central

    Dmitrienko, V. D; Zakovorotnyi, A. Yu.; Leonov, S. Yu.; Khavina, I. P

    2014-01-01

    A new discrete neural networks adaptive resonance theory (ART), which allows solving problems with multiple solutions, is developed. New algorithms neural networks teaching ART to prevent degradation and reproduction classes at training noisy input data is developed. Proposed learning algorithms discrete ART networks, allowing obtaining different classification methods of input. PMID:25246988

  19. Changes in Connectivity after Visual Cortical Brain Damage Underlie Altered Visual Function

    ERIC Educational Resources Information Center

    Bridge, Holly; Thomas, Owen; Jbabdi, Saad; Cowey, Alan

    2008-01-01

    The full extent of the brain's ability to compensate for damage or changed experience is yet to be established. One question particularly important for evaluating and understanding rehabilitation following brain damage is whether recovery involves new and aberrant neural connections or whether any change in function is due to the functional…

  20. STAT3 modulation to enhance motor neuron differentiation in human neural stem cells.

    PubMed

    Natarajan, Rajalaxmi; Singal, Vinamrata; Benes, Richard; Gao, Junling; Chan, Hoi; Chen, Haijun; Yu, Yongjia; Zhou, Jia; Wu, Ping

    2014-01-01

    Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs). In vitro hNSCs primed with fibroblast growth factor 2 (FGF2) exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF), which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs. Treatment with STAT3 inhibitors, Stattic and Niclosamide, enhanced motor neuron differentiation only in FGF2-primed hNSCs, as shown by increased homeobox gene Hb9 mRNA levels as well as HB9+ and microtubule-associated protein 2 (MAP2)+ co-labeled cells. The increased motor neuron differentiation was accompanied by a decrease in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes. Interestingly, Stattic and Niclosamide did not affect the level of STAT3 phosphorylation; rather, they perturbed the nuclear translocation of phosphorylated STAT3. In summary, we demonstrate that FGF2 is required for motor neuron differentiation from hNSCs and that inhibition of STAT3 further increases motor neuron differentiation at the expense of astrogliogenesis. Our study thus suggests a potential benefit of targeting the STAT3 pathway for neurotrauma or neurodegenerative diseases. PMID:24945434

  1. Femoral nerve damage (image)

    MedlinePlus

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  2. Deep neural network and random forest hybrid architecture for learning to detect retinal vessels in fundus images.

    PubMed

    Maji, Debapriya; Santara, Anirban; Ghosh, Sambuddha; Sheet, Debdoot; Mitra, Pabitra

    2015-08-01

    Vision impairment due to pathological damage of the retina can largely be prevented through periodic screening using fundus color imaging. However the challenge with large-scale screening is the inability to exhaustively detect fine blood vessels crucial to disease diagnosis. In this work we present a computational imaging framework using deep and ensemble learning based hybrid architecture for reliable detection of blood vessels in fundus color images. A deep neural network (DNN) is used for unsupervised learning of vesselness dictionaries using sparse trained denoising auto-encoders (DAE), followed by supervised learning of the DNN response using a random forest for detecting vessels in color fundus images. In experimental evaluation with the DRIVE database, we achieve the objective of vessel detection with max. avg. accuracy of 0.9327 and area under ROC curve of 0.9195. PMID:26736930

  3. Preventing Rejection

    MedlinePlus

    ... Drug Assistance Lifestyle Changes Back to Work or School Physical Changes Relationship Changes Pregnancy Precautions Fertility Labor & Delivery Breastfeeding Risks Cancer Types Risk Factors Prevention & Early Detection ...

  4. 1,25-(OH){sub 2}-vitamin D{sub 3} prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4{sup −/−} model

    SciTech Connect

    Reiter, Florian P.; Hohenester, Simon; Nagel, Jutta M.; Wimmer, Ralf; Artmann, Renate; Wottke, Lena; Makeschin, Marie-Christine; Mayr, Doris; Rust, Christian; Trauner, Michael; Denk, Gerald U.

