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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

    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 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

  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. 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

  5. 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

  6. 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

  7. 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

  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. 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

  11. 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)

  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 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

  15. 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

  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. 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

  18. 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

  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

    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

  20. 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

  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. 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.

  3. 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

  4. 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

  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. 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

  16. 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

  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. 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

  17. 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.

  18. 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

  19. 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

  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. 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

  11. 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

  12. 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

  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. 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

  15. 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

  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. 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

  16. 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

  17. 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

  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

    1986-07-01

    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.

  19. 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.

  20. 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.

  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

    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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  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.

    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

  12. 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.

  13. 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

  14. 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.

  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

    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

  1. 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

  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. 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

  8. 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

  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