WorldWideScience

Sample records for aasld-fda-nih-phrma hepatotoxicity steering

  1. Steering handbook

    CERN Document Server

    Pfeffer, Peter

    2017-01-01

    This edited volume presents basic principles as well as advanced concepts of the computational modeling of steering systems. Moreover, the book includes the components and functionalities of modern steering system, which are presented comprehensively and in a practical way. The book is written by more than 15 leading experts from the automotive industry and its components suppliers. The target audience primarily comprises practicing engineers, developers, researchers as well as graduate students who want to specialize in this field.

  2. Steering Performance, Tactical Vehicles

    Science.gov (United States)

    2015-07-29

    NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Automotive Instrumentation Division (TEDT-AT-AD-I) U.S. Army Aberdeen Test Center 400...characterize the on-center vehicle responses of military vehicles for the purposes of influencing vehicle design and ensuring military truck steering... mechanism attached to the test vehicle’s steering wheel (or replaces the steering wheel) that is strain gaged and calibrated to measure the steering effort

  3. Quantum steering without inequalities

    CERN Document Server

    Chen, Jing-Ling; Wu, Chunfeng; Su, Hong-Yi; Cabello, Adan; Kwek, L C; Oh, C H

    2012-01-01

    We show that, for any two-qubit state, quantum steering can be proven without testing the violation of steering inequalities. We show that steerability is proven if Bob's normalized conditional states after Alice's measurements are pure. This method, which may be seen as the quantum steering analog of Greenberger-Horne-Zeilinger-like tests of Bell nonlocality without Bell inequalities, offers advantages with respect to the existing methods for experimentally testing quantum steering.

  4. Steering and evasion assist

    NARCIS (Netherlands)

    Dang, T.; Desens, J.; Franke, U.; Gavrila, D.; Schäfers, L.; Ziegler, W.; Eskandarian, A.

    2012-01-01

    Steering and evasion assistance defines a new and future class of driver assistance systems to avoid an impending collision with other traffic participants. Dynamic and kinematic considerations reveal that an evasive steering maneuver has high potential for collision avoidance in many driving

  5. Experimental temporal quantum steering

    Science.gov (United States)

    Bartkiewicz, Karol; Černoch, Antonín; Lemr, Karel; Miranowicz, Adam; Nori, Franco

    2016-01-01

    Temporal steering is a form of temporal correlation between the initial and final state of a quantum system. It is a temporal analogue of the famous Einstein-Podolsky-Rosen (spatial) steering. We demonstrate, by measuring the photon polarization, that temporal steering allows two parties to verify if they have been interacting with the same particle, even if they have no information about what happened with the particle in between the measurements. This is the first experimental study of temporal steering. We also performed experimental tests, based on the violation of temporal steering inequalities, of the security of two quantum key distribution protocols against individual attacks. Thus, these results can lead to applications for secure quantum communications and quantum engineering. PMID:27901121

  6. Method of steering a vehicle

    NARCIS (Netherlands)

    Della Penna, M.; Van Passen, M.M.; Abbink, D.A.; Mulder, M.

    2011-01-01

    Vehicle and method of steering such a vehicle, wherein the vehicle has a steering wheel and steerable driving wheels and a transfer system for converting steering wheel actions to a steering angle of the steerable driving wheels, and wherein the transfer system is provided with a predefined stiffnes

  7. Herbal and dietary supplement hepatotoxicity.

    Science.gov (United States)

    Navarro, Victor J

    2009-11-01

    Herbal and dietary supplements (HDS) are commonly used in the United States and throughout the world. The Dietary Supplement Health and Education Act and public standards set through the U.S. Pharmacopeia provide regulatory framework for these products. These regulations help to ensure the safety of grandfathered and new HDS coming onto the market, and the opportunity to identify and take action against unsafe products that have been distributed. The clinical patterns of presentation and severity of HDS-associated hepatotoxicity can be highly variable, even for the same product. In addition, accurate causality assessment in cases of suspected HDS hepatotoxicity is confounded by infrequent ascertainment of product intake by healthcare providers, under-reporting of HDS use by patients, the ubiquity of HDS and the complexity of their components, and the possibility for product adulteration. Additional measures to prevent HDS-induced hepatotoxicity include greater consumer and provider awareness, increased spontaneous reporting, and reassessment of regulations regarding the manufacturing, distribution, and marketing of these products.

  8. Design of Pneumatic Collapsible Steering

    Directory of Open Access Journals (Sweden)

    Anish Nair

    2013-08-01

    Full Text Available The steering wheel is the important cause of fatal injury for drivers in frontal collision. When frontal collision occurs, due to the kinetic energy of driver or occupant body, it moves forward against steering wheel and wind shield. Actually in a frontal collision forces will be first transmitted through driver’s feet which act as fulcrum so the body will rotate about it. For the taller driver steering works as fulcrum. Driver head & chest hit the steering or windshield which may cause severe injury or death. Considering the injury potential of steering wheel we are presenting a new idea Pneumatic Collapsible Steering Column (PCS.

  9. CCCT - Patient Advocate Steering Committee

    Science.gov (United States)

    The Patient Advocate Steering Committee (PASC) works to ensure advocates involved with the Scientific Steering Committees (SSCs) are completely integrated in the development, implementation, and monitoring of clinical trials within those groups.

  10. 49 CFR 570.60 - Steering system.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Steering system. 570.60 Section 570.60... 10,000 Pounds § 570.60 Steering system. (a) System play. Lash or free play in the steering system... excessive lash or free play in the steering system. Table 2. Steering Wheel Free Play Values Steering...

  11. 49 CFR 570.7 - Steering systems.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Steering systems. 570.7 Section 570.7... Pounds or Less § 570.7 Steering systems. (a) System play. Lash or free play in the steering system shall... in the steering system. Table 1—Steering System Free Play Values Steering wheel diameter (inches...

  12. Electrical steering of vehicles

    DEFF Research Database (Denmark)

    Blanke, Mogens; Thomsen, Jesper Sandberg

    2006-01-01

    solutions and still meet strict requirements to functional safety. The paper applies graph-based analysis of functional system structure to find a novel fault-tolerant architecture for an electrical steering where a dedicated AC-motor design and cheap voltage measurements ensure ability to detect all...

  13. Steering Your Mysterious Mind

    DEFF Research Database (Denmark)

    Prasad, Ramjee

    Steering the Mysterious Mind, describes a unique, novel concept for a way to gain control of your mind. The five basic elements of human life, that is; Creativity, Content­ment, Confidence, Calmness, and Concentration (C5) have been introduced in my previous book Unlock Your Personalization...

  14. Greater Celandine hepatotoxicity: a clinical review.

    Science.gov (United States)

    Teschke, Rolf; Frenzel, Christian; Glass, Xaver; Schulze, Johannes; Eickhoff, Axel

    2012-01-01

    Herbal hepatotoxicity is a rare and poorly described disease because reported cases are mostly scattered and lack an appropriate causality assessment. We now describe in detail the clinical picture of herbal hepatotoxicity by extracts of Greater Celandine (GC), syn. Chelidonium majus L. from the Papaveraceae family, which contain more than 20 ingredients including various biologically active isoquinoline alkaloids. For this purpose, we analyzed and reviewed published cases of 16 patients from various European countries. In all patients, herbal hepatotoxicity was of probable and highly probable causality for GC, using the original and updated scale of CIOMS (Council for International Organizations of Medical Sciences). GC associated hepatotoxicity usually has an acute clinical course exhibiting a hepatocellular pattern of injury and is correlated to an idiosyncratic reaction with its metabolic subtype. Jaundice combined with high values of serum aminotransferases was present in virtually all cases with favourable outcome despite severe clinical course. In conclusion, GC hepatotoxicity is a typical herbal hepatotoxicity with a sound causality track for GC, but there is uncertainty regarding the respective causative compound(s). The present detailed review of GC hepatotoxicity may serve as an example for clinical causality assessments of future cases of liver injury due to other herbs.

  15. Anabolic androgenic steroid-induced hepatotoxicity.

    Science.gov (United States)

    Bond, Peter; Llewellyn, William; Van Mol, Peter

    2016-08-01

    Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17α-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17α-alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17α-alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor.

  16. Steering Your Mysterious Mind

    DEFF Research Database (Denmark)

    Prasad, Ramjee

    well-being is key for happy and stress free life. Mind has enormous energy. Everyone has access to tre­mendous mental energies; what matters is being aware of this and to work on concentrating your energy into creative work. To achieve mental strength, C5 is a su­preme powerful exercise for the mind......Steering the Mysterious Mind, describes a unique, novel concept for a way to gain control of your mind. The five basic elements of human life, that is; Creativity, Content­ment, Confidence, Calmness, and Concentration (C5) have been introduced in my previous book Unlock Your Personalization....... Compare it with going to the gym where you work on the physical body. In the same way as with arms and legs, the mind is a mus­cle which you exercise through C5 practice. Steering the mind on your personal goal will help you to be creative....

  17. A review of methotrexate-associated hepatotoxicity.

    Science.gov (United States)

    Bath, Roopjeet K; Brar, Navkiran K; Forouhar, Faripour A; Wu, George Y

    2014-10-01

    Methotrexate is effective not only in treating psoriasis and rheumatoid arthritis but also various other disorders. The use of methotrexate has been somewhat limited by concerns regarding its adverse effects, including its potential for hepatotoxicity. The purpose of this article is to provide an overview of methotrexate-associated hepatotoxicity, including risk factors, pathogenesis and recommendations for monitoring it by US, UK and European guidelines, as well as providing a brief overview of its mechanism of action and of high-dose methotrexate.

  18. Loophole-free quantum steering

    CERN Document Server

    Wittmann, Bernhard; Steinlechner, Fabian; Langford, Nathan K; Brunner, Nicolas; Wiseman, Howard; Ursin, Rupert; Zeilinger, Anton

    2011-01-01

    Tests of the predictions of quantum mechanics for entangled systems have provided increasing evidence against local realistic theories 1-6. However, there still remains the crucial challenge of simultaneously closing all major loopholes - the locality, freedom-of-choice, and detection loopholes - in a single experiment. An important sub-class of local realistic theories can be tested with the concept of "steering". The term steering was introduced by Schr\\"odinger in 1935 for the fact that entanglement would seem to allow an experimenter to remotely steer the state of a distant system 7. Einstein called this "spooky action at a distance" 8. Steering has recently been rigorously formulated as a quantum information task opening it up to new experimental tests 9-11. Here, we present the first loophole-free demonstration of steering by violating three-setting quadratic steering inequality, tested with polarization entangled photons shared between two distant laboratories. Our experiment demonstrates this effect w...

  19. Computational Steering with Reduced Complexity

    OpenAIRE

    Butnaru, Daniel

    2014-01-01

    Computational Steering increases the understanding of relationships between the output of a simulation and its parametrized input, such as boundary conditions, physical parameters, or domain geometry. Steering relies on a running simulation which delivers results to a visualization system. However, many simulation codes cannot deliver the required interactive results. For the first time, this work investigates the use of surrogate models to augment computational steering approaches. Based...

  20. Hepatotoxicity and the present herbal hepatoprotective scenario

    Directory of Open Access Journals (Sweden)

    Priyankar Dey

    2013-01-01

    Full Text Available Most of the metabolic and physiological processes of our body as well as the detoxification of various drugs and xenobiotic chemicals occur in the liver. During this detoxification process, the reactive chemical intermediates damage the liver severely. There are several commercially available drugs, consumption of which results in idiosyncratic drug reaction mediated hepatotoxicity. Drug induced hepatotoxicity is a burning problem in this regard and several drugs are withdrawn from the market due to their hepatotoxic nature. Today, worldwide search of non-hepatotoxic drugs, especially potent hepatoprotective drugs have led towards the screening of numerous herbal products. Pharmaceutical companies and scientific communities have started to consider the therapeutic efficiency of the plant-based hepatoprotective remedies. Different herbs are mentioned in various ethnopharmacological practices possessing hepatoprotective capacities and around the globe, such herbs are still used by people to cure certain liver diseases. Therefore, we have documented the various aspects of hepatotoxicity and an overview on the current scenario of the hepatoprotective herbal remedies.

  1. Research on the Variable Steering Ratio of Four-Wheel-Steering Vehicle

    Institute of Scientific and Technical Information of China (English)

    林程; 陈思忠; 任良成

    2004-01-01

    The steering characteristic of a four-wheel-steering vehicle is numerically simulated for in-depth research of the handling stability of four-wheel steering. The research results show that the deteriorating tendency of the steering stability due to the increase of the vehicle speed is improved obviously in the case of four-wheel steering. The approach of variable steering ratio is discussed. The use of the variable steering ratio can not only raise the steering stability of vechicles at high vehicle speed, but also reduce the dicomfort and steering burden of drivers; and hence is helpful for the subjective evaluation of four-wheel steering vehicles.

  2. Quantum coherence of steered states

    Science.gov (United States)

    Hu, Xueyuan; Milne, Antony; Zhang, Boyang; Fan, Heng

    2016-01-01

    Lying at the heart of quantum mechanics, coherence has recently been studied as a key resource in quantum information theory. Quantum steering, a fundamental notion originally considered by Schödinger, has also recently received much attention. When Alice and Bob share a correlated quantum system, Alice can perform a local measurement to ‘steer’ Bob’s reduced state. We introduce the maximal steered coherence as a measure describing the extent to which steering can remotely create coherence; more precisely, we find the maximal coherence of Bob’s steered state in the eigenbasis of his original reduced state, where maximization is performed over all positive-operator valued measurements for Alice. We prove that maximal steered coherence vanishes for quantum-classical states whilst reaching a maximum for pure entangled states with full Schmidt rank. Although invariant under local unitary operations, maximal steered coherence may be increased when Bob performs a channel. For a two-qubit state we find that Bob’s channel can increase maximal steered coherence if and only if it is neither unital nor semi-classical, which coincides with the condition for increasing discord. Our results show that the power of steering for coherence generation, though related to discord, is distinct from existing measures of quantum correlation.

  3. Mechanisms underlying the hepatotoxic effects of ecstasy.

    Science.gov (United States)

    Carvalho, Márcia; Pontes, Helena; Remião, Fernando; Bastos, Maria L; Carvalho, Félix

    2010-08-01

    3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a worldwide illegally used amphetamine-derived designer drug known to be hepatotoxic to humans. Jaundice, hepatomegaly, centrilobular necrosis, hepatitis and fibrosis represent some of the adverse effects caused by MDMA in the liver. Although there is irrefutable evidence of MDMA-induced hepatocellular damage, the mechanisms responsible for that toxicity remain to be thoroughly clarified. One well thought-of mechanism imply MDMA metabolism in the liver into reactive metabolites as responsible for the MDMA-elicited hepatotoxicity. However, other factors, including MDMA-induced hyperthermia, the increase in neurotransmitters efflux, the oxidation of biogenic amines, polydrug abuse pattern, and environmental features accompanying illicit MDMA use, may increase the risk for liver complications. Liver damage patterns of MDMA in animals and humans and current research on the mechanisms underlying the hepatotoxic effects of MDMA will be highlighted in this review.

  4. Current and emerging biomarkers of hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yang X

    2012-08-01

    Full Text Available Xi Yang, William F Salminen, Laura K SchnackenbergDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USAAbstract: Drug-induced liver injury (DILI is of great concern to human health. Generally, liver function and injury is evaluated based upon clinical signs, a select group of serum clinical biomarkers, and occasionally liver biopsies. While alanine aminotransferase, the most commonly used biomarker of hepatocellular injury, is a sensitive marker of liver injury, it is not necessarily specific for liver injury. Furthermore, alanine aminotransferase levels may not always correlate with the extent of injury. Therefore, new hepatotoxicity biomarkers are needed that are more predictive and specific indicators of liver injury and altered function. In addition, no current biomarker provides prognostic information about ultimate outcome once injury occurs, and any new biomarker filling this need is desperately needed. The omics technologies, including genomics, proteomics, and metabolomics, are being used in preclinical animal studies as well as clinical studies to evaluate markers of hepatotoxicity in easily obtained biofluids, such as urine and serum. Recently, the evaluation of circulating microRNAs in urine and blood has also shown promise for the identification of novel, sensitive markers of liver injury. This review evaluates the current status of proposed biomarkers of hepatotoxicity from the omics platforms, as well as from analysis of microRNAs. A brief description of the qualification of proposed biomarkers is also given.Keywords: biomarkers, hepatotoxicity, metabolomics, microRNA, proteomics, transcriptomics

  5. Frequency Steered Acoustic Transducer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This Small Business Innovation Research Phase II project is to fabricate, characterize, and verify performance of a new type of frequency steered acoustic transducer...

  6. Quantification of Gaussian quantum steering

    CERN Document Server

    Kogias, Ioannis; Ragy, Sammy; Adesso, Gerardo

    2014-01-01

    Einstein-Podolsky-Rosen steering incarnates a useful nonclassical correlation which sits in-between entanglement and Bell nonlocality. While a number of qualitative steering criteria exist, very little has been achieved for what concerns quantifying steerability. We introduce a computable measure of steering for arbitrary bipartite Gaussian states of continuous variable systems. For two-mode Gaussian states, the measure reduces to a form of coherent information, which is proven never to exceed entanglement, and to reduce to it on pure states. We provide an operational connection between our measure and the key rate in one-sided device-independent quantum key distribution. We further prove that steering bound entangled Gaussian states by Gaussian measurements is impossible.

  7. STEER Coastal Use Mapping Project

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Coastal Use Mapping Project is designed to collect critical information on human activities in and near the St. Thomas East End Reserves (STEER). The project...

  8. Frequency Steered Acoustic Transducer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This Small Business Innovation Research Phase I project is to develop, fabricate, and characterize a novel frequency steered acoustic transducer (FSAT) for the...

  9. STEER Coastal Use Mapping Project

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Coastal Use Mapping Project is designed to collect critical information on human activities in and near the St. Thomas East End Reserves (STEER). The project...

  10. Responder fast steering mirror

    Science.gov (United States)

    Bullard, Andrew; Shawki, Islam

    2013-10-01

    Raytheon Space and Airborne Systems (SAS) has designed, built and tested a 3.3-inch diameter fast steering mirror (FSM) for space application. This 2-axis FSM operates over a large angle (over 10 degree range), has a very high servo bandwidth (over 3.3 Khz closed loop bandwidth), has nanoradian-class noise, and is designed to support microradian class line of sight accuracy. The FSM maintains excellent performance over large temperature ranges (which includes wave front error) and has very high reliability with the help of fully redundant angle sensors and actuator circuits. The FSM is capable of achieving all its design requirements while also being reaction-compensated. The reaction compensation is achieved passively and does not need a separate control loop. The FSM has undergone various environmental testing which include exported forces and torques and thermal vacuum testing that support the FSM design claims. This paper presents the mechanical design and test results of the mechanism which satisfies the rigorous vacuum and space application requirements.

  11. Hepatotoxicity Induced by "the 3Ks": Kava, Kratom and Khat.

    Science.gov (United States)

    Pantano, Flaminia; Tittarelli, Roberta; Mannocchi, Giulio; Zaami, Simona; Ricci, Serafino; Giorgetti, Raffaele; Terranova, Daniela; Busardò, Francesco P; Marinelli, Enrico

    2016-04-16

    The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by "the 3Ks", while trying to clarify the numerous aspects that still need to be addressed.

  12. Fermilab Steering Group Report

    Energy Technology Data Exchange (ETDEWEB)

    Steering Group, Fermilab; /Fermilab

    2007-12-01

    The Fermilab Steering Group has developed a plan to keep U.S. accelerator-based particle physics on the pathway to discovery, both at the Terascale with the LHC and the ILC and in the domain of neutrinos and precision physics with a high-intensity accelerator. The plan puts discovering Terascale physics with the LHC and the ILC as Fermilab's highest priority. While supporting ILC development, the plan creates opportunities for exciting science at the intensity frontier. If the ILC remains near the Global Design Effort's technically driven timeline, Fermilab would continue neutrino science with the NOvA experiment, using the NuMI (Neutrinos at the Main Injector) proton plan, scheduled to begin operating in 2011. If ILC construction must wait somewhat longer, Fermilab's plan proposes SNuMI, an upgrade of NuMI to create a more powerful neutrino beam. If the ILC start is postponed significantly, a central feature of the proposed Fermilab plan calls for building an intense proton facility, Project X, consisting of a linear accelerator with the currently planned characteristics of the ILC combined with Fermilab's existing Recycler Ring and the Main Injector accelerator. The major component of Project X is the linac. Cryomodules, radio-frequency distribution, cryogenics and instrumentation for the linac are the same as or similar to those used in the ILC at a scale of about one percent of a full ILC linac. Project X's intense proton beams would open a path to discovery in neutrino science and in precision physics with charged leptons and quarks. World-leading experiments would allow physicists to address key questions of the Quantum Universe: How did the universe come to be? Are there undiscovered principles of nature: new symmetries, new physical laws? Do all the particles and forces become one? What happened to the antimatter? Building Project X's ILC-like linac would offer substantial support for ILC development by accelerating the

  13. Fermilab Steering Group Report

    Energy Technology Data Exchange (ETDEWEB)

    Beier, Eugene; /Pennsylvania U.; Butler, Joel; /Fermilab; Dawson, Sally; /Brookhaven; Edwards, Helen; /Fermilab; Himel, Thomas; /SLAC; Holmes, Stephen; /Fermilab; Kim, Young-Kee; /Fermilab /Chicago U.; Lankford, Andrew; /UC, Irvine; McGinnis, David; /Fermilab; Nagaitsev, Sergei; /Fermilab; Raubenheimer, Tor; /SLAC /Fermilab

    2007-01-01

    The Fermilab Steering Group has developed a plan to keep U.S. accelerator-based particle physics on the pathway to discovery, both at the Terascale with the LHC and the ILC and in the domain of neutrinos and precision physics with a high-intensity accelerator. The plan puts discovering Terascale physics with the LHC and the ILC as Fermilab's highest priority. While supporting ILC development, the plan creates opportunities for exciting science at the intensity frontier. If the ILC remains near the Global Design Effort's technically driven timeline, Fermilab would continue neutrino science with the NOVA experiment, using the NuMI (Neutrinos at the Main Injector) proton plan, scheduled to begin operating in 2011. If ILC construction must wait somewhat longer, Fermilab's plan proposes SNuMI, an upgrade of NuMI to create a more powerful neutrino beam. If the ILC start is postponed significantly, a central feature of the proposed Fermilab plan calls for building an intense proton facility, Project X, consisting of a linear accelerator with the currently planned characteristics of the ILC combined with Fermilab's existing Recycler Ring and the Main Injector accelerator. The major component of Project X is the linac. Cryomodules, radio-frequency distribution, cryogenics and instrumentation for the linac are the same as or similar to those used in the ILC at a scale of about one percent of a full ILC linac. Project X's intense proton beams would open a path to discovery in neutrino science and in precision physics with charged leptons and quarks. World-leading experiments would allow physicists to address key questions of the Quantum Universe: How did the universe come to be? Are there undiscovered principles of nature: new symmetries, new physical laws? Do all the particles and forces become one? What happened to the antimatter? Building Project X's ILC-like linac would offer substantial support for ILC development by accelerating the

  14. A Novel Mechanism Underlies the Hepatotoxicity of Pyrazinamide

    OpenAIRE

    Shih, Tung-Yuan; Pai, Chien-Yi; Yang, Ping; Chang, Wen-Liang; Wang, Ning-Chi; Hu, Oliver Yoa-Pu

    2013-01-01

    Relatively little is known about the hepatotoxicity of pyrazinamide (PZA). PZA requires activation by amidase to form pyrazinoic acid (PA). Xanthine oxidase then hydroxylates PA to form 5-hydroxypyrazinoic acid (5-OH-PA). PZA can also be directly oxidized to form 5-OH-PZA. Before this study, it was unclear which metabolic pathway or PZA metabolites led to hepatotoxicity. This study determines whether PZA metabolites are responsible for PZA-induced hepatotoxicity. PZA metabolites were identifi...

  15. Large animal hepatotoxic and nephrotoxic plants.

    Science.gov (United States)

    Oladosu, L A; Case, A A

    1979-10-01

    The hepatotoxic and nephrotoxic plants of large domestic animals have been reviewed. The most important ones are those widely distributed as weeds over pastures, negelcted forests and grasslands, those used as ornamentals, the nitrate concentrating forage crops, and the cyanophoric plants. Crotolaria spp, the ragwort (Senecia jacobaea), the lantana spp. and heliotopum are common hepatoxic plants. Amaranthus retroflexus, Datura stramonium, Solanum rostratum, and the castor oil plant (Ricinus communis) are nephrotoxic plants.

  16. Black Cohosh Hepatotoxicity with Autoimmune Hepatitis Presentation

    Science.gov (United States)

    Franco, Diana L.; Kale, Santosh; Lam-Himlin, Dora M.; Harrison, M. Edwyn

    2017-01-01

    Herbal medicines have been used for the treatment of various ailments since time immemorial. Black cohosh (BC) is well known for the treatment of postmenopausal symptoms, with conflicting evidence supporting its safety and benefits. We present a rare case of BC-induced autoimmune hepatitis (AIH) with hepatotoxicity in a 69-year-old female. To our knowledge, this represents the third case of BC-induced AIH. PMID:28203134

  17. Alpha methyldopa induced hepatotoxicity in pregnancy

    Directory of Open Access Journals (Sweden)

    Padmasri Ramalingappa

    2014-06-01

    Full Text Available We report a case of gestational hepatitis due to alpha-methyldopa and briefly review the literature on alpha-methyldopa-induced hepatotoxicity in pregnancy. A 32 year old woman, primigravida with 34 weeks of gestation with pre eclampsia, presented with symptoms of nausea, dark coloured urine and jaundice. She was on alpha methyldopa (Aldomet 250 mg thrice a day since the last five weeks. Laboratory investigations revealed raised bilirubin, serum aspartate transaminases and serum alanine transaminases. Platelets were normal. Peripheral smear did not show haemolysis. With the exclusion of viral, haemolytic and obstructive causes, drug induced jaundice was considered as a differential diagnosis. Alpha methyldopa was withdrawn and replaced with nifedipine for her pre eclampsia treatment. Her repeat bilirubin level done two weeks later showed a drop. She went into labour at 38 weeks and delivered vaginally. In postpartum follow up her liver tests returned to normal in two weeks, about six weeks after stopping methyldopa. Hepatotoxicity should be considered as one of the adverse drug reaction of alpha methyldopa. It is not possible at present to predict which patients will develop liver disease following the administration of this drug. An awareness of the possibility of methyldopa induced hepatotoxicity should be present in the clinician's mind and liver function tests should be done at regular intervals. The occasional occurrence of this harmful side effect is not a contraindication to the use of this antihypertensive agent. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 805-807

  18. Multi-Layer Traffic Steering

    DEFF Research Database (Denmark)

    Fotiadis, Panagiotis; Polignano, Michele; Gimenez, Lucas Chavarria

    2013-01-01

    This paper investigates the potentials of traffic steering in the Radio Resource Control (RRC) Idle state by evaluating the Absolute Priorities (AP) framework in a multilayer Long Term Evolution (LTE) macrocell scenario. Frequency priorities are broadcast on the system information and RRC Idle...... users can be steered towards higher priority carriers whenever coverage allows it. However, such an approach may overload the prioritized layers. For that purpose, an enhanced scheme is proposed, where priorities are adjusted on a user basis and are provided to the terminal via the connection release...

  19. Joint Measurability and Temporal Steering

    OpenAIRE

    Karthik, H. S.; Tej, J Prabhu; Devi, A. R. Usha; Rajagopal, A. K.

    2014-01-01

    Quintino et. al. (Phys. Rev. Lett. 113, 160402 (2014)) and Uola et. al. (Phys. Rev. Lett. 113, 160403 (2014)) have recently established an intrinsic relation between non-joint measurability and Einstein-Podolsky- Rosen steering. They showed that a set of measurements is incompatible (i.e., not jointly measurable) if and only if it can be used for the demonstration of steering. In this paper, we prove the temporal analog of this result viz., a set of measurements are incompatible if and only i...

  20. Bulling among yearling feedlot steers.

    Science.gov (United States)

    Pierson, R E; Jensen, R; Braddy, P M; Horton, D P; Christie, R M

    1976-09-01

    In a survey to determine the cause of illness and deaths among yearling feedlot cattle, bulling was found to be one of the major problems. During the years 1971-1974, 54,913 (2.88%) steers became bullers and represented an annual loss of around +325,000. Some of the causes of bulling were found to be hormones, either as implants or in the feed. In 1974, from 1,988 necropsies, it was determined that 83 steers died from riding injuries.

  1. 46 CFR 176.814 - Steering systems.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Steering systems. 176.814 Section 176.814 Shipping COAST...) INSPECTION AND CERTIFICATION Material Inspections § 176.814 Steering systems. At each initial and subsequent inspection for certification the owner or managing operator shall be prepared to test the steering systems of...

  2. A survey of computational steering environments

    NARCIS (Netherlands)

    Mulder, J.D.; Wijk, J.J. van; Liere, R. van

    1998-01-01

    Computational steering is a powerful concept that allows scientists to interactively control a computational process during its execution. In this paper, a survey of computational steering environments for the on-line steering of ongoing scientific and engineering simulations is presented. These env

  3. Objective Evaluation Method of Steering Comfort Based on Movement Quality Evaluation of Driver Steering Maneuver

    Institute of Scientific and Technical Information of China (English)

    YANG Yiyong; LIU Yahui; WANG Man; JI Run; JI Xuewu

    2014-01-01

    The existing research of steering comfort mainly focuses on the subjective evaluation, aiming at designing and optimizing the steering system. In the development of steering system, especially the evaluation of steering comfort, the objective evaluation methods considered the kinematic characteristics of driver steering maneuver are not proposed, which means that the objective evaluation of steering cannot be conducted with the evaluation of kinematic characteristics of driver in steering maneuver. In order to propose the objective evaluation methods of steering comfort, the evaluation of steering movement quality of driver is developed on the basis of the study of the kinematic characteristics of steering maneuver. First, the steering motion trajectories of the driver in both comfortable and certain extreme uncomfortable operation conditions are detected using the Vicon motion capture system. The operation conditions are under the restrictions of the vertical height and horizontal distance between steering wheel center and the H-point of driver, and the steering resisting torque else. Next, the movement quality evaluation of driver steering maneuver is assessed using twelve kinds of evaluation indices based on the kinematic analyses of the steering motion trajectories to propose an objective evaluation method. Finally, an integrated discomfort index of steering maneuver is proposed on the basis of the regression analysis of subjective evaluation rating and the movement quality evaluation indices, including the Jerk, Discomfort and Joint Torque indices. The test results show that the proposed integrated discomfort index gives a good fitting with the subjective evaluation of discomfort, which means it can be used to evaluate or predict the discomfort level of steering maneuver. This paper proposes an objective evaluation method of steering comfort based on the movement quality evaluation of driver steering maneuver.

  4. Statin Hepatotoxicity: Is it a Real Concern?

    Science.gov (United States)

    Sikka, Pranav; Saxena, K. K.; Kapoor, Seema

    2011-01-01

    Statins are the most effective and widely used drugs for treating dyslipidemia, a major risk factor for coronary heart disease. These are one of the safest hypolipidemic drugs but many patients are advised to discontinue statins for the fear of hepatotoxicity. Despite a lack of evidence that statins cause liver diseases, many physicians are reluctant to start statins in patients with an out-of-range liver enzymes value and this reluctance to initiate or interrupt the therapy with statins leads to dyslipidemia and its grave consequences. Further, there are some reports showing an additional benefit of statins in reducing cardiovascular events in patients with abnormal liver function tests. PMID:22567196

  5. Statin Hepatotoxicity: Is it a Real Concern?

    Directory of Open Access Journals (Sweden)

    Pranav Sikka

    2011-01-01

    Full Text Available Statins are the most effective and widely used drugs for treating dyslipidemia, a major risk factor for coronary heart disease. These are one of the safest hypolipidemic drugs but many patients are advised to discontinue statins for the fear of hepatotoxicity. Despite a lack of evidence that statins cause liver diseases, many physicians are reluctant to start statins in patients with an out-of-range liver enzymes value and this reluctance to initiate or interrupt the therapy with statins leads to dyslipidemia and its grave consequences. Further, there are some reports showing an additional benefit of statins in reducing cardiovascular events in patients with abnormal liver function tests.

  6. Lead hepatotoxicity: Selected aspects of pathobiochemistry

    Directory of Open Access Journals (Sweden)

    Mateusz Labudda

    2013-08-01

    Full Text Available Lead (Pb that belongs to heavy metals is one of the major pollution components of the environment. Occupational and environmental exposure to lead can cause its absorption by the body and consequently exert toxic effects in the liver. In this paper biochemical determinants of hepatotoxicity caused by lead are presented. Generation of reactive oxygen species, disturbances in the cellular antioxidant system, lipid peroxidation, inhibition of enzymatic proteins and intercellular signaling are also discussed. Med Pr 2013;64(4:565–568

  7. [Herbals and herbal nutritional products hepatotoxicity].

    Science.gov (United States)

    Mengual-Moreno, Edgardo; Lizarzábal-García, Maribel; Hernández-Rincón, Ileana; Barboza-Nobrega, María De Freitas

    2015-09-01

    Herbs and other botanicals have been used in different cultures with medicinal and dietary purposes for centuries. Contrary to the belief of being natural and safe products, their hepatotoxic potential is recognized in several studies worldwide, and represent a health problem that deserves greater attention. The reported prevalence of hepatotoxicity associated with botanicals is variable and depends on various factors such as population, period and design of the study. There have been reports of a total of 60 products with herbal medicinal and dietary purposes, which may cause liver damage; however, the pathophysiological mechanisms involved are not fully elucidated. Their clinical and histological features, not unlike liver injury associated with drugs in most patients, have a pattern of hepatocellular injury. Diagnosis is by exclusion, and represents a clinical challenge. It is essential the clinical suspicion and the differential diagnosis with other acute and chronic conditions. Hence, future researches are aimed at improving existing diagnostic methods and introducing new toxicological, genetic and immunological technologies. Treatment is complex and presents a challenge for the specialist, as there are no antidotes. Management based on the discontinued use of the product and in the symptomatic treatment, decreases the progression to an acute fulminant hepatic failure.

  8. Rutin Attenuates Hepatotoxicity in High-Cholesterol-Diet-Fed Rats.

    Science.gov (United States)

    AlSharari, Shakir D; Al-Rejaie, Salim S; Abuohashish, Hatem M; Ahmed, Mohamed M; Hafez, Mohamed M

    2016-01-01

    Background and Objective. High-cholesterol diet (HCD) intends to increase the oxidative stress in liver tissues inducing hepatotoxicity. Rutin is a natural flavonoid (vitamin p) which is known to have antioxidative properties. The aim of the present study was to investigate the potential effects of Rutin on hypercholesterolemia-induced hepatotoxicity in rats. Materials and Methods. Male Wistar rats were divided into four groups: G-I control, G-II Rutin, G-III HCD, and G-IV Rutin + HCD. The liver functions and lipid profile were used to evaluate the HCD-induced hepatotoxicity. Quantitative real time-PCR was carried out to evaluate the expression levels of genes in TGF-β/Smad signaling pathway. Results. Rutin in combination with HCD showed a significant protective effect against hepatotoxicity. HCD caused significant increase in the mRNA expression of transforming growth factor beta (TGF-β), Mothers Against Decapentaplegic Homolog 2 (Smad-2), Mothers Against Decapentaplegic Homolog 4 (Smad-4), Bcl-2-binding component 3 (Bbc3), caspase-3, P53 and Interleukin-6 (IL-6) and decrease in the expression levels of Cyclin depended kinase inhibitor (P21) and Interleukin-3 (IL-3) in hepatic cells. Conclusion. TGF-β/Smad signaling pathway is involved in HCD-induced hepatotoxicity and Rutin inhibits the hepatotoxicity via suppressing this pathway. Therefore, Rutin might be considered as a protective agent for hepatotoxicity.