    2015-04-03

    Background/Purpose of the study: Vitamin D{sub 3}-deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D{sub 3}-administration has thus been proposed as a therapeutic approach. Vitamin D{sub 3} has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH){sub 2}-vitamin D{sub 3} inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen{sup ®}-assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, and zymography following calcitriol-treatment. Wild-type and ATP-binding cassette transporter b4{sup −/−} (Abcb4{sup −/−})-mice received calcitriol for 4 weeks. Liver-damage, inflammation, and fibrosis were assessed by serum liver-tests, Sirius-red staining, quantitative-PCR, immunoblotting, immunohistochemistry and hydroxyproline quantification. Results: In vitro, calcitriol inhibited activation and proliferation of murine HSC as shown by reduced α-smooth muscle actin and platelet-derived growth factor-receptor-β-protein-levels, BrdU and PicoGreen®-assays. Furthermore, mRNA-levels and activity of matrix metalloproteinase 13 were profoundly increased. In vivo, calcitriol ameliorated inflammatory liver-injury reflected by reduced levels of alanine aminotransferase in Abcb4{sup −/−}-mice. In accordance, their livers had lower mRNA-levels of F4/80, tumor necrosis factor-receptor 1 and a lower count of portal CD11b positive cells. In contrast, no effect on overall fibrosis was observed. Conclusion: Calcitriol inhibits activation and proliferation of HSCs in vitro. In Abcb4{sup −/−}-mice, administration of calcitriol ameliorates inflammatory liver-damage but has

  5. Verification and Validation Methodology of Real-Time Adaptive Neural Networks for Aerospace Applications

    NASA Technical Reports Server (NTRS)

    Gupta, Pramod; Loparo, Kenneth; Mackall, Dale; Schumann, Johann; Soares, Fola

    2004-01-01

    Recent research has shown that adaptive neural based control systems are very effective in restoring stability and control of an aircraft in the presence of damage or failures. The application of an adaptive neural network with a flight critical control system requires a thorough and proven process to ensure safe and proper flight operation. Unique testing tools have been developed as part of a process to perform verification and validation (V&V) of real time adaptive neural networks used in recent adaptive flight control system, to evaluate the performance of the on line trained neural networks. The tools will help in certification from FAA and will help in the successful deployment of neural network based adaptive controllers in safety-critical applications. The process to perform verification and validation is evaluated against a typical neural adaptive controller and the results are discussed.

  6. Protective effects of total flavonoids from Flos Puerariae on retinal neuronal damage in diabetic mice

    PubMed Central

    Li, Dai; Yang, Fang; Cheng, Hongke; Liu, Chao; Sun, Ming; Wu, Kaili

    2013-01-01

    Purpose To investigate the potential protective effects of total flavonoids from Flos Puerariae (TFF) on retinal neural cells in diabetic mice. Methods C57BL/6J mice were intraperitoneally injected with streptozotocin to generate type I diabetes in a murine model, as indicated by blood glucose levels ≥11.1 mmol/l. TFF was administered intragastrically at a dose of 50, 100, or 200 mg/kg/day. After 10 weeks of administration, the mice were euthanized, and the eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes in the retinal ganglion cells and capillary basement membrane were observed with electron microscopy. Apoptosis of retinal neural cells was determined with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay. Bax and Bcl-2 expression in the retinal tissues was determined with immunohistochemical staining and western blotting. Results Compared with the diabetic mice, the blood glucose level decreased (p<0.01) and the bodyweight increased (p<0.05) in the 100 and 200 mg/kg TFF-treated groups. The thickness of the retina significantly increased (p<0.01), and the retinal capillary basement membrane (BM) thickness was reduced in the 100 and 200 mg/kg TFF-treated diabetic mice (DM). The 100 and 200 mg/kg TFF treatments also attenuated the diabetes-induced apoptosis of retinal neural cells. Consistent with these effects, TFF treatment decreased the Bax expression level and, concurrently, increased the ratio of Bcl-2 to Bax. Conclusions TFF attenuated diabetes-induced apoptosis in retinal neurons by inhibiting Bax expression and increasing the ratio of Bcl-2 to Bax, which suggests that TFF might prevent retinal neuronal damage in diabetes mellitus. PMID:24146535

  7. A real time neural net estimator of fatigue life

    NASA Technical Reports Server (NTRS)

    Troudet, T.; Merrill, W.