  9. Rutin Attenuates Hepatotoxicity in High-Cholesterol-Diet-Fed Rats

    Directory of Open Access Journals (Sweden)

    Shakir D. AlSharari

    2016-01-01

    Full Text Available Background and Objective. High-cholesterol diet (HCD intends to increase the oxidative stress in liver tissues inducing hepatotoxicity. Rutin is a natural flavonoid (vitamin p which is known to have antioxidative properties. The aim of the present study was to investigate the potential effects of Rutin on hypercholesterolemia-induced hepatotoxicity in rats. Materials and Methods. Male Wistar rats were divided into four groups: G-I control, G-II Rutin, G-III HCD, and G-IV Rutin + HCD. The liver functions and lipid profile were used to evaluate the HCD-induced hepatotoxicity. Quantitative real time-PCR was carried out to evaluate the expression levels of genes in TGF-β/Smad signaling pathway. Results. Rutin in combination with HCD showed a significant protective effect against hepatotoxicity. HCD caused significant increase in the mRNA expression of transforming growth factor beta (TGF-β, Mothers Against Decapentaplegic Homolog 2 (Smad-2, Mothers Against Decapentaplegic Homolog 4 (Smad-4, Bcl-2-binding component 3 (Bbc3, caspase-3, P53 and Interleukin-6 (IL-6 and decrease in the expression levels of Cyclin depended kinase inhibitor (P21 and Interleukin-3 (IL-3 in hepatic cells. Conclusion. TGF-β/Smad signaling pathway is involved in HCD-induced hepatotoxicity and Rutin inhibits the hepatotoxicity via suppressing this pathway. Therefore, Rutin might be considered as a protective agent for hepatotoxicity.

  10. Proteomic investigation of signatures for geniposide-induced hepatotoxicity.

    Science.gov (United States)

    Wei, Junying; Zhang, Fangbo; Zhang, Yi; Cao, Chunyu; Li, Xianyu; Li, Defeng; Liu, Xin; Yang, Hongjun; Huang, Luqi

    2014-12-05

    Evaluating the safety of traditional medicinal herbs and their major active constituents is critical for their widespread usage. Geniposide, a major active constituent with a defined structure from the traditional medicinal herb Gardenia jasminoides ELLIS fruit, exhibits remarkable anti-inflammatory, antiapoptotic, and antifibrotic properties and has been used in a variety of medical fields, mainly for the treatment of liver diseases. However, geniposide-induced hepatotoxicity and methods for the early detection of hepatotoxicity have yet to be reported. In this study, geniposide-induced hepatotoxicity was investigated. In addition, candidate biomarkers for the earlier detection of geniposide-induced hepatotoxicity were identified using a label-free quantitative proteomics approach on a geniposide overdose-induced liver injury in a rat model. Using an accurate intensity-based, absolute quantification (iBAQ)-based, one-step discovery and verification approach, a candidate biomarker panel was easily obtained from individual samples in response to different conditions. To determine the biomarkers' early detection abilities, five candidate biomarkers were selected and tested using enzyme-linked immunosorbent assays (ELISAs). Two biomarkers, glycine N-methyltransferase (GNMT) and glycogen phosphorylase (PYGL), were found to indicate hepatic injuries significantly earlier than the current gold standard liver biomarker. This study provides a first insight into geniposide-induced hepatotoxicity in a rat model and describes a method for the earlier detection of this hepatotoxicity, facilitating the efficient monitoring of drug-induced hepatotoxicity.

  11. HUMAN-SIMULATING VEHICLE STEERING CONTROL ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    XU Youchun; LI Keqiang; CHANG Ming; CHEN Jun

    2006-01-01

    A new vehicle steering control algorithm is presented. Unlike the traditional methods do,the algorithm uses a sigmoid function to describe the principle of the human driver's steering strategy.Based on this function, a human simulating vehicle steering model, human-simulating steering control(HS) algorithm is designed. In order to improve the adaptability to different environments, a parameter adaptive adjustment algorithm is presented. This algorithm can online modify the value of the key parameters of the HS real time. HS controller is used on a vehicle equipped with computer vision system and computer controlled steering actuator system, the result from the automatic vehicle steering experiment shows that the HS algorithm gives good performance at different speed, even at the maximum speed of 172 km/h.

  12. 46 CFR 182.610 - Main steering gear.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Main steering gear. 182.610 Section 182.610 Shipping...) MACHINERY INSTALLATION Steering Systems § 182.610 Main steering gear. (a) A vessel must be provided with a main steering gear that is: (1) Of adequate strength and capable of steering the vessel at all...

  13. Driver behavior following an automatic steering intervention.

    Science.gov (United States)

    Fricke, Nicola; Griesche, Stefan; Schieben, Anna; Hesse, Tobias; Baumann, Martin

    2015-10-01

    The study investigated driver behavior toward an automatic steering intervention of a collision mitigation system. Forty participants were tested in a driving simulator and confronted with an inevitable collision. They performed a naïve drive and afterwards a repeated exposure in which they were told to hold the steering wheel loosely. In a third drive they experienced a false alarm situation. Data on driving behavior, i.e. steering and braking behavior as well as subjective data was assessed in the scenarios. Results showed that most participants held on to the steering wheel strongly or counter-steered during the system intervention during the first encounter. Moreover, subjective data collected after the first drive showed that the majority of drivers was not aware of the system intervention. Data from the repeated drive in which participants were instructed to hold the steering wheel loosely, led to significantly more participants holding the steering wheel loosely and thus complying with the instruction. This study seems to imply that without knowledge and information of the system about an upcoming intervention, the most prevalent driving behavior is a strong reaction with the steering wheel similar to an automatic steering reflex which decreases the system's effectiveness. Results of the second drive show some potential for countermeasures, such as informing drivers shortly before a system intervention in order to prevent inhibiting reactions.

  14. Possible hepatotoxicity of chronic marijuana usage

    Directory of Open Access Journals (Sweden)

    Paulo Borini

    Full Text Available CONTEXT: Hepatotoxicity is a potential complication from the usage of various illicit drugs, possibly consequent to their liver metabolism, but information on this is scarce in the medical literature. OBJECTIVE: To study the occurrence of clinical and laboratory hepatic alterations in chronic marijuana users, from the use of marijuana on its own or in association with other legal or illicit drugs. TYPE OF STUDY: transversal study SETTING: Hospital Espírita de Marília, Marília, São Paulo, Brazil PARTICIPANTS: The study was made among 123 patients interned in the Hospital Espírita de Marília from October 1996 to December 1998, divided into 3 groups: 26 (21% using only marijuana, 83 (67.5% using marijuana and crack, and 14 (11.4% consuming marijuana and alcohol. PROCEDURES AND MAIN MEASUREMENTS: Patients were examined clinically with special emphasis on types of drugs used, drug intake route, age when consumption began, length and pattern of usage, presence of tattooing, jaundice, hepatomegaly and splenomegaly. Serum determinations of total proteins, albumin, globulin, total and fractions of bilirubin, aspartate (AST and alanine (ALT aminotransferases, alkaline phosphatase (AP, gamma-glutamyltransferase and prothrombin activity were performed. RESULTS: Among users of only marijuana, hepatomegaly was observed in 57.7% and splenomegaly in 73.1%, and slightly elevated AST (42.3%, ALT (34.6% and AP (53.8%. The three groups did not differ significantly in the prevalence of hepatomegaly, splenomegaly and hepatosplenomegaly. The group using both marijuana and alcohol showed the highest prevalence of alterations and highest levels of aminotransferases. Mean AP levels were above normal in all groups. CONCLUSIONS: Chronic marijuana usage, on its own or in association with other drugs, was associated with hepatic morphologic and enzymatic alterations. This indicates that cannabinoids are possible hepatotoxic substances.

  15. Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Das S

    2011-06-01

    Full Text Available Suvadra Das, Partha Roy, Runa Ghosh Auddy, Arup MukherjeeDepartment of Chemical Technology, University of Calcutta, Kolkata, West Bengal, IndiaAbstract: Silymarin (Sm is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low aqueous solubility and associated biopharmaceutical limitations. Sm flavonolignans are also susceptible to ion-catalyzed degradation in the gut. Proven antihepatotoxic activity of Sm cannot therefore be fully exploited in acute chemical poisoning conditions like that in paracetamol overdose. Moreover, a synchronous delivery that is required for hepatic regeneration is difficult to achieve by itself. This work is meant to circumvent the inherent limitations of Sm through the use of nanotechnology. Sm nanoparticles (Smnps were prepared by nanoprecipitation in polyvinyl alcohol stabilized Eudragit RS100® polymer (Rohm Pharma GmbH, Darmstadt, Germany. Process parameter optimization provided 67.39% entrapment efficiency and a Gaussian particle distribution of average size 120.37 nm. Sm release from the nanoparticles was considerably sustained for all formulations. Smnps were strongly protective against hepatic damage when tested in a paracetamol overdose hepatotoxicity model. Nanoparticles recorded no animal death even when administered after an established paracetamol-induced hepatic necrosis. Preventing progress of paracetamol hepatic damage was traced for an efficient glutathione regeneration to a level of 11.3 µmol/g in hepatic tissue due to Smnps.Keywords: silymarin, paracetamol, nanoparticle, glutathione, mouse hepatotoxicity

  16. A Rare Side Effect of Metformin: Metformin-Induced Hepatotoxicity

    OpenAIRE

    2007-01-01

    Metformin is an oral hypoglycemic agent that is commonly used in the treatment of type 2 diabetes mellitus. While metformin-associated metabolic acidosis is a widely recognized side effect of this drug, metformin-induced hepatotoxicity has been rarely reported in the literature. We present herein the case of a 52-year-old male in whom metformin-associated lactic acidosis and metformin-induced hepatotoxicity developed.

  17. Steering control system for a mobile robot

    Science.gov (United States)

    Kolli, Kaylan C.; Hall, Ernest L.

    1997-09-01

    Automated guided vehicles (AGVs) have many potential applications in manufacturing, medicine, space and defense. The purpose of this paper is to describe the design of a steering mechanism for an autonomous mobile robot. The steering mechanism replaces a manually turned rack and pinion arrangement with a crank mechanism driven by a linear actuator that in turn is powered by a brushless dc motor. The system was modeled, analyzed, and redesigned to meet the requirements. A 486 computer through a 3-axis motion controller supervises the steering control. The steering motor is a brushless dc motor powered by three phase signals. It is run in current loop mode. The steering control system is supervised by a personal computer through a multi-axis motion controller. Testing of these systems has been done in the lab as well as on an outside test track with positive results.

  18. Wireless traffic steering for green cellular networks

    CERN Document Server

    Zhang, Shan; Zhou, Sheng; Niu, Zhisheng; Shen, Xuemin (Sherman)

    2016-01-01

    This book introduces wireless traffic steering as a paradigm to realize green communication in multi-tier heterogeneous cellular networks. By matching network resources and dynamic mobile traffic demand, traffic steering helps to reduce on-grid power consumption with on-demand services provided. This book reviews existing solutions from the perspectives of energy consumption reduction and renewable energy harvesting. Specifically, it explains how traffic steering can improve energy efficiency through intelligent traffic-resource matching. Several promising traffic steering approaches for dynamic network planning and renewable energy demand-supply balancing are discussed. This book presents an energy-aware traffic steering method for networks with energy harvesting, which optimizes the traffic allocated to each cell based on the renewable energy status. Renewable energy demand-supply balancing is a key factor in energy dynamics, aimed at enhancing renewable energy sustainability to reduce on-grid energy consum...

  19. Mecanismos de hepatotoxicidade Mechanisms of hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Marcelo Chiara Bertolami

    2005-10-01

    Full Text Available Hepatopatia relacionada ao uso de drogas hipolipemiantes tem sido definida como um dano celular (aumento das enzimas AST e ALT sem alterações colestáticas (aumento de bilirrubinas e/ou fosfatase alcalina. Seis mecanismos são propostos para a hepatopatia: 1. Reações de alta energia no citocromo P450 comprometendo a homeostase do cálcio com a ruptura de fibrilas intracelulares e lise de hepatócitos. 2. Disfunção de proteínas transportadoras relacionadas com o fluxo de ácidos biliares (mecanismo proposto para a toxicidade hepática dos fibratos. 3. Reações imunes geradas pela formação de metabólitos das drogas hipolipemiantes formados no fígado. 4. Hepatoxicidade promovida por células T com inflamação adicional mediada por neutrófilos. 5. Apoptose mediada por TNF e Fas (imune-mediada. 6. Estresse oxidativo gerado por dano a organelas intracelulares. Ainda, idade avançada, consumo excessivo de álcool, altas doses de drogas hipolipemiantes, interação com outros fármacos, e doença hepática ativa prévia podem aumentar a hepatotoxidade.Liver disease following the use of hypolipidemic drugs has been reported as a cellular damage (increases in AST or ALT enzymes without cholestatic alterations (bilirubin and or alkaline phosphatase increases. Six mechanisms were proposed for hepatotoxicity : 1. High energy reactions on P450 cytochrome impairing calcium homestasis with rupture of intracellular fibrils and hepatocyte lysis. 2. Impairment of transporter proteins related to the bile acids flux (mechanism proposed for fibrate liver toxicity. 3. Immune reactions due to the formation of metabolites linked to enzymes following liver metabolism of hypolipidemic drugs. 4. Hepatotoxicity by T cells with additional inflammation mediated by neutrophils. 5. Apoptosis mediated by TNF and Fas (immune mediated. 6. Oxidative stress due to damage of intracellular organelles. In addition, advanced age, alcohol in excess, high doses of

  20. Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats.

    Science.gov (United States)

    Mochizuki, Masahiro; Shimizu, Satomi; Urasoko, Yoshinaka; Umeshita, Kazuhiko; Kamata, Takashi; Kitazawa, Takahiro; Nakamura, Daichi; Nishihata, Yoshito; Ohishi, Takumi; Edamoto, Hiroshi

    2009-04-01

    Carbon tetrachloride (CCl4) is well known to induce hepatotoxicity after being metabolized to trichloromethyl free radical ((.)CCl3) by CYP2E1. In the present study, the hepatotoxicity induced by a single oral dose (2,000 mg/kg) of CCl4 was compared between pregnant (gestation days (GD) 13 and 19) or postpartum (postpartum days (PPD) 1, 13 and 27) and non-pregnant rats. Hepatotoxicity in CCl4-treated pregnant rats evaluated by blood chemistry (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities) and histopathological finding (area of damaged hepatocytes) was minimal on GD19, being weaker than that in non-pregnant rats. CYP2E1 expression in non-treated pregnant rats decreased as pregnancy progressed and reached minimum level on GD19. Thus, the degree of CCl4-induced hepatotoxicity roughly corresponded to CYP2E1 levels during pregnancy. After delivery, hepatotoxicity in CCl4-treated lactating rats was maximal on PPD13, being stronger than that in non-pregnant rats, and then it decreased slightly on PPD27. The CYP2E1 level in the non-treated lactating rats tended to increase but remained at lower levels until PPD13 compared with that in non-pregnant rats. Thus, the degree of CCl4-induced hepatotoxicity did not correspond to CYP2E1 levels during lactation. This suggests that during lactation, there may be certain factors other than CYP2E1 expression responsible for the degree of CCl4-induced hepatotoxicity.

  1. Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Nesreen E.M. Mohammed

    2016-11-01

    Conclusion: Amlodipine, lisinopril or allopurinol can protect against acetaminophen-induced hepatotoxicity, showing mechanistic roles of calcium channels, angiotensin converting enzyme and xanthine oxidase enzyme in the pathogenesis of hepatotoxicity induced by acetaminophen.

  2. Hepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Ebbesen, Maria S.; Nygaard, Ulrikka; Rosthøj, Susanne

    2017-01-01

    Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine...

  3. Hepatotoxicity Induced by “the 3Ks”: Kava, Kratom and Khat

    OpenAIRE

    Flaminia Pantano; Roberta Tittarelli; Giulio Mannocchi; Simona Zaami; Serafino Ricci; Raffaele Giorgetti; Daniela Terranova; Busardò, Francesco P.; Enrico Marinelli

    2016-01-01

    The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, lea...

  4. Joint measurability and temporal steering [Invited

    Science.gov (United States)

    Karthik, H. S.; Prabhu Tej, J.; Usha Devi, A. R.; Rajagopal, A. K.

    2015-04-01

    Quintino et. al. (Phys. Rev. Lett. 113, 160402 (2014)) and Uola et. al. (Phys. Rev. Lett. 113, 160403 (2014)) have recently established an intrinsic relation between non-joint measurability and Einstein-Podolsky- Rosen steering. They showed that a set of measurements is incompatible (i.e., not jointly measurable) if and only if it can be used for the demonstration of steering. In this paper, we prove the temporal analog of this result viz., a set of measurements are incompatible if and only if it exhibits temporal steering.

  5. 46 CFR 108.641 - Instructions for changing steering gear.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Instructions for changing steering gear. 108.641 Section... steering gear. Instructions stating, in order, the different steps to be taken for changing to emergency and secondary steering gear must be posted in the steering gear room and at each secondary...

  6. 46 CFR 169.623 - Power-driven steering systems.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Power-driven steering systems. 169.623 Section 169.623 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Steering Systems § 169.623 Power-driven steering systems. (a) Power-driven steering...

  7. Steer-by-wire steering system with enhanced functionality for rear steered vehicles

    Directory of Open Access Journals (Sweden)

    Christoph Dillmann

    2015-12-01

    Full Text Available Heckgelenkte selbstfahrende Erntemaschinen sind die zentralen Elemente moderner Ernteketten in der Landwirtschaft. Das primär auf Bodenschonung ausgelegte Fahrwerk, die aktuelle Höchstgeschwindigkeit von 40 km/h sowie die systembedingten, fahrdynamischen Nachteile einer heckgelenkten Maschine erschweren jedoch die Fahrzeugführung auf der Straße. Das Spurhalten und Stabilisieren erfordert daher viel Erfahrung und eine hohe Konzentration des Fahrers. Fahrdynamiksysteme können den Fahrzeugführer entlasten und somit das Fahren mit hohen Geschwindigkeiten sicherer und komfortabler gestalten. Im hier vorgestellten Projekt wird in diesem Kontext eine Steer-by-wire-Lenkung mit parametrierbarer Lenkcharakteristik vorgestellt, die auf die unterschiedlichen Vorzüge des Fahrers einstellbar ist und fahrzustandsabhängige Informationen über das Lenkrad an den Bediener übermittelt.

  8. Experimental models of hepatotoxicity related to acute liver failure

    Science.gov (United States)

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2015-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. PMID:26631581

  9. DIFFERENT MODELS OF HEPATOTOXICITY AND RELATED LIVER DISEASES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Singh Robin

    2012-07-01

    Full Text Available The liver is among the most complex and important organs in the human body. Its primary function is to control the flow and safety of substances absorbed from the digestive system before distribution of these substances to the systemic circulatory system. Hepatotoxicity implies chemical-driven liver damage. Chemicals that cause liver injury are called hepatotoxins. Hepatic injury leads to disturbances in transport function of hepatocytes resulting in leakage of plasma membrane thereby causing an increased enzyme level in serum. There are many diseases that are related with hepatotoxicity caused by certain chemicals or hepatotoxins. Herbal medicines are great demand in various chemicals and drugs disordered hepatic, the developed world for primary health care because of their efficacy, safety, lesser side effects and narrow therapeutic window. This review focus on liver, its function, liver diseases and different models of hepatotoxicity.

  10. Herbal Hepatotoxicity: Clinical Characteristics and Listing Compilation.

    Science.gov (United States)

    Frenzel, Christian; Teschke, Rolf

    2016-04-27

    Herb induced liver injury (HILI) and drug induced liver injury (DILI) share the common characteristic of chemical compounds as their causative agents, which were either produced by the plant or synthetic processes. Both, natural and synthetic chemicals are foreign products to the body and need metabolic degradation to be eliminated. During this process, hepatotoxic metabolites may be generated causing liver injury in susceptible patients. There is uncertainty, whether risk factors such as high lipophilicity or high daily and cumulative doses play a pathogenetic role for HILI, as these are under discussion for DILI. It is also often unclear, whether a HILI case has an idiosyncratic or an intrinsic background. Treatment with herbs of Western medicine or traditional Chinese medicine (TCM) rarely causes elevated liver tests (LT). However, HILI can develop to acute liver failure requiring liver transplantation in single cases. HILI is a diagnosis of exclusion, because clinical features of HILI are not specific as they are also found in many other liver diseases unrelated to herbal use. In strikingly increased liver tests signifying severe liver injury, herbal use has to be stopped. To establish HILI as the cause of liver damage, RUCAM (Roussel Uclaf Causality Assessment Method) is a useful tool. Diagnostic problems may emerge when alternative causes were not carefully excluded and the correct therapy is withheld. Future strategies should focus on RUCAM based causality assessment in suspected HILI cases and more regulatory efforts to provide all herbal medicines and herbal dietary supplements used as medicine with strict regulatory surveillance, considering them as herbal drugs and ascertaining an appropriate risk benefit balance.

  11. Herbal Hepatotoxicity: Clinical Characteristics and Listing Compilation

    Directory of Open Access Journals (Sweden)

    Christian Frenzel

    2016-04-01

    Full Text Available Herb induced liver injury (HILI and drug induced liver injury (DILI share the common characteristic of chemical compounds as their causative agents, which were either produced by the plant or synthetic processes. Both, natural and synthetic chemicals are foreign products to the body and need metabolic degradation to be eliminated. During this process, hepatotoxic metabolites may be generated causing liver injury in susceptible patients. There is uncertainty, whether risk factors such as high lipophilicity or high daily and cumulative doses play a pathogenetic role for HILI, as these are under discussion for DILI. It is also often unclear, whether a HILI case has an idiosyncratic or an intrinsic background. Treatment with herbs of Western medicine or traditional Chinese medicine (TCM rarely causes elevated liver tests (LT. However, HILI can develop to acute liver failure requiring liver transplantation in single cases. HILI is a diagnosis of exclusion, because clinical features of HILI are not specific as they are also found in many other liver diseases unrelated to herbal use. In strikingly increased liver tests signifying severe liver injury, herbal use has to be stopped. To establish HILI as the cause of liver damage, RUCAM (Roussel Uclaf Causality Assessment Method is a useful tool. Diagnostic problems may emerge when alternative causes were not carefully excluded and the correct therapy is withheld. Future strategies should focus on RUCAM based causality assessment in suspected HILI cases and more regulatory efforts to provide all herbal medicines and herbal dietary supplements used as medicine with strict regulatory surveillance, considering them as herbal drugs and ascertaining an appropriate risk benefit balance.

  12. Biochemical effects of Calotropis procera on hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Ali Ismaiel Ali Abd Alrheam

    2015-12-01

    Full Text Available Introduction: Calotropis procera commonly known as Sodom apple is a 6-meter high shrub that belongs to the Aclepiadaceae plant family and is commonly found in West Africa and other tropical places. In Saudi Arabia the plant is commonly used in traditional medicine for the treatment of variety of diseases including fever, constipation, muscular spasm and joint pain. Aim: In the present study C. procera were investigated for the hepatoprotective activity. Material and Methods: Carbon tetrachloride is used to produce hepatotoxicity. Forty two male albino rats, weighting 150-200 gm divided into seven groups, each consisted of 6 rats. Carbon tetrachloride 2ml/kg was administered twice a week to all of the groups of animals except group I, which served as control and given the normal saline. Group II served as Carbon tetrachloirde control. Group III received Silymarin at 100 mg/kg/day dose, Group IV received aqueous leaves extracts C. procera 200mg/kg, Group V received chloroform leaves extracts C. procera 200mg/kg, Group VI received ethanol leaves extracts C. procera 200 mg/kg, Group VII received latex of C. procera 200mg/kg. The effect of aqueous, chloroform, ethanol leaves extract and latex C. procera on biochemical parameters of liver was measured. Results: The results showed that the aqueous, chloroform, ethanol leaves extract and latex C. procera produced significant decrease in Acid phosphatase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Total protein, Albumin and total bilirubin levels compared to the CCL4 treated group II. Conclusion: Calotropis procera appears to to have hepatoprotective activity and these may be due to enrich of the plant by phytoconstituents that activate and in hence a pharmacological response of different parts of the body and this study need further studies to shows the complete properties of the plant. [Biomed Res Ther 2015; 2(12.000: 446-453

  13. Performance assessment of PEFP steering magnet

    Energy Technology Data Exchange (ETDEWEB)

    Han, S. H.; Jeo, Y. S. [KAERI, Taejon (Korea, Republic of)

    2003-10-01

    PEFP LEBT uses two solenoid and two steering magnets for the beam position and angle control at the RFQ match point. The dependence of magnetic field and coil temperature on time was assessed and the linearity was also measured.

  14. CCCT - NCTN Steering Committees - Gynecologic Cancers

    Science.gov (United States)

    The Gynecologic Cancers Steering Committee evaluates and prioritizes concepts for phase 2 and 3 clinical trials in adult gynecologic cancers. The GCSC is also intent on fostering collaboration with international groups and institutions conducting trials.

  15. Omni rotational driving and steering wheel

    DEFF Research Database (Denmark)

    2008-01-01

    Abstract of WO 2008138346  (A1) There is disclosed a driving and steering wheel (112) module (102) with an omni rotational part (106), the module comprising a flange part (104) fixable on a robot, and the omni rotational part (106) comprises an upper omni rotational part (105) and a driving...... and steering wheel part (108), where the omni rotational part (106) is provided for infinite rotation relative to the flange part (104) by both a drive motor (110) and a steering motor (114) being positionable on the flange part (104), and the driving and steering wheel part (108) is suspended from the upper...... omni rotational part (105) with a suspension (116) such that wheel part (108) can move relatively to the upper omni rotational part (105) in a suspension direction (118), and a reduction gear (120) for gearing the drive torque is provided in the wheel part (108) in order e.g. to assure traction...

  16. CCCT - NCTN Steering Committees - Clinical Imaging

    Science.gov (United States)

    The Clinical Imaging Steering Committee serves as a forum for the extramural imaging and oncology communities to provide strategic input to the NCI regarding its significant investment in imaging activities in clinical trials.

  17. CCCT - NCORP Cancer Control Steering Committees

    Science.gov (United States)

    The National Community Oncology Research Program (NCORP) Steering Committees review concepts for clinical trials to control cancer symptoms and cancer treatment side effects, and concepts for studies of cancer care delivery.

  18. Rutin Attenuates Hepatotoxicity in High-Cholesterol-Diet-Fed Rats

    OpenAIRE

    AlSharari, Shakir D.; Al-Rejaie, Salim S.; Abuohashish, Hatem M.; Ahmed, Mohamed M.; Hafez, Mohamed M

    2016-01-01

    Background and Objective. High-cholesterol diet (HCD) intends to increase the oxidative stress in liver tissues inducing hepatotoxicity. Rutin is a natural flavonoid (vitamin p) which is known to have antioxidative properties. The aim of the present study was to investigate the potential effects of Rutin on hypercholesterolemia-induced hepatotoxicity in rats. Materials and Methods. Male Wistar rats were divided into four groups: G-I control, G-II Rutin, G-III HCD, and G-IV Rutin + HCD. The li...

  19. New steering mechanism for wheeled mobile robots

    Institute of Scientific and Technical Information of China (English)

    Sidibe Marie Bernard; FU Yi-li; XU He; MA Yu-lin

    2007-01-01

    A new castor wheel mechanism for omni-directional mobile platform is presented. A motion of translation is transformed into a rotation to steer the wheel with the help of a helical path fits into a translation joint and three rollers whose axes are connected to the driving shaft of the wheel. When the path moves in translation it acts on the rollers for steering. The path-roller friction transmission, the wheel kinematics and the maneuverability have been analyzed.

  20. Quantum steering in cascaded four-wave mixing processes.

    Science.gov (United States)

    Wang, Li; Lv, Shuchao; Jing, Jietai

    2017-07-24

    Quantum steering is used to describe the "spooky action-at-a-distance" nonlocality raised in the Einstein-Podolsky-Rosen (EPR) paradox, which is important for understanding entanglement distribution and constructing quantum networks. Here, in this paper, we study an experimentally feasible scheme for generating quantum steering based on cascaded four-wave-mixing (FWM) processes in hot rubidium (Rb) vapor. Quantum steering, including bipartite steering and genuine tripartite steering among the output light fields, is theoretically analyzed. We find the corresponding gain regions in which the bipartite and tripartite steering exist. The results of bipartite steering can be used to establish a hierarchical steering model in which one beam can steer the other two beams in the whole gain region; however, the other two beams cannot steer the first beam simultaneously. Moreover, the other two beams cannot steer with each other in the whole gain region. More importantly, we investigate the gain dependence of the existence of the genuine tripartite steering and we find that the genuine tripartite steering exists in most of the whole gain region in the ideal case. Also we discuss the effect of losses on the genuine tripartite steering. Our results pave the way to experimental demonstration of quantum steering in cascaded FWM process.

  1. Active steering control strategy for articulated vehicles

    Institute of Scientific and Technical Information of China (English)

    Kyong-il KIM; Hsin GUAN; Bo WANG; Rui GUO; Fan LIANG

    2016-01-01

    To improve maneuverability and stability of articulated vehicles, we design an active steering controller, including tractor and trailer controllers, based on linear quadratic regulator (LQR) theory. First, a three-degree-of-freedom (3-DOF) model of the tractor-trailer with steered trailer axles is built. The simulated annealing particle swarm optimization (SAPSO) algorithm is applied to identify the key parameters of the model under specified vehicle speed and steering wheel angle. Thus, the key pa-rameters of the simplified model can be obtained according to the vehicle conditions using an online look-up table and interpola-tion. Simulation results show that vehicle parameter outputs of the simplified model and TruckSim agree well, thus providing the ideal reference yaw rate for the controller. Then the active steering controller of the tractor and trailer based on LQR is designed to follow the desired yaw rate and minimize their side-slip angle of the center of gravity (CG) at the same time. Finally, simulation tests at both low speed and high speed are conducted based on the TruckSim-Simulink program. The results show significant effects on the active steering controller on improving maneuverability at low speed and lateral stability at high speed for the articulated vehicle. The control strategy is applicable for steering not only along gentle curves but also along sharp curves.

  2. Improvement of motor inertia influence of electric power steering; Dendoshiki power steering no motor kansei no eikyo to hosho

    Energy Technology Data Exchange (ETDEWEB)

    Takehara, S.; Sakamoto, K.; Hanamoto, Y. [Mazda Motor Corp., Hiroshima (Japan); Noritsugu, T. [Okayama University, Okayama (Japan)

    1997-10-01

    Motor inertia of electric power steering affects not only steering characteristics but vehicle dynamics. We have investigated the influence of motor inertia and proposed a feedback strategy to compensate it. Weight of the test vehicle is 1100Kg and the steering system is pinion type electric power steering. By using simulation model and vehicle test, we have realized natural steering maneuvering and stable vehicle dynamics. 4 refs., 11 figs.

  3. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism.

    Science.gov (United States)

    Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

    2016-03-07

    Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

  4. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

    Directory of Open Access Journals (Sweden)

    Xinmiao Yan

    2016-03-01

    Full Text Available Pyrrolizidine Alkaloids (PAs are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1 and glutathione peroxidase 1 (GPX1 targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

  5. Activation of Nrf2 protects against triptolide-induced hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Jia Li

    Full Text Available Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF, has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2 in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN, attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.

  6. Hepatotoxicity induced by cyproterone acetate: A report of three cases

    Institute of Scientific and Technical Information of China (English)

    Ioanna Savidou; Melanie Deutsch; Aspasia S Soultati; Dimitrios Koudouras; Georgia Kafiri; Spyridon P Dourakis

    2006-01-01

    Cyproterone acetate (CPA) is a steroidal synthetic progestagen and anti-androgenic compound widely administered in prostate cancer which has been evidentially correlated with a severe hepatotoxic potency.Three male patients aged 78-83 years are presented, in whom severe hepatotoxic reactions emerged after CPA administration. Patients were treated with CPA at the doses of 200-300 mg/d for malignant prostate disease for 3-12 mo prior to the acute manifestation of the hepatic disease. Clinical features compatible with mixed hepatocellular and cholestatic liver disease including jaundice, white stools and dark urine, manifested in all three cases whereas encephalopathy and ascites were present in two of the patients. Other primary causes of hepatotoxicity (alcohol consumption and viral hepatitis)were also verified in two cases, and in those patients biopsy findings revealed the presence of cirrhotic lesions in liver parenchyma. Discontinuation of the therapeutic agent led to the amelioration of the clinical profile in all the patients whereas a patient died 40 d after hospital admission due to sepsis, despite acute liver disease improvement. The current article highlights the hepatotoxic potency of a widely administered therapeutic agent and illustrates the importance of clinical surveillance especially in patients with previous hepatic diseases. Three relevant cases are reported and a review of the published literature is made.

  7. Research on Modeling and Active Steering Control Algorithm for Electric Forklift Steer-by-Wire System

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2016-11-01

    Full Text Available In this paper, according to the structure characteristics of steer-by-wire (SBW system for the TFC20 electric forklift, steering dynamics model and two degree of freedom vehicle model are deduced for SBW forklift. Aiming at the free design features of the angular transmission characteristics in the SBW system of electric forklift, the theory of active steering control strategy is studied. After analyzing the influence factors of the angular trans mission ratio of the steering system, the ideal angular transmission ratio is proposed, which is based on the yaw rate gain invariance. Also, the control strategy of the yaw rate feedback and the full state feedback is studied. The simulation results show that the above strategy is effective for the active steering control; it can improve the operating stability and the response speed of the forklift.

  8. Enhanced acetaminophen hepatotoxicity in transgenic mice overexpressing BCL-2.

    Science.gov (United States)

    Adams, M L; Pierce, R H; Vail, M E; White, C C; Tonge, R P; Kavanagh, T J; Fausto, N; Nelson, S D; Bruschi, S A

    2001-11-01

    Mitochondria play an important role in the cell death induced by many drugs, including hepatotoxicity from overdose of the popular analgesic, acetaminophen (APAP). To investigate mitochondrial alterations associated with APAP-induced hepatotoxicity, the subcellular distribution of proapoptotic BAX was determined. Based on the antiapoptotic characteristics of BCL-2, we further hypothesized that if a BAX component was evident then BCL-2 overexpression may be hepatoprotective. Mice, either with a human bcl-2 transgene (-/+) or wild-type mice (WT; -/-), were dosed with 500 or 600 mg/kg (i.p.) APAP or a nonhepatotoxic isomer, N-acetyl-m-aminophenol (AMAP). Immunoblot analyses indicated increased mitochondrial BAX-beta content very early after APAP or AMAP treatment. This was paralleled by disappearance of BAX-alpha from the cytosol of APAP treated animals and, to a lesser extent, with AMAP treatment. Early pathological evidence of APAP-induced zone 3 necrosis was seen in bcl-2 (-/+) mice, which progressed to massive panlobular necrosis with hemorrhage by 24 h. In contrast, WT mice dosed with APAP showed a more typical, and less severe, centrilobular necrosis. AMAP-treated bcl-2 (-/+) mice displayed only early microvesicular steatosis without progression to extensive necrosis. Decreased complex III activity, evident as early as 6 h after treatment, correlated well with plasma enzyme activities at 24 h (AST r(2) = 0.89, ALT r(2) = 0.87) thereby confirming a role for mitochondria in APAP-mediated hepatotoxicity. In conclusion, these data suggest for the first time that BAX may be an early determinant of APAP-mediated hepatotoxicity and that BCL-2 overexpression unexpectedly enhances APAP hepatotoxicity.

  9. No-cloning of quantum steering

    Science.gov (United States)

    Chiu, Ching-Yi; Lambert, Neill; Liao, Teh-Lu; Nori, Franco; Li, Che-Ming

    2016-06-01

    Einstein-Podolsky-Rosen (EPR) steering allows two parties to verify their entanglement, even if one party’s measurements are untrusted. This concept has not only provided new insights into the nature of non-local spatial correlations in quantum mechanics, but also serves as a resource for one-sided device-independent quantum information tasks. Here, we investigate how EPR steering behaves when one-half of a maximally entangled pair of qudits (multidimensional quantum systems) is cloned by a universal cloning machine. We find that EPR steering, as verified by a criterion based on the mutual information between qudits, can only be found in one of the copy subsystems but not both. We prove that this is also true for the single-system analogue of EPR steering. We find that this restriction, which we term ‘no-cloning of quantum steering’, elucidates the physical reason why steering can be used to secure sources and channels against cloning-based attacks when implementing quantum communication and quantum computation protocols.

  10. Research on Torque Ratio Based on the Steering Wheel Torque Characteristic for Steer-by-Wire System

    OpenAIRE

    Yandong Han; Lei He; Xiang Wang; Changfu Zong

    2014-01-01

    Steer-by-wire system can improve the performance of vehicle handling stability. Removing the mechanical linkages between the front wheels and the steering wheel leads to a key technique of force feedback for steer-by-wire system. In view of the characteristic of variable torque transmission ratio for steer-by-wire system, this paper proposes a method for designing torque ratio based on the steering wheel torque characteristic for steer-by-wire system. It converts the torque ratio design into ...

  11. Tunable beam steering enabled by graphene metamaterials.

    Science.gov (United States)

    Orazbayev, B; Beruete, M; Khromova, I

    2016-04-18

    We demonstrate tunable mid-infrared (MIR) beam steering devices based on multilayer graphene-dielectric metamaterials. The effective refractive index of such metamaterials can be manipulated by changing the chemical potential of each graphene layer. This can arbitrarily tailor the spatial distribution of the phase of the transmitted beam, providing mechanisms for active beam steering. Three different beam steerer (BS) designs are discussed: a graded-index (GRIN) graphene-based metamaterial block, an array of metallic waveguides filled with graphene-dielectric metamaterial and an array of planar waveguides created in a graphene-dielectric metamaterial block with a specific spatial profile of graphene sheets doping. The performances of the BSs are numerically analyzed, showing the tunability of the proposed designs for a wide range of output angles (up to approximately 70°). The proposed graphene-based tunable beam steering can be used in tunable transmitter/receiver modules for infrared imaging and sensing.

  12. Steering object-oriented computations with Python

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T.-Y.B.; Dubois, P.F.; Furnish, G. [Lawrence Livermore National Lab., CA (United States); Beazley, D.M. [Utah Univ., Salt Lake City, UT (United States). Dept. of Computer Science

    1996-10-01

    We have described current approaches and future plans for steering C++ application, running Python on parallel platforms, and combination of Tk interface and Python interpreter in steering computations. In addition, there has been significant enhancement in the Gist module. Tk mega widgets has been implemented for a few physics applications. We have also written Python interface to SIJLO, a data storage package used as an interface to a visualization system named MeshTv. Python is being used to control large-scale simulations (molecular dynamics in particular) running on the CM-5 and T3D at LANL as well. A few other code development projects at LLNL are either using or considering Python as their steering shells. In summary, the merits of Python have been appreciated by more and more people in the scientific computation community.

  13. Stability analysis of automobile driver steering control

    Science.gov (United States)

    Allen, R. W.

    1981-01-01

    In steering an automobile, the driver must basically control the direction of the car's trajectory (heading angle) and the lateral deviation of the car relative to a delineated pathway. A previously published linear control model of driver steering behavior which is analyzed from a stability point of view is considered. A simple approximate expression for a stability parameter, phase margin, is derived in terms of various driver and vehicle control parameters, and boundaries for stability are discussed. A field test study is reviewed that includes the measurement of driver steering control parameters. Phase margins derived for a range of vehicle characteristics are found to be generally consistent with known adaptive properties of the human operator. The implications of these results are discussed in terms of driver adaptive behavior.

  14. Influence of different shoulder-elbow configurations on steering precision and steering velocity in automotive context.

    Science.gov (United States)

    Schmidt, Susanne; Seiberl, Wolfgang; Schwirtz, Ansgar

    2015-01-01

    Ergonomic design requirements are needed to develop optimum vehicle interfaces for the driver. The majority of the current specifications consider only anthropometric conditions and subjective evaluations of comfort. This paper examines specific biomechanical aspects to improve the current ergonomic requirements. Therefore, a research which involved 40 subjects was carried out to obtain more knowledge in the field of steering movement while driving a car. Five different shoulder-elbow joint configurations were analyzed using a driving simulator to find optimum posture for driving in respect of steering precision and steering velocity. Therefore, a 20 s precision test and a test to assess maximum steering velocity over a range of 90° steering motion have been conducted. The results show that driving precision, as well as maximum steering velocity, are significantly increased in mid-positions (elbow angles of 95° and 120°) compared to more flexed (70°) or extended (145° and 160°) postures. We conclude that driver safety can be enhanced by implementing these data in the automotive design process because faster and highly precise steering can be important during evasive actions and in accident situations. In addition, subjective comfort rating, analyzed with questionnaires, confirmed experimental results.

  15. Online optimized hysteresis-based steering feel model for steer-by-wire systems

    Directory of Open Access Journals (Sweden)

    Ahmet Kirli

    2016-06-01

    Full Text Available In rubber-wheeled road vehicles, the mechanical connection between steering wheel and front wheels provides steering-related feedback to the driver. The torque fed back to the driver through the steering linkages and steering wheel, which is called steering feel, helps the driver in controlling the vehicle. The torque feedback is reproduced via artificial methods in steer-by-wire systems due to the lack of mechanical connection. In this work, in order to minimize the physical workload and the lateral acceleration under the consideration of handling performance, optimization of a hysteresis-based steering feel has been studied. A 2-degree-of-freedom bicycle model based on the magic formula tire model has been used for simulations and hardware-in-the-loop experiments. A mathematical model is proposed in order to create an adaptive model-based optimization of the hysteresis parameters simultaneously while driving. A hardware-in-the-loop experimental setup has been used for the driving tests. The weave and the double-lane change tests have been performed with different drivers in order to demonstrate and quantify the optimization methods that are presented in this work.

  16. Self-steering partially coherent beams

    Science.gov (United States)

    Chen, Yahong; Ponomarenko, Sergey A.; Cai, Yangjian

    2017-01-01

    We introduce a class of shape-invariant partially coherent beams with a moving guiding center which we term self-steering partially coherent beams. The guiding center of each such beam evolves along a straight line trajectory which can be engineered to make any angle with the x-axis. We show that the straight line trajectory of the guiding center is the only option in free space due to the linear momentum conservation. We experimentally generate a particular subclass of new beams, self-steering Gaussian Schell beams and argue that they can find applications for mobile target tracing and trapped micro- and/or nanoparticle transport. PMID:28051164

  17. A control theory approach to clock steering techniques.

    Science.gov (United States)

    Farina, Marcello; Galleani, Lorenzo; Tavella, Patrizia; Bittanti, Sergio

    2010-10-01

    Several clock and time scale steering methods have been developed according to different viewpoints by various time laboratories. By resorting to control theory ideas, we propose a common theoretical framework encompassing these methods. A comparison of the most common steering methodologies, namely, the classical steering approach, the GPS bang-bang method, and the linear quadratic Gaussian technique, is carried out. We believe that the use of control theory methods can potentially lead to a better understanding of clock steering algorithms.

  18. Hepatotoxicity Induced by “the 3Ks”: Kava, Kratom and Khat

    Science.gov (United States)

    Pantano, Flaminia; Tittarelli, Roberta; Mannocchi, Giulio; Zaami, Simona; Ricci, Serafino; Giorgetti, Raffaele; Terranova, Daniela; Busardò, Francesco P.; Marinelli, Enrico

    2016-01-01

    The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by “the 3Ks”, while trying to clarify the numerous aspects that still need to be addressed. PMID:27092496

  19. Hepatotoxicity Induced by “the 3Ks”: Kava, Kratom and Khat

    Directory of Open Access Journals (Sweden)

    Flaminia Pantano

    2016-04-01

    Full Text Available The 3Ks (kava, kratom and khat are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by “the 3Ks”, while trying to clarify the numerous aspects that still need to be addressed.

  20. 46 CFR 58.25-20 - Piping for steering gear.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Piping for steering gear. 58.25-20 Section 58.25-20... MACHINERY AND RELATED SYSTEMS Steering Gear § 58.25-20 Piping for steering gear. (a) Pressure piping must... actuating system including the reservoir. The storage tank must be permanently connected by piping so...

  1. 46 CFR 61.20-1 - Steering gear.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Steering gear. 61.20-1 Section 61.20-1 Shipping COAST... Periodic Tests of Machinery and Equipment § 61.20-1 Steering gear. (a) The marine inspector must inspect the steering gear at each inspection for certification for vessels whose Certificate of...

  2. 46 CFR 167.65-25 - Steering gear tests.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Steering gear tests. 167.65-25 Section 167.65-25... SHIPS Special Operating Requirements § 167.65-25 Steering gear tests. On all nautical school ships making voyages of more than 48 hours' duration, the entire steering gear, the whistle, the means...

  3. 9 CFR 78.6 - Steers and spayed heifers.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Steers and spayed heifers. 78.6... Restrictions on Interstate Movement of Cattle Because of Brucellosis § 78.6 Steers and spayed heifers. Steers and spayed heifers may be moved interstate without restriction under this subpart....

  4. 9 CFR 78.21 - Bison steers and spayed heifers.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bison steers and spayed heifers. 78.21... Restrictions on Interstate Movement of Bison Because of Brucellosis § 78.21 Bison steers and spayed heifers. Bison steers and spayed heifers may be moved interstate without restriction under this subpart....

  5. Working paper on public steering of privately owned sports facilities

    DEFF Research Database (Denmark)

    Iversen, Evald Bundgård

    This short paper discusses how municipalities can steer privately owned sports facilities. Firstly I analyse why steering of privately owned facilities is an interesting subject. Secondly I discuss what the advantages and drawbacks of using different approaches for steering sports facilities are....

  6. Hepatoprotective Potential of Prosopis farcta Beans Extracts against Acetaminophen-induced Hepatotoxicity in Wister Rats

    OpenAIRE

    Akram Asadollahi; Hadi Sarir; Arash Omidi; Mohammad Bagher Montazar Torbati

    2014-01-01

    Background: Hepatotoxicity by acetaminophen is the most frequent cause of acute liver failure in many countries. Prosopis farcta beans extract (PFE) has some antioxidant property and may alleviate hepatotoxicity. Therefore, the aim of this study was to evaluate effects of PFE against acetaminophen-induced hepatotoxicity. Methods: Thirty-six male Wistar albino rats weighing 220 ± 30 g were distributed into six groups. Two groups were pretreated with PFE (50 and 75 mg/kg) for 7 days before ...

  7. Proteomics Investigations of Drug-Induced Hepatotoxicity in HepG2 Cells

    OpenAIRE

    Van Summeren, Anke; Renes, Johan; Bouwman, Freek G.; Noben, Jean-Paul; van Delft, Joost H. M.; Kleinjans, Jos C.S.; Mariman, Edwin C. M.

    2011-01-01

    Unexpected hepatotoxicity is one of the major reasons of drugs failing in clinical trials. This emphasizes the need for new screening methods that address toxicological hazards early in the drug discovery process. Here, proteomics techniques were used to gain further insight into the mechanistic processes of the hepatotoxic compounds. Drug-induced hepatotoxicity is mainly divided in hepatic steatosis, cholestasis, or necrosis. For each class, a compound was selected, respectively amiodarone, ...

  8. The Possible Efficacy of Artichoke in Fluconazole Related Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Hüseyin Kurt

    2014-01-01

    Full Text Available Although fluconazole related hepatotoxicity (FRH is rare, mortal acute hepatic necrosis and jaundice were reported in immunocompromised states such as acquired immunodeficiency syndrome (AIDS and bone marrow transplant (BMT. We present a case of a patient with multiple sclerosis who developed hepatotoxicity with the use of a single 150 mg fluconazole tablet for fungal vaginitis, 10 days after methylprednisolone pulse treatment. Our patient’s alanine aminotransferase (ALT and aspartate aminotransferase (AST levels were decreased, 1200 U/L and 800 U/L, respectively, and bilirubin levels were consistent at 37 mg/dL. Artichoke which has anticholestatic and antioxidant properties was used by our patient. She consumed a 30 mg artichoke leaf extract tea 3 times a day. The bilirubin levels significantly declined at the end of the first week and all liver function tests were normalized within 2 months.

  9. Hepatotoxicity by Drugs: The Most Common Implicated Agents

    Directory of Open Access Journals (Sweden)

    Einar S. Björnsson

    2016-02-01

    Full Text Available Idiosyncratic drug-induced liver injury (DILI is an underreported and underestimated adverse drug reaction. Information on the documented hepatotoxicity of drugs has recently been made available by a website that can be accessed in the public domain: LiverTox (http://livertox.nlm.nih.gov. According to critical analysis of the hepatotoxicity of drugs in LiverTox, 53% of drugs had at least one case report of convincing reports of liver injury. Only 48 drugs had more than 50 case reports of DILI. Amoxicillin-clavulanate is the most commonly implicated agent leading to DILI in the prospective series. In a recent prospective study, liver injury due to amoxicillin-clavulanate was found to occur in approximately one out of 2300 users. Drugs with the highest risk of DILI in this study were azathioprine and infliximab.

  10. Hepatotoxicity caused by montelukast in a paediatric patient.

    Science.gov (United States)

    Lebensztejn, Dariusz M; Bobrus-Chociej, Anna; Kłusek, Monika; Uscinowicz, Miroslawa; Lotowska, Joanna; Sobaniec-Lotowska, Maria; Kaczmarski, Maciej

    2014-01-01

    Montelukast is a selective and competitive cysteinyl leukotriene receptor antagonist (CystLTRA) which is increasingly used for the treatment of allergic asthma. Recently, hepatotoxicity has been reported with this drug in adult patients, but only one letter to the editor has reported a case of probable montelukast-induced hepatotoxicity in a child. We present a case of a 3.5-year-old boy, receiving treatment with montelukast, who developed hepatocellular injury. The exclusion of other causes of increased activity of aminotransferases (viral, metabolic, autoimmune), improvement after dechallenge, the morphological findings and previous reports of comparable cases support the diagnosis of montelukast-induced liver injury in this boy. Physicians should strictly analyse indications for this drug and be aware of potential drug-induced liver disease caused by this agent. Therefore, the periodical assessment of aminotransferases should be recommended during treatment with this leukotriene modifier.

  11. Hepatotoxicity by Drugs: The Most Common Implicated Agents.

    Science.gov (United States)

    Björnsson, Einar S

    2016-02-06

    Idiosyncratic drug-induced liver injury (DILI) is an underreported and underestimated adverse drug reaction. Information on the documented hepatotoxicity of drugs has recently been made available by a website that can be accessed in the public domain: LiverTox (http://livertox.nlm.nih.gov). According to critical analysis of the hepatotoxicity of drugs in LiverTox, 53% of drugs had at least one case report of convincing reports of liver injury. Only 48 drugs had more than 50 case reports of DILI. Amoxicillin-clavulanate is the most commonly implicated agent leading to DILI in the prospective series. In a recent prospective study, liver injury due to amoxicillin-clavulanate was found to occur in approximately one out of 2300 users. Drugs with the highest risk of DILI in this study were azathioprine and infliximab.

  12. Exacerbation of acetaminophen hepatotoxicity by the anthelmentic drug fenbendazole.

    Science.gov (United States)

    Gardner, Carol R; Mishin, Vladimir; Laskin, Jeffrey D; Laskin, Debra L

    2012-02-01

    Fenbendazole is a broad-spectrum anthelmintic drug widely used to prevent or treat nematode infections in laboratory rodent colonies. Potential interactions between fenbendazole and hepatotoxicants such as acetaminophen are unknown, and this was investigated in this study. Mice were fed a control diet or a diet containing fenbendazole (8-12 mg/kg/day) for 7 days prior to treatment with acetaminophen (300 mg/kg) or phosphate buffered saline. In mice fed a control diet, acetaminophen administration resulted in centrilobular hepatic necrosis and increases in serum transaminases, which were evident within 12 h. Acetaminophen-induced hepatotoxicity was markedly increased in mice fed the fenbendazole-containing diet, as measured histologically and by significant increases in serum transaminase levels. Moreover, in mice fed the fenbendazole-containing diet, but not the control diet, 63% mortality was observed within 24 h of acetaminophen administration. Fenbendazole by itself had no effect on liver histology or serum transaminases. To determine if exaggerated hepatotoxicity was due to alterations in acetaminophen metabolism, we analyzed sera for the presence of free acetaminophen and acetaminophen-glucuronide. We found that there were no differences in acetaminophen turnover. We also measured cytochrome P450 (cyp) 2e1, cyp3a, and cyp1a2 activity. Whereas fenbendazole had no effect on the activity of cyp2e1 or cyp3a, cyp1a2 was suppressed. A prolonged suppression of hepatic glutathione (GSH) was also observed in acetaminophen-treated mice fed the fenbendazole-containing diet when compared with the control diet. These data demonstrate that fenbendazole exacerbates the hepatotoxicity of acetaminophen, an effect that is related to persistent GSH depletion. These findings are novel and suggest a potential drug-drug interaction that should be considered in experimental protocols evaluating mechanisms of hepatotoxicity in rodent colonies treated with fenbendazole.

  13. Propylthiouracil Hepatotoxicity Seen with Jaundice and its Treatment by Steroids

    Directory of Open Access Journals (Sweden)

    Oguzhan Aksu

    2014-08-01

    Full Text Available Propylthiouracil (PTU is widely used in the treatment of hyperthyroidism and rarely leads to hepatotoxicity by an unknown mechanism. The hepatic damage caused by propylthiouracil is generally subclinical, but very rarely, it may be associated with severe liver injury and submassive hepatic necrosis. Although discontinuing of the drug result in full recovery in most cases, hyperbilirubinemia and liver damage may increasingly continue in spite of discontinuation of the drug.

  14. [Hepatotoxicity in healthy infants exposed to nevirapine during pregnancy].

    Science.gov (United States)

    Iveli, Pablo; Noguera-Julian, Antoni; Soler-Palacín, Pere; Martín-Nalda, Andrea; Rovira-Girabal, Núria; Fortuny-Guasch, Clàudia; Figueras-Nadal, Concepció

    2016-01-01

    The use of nevirapine in HIV-infected pregnant women is discouraged due to its potential to cause hepatotoxicity. There is limited information available on the toxicity in non-HIV infected newborn exposed to this drug during pregnancy. The aim of the study is to determine the extent of hepatotoxicity in the newborn exposed to nevirapine and HIV during pregnancy. A cross-sectional, observational, multicenter study was conducted on a cohort of healthy infants born to HIV-infected mothers, in whom the first determination of alanine aminotransferase (ALT), before 6weeks of age, was collected. Patients were allocated to 2groups according to exposure to nevirapine during pregnancy. Hepatotoxicity was rated according to the AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). This study included 160newborns from 159pregnancies (88exposed to nevirapine-based regimens and 71 exposed to protease inhibitors-based therapies). No cases of hepatotoxicity were observed according to the DAIDS Table for Grading. Two cases of ALT above normal values (2.8%; 95%CI: 0.3-9.8%) were observed in patients not exposed to nevirapine, and one case (1.1%; 95%CI: 0.0-6.1%) in the group exposed to nevirapine (P=.585). The lack of differences between groups suggests that highly active antiretroviral treatment regimens including nevirapine administered during pregnancy do not involve a higher risk of liver disease compared to other treatment combinations. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  15. Effect of coriander on thioacetamide-induced hepatotoxicity in rats.

    Science.gov (United States)

    Moustafa, Abdel Halim A; Ali, Ehab Mostafa M; Moselhey, Said S; Tousson, Ehab; El-Said, Karim S

    2014-08-01

    Thioacetamide (TAA) is a potent hepatotoxin that causes centrilobulal necrosis and nephrotoxic damage following acute administration. Prolonged exposure to TAA can result in bile duct proliferation and liver cirrhosis histologically similar to that caused due to viral hepatitis infection. Coriander in food increases the antioxidant content, acting as a natural antioxidant and inhibiting undesirable oxidation processes. The present study investigated the antioxidant activity of Coriandrum sativum on TAA-induced hepatotoxicity in the male rats. Phenolic content and antioxidant activity were evaluated in the coriander leaves and seeds. Forty-eight adult male rats were divided into four groups. Group I (control), group II (TAA injected rats), group III (TAA injected rats fed coriander leaves) and group IV (TAA injected rats fed coriander seeds). The results revealed that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were significantly increased in the groups II, III and IV as compared to the normal control. Oxidative stress in the group II was manifested by a significant rise in nitric oxide (NO), thiobarbituric acid reactive substance (TBARS) levels and myloperoxidase (MPO) activities in the liver tissues as compared with the control group. Rats fed with coriander leaves and seeds showed a decrease in the serum ALT, AST and ALP activities and in the liver NO and TBARS levels as compared to the group II. Histopathological study revealed that coriander feeding attenuated TAA-induced hepatotoxicity in the rats. In conclusion, coriander leaves attenuate hepatotoxicity induced by TAA more than that of seeds due to the higher content of phenolic compounds and antioxidants in the leaves of coriander. Liver of rats intoxicated with TAA exhibited advanced CIRRHOSIS: in the form of macronodular and micronodular structure surrounded by fibrous tissue. Treatment with coriander leaves and seeds helps in improving

  16. Food Color Induced Hepatotoxicity in Swiss Albino Rats, Rattus norvegicus

    OpenAIRE

    Saxena, Beenam; Sharma, Shiv

    2015-01-01

    Objective: Certain dietary constituents can induce toxicity and play a critical role in the development of several hepatic disorders. Tartrazine, metanil yellow and sunset yellow are widely used azo dyes in food products, so the present study is aimed to investigate the food color induced hepatotoxicity in Swiss albino rats. Materials and Methods: Swiss albino rats were divided into four groups, each group having six animals. Group I served as control, Group II, Group III and Group IV were ad...

  17. A Novel Resolvin-Based Strategy for Limiting Acetaminophen Hepatotoxicity

    Science.gov (United States)

    Patel, Suraj J; Luther, Jay; Bohr, Stefan; Iracheta-Vellve, Arvin; Li, Matthew; King, Kevin R; Chung, Raymond T; Yarmush, Martin L

    2016-01-01

    Objectives: Acetaminophen (APAP)-induced hepatotoxicity is a major cause of morbidity and mortality. The current pharmacologic treatment for APAP hepatotoxicity, N-acetyl cysteine (NAC), targets the initial metabolite-driven injury but does not directly affect the host inflammatory response. Because of this, NAC is less effective if given at later stages in the disease course. Resolvins, a novel group of lipid mediators shown to attenuate host inflammation, may be a therapeutic intervention for APAP hepatotoxicity. Methods: The temporal patterns of liver injury and neutrophil activation were investigated in a murine model of APAP hepatotoxicity. In addition, the effect of neutrophil depletion and resolvin administration on the severity of liver injury induced by APAP was studied. In vitro studies to investigate the mechanism of resolvin effect on hepatocyte injury and neutrophil adhesion were performed. Results: We demonstrate that hepatic neutrophil activation occurs secondary to the initial liver injury induced directly by APAP. We also show that neutrophil depletion attenuates APAP-induced liver injury, and administration of resolvins hours after APAP challenge not only attenuates liver injury, but also extends the therapeutic window eightfold compared to NAC. Mechanistic in vitro analysis highlights resolvins' ability to inhibit neutrophil attachment to endothelial cells in the presence of the reactive metabolite of APAP. Conclusions: This study highlights the ability of resolvins to protect against APAP-induced liver injury and extend the therapeutic window compared to NAC. Although the mechanism for resolvin-mediated hepatoprotection is likely multifactorial, inhibition of neutrophil infiltration and activation appears to play an important role. PMID:26986653

  18. Parametrizable cameras for 3D computational steering

    NARCIS (Netherlands)

    Mulder, J.D.; Wijk, J.J. van

    1997-01-01

    We present a method for the definition of multiple views in 3D interfaces for computational steering. The method uses the concept of a point-based parametrizable camera object. This concept enables a user to create and configure multiple views on his custom 3D interface in an intuitive graphical man

  19. Steered wheel for the support and/or steering of a vehicle, particularly hovercraft

    Energy Technology Data Exchange (ETDEWEB)

    Duell, H.J.; Kirchner, G.

    1977-04-07

    The invention concerns a steered wheel for the support or steering of a hovercraft, whose wheel suspension is provided with an eccentric journal for automatic setting in the direction of travel. So that the vehicle will not leave its track during changes of direction when the wheel is turned around the eccentric axis, according to the invention the wheel is supported on movable bearings at the journal in the direction of the driving axle.

  20. Methotrexate Hepatotoxicity; the Danger Not to Be Ignored

    Directory of Open Access Journals (Sweden)

    M Baghbanian

    2013-06-01

    Full Text Available Introduction: Methotrexate is used increasingly for treatment of some diseases such as rheumatoid arthritis, psoriasis and Crohn. Bone marrow suppression, mucocutaneous lesions, pneumonitis, and hepatotoxicity are major side effects of this drug. Since methotrexate toxicity is dose dependent and is usually administered with low dose via a weekly regimen, its side effects are not commonly seen. But due to long term prescription of this drug over the recent years especially for rheumatoid arthritis, growing cases of methotrexate hepatotoxicity are referred to Gastroenterologist. High dose of drug, high age, alcohol consumption, renal failure and preexisting liver disease are main risk factors for this toxicity. In this study, in addition to presenting two cases with cirrhosis and two cases with hepatitis linked to methotrexate, the clinical aspects on this field are discussed. Conclusions: Methotrexate hepatotoxicity is not a theoretical issue that can be ignored because it can lead to cirrhosis and liver failure. We can prevent the onset of this growing side effect with appropriate patient selection and investigating the patients’ liver function before and during Methotrexate therapy. Periodic testing the liver enzymes is used for monitoring the liver condition, but because interpretation of these tests is sometimes difficult, liver biopsy is needed in particular cases.

  1. Antioxidant modulation of nevirapine induced hepatotoxicity in rats.

    Science.gov (United States)

    Awodele, Olufunsho; Popoola, Temidayo; Rotimi, Kunle; Ikumawoyi, Victor; Okunowo, Wahab

    2015-03-01

    HIV/AIDS related mortality has been dramatically reduced by the advent of antiretroviral therapy (ART). However, ART presents with associated adverse effects. One of such adverse effects is hepatotoxicity observed with nevirapine (NVP) containing ART. Since previous studies showed that NVP hepatotoxicity may be due to oxidative stress via generation of oxidative radicals, this study sought to evaluate the protective effects of antioxidants in alleviating NVP induced hepatotoxicity. Rats were divided into 6 groups with 8 animals per group and received doses of the antioxidants jobelyn (10.7 mg/kg/day), vitamin C (8 mg/kg/day), vitamin E (5 mg/kg/day) and/or NVP (6 mg/kg/day) for 60 days. The animals were sacrificed on day 61 by cervical dislocation, blood samples were collected for biochemical and hematological examination. The liver of the sacrificed animals was weighed and subjected to histopathological examination. There was a statistically significant (prats. A significantly (prats showed no visible pathology across the groups. Observations from this study suggest a potentially positive modulatory effect of antioxidants and may be indicative for the inclusion of antioxidants in nevirapine containing ART.

  2. Acetaminophen-induced hepatotoxicity: Preventive effect of trans anethole.

    Science.gov (United States)

    da Rocha, Bruno Ambrósio; Ritter, Alessandra M Versuti; Ames, Franciele Queiroz; Gonçalves, Odinei Hess; Leimann, Fernanda Vitória; Bracht, Lívia; Natali, Maria Raquel Marçal; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Ap

    2017-02-01

    The hepatotoxicity induced by APAP is caused by the excessive production of N-acetyl-para-benzoquinone imine (NAPQI), which, when reacting with hepatic proteins proved to cause irreversible lesions. Associated with this process, an intense inflammatory process is also evidenced, characterized by the increased cell influx and production/release of inflammatory mediators. Trans anethole, an aromatic compounds has been showed anti-inflammatory efficacy by inhibit the cellular recruitment and synthesis/releases of many proinflammatory mediators such as prostaglandin (PGE2), cytokines (TNF, IL-1) and nitrico oxide (NO). The aim of this study is to investigate the effect of trans anethole on some inflammatory parameters that are involved in hepatotoxicity induced by high doses of acetaminophen. Our results demonstrate that treatment with AN at doses 125 and 250mg/kg once a day for seven days prevented the changes caused by the APAP overdose, showing less intensity in the histological changes (necrosis, size of hepatocyte area and inflammatory infiltration), and corroborating the findings of serum activities of transaminases and phosphatases and the activity of the enzyme myeloperoxidase. In addition, the treatment prevented the up-regulation of proinflammatory mediators such as NO, TNF, IL-1α, MIP-1α and MCP-1 and induced the up-regulation of anti-inflammatory cytokines (IL-4 and IL-10). Thus, our results demonstrate a possible protective effect of trans anethole on the hepatotoxicity induced by APAP. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Hepatotoxicity of NONI juice: Report of two cases

    Institute of Scientific and Technical Information of China (English)

    Vanessa Stadlbauer; Peter Fickert; Carolin Lackner; Jutta Schmerlaib; Peter Krisper; Michael Trauner; Rudolf E Stauber

    2005-01-01

    NONI juice (Morinda citrifolia) is an increasingly popular wellness drink claimed to be beneficial for many illnesses.No overt toxicity has been reported to date. We present two cases of novel hepatotoxicity of NONI juice. Causality of liver injury by NONI juice was asses-sed. Routine laboratory tests and transjugular or percutaneous liver biopsy were performed. The first patient underwent successful liver transplantation while the second patient recovered spontaneously after cessation of NONI juice.A 29-year-old man with previous toxic hepatitis associated with small doses of paracetamol developed sub-acute hepatic failure following consumption of 1.5 L NONI juice over 3 wk necessitating urgent liver transplantation. A 62-year-old woman without evidence of previous liver disease developed an episode of self-limited acutehepatitis following consumption of 2 L NONI juice for over 3 mo. The most likely hepatotoxic components of Morinda citrifolia were anthraquinones. Physicians should be aware of potential hepatotoxicity of NONI juice.

  4. Hepatotoxic potential of asarones: In vitro evaluation of hepatotoxicity and quantitative determination in herbal products

    Directory of Open Access Journals (Sweden)

    Dhavalkumar Narendrabha Patel

    2015-02-01

    Full Text Available α and β asarones are natural constituents of some aromatic plants, especially species of the genus Acorus. In addition to beneficial properties of asarones, genotoxicity and carcinogenicity are also reported. Due to potential toxic effects of β-asarone, a limit of exposure from herbal products of approximately 2 μg/kg body weight/day has been set temporarily until a full benefit/risk assessment has been carried out by the European Medicines Agency. Therefore, it is important to monitor levels of β-asarone in herbal products. In this study, we developed a simple, rapid and validated GC-MS method for quantitative determination of asarones and applied it in 20 pediatric herbal products after detecting high concentrations of β-asarone in a product suspected to be implicated in hepatotoxicity in a 3 month old infant. Furthermore, targeted toxicological effects were further investigated in human hepatocytes (THLE-2 cells by employing various in vitro assays, with the goal of elucidating possible mechanisms for the observed toxicity. Results showed that some of the products contained as much as 4 to 25 times greater amounts of β-asarone than the recommended levels. In 4 of 10 samples found to contain asarones, the presence of asarones could not be linked to the labeled ingredients, possibly due to poor quality control. Cell-based investigations in THLE2 cells confirmed the cytotoxicity of -asarone (IC50 = 40.0 ± 2.0 µg/mL which was associated with significant lipid peroxidation and glutathione depletion. This observed cytotoxicity effect is likely due to induction of oxidative stress by asarones. Overall, the results of this study ascertained the usability of this GC-MS method for the quantitative determination of asarones from herbal products, and shed light on the importance of controlling the concentration of potentially toxic asarones in herbal products to safeguard consumer safety. Further investigations of the toxicity of asarones are

  5. Einstein-Podolsky-Rosen steering inequalities from entropic uncertainty relations

    Science.gov (United States)

    Schneeloch, James; Broadbent, Curtis J.; Walborn, Stephen P.; Cavalcanti, Eric G.; Howell, John C.

    2013-06-01

    We use entropic uncertainty relations to formulate inequalities that witness Einstein-Podolsky-Rosen (EPR)-steering correlations in diverse quantum systems. We then use these inequalities to formulate symmetric EPR-steering inequalities using the mutual information. We explore the differing natures of the correlations captured by one-way and symmetric steering inequalities and examine the possibility of exclusive one-way steerability in two-qubit states. Furthermore, we show that steering inequalities can be extended to generalized positive operator-valued measures, and we also derive hybrid steering inequalities between alternate degrees of freedom.

  6. How relativistic motion affects Einstein-Podolsky-Rosen steering

    Science.gov (United States)

    Sun, Wen-Yang; Wang, Dong; Ye, Liu

    2017-09-01

    In this letter, the dynamic behavior of Einstein-Podolsky-Rosen (EPR) steering and the redistribution of EPR steering under a relativistic framework are investigated. Specifically, we explore the scenario that particle A held by Alice is in a flat space-time and another particle B held by Bob entangled with A is in a non-inertial framework. The results show that EPR steering from Alice to Bob is dramatically destroyed by the Unruh effect caused by the acceleration of Bob. Besides, EPR steering possess asymmetry, and EPR steering asymmetry increases with growing intensity of the Unruh effect, implying that the Unruh effect can bring about EPR steering asymmetry. Furthermore, the reduced physically accessible EPR steering from Alice to Bob is distributed to the physically inaccessible EPR steering (from Alice to anti-Bob or from Bob to anti-Bob). Notably, unlike entanglement and quantum discord, only one of the EPR steering from Alice to anti-Bob and Bob to anti-Bob experiences a sudden birth with increase in the acceleration parameter, which means that they cannot simultaneously survive. That is, the monogamous relationship of EPR steering is still tenable in such a scenario. Consequently, we believe that EPR steering could also serve as an important information resource within long-distance quantum secure communication under the relativistic framework.