    1990-01-01

    A neural network architecture is proposed to estimate, in real-time, the fatigue life of mechanical components, as part of the intelligent Control System for Reusable Rocket Engines. Arbitrary component loading values were used as input to train a two hidden-layer feedforward neural net to estimate component fatigue damage. The ability of the net to learn, based on a local strain approach, the mapping between load sequence and fatigue damage has been demonstrated for a uniaxial specimen. Because of its demonstrated performance, the neural computation may be extended to complex cases where the loads are biaxial or triaxial, and the geometry of the component is complex (e.g., turbopumps blades). The generality of the approach is such that load/damage mappings can be directly extracted from experimental data without requiring any knowledge of the stress/strain profile of the component. In addition, the parallel network architecture allows real-time life calculations even for high-frequency vibrations. Owing to its distributed nature, the neural implementation will be robust and reliable, enabling its use in hostile environments such as rocket engines.

  8. Involvement of leukotrienes in acute gastric damage.

    PubMed

    Boughton-Smith, N K

    1989-01-01

    The leukotrienes have potent inflammatory actions which could be of importance in gastric mucosal integrity. In animals, LTC4 produces vasoconstriction in the gastric mucosa. Furthermore, acute gastric damage produced by ethanol is accompanied by marked increases in the mucosal formation of LTC4 and LTB4. Depending on the extent of protection, prostaglandins either have no effect or prevent the increases in leukotriene formation which accompany ethanol-induced damage. Various non-specific inhibitors of leukotriene synthesis prevent ethanol and indomethacin-induced damage to the gastric mucosa. However, a novel selective 5-lipoxygenase inhibitor (BW A4C) had no effect on these models of acute gastric damage at doses which completely inhibited gastric mucosal leukotriene synthesis. These studies cast doubt on the role of the leukotrienes in these models of acute gastric damage. However, the potent biological actions of the leukotrienes may be of importance in the pathogenesis of other forms of gastric damage, or as mediators of chronic gastric ulceration or inflammation. PMID:2657289

  9. Fault damage zones

    NASA Astrophysics Data System (ADS)

    Kim, Young-Seog; Peacock, David C. P.; Sanderson, David J.

    2004-03-01

    Damage zones show very similar geometries across a wide range of scales and fault types, including strike-slip, normal and thrust faults. We use a geometric classification of damage zones into tip-, wall-, and linking-damage zones, based on their location around faults. These classes can be sub-divided in terms of fault and fracture patterns within the damage zone. A variety of damage zone structures can occur at mode II tips of strike-slip faults, including wing cracks, horsetail fractures, antithetic faults, and synthetic branch faults. Wall damage zones result from the propagation of mode II and mode III fault tips through a rock, or from damage associated with the increase in slip on a fault. Wall damage zone structures include extension fractures, antithetic faults, synthetic faults, and rotated blocks with associated triangular openings. The damage formed at the mode III tips of strike-slip faults (e.g. observed in cliff sections) are classified as wall damage zones, because the damage zone structures are distributed along a fault trace in map view. Mixed-mode tips are likely to show characteristics of both mode II and mode III tips. Linking damage zones are developed at steps between two sub-parallel faults, and the structures developed depend on whether the step is extensional or contractional. Extension fractures and pull-aparts typically develop in extensional steps, whilst solution seams, antithetic faults and synthetic faults commonly develop in contractional steps. Rotated blocks, isolated lenses or strike-slip duplexes may occur in both extensional and contractional steps. Damage zone geometries and structures are strongly controlled by the location around a fault, the slip mode at a fault tip, and by the evolutionary stage of the fault. Although other factors control the nature of damage zones (e.g. lithology, rheology and stress system), the three-dimensional fault geometry and slip mode at each tip must be considered to gain an understanding of

  10. Less interclass disturbance learning for unsupervised neural computing

    NASA Astrophysics Data System (ADS)

    Liu, Lurng-Kuo; Ligomenides, Panos A.

    1991-11-01

    A number of training algorithms for neural networks are based on the 'competition' learning method. This is regarded as an adaptive process for tuning neural networks to specific features of input. The responses from the neural network, then, tend to become localized. However, a shortcoming of this model is that some neural units can remain inactive. Since a neural unit never learns unless it wins, it is possible that some of the neural units are always outperformed by others, and therefore never learn. This paper presents a new unsupervised learning algorithm, less-interclass-disturbance learning (LID), which deals with the limitations of the simple competitive neural network. The main idea of the method is that it reinforces the competing neurons in such a way as to prevent the weights from 'fooling around.' A new compound similarity metric is introduced in this algorithm to reduce the interclass disturbance during the training process. The behavior of this algorithm was investigated through computer simulations. It is shown that LID learning is quite effective.