  7. Improving Einstein–Podolsky–Rosen steering inequalities with state information

    Energy Technology Data Exchange (ETDEWEB)

    Schneeloch, James [Department of Physics and Astronomy, University of Rochester, Rochester, NY 14627 (United States); Broadbent, Curtis J. [Department of Physics and Astronomy, University of Rochester, Rochester, NY 14627 (United States); Rochester Theory Center, University of Rochester, Rochester, NY 14627 (United States); Howell, John C. [Department of Physics and Astronomy, University of Rochester, Rochester, NY 14627 (United States)

    2014-02-01

    We discuss the relationship between entropic Einstein–Podolsky–Rosen (EPR)-steering inequalities and their underlying uncertainty relations along with the hypothesis that improved uncertainty relations lead to tighter EPR-steering inequalities. In particular, we discuss how using information about the state of a quantum system affects one's ability to witness EPR-steering. As an example, we consider the recent improvement to the entropic uncertainty relation between pairs of discrete observables (Berta et al., 2010 [10]). By considering the assumptions that enter into the development of a steering inequality, we derive correct steering inequalities from these improved uncertainty relations and find that they are identical to ones already developed (Schneeloch et al., 2013 [9]). In addition, we consider how one can use state information to improve our ability to witness EPR-steering, and develop a new continuous variable symmetric EPR-steering inequality as a result.

  8. Active disturbance rejection control in steering by wire haptic systems.

    Science.gov (United States)

    Rodriguez-Angeles, A; Garcia-Antonio, J A

    2014-07-01

    This paper introduces a steering by wired haptic system based on disturbance rejection control techniques. High gain Generalized Proportional Integral (GPI) observers are considered for the estimation of tire and steering wheel dynamic disturbances. These disturbances are on line canceled to ensure tracking between the commanded steering wheel angle and the tire orientation angle. The estimated disturbances at the steering rack are feedback to the steering wheel to provide a haptic interface with the driver. The overall system behaves as a bilateral master-slave system. Very few sensors and minimum knowledge of the dynamic model are required. Experimental results are presented on a prototype platform that consists on: (1) half of the steering rack of a beetle VW vehicle, (2) a steering wheel.

  9. Improving Einstein-Podolsky-Rosen steering inequalities with state information

    Science.gov (United States)

    Schneeloch, James; Broadbent, Curtis J.; Howell, John C.

    2014-02-01

    We discuss the relationship between entropic Einstein-Podolsky-Rosen (EPR)-steering inequalities and their underlying uncertainty relations along with the hypothesis that improved uncertainty relations lead to tighter EPR-steering inequalities. In particular, we discuss how using information about the state of a quantum system affects one's ability to witness EPR-steering. As an example, we consider the recent improvement to the entropic uncertainty relation between pairs of discrete observables (Berta et al., 2010 [10]). By considering the assumptions that enter into the development of a steering inequality, we derive correct steering inequalities from these improved uncertainty relations and find that they are identical to ones already developed (Schneeloch et al., 2013 [9]). In addition, we consider how one can use state information to improve our ability to witness EPR-steering, and develop a new continuous variable symmetric EPR-steering inequality as a result.

  10. Hepatotoxicity of antiretrovirals in patients with human immunodeficiency virus and viral hepatitis coinfections

    Directory of Open Access Journals (Sweden)

    P Parenti

    2012-11-01

    Full Text Available Background: Antiretroviral drugs used to treat HIV may cause hepatotoxicity. The high prevalence of persons with chronic hepatitis B or C coinfected, raised aminotransferases have many causes and neither specific markers is a indicator of liver injury, difficulties in interpreting the hepatotoxicity. Objective: We evaluated hepatotoxicity in HIV/HCV- and/or HBV-coinfected patients, risk factors and severity. Methods: Prospective study of HIV-1 patients with start HAART in Hospital Provincial del Centenario from Rosario, Argentina. Patients were classified into two groups, HCV and/or HBV coinfected vs. no coinfected. The major endpoint was hepatotoxicity defined as Benichou's Score within the first 6 months. This score is among the few validated, but little used in clinical practice. Secondary endpoints were risk factors and severity of hepatotoxicity. Results: 140 patients were included, 39% coinfected and 61% no coinfected. Females were similar in both groups; 21% and 27% respectively. The hepatotoxicity within the first 6 month was 44.3%, 75% in coinfected patients and 25% in no-coinfected. RR 3.97 (95% confidence interval 2.34–6.75, p<0.0001. The hepatotoxicity was associated with the use of illicit drugs and alcohol, symptoms, high level aminotransferases previous to HAART and NNRTI+PI. 3% of hepatotoxicity was severe. Conclusions: 44% of HIV patients experienced hepatotoxicity, 75% in coinfected vs 25% in no coinfected. The relative risk of hepatoxocity was almost 4 times higher among in chronic hepatitis-coinfected patients, compared with those with HIV non-coinfected. In multivariate analysis, the risk factors were illicit drugs, alcohol, symptoms, high level aminotransferases and NRTI+PI. Only 3% of hepatotoxicity was severe. The Benichou's Score is better than level of aminotransferase for evaluated hepatotoxicity, so it would be recommended for use in clinical practice.

  11. Improvement of Steering Feel of Electric Power Steering System with Variable Gear Transmission System Using Decoupling Control

    Science.gov (United States)

    Morita, Yoshifumi; Yokoi, Akitoshi; Iwasaki, Makoto; Ukai, Hiroyuki; Matsui, Nobuyuki; Ito, Norihisa; Uryu, Nobuhiko; Mukai, Yasuhiko

    In this paper a new control method of Electric Power Steering (EPS) system with Variable Gear Transmission System (VGTS) is proposed. The control purpose is to achieve the desired steering gear ratio and the desired power assist with good steering feel. The basic idea of controller design is to apply decoupling control to this system and to separately design controllers for two decoupled systems. The angle control system and the torque control system are designed for the decoupled systems. In the angle control system the PID control is used for the desired gear ratio. In the torque control system the PID control is used for the desired assist torque designed so as to achieve good steering feel. In order to evaluate steering feel the Lissajous curve between the steering torque and steering angle is used. The effectiveness of the proposed controller is verified experimentally.

  12. Research on Torque Ratio Based on the Steering Wheel Torque Characteristic for Steer-by-Wire System

    Directory of Open Access Journals (Sweden)

    Yandong Han

    2014-01-01

    Full Text Available Steer-by-wire system can improve the performance of vehicle handling stability. Removing the mechanical linkages between the front wheels and the steering wheel leads to a key technique of force feedback for steer-by-wire system. In view of the characteristic of variable torque transmission ratio for steer-by-wire system, this paper proposes a method for designing torque ratio based on the steering wheel torque characteristic for steer-by-wire system. It converts the torque ratio design into equivalent assist torque design by analyzing their relationship. It achieves the torque ratio design at different conditions based on the negative equivalent assist torque characteristic curve. Simulations and vehicle experiments are conducted by the proposed method, and the results show that the design goal has been achieved and the steering wheel torque characteristic obtained is very similar to that of the reference car.

  13. Hepatotoxicity during Treatment for Tuberculosis in People Living with HIV/AIDS

    Science.gov (United States)

    Araújo-Mariz, Carolline; Lopes, Edmundo Pessoa; Acioli-Santos, Bartolomeu; Maruza, Magda; Montarroyos, Ulisses Ramos; Ximenes, Ricardo Arraes de Alencar; Lacerda, Heloísa Ramos; Miranda-Filho, Demócrito de Barros; de Albuquerque, Maria de Fátima P. Militão

    2016-01-01

    Hepatotoxicity is frequently reported as an adverse reaction during the treatment of tuberculosis. The aim of this study was to determine the incidence of hepatotoxicity and to identify predictive factors for developing hepatotoxicity after people living with HIV/AIDS (PLWHA) start treatment for tuberculosis. This was a prospective cohort study with PLWHA who were monitored during the first 60 days of tuberculosis treatment in Pernambuco, Brazil. Hepatotoxicity was considered increased levels of aminotransferase, namely those that rose to three times higher than the level before initiating tuberculosis treatment, these levels being associated with symptoms of hepatitis. We conducted a multivariate logistic regression analysis and the magnitude of the associations was expressed by the odds ratio with a confidence interval of 95%. Hepatotoxicity was observed in 53 (30.6%) of the 173 patients who started tuberculosis treatment. The final multivariate logistic regression model demonstrated that the use of fluconazole, malnutrition and the subject being classified as a phenotypically slow acetylator increased the risk of hepatotoxicity significantly. The incidence of hepatotoxicity during treatment for tuberculosis in PLWHA was high. Those classified as phenotypically slow acetylators and as malnourished should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis. The use of fluconazole should be avoided during tuberculosis treatment in PLWHA. PMID:27332812

  14. Hepatotoxicity during Treatment for Tuberculosis in People Living with HIV/AIDS.

    Science.gov (United States)

    Araújo-Mariz, Carolline; Lopes, Edmundo Pessoa; Acioli-Santos, Bartolomeu; Maruza, Magda; Montarroyos, Ulisses Ramos; Ximenes, Ricardo Arraes de Alencar; Lacerda, Heloísa Ramos; Miranda-Filho, Demócrito de Barros; Albuquerque, Maria de Fátima P Militão de

    2016-01-01

    Hepatotoxicity is frequently reported as an adverse reaction during the treatment of tuberculosis. The aim of this study was to determine the incidence of hepatotoxicity and to identify predictive factors for developing hepatotoxicity after people living with HIV/AIDS (PLWHA) start treatment for tuberculosis. This was a prospective cohort study with PLWHA who were monitored during the first 60 days of tuberculosis treatment in Pernambuco, Brazil. Hepatotoxicity was considered increased levels of aminotransferase, namely those that rose to three times higher than the level before initiating tuberculosis treatment, these levels being associated with symptoms of hepatitis. We conducted a multivariate logistic regression analysis and the magnitude of the associations was expressed by the odds ratio with a confidence interval of 95%. Hepatotoxicity was observed in 53 (30.6%) of the 173 patients who started tuberculosis treatment. The final multivariate logistic regression model demonstrated that the use of fluconazole, malnutrition and the subject being classified as a phenotypically slow acetylator increased the risk of hepatotoxicity significantly. The incidence of hepatotoxicity during treatment for tuberculosis in PLWHA was high. Those classified as phenotypically slow acetylators and as malnourished should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis. The use of fluconazole should be avoided during tuberculosis treatment in PLWHA.

  15. Infliximab exerts no direct hepatotoxic effect on HepG2 cells in vitro.

    NARCIS (Netherlands)

    Vries, H.S. de; Heij, T. de; Schaap-Roelofs, H.M.J.; Morsche, R.H.M. te; Peters, W.H.M.; Jong, D.J. de

    2012-01-01

    BACKGROUND: Infliximab-induced hepatotoxicity is reported in several case studies involving patients with inflammatory bowel disease (IBD) and a direct hepatotoxic effect has been proposed. OBJECTIVE: The aim of this study was to determine the direct in vitro toxicity of infliximab. As a proof of

  16. Croton zehntneri Essential oil prevents acetaminophen-induced acute hepatotoxicity in mice

    OpenAIRE

    Maria Goretti R. Queiroz; José Henrique L. Cardoso; Tomé, Adriana R; Roberto C. P. Lima Jr.; Jamile M. Ferreira; Daniel F. Sousa; Felipe C. Lima; Campos, Adriana R.

    2008-01-01

    Hepatoprotective activity of Croton zehntneri Pax & Hoffman (Euphorbiaceae) leaf essential oil (EOCz) was evaluated against single dose of acetaminophen-induced (500 mg/kg, p.o.) acute hepatotoxicity in mice. EOCz significantly protected the hepatotoxicity as evident from the activities of serum glutamate pyruvate transaminase (GPT), serum glutamate oxaloacetate transaminase (GOT) activities, that were significantly (p

  17. Conditional steering under the von Neumann scenario

    Science.gov (United States)

    Mukherjee, Kaushiki; Paul, Biswajit; Karmakar, Sumana; Sarkar, Debasis; Mukherjee, Amit; Bhattacharya, Some Sankar; Roy, Arup

    2017-08-01

    In Phys. Lett. A 166, 293 (1992), 10.1016/0375-9601(92)90711-T, Popescu and Rohrlich characterized nonlocality of pure n -partite entangled systems by studying bipartite violation of local realism when n -2 number of parties perform projective measurements on their particles. A pertinent question in this scenario is whether similar characterization is possible for n -partite mixed entangled states also. In the present work we have followed an analogous approach so as to explore whether given a tripartite mixed entangled state the conditional bipartite states obtained by performing projective measurement on the third party demonstrate a weaker form of nonlocality, quantum steering. We also compare this phenomenon of conditional steering with existing notions of tripartite correlations.

  18. SPS Beam Steering for LHC Extraction

    Energy Technology Data Exchange (ETDEWEB)

    Gianfelice-Wendt, Eliana [Fermilab; Bartosik, Hannes [CERN; Cornelis, Karel [CERN; Norderhaug Drøsdal, Lene [CERN; Goddard, Brennan [CERN; Kain, Verena [CERN; Meddahi, Malika [CERN; Papaphilippou, Yannis [CERN; Wenninger, Jorg [CERN

    2014-07-01

    The CERN Super Proton Synchrotron accelerates beams for the Large Hadron Collider to 450 GeV. In addition it produces beams for fixed target facilities which adds complexity to the SPS operation. During the run 2012-2013 drifts of the extracted beam trajectories have been observed and lengthy optimizations in the transfer lines were performed to reduce particle losses in the LHC. The observed trajectory drifts are consistent with the measured SPS orbit drifts at extraction. While extensive studies are going on to understand, and possibly suppress, the source of such SPS orbit drifts the feasibility of an automatic beam steering towards a “golden” orbit at the extraction septa, by means of the interlocked correctors, is also being investigated. The challenges and constraints related to the implementation of such a correction in the SPS are described. Simulation results are presented and a possible operational steering strategy is proposed.

  19. SPS Beam Steering for LHC Extraction

    CERN Document Server

    Gianfelice Wendt, E; Cornelis, K; Norderhaug Drosdal, L; Goddard, B; Kain, V; Meddahi, M; Papaphilippou, Y; Wenninger, J

    2014-01-01

    Beside producing beams for fixed target operation, the CERN Super Proton Synchrotron (SPS) accelerates beams for injection into the Large Hadron Collider (LHC). During the 2012-2013 run drifts of the extracted beam horizontal trajectories have been observed and lengthy optimizations in the transfer lines were performed to reduce particle losses. The observed trajectory drifts are consistent with the measured SPS orbit drifts at extraction. The feasibility of an automatic beam steering towards a “golden” orbit at the extraction septa, has been therefore investigated. The challenges and constraints related to the implementation of such a correction in the SPS are described. Simulation results are presented and a possible operational steering strategy is proposed. As the observed drift is mainly horizontal, the horizontal plane only will be considered.

  20. ACTIVE FRONT STEERING DURING BRAKING PROCESS

    Institute of Scientific and Technical Information of China (English)

    CHEN Deling; CHEN Li; YIN Chengliang; ZHANG Yong

    2008-01-01

    An active front steering (AFS) intervention control during braking for vehicle stability is presented. Based on the investigation of AFS mechanism, a simplified model of steering system is established and integrated with vehicle model. Then the AFS control on vehicle handling dynamics during braking is designed. Due to the difficulties associated with the sideslip angle measurement of vehicle, a state observer is designed to provide real time estimation. Thereafter, the controller with the feedback of both sideslip and yaw angle is implemented. To evaluate the system control, the proposed AFS controlled vehicle has been tested in the Hardware-in-the-loop-simulation (HILS) system and compared with that of conventional vehicle. Results show that AFS can improve vehicle lateral stability effectively without reducing the braking performance.

  1. Boundaries can steer active Janus spheres

    Science.gov (United States)

    Das, Sambeeta; Garg, Astha; Campbell, Andrew I.; Howse, Jonathan; Sen, Ayusman; Velegol, Darrell; Golestanian, Ramin; Ebbens, Stephen J.

    2015-12-01

    The advent of autonomous self-propulsion has instigated research towards making colloidal machines that can deliver mechanical work in the form of transport, and other functions such as sensing and cleaning. While much progress has been made in the last 10 years on various mechanisms to generate self-propulsion, the ability to steer self-propelled colloidal devices has so far been much more limited. A critical barrier in increasing the impact of such motors is in directing their motion against the Brownian rotation, which randomizes particle orientations. In this context, here we report directed motion of a specific class of catalytic motors when moving in close proximity to solid surfaces. This is achieved through active quenching of their Brownian rotation by constraining it in a rotational well, caused not by equilibrium, but by hydrodynamic effects. We demonstrate how combining these geometric constraints can be utilized to steer these active colloids along arbitrary trajectories.

  2. Indexing system for optical beam steering

    Science.gov (United States)

    Sullivan, Mark T.; Cannon, David M.; Debra, Daniel B.; Young, Jeffrey A.; Mansfield, Joseph A.; Carmichael, Roger E.; Lissol, Peter S.; Pryor, G. M.; Miklosy, Les G.; Lee, Jeffrey H.

    1990-01-01

    This paper describes the design and testing of an indexing system for optical-beam steering. The cryogenic beam-steering mechanism is a 360-degree rotation device capable of discrete, high-precision alignment positions. It uses low-precision components for its rough alignment and kinematic design to meet its stringent repeatability and stability requirements (of about 5 arcsec). The principal advantages of this design include a decoupling of the low-precision, large angular motion from the high-precision alignment, and a power-off alignment position that potentially extends the life or hold time of cryogenic systems. An alternate design, which takes advantage of these attributes while reducing overall motion, is also presented. Preliminary test results show the kinematic mount capable of sub-arc second repeatability.

  3. Self-testing through EPR-steering

    Science.gov (United States)

    Šupić, Ivan; Hoban, Matty J.

    2016-07-01

    The verification of quantum devices is an important aspect of quantum information, especially with the emergence of more advanced experimental implementations of quantum computation and secure communication. Within this, the theory of device-independent robust self-testing via Bell tests has reached a level of maturity now that many quantum states and measurements can be verified without direct access to the quantum systems: interaction with the devices is solely classical. However, the requirements for this robust level of verification are daunting and require high levels of experimental accuracy. In this paper we discuss the possibility of self-testing where we only have direct access to one part of the quantum device. This motivates the study of self-testing via EPR-steering, an intermediate form of entanglement verification between full state tomography and Bell tests. Quantum non-locality implies EPR-steering so results in the former can apply in the latter, but we ask what advantages may be gleaned from the latter over the former given that one can do partial state tomography? We show that in the case of self-testing a maximally entangled two-qubit state, or ebit, EPR-steering allows for simpler analysis and better error tolerance than in the case of full device-independence. On the other hand, this improvement is only a constant improvement and (up to constants) is the best one can hope for. Finally, we indicate that the main advantage in self-testing based on EPR-steering could be in the case of self-testing multi-partite quantum states and measurements. For example, it may be easier to establish a tensor product structure for a particular party’s Hilbert space even if we do not have access to their part of the global quantum system.

  4. TRANSFERRING OF MOVEMENT FOR STEERING EQUIPMENT

    OpenAIRE

    Outhier, Maxime; Rydström, Vilhelm; Sanz, Imanol

    2001-01-01

    This Examination Thesis was done at the Blekinge Institute of Technology of Karlskrona. The work is a part of the education to Bachelor of Science in product development. The task consists of changing the steering wheel transmission of the DYNAPAC CA soil compactor machine made by Svedala Compaction Equipment AB. During the work we have followed the Fredy Olsson product development method. The work is divided in two parts: The Concept phase and The Primary Construction phase. In the Concept p...

  5. Design and Analysis of a Fast Steering Mirror for Precision Laser Beams Steering

    Directory of Open Access Journals (Sweden)

    Qingkun ZHOU

    2009-03-01

    Full Text Available Precision laser beam steering is critical in numerous applications. Also, precise pointing of laser beams is essential in challenging environments. The optical signal may be deflected, drift and wander due to environmental influences. The core problem of steering performances is to deal with the jitter disturbance. Based on the analysis of the beam angle steering system, some important factors to design the structure of a Fast Steering Mirror (FSM and the layout of laser optics steering system are presented. Flexure hinges with compliant mechanisms are used to build the FSM structure. A 4-quadrant detector is used as the sensor for the incoming light. A design of the developed control loop and concepts of the FSM model are discussed. A comparison between the measured gain response and the simulation model of the FSM reveals similarity between the theoretical simulation model and the real system, and offers a way to improve the model to better resemble the real system. A laser beam jitter control test bed is also introduced to improve jitter control techniques.

  6. On the Feasibility of Dynamic Power Steering

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Kevin J.; Kerbyson, Darren J.; Anger, Eric A.

    2014-11-16

    While high performance has always been the primary constraint behind large-scale system design, future systems will be built with increasing energy efficiency in mind. Mechanisms such as fine-grained power scaling and gating will provide tools to system-software and application developers to ensure the most efficient use of tightly constrained power budgets. Such approaches to-date have been focused on node level optimizations to impact overall system energy efficiency. In this work we introduce Dynamic Power Steering, in which power can be dynamically routed across a system to resources where it will be of most benefit and away from other resources to maintain a near-constant overall power budget. This, a higher level algorithmic approach to improving energy efficiency, considers the whole extent of a system being used by an application. It can be used for applications in which there is load imbalance that varies over its execution. Using two classes of applications, namely those that contain a wave front type processing, and a particle-in-cell, we quantify the benefit of Dynamic Power Steering for a variety of workload characteristics and derive some insight into the ways in which workload behavior affect Power Steering applicability.

  7. Contaminant hepatotoxins as culprits for kava hepatotoxicity--fact or fiction?

    Science.gov (United States)

    Teschke, Rolf; Sarris, Jerome; Lebot, Vincent

    2013-03-01

    The culprit of kava hepatotoxicity will continue to remain a mystery in humans, if the underlying reaction is of idiosyncratic, unpredictable, and dose-independent nature due potentially to some metabolic aberration in a few individuals emerging from kava use. In addition, kava hepatotoxicity is presently not reproducible experimentally in preclinical models, as demonstrated by studies showing whole kava extracts are not hepatotoxic. This led us to propose our 'working hypothesis' that contaminant hepatotoxins including moulds might have caused rare kava hepatotoxicity in humans. Further studies are now warranted to proof or disproof our working hypothesis, because kava hepatotoxicity possibly based on contaminant hepatotoxins could be a preventable disease. In the meantime, however, for minimizing toxicity risk in kava users, a pragmatic approach should focus on the medicinal use of an aqueous extract derived from peeled rhizomes and roots of a non-mouldy noble kava cultivar, limited to maximum 250-mg kavalactones daily for acute or intermittent use.

  8. Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity.

    Science.gov (United States)

    Vassallo, Jeffrey D; Hicks, Sarah M; Daston, George P; Lehman-McKeeman, Lois D

    2004-08-01

    Hepatotoxicity of coumarin is attributed to metabolic activation to an epoxide intermediate, coumarin 3,4-epoxide (CE). However, whereas rats are most susceptible to coumarin-induced hepatotoxicity, formation of CE is greatest in mouse liver microsomes, a species showing little evidence of hepatotoxicity. Therefore, the present work was designed to test the hypothesis that detoxification of CE is a major determinant of coumarin hepatotoxicity. CE can either rearrange spontaneously to o-hydroxyphenylacetaldehyde (o-HPA) or be conjugated with gluatathione (GSH). o-HPA is hepatotoxic and is further detoxified by oxidation to o-hydroxyphenylacetic acid (o-HPAA). In vitro experiments were conducted using mouse liver microsomes to generate a constant amount of CE, and cytosols from F344 rats, B6C3F1 mice, and human liver were used to characterize CE detoxification. All metabolites were quantified by HPLC methods with UV detection. In rats and mice, GSH conjugation occurred non-enzymatically and through glutathione-S-transferases (GSTs), and the kinetics of GSH conjugation were similar in rats and mice. In rat liver cytosol, oxidation of o-HPA to o-HPAA was characterized with a high affinity K(m) of approximately 12 microM, and a V(max) of approximately 1.5 nmol/min/mg protein. In contrast, the K(m) and V(max) for o-HPA oxidation in mouse liver cytosol were approximately 1.7 microM and 5 nmol/min/mg protein, respectively, yielding a total intrinsic clearance through oxidation to o-HPAA that was 20 times higher in mouse than in rats. Human cytosols (two separate pools) detoxified CE through o-HPA oxidation with an apparent K(m) of 0.84 microM and a V(max) of 5.7 nmol/min/mg protein, for a net intrinsic clearance that was more than 50 times higher than the rat. All species also reduced o-HPA to o-hydroxyphenylethanol (o-HPE), but this was only a major reaction in rats. In the presence of a metabolic reaction replete with all necessary cofactors, GSH conjugation accounted

  9. Green Tea Extract-induced Acute Hepatotoxicity in Rats.

    Science.gov (United States)

    Emoto, Yuko; Yoshizawa, Katsuhiko; Kinoshita, Yuichi; Yuki, Michiko; Yuri, Takashi; Yoshikawa, Yutaka; Sayama, Kazutoshi; Tsubura, Airo

    2014-10-01

    Although green tea is considered to be a healthy beverage, hepatotoxicity associated with the consumption of green tea extract has been reported. In the present study, we characterized the hepatotoxicity of green tea extract in rats and explored the responsible mechanism. Six-week-old IGS rats received a single intraperitoneal (ip) injection of 200 mg/kg green tea extract (THEA-FLAN 90S). At 8, 24, 48 and 72 hrs and 1 and 3 months after exposure, liver damage was assessed by using blood-chemistry, histopathology, and immunohistochemistry to detect cell death (TUNEL and caspase-3) and proliferative activity (PCNA). Analyses of malondialdehyde (MDA) in serum and the liver and of MDA and thymidine glycol (TG) by immunohistochemistry, as oxidative stress markers, were performed. Placental glutathione S-transferase (GST-P), which is a marker of hepatocarcinogenesis, was also immunohistochemically stained. To examine toxicity at older ages, 200 mg/kg green tea extract was administered to 18-wk-old female rats. In 6-wk-old rats, 12% of males and 50% of females died within 72 hrs. In 18-wk-old rats, 88% died within 72 hrs. The serum levels of aspartate aminotransferase, alanine aminotransferase and/or total bilirubin increased in both males and females. Single-cell necrosis with positive signs of TUNEL and caspase-3 was seen in perilobular hepatocytes from 8 hrs onward in all lobular areas. PCNA-positive hepatocytes increased at 48 hrs. MDA levels in the serum and liver tended to increase, and MDA- and TG-positive hepatocytes were seen immunohistochemically. GST-P-positive hepatocellular altered foci were detected in one female rat at the 3-month time point. In conclusion, a single injection of green tea extract induced acute and severe hepatotoxicity, which might be associated with lipid peroxidation and DNA oxidative stress in hepatocytes.

  10. Involvement of Toll-like receptor 4 in acetaminophen hepatotoxicity.

    Science.gov (United States)

    Yohe, Herbert C; O'Hara, Kimberley A; Hunt, Jane A; Kitzmiller, Tamar J; Wood, Sheryl G; Bement, Jenna L; Bement, William J; Szakacs, Juliana G; Wrighton, Steven A; Jacobs, Judith M; Kostrubsky, Vsevolod; Sinclair, Peter R; Sinclair, Jacqueline F

    2006-06-01

    The objective of this study was to determine whether Toll-like receptor 4 (TLR4) has a role in alcohol-mediated acetaminophen (APAP) hepatotoxicity. TLR4 is involved in the inflammatory response to endotoxin. Others have found that ethanol-mediated liver disease is decreased in C3H/HeJ mice, which have a mutated TLR4 resulting in a decreased response to endotoxin compared with endotoxin-responsive mice. In the present study, short-term (1 wk) pretreatment with ethanol plus isopentanol, the predominant alcohols in alcoholic beverages, caused no histologically observed liver damage in either C3H/HeJ mice or endotoxin-responsive C3H/HeN mice, despite an increase in nitrotyrosine levels in the livers of C3H/HeN mice. In C3H/HeN mice pretreated with the alcohols, subsequent exposure to APAP caused a transient decrease in liver nitrotyrosine formation, possibly due to competitive interaction of peroxynitrite with APAP producing 3-nitroacetaminophen. Treatment with APAP alone resulted in steatosis in addition to congestion and necrosis in both C3H/HeN and C3H/HeJ mice, but the effects were more severe in endotoxin-responsive C3H/HeN mice. In alcohol-pretreated endotoxin-responsive C3H/HeN mice, subsequent exposure to APAP resulted in further increases in liver damage, including severe steatosis, associated with elevated plasma levels of TNF-alpha. In contrast, alcohol pretreatment of C3H/HeJ mice caused little to no increase in APAP hepatotoxicity and no increase in plasma TNF-alpha. Portal blood endotoxin levels were very low and were not detectably elevated by any of the treatments. In conclusion, this study implicates a role of TLR4 in APAP-mediated hepatotoxicity.

  11. Comparison of manual steering and steering via joystick of a flexible rhino endoscope.

    Science.gov (United States)

    Eckl, R; Gumprecht, J J; Strauss, G; Hofer, M; Dietz, A; Lueth, T C

    2010-01-01

    Flexible endoscopes are used in ENT surgery for examination tasks in cases wherever rigid endoscopes are unsuitable to reach certain positions in the nasal cavity. Until today they are steered by hand and no robotized system has been put into clinical practice. One qualification a robot manipulator system has to fulfill to be accepted is not to create new disadvantages compared to the conventional method in surgery. An important factor is the time needed to steer the new system compared to the time needed to steer the conventional system. In this article a robot manipulator system and an experiment are presented to compare the particular times test persons need to perform a certain task. This approach offers the possibility to benchmark the developed robot manipulator system and future systems for flexible rhino endoscopes.

  12. Oblique incidence effect on steering efficiency of liquid crystal polarization gratings used for optical phased array beam steering amplification

    Science.gov (United States)

    Xiangjie, Zhao; Jiazhu, Duan; Dayong, Zhang; Cangli, Liu; Yongquan, Luo

    2016-07-01

    A liquid crystal polarization grating (LCPG) is proposed that amplifies the steering angle of a liquid crystal optical phased array for non-mechanical beam steering, taking advantage of its high steering efficiency under normal incidence. However, oblique incidence may play an important role in the overall steering efficiency. The effect of oblique incidence on steering efficiency of a LCPG was analyzed by numerically solving the extended Jones matrix and considering propagation crosstalk. The results indicate that the outgoing laser beam is amplitude-modulated under the effect of oblique incidence and behaves as a sinusoidal-modulated amplitude grating, which diffracts certain energies to non-blazed orders. Over-oblique incidence may even eliminate the steering effect of the incident beam. The modulation depth of the induced amplitude grating was found to be proportional to the product of sinusoidal value of oblique incidence angle and the LC layer thickness, and inversely proportional to the periodic pitch length of the LCPG. Both in-plane incidence and out-of-plane incidence behave similarly to influence the steering efficiency. Finally, the overall steering efficiency for cascaded LCPGs was analyzed and a difference of up to 11 % steering efficiency can be induced between different LCPG configurations, even without considering the over-oblique incidence effect. Both the modulation depth and final steering efficiency can be optimized by varying the LC birefringence and layer thickness.

  13. Oblique incidence effect on steering efficiency of liquid crystal polarization gratings used for optical phased array beam steering amplification

    Science.gov (United States)

    Xiangjie, Zhao; Jiazhu, Duan; Dayong, Zhang; Cangli, Liu; Yongquan, Luo

    2016-10-01

    A liquid crystal polarization grating (LCPG) is proposed that amplifies the steering angle of a liquid crystal optical phased array for non-mechanical beam steering, taking advantage of its high steering efficiency under normal incidence. However, oblique incidence may play an important role in the overall steering efficiency. The effect of oblique incidence on steering efficiency of a LCPG was analyzed by numerically solving the extended Jones matrix and considering propagation crosstalk. The results indicate that the outgoing laser beam is amplitude-modulated under the effect of oblique incidence and behaves as a sinusoidal-modulated amplitude grating, which diffracts certain energies to non-blazed orders. Over-oblique incidence may even eliminate the steering effect of the incident beam. The modulation depth of the induced amplitude grating was found to be proportional to the product of sinusoidal value of oblique incidence angle and the LC layer thickness, and inversely proportional to the periodic pitch length of the LCPG. Both in-plane incidence and out-of-plane incidence behave similarly to influence the steering efficiency. Finally, the overall steering efficiency for cascaded LCPGs was analyzed and a difference of up to 11 % steering efficiency can be induced between different LCPG configurations, even without considering the over-oblique incidence effect. Both the modulation depth and final steering efficiency can be optimized by varying the LC birefringence and layer thickness.

  14. Fault-tolerant Actuator System for Electrical Steering of Vehicles

    DEFF Research Database (Denmark)

    Sørensen, Jesper Sandberg; Blanke, Mogens

    2006-01-01

    Being critical to the safety of vehicles, the steering system is required to maintain the vehicles ability to steer until it is brought to halt, should a fault occur. With electrical steering becoming a cost-effective candidate for electrical powered vehicles, a fault-tolerant architecture...... is needed that meets this requirement. This paper studies the fault-tolerance properties of an electrical steering system. It presents a fault-tolerant architecture where a dedicated AC motor design used in conjunction with cheap voltage measurements can ensure detection of all relevant faults...... in the steering system. The paper shows how active control reconfiguration can accommodate all critical faults. The fault-tolerant abilities of the steering system are demonstrated on the hardware of a warehouse truck....

  15. Gaussian quantum steering and its asymmetry in curved spacetime

    CERN Document Server

    Wang, Jieci; Jing, Jiliang; Fan, Heng

    2015-01-01

    We study Gaussian quantum steering and its asymmetry in the background of a Schwarzschild black hole. We present a Gaussian channel description of quantum state evolution under the influence of Hawking radiation. We find that thermal noise introduced by Hawking effect will destroy the steerability between an inertial observer Alice and an accelerated observer Bob who hovers outside an event horizon, while it generates steerability between Bob and a hypothetical observer Anti-Bob inside the event horizon. Besides, unlike entanglement behaviors in curved spacetime, here the steering from Alice to Bob suffers from a ``sudden death" and the steering from Anti-Bob to Bob appears a ``sudden birth" with the increasing of Hawking temperature. We also find that the Gaussian steering is always asymmetric and the maximum steering asymmetry can \\emph{ exceed} $\\ln 2$ in curved spacetime, which is quite different from the flat spacetime case [Phys. Rev. Lett. 114, 060403 (2015)] where the steering asymmetry can \\emph{neve...

  16. Multipartite Gaussian steering: monogamy constraints and cryptographical applications

    CERN Document Server

    Xiang, Yu; Adesso, Gerardo; He, Qiongyi

    2016-01-01

    We derive laws for the distribution of quantum steering among different parties in multipartite Gaussian states under Gaussian measurements. We prove that a monogamy relation akin to the generalized Coffman-Kundu-Wootters inequality holds quantitatively for a recently introduced measure of Gaussian steering. We then define the residual Gaussian steering, stemming from the monogamy inequality, as an indicator of collective steering-type correlations. For pure three-mode Gaussian states, the residual acts a quantifier of genuine multipartite steering, and is interpreted operationally in terms of the guaranteed key rate in the task of secure quantum secret sharing. Optimal resource states for the latter protocol are identified, and their possible experimental implementation discussed. Our results pin down the role of multipartite steering for quantum communication.

  17. Multi-axle dynamic steering system of truck-howitzer

    Institute of Scientific and Technical Information of China (English)

    Yanliang LI; Xiuhua GAO; Chunqiu ZHANG; Yubo SUN

    2008-01-01

    A two-degree-of-freedom (2-DOF) steering model of multi-axle vehicle was established. The steering center position, the relationship between the steering angle and the vehicle velocity, and the minimum turn radius were deduced on the basis of the proportional control with a zero sideslip angle. Results indicate that the system stability is decided by the vehicle barycenter position and the lateral stiffness of a tire. Under this control, the steady value of the lateral acceleration is obviously diminished and the yaw angular velocity changes little under any vehicle velocity. The system rapidly responds, the vehicle smoothly steers, and its handling stability is prominently improved.