  11. Preventative Maintenance.

    ERIC Educational Resources Information Center

    Migliorino, James

    Boards of education must be convinced that spending money up front for preventive maintenance will, in the long run, save districts' tax dollars. A good program of preventive maintenance can minimize disruption of service; reduce repair costs, energy consumption, and overtime; improve labor productivity and system equipment reliability; handle…

  12. Preventing Falls

    MedlinePlus

    ... from osteoporosis. Lower-body strength exercises and balance exercises can help you prevent falls and avoid the disability that may result from falling. Here are some fall prevention tips from Go4Life : l Have your eyes and hearing tested often. Always wear your glasses when you ...

  13. Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles.

    PubMed

    Pongrac, Igor M; Pavičić, Ivan; Milić, Mirta; Brkić Ahmed, Lada; Babič, Michal; Horák, Daniel; Vinković Vrček, Ivana; Gajović, Srećko

    2016-01-01

    Biocompatibility, safety, and risk assessments of superparamagnetic iron oxide nanoparticles (SPIONs) are of the highest priority in researching their application in biomedicine. One improvement in the biological properties of SPIONs may be achieved by different functionalization and surface modifications. This study aims to investigate how a different surface functionalization of SPIONs - uncoated, coated with d-mannose, or coated with poly-l-lysine - affects biocompatibility. We sought to investigate murine neural stem cells (NSCs) as important model system for regenerative medicine. To reveal the possible mechanism of toxicity of SPIONs on NSCs, levels of reactive oxygen species, intracellular glutathione, mitochondrial membrane potential, cell-membrane potential, DNA damage, and activities of SOD and GPx were examined. Even in cases where reactive oxygen species levels were significantly lowered in NSCs exposed to SPIONs, we found depleted intracellular glutathione levels, altered activities of SOD and GPx, hyperpolarization of the mitochondrial membrane, dissipated cell-membrane potential, and increased DNA damage, irrespective of the surface coating applied for SPION stabilization. Although surface coating should prevent the toxic effects of SPIONs, our results showed that all of the tested SPION types affected the NSCs similarly, indicating that mitochondrial homeostasis is their major cellular target. Despite the claimed biomedical benefits of SPIONs, the refined determination of their effects on various cellular functions presented in this work highlights the need for further safety evaluations. This investigation helps to fill the knowledge gaps on the criteria that should be considered in evaluating the biocompatibility and safety of novel nanoparticles. PMID:27217748

  14. CHARACTERIZATION OF DAMAGED MATERIALS

    SciTech Connect

    Hsu, P C; Dehaven, M; McClelland, M; Chidester, S; Maienschein, J L

    2006-06-23

    Thermal damage experiments were conducted on LX-04, LX-10, and LX-17 at high temperatures. Both pristine and damaged samples were characterized for their material properties. A pycnometer was used to determine sample true density and porosity. Gas permeability was measured in a newly procured system (diffusion permeameter). Burn rate was measured in the LLNL strand burner. Weight losses upon thermal exposure were insignificant. Damaged pressed parts expanded, resulting in a reduction of bulk density by up to 10%. Both gas permeabilities and burn rates of the damaged samples increased by several orders of magnitude due to higher porosity and lower density. Moduli of the damaged materials decreased significantly, an indication that the materials became weaker mechanically. Damaged materials were more sensitive to shock initiation at high temperatures. No significant sensitization was observed when the damaged samples were tested at room temperature.

  15. Gamma globulin, Evan's blue, aprotinin A PLA2 inhibitor, tetracycline and antioxidants protect epithelial cells against damage induced by synergism among streptococcal hemolysins, oxidants and proteinases: relation to the prevention of post-streptococcal sequelae and septic shock.

    PubMed

    Ginsburg, I; Sadovnic, M

    1998-11-01

    An in vitro model was employed to study the potential role of streptococcal extra-cellular products, rich in streptolysin O, in cellular injury as related to streptococcal infections and post-streptococcal sequelae. Extra-cellular products (EXPA) rich in streptolysin O were isolated from type 4, group A hemolytic streptococci grown in a chemostat, in a synthetic medium. EXPA induced moderate cytopathogenic changes in monkey kidney epithelial cells and in rat heart cells pre-labeled with 3H-arachidonate. However very strong toxic effects were induced when EXP was combined with oxidants (glucose oxides generated H2O2, AAPH-induced peroxyl radical (ROO.), NO generated by sodium nitroprusside) and proteinases (plasmin, trypsin). Cell killing was distinctly synergistic in nature. Cell damage induced by the multi-component cocktails was strongly inhibited either by micromolar amounts of gamma globulin, and Evan's blue which neutralized SLO activity, by tetracycline, trasylol (aprotinin), epsilon amino caproic acid and by soybean trypsin inhibitor, all proteinase inhibitors as well as by a non-penetrating PLA2 inhibitor A. The results suggest that fasciitis, myositis and sepsis resulting from infections with hemolytic streptococci might be caused by a coordinated 'cross-talk' among microbial, leukocyte and additional host-derived pro-inflammatory agents. Since attempts to prolong lives of septic patients by the exclusive administration of single antagonists invariably failed, it is proposed that the administration of 'cocktails' of putative inhibitors against major pro-inflammatory agonizes generated in inflammation and infection might protect against the deleterious effects caused by the biochemical and pharmacological cascades which are known to be activated in sepsis. PMID:9848686

  16. Wood Defect Identification Based on Artificial Neural Network

    NASA Astrophysics Data System (ADS)

    Zhu, Xiao-Dong; Cao, Jun; Wang, Feng-Hu; Sun, Jian-Ping; Liu, Yu

    Defects in wooden material reduce the value of timber. In order to save and improve the utilization of the timber, many studies are carried out on the ways to detect defects in wood. The recent development of computer technology, data processing technology and signal processing technology provides researchers with more damage identification problem solution ideas and methods. This article studies the vibration characteristics of wood. With an exploration of the wavelet analysis and artificial neural network for the wood composite material defects based on non-destructive testing, an artificial neural network model is established for wood-based composite materials non-destructive testing technology.

  17. Vibrational Analysis of Engine Components Using Neural-Net Processing and Electronic Holography

    NASA Technical Reports Server (NTRS)

    Decker, Arthur J.; Fite, E. Brian; Mehmed, Oral; Thorp, Scott A.

    1998-01-01

    The use of computational-model trained artificial neural networks to acquire damage specific information from electronic holograms is discussed. A neural network is trained to transform two time-average holograms into a pattern related to the bending-induced-strain distribution of the vibrating component. The bending distribution is very sensitive to component damage unlike the characteristic fringe pattern or the displacement amplitude distribution. The neural network processor is fast for real-time visualization of damage. The two-hologram limit makes the processor more robust to speckle pattern decorrelation. Undamaged and cracked cantilever plates serve as effective objects for testing the combination of electronic holography and neural-net processing. The requirements are discussed for using finite-element-model trained neural networks for field inspections of engine components. The paper specifically discusses neural-network fringe pattern analysis in the presence of the laser speckle effect and the performances of two limiting cases of the neural-net architecture.

  18. Vibrational Analysis of Engine Components Using Neural-Net Processing and Electronic Holography

    NASA Technical Reports Server (NTRS)

    Decker, Arthur J.; Fite, E. Brian; Mehmed, Oral; Thorp, Scott A.

    1997-01-01

    The use of computational-model trained artificial neural networks to acquire damage specific information from electronic holograms is discussed. A neural network is trained to transform two time-average holograms into a pattern related to the bending-induced-strain distribution of the vibrating component. The bending distribution is very sensitive to component damage unlike the characteristic fringe pattern or the displacement amplitude distribution. The neural network processor is fast for real-time visualization of damage. The two-hologram limit makes the processor more robust to speckle pattern decorrelation. Undamaged and cracked cantilever plates serve as effective objects for testing the combination of electronic holography and neural-net processing. The requirements are discussed for using finite-element-model trained neural networks for field inspections of engine components. The paper specifically discusses neural-network fringe pattern analysis in the presence of the laser speckle effect and the performances of two limiting cases of the neural-net architecture.

  19. Rare complications after lung percutaneous radiofrequency ablation: Incidence, risk factors, prevention and management.