  18. Analysis of Vehicle Steering and Driving Bifurcation Characteristics

    Directory of Open Access Journals (Sweden)

    Xianbin Wang

    2015-01-01

    Full Text Available The typical method of vehicle steering bifurcation analysis is based on the nonlinear autonomous vehicle model deriving from the classic two degrees of freedom (2DOF linear vehicle model. This method usually neglects the driving effect on steering bifurcation characteristics. However, in the steering and driving combined conditions, the tyre under different driving conditions can provide different lateral force. The steering bifurcation mechanism without the driving effect is not able to fully reveal the vehicle steering and driving bifurcation characteristics. Aiming at the aforementioned problem, this paper analyzed the vehicle steering and driving bifurcation characteristics with the consideration of driving effect. Based on the 5DOF vehicle system dynamics model with the consideration of driving effect, the 7DOF autonomous system model was established. The vehicle steering and driving bifurcation dynamic characteristics were analyzed with different driving mode and driving torque. Taking the front-wheel-drive system as an example, the dynamic evolution process of steering and driving bifurcation was analyzed by phase space, system state variables, power spectral density, and Lyapunov index. The numerical recognition results of chaos were also provided. The research results show that the driving mode and driving torque have the obvious effect on steering and driving bifurcation characteristics.

  19. Hepatotoxicity by Dietary Supplements: A Tabular Listing and Clinical Characteristics

    Directory of Open Access Journals (Sweden)

    Miren García-Cortés

    2016-04-01

    Full Text Available Dietary supplements (DS are extensively consumed worldwide despite unproven efficacy. The true incidence of DS-induced liver injury (DSILI is unknown but is probably under-diagnosed due to the general belief of safety of these products. Reported cases of herbals and DS-induced liver injury are increasing worldwide. The aim of this manuscript is to report a tabular listing with a description of DS associated with hepatotoxicity as well as review the phenotype and severity of DSILI. Natural remedies related to hepatotoxicity can be divided into herbal product-induced liver injury and DS-induced liver injury. In this article, we describe different DS associated with liver injury, some of them manufactured DS containing several ingredients (Herbalife™ products, Hydroxycut™, LipoKinetix™, UCP-1 and OxyELITE™ while others have a single ingredient (green tea extract, linoleic acid, usnic acid, 1,3-Dimethylamylamine, vitamin A, Garcinia cambogia and ma huang. Additional DS containing some of the aforementioned ingredients implicated in liver injury are also covered. We have also included illicit androgenic anabolic steroids for bodybuilding in this work, as they are frequently sold under the denomination of DS despite being conventional drugs.

  20. Hepatotoxicity by Dietary Supplements: A Tabular Listing and Clinical Characteristics.

    Science.gov (United States)

    García-Cortés, Miren; Robles-Díaz, Mercedes; Ortega-Alonso, Aida; Medina-Caliz, Inmaculada; Andrade, Raul J

    2016-04-09

    Dietary supplements (DS) are extensively consumed worldwide despite unproven efficacy. The true incidence of DS-induced liver injury (DSILI) is unknown but is probably under-diagnosed due to the general belief of safety of these products. Reported cases of herbals and DS-induced liver injury are increasing worldwide. The aim of this manuscript is to report a tabular listing with a description of DS associated with hepatotoxicity as well as review the phenotype and severity of DSILI. Natural remedies related to hepatotoxicity can be divided into herbal product-induced liver injury and DS-induced liver injury. In this article, we describe different DS associated with liver injury, some of them manufactured DS containing several ingredients (Herbalife™ products, Hydroxycut™, LipoKinetix™, UCP-1 and OxyELITE™) while others have a single ingredient (green tea extract, linoleic acid, usnic acid, 1,3-Dimethylamylamine, vitamin A, Garcinia cambogia and ma huang). Additional DS containing some of the aforementioned ingredients implicated in liver injury are also covered. We have also included illicit androgenic anabolic steroids for bodybuilding in this work, as they are frequently sold under the denomination of DS despite being conventional drugs.

  1. Gadolinium chloride pretreatment ameliorates acute cadmium-induced hepatotoxicity.

    Science.gov (United States)

    Kyriakou, Loukas G; Tzirogiannis, Konstantinos N; Demonakou, Maria D; Kourentzi, Kalliopi T; Mykoniatis, Michael G; Panoutsopoulos, Georgios I

    2013-08-01

    Cadmium is a known industrial and environmental pollutant. It causes hepatotoxicity upon acute administration. Features of cadmium-induced acute hepatoxicity encompass necrosis, apoptosis, peliosis and inflammatory infiltration. Gadolinium chloride (GdCl3) may prevent cadmium-induced hepatotoxicity by suppressing Kupffer cells. The effect of GdCl3 pretreatment on a model of acute cadmium-induced liver injury was investigated. Male Wistar rats 4-5 months old were injected intraperitoneally with normal saline followed by cadmium chloride (CdCl2; 6.5 mg/kg) or GdCl3 (10 mg/kg) followed by CdCl2 (6.5 mg/kg; groups I and II, respectively). Rats of both the groups were killed at 9, 12, 16, 24, 48 and 60 h after cadmium intoxication. Liver sections were analyzed for necrosis, apoptosis, peliosis and mitoses. Liver regeneration was also evaluated by tritiated thymidine incorporation into hepatic DNA. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also determined. Hepatic necrosis, hepatocyte and nonparenchymal cell apoptosis and macroscopic and microscopic types of peliosis hepatis were minimized by gadolinium pretreatment. Serum levels of AST and ALT were also greatly diminished in rats of group II. Tritiated thymidine incorporation into hepatic DNA was increased in gadolinium pretreatment rats. Kupffer cell activation was minimal in both the groups of rats. Gadolinium pretreatment attenuates acute cadmium-induced liver injury in young Wistar rats, with mechanisms other than Kupffer cell elimination.

  2. Fullerenol nanoparticles prevents doxorubicin-induced acute hepatotoxicity in rats.

    Science.gov (United States)

    Jacevic, Vesna; Djordjevic, Aleksandar; Srdjenovic, Branislava; Milic-Tores, Vukosava; Segrt, Zoran; Dragojevic-Simic, Viktorija; Kuca, Kamil

    2017-03-16

    Doxorubicin (DOX), commonly used antineoplastic agent, affects bone marrow, intestinal tract and heart, but it also has some hepatotoxic effects. Main mechanism of its toxicity is the production of free reactive oxygen species. Polyhidroxilated C60 fullerene derivatives, fullerenol nanoparticles (FNP), act as free radical scavengers in in vitro systems. The aim of the study was to investigate potential FNP protective role against DOX-induced hepatotoxicity in rats. Experiments were performed on adult male Wistar rats. Animals were divided into five groups: (1) 0.9% NaCl (control), (2) 100mg/kg ip FNP, (3) 10mg/kg DOX iv, (4) 50mg/kg ip FNP 30min before 10mg/kg iv DOX, (5) 100mg/kg ip FNP 30min before 10mg/kg iv DOX. A general health condition, body and liver weight, TBARS level and antioxidative enzyme activity, as well as pathohistological examination of the liver tissue were conducted on days 2 and 14 of the study. FNP, applied alone, did not alter any examinated parameters. However, when used as a pretreatment it significantly increased survival rate, body and liver weight, and decreased TBARS level, antioxidative enzyme activity and hepatic damage score in DOX-treated rats. FNP administered at a dose of 100mg/kg significantly attenuated effects of doxorubicin administered in a single high dose in rats, concerning general condition, body and liver weight, lipid peroxidation level and antioxidative enzyme activity as well as structural alterations of the hepatic tissue.

  3. Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

    Science.gov (United States)

    Aly, Hamdy A A; Mansour, Ahmed M; Hassan, Memy H; Abd-Ellah, Mohamed F

    2016-08-01

    The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016.

  4. Hepatotoxic Alterations Induced by Inhalation of Trichloroethylene (TCE) in Rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective Trichloroethylene (TCE) is one of the most potent organic unsaturated solvents being used in dry cleaning, metal degreasing, thinner for paints varnishes and electroplating, etc. and has been reported to be a hepatotoxicant through oral and dermal exposure. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation toxicity study was carried out for hepatotoxic studies. Method Inhalation toxicity studies was carried out by exposing rats to TCE for 8, 12 and 24 weeks in a dynamically operated whole body inhalation chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. Results Significant increase in liver weight (liver enlargement) appearance of necrotic lesions with fatty changes and marked necrosis were observed after longer duration (12 and 24 weeks) of TCE exposure. The lysosomal rupture resulted in increased activity of acid and alkaline phosphatase alongwith reduced glutathione content and total increased sulfhydryl content in liver tissue. Conclusion TCE exposure through Inhalation route induces hepatotoxicity in terms of marked necrosis with fatty changes and by modulating the lysosomal enzymes.

  5. Food Color Induced Hepatotoxicity in Swiss Albino Rats, Rattus norvegicus

    Science.gov (United States)

    Saxena, Beenam; Sharma, Shiv

    2015-01-01

    Objective: Certain dietary constituents can induce toxicity and play a critical role in the development of several hepatic disorders. Tartrazine, metanil yellow and sunset yellow are widely used azo dyes in food products, so the present study is aimed to investigate the food color induced hepatotoxicity in Swiss albino rats. Materials and Methods: Swiss albino rats were divided into four groups, each group having six animals. Group I served as control, Group II, Group III and Group IV were administered with 25, 50 and 75 mg/kg body weight blend of sunset yellow, metanil yellow and tartrazine for 30 days. Hepatotoxicity in rats treated with a blend of these food colors was studied by assessing parameters such as serum total protein, serum albumin, serum alkaline phosphatase (ALP) as well as hepatic malondialdehyde (MDA). The activity of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) were assessed. Results: Significantly increased concentrations of serum total protein, serum albumin, serum ALP and hepatic MDA and significantly lowered levels of SOD, reduced GSH and CAT in the liver tissue of treated animals were observed when compared with control animals. The alteration in the liver includes necrosis of hepatocytes, infiltration and vacuolation. Conclusion: The result indicates that consumption of food color in diet induces liver tissue damage. The used doses of food color were mostly attributable to hepatocellular damage and drastic alteration in antioxidant defense system. PMID:26862277

  6. Hepatotoxic Potential of Therapeutic Oligonucleotides Can Be Predicted from Their Sequence and Modification Pattern

    Science.gov (United States)

    Hagedorn, Peter H.; Yakimov, Victor; Ottosen, Søren; Kammler, Susanne; Nielsen, Niels F.; Høg, Anja M.; Hedtjärn, Maj; Meldgaard, Michael; Møller, Marianne R.; Ørum, Henrik; Koch, Troels

    2013-01-01

    Antisense oligonucleotides that recruit RNase H and thereby cleave complementary messenger RNAs are being developed as therapeutics. Dose-dependent hepatic changes associated with hepatocyte necrosis and increases in serum alanine-aminotransferase levels have been observed after treatment with certain oligonucleotides. Although general mechanisms for drug-induced hepatic injury are known, the characteristics of oligonucleotides that determine their hepatotoxic potential are not well understood. Here, we present a comprehensive analysis of the hepatotoxic potential of locked nucleic acid-modified oligonucleotides in mice. We developed a random forests classifier, in which oligonucleotides are regarded as being composed of dinucleotide units, which distinguished between 206 oligonucleotides with high and low hepatotoxic potential with 80% accuracy as estimated by out-of-bag validation. In a validation set, 17 out of 23 oligonucleotides were correctly predicted (74% accuracy). In isolation, some dinucleotide units increase, and others decrease, the hepatotoxic potential of the oligonucleotides within which they are found. However, a complex interplay between all parts of an oligonucleotide can influence the hepatotoxic potential. Using the classifier, we demonstrate how an oligonucleotide with otherwise high hepatotoxic potential can be efficiently redesigned to abate hepatotoxic potential. These insights establish analysis of sequence and modification patterns as a powerful tool in the preclinical discovery process for oligonucleotide-based medicines. PMID:23952551

  7. Predicting water intake by yearling feedlot steers.

    Science.gov (United States)

    Sexson, J L; Wagner, J J; Engle, T E; Eickhoff, J

    2012-06-01

    Data from 4 separate beef cattle feedlot experiments, which were conducted at the Southeast Colorado Research Center (SECRC) in Lamar, CO, in 2001, 2003, 2004, and 2007, were utilized in a retrospective longitudinal study investigating possible relationships between daily water consumption (WC), DMI, and weather variables. The data set consisted of 8,209 records from 2001, 2003, 2004, and 2007, with pen based daily WC (L•animal(-1)) and DMI measurements and calculated daily steer BW from April to October in each year. Daily weather data were obtained from the weather station located at Lamar Municipal Airport located approximately 1.9 km from SECRC. Data collected consisted of daily high, low, and mean temperature; high, low, and mean humidity; high, low, and mean sea level pressure; mean wind speed; total precipitation; and average daily wind direction (cosine of radians from due north). Univariate analysis demonstrated that the continuous variables of BW, humidity, and sea level pressure were negatively related (P high temperature squared, high humidity squared, low temperature, low temperature squared, low humidity, average sea level pressure, average wind speed, average daily BW, high sea level pressure, low sea level pressure, high humidity, and low humidity. The generalized R(2) of the parsimonious multivariate model was 0.32. These results indicate that BW and numerous weather factors are related to WC by yearling feedlot steers. Dry matter intake had minimal impact on WC for yearling feedlot steers consuming steam-flaked corn-based high concentrate diets from mid-spring to early fall.

  8. Einstein-Podolsky-Rosen steering and quantum steering ellipsoids: Optimal two-qubit states and projective measurements

    Science.gov (United States)

    McCloskey, R.; Ferraro, A.; Paternostro, M.

    2017-01-01

    We identify the families of states that maximize some recently proposed quantifiers of Einstein-Podolsky-Rosen (EPR) steering and the volume of the quantum steering ellipsoid (QSE). The optimal measurements which maximize genuine EPR steering measures are discussed and we develop a way to find them using the QSE. We thus explore the links between genuine EPR steering and the QSE and introduce states that can be the most useful for one-sided device-independent quantum cryptography for a given amount of noise.

  9. Study on control schemes of flexible steering system of a multi-axle all-wheel-steering robot

    Directory of Open Access Journals (Sweden)

    Pingxia Zhang

    2016-05-01

    Full Text Available It is well known that a multi-axle wheeled robot possesses larger load capability and also higher drive performance. However, its steering flexibility is degraded due to the large number of wheels. In order to solve this problem, in this article, we proposed three control schemes based on the center of rotation or the steering angles of both the first- and last-axle wheels. To release these control schemes, steering mode selection and also the left wheel’s steering angle in a specific axle are added approaching a practical application. Thereafter, the remaining wheels’ steering angles can be calculated with the Ackerman steering theorem. In order to verify the control effects, a five-axle all-wheel-steering wheeled robot has been developed with the Bluetooth wireless monitor system. Based on the newly designed robot, validation experiments are carried out, such as lateral movement, situ rotation, and multi-mode steering within a narrow space. The results indicate that the proposed design in this article can ensure a more flexible and faster movement within a narrow space. It shows large potential in obstacle avoidance compared with the conventional partial-wheel steering mode.

  10. Gene expression profiling reveals potential key pathways involved in pyrazinamide-mediated hepatotoxicity in Wistar rats.

    Science.gov (United States)

    Zhang, Yun; Jiang, Zhenzhou; Su, Yijing; Chen, Mi; Li, Fu; Liu, Li; Sun, Lixin; Wang, Yun; Zhang, Shuang; Zhang, Luyong

    2013-08-01

    Pyrazinamide (PZA) is an important sterilizing prodrug that shortens the duration of tuberculosis therapy. However, hepatotoxicity has been reported during clinical trials investigating PZA. To determine the hepatotoxic effects of PZA in vivo and to further investigate the underlying cellular mechanism, we profiled the gene expression patterns of PZA-treated rat livers by microarray analysis. Wistar rats of both sexes were orally administered PZA at doses of 0.5, 1.0 and 2.0 g kg(-1) for 28 days. Body weight, absolute and relative liver weight, biochemical analysis, histopathology, oxidative stress parameters in liver homogenates and changes in global transcriptomic expression were evaluated to study the hepatotoxic effects of PZA. Our results confirm the dose-dependent and sex-related hepatotoxicity of PZA. Female rats were more sensitive to PZA-induced hepatotoxicity than males. Furthermore, changes in the activity of major antioxidant enzymes and nonenzymatic antioxidants (superoxide dismutase, total antioxidant capacity, glutathione and malondialdehyde), indicating the development of oxidative stress, were more significant in the PZA-treated group. PZA-induced gene expression changes were related to pathways involved in drug metabolism, peroxisome proliferator-activated receptor (PPAR) signaling, oxidative stress and apoptosis. Real-time polymerase chain reaction confirmed the regulation of selected genes involved in PZA-hepatotoxicity (Ephx1, Cyp2b1, Gstm1, Gstp1, Fabp7, Acaa1, Cpt-1b, Cyp8b1, Hmox1 and Ntrk1). We observed for the first time that these genes have effects on PZA-induced hepatotoxicity. In addition, drug metabolism and PPAR signaling pathways may play an important role in PZA hepatotoxicity. Taken together, these findings will be useful for future PZA hepatotoxicity studies.

  11. Stress indicators in steers at slaughtering

    Directory of Open Access Journals (Sweden)

    A. Zarrilli

    2010-04-01

    Full Text Available This work aimed to assess the blood modifications of some slaughtering-linked stress hormones in cattle subject to butcher standardized procedures. The blood samples of 20 Limousine 12-13 months old steers have been collected before slaughtering, during lairage, and after stunning by captive bolt gun, during exsanguination. The plasma level of epinephrine, norepinephrine, cortisol and beta-endorphin have been assayed by EIA. The data indicate that catecholamines, cortisol and beta-endorphin did not significantly increase after stunning in these animals.

  12. Internal models direct dragonfly interception steering.

    Science.gov (United States)

    Mischiati, Matteo; Lin, Huai-Ti; Herold, Paul; Imler, Elliot; Olberg, Robert; Leonardo, Anthony

    2015-01-15

    Sensorimotor control in vertebrates relies on internal models. When extending an arm to reach for an object, the brain uses predictive models of both limb dynamics and target properties. Whether invertebrates use such models remains unclear. Here we examine to what extent prey interception by dragonflies (Plathemis lydia), a behaviour analogous to targeted reaching, requires internal models. By simultaneously tracking the position and orientation of a dragonfly's head and body during flight, we provide evidence that interception steering is driven by forward and inverse models of dragonfly body dynamics and by models of prey motion. Predictive rotations of the dragonfly's head continuously track the prey's angular position. The head-body angles established by prey tracking appear to guide systematic rotations of the dragonfly's body to align it with the prey's flight path. Model-driven control thus underlies the bulk of interception steering manoeuvres, while vision is used for reactions to unexpected prey movements. These findings illuminate the computational sophistication with which insects construct behaviour.

  13. Optimization Under Uncertainty for Wake Steering Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Quick, Julian [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Annoni, Jennifer [National Renewable Energy Laboratory (NREL), Golden, CO (United States); King, Ryan N [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Dykes, Katherine L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Fleming, Paul A [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ning, Andrew [Brigham Young University

    2017-08-03

    Offsetting turbines' yaw orientations from incoming wind is a powerful tool that may be leveraged to reduce undesirable wake effects on downstream turbines. First, we examine a simple two-turbine case to gain intuition as to how inflow direction uncertainty affects the optimal solution. The turbines are modeled with unidirectional inflow such that one turbine directly wakes the other, using ten rotor diameter spacing. We perform optimization under uncertainty (OUU) via a parameter sweep of the front turbine. The OUU solution generally prefers less steering. We then do this optimization for a 60-turbine wind farm with unidirectional inflow, varying the degree of inflow uncertainty and approaching this OUU problem by nesting a polynomial chaos expansion uncertainty quantification routine within an outer optimization. We examined how different levels of uncertainty in the inflow direction effect the ratio of the expected values of deterministic and OUU solutions for steering strategies in the large wind farm, assuming the directional uncertainty used to reach said OUU solution (this ratio is defined as the value of the stochastic solution or VSS).

  14. The effect of varying path properties in path steering tasks

    NARCIS (Netherlands)

    Liu, L.; Liere, R. van

    2010-01-01

    Path steering is a primitive 3D interaction task that requires the user to navigate through a path of a given length and width. In a previous paper, we have conducted controlled experiments in which users operated a pen input device to steer a cursor through a 3D path subject to fixed path propertie

  15. Robotic needle steering: design, modeling, planning, and image guidance

    NARCIS (Netherlands)

    Cowan, Noah J.; Goldberg, Ken; Chirikjian, Gregory S.; Fichtinger, Gabor; Alterovitz, Ron; Reed, Kyle B.; Kallem, Vinutha; Park, Wooram; Misra, Sarthak; Okamura, Allison M.; Rosen, Jacob; Hannaford, Blake; Satava, Richard M.

    2010-01-01

    This chapter describes how advances in needle design, modeling, planning, and image guidance make it possible to steer flexible needles from outside the body to reach specified anatomical targets not accessible using traditional needle insertion methods. Steering can be achieved using a variety of m

  16. 3D computational steering with parametrized geometric objects

    NARCIS (Netherlands)

    Mulder, J.D.; Wijk, J.J. van

    1996-01-01

    Computational Steering is the ultimate goal of interactive simulation: researchers change parameters of their simulation and immediately receive feedback on the effect. We present a general and flexible graphics tool that is part of an environment for Computational Steering developed at CWI. It enab

  17. Gaussian quantum steering and its asymmetry in curved spacetime

    Science.gov (United States)

    Wang, Jieci; Cao, Haixin; Jing, Jiliang; Fan, Heng

    2016-06-01

    We study Gaussian quantum steering and its asymmetry in the background of a Schwarzschild black hole. We present a Gaussian channel description of quantum state evolution under the influence of Hawking radiation. We find that thermal noise introduced by the Hawking effect will destroy the steerability between an inertial observer Alice and an accelerated observer Bob who hovers outside the event horizon, while it generates steerability between Bob and a hypothetical observer anti-Bob inside the event horizon. Unlike entanglement behaviors in curved spacetime, here the steering from Alice to Bob suffers from a "sudden death" and the steering from anti-Bob to Bob experiences a "sudden birth" with increasing Hawking temperature. We also find that the Gaussian steering is always asymmetric and the maximum steering asymmetry cannot exceed ln 2 , which means the state never evolves to an extremal asymmetry state. Furthermore, we obtain the parameter settings that maximize steering asymmetry and find that (i) s =arccosh cosh/2r 1 -sinh2r is the critical point of steering asymmetry and (ii) the attainment of maximal steering asymmetry indicates the transition between one-way steerability and both-way steerability for the two-mode Gaussian state under the influence of Hawking radiation.

  18. The impact of force feedback level on steering performance

    NARCIS (Netherlands)

    Anand, S.; Terken, J.; Hogema, J.H.

    2013-01-01

    Steer-by-wire systems provide designers the ability to customize and personalize force feedback on the steering wheel, based on individual preferences. Earlier studies using subjective responses have shown that there are individual differences in preferences for force feedback. It has also been foun

  19. Experimental Study on Antivibration Control of Electrical Power Steering Systems

    Directory of Open Access Journals (Sweden)

    Zhaojian Wang

    2014-01-01

    Full Text Available We focus on the antivibration controller design problem for electrical power steering (EPS systems. The EPS system has significant advantages over the traditional hydraulic steering system. However, the improper motor controller design would lead to the steering wheel vibration. Therefore, it is necessary to investigate the antivibration control strategy. For the implementation study, we also present the motor driver design and the software design which is used to monitor the sensors and the control signal. Based on the investigation on the regular assistant algorithm, we summarize the difficulties and problems encountered by the regular algorithm. After that, in order to improve the performance of antivibration and the human-like steering feeling, we propose a new assistant strategy for the EPS. The experiment results of the bench test illustrate the effectiveness and flexibility of the proposed control strategy. Compared with the regular controller, the proposed antivibration control reduces the vibration of the steering wheel a lot.

  20. Sidelobe Suppression with Null Steering by Independent Weight Control

    Directory of Open Access Journals (Sweden)

    Zafar-Ullah Khan

    2015-01-01

    Full Text Available A uniform linear array of n antenna elements can steer up to n-1 nulls. In situations where less than n-1 nulls are required to be steered, the existing algorithms have no criterion to utilize the remaining weights for sidelobe suppression. This work combines sidelobe suppression capability with null steering by independent weight control. For this purpose, the array factor is transformed as the product of two polynomials. One of the polynomials is used for null steering by independent weight control, while the second one is for sidelobe suppression whose coefficients or weights are determined by using convex optimization. Finally, a new structure is proposed to incorporate the product of two polynomials such that sidelobe suppression weights are decoupled from those of null steering weights. Simulation results validate the effectiveness of the proposed scheme.

  1. Conclusive quantum steering with superconducting transition edge sensors

    CERN Document Server

    Smith, Devin H; de Almeida, Marcelo; Branciard, Cyril; Fedrizzi, Alessandro; Weinhold, Till J; Lita, Adriana; Calkins, Brice; Gerrits, Thomas; Nam, Sae Woo; White, Andrew G

    2011-01-01

    Quantum steering allows two parties to verify shared entanglement even if one measurement device is untrusted. A conclusive demonstration of steering through the violation of a steering inequality is of considerable fundamental interest and opens up applications in quantum communication. To date all experimental tests with single photon states have relied on post-selection, allowing untrusted devices to cheat by hiding unfavorable events in losses. Here we close this "detection loophole" by combining a highly efficient source of entangled photon pairs with superconducting transition edge sensors. We achieve an unprecedented $\\sim$62% conditional detection efficiency of entangled photons and violate a steering inequality with the minimal number of measurement settings by 48 standard deviations. Our results provide a clear path to practical applications of steering and to a photonic loophole-free Bell test.

  2. Study on classification and identification methods of driver steering characteristics

    Directory of Open Access Journals (Sweden)

    Gang LI

    2015-12-01

    Full Text Available Aiming at the vehicle driver's steering characteristic classification and identification, the research method is initially explored based on CarSim simulation platform. The simulation experiment of steering condition is designed and the test data is collected. According to the maximum yaw rate of the vehicle, the driver steering characteristics are classified by K-means clustering algorithm. The driver steering characteristics identification models are established by learning vector quantization (LVQ neural network, BP neural network, and support vector machine (SVM respectively in the environment of Matlab software. The test experiment and comparison are done for the three kinds of approaches, and the results show that all those three kinds of identification approaches have high accuracy, and the SVM method has a certain advantage on driver steering characteristics identification.

  3. Leflunomide for the treatment of rheumatoid arthritis in clinical practice - Incidence and severity of hepatotoxicity

    NARCIS (Netherlands)

    van Roon, EN; Jansen, TLTA; Houtman, NM; Spoelstra, P; Brouwers, JRBJ

    2004-01-01

    Objective: Leflunomide is a novel disease modifying antirheumatic drug (DMARD). Because of reports on possible hepatotoxicity and adaptations in the recommendations for monitoring liver function during leflunomide treatment, we conducted a study to evaluate the incidence and severity of hepatotoxici

  4. A study of effect of Nigella sativa oil in paracetamol induced hepatotoxicity in albino rats

    Directory of Open Access Journals (Sweden)

    Manik S. Ghadlinge

    2014-06-01

    Conclusion: This study demonstrated that NS oil has hepatoprotective effect. NS oil administration can prevent or reverse the hepatotoxicity induced by paracetamol. [Int J Basic Clin Pharmacol 2014; 3(3.000: 539-546

  5. Nrf2 protects against furosemide-induced hepatotoxicity.

    Science.gov (United States)

    Qu, Qiang; Liu, Jie; Zhou, Hong-Hao; Klaassen, Curtis D

    2014-10-01

    Furosemide is a diuretic drug, but its reactive intermediates lead to acute liver injury in mice. Given the essential role of Nrf2 as a cellular defense regulator, we investigated whether Nrf2 would protect against furosemide-induced liver injury using the Nrf2 "gene-dose response" mouse model (Nrf2-null with Nrf2 knock-out, wild-type with normal expression of Nrf2, Keap1-KD with enhanced Nrf2 activation and Keap1-HKO mice with maximum Nrf2 activation). Twenty-four hours after furosemide administration (250mg/kg, i.p.), serum ALT activities and histopathological analysis indicated severe hepatotoxicity in Nrf2-null and WT mice, but significantly less in the Nrf2-overexpressing Keap1-KD and Keap1-HKO mice. Furosemide increased the mRNA of genes involved in the acute phase response (hemeoxygenase-1 and metallothionein-1), ER stress (C/Ebp-homologous protein and Growth arrest and DNA-damage-inducible protein), inflammatory cytokine (interleukin 1 beta), chemokines (macrophage inflammatory protein 2 and mouse keratinocyte-derived chemokine), as well as apoptosis (early growth response factor and BCL2-associated X protein) in livers of Nrf2-null and wild-type mice, but these genes increased less in mice with more Nrf2. The two genotypes of over-expressed Nrf2 mice had increased expression of the Nrf2 target genes Gclm, Gclc and Nqo1 prior to furosemide administration, and the expressions of these genes were increased further after furosemide administration. Thus, our findings provide strong evidence that over-expression of Nrf2 in Keap1-KD and Keap1-HKO mice and the increases in mRNA of a number of genes involved in anti-oxidative stress, anti-inflammation, anti-ER stress and anti-apoptosis protect against furosemide-induced hepatotoxicity.

  6. Identification of a metabolic biomarker panel in rats for prediction of acute and idiosyncratic hepatotoxicity.

    Science.gov (United States)

    Sun, Jinchun; Slavov, Svetoslav; Schnackenberg, Laura K; Ando, Yosuke; Greenhaw, James; Yang, Xi; Salminen, William; Mendrick, Donna L; Beger, Richard

    2014-07-01

    It has been estimated that 10% of acute liver failure is due to "idiosyncratic hepatotoxicity". The inability to identify such compounds with classical preclinical markers of hepatotoxicity has driven the need to discover a mechanism-based biomarker panel for hepatotoxicity. Seven compounds were included in this study: two overt hepatotoxicants (acetaminophen and carbon tetrachloride), two idiosyncratic hepatotoxicants (felbamate and dantrolene), and three non-hepatotoxicants (meloxicam, penicillin and metformin). Male Sprague-Dawley rats were orally gavaged with a single dose of vehicle, low dose or high dose of the compounds. At 6 h and 24 h post-dosing, blood was collected for metabolomics and clinical chemistry analyses, while organs were collected for histopathology analysis. Forty-one metabolites from previous hepatotoxicity studies were semi-quantified and were used to build models to predict hepatotoxicity. The selected metabolites were involved in various pathways, which have been noted to be linked to the underlying mechanisms of hepatotoxicity. PLS models based on all 41 metabolite or smaller subsets of 6 (6 h), 7 (24 h) and 20 (6 h and 24 h) metabolites resulted in models with an accuracy of at least 97.4% for the hold-out test set and 100% for training sets. When applied to the external test sets, the PLS models predicted that 1 of 9 rats at both 6 h and 24 h treated with idiosyncratic liver toxicants was exposed to a hepatotoxic chemical. In conclusion, the biomarker panel might provide information that along with other endpoint data (e.g., transcriptomics and proteomics) may diagnose acute and idiosyncratic hepatotoxicity in a clinical setting.

  7. Effect of honey on hepatotoxicity induced by antitubercular drugs in albino rats

    OpenAIRE

    Rakhamaji D. Chandane; Jugalkishor B. Jaju; Manik S. Ghadlinge; Rama R. Bhosale; Ajay R. Chandrakapure

    2013-01-01

    Background: Drug-induced hepatotoxicity is a potentially serious adverse effect of antituberculosis treatment (ATT) regimens containing isoniazid, rifampicin and pyrazinamide. Many in vitro and in vivo studies revealed that honey possess antioxidant property and hepotoprotective property but there is no systematic work available to test the effect of honey on antitubercular drugs induced hepatotoxicity in rats. Hence present study was carried out to explore the prophylactic and therapeutic ef...

  8. Enhancement of acetaminophen-induced chronic hepatotoxicity in restricted fed rats: a nonclinical approach to acetaminophen-induced chronic hepatotoxicity in susceptible patients.

    Science.gov (United States)

    Kondo, Kazuma; Yamada, Naohito; Suzuki, Yusuke; Toyoda, Kaoru; Hashimoto, Tatsuji; Takahashi, Akemi; Kobayashi, Akio; Shoda, Toshiyuki; Kuno, Hideyuki; Sugai, Shoichiro

    2012-01-01

    Acetaminophen (APAP) is a commonly used and effective analgesic and antipyretic agent. However, some patients encounter hepatotoxicity after repeated APAP dosing at therapeutic doses. In the present study, we focused on the nutritional state as one of the risk factors of APAP-induced chronic hepatotoxicity in humans and investigated the contribution of undernourishment to susceptibility to APAP-induced chronic hepatotoxicity using an animal model mimicking undernourished patients. Rats were divided into 2 groups: the ad libitum fed (ALF) and the restricted fed (RF) rats and were assigned to 3 groups (n = 8/group) for each feeding condition. The animals were given APAP at 0, 300 and 500mg/kg for 99 days under each feeding condition. Plasma and urinary glutathione-related metabolites and liver function parameters were measured during the dosing period and hepatic glutathione levels were measured at the end of the dosing period. In the APAP-treated ALF rats hepatic glutathione levels were increased and hepatic function parameters were not changed, but in the APAP-treated RF rats hepatic glutathione levels were decreased at 500mg/kg and hepatic function parameters were increased at 300 and 500mg/kg. Moreover the urinary endogenous metabolite profile after long-term treatment with APAP in the ALF and RF rats was similar to that in human non-responders and responders to APAP-induced chronic hepatotoxicity, respectively. In conclusion, the RF rats were more sensitive to APAP-induced chronic hepatotoxicity than the ALF rats and were considered to be a useful model to estimate the contribution of the nutritional state of patients to APAP-induced chronic hepatotoxicity.

  9. Phase shifter for antenna beam steering

    Science.gov (United States)

    Jindal, Ravi; Razban, Tchanguiz

    2016-03-01

    Wide band Array Antenna operates in Ku-band (10.7-12.7 GHz) frequency composed of N×N radiating elements. This antenna aims at the reception of television satellite signals. The goal of this research is to provide better possibility of electronic beam control instead of manual or mechanical control, and design compact and low cost phase shifters to be inserted in the feeding network of this antenna. The electronic control of the phase shifter will allow the control of beam steering. The emphasis of this project will be done at the beginning on the design of a good phase shifter in Ku band. The aim of this research is to define, simulate, release and measure a continuous phase shifter. Better reflection loss, low transmission loss, low Cost of array antennas, large range of phase-shifter, phase flatness and bandwidth will be achieved by providing better gain.

  10. Beam Steering Mechanism (BSM) Lessons Learned

    Science.gov (United States)

    Blumenstock, Kenneth A.; Cramer, Alexander K.; Gostin, Alan B.; Hakun, Claef F.; Haney, Paul G.; Hinkle, Matthew R.; Lee, Kenneth Y.; Lugo, Carlos F.; Matuszeski, Adam J.; Morell, Armando; Armani, Nerses V.; Bonafede, Joseph; Jackson, Molly I.; Steigner, Peter J.; Stromsdorfer, Juan J.

    2016-01-01

    This paper describes the design, testing, and lessons learned during the development of the Advanced Topographic Laser Altimeter System (ATLAS) Beam Steering Mechanism (BSM). The BSM is a 2 degree-of-freedom tip-tilt mechanism for the purpose of pointing a flat mirror to tightly control the co-alignment of the transmitted laser and the receiver telescope of the ATLAS instrument. High resolution needs of the mission resulted in sub-arcsecond pointing and knowledge requirements, which have been met. Development of methodology to verify performance was a significant effortadvancement. The BSM will fly as part of the Ice, Cloud, and Elevation Satellite 2 Mission (ICESat 2), which is scheduled to be launched in 2017. The ICESat 2 primary mission is to map the earths surface topography for the determination of seasonal changes of ice sheet thickness as well as vegetation canopy thickness.

  11. ATLAS Beam Steering Mechanism (BSM) Lessons Learned

    Science.gov (United States)

    Blumenstock, Kenneth A.; Cramer, Alexander K.; Gosten, Alan B.; Hakun, Claef F.; Haney, Paul G.; Hinkle, Matthew R.; Lee, Kenneth Y.; Lugo, Carlos F.; Matuszeski, Adam J.; Morell, Armando; Armani, Nerses V.; Bonafede, Joseph; Jackson, Molly I.; Steigner, Peter J.; Stromsdorfer, Juan J.

    2016-01-01

    This paper describes the design, testing, and lessons learned during the development of the Advanced Topographic Laser Altimeter System (ATLAS) Beam Steering Mechanism (BSM). The BSM is a 2 degree-of-freedom tip-tilt mechanism for the purpose of pointing a flat mirror to tightly control the co-alignment of the transmitted laser and the receiver telescope of the ATLAS instrument. The high resolution needs of the mission resulted in sub-arcsecond pointing and knowledge requirements, which have been met. Development of the methodology to verify performance required significant effort. The BSM will fly as part of the Ice, Cloud, and Elevation Satellite II Mission (ICESat II), which is scheduled to be launched in 2017. The ICESat II primary mission is to map the Earth's surface topography for the determination of seasonal changes of ice sheet thickness and vegetation canopy thickness to establish long-term trends.

  12. ATLAS Beam Steering Mechanism Lessons Learned

    Science.gov (United States)

    Blumenstock, Kenneth A.; Cramer, Alexander K.; Gostin, Alan B.; Hakun, Claef F.; Haney, Paul G.; Hinkle, Matthew R.; Lee, Kenneth Y.; Lugo, Carlos F.; Matuszeski, Adam J.; Morrell, Armando; Armani, Nerses V.; Bonafede, Joseph; Jackson, Molly I.; Steigner, Peter J.; Stromsdorfer, Juan J.

    2016-01-01

    This paper describes the design, testing, and lessons learned during the development of the Advanced Topographic Laser Altimeter System (ATLAS) Beam Steering Mechanism (BSM). The BSM is a 2 degree-of-freedom tip-tilt mechanism for the purpose of pointing a flat mirror to tightly control the co-alignment of the transmitted laser and the receiver telescope of the ATLAS instrument. The high resolution needs of the mission resulted in sub-arcsecond pointing and knowledge requirements, which have been met. Development of the methodology to verify performance required significant effort. The BSM will fly as part of the Ice, Cloud, and Elevation Satellite II Mission (ICESat II), which is scheduled to be launched in 2017. The ICESat II primary mission is to map the earth's surface topography for the determination of seasonal changes of ice sheet thickness and vegetation canopy thickness to establish long-term trends.

  13. Phase shifter for antenna beam steering

    Energy Technology Data Exchange (ETDEWEB)

    Jindal, Ravi, E-mail: rjindal21@gmail.com [Master’s(MS) in System Electronics and General Electrical, Ecole Polytechnique of university of Nantes France, IETR, Nantes (France); Razban, Tchanguiz, E-mail: tchanguiz.razban-haghighi@univ-nantes.fr [Electronics and Telecommunication Institute of Rennes (IETR-UMR 6164), Ecole Polytechnique of university of Nantes France, IETR, Nantes (France)

    2016-03-09

    Wide band Array Antenna operates in Ku-band (10.7-12.7 GHz) frequency composed of N×N radiating elements. This antenna aims at the reception of television satellite signals. The goal of this research is to provide better possibility of electronic beam control instead of manual or mechanical control, and design compact and low cost phase shifters to be inserted in the feeding network of this antenna. The electronic control of the phase shifter will allow the control of beam steering. The emphasis of this project will be done at the beginning on the design of a good phase shifter in Ku band. The aim of this research is to define, simulate, release and measure a continuous phase shifter. Better reflection loss, low transmission loss, low Cost of array antennas, large range of phase-shifter, phase flatness and bandwidth will be achieved by providing better gain.

  14. On fractional control method for four-wheel-steering vehicle

    Institute of Scientific and Technical Information of China (English)

    CHEN Ning; CHEN Nan; CHEN YanDong

    2009-01-01

    Four-wheel-steering (4WS) system can enhance vehicle cornering ability by steering the rear wheels in accordance with the front wheels steering and vehicle status. With such steering control system, it becomes possible to improve the lateral stability and handling performance, in this paper, a new control method for 4WS vehicle is proposed, its rear wheels steering angle is in accordance with the angle of front wheels steering and vehicle yaw rate, and the effects of front wheels steering angle velocity are considered by adopting the fractional derivative theory. Some design specifications for control law are also given. The effects of the control method are verified by a kind of numerical scheme presented in this paper. The dynamic characteristics such as the side-slip angle and the yaw angle velocity of the vehicle gravity center are compared among three kinds of vehicles with different control methods. And the kinematics characteristics such as turning radius between 4WS and 2WS are also discussed. Nu-merical simulation shows that the control method presented can improve the transient response and reduce the turning radius of 4WS vehicle.

  15. On fractional control method for four-wheel-steering vehicle

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Four-wheel-steering (4WS) system can enhance vehicle cornering ability by steering the rear wheels in accordance with the front wheels steering and vehicle status. With such steering control system, it becomes possible to improve the lateral stability and handling performance. In this paper, a new control method for 4WS vehicle is proposed, its rear wheels steering angle is in accordance with the angle of front wheels steering and vehicle yaw rate, and the effects of front wheels steering angle velocity are considered by adopting the fractional derivative theory. Some design specifications for control law are also given. The effects of the control method are verified by a kind of numerical scheme presented in this paper. The dynamic characteristics such as the side-slip angle and the yaw angle velocity of the vehicle gravity center are compared among three kinds of vehicles with different control methods. And the kinematics characteristics such as turning radius between 4WS and 2WS are also discussed. Nu- merical simulation shows that the control method presented can improve the transient response and reduce the turning radius of 4WS vehicle.

  16. Quantum steering: a review with focus on semidefinite programming

    Science.gov (United States)

    Cavalcanti, D.; Skrzypczyk, P.

    2017-02-01

    Quantum steering refers to the non-classical correlations that can be observed between the outcomes of measurements applied on half of an entangled state and the resulting post-measured states that are left with the other party. From an operational point of view, a steering test can be seen as an entanglement test where one of the parties performs uncharacterised measurements. Thus, quantum steering is a form of quantum inseparability that lies in between the well-known notions of Bell nonlocality and entanglement. Moreover, quantum steering is also related to several asymmetric quantum information protocols where some of the parties are considered untrusted. Because of these facts, quantum steering has received a lot of attention both theoretically and experimentally. The main goal of this review is to give an overview of how to characterise quantum steering through semidefinite programming. This characterisation provides efficient numerical methods to address a number of problems, including steering detection, quantification, and applications. We also give a brief overview of some important results that are not directly related to semidefinite programming. Finally, we make available a collection of semidefinite programming codes that can be used to study the topics discussed in this article.

  17. Monkey steering responses reveal rapid visual-motor feedback.

    Directory of Open Access Journals (Sweden)

    Seth W Egger

    Full Text Available The neural mechanisms underlying primate locomotion are largely unknown. While behavioral and theoretical work has provided a number of ideas of how navigation is controlled, progress will require direct physiolgical tests of the underlying mechanisms. In turn, this will require development of appropriate animal models. We trained three monkeys to track a moving visual target in a simple virtual environment, using a joystick to control their direction. The monkeys learned to quickly and accurately turn to the target, and their steering behavior was quite stereotyped and reliable. Monkeys typically responded to abrupt steps of target direction with a biphasic steering movement, exhibiting modest but transient overshoot. Response latencies averaged approximately 300 ms, and monkeys were typically back on target after about 1 s. We also exploited the variability of responses about the mean to explore the time-course of correlation between target direction and steering response. This analysis revealed a broad peak of correlation spanning approximately 400 ms in the recent past, during which steering errors provoke a compensatory response. This suggests a continuous, visual-motor loop controls steering behavior, even during the epoch surrounding transient inputs. Many results from the human literature also suggest that steering is controlled by such a closed loop. The similarity of our results to those in humans suggests the monkey is a very good animal model for human visually guided steering.

  18. Lean color characteristics of bullock and steer beef.

    Science.gov (United States)

    Shackelford, S D; Purser, D E; Smith, G C; Griffin, C L; Stiffler, D M; Savell, J W

    1992-02-01

    Twelve young bulls and 12 steers were slaughtered and the carcasses were fabricated at 48 h postmortem. Top rounds, bottom rounds, and rib eyes were vacuum-packaged and stored at 0 degrees C until 21 d postmortem. After subprimal storage, steaks were removed from each cut and displayed under simulated retail conditions for 3 d. Consumer panelists (n = 110) showed little difference in buying preference for top round, bottom round, and rib eye steaks from steers vs bullocks. Also, consumer panelists could not detect color differences between steaks from steers and bullocks. Experienced panelists (n = 6) detected brighter (P less than .05) muscle color for top round and rib eye steaks from steers but detected no difference in muscle color of bottom round steaks from bullocks and steers. Generally, overall desirability scores favored steaks from steer carcasses. This was particularly true of rib eye steaks. Sex-class of carcass did not affect aerobic plate counts of top round, bottom round, or rib eye steaks either before or after 3 d of retail display. Muscle pH was lower for top round and rib eye steaks from steer carcasses; however, the magnitude of this difference was not large enough to affect retail display stability. Muscle pH of bottom round steaks was not affected by sex-class. Although experienced panelists could detect differences in visual appearance of beef retail cuts from steers and bullocks, consumer panelists did not show a clear purchase preference for steer vs bullock beef. These data suggest that beef retail cuts from bullocks are acceptable in visual appearance.

  19. FLOW CHARACTERISTICS FORMATION OF POWER STEERING WITH ROTARY DISTRIBUTOR

    OpenAIRE

    Mikhailov, V; E. Strock

    2012-01-01

    In order to obtain an adequate mathematical model of vehicle hydro-mechanical steering which is  equipped with a steering mechanism combined with power steering and a rotary distributor  it is initially   necessary to get current consumption values in the units of hydraulic scheme which are determined by dynamic changes of flow passages of pressure and drain circuits according to turning angle of the distributor. Such characteristics are usually determined experimentally.The paper  proposes  ...

  20. Selection and Simulation of Electric Steering Gear Control System

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2013-06-01

    Full Text Available For the electric steering gear control systems, the principle of the system is introduced. Specific model and parameters are selected to deduce the optimal combination of control system and choices method of the steering system model is determined. The transfer function of motor according to the parameters is achieved and simulation results are gained based on MATLAB. Simulation results show that this method can meet the performance requirements of electric steering gear, the control method is simple and easy to work to achieve.

  1. Steering Control of Wheeled Armored Vehicle with Brushless DC Motor

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Considering the steering characters of one type of wheeled armored vehicle, a brushless direct current (DC) motor is adapted as the actuator for steering control. After investigating the known algorithms, one kind of algorithm, which combines the fuzzy logic control with the self-adapting PID control and the startup and pre-brake control, is put forward. Then a test-bed is constructed, and an experiment is conducted. The result of experiment confirms the validity of this algorithm in steering control of wheeled armored vehicle with brushless DC motor.

  2. 46 CFR 58.25-10 - Main and auxiliary steering gear.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Main and auxiliary steering gear. 58.25-10 Section 58.25... AUXILIARY MACHINERY AND RELATED SYSTEMS Steering Gear § 58.25-10 Main and auxiliary steering gear. (a) Power-operated main and auxiliary steering gear must be separate systems that are independent throughout...

  3. 46 CFR 196.37-33 - Instructions for changing steering gear.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Instructions for changing steering gear. 196.37-33... steering gear. (a) Instructions in at least 1/2 inch letters and figures shall be posted in the steering engineroom, relating in order, the different steps to be taken in changing to the emergency steering...

  4. Impact of feedback torque level on perceived comfort and control in steer-by-wire systems

    NARCIS (Netherlands)

    Anand, S.; Terken, J.; Hogema, J.H.; Martens, J.B.

    2012-01-01

    Steer-by-Wire systems enable designers to offer completely personalized steering feel to drivers, unlike existing steering systems that offer limited or no personalization. In this paper we focus on feedback torque level, a significant factor for steering feel. Earlier studies indicate that the pref

  5. Dynamic characteristics of hydraulic power steering system with accumulator in load-haul-dump vehicle

    Institute of Scientific and Technical Information of China (English)

    杨忠炯; 何清华; 柳波

    2004-01-01

    Using hydraulic power steering system of model EIMCO 922 load-haul-dump vehicle as a simulation example, the dynamic characteristics of hydraulic power steering system in load-haul-dump vehicle were simulated and discussed with SIMULINK software and hydraulic control theory. The results show that the dynamic characteristics of hydraulic power steering system are improved obviously by using bladder accumulator, the hydraulic power steering system of model EIMCO 922 load-haul-dump vehicle generates vibration at the initial stage under the normal steering condition of pulse input, and its static response time is 0.25 s shorter than that without bladder accumulator. Under the normal steering working condition, the capacity of steering accumulator for absorbing pulse is directly proportional to the cross section area of connecting pipeline, and inversely proportional to the length of connecting pipeline. At the same time, the precharge pressure of nitrogen in steering accumulator should be 60%- 80% of the rated minimum working pressure of hydraulic power steering system. Under the abnormal steering working condition, the steering cylinder piston may obtain higher motion velocity, and the dynamic response velocity of hydraulic power steering system can be increased by reducing the pressure drop of hydraulic pipelines between the accumulator and steering cylinder and by increasing the rated pressure of hydraulic power steering system, but the dynamic characteristics of hydraulic power steering system in load-haul-dump vehicle have nothing to do with the precharge pressure of nitrogen in steering accumulator.

  6. FLEXIBLE 2-DOF STEERING MODEL OF MULTI-AXLE HEAVY-DUTY VEHICLE

    Institute of Scientific and Technical Information of China (English)

    Yang Bo; Wang Xuelin; Hu Yujin; Li Chenggang

    2004-01-01

    A flexible two degrees of freedom (2-DOF) steering model of multi-axle vehicle (MAV) is presented with considering the effect of frame flexibility based on the classic 2-DOF model. A method to calculate the frame flexibility is derived by using three moments equation. The steering stability of MAV is analyzed. The steering performance of MAV is also researched in frequency domain. Simulation results show that the dynamic effects of flexible model are more severe than rigid model and the flexible effect of frame will weaken the steering stability of MAV. Different disposals of steering axles lead to different steering characteristics of MAV. The in-phase steering mode improves the steering characteristics and stability at high speed. The anti-phase steering mode increases the steering mobility at low vehicle speed.

  7. Potentiation of carbon tetrachloride hepatotoxicity by pentosan polysulfate in rats

    Directory of Open Access Journals (Sweden)

    Zim M.C.A.

    2002-01-01

    Full Text Available Few data are available in the literature regarding the effect of pentosan polysulfate (PPS on normal and fibrotic rat livers. In addition, the combination of PPS and carbon tetrachloride (CCl4 has not been studied so far. The objective of this study was to assess the effect of PPS on rat livers treated or not with CCl4 for the induction of liver fibrosis. The study consisted of four stages: 1 hepatic fibrosis induction with CCl4 (N = 36 rats; 2 evaluation of the effect of PPS on CCl4-induced hepatic fibrosis (N = 36 rats; 3 evaluation of the effect of higher doses of PPS in combination with CCl4 (N = 50 rats; 4 evaluation of the presence of an enzymatic inductor effect by PPS (N = 18 rats using the sodium pentobarbital test which indirectly evaluates hepatic microsomal enzyme activity in vivo. Adult (60 to 70 days male Wistar rats weighing 180 to 220 g were used. All animals receiving 0.5 ml 8% CCl4 (N = 36 developed hepatic fibrosis, and after 8 weeks they also developed cirrhosis. No delay or prevention of hepatic fibrosis was observed with the administration of 5 mg/kg PPS (N = 8 and 1 mg/kg PPS (N = 8 1 h after the administration of CCl4, but the increased hepatotoxicity resulting from the combination of the two substances caused massive hepatic necrosis in most rats (N = 45. PPS (40 mg/kg alone caused hepatic congestion only after 8 weeks, but massive hepatic necrosis was again observed in association with 0.5 ml CCl4 after 1 to 4 weeks of treatment. Unexpectedly, sleeping time increased with time of PPS administration (1, 2, or 3 weeks. This suggests that PPS does not function as an activator of the hepatic microsomal enzymatic system. Further studies are necessary in order to clarify the unexpected increase in hepatotoxicity caused by the combination of CCl4 and high doses of PPS, which results in massive hepatic necrosis.

  8. Potentiation of carbon tetrachloride hepatotoxicity by pentosan polysulfate in rats.

    Science.gov (United States)

    Zim, M C A; Silveira, T R; Schwartsmann, G; Cerski, T; Motta, A

    2002-11-01

    Few data are available in the literature regarding the effect of pentosan polysulfate (PPS) on normal and fibrotic rat livers. In addition, the combination of PPS and carbon tetrachloride (CCl4) has not been studied so far. The objective of this study was to assess the effect of PPS on rat livers treated or not with CCl4 for the induction of liver fibrosis. The study consisted of four stages: 1) hepatic fibrosis induction with CCl4 (N = 36 rats); 2) evaluation of the effect of PPS on CCl4-induced hepatic fibrosis (N = 36 rats); 3) evaluation of the effect of higher doses of PPS in combination with CCl4 (N = 50 rats); 4) evaluation of the presence of an enzymatic inductor effect by PPS (N = 18 rats) using the sodium pentobarbital test which indirectly evaluates hepatic microsomal enzyme activity in vivo. Adult (60 to 70 days) male Wistar rats weighing 180 to 220 g were used. All animals receiving 0.5 ml 8% CCl4 (N = 36) developed hepatic fibrosis, and after 8 weeks they also developed cirrhosis. No delay or prevention of hepatic fibrosis was observed with the administration of 5 mg/kg PPS (N = 8) and 1 mg/kg PPS (N = 8) 1 h after the administration of CCl4, but the increased hepatotoxicity resulting from the combination of the two substances caused massive hepatic necrosis in most rats (N = 45). PPS (40 mg/kg) alone caused hepatic congestion only after 8 weeks, but massive hepatic necrosis was again observed in association with 0.5 ml CCl4 after 1 to 4 weeks of treatment. Unexpectedly, sleeping time increased with time of PPS administration (1, 2, or 3 weeks). This suggests that PPS does not function as an activator of the hepatic microsomal enzymatic system. Further studies are necessary in order to clarify the unexpected increase in hepatotoxicity caused by the combination of CCl4 and high doses of PPS, which results in massive hepatic necrosis.

  9. Identification of a metabolic biomarker panel in rats for prediction of acute and idiosyncratic hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Jinchun Sun

    2014-07-01

    Full Text Available It has been estimated that 10% of acute liver failure is due to “idiosyncratic hepatotoxicity”. The inability to identify such compounds with classical preclinical markers of hepatotoxicity has driven the need to discover a mechanism-based biomarker panel for hepatotoxicity. Seven compounds were included in this study: two overt hepatotoxicants (acetaminophen and carbon tetrachloride, two idiosyncratic hepatotoxicants (felbamate and dantrolene, and three non-hepatotoxicants (meloxicam, penicillin and metformin. Male Sprague–Dawley rats were orally gavaged with a single dose of vehicle, low dose or high dose of the compounds. At 6 h and 24 h post-dosing, blood was collected for metabolomics and clinical chemistry analyses, while organs were collected for histopathology analysis. Forty-one metabolites from previous hepatotoxicity studies were semi-quantified and were used to build models to predict hepatotoxicity. The selected metabolites were involved in various pathways, which have been noted to be linked to the underlying mechanisms of hepatotoxicity. PLS models based on all 41 metabolite or smaller subsets of 6 (6 h, 7 (24 h and 20 (6 h and 24 h metabolites resulted in models with an accuracy of at least 97.4% for the hold-out test set and 100% for training sets. When applied to the external test sets, the PLS models predicted that 1 of 9 rats at both 6 h and 24 h treated with idiosyncratic liver toxicants was exposed to a hepatotoxic chemical. In conclusion, the biomarker panel might provide information that along with other endpoint data (e.g., transcriptomics and proteomics may diagnose acute and idiosyncratic hepatotoxicity in a clinical setting.

  10. Early prediction of thiopurine-induced hepatotoxicity in inflammatory bowel disease.

    Science.gov (United States)

    Wong, D R; Coenen, M J H; Derijks, L J J; Vermeulen, S H; van Marrewijk, C J; Klungel, O H; Scheffer, H; Franke, B; Guchelaar, H-J; de Jong, D J; Engels, L G J B; Verbeek, A L M; Hooymans, P M

    2017-02-01

    Hepatotoxicity, gastrointestinal complaints and general malaise are common limiting adverse reactions of azathioprine and mercaptopurine in IBD patients, often related to high steady-state 6-methylmercaptopurine ribonucleotide (6-MMPR) metabolite concentrations. To determine the predictive value of 6-MMPR concentrations 1 week after treatment initiation (T1) for the development of these adverse reactions, especially hepatotoxicity, during the first 20 weeks of treatment. The cohort study consisted of the first 270 IBD patients starting thiopurine treatment as part of the Dutch randomised-controlled trial evaluating pre-treatment thiopurine S-methyltransferase genotype testing (ClinicalTrials.gov NCT00521950). Blood samples for metabolite assessment were collected at T1. Hepatotoxicity was defined by alanine aminotransaminase elevations >2 times the upper normal limit or a ratio of alanine aminotransaminase/alkaline phosphatase ≥5. Forty-seven patients (17%) presented hepatotoxicity during the first 20 weeks of thiopurine treatment. A T1 6-MMPR threshold of 3615 pmol/8 × 10(8) erythrocytes was defined. Analysis of patients on stable thiopurine dose (n = 174) showed that those exceeding the 6-MMPR threshold were at increased risk of hepatotoxicity: OR = 3.8 (95% CI: 1.8-8.0). Age, male gender and BMI were significant determinants. A predictive algorithm was developed based on these determinants and the 6-MMPR threshold to assess hepatotoxicity risk [AUC = 0.83 (95% CI: 0.75-0.91)]. 6-MMPR concentrations above the threshold also correlated with gastrointestinal complaints: OR = 2.4 (95% CI: 1.4-4.3), and general malaise: OR = 2.0 (95% CI: 1.1-3.7). In more than 80% of patients, thiopurine-induced hepatotoxicity could be explained by elevated T1 6-MMPR concentrations and the independent risk factors age, gender and BMI, allowing personalised thiopurine treatment in IBD to prevent early failure. © 2016 John Wiley & Sons Ltd.

  11. How Insect Flight Steering Muscles Work: e1001822

    National Research Council Canada - National Science Library

    Hedenstrom, Anders

    2014-01-01

    .... The hinge consists of several hardened and articulated cuticle elements called sclerites. This articulation is controlled by a great number of small steering muscles, whose function has been studied by means of kinematics and muscle activity...

  12. FLOW CHARACTERISTICS FORMATION OF POWER STEERING WITH ROTARY DISTRIBUTOR

    Directory of Open Access Journals (Sweden)

    V. Mikhailov

    2012-01-01

    Full Text Available In order to obtain an adequate mathematical model of vehicle hydro-mechanical steering which is  equipped with a steering mechanism combined with power steering and a rotary distributor  it is initially   necessary to get current consumption values in the units of hydraulic scheme which are determined by dynamic changes of flow passages of pressure and drain circuits according to turning angle of the distributor. Such characteristics are usually determined experimentally.The paper  proposes  a sequence which is recommended for determination of consumption characteristics which is formed with due account of multi-directional kinematic perturbations, mechanical clearance, possible emergence of hydraulic backlash and desired throttling law. The factors account makes it possible to obtain an acceptable mathematical analogue of a hydro-mechanical steering for execution of robust investigations. 

  13. CCCT - NCTN Steering Committees - Pediatric and Adolescent Tumor

    Science.gov (United States)

    The Pediatric and Adolescent Solid Tumor Steering Committee addresses the design, prioritization and evaluation of concepts for large phase 2 and phase 3 clinical trials in extracranial solid tumors of children and youth.

  14. Current focusing and steering: modeling, physiology, and psychophysics.

    Science.gov (United States)

    Bonham, Ben H; Litvak, Leonid M

    2008-08-01

    Current steering and current focusing are stimulation techniques designed to increase the number of distinct perceptual channels available to cochlear implant (CI) users by adjusting currents applied simultaneously to multiple CI electrodes. Previous studies exploring current steering and current focusing stimulation strategies are reviewed, including results of research using computational models, animal neurophysiology, and human psychophysics. Preliminary results of additional neurophysiological and human psychophysical studies are presented that demonstrate the success of current steering strategies in stimulating auditory nerve regions lying between physical CI electrodes, as well as current focusing strategies that excite regions narrower than those stimulated using monopolar configurations. These results are interpreted in the context of perception and speech reception by CI users. Disparities between results of physiological and psychophysical studies are discussed. The differences in stimulation used for physiological and psychophysical studies are hypothesized to contribute to these disparities. Finally, application of current steering and focusing strategies to other types of auditory prostheses is also discussed.

  15. A control theoretic model of driver steering behavior

    Science.gov (United States)

    Donges, E.

    1977-01-01

    A quantitative description of driver steering behavior such as a mathematical model is presented. The steering task is divided into two levels: (1) the guidance level involving the perception of the instantaneous and future course of the forcing function provided by the forward view of the road, and the response to it in an anticipatory open-loop control mode; (2) the stabilization level whereby any occuring deviations from the forcing function are compensated for in a closed-loop control mode. This concept of the duality of the driver's steering activity led to a newly developed two-level model of driver steering behavior. Its parameters are identified on the basis of data measured in driving simulator experiments. The parameter estimates of both levels of the model show significant dependence on the experimental situation which can be characterized by variables such as vehicle speed and desired path curvature.

  16. Steering of Solar Sails Using Optical Lift Force Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This study seeks to look beyond the use of radiation pressure for thrust, and to explore a means of solar navigation whereby a solar craft would be steered by use...

  17. Improvement for the steering performance of liquid crystal phased array

    Institute of Scientific and Technical Information of China (English)

    SONG Yan; KONG Ling-jiang; CHEN Jun; ZHU Ying; YANG Jian-yu

    2009-01-01

    Optical phased array technology is introduced and the steering performances of liquid crystal phased array are discussed, several factors affecting the beam steering performances arc analyzed completely, also simple models for some typical factors are developed. Then, a new method based on iterating and modifying the output phase pattern of liquid crystal phase shifters is proposed. Using this method, the modified voltages applied on electrodes of liquid crystal phase shifters can be obtained, after applying the voltages, the influence of factors can be compensated to some extent; the steering angle accu-racy and efficiency with liquid crystal phased array can be improved. Through the simulation for the angle range from 0° to -1°, the error of steering angle can be reduced three orders of magnitude, and the efficiency can be increased almost 30% after several iterations.

  18. An improved constrained steering law for SGCMGs with DPC

    Institute of Scientific and Technical Information of China (English)

    Lei Jin; Shijie Xu

    2009-01-01

    An improved constrained (IC) steering law for single girnbal control moment gyros (SGCMGs) with deformed pyramid configuration (DPC) is proposed. First of all, the original system with five pyramid configuration (FPC) whose two adjacent gyros are in failure state is reconfigured as a degraded system with DPC. Then, the singular angular momentum hypersurfaces of the original and the degraded systems are plotted via the singular angular momentum equation of SGCMGs. Based on singular surfaces, the differences between FPC and DPC in singularity and momentum envelope are obtained directly, which provide an important reference for steering law design of DPC. Finally, an IC steering law is designed and applied to DPC. The simulation results demonstrate that the IC steering law has advantages in simplicity of calculation, avoidance of singularity and exactness of output torque, which endow the degraded system with fine controllability in a restricted workspace.

  19. Electrical power assisted steering for EVs and HEVs

    Institute of Scientific and Technical Information of China (English)

    Ma Haibo; Yang Ying

    2011-01-01

    Electrical power assisted steering (EPAS) is one of the key components, especially for electrical vehicle. It has attracted much attention for their advantages with respect to improved fuel economy and has been widely adopted as automotive power-steering equipment in recent years. EPS (electrical power steering) controllers contain MCU (microprocessor control unit) to implement the complex control algorithms. EPS control strategy development is the core technology of the whole system. To achieve the better performance of driving, both mechanical structures and electrical structures are totally designed as a whole. Model-based development is recommended to software design. There are several trends about EPS' future, such as high power EPS development, high voltage EPS development and steering-bywire technology.

  20. 46 CFR 58.25-70 - Steering-gear control systems.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Steering-gear control systems. 58.25-70 Section 58.25-70... MACHINERY AND RELATED SYSTEMS Steering Gear § 58.25-70 Steering-gear control systems. (a) Each power-driven steering-gear system must be provided with at least one steering-gear control system. (b) The main...

  1. Optimization Under Uncertainty for Wake Steering Strategies: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Quick, Julian [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Annoni, Jennifer [National Renewable Energy Laboratory (NREL), Golden, CO (United States); King, Ryan N [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Dykes, Katherine L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Fleming, Paul A [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ning, Andrew [Brigham Young University

    2017-05-01

    Wind turbines in a wind power plant experience significant power losses because of aerodynamic interactions between turbines. One control strategy to reduce these losses is known as 'wake steering,' in which upstream turbines are yawed to direct wakes away from downstream turbines. Previous wake steering research has assumed perfect information, however, there can be significant uncertainty in many aspects of the problem, including wind inflow and various turbine measurements. Uncertainty has significant implications for performance of wake steering strategies. Consequently, the authors formulate and solve an optimization under uncertainty (OUU) problem for finding optimal wake steering strategies in the presence of yaw angle uncertainty. The OUU wake steering strategy is demonstrated on a two-turbine test case and on the utility-scale, offshore Princess Amalia Wind Farm. When we accounted for yaw angle uncertainty in the Princess Amalia Wind Farm case, inflow-direction-specific OUU solutions produced between 0% and 1.4% more power than the deterministically optimized steering strategies, resulting in an overall annual average improvement of 0.2%. More importantly, the deterministic optimization is expected to perform worse and with more downside risk than the OUU result when realistic uncertainty is taken into account. Additionally, the OUU solution produces fewer extreme yaw situations than the deterministic solution.

  2. Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity.

    Science.gov (United States)

    Wang, Kun-Peng; Bai, Yu; Wang, Jian; Zhang, Jin-Zhen

    2014-05-01

    Schisandra chinensis is a well-known traditional medicinal herb. Acetaminophen is a commonly used over-the-counter analgesic and overdose of acetaminophen was the most frequent cause of acute liver failure. However, no studies have demonstrated the role of Schisandra chinensis in acetaminophen-induced acute liver failure to the best of our knowledge. In this study, an acute liver injury model was established in mice using acetaminophen. The protective role of Schisandra chinensis was detected by histopathological analysis, and measurement of the serum transaminase levels and hepatic Cyp activity levels in the mouse model. Subsequently, hepatocytes were isolated from the livers of the mouse model. The cell cycle, apoptosis, mitochondrial membrane potential and reactive oxygen species were determined using flow cytometry. Cell proliferation and 26S proteasome activity were determined using spectrophotometry. Schisandra chinensis was found to resist acetaminophen-induced hepatotoxicity by protecting mitochondria and lysosomes and inhibiting the phosphor-c-Jun N-terminal kinase signaling pathway. These findings provide a novel application of Schisandra chinensis against acetaminophen-induced acute liver failure.

  3. Effects of erdosteine on acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Kuvandik, Guven; Duru, Mehmet; Nacar, Ahmet; Yonden, Zafer; Helvaci, Rami; Koc, Ahmet; Kozlu, Tolunay; Kaya, Hasan; Sogüt, Sadik

    2008-07-01

    We investigated the effects of erdosteine on acetaminophen (APAP)-induced hepatotoxicity in rats. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), AST (aspartate aminotransferase), and ALT (alanine transaminase) activities, and malonyldialdehyde (MDA) and nitric oxide levels as oxidant/antioxidant biochemical parameters were investigated with light microscopic evaluation in adult female Wistar Albino rats. APAP administration produced a decrease in hepatic SOD, CAT, and GSH-Px activities, and coadministration of erdosteine (150 and 300 mg/kg) resulted in increases in the activities. MDA and NO levels increased in the APAP group, and erdosteine treatments prevented these increases. Significant elevations in serum AST and ALT levels were observed in the APAP group, and when erdosteine and APAP were coadministered, their serum levels were close to those in the control group. Light microscopic evaluation of livers showed that there were remarkable centrilobular (zone III) hepatic necrosis and mild to moderate sinusoidal congestion in the APAP group, whereas in the erdosteine group, cellular necrosis was minimal and the hepatocytes maintained a better morphology when compared to the APAP group. Erdosteine prevented APAP-induced liver injury and toxic side effects probably through the antioxidant and radical scavenging effects of erdosteine.

  4. Acetaminophen hepatotoxicity: studies on the mechanism of cysteamine protection

    Energy Technology Data Exchange (ETDEWEB)

    Miller, M.G.; Jollow, D.J.

    1986-03-30

    Inhibition of the cytochrome P-450-dependent formation of the acetaminophen-reactive metabolite was investigated as a possible mechanism for cysteamine protection against acetaminophen hepatotoxicity. Studies in isolated hamster hepatocytes indicated that cysteamine competitively inhibited the cytochrome P-450 enzyme system as represented by formation of the acetaminophen-glutathione conjugate. However, cysteamine was not a potent inhibitor of glutathione conjugate formation (Ki = 1.17 mM). Cysteamine also weakly inhibited the glucuronidation of acetaminophen (Ki = 2.44 mM). In vivo studies were in agreement with the results obtained in isolated hepatocytes; cysteamine moderately inhibited both glucuronidation and the cytochrome P-450-dependent formation of acetaminophen mercapturate. The overall elimination rate constant (beta) for acetaminophen was correspondingly decreased. Since cysteamine decreased both beta and the apparent rate constant for mercapturate formation (K'MA), the proportion of the dose of acetaminophen which is converted to the toxic metabolite (K'MA/beta) was not significantly decreased in the presence of cysteamine. Apparently, cysteamine does inhibit the cytochrome P-450-dependent formation of the acetaminophen-reactive metabolite, but this effect is not sufficient to explain antidotal protection.