    PubMed

    Alberti, Nicolas; Buy, Xavier; Frulio, Nora; Montaudon, Michel; Canella, Mathieu; Gangi, Afshin; Crombe, Amandine; Palussière, Jean

    2016-06-01

    Among image-guided thermo-ablative techniques, percutaneous radiofrequency ablation (PRFA) is the most widely used technique for the treatment of primary and secondary lung malignancies. Tolerance of PRFA in the lung is excellent. However, relatively little is known about potential rare complications. This article presents both the clinical and imaging features of lung PRFA complications as well as their prevention and management. Complications may be classified in four groups: pleuropulmonary (e.g., bronchopleural or bronchial fistula, delayed abscess or aspergilloma inside post-PRFA cavitations, pulmonary artery pseudo aneurysm, gas embolism and interstitial pneumonia); thoracic wall and vertebral (e.g., rib or vertebral fractures and intercostal artery injury); mediastinal and apical (e.g., neural damage); or diaphragmatic. Most complications can be managed with conservative treatment, percutaneous or endoscopic drainage, or surgical repair. PMID:27161069

  20. Neural signatures of autism

    PubMed Central

    Kaiser, Martha D.; Hudac, Caitlin M.; Shultz, Sarah; Lee, Su Mei; Cheung, Celeste; Berken, Allison M.; Deen, Ben; Pitskel, Naomi B.; Sugrue, Daniel R.; Voos, Avery C.; Saulnier, Celine A.; Ventola, Pamela; Wolf, Julie M.; Klin, Ami; Vander Wyk, Brent C.; Pelphrey, Kevin A.

    2010-01-01

    Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural system–level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism. PMID:21078973

  1. Hyperbolic Hopfield neural networks.

    PubMed

    Kobayashi, M

    2013-02-01

    In recent years, several neural networks using Clifford algebra have been studied. Clifford algebra is also called geometric algebra. Complex-valued Hopfield neural networks (CHNNs) are the most popular neural networks using Clifford algebra. The aim of this brief is to construct hyperbolic HNNs (HHNNs) as an analog of CHNNs. Hyperbolic algebra is a Clifford algebra based on Lorentzian geometry. In this brief, a hyperbolic neuron is defined in a manner analogous to a phasor neuron, which is a typical complex-valued neuron model. HHNNs share common concepts with CHNNs, such as the angle and energy. However, HHNNs and CHNNs are different in several aspects. The states of hyperbolic neurons do not form a circle, and, therefore, the start and end states are not identical. In the quantized version, unlike complex-valued neurons, hyperbolic neurons have an infinite number of states. PMID:24808287

  2. Cognitive Neural Prosthetics

    PubMed Central

    Andersen, Richard A.; Hwang, Eun Jung; Mulliken, Grant H.

    2010-01-01

    The cognitive neural prosthetic (CNP) is a very versatile method for assisting paralyzed patients and patients with amputations. The CNP records the cognitive state of the subject, rather than signals strictly related to motor execution or sensation. We review a number of high-level cortical signals and their application for CNPs, including intention, motor imagery, decision making, forward estimation, executive function, attention, learning, and multi-effector movement planning. CNPs are defined by the cognitive function they extract, not the cortical region from which the signals are recorded. However, some cortical areas may be better than others for particular applications. Signals can also be extracted in parallel from multiple cortical areas using multiple implants, which in many circumstances can increase the range of applications of CNPs. The CNP approach relies on scientific understanding of the neural processes involved in cognition, and many of the decoding algorithms it uses also have parallels to underlying neural circuit functions. PMID:19575625

  3. The ''neural'' phonetic typewriter

    SciTech Connect

    Kohonen, T.

    1988-03-01

    Recently, researchers have placed great hopes on artificial neural networks to perform such ''natural'' tasks as speech recognition. This was indeed one motivation for us to start research in this area many years ago at Helsinki University of Technology. This article describes the result of that research - a complete ''neural'' speech recognition system, which recognizes phonetic units, called phonemes, from a continuous speech signal. Although motivated by neural network principles, the choices in design must be regarded as a compromise of many technical aspects of those principles. As our system is a genuine ''phonetic typewriter'' intended to transcribe orthographically edited text from an unlimited vocabulary, it cannot be directed compared with any more conventional, word-based system that applies classical concepts such as dynamic time warping and hidden Markov models.

  4. Dynamics and Adaptive Control for Stability Recovery of Damaged Aircraft

    NASA Technical Reports Server (NTRS)

    Nguyen, Nhan; Krishnakumar, Kalmanje; Kaneshige, John; Nespeca, Pascal

    2006-01-01

    This paper presents a recent study of a damaged generic transport model as part of a NASA research project to investigate adaptive control methods for stability recovery of damaged aircraft operating in off-nominal flight conditions under damage and or failures. Aerodynamic modeling of damage effects is performed using an aerodynamic code to assess changes in the stability and control derivatives of a generic transport aircraft. Certain types of damage such as damage to one of the wings or horizontal stabilizers can cause the aircraft to become asymmetric, thus resulting in a coupling between the longitudinal and lateral motions. Flight dynamics for a general asymmetric aircraft is derived to account for changes in the center of gravity that can compromise the stability of the damaged aircraft. An iterative trim analysis for the translational motion is developed to refine the trim procedure by accounting for the effects of the control surface deflection. A hybrid direct-indirect neural network, adaptive flight control is proposed as an adaptive law for stabilizing the rotational motion of the damaged aircraft. The indirect adaptation is designed to estimate the plant dynamics of the damaged aircraft in conjunction with the direct adaptation that computes the control augmentation. Two approaches are presented 1) an adaptive law derived from the Lyapunov stability theory to ensure that the signals are bounded, and 2) a recursive least-square method for parameter identification. A hardware-in-the-loop simulation is conducted and demonstrates the effectiveness of the direct neural network adaptive flight control in the stability recovery of the damaged aircraft. A preliminary simulation of the hybrid adaptive flight control has been performed and initial data have shown the effectiveness of the proposed hybrid approach. Future work will include further investigations and high-fidelity simulations of the proposed hybrid adaptive Bight control approach.

  5. DNA Damage in Major Psychiatric Diseases.

    PubMed

    Raza, Muhammad Ummear; Tufan, Turan; Wang, Yan; Hill, Christopher; Zhu, Meng-Yang

    2016-08-01

    Human cells are exposed to exogenous insults and continuous production of different metabolites. These insults and unwanted metabolic products might interfere with the stability of genomic DNA. Recently, many studies have demonstrated that different psychiatric disorders show substantially high levels of oxidative DNA damage in the brain accompanied with morphological and functional alterations. It reveals that damaged genomic DNA may contribute to the pathophysiology of these mental illnesses. In this article, we review the roles of oxidative damage and reduced antioxidant ability in some vastly studied psychiatric disorders and emphasize the inclusion of treatment options involving DNA repair. In addition, while most currently used antidepressants are based on the manipulation of the neurotransmitter regulation in managing different mental abnormalities, they are able to prevent or reverse neurotoxin-induced DNA damage. Therefore, it may be plausible to target on genomic DNA alterations for psychiatric therapies, which is of pivotal importance for future antipsychiatric drug development. PMID:27126805

  6. Neural Architectures for Control

    NASA Technical Reports Server (NTRS)

    Peterson, James K.

    1991-01-01

    The cerebellar model articulated controller (CMAC) neural architectures are shown to be viable for the purposes of real-time learning and control. Software tools for the exploration of CMAC performance are developed for three hardware platforms, the MacIntosh, the IBM PC, and the SUN workstation. All algorithm development was done using the C programming language. These software tools were then used to implement an adaptive critic neuro-control design that learns in real-time how to back up a trailer truck. The truck backer-upper experiment is a standard performance measure in the neural network literature, but previously the training of the controllers was done off-line. With the CMAC neural architectures, it was possible to train the neuro-controllers on-line in real-time on a MS-DOS PC 386. CMAC neural architectures are also used in conjunction with a hierarchical planning approach to find collision-free paths over 2-D analog valued obstacle fields. The method constructs a coarse resolution version of the original problem and then finds the corresponding coarse optimal path using multipass dynamic programming. CMAC artificial neural architectures are used to estimate the analog transition costs that dynamic programming requires. The CMAC architectures are trained in real-time for each obstacle field presented. The coarse optimal path is then used as a baseline for the construction of a fine scale optimal path through the original obstacle array. These results are a very good indication of the potential power of the neural architectures in control design. In order to reach as wide an audience as possible, we have run a seminar on neuro-control that has met once per week since 20 May 1991. This seminar has thoroughly discussed the CMAC architecture, relevant portions of classical control, back propagation through time, and adaptive critic designs.

  7. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus.

    PubMed

    Li, Yu-Qing; Cheng, Zoey; Wong, Shun

    2016-01-01

    Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53) gene but absence of Cdkn1a (p21) did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation. PMID:27331809

  8. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

    PubMed Central

    Li, Yu-Qing; Cheng, Zoey; Wong, Shun

    2016-01-01

    Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53) gene but absence of Cdkn1a (p21) did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation. PMID:27331809

  9. Application of information fusion and Shannon entropy in structural damage detection

    NASA Astrophysics Data System (ADS)

    Bao, Yuequan; Li, Hui

    2007-04-01

    Vibration-based damage identification is a useful tool for structural health monitoring. But, the damage detection results always have uncertainty because of the measurement noise, modeling error and environment changes. In this paper, information fusion based on D-S (Dempster-Shafer) evidence theory and Shannon entropy are employed for decreasing the uncertainty and improving accuracy of damage identification. Regarding that the multiple evidence from different information sources are different importance and not all the evidences are effective for the final decision. The different importance of the evidences is considered by assigning weighting coefficient. Shannon entropy is a measurement of uncertainty. In this paper it is employed to measure the uncertainty of damage identification results. The first step of the procedure is training several artificial neural networks with different input parameters to obtain the damage decisions respectively. Second, weighing coefficients are assigned to neural networks according to the reliability of the neural networks. The Genetic Algorithm is employed to optimize the weighing coefficients. Third, the weighted decisions are assigned to information fusion center. And in fusion center, a selective fusion method is proposed. Numerical studies on the Binzhou Yellow River Highway Bridge are carried out. The results indicate that the method proposed can improve the damage identification accuracy and increase the reliability of damage identification to compare with the method by neural networks alone.

  10. Neural Analog Information Processing

    NASA Astrophysics Data System (ADS)

    Hecht-Nielsen, Robert

    1982-07-01

    Neural Analog Information Processing (NAIP) is an effort to develop general purpose pattern classification architectures based upon biological information processing principles. This paper gives an overview of NAIP and its relationship to the previous work in neural modeling from which its fundamental principles are derived. It also presents a theorem concerning the stability of response of a slab (a two dimensional array of identical simple processing units) to time-invariant (spatial) patterns. An experiment (via computer emulation) demonstrating classification of a spatial pattern by a simple, but complete NAIP architecture is described. A concept for hardware implementation of NAIP architectures is briefly discussed.

  11. Imaging the Neural Symphony.

    PubMed

    Svoboda, Karel

    2016-01-01

    Since the start of the new millennium, a method called two-photon microscopy has allowed scientists to peer farther into the brain than ever before. Our author, one of the pioneers in the development of this new technology, writes that "directly observing the dynamics of neural networks in an intact brain has become one of the holy grails of brain research." His article describes the advances that led to this remarkable breakthrough-one that is helping neuroscientists better understand neural networks. PMID:27408677

  12. Nested neural networks

    NASA Technical Reports Server (NTRS)

    Baram, Yoram

    1988-01-01

    Nested neural networks, consisting of small interconnected subnetworks, allow for the storage and retrieval of neural state patterns of different sizes. The subnetworks are naturally categorized by layers of corresponding to spatial frequencies in the pattern field. The storage capacity and the error correction capability of the subnetworks generally increase with the degree of connectivity between layers (the nesting degree). Storage of only few subpatterns in each subnetworks results in a vast storage capacity of patterns and subpatterns in the nested network, maintaining high stability and error correction capability.

  13. Neural processing of itch

    PubMed Central

    Akiyama, Tasuku; Carstens, E.

    2013-01-01

    While considerable effort has been made to investigate the neural mechanisms of pain, much less effort has been devoted to itch, at least until recently. However, itch is now gaining increasing recognition as a widespread and costly medical and socioeconomic issue. This is accompanied by increasing interest in the underlying neural mechanisms of itch, which has become a vibrant and rapidly-advancing field of research. The goal of the present forefront review is to describe the recent progress that has been made in our understanding of itch mechanisms. PMID:23891755

  14. Neural Plasticity: For Good and Bad

    NASA Astrophysics Data System (ADS)

    Møller, A. R.

    The brain's ability to change its organization and function is necessary for normal development of the nervous system and it makes it possible to adapt to changing demands but it can also cause disorders when going awry. This property, known as neural plasticity, is only evident when induced, very much like genes. Plastic changes may be programmed and providing a ``midcourse correction" during childhood development. If that is not executed in the normal way severe developmental disorders such as autism may results. Normal development of functions and anatomical organization of the brain and the spinal cord depend on appropriate sensory stimulation and motor activations. So-called enriched sensory environments have been shown to be beneficial for cognitive development and enriched acoustic environment may even slow the progression of age-related hearing loss. It is possible that the beneficial effect of physical exercise is achieved through activation of neural plasticity. The beneficial effect of training after trauma to the brain or spinal cord is mainly achieved through shifting functions from damaged brain area to other parts of the central nervous system and adapting these parts to t