  5. The ATLAS High Level Trigger Steering

    CERN Document Server

    Berger, N; Eifert, T; Fischer, G; George, S; Haller, J; Höcker, A; Masik, J; Zur Nedden, M; Pérez-Réale, V; Risler, C; Schiavi, C; Stelzer, J; Wu, X; International Conference on Computing in High Energy and Nuclear Physics

    2008-01-01

    The High Level Trigger (HLT) of the ATLAS experiment at the Large Hadron Collider receives events which pass the LVL1 trigger at ~75 kHz and has to reduce the rate to ~200 Hz while retaining the most interesting physics. It is a software trigger and performs the reduction in two stages: the LVL2 trigger and the Event Filter (EF). At the heart of the HLT is the Steering software. To minimise processing time and data transfers it implements the novel event selection strategies of seeded, step-wise reconstruction and early rejection. The HLT is seeded by regions of interest identified at LVL1. These and the static configuration determine which algorithms are run to reconstruct event data and test the validity of trigger signatures. The decision to reject the event or continue is based on the valid signatures, taking into account pre-scale and pass-through. After the EF, event classification tags are assigned for streaming purposes. Several powerful new features for commissioning and operation have been added: co...

  6. Role of metabolism in 1-bromopropane-induced hepatotoxicity in mice.

    Science.gov (United States)

    Lee, Sang Kyu; Kang, Mi Jeong; Jeon, Tae Won; Ha, Hyun Woo; Yoo, Jin Woo; Ko, Gyu Sub; Kang, Wonku; Jeong, Hye Gwang; Lyoo, Won Seok; Jeong, Tae Cheon

    2010-01-01

    A possible role of metabolism in 1-bromopropane (1-BP)-induced hepatotoxicity was investigated in male ICR mice. The depletion of glutathione (GSH) by formation of GSH conjugates was associated with increased hepatotoxicity in 1-BP-treated mice. The formation of S-propyl and 2-hydroxypropyl GSH conjugates were identified in the liver following 1-BP treatment. In addition, the formation of reactive metabolites of 1-BP by certain cytochrome P-450 (CYP) may be involved in 1-BP-induced hepatotoxicity. The decreased content of hepatic GSH produced by 1-BP was associated not only with increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but also with elevated levels of hepatic thiobarbituric acid-reactive substance (TBARS) in mice where metabolic enzymes were induced by pretreatment with phenobarbital. In addition, the hepatotoxicity induced by 1-BP was prevented by pretreatment with SKF-525A. Taken together, the formation of reactive metabolites by CYP and depletion of GSH may play important roles in hepatotoxicity induced by 1-BP.

  7. Sequence motifs associated with hepatotoxicity of locked nucleic acid--modified antisense oligonucleotides.

    Science.gov (United States)

    Burdick, Andrew D; Sciabola, Simone; Mantena, Srinivasa R; Hollingshead, Brett D; Stanton, Robert; Warneke, James A; Zeng, Ming; Martsen, Elena; Medvedev, Alexander; Makarov, Sergei S; Reed, Lori A; Davis, John W; Whiteley, Laurence O

    2014-04-01

    Fully phosphorothioate antisense oligonucleotides (ASOs) with locked nucleic acids (LNAs) improve target affinity, RNase H activation and stability. LNA modified ASOs can cause hepatotoxicity, and this risk is currently not fully understood. In vitro cytotoxicity screens have not been reliable predictors of hepatic toxicity in non-clinical testing; however, mice are considered to be a sensitive test species. To better understand the relationship between nucleotide sequence and hepatotoxicity, a structure-toxicity analysis was performed using results from 2 week repeated-dose-tolerability studies in mice administered LNA-modified ASOs. ASOs targeting human Apolipoprotien C3 (Apoc3), CREB (cAMP Response Element Binding Protein) Regulated Transcription Coactivator 2 (Crtc2) or Glucocorticoid Receptor (GR, NR3C1) were classified based upon the presence or absence of hepatotoxicity in mice. From these data, a random-decision forest-classification model generated from nucleotide sequence descriptors identified two trinucleotide motifs (TCC and TGC) that were present only in hepatotoxic sequences. We found that motif containing sequences were more likely to bind to hepatocellular proteins in vitro and increased P53 and NRF2 stress pathway activity in vivo. These results suggest in silico approaches can be utilized to establish structure-toxicity relationships of LNA-modified ASOs and decrease the likelihood of hepatotoxicity in preclinical testing.

  8. Sequence motifs associated with hepatotoxicity of locked nucleic acid—modified antisense oligonucleotides

    Science.gov (United States)

    Burdick, Andrew D.; Sciabola, Simone; Mantena, Srinivasa R.; Hollingshead, Brett D.; Stanton, Robert; Warneke, James A.; Zeng, Ming; Martsen, Elena; Medvedev, Alexander; Makarov, Sergei S.; Reed, Lori A.; Davis, John W.; Whiteley, Laurence O.

    2014-01-01

    Fully phosphorothioate antisense oligonucleotides (ASOs) with locked nucleic acids (LNAs) improve target affinity, RNase H activation and stability. LNA modified ASOs can cause hepatotoxicity, and this risk is currently not fully understood. In vitro cytotoxicity screens have not been reliable predictors of hepatic toxicity in non-clinical testing; however, mice are considered to be a sensitive test species. To better understand the relationship between nucleotide sequence and hepatotoxicity, a structure–toxicity analysis was performed using results from 2 week repeated-dose-tolerability studies in mice administered LNA-modified ASOs. ASOs targeting human Apolipoprotien C3 (Apoc3), CREB (cAMP Response Element Binding Protein) Regulated Transcription Coactivator 2 (Crtc2) or Glucocorticoid Receptor (GR, NR3C1) were classified based upon the presence or absence of hepatotoxicity in mice. From these data, a random-decision forest-classification model generated from nucleotide sequence descriptors identified two trinucleotide motifs (TCC and TGC) that were present only in hepatotoxic sequences. We found that motif containing sequences were more likely to bind to hepatocellular proteins in vitro and increased P53 and NRF2 stress pathway activity in vivo. These results suggest in silico approaches can be utilized to establish structure–toxicity relationships of LNA-modified ASOs and decrease the likelihood of hepatotoxicity in preclinical testing. PMID:24550163

  9. Integrated analysis of transcriptomics and metabonomics profiles in aflatoxin B1-induced hepatotoxicity in rat.

    Science.gov (United States)

    Lu, Xiaoyan; Hu, Bin; Shao, Li; Tian, Yu; Jin, Tingting; Jin, Yachao; Ji, Shen; Fan, Xiaohui

    2013-05-01

    The aim of this work was to identify mechanisms and potential biomarkers for predicting the development and progression of aflatoxin B1 (AFB1)-induced acute hepatotoxicity. In this study, microarray analysis and metabolites profiles were used to identify shifts in gene expression and metabolite levels associated with the affected physiological processes of rats treated with AFB1. Histopathological examinations and serum biochemical analysis were simultaneously performed; the results indicated that hepatotoxicity occurred in higher dosage groups. However, gene expression analysis and metabolite profiles are more sensitive than general toxicity studies for detecting AFB1-induced acute hepatotoxicity as the patterns of low-dose AFB1-treated rats in these two technique platforms were more similar to the rats in higher dosage groups than to the control rats. Integrated analysis of the results from general toxicity studies, transcriptomics and metabonomics profiles suggested that p53 signaling pathway induced by oxidative damage was the crucial step in AFB1-induced acute hepatotoxicity, whereas gluconeogenesis and lipid metabolism disorder were found to be the major metabolic effects after acute AFB1 exposure. The genes and metabolites significantly affected in common in rat liver or serum of three doses AFB1 treatments served as potential biomarkers for detecting AFB1-induced acute hepatotoxicity.

  10. Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Andreas Buness

    Full Text Available Early and accurate pre-clinical and clinical biomarkers of hepatotoxicity facilitate the drug development process and the safety monitoring in clinical studies. We selected eight known model compounds to be administered to male Wistar rats to identify biomarkers of drug induced liver injury (DILI using transcriptomics, metabolite profiling (metabolomics and conventional endpoints. We specifically explored early biomarkers in serum and liver tissue associated with histopathologically evident acute hepatotoxicity. A tailored data analysis strategy was implemented to better differentiate animals with no treatment-related findings in the liver from animals showing evident hepatotoxicity as assessed by histopathological analysis. From the large number of assessed parameters, our data analysis strategy allowed us to identify five metabolites in serum and five in liver tissue, 58 transcripts in liver tissue and seven clinical chemistry markers in serum that were significantly associated with acute hepatotoxicity. The identified markers comprised metabolites such as taurocholic acid and putrescine (measured as sum parameter together with agmatine, classical clinical chemistry markers like AST (aspartate aminotransferase, ALT (alanine aminotransferase, and bilirubin, as well as gene transcripts like Igfbp1 (insulin-like growth factor-binding protein 1 and Egr1 (early growth response protein 1. The response pattern of the identified biomarkers was concordant across all types of parameters and sample matrices. Our results suggest that a combination of several of these biomarkers could significantly improve the robustness and accuracy of an early diagnosis of hepatotoxicity.

  11. Gene expression profiling and pathway analysis of hepatotoxicity induced by triptolide in Wistar rats.

    Science.gov (United States)

    Wang, Jiaying; Jiang, Zhenzhou; Ji, Jinzi; Wang, Xinzhi; Wang, Tao; Zhang, Yun; Tai, Ting; Chen, Mi; Sun, Lixin; Li, Xia; Zhang, Luyong

    2013-08-01

    Triptolide (TP), a major component of TWHF, is widely used to treat rheumatoid arthritis, systemic lupus erythematosus, nephritis and leprosy. However, its clinical use is limited by hepatotoxicity. To further elucidate the underlying mechanism of its hepatotoxic effects, hepatic gene expression profiles were analyzed. TP (1000 and 300 μg/kg) was orally administered to Wistar rats for 14 days. Current study indicated that female rats were more sensitive to TP-induced hepatotoxicity than males. Genome-wide microarray analyses identified 3329 differentially expressed genes in liver of female rats. Analyses of these genes identified over-represented functions associated with insulin signaling pathway, glucose metabolism, cell cycle, oxidative stress and apoptosis, which were consistent with the results of significant increase of Caspase-3 activity and reduction of serum glucose, GSH/GSSG ratio, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities, liver glycogen. In addition, it was observed for the first time that glucocorticoids and IGF1 might get involved in TP-induced hepatotoxicity. These data suggest that TP treatment could alter the hepatic redox status, reduce serum glucose and induce hepatocyte apoptosis, consistent with the differential expression of genes involved in insulin signaling pathway, glucose metabolism pathway and cell stress pathway, all of which might contribute to the overall TP-induced hepatotoxicity.

  12. Treatment of Non-Small-Cell Lung Cancer with Erlotinib following Gefitinib-Induced Hepatotoxicity: Review of 8 Clinical Cases

    Directory of Open Access Journals (Sweden)

    Yukihiro Yano

    2012-01-01

    Full Text Available Objective. Gefitinib often induces liver damage. A few reports have described that the subsequent administration of erlotinib was associated with less hepatotoxicity, but the safety and efficacy of this treatment are still not fully investigated. Therefore, we evaluated retrospectively the patients with erlotinib following gefitinib-induced hepatotoxicity. Methods and Patients. We retrospectively reviewed the medical records between December 2007 and March 2010. The patients were evaluated including the following information: age, gender, histology of lung cancer, performance status, smoking status, epidermal growth factor receptor (EGFR mutation status, liver metastasis, viral hepatitis, alcoholic liver injury, clinical response, and hepatotoxicity due to EGFR tyrosine kinase inhibitors. Results. We identified 8 patients with erlotinib following gefitinib-induced hepatotoxicity. All achieved disease control by gefitinib. Hepatotoxicity was grades 2 and 3 in 3 and 5 patients, respectively. The median duration of treatment with gefitinib was 112.5 days and the median time to gefitinib-induced hepatotoxicity was 51.5 days. The median duration of treatment with erlotinib was 171.5 days. Grade 1 and 2 erlotinib-induced hepatotoxicity was observed in 2 and 1 patient, respectively. Conclusions. Erlotinib administration with careful monitoring is thought to be a good alternative strategy for patients who respond well to gefitinib treatment but experience hepatotoxicity.

  13. BEAMLINE-CONTROLLED STEERING OF SOURCE-POINT ANGLE AT THE ADVANCED PHOTON SOURCE

    Energy Technology Data Exchange (ETDEWEB)

    Emery, L.; Fystro, G.; Shang, H.; Smith, M.

    2017-06-25

    An EPICS-based steering software system has been implemented for beamline personnel to directly steer the angle of the synchrotron radiation sources at the Advanced Photon Source. A script running on a workstation monitors "start steering" beamline EPICS records, and effects a steering given by the value of the "angle request" EPICS record. The new system makes the steering process much faster than before, although the older steering protocols can still be used. The robustness features of the original steering remain. Feedback messages are provided to the beamlines and the accelerator operators. Underpinning this new steering protocol is the recent refinement of the global orbit feedback process whereby feedforward of dipole corrector set points and orbit set points are used to create a local steering bump in a rapid and seamless way.

  14. Croton zehntneri Essential oil prevents acetaminophen-induced acute hepatotoxicity in mice

    Directory of Open Access Journals (Sweden)

    Maria Goretti R. Queiroz

    2008-10-01

    Full Text Available Hepatoprotective activity of Croton zehntneri Pax & Hoffman (Euphorbiaceae leaf essential oil (EOCz was evaluated against single dose of acetaminophen-induced (500 mg/kg, p.o. acute hepatotoxicity in mice. EOCz significantly protected the hepatotoxicity as evident from the activities of serum glutamate pyruvate transaminase (GPT, serum glutamate oxaloacetate transaminase (GOT activities, that were significantly (p<0.01 elevated in the acetaminophen alone treated animals. Histopathological examinations of liver tissue corroborated well with the biochemical changes. Hepatic steatosis, hydropic degeneration and necrosis were observed in the acetaminophen treated group, while these were completely absent in the standard and EOCz treated groups. In conclusion, these data suggest that the Croton zehntneri essential oil can prevent hepatic injuries from acetaminophen-induced hepatotoxicity in mice.

  15. Backwards planning approach for rapid attitude maneuvers steering

    Science.gov (United States)

    Verbin, D.

    Remote sensing satellites are often built with payloads that do not include line of sight steering mechanisms. In cases, when frequent line of sight retargeting is required, there is a need for efficient actuators and control schemes that would support rapid attitude manoeuvring together with adequate pointing accuracy and stability between the manoeuvres. Within this frame, this research develops the Backwards Planning approach as one of the possible control methods for rapid manoeuvring. The method is based on state feedback and combines time efficient together with straight forward computation flow. Novel efficient methods to execute the Backwards Planning Control in the 3D attitude space are proposed here. The methods refer both for the first saturated control phase of the manoeuvre and for the last braking phase. The actuators used for the spacecraft control in this research are either Reaction Wheels (RWs) or Single Gimbal Control Moments Gyros (SGCMGs) or both of them together. The advantage of the SGCMG is in rapid rotational manoeuvring, but their application for high quality pointing requires very accurate gimbal mechanisms. On the other hand, RWs are usually more suitable for accurate pointing, but their torque to power performance is inferior in manoeuvring. It is shown that the coordination of SGCMGs and RWs together enables to draw more performance from the SGCMGs in terms of agility and meet the pointing requirements between manoeuvres where only the RWs are used. Novel SGCMG steering laws are suggested as well. While the steering laws determine the required angular rate for each gimbal, most steering laws are defined in the angular momentum domain and output the gimbals angular rates to produce a given required torque or angular momentum increment. This research however, practices a novel steering law in the gimbal angles domain. While both steering laws turn to be dynamically equivalent for small control signals, as in the steady state, it is shown

  16. Resistance to acetaminophen-induced hepatotoxicity in glutathione S-transferase Mu 1-null mice.

    Science.gov (United States)

    Arakawa, Shingo; Maejima, Takanori; Fujimoto, Kazunori; Yamaguchi, Takashi; Yagi, Masae; Sugiura, Tomomi; Atsumi, Ryo; Yamazoe, Yasushi

    2012-01-01

    We investigated the role of glutathione S-transferases Mu 1 (GSTM1) in acetaminophen (APAP)-induced hepatotoxicity using Gstm1-null mice. A single oral administration of APAP resulted in a marked increase in plasma alanine aminotransferase accompanied by hepatocyte necrosis 24 hr after administration in wild-type mice, but its magnitude was unexpectedly attenuated in Gstm1-null mice. Therefore, it is suggested that Gstm1-null mice are resistant to APAP-induced hepatotoxicity. To examine the mechanism of this resistance in Gstm1-null mice, we measured phosphorylation of c-jun N-terminal kinase (JNK), which mediates the signal of APAP-induced hepatocyte necrosis, by Western blot analysis 2 and 6 hr after APAP administration. A marked increase in phosphorylated JNK was observed in wild-type mice, but the increase was markedly suppressed in Gstm1-null mice. Therefore, it is suggested that suppressed phosphorylation of JNK may be a main mechanism of the resistance to APAP-induced hepatotoxicity in Gstm1-null mice, although other possibilities of the mechanism cannot be eliminated. Additionally, phosphorylation of glycogen synthase kinase-3β and mitogen-activated protein kinase kinase 4, which are upstream kinases of JNK in APAP-induced hepatotoxicity, were also suppressed in Gstm1-null mice. A decrease in liver total glutathione 2 hr after APAP administration, which is an indicator for exposure to N-acetyl-p-benzoquinoneimine, the reactive metabolite of APAP, were similar in wild-type and Gstm1-null mice. In conclusion, Gstm1-null mice are considered to be resistant to APAP-induced hepatotoxicity perhaps by the suppression of JNK phosphorylation. This study indicates the novel role of GSTM1 as a factor mediating the cellular signal for APAP-induced hepatotoxicity.

  17. Dexamethasone Pretreatment Alleviates Isoniazid/Lipopolysaccharide Hepatotoxicity: Inhibition of Inflammatory and Oxidative Stress

    Science.gov (United States)

    Hassan, Hozeifa M.; Guo, Hongli; Yousef, Bashir A.; Ping-Ping, Ding; Zhang, Luyong; Jiang, Zhenzhou

    2017-01-01

    Isoniazid (INH) remains a cornerstone key constitute of the current tuberculosis management strategy, but its hepatotoxic potentiality remains a significant clinical problem. Our previous findings succeed to establish a rat model of INH hepatotoxicity employing the inflammatory stress theory in which non-injurious doses of inflammatory-mediating agent bacterial lipopolysaccharides (LPS) augmented the toxicity of INH that assist to uncover the mechanisms behind INH hepatotoxicity. Following LPS exposure, several inflammatory cells are activated and it is likely that the consequences of this activation rather than direct hepatocellular effects of LPS underlie the ability of LPS to augment toxic responses. In this study, we investigated the potential protective role of the anti-inflammatory agent dexamethasone (DEX), a potent synthetic glucocorticoid, in INH/LPS hepatotoxic rat model. DEX pre-treatment successfully eliminates the components of the inflammatory stress as shown through analysis of blood biochemistry and liver histopathology. DEX potentiated hepatic anti-oxidant mechanisms while serum and hepatic lipid profiles were reduced. However, DEX administration was not able to revoke the principal effects of cytochrome P450 2E1 (CYP2E1) in INH/LPS-induced liver damage. In conclusion, this study illustrated the DEX-preventive capabilities on INH/LPS-induced hepatotoxicity model through DEX-induced potent anti-inflammatory activity whereas the partial toxicity seen in the model could be attributed to the expression of hepatic CYP2E1. These findings potentiate the clinical applications of DEX co-administration with INH therapy in order to reduce the potential incidences of hepatotoxicity.

  18. The hepatotoxicity of multi-walled carbon nanotubes in mice

    Science.gov (United States)

    Ji, Zongfei; Zhang, Danying; Li, Ling; Shen, Xizhong; Deng, Xiaoyong; Dong, Ling; Wu, Minhong; Liu, Yuanfang

    2009-11-01

    The hepatotoxicity of two types of multi-walled carbon nanotubes (MWCNTs), acid-oxidized MWCNTs (O-MWCNTs) and Tween-80-dispersed MWCNTs (T-MWCNTs), were investigated with Kunming mice exposed to 10 and 60 mg kg-1 by intravenous injection for 15 and 60 d. Compared with the PBS group, the body-weight gain of the mice decreased and the level of total bilirubin and aspartate aminotransferase increased in the MWCNT-exposed group with a significant dose-effect relationship, while tumor necrosis factor alpha level did not show significant statistical change within 60 d. Spotty necrosis, inflammatory cell infiltration in portal region, hepatocyte mitochondria swelling and lysis were observed with a significant dose-effect relationship in the MWCNT groups. Liver damage of the T-MWCNT group was more severe than that of the O-MWCNT group according to the Roenigk classification system. Furthermore, T-MWCNTs induce slight liver oxidative damage in mice at 15 d, which was recovered at 60 d. Part of the gene expressions of mouse liver in the MWCNT groups changed compared to the PBS group, including GPCRs (G protein-coupled receptors), cholesterol biosynthesis, metabolism by cytochrome P450, natural-killer-cell-mediated cytotoxicity, TNF- α, NF-κB signaling pathway, etc. In the P450 pathway, the gene expressions of Gsta2 (down-regulated), Cyp2B19 (up-regulated) and Cyp2C50 (down-regulated) had significant changes in the MWCNT groups. These results show that a high dose of T-MWCNTs can induce hepatic toxicity in mice while O-MWCNTs seem to have less toxicity.

  19. Telmisartan ameliorates carbon tetrachloride-induced acute hepatotoxicity in rats.

    Science.gov (United States)

    Atawia, Reem T; Esmat, Ahmed; Elsherbiny, Doaa A; El-Demerdash, Ebtehal

    2017-02-01

    This study assessed the potential hepatoprotective effect of telmisartan (TLM), a selective angiotensin II type 1 (AT1 ) receptor blocker, on carbon tetrachloride (CCl4 )-induced acute hepatotoxity in rats. Intraperitoneal injection of male Wistar rats with CCl4 1 mL kg(-1) , 1:1 mixture with corn oil for 3 days increased serum alanine transaminase, aspartate transaminase, and alkaline phosphatase activities as well as total bilirubin, triglycerides and total cholesterol levels. This is in addition to the disrupted histological architecture in the CCl4 group. Rats receiving CCl4 and co-treated with TLM (3 and 10 mg kg(-1) , orally) showed ameliorated serum biochemical and histological changes almost to the control level. Nevertheless, rats treated with TLM (1 mg kg(-1) ) didn't show any significant changes compared to CCl4 intoxicated group. In addition, TLM rectified oxidative status disrupted by CCl4 intoxication. Interestingly, TLM protected against CCl4 -induced expressions of nuclear factor-κB, inducible nitric oxide synthase and cyclooxygenase-II, in a dose related manner. Moreover, TLM (3 and 10 mg kg(-1) ) significantly modified CCl4 -induced elevation in tumor necrosis factor-α and nitric oxide levels. Furthermore, TLM showed a marked decline in CD68+ cells stained areas and reduced activity of myeloperoxidase enzyme compared to CCl4 -intoxicated group. In conclusion, both doses of TLM (3 and 10 mg kg(-1) ) showed significant hepato-protective effects. However, TLM at a dose of 10 mg kg(-1) didn't show significant efficacy above 3 mg kg(-1) which is nearly equivalent to the human anti-hypertensive dose of 40 mg. Thus, may be effective in guarding against several hepatic complications due to its antioxidant and anti-inflammatory activities. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 359-370, 2017.

  20. The hepatotoxicity of multi-walled carbon nanotubes in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ji Zongfei; Zhang Danying; Shen Xizhong; Dong Ling [Department of Gastroenterology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Li Ling; Deng Xiaoyong; Wu Minhong; Liu Yuanfang, E-mail: xydeng@shu.edu.c, E-mail: dltalk@tom.co [Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444 (China)

    2009-11-04

    The hepatotoxicity of two types of multi-walled carbon nanotubes (MWCNTs), acid-oxidized MWCNTs (O-MWCNTs) and Tween-80-dispersed MWCNTs (T-MWCNTs), were investigated with Kunming mice exposed to 10 and 60 mg kg{sup -1} by intravenous injection for 15 and 60 d. Compared with the PBS group, the body-weight gain of the mice decreased and the level of total bilirubin and aspartate aminotransferase increased in the MWCNT-exposed group with a significant dose-effect relationship, while tumor necrosis factor alpha level did not show significant statistical change within 60 d. Spotty necrosis, inflammatory cell infiltration in portal region, hepatocyte mitochondria swelling and lysis were observed with a significant dose-effect relationship in the MWCNT groups. Liver damage of the T-MWCNT group was more severe than that of the O-MWCNT group according to the Roenigk classification system. Furthermore, T-MWCNTs induce slight liver oxidative damage in mice at 15 d, which was recovered at 60 d. Part of the gene expressions of mouse liver in the MWCNT groups changed compared to the PBS group, including GPCRs (G protein-coupled receptors), cholesterol biosynthesis, metabolism by cytochrome P450, natural-killer-cell-mediated cytotoxicity, TNF- {alpha}, NF-{kappa}B signaling pathway, etc. In the P450 pathway, the gene expressions of Gsta2 (down-regulated), Cyp2B19 (up-regulated) and Cyp2C50 (down-regulated) had significant changes in the MWCNT groups. These results show that a high dose of T-MWCNTs can induce hepatic toxicity in mice while O-MWCNTs seem to have less toxicity.

  1. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality

    Directory of Open Access Journals (Sweden)

    Miriam S. N. Hohmann

    2013-01-01

    Full Text Available 5-Lipoxygenase (5-LO converts arachidonic acid into leukotrienes (LTs and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO-/- mice and background wild type mice were challenged with APAP (0.3–6 g/kg or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO-/- mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10, superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate assay were prevented in 5-LO-/- mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage.

  2. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  3. Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats

    OpenAIRE

    Ko, Je-Won; Lee,In-Chul; Park, Sung-Hyuk; Moon, Changjong; Kang, Seong-Soo; Kim, Sung-Ho; Kim, Jong-Choon

    2014-01-01

    We investigated the protective effects of pine bark extract (pycnogenol®, PYC) against cisplatin-induced hepatotoxicity and oxidative stress in rats. Twenty-four male rats were divided into the following four groups: (1) vehicle control, (2) cisplatin (7.5 mg/kg), (3) cisplatin & PYC 10 (10 mg/kg/day), and (4) cisplatin & PYC 20 (20 mg/kg/day). A single intraperitoneal injection of cisplatin induced hepatotoxicity, as evidenced by an increase in serum aminotransferase and histopathological al...

  4. A critical analysis of the hepatotoxicity cases described in the literature related to Herbalife (r) products

    OpenAIRE

    Flávio Ailton Duque Zambrone; Cristiana Leslie Corrêa; Ligia Mesquita Sampaio do Amaral

    2015-01-01

    Abstract The aim of this study was to assess the hepatotoxicity cases described in the literature, attributed to the consumption of Herbalife(r) products, and to determine whether a causal relationship exists between the reported cases of liver injury and the use of these products. A literature search was performed on the PubMed, LILACS and PAHO databases. Seven publications reporting a total of 53 cases of hepatotoxicity linked to the use of Herbalife(r) products were retrieved. All of the s...

  5. Field Test of Wake Steering at an Offshore Wind Farm

    Energy Technology Data Exchange (ETDEWEB)

    Fleming, Paul; Annoni, Jennifer; Shah, Jigar J.; Wang, Linpeng; Ananthan, Shreyas; Zhang, Zhijun; Hutchings, Kyle; Wang, Peng; Chen, Weiguo; Chen, Lin

    2017-02-06

    In this paper, a field test of wake steering control is presented. The field test is the result of a collaboration between the National Renewable Energy Laboratory (NREL) and Envision Energy, a smart energy management company and turbine manufacturer. In the campaign, an array of turbines within an operating commercial offshore wind farm in China have the normal yaw controller modified to implement wake steering according to a yaw control strategy. The strategy was designed using NREL wind farm models, including a computational fluid dynamics model, SOWFA, for understanding wake dynamics and an engineering model, FLORIS, for yaw control optimization. Results indicate that, within the certainty afforded by the data, the wake-steering controller was successful in increasing power capture, by amounts similar to those predicted from the models.

  6. Application of H infinite control to ship steering system

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Because the general object of ship steering control system is singular, the state of rudder force and the state of disturbance are separated, and the generalized yaw output disturbance is obtained. Furthermore, singular system control problem of ship yaw and sway coupled system is transferred into nonsingular standard control problem. Then according to the linear fractional denoting algorithm of the rational function parameter perturbation system, the Linear Fractional Transform (LFT) model of yaw and sway coupled motion is solved, which is used to design the ship steering robust control system. For the ship steering system with the uncertain parameters, the robust control law is designed based on H∞μ-synthesis. And the robust performance of the system is analyzed and the simulation validation is made. Simulation results show that the designed control system has excellent control effect and robustness.

  7. A Parallel and Distributed Surrogate Model Implementation for Computational Steering

    KAUST Repository

    Butnaru, Daniel

    2012-06-01

    Understanding the influence of multiple parameters in a complex simulation setting is a difficult task. In the ideal case, the scientist can freely steer such a simulation and is immediately presented with the results for a certain configuration of the input parameters. Such an exploration process is however not possible if the simulation is computationally too expensive. For these cases we present in this paper a scalable computational steering approach utilizing a fast surrogate model as substitute for the time-consuming simulation. The surrogate model we propose is based on the sparse grid technique, and we identify the main computational tasks associated with its evaluation and its extension. We further show how distributed data management combined with the specific use of accelerators allows us to approximate and deliver simulation results to a high-resolution visualization system in real-time. This significantly enhances the steering workflow and facilitates the interactive exploration of large datasets. © 2012 IEEE.

  8. Signal Processing Strategies for Cochlear Implants Using Current Steering

    Directory of Open Access Journals (Sweden)

    Waldo Nogueira

    2009-01-01

    Full Text Available In contemporary cochlear implant systems, the audio signal is decomposed into different frequency bands, each assigned to one electrode. Thus, pitch perception is limited by the number of physical electrodes implanted into the cochlea and by the wide bandwidth assigned to each electrode. The Harmony HiResolution bionic ear (Advanced Bionics LLC, Valencia, CA, USA has the capability of creating virtual spectral channels through simultaneous delivery of current to pairs of adjacent electrodes. By steering the locus of stimulation to sites between the electrodes, additional pitch percepts can be generated. Two new sound processing strategies based on current steering have been designed, SpecRes and SineEx. In a chronic trial, speech intelligibility, pitch perception, and subjective appreciation of sound were compared between the two current steering strategies and standard HiRes strategy in 9 adult Harmony users. There was considerable variability in benefit, and the mean results show similar performance with all three strategies.

  9. Reconfigurable time-steered array-antenna beam former.

    Science.gov (United States)

    Frankel, M Y; Esman, R D

    1997-12-10

    We present and analyze a hardware-optimized technique that provides true-time-delay steering for broadband two-dimensional array-antenna applications. The technique improves on previous approaches by the reduction of the two-dimensional beam-former architecture complexity, by the provision of flexibility in time-delay unit selection, and by the potential reduction of optical loss. The technique relies on a one-dimensional bank of time-delay units to form the required time-delay gradient for proper off-broadside angle steering. A reconfigurable optical interconnection fabric is used to reassign dynamically the connections between the time-delay units and individual array elements of a two-dimensional array to effect the proper steering angle along the off-broadside cone.

  10. Current steering effect of GaN nanoporous structure

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chia-Feng, E-mail: cflin@dragon.nchu.edu.tw [Department of Materials Science and Engineering, National Chung Hsing University, Taichung 402, Taiwan (China); Department of Electrical Engineering, Yale University, New Haven, CT 06520 (United States); Wang, Jing-Hao; Cheng, Po-Fu; Tseng, Wang-Po; Fan, Feng-Hsu; Wu, Kaun-Chun; Lee, Wen-Che [Department of Materials Science and Engineering, National Chung Hsing University, Taichung 402, Taiwan (China); Han, Jung [Department of Electrical Engineering, Yale University, New Haven, CT 06520 (United States)

    2014-11-03

    Current steering effect of InGaN light emitting diode (LED) structure was demonstrated by forming a high resistivity GaN nanoporous structure. Disk-array patterns with current-injection bridge structures were fabricated on InGaN LED devices through a focused ion beam (FIB) system. GaN nanoporous structure was formed around the FIB-drilled holes through a electrochemical (EC) wet-etching process on a n-type GaN:Si layer under the InGaN active layer. High emission intensity and small peak wavelength blueshift phenomenon of the electroluminescence spectra were observed in the EC-treated region compared with the non-treated region. The branch-like nanoporous structure was formed along the lateral etched direction to steer the injection current in 5 μm-width bridge structures. In the FIB-drilled hole structure, high light emission intensity of the central-disk region was observed by enlarging the bridge width to 10 μm, with a 5 μm EC-treated width, that reduced the current steering effect and increased the light scattering effect on the nanoporous structure. The EC-treated GaN:Si nanoporous structure acted as a high light scattering structure and a current steering structure that has potential on the current confinement for vertical cavity surface emitting laser applications. - Highlights: • High resistivity nanoporous-GaN formed in InGaN LED through electrochemical process. • Branch-like nanoporous in 5 μm-width bridge structure can steer the injection current. • Nanoporous GaN acted as s light scattering and current steering structures in InGaN LED.

  11. Hepatotoxicity associated with agomelatine and other antidepressants: Disproportionality analysis using pooled pharmacovigilance data from the Uppsala Monitoring Centre.

    Science.gov (United States)

    Gahr, Maximilian; Zeiss, René; Lang, Dirk; Connemann, Bernhard J; Schönfeldt-Lecuona, Carlos

    2015-07-01

    Since its marketing approval, the attention to the hepatic side-effect profile of the antidepressant agomelatine (AGM) has gradually increased. Several cases of severe hepatotoxic adverse drug reactions (ADR) have been reported and the European Medicines Agency has released a safety warning regarding AGM-associated hepatotoxicity. However, there are insufficient data for an adequate safety assessment of AGM-related hepatotoxicity. Therefore, we performed a quantitative signal detection analysis using pharmacovigilance data from the Uppsala Monitoring Centre from the WHO that records ADR data from worldwide sources; we calculated reporting odds ratios (ROR) as measures for disproportionality within a case/non-case approach for AGM and several other antidepressants. AGM was statistically associated with an increased risk of hepatotoxicity (ROR 6.4 [95%CI 5.7-7.2]) as well as both positive controls: amineptine (ROR 38.4 [95%CI 33.8-43.6]) and nefazodone (ROR 3.2 [95%CI 3.0-3.5]). Following amineptine, AGM was associated with the second highest ROR, followed by tianeptine (ROR 4.4 [95%CI 3.6-5.3]), mianserin (ROR 3.6 [95%CI 3.3-3.9]), and nefazodone. These results support the hypothesis that AGM is associated with relevant hepatotoxicity. However, the used data and applied method do not allow a quantitative evaluation of hepatotoxicity or assessment of substance-specific differences regarding the extent of hepatotoxicity. © 2015, The American College of Clinical Pharmacology.

  12. Improved LTVMPC design for steering control of autonomous vehicle

    Science.gov (United States)

    Velhal, Shridhar; Thomas, Susy

    2017-01-01

    An improved linear time varying model predictive control for steering control of autonomous vehicle running on slippery road is presented. Control strategy is designed such that the vehicle will follow the predefined trajectory with highest possible entry speed. In linear time varying model predictive control, nonlinear vehicle model is successively linearized at each sampling instant. This linear time varying model is used to design MPC which will predict the future horizon. By incorporating predicted input horizon in each successive linearization the effectiveness of controller has been improved. The tracking performance using steering with front wheel and braking at four wheels are presented to illustrate the effectiveness of the proposed method.

  13. Study on Characteristic of Electric Power Assist Steering System

    Institute of Scientific and Technical Information of China (English)

    许镇琳; 王豪; 尚喆; 张海华; 王家军

    2003-01-01

    A pinion-type electric power steering (EPS) equipped on a sedan is reached in this paper. A three-freedom dynamic model of this system is created. The variables affecting assist character is analyzed. The formulas of simpled steering resistance force and the relationship between assist gain and vehicle speed are presented for the first time. Assist character is found based on the parameters of a sedan at last. This assist character is fit for the control rule of the EPS system through analyzing this character. The assist character figure offers reference for system design and control. Furthermore, this research method has generality for assist character of different kinds of vehicles.

  14. Detailed field test of yaw-based wake steering

    DEFF Research Database (Denmark)

    Fleming, P.; Churchfield, M.; Scholbrock, A.

    2016-01-01

    This paper describes a detailed field-test campaign to investigate yaw-based wake steering. In yaw-based wake steering, an upstream turbine intentionally misaligns its yaw with respect to the inflow to deflect its wake away from a downstream turbine, with the goal of increasing total power...... production. In the first phase, a nacelle-mounted scanning lidar was used to verify wake deflection of a misaligned turbine and calibrate wake deflection models. In the second phase, these models were used within a yaw controller to achieve a desired wake deflection. This paper details the experimental...

  15. Steering of Educational Processes in a Digital Medium Environment

    DEFF Research Database (Denmark)

    Tække, Jesper; Paulsen, Michael

    2015-01-01

    by systems theory we outline a more adequate way of teaching in the new medium environment – a teaching that can manage the new situation and use the new possibilities provided by the digital media. The argumentation builds on empirical findings from the action research project Socio Media Education (SME......This paper is about challenges to steering and leadership of educational interaction in classrooms provided by the new medium environment that comes with digital media. In the new medium environment, the old way of steering what is going on in the classroom appears not to work since...

  16. 76 FR 69769 - Annual Public Meeting of the Interagency Steering Committee on Multimedia Environmental Modeling

    Science.gov (United States)

    2011-11-09

    ... indication of citizenship and affiliation) may be faxed or emailed to: Mark Fuhrmann, Environmental Transport... COMMISSION Annual Public Meeting of the Interagency Steering Committee on Multimedia Environmental Modeling... the Federal Interagency Steering Committee on Multimedia Environmental Modeling (ISCMEM) will...

  17. Hepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature.

    Science.gov (United States)

    Pantano, F; Mannocchi, G; Marinelli, E; Gentili, S; Graziano, S; Busardò, F P; di Luca, N M

    2017-03-01

    The available literature assessing Chelidonium majus L. (CM) hepatotoxicity potential, and its risk to benefit assessment has been reviewed in this paper. Identification of significant scientific literature was performed via the following research databases: Cochrane Central, Google Scholar, EMBASE, Medline, Science Direct, Scopus, Web of Science, using the following keywords: "Chelidonium majus", "greater celandine", "Hepatotoxicity", "Liver" "Injury", "Toxicity" individually investigated and then again in association. CM named also greater celandine, swallow-wort, or bai-qu-cai (Chinese), has been used for a long time in traditional Chinese medicine and phytotherapy. Its extracts have been claimed to display a wide variety of biological activities: antimicrobial, anti-inflammatory, spasmolytic, antineoplastic, hepatoprotective, and analgesic. Moreover, herbal medicine suggests this plant have numerous additional effects which have not yet been scientifically evaluated, such as antitussive, diuretic, and eye-regenerative. However, despite its claimed hepatoprotective effects, several hepatotoxicity cases have been reported to be probably or highly probably connected with CM exposure, after their evaluation through liver-targeted causality assessment methods. CM hepatotoxicity has been defined as a distinct form of herb-induced liver injury (HILI), due to an idiosyncratic reaction of the metabolic type. This evidence has to be considered in relationship with the absence of considerable benefits of CM therapy. Therefore, the risk to benefit ratio of the use of herbal products containing greater celandine can actually be considered as negative.

  18. Hepatoprotective Activity of Herbal Preparation (Hp-4 against Alcohol Induced Hepatotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    P. Padmanabhan

    2014-03-01

    Full Text Available Free radicals include both Reactive Oxygen Species (ROS and Reactive Nitrogen Species (RNS.When free radicals are produced in a regulated manner in a healthy human body it is scavenged efficiently by antioxidant defense system. But excess generation of pro-oxidants by continuous chain reaction in the form of ROS and RNS cause several human diseases. The shift of the balance in the favour of pro-oxidants results in a condition called “oxidative stress”. Alcohol is primarily metabolized in the liver to generate ROS and RNS, leading to diseases such as cirrhosis, fatty liver and chronic hepatitis. Alcohol induced damage is associated with oxidative stress. The excess generation of prooxidants and reduced antioxidant levels provide an effective model of Hepatotoxicity which is noteworthy. Recent trend is to discover polyherbal formulation of medicinal plants which have hepatoprotective function. In the present study 80% alcoholic extract of leaves of Aloe vera, Bacopa monniera, Moringa oleifera and rhizome of Zingiber officinale were utilized to prepare Herbal Preparation or HP-4.Further the hepatoprotective effects of HP-4 was tested in alcohol induced Hepatotoxicity in mice. Silymarin is a well known hepatoprotective drug was used as a standard for comparison. Biochemical and histopathological studies provided ample evidence that HP-4 provided a hepatoprotective role in alcohol induced hepatotoxicity which was comparable to drug Silymarin. The presence of phytochemicals in HP-4 provided a synergistic, supra-additive and co-operative effects in the hepatoprotective function in alcohol induced hepatotoxicity mice model.

  19. Hepatoprotective activity of Eclipta alba against carbon tetrachloride-induced hepatotoxicity in albino rats

    Directory of Open Access Journals (Sweden)

    Ravindra S. Beedimani

    2015-06-01

    Conclusion: The results of the study confirmed the hepatoprotective activity of aqueous extracts of E. alba at doses of 250 mg/kg and 500 mg/kg against CCl4 induced hepatotoxicity in rats. However, the dose adjustments may be necessary to optimize the similar hepatoprotective efficacy in clinical settings. [Int J Basic Clin Pharmacol 2015; 4(3.000: 404-409

  20. Beneficial effects of Chrysin against Methotrexate-induced hepatotoxicity via attenuation of oxidative stress and apoptosis.

    Science.gov (United States)

    Ali, Nemat; Rashid, Summya; Nafees, Sana; Hasan, Syed Kazim; Sultana, Sarwat

    2014-01-01

    Methotrexate (MTX), a folic acid antagonist, an effective chemotherapeutic agent is used in the treatment of a wide range of tumors and autoimmune diseases. Moreover, hepatotoxicity limits its clinical use. Several studies have already confirmed that the oxidative stress plays a major role in the pathogenesis of MTX-induced damage in the various organs especially in liver. The aim of this study was to determine the protective effect of Chrysin against MTX-induced hepatic oxidative stress and apoptosis in rats. In the present study, efficacy of Chrysin was investigated against hepatotoxicity caused by MTX in terms of biochemical investigations of antioxidant enzymes, apoptosis, and histopathological alteration in rat liver. In the MTX-treated group there was a significant increase in alanine transaminase, aspartate aminotransferase, lactate dehydrogenase activity and malondialdehyde content as well as decreased glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase activities and reduced glutathione content were also observed compared to the control group as a marker of oxidative stress. Histopathological alterations and apoptosis through the immunopositive staining of p53, cleaved caspases-3 and Bcl-2-associated X protein in rat liver were observed. Pretreatment of Chrysin at both doses prevents the hepatotoxicity by ameliorating oxidative stress, histopathological alterations, and apoptosis and thus our results suggest that Chrysin has a protective effect against hepatotoxicity induced by MTX and it may, therefore, improve the therapeutic index of MTX if co-administration is done.

  1. The protective effect of intraperitoneal medical ozone preconditioning and treatment on hepatotoxicity induced by methotrexate.

    Science.gov (United States)

    Aslaner, Arif; Çakır, Tuğrul; Çelik, Betül; Doğan, Uğur; Akyüz, Cebrail; Baştürk, Ahmet; Polat, Cemal; Gündüz, Umut; Mayir, Burhan; Şehirli, Ahmet Özer

    2015-01-01

    The aim of this study is to determine the effects of medical ozone preconditioning and treatment on the methotrexate acute induced hepatotoxicity in rats that has not reports elsewhere. Eighteen rats were randomly assigned into three equal groups; control, Mtx and Mtx with ozone. Hepatotoxicity was performed with a single dose of 20 mg/kg Mtx to group 2 and group 3 at the fifteenth day. The medical ozone preconditioning was administered intraperitonealy in group 3 for fifteen days and more five days after inducing Mtx. The other rats of the group 1 and 2 received saline injection. At the twentyfirst day the blood and the liver tissue samples were obtained to measure the levels of liver enzymes ALT and AST, proinflamatory cytokines TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. And the histolopatological examination was evaluated for injury score. In our study Mtx administration caused a significant increase on the liver enzymes ALT and AST, the tissue MDA and MPO activity and significant decrease in the tissue GSH. Moreover the both pro-inflammatory cytokines were significantly increased in the Mtx group. Medical ozone preconditioning and treatment reversed all these biochemical parameters and histopathological changes of the hepatotoxicity induced by Mtx. We conclude that medical ozone ameliorates Mtx induced hepatotoxicity in rats.

  2. Hepatoprotective effect of Origanum vulgare in Wistar rats against carbon tetrachloride-induced hepatotoxicity.

    Science.gov (United States)

    Sikander, Mohammad; Malik, Shabnam; Parveen, Kehkashan; Ahmad, Maqsood; Yadav, Deepak; Hafeez, Zubair Bin; Bansal, Manish

    2013-04-01

    The effect of an aqueous extract of Origanum vulgare (OV) leaves extract on CCl4-induced hepatotoxicity was investigated in normal and hepatotoxic rats. To evaluate the hepatoprotective activity of OV, rats were divided into six groups: control group, O. vulgare group, carbon tetrachloride (CCl4; 2 ml/kg body weight) group, and three treatment groups that received CCl4 and OV at doses of 50, 100, 150 mg/kg body weight orally for 15 days. Alanine amino transferase (ALT), alkaline phosphatase (ALP), and aspartate amino transferase (AST) in serum, lipid peroxide (LPO), GST, CAT, SOD, GPx, GR, and GSH in liver tissue were estimated to assess liver function. CCl4 administration led to pathological and biochemical evidence of liver injury as compared to controls. OV administration led to significant protection against CCl4-induced hepatotoxicity in dose-dependent manner, maximum activity was found in CCl4 + OV3 (150 mg/kg body weight) groups and changes in the hepatocytes were confirmed through histopathological analysis of liver tissues. It was also associated with significantly lower serum ALT, ALP, and AST levels, higher GST, CAT, SOD, GPx, GR, and GSH level in liver tissue. The level of LPO also decreases significantly after the administration of OV leaves extract. The biochemical observations were supplemented with histopathological examination of rat liver sections. Thus, the study suggests O. vulgare showed protective activity against CCl4-induced hepatotoxicity in Wistar rats and might be beneficial for the liver toxicity.

  3. Protective effect of rutin in comparison to silymarin against induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    M. Kasi Reddy

    2017-01-01

    Full Text Available Aim: The aim of this study is to evaluate the hepatoprotective effect of rutin (RTN in comparison to silymarin (SLM against acetaminophen (APAP-induced hepatotoxicity in rats. Materials and Methods: Male Wistar albino rats (n=24 of 3 months age were equally divided into four groups. Group 1 served as normal control. Hepatotoxicity was induced in the remaining three groups with administration of 500 mg/kg po APAP from day 1-3. Groups 2, 3, and 4 were subsequently administered orally with distilled water, 25 mg/kg of SLM, and 20 mg/kg of RTN, respectively, for 11 days. The mean body weights and biomarkers of hepatotoxicity were estimated on day 0, 4 (confirmation of toxicity, and 15 (at the end of treatment. Hematological parameters were evaluated on day 4 and 15. Antioxidant profile and adenosine triphosphatases (ATPases were assessed at the end of the experiment. Liver tissues were subjected to histopathology and transmission electron microscopy after the sacrifice on day 15. Results: Antioxidant profile, ATPases, and hematological and sero-biochemical parameters were significantly altered, and histopathological changes were noticed in the liver of toxic control group. These changes were reversed in groups 3 and 4 that were administered with SLM and RTN, respectively. Conclusion: The results of the present investigation enunciated that SLM has potent hepatoprotective activity though the RTN was found superior in restoring the pathological alterations in paracetamol-induced hepatotoxicity in Wistar albino rats.

  4. Screening of herbal components for attenuating amiodarone-induced hepatotoxicity on gel-entrapped rat hepatocytes.

    Science.gov (United States)

    Deng, Xudong; Shen, Chong; Meng, Qin

    2014-01-01

    Amiodarone (AMD) is a hepatotoxic drug that has been widely used as a class III antiarrhythmic drug. Because, to date, only a few kinds of protectants are able to reduce AMD hepatotoxicity, this article utilized gel-entrapped rat hepatocytes to screen effective protectants from a series of herbal compounds for their effects against AMD-induced toxicity. Herbal compounds, including matrine, silibinin, glycyrrhizic acid, schisandrin B, epigallocatechin gallate and anisodamine, were cotreated with AMD to assess their protective effect, whereas vitamin E, which has been shown to be protective in rats, was selected as a control. It was found that vitamin E, as with its function in rats, provided the best protection in gel-entrapped rat hepatocytes, whereas silibinin, a major component of silymarin, could largely reduce AMD-induced hepatotoxicity, performing a similar function as silymarin in rats. The results illustrated that gel-entrapped hepatocytes may reflect the protective effects of drugs and serve as a reliable model for screening hepatoprotectants. Moreover, matrine, a widely used monomer of the traditional Chinese medicine, Sophora flavescens, for treatment of arrhythmia, was evidenced to show some effective protections against AMD hepatotoxicity. Taken together, gel-entrapped rat hepatocytes may provide a platform for screening effective candidates from the herbal component library.

  5. Means of evaluation and protection from doxorubicin-induced cardiotoxicity and hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Issam Salouege

    2014-01-01

    Conclusion: We have evaluated the protective effect of trimetazidine on an animal model of doxorubicin-induced cardiotoxicity and hepatotoxicity. The evaluation of these effects were assessed by several means; tissular distribution of doxorubicin, histological examination, assessment of liver function, and EF LV by scintigraphy that characterizes the originality of this study.

  6. Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats.

    Science.gov (United States)

    Ko, Je-Won; Lee, In-Chul; Park, Sung-Hyuk; Moon, Changjong; Kang, Seong-Soo; Kim, Sung-Ho; Kim, Jong-Choon

    2014-12-01

    We investigated the protective effects of pine bark extract (pycnogenol®, PYC) against cisplatin-induced hepatotoxicity and oxidative stress in rats. Twenty-four male rats were divided into the following four groups: (1) vehicle control, (2) cisplatin (7.5 mg/kg), (3) cisplatin & PYC 10 (10 mg/kg/day), and (4) cisplatin & PYC 20 (20 mg/kg/day). A single intraperitoneal injection of cisplatin induced hepatotoxicity, as evidenced by an increase in serum aminotransferase and histopathological alterations, including degeneration/necrosis of hepatocytes, vacuolation, and sinusoidal dilation. In addition, an increase in the malondialdehyde (MDA) concentration and a decrease in the reduced glutathione (GSH) content and catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) activities were observed in the cisplatin-treated rat hepatic tissues. In contrast, PYC treatment effectively prevented cisplatin-induced hepatotoxicity, including the elevation of aminotransferase and histopathological lesions, in a dosedependent manner. Moreover, PYC treatment also induced antioxidant activity by decreasing MDA level and increasing GSH content and SOD and GST activities in liver tissues. These results indicate that PYC has a protective effect against acute hepatotoxicity induced by cisplatin in rats, and that the protective effects of PYC may be due to inhibiting lipid peroxidation and increasing antioxidant activity.

  7. Caffeic acid, a phyto polyphenol mitigates fluoride induced hepatotoxicity in rats: A possible mechanism.

    Science.gov (United States)

    Kanagaraj, Vishnu Vignesh; Panneerselvam, Lakshmikanthan; Govindarajan, Vimal; Ameeramja, Jaishabanu; Perumal, Ekambaram

    2015-01-01

    Fluoride induced hepatotoxicity has been extensively studied in both humans and animals. However, the mechanism underlying in the hepatotoxicity of experimental fluorosis remains obscure. The severity of fluoride toxicity was reduced by oral administration of certain plant derived antioxidants. Caffeic acid (CA) a polyphenolic compound has diverse range of pharmacological activity in the biological system. Therefore, the present study was aimed to investigate the protective mechanism of CA, against fluoride induced hepatotoxicity in rats. The rats were treated with 300 ppm of NaF via drinking water ad libitum alone and in combination with CA at a dose of 50 mg/kg daily for 30 days by oral intubation. CA treatment significantly prevented fluoride induced hepatic damage as evident from the histopathological studies and declined levels of serum fluoride and liver marker enzymes. A significant decrease in the levels of enzymatic (SOD2, CAT, GPx, and GSTpi class) and nonenzymatic (GSH and Vitamin C) antioxidants along with increased ROS, lipid peroxidation, protein carbonyl content, and nitrate levels by fluoride were also prevented in these groups. In addition, CA inhibits fluoride induced apoptosis by altering the Bax and caspase-3p20 expressions. Further, fluoride induced upregulation of Nox4, p38α MAPK, Hsp60, and downregulation of Hsp27 are the indicators for the detection of oxidative damage, apoptosis, and mitochondrial stress was also modulated by CA. These findings reveal that CA supplementation has a protective effect against fluoride induced hepatotoxicity in rats.

  8. Calcium transport, thiol status, and hepatotoxicity following N-nitrosodimethylamine exposure in mice

    Energy Technology Data Exchange (ETDEWEB)

    Reitman, F.A.; Berger, M.L.; Minnema, D.J.; Shertzer, H.G.

    1988-01-01

    The hepatotoxicant N-nitrosodimethylamine (NDMA) is presumed to exert toxicity through reactive metabolites. NDMA is similar in this respect to numerous other hepatotoxicants, for which hepatotoxicity is also associated with a rapid depletion of soluble and/or protein thiols, and an inhibition of calcium transport systems. The authors examined the hypothesis that hepatotoxicity for NDMA is preceded by thiol depletion and/or inhibition of calcium transport in isolated liver subcellular fractions. Centrizonal liver necrosis in mice was evident at 24 but not at 12 h subsequent to intraperitoneal administration of 40 mg NDMA/kg. Hepatotoxicity was not preceded by depletion of liver protein-free sulfhydryls, nor by protein sulfhydryl depletion in liver whole homogenate, microsomal, or plasma membrane fractions. NDMA-mediated toxicity was also not preceded by inhibition of calcium uptake capability by microsomal, mitochondrial, or plasma membrane fractions. In contrast, carbon tetrachloride produced the expected rapid decrease in microsomal calcium uptake capability, followed by a centrizonal necrosis that was maximal at about 24 h. These studies suggest that the mechanism of NDMA hepatotoxicity may differ from that of a number of other hepatotoxicants (e.g., carbon tetrachloride, acetaminophen, bromobenzene) for which toxicity is also mediated through reactive metabolites.

  9. Allopurinol and 5-aminosalicylic acid influence thiopurine-induced hepatotoxicity in vitro

    NARCIS (Netherlands)

    Broekman, M.M.T.J.; Roelofs, H.M.; Wong, D.R.; Kerstholt, M.; Leijten, A.; Hoentjen, F.; Peters, W.H.M.; Wanten, G.J.A.; Jong, D.J. de

    2015-01-01

    INTRODUCTION: The use of thiopurines is frequently accompanied by hepatotoxicity. Studies on hepatocyte cultures showed a time- and dose-dependent increase of thiopurine toxicity. 5-Aminosalicylic acid (5-ASA) and allopurinol can influence thiopurine metabolism; however, it is unknown whether this a

  10. Establishment of a Predictive In Vitro Assay for Assessment of the Hepatotoxic Potential of Oligonucleotide Drugs

    Science.gov (United States)

    Sewing, Sabine; Boess, Franziska; Moisan, Annie; Bertinetti-Lapatki, Cristina; Minz, Tanja; Hedtjaern, Maj; Tessier, Yann; Schuler, Franz; Singer, Thomas; Roth, Adrian B.

    2016-01-01

    Single stranded oligonucleotides (SSO) represent a novel therapeutic modality that opens new space to address previously undruggable targets. In spite of their proven efficacy, the development of promising SSO drug candidates has been limited by reported cases of SSO-associated hepatotoxicity. The mechanisms of SSO induced liver toxicity are poorly understood, and up to now no preclinical in vitro model has been established that allows prediction of the hepatotoxicity risk of a given SSO. Therefore, preclinical assessment of hepatic liability currently relies on rodent studies that require large cohorts of animals and lengthy protocols. Here, we describe the establishment and validation of an in vitro assay using primary hepatocytes that recapitulates the hepatotoxic profile of SSOs previously observed in rodents. In vitro cytotoxicity upon unassisted delivery was measured as an increase in extracellular lactate dehydrogenase (LDH) levels and concomitant reduction in intracellular glutathione and ATP levels after 3 days of treatment. Furthermore, toxic, but not safe, SSOs led to an increase in miR-122 in cell culture supernatants after 2 days of exposure, revealing the potential use of miR122 as a selective translational biomarker for detection of SSO-induced hepatotoxicity. Overall, we have developed and validated for the first time a robust in vitro screening assay for SSO liver safety profiling which allows rapid prioritization of candidate molecules early on in development. PMID:27442522

  11. Establishment of a Predictive In Vitro Assay for Assessment of the Hepatotoxic Potential of Oligonucleotide Drugs.

    Directory of Open Access Journals (Sweden)

    Sabine Sewing

    Full Text Available Single stranded oligonucleotides (SSO represent a novel therapeutic modality that opens new space to address previously undruggable targets. In spite of their proven efficacy, the development of promising SSO drug candidates has been limited by reported cases of SSO-associated hepatotoxicity. The mechanisms of SSO induced liver toxicity are poorly understood, and up to now no preclinical in vitro model has been established that allows prediction of the hepatotoxicity risk of a given SSO. Therefore, preclinical assessment of hepatic liability currently relies on rodent studies that require large cohorts of animals and lengthy protocols. Here, we describe the establishment and validation of an in vitro assay using primary hepatocytes that recapitulates the hepatotoxic profile of SSOs previously observed in rodents. In vitro cytotoxicity upon unassisted delivery was measured as an increase in extracellular lactate dehydrogenase (LDH levels and concomitant reduction in intracellular glutathione and ATP levels after 3 days of treatment. Furthermore, toxic, but not safe, SSOs led to an increase in miR-122 in cell culture supernatants after 2 days of exposure, revealing the potential use of miR122 as a selective translational biomarker for detection of SSO-induced hepatotoxicity. Overall, we have developed and validated for the first time a robust in vitro screening assay for SSO liver safety profiling which allows rapid prioritization of candidate molecules early on in development.

  12. Effects of slow-release urea on ruminal digesta characteristics and growth performance in beef steers

    DEFF Research Database (Denmark)

    Taylor-Edwards, C C; Hibbard, G; Kitts, S E

    2009-01-01

    Two experiments were conducted to evaluate the effects of slow urea (SRU) versus feed-grade urea on ruminal metabolite characteristics in steers and DMI, gain, and G:F in growing beef steers.......Two experiments were conducted to evaluate the effects of slow urea (SRU) versus feed-grade urea on ruminal metabolite characteristics in steers and DMI, gain, and G:F in growing beef steers....

  13. Steering laws analysis of SGCMGs based on singular value decomposition theory

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jing-rui

    2008-01-01

    The steering laws of single gimbal control moment gyros (SGCMGs) are analyzed and compared in this paper for a spacecraft attitude control system based on singular value decomposition (SVD) theory. The mechanism of steering laws escaping singularity, especially how the steering laws affect singularity of gimbal configuration and the output torque error, is studied using SVD theory. Performance of various steering laws are analyzed and compared quantitatively by simulation. The obtained results can be used as a reference for designers.

  14. Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

    Institute of Scientific and Technical Information of China (English)

    Raúl J Andrade; Mercedes Robles; Alejandra Fernández-Casta(n)er; Susana López-Ortega; M Carmen López-Vega; M Isabel Lucena

    2007-01-01

    Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and postcommercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice.To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be finetuned as further information is collected.

  15. Role of the sympathetic nervous system in carbon tetrachloride-induced hepatotoxicity and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Jung-Chun Lin

    Full Text Available Carbon tetrachloride (CCl4 is widely used as an animal model of hepatotoxicity and the mechanisms have been arduously studied, however, the contribution of the sympathetic nervous system (SNS in CCl4-induced acute hepatotoxicity remains controversial. It is also known that either CCl4 or SNS can affect systemic inflammatory responses. The aim of this study was to establish the effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA in a mouse model of CCl4-induced acute hepatotoxicity and systemic inflammatory response. Mice exposed to CCl4 or vehicle were pretreated with 6-OHDA or saline. The serum levels of aminotransferases and alkaline phosphatase in the CCl4-poisoning mice with sympathetic denervation were significantly lower than those without sympathetic denervation. With sympathetic denervation, hepatocellular necrosis and fat infiltration induced by CCl4 were greatly decreased. Sympathetic denervation significantly attenuated CCl4-induced lipid peroxidation in liver and serum. Acute CCl4 intoxication showed increased expression of inflammatory cytokines/chemokines [eotaxin-2/CCL24, Fas ligand, interleukin (IL-1α, IL-6, IL-12p40p70, monocyte chemoattractant protein-1 (MCP-1/CCL2, and tumor necrosis factor-α (TNF-α], as well as decreased expression of granulocyte colony-stimulating factor and keratinocyte-derived chemokine. The overexpressed levels of IL-1α, IL-6, IL-12p40p70, MCP-1/CCL2, and TNF-α were attenuated by sympathetic denervation. Pretreatment with dexamethasone significantly reduced CCl4-induced hepatic injury. Collectively, this study demonstrates that the SNS plays an important role in CCl4-induced acute hepatotoxicity and systemic inflammation and the effect may be connected with chemical- or drug-induced hepatotoxicity and circulating immune response.

  16. Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Ana Cecília Montes Gil

    Full Text Available CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART. We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6, A (29, B (78 and C (39. Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN, grade 2 (5.0-9.9 times ULN, grade 3 (10.0-15.0 times ULN and grade 4 (> 15.0 times ULN. To assess hepatotoxicity risk factors, odds ratios (OR and adjusted odds ratios (aOR for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152 patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI, 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85 and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25. No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.

  17. Herbal hepatotoxicity in traditional and modern medicine: Actual key issues and new encouraging steps

    Directory of Open Access Journals (Sweden)

    Rolf eTeschke

    2015-04-01

    Full Text Available Plants are natural producers of chemical substances, providing potential treatment of human ailments since ancient times. Some herbal chemicals in medicinal plants of traditional and modern medicine carry the risk of herb induced liver injury (HILI with a severe or potentially lethal clinical course, and the requirement of a liver transplant. Discontinuation of herbal use is mandatory in time when HILI is first suspected as diagnosis. Although herbal hepatotoxicity is of utmost clinical and regulatory importance, lack of a stringent causality assessment remains a major issue for patients with suspected HILI, while this problem is best overcome by the use of the hepatotoxicity specific CIOMS (Council for International Organizations of Medical Sciences scale and the evaluation of unintentional reexposure test results. Sixty five different commonly used herbs, herbal drugs, and herbal supplements and 111 different herbs or herbal mixtures of the traditional Chinese medicine (TCM are reported causative for liver disease, with levels of causality proof that appear rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus on introducing analytical methods that identify cases of intrinsic hepatotoxicity caused by pyrrolizidine alkaloids, and on omics technologies, including genomics, proteomics, metabolomics, and assessing circulating micro-RNA in the serum of some patients with intrinsic hepatotoxicity. It remains to be established whether these new technologies can identify idiosyncratic HILI cases. To enhance its globalization, herbal medicine should universally be marketed as herbal drugs under strict regulatory surveillance in analogy to regulatory approved chemical drugs, proving a positive risk/benefit profile by enforcing evidence based clinical trials and excellent herbal drug quality.

  18. Role of nuclear receptor CAR in carbon tetrachloride-induced hepatotoxicity

    Institute of Scientific and Technical Information of China (English)

    Yuichi Yamazaki; Satoru Kakizaki; Norio Horiguchi; Hitoshi Takagi; Masatomo Mori; Masahiko Negishi

    2005-01-01

    AIM: To investigate the precise roles of CAR in CCl4-induced acute hepatotoxicity.METHODS: To prepare an acute liver injury model, CCl4 was intraperitoneally injected in CAR+/+ and CAR-/- mice.RESULTS: Elevation of serum alanine aminotransferase and extension of centrilobular necrosis were slightly inhibited in CAR-/- mice compared to CAR+/+ mice without PB. Administration of a CAR inducer, PB, revealed that CCl4-induced liver toxicity was partially inhibited in CAR-/- mice compared with CAR+/+ mice. On the other hand,androstanol, an inverse agonist ligand, inhibited hepatotoxicity in CAR+/+ but not in CAR-/- mice. Thus, CAR activation caused CCl4 hepatotoxicity while CAR inhibition resulted in partial protection against CCl4-induced hepatotoxicity.There were no differences in the expression of CYP2E1, the main metabolizing enzyme for CCl4, between CAR+/+ and CAR-/- mice. However, the expression of other CCl4-metabolizing enzymes, such as CYP2B10 and 3A11, was induced by PB in CAR+/+ but not in CAR-/- mice. Although the main pathway of CCl4-induced acute liver injury is mediated by CYP2E1, CAR modulates its pathway via induction of CYP2B10 and 3A11 in the presence of activator or inhibitor.CONCLUSION: The nuclear receptor CAR modulates CCl4-induced liver injury via induction of CCl4-metabolizing enzymes in the presence of an activator. Our results suggest that drugs interacting with nuclear receptors such as PB might play critical roles in drug-induced liver injury or drugdrug interaction even though such drugs themselves are not hepatotoxic.

  19. Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation.

    Science.gov (United States)

    Dalaklioglu, S; Genc, G E; Aksoy, N H; Akcit, F; Gumuslu, S

    2013-06-01

    Hepatotoxicity is one of the major complications of methotrexate (MTX) therapy. This study was carried out to evaluate the possible protective effect of resveratrol (trans-3,5,4'-trihydroxystilbene, RVT) against MTX-induced hepatotoxicity. Rats were randomly divided into four groups as control, MTX treated (7 mg/kg/day, intraperitoneally (i.p.), once daily for 3 consecutive days), MTX + RVT treated (20 mg/kg/day, i.p.), and RVT treated. First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days. Histopathology of liver was evaluated by light microscopy. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. The levels of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and activities of hepatic antioxidant enzymes such as catalase (CAT) and glutathione-S-transferase (GST) were used to analyze the oxidative stress-mediated lipid peroxidation in liver sections. Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels. TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration. RVT treatment significantly prevented MTX-induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology. Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX-treated group. These results revealed that RVT may have a protective effect against MTX-induced hepatotoxicity by inhibiting oxidative stress-mediated lipid peroxidation. Consequently, RVT treatment might be a promising strategy against MTX-induced hepatotoxicity.

  20. Protective effect of pioglitazone, a PPARγ agonist against acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Gupta, Gaurav; Krishna, Gopala; Chellappan, Dinesh Kumar; Gubbiyappa, Kumar Shiva; Candasamy, Mayuren; Dua, Kamal

    2014-08-01

    Acetaminophen has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Pioglitazone, PPARγ ligand, is clinically tested and used in treatment of diabetes. PPARγ is a key nuclear hormone receptor of lipid metabolisms and regulates several gene transcriptions associated with differentiation, growth arrest, and apoptosis. The aim of our study was to evaluate the hepatoprotective activity of pioglitazone on acetaminophen-induced hepatotoxicity and to understand the relationship between the PPARγ and acetaminophen-induced hepato injury. For the experiment, Sprague-Dawley rats (160-180 g) were used and divided into four groups. Groups I and II were normal and experimental controls, respectively. Groups III and IV received the pioglitazone 20 mg/kg for 10 days. Hepatotoxicity was induced in Groups II and III on the eighth day with acetaminophen (i.p. 350 mg/kg body weight). The hepatoprotective effect was evaluated by performing an assay of the total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and α-fetoprotein as well as glutathione peroxidase, lipid peroxidation, catalase, superoxide dismutase, and glutathione transferase and liver histopathology. The assay results were presented as mean and standard error of mean for each group. The study group was compared with the control group by one-way ANOVA test. A p value of hepatotoxicity. Liver histopathological examination showed that pioglitazone administration antagonized acetaminophen -induced liver pathological damage. Various biochemical estimations of different hepatic markers and antioxidant enzymes and histopathological studies of liver tissues glimpse a support to its significant hepatoprotective activity on acetaminophen -induced hepatotoxicity.

  1. A monkey model of acetaminophen-induced hepatotoxicity; phenotypic similarity to human.

    Science.gov (United States)

    Tamai, Satoshi; Iguchi, Takuma; Niino, Noriyo; Mikamoto, Kei; Sakurai, Ken; Sayama, Ayako; Shimoda, Hitomi; Takasaki, Wataru; Mori, Kazuhiko

    2017-01-01

    Species-specific differences in the hepatotoxicity of acetaminophen (APAP) have been shown. To establish a monkey model of APAP-induced hepatotoxicity, which has not been previously reported, APAP at doses up to 2,000 mg/kg was administered orally to fasting male and female cynomolgus monkeys (n = 3-5/group) pretreated intravenously with or without 300 mg/kg of the glutathione biosynthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). In all the animals, APAP at 2,000 mg/kg with BSO but not without BSO induced hepatotoxicity, which was characterized histopathologically by centrilobular necrosis and vacuolation of hepatocytes. Plasma levels of APAP and its reactive metabolite N-acethyl-p-benzoquinone imine (NAPQI) increased 4 to 7 hr after the APAP treatment. The mean Cmax level of APAP at 2,000 mg/kg with BSO was approximately 200 µg/mL, which was comparable to high-risk cutoff value of the Rumack-Matthew nomogram. Interestingly, plasma alanine aminotransferase (ALT) did not change until 7 hr and increased 24 hr or later after the APAP treatment, indicating that this phenotypic outcome was similar to that in humans. In addition, circulating liver-specific miR-122 and miR-192 levels also increased 24 hr or later compared with ALT, suggesting that circulating miR-122 and miR-192 may serve as potential biomarkers to detect hepatotoxicity in cynomolgus monkeys. These results suggest that the hepatotoxicity induced by APAP in the monkey model shown here was translatable to humans in terms of toxicokinetics and its toxic nature, and this model would be useful to investigate mechanisms of drug-induced liver injury and also potential translational biomarkers in humans.

  2. CYP2E1 mediated isoniazid-induced hepatotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Jiang YUE; Ren-xiu PENG; Jing YANG; Rui KONG; Juan LIU

    2004-01-01

    AIM: To investigate the role of CYP2E1 in isoniazid (INH)-induced hepatotoxicity and the influence of rifampicin (RFP) on INH-induced liver injury. METHODS: Rats were treated with INH alone (100 mg/kg, ip) or co-administered with RFP (100 mg/kg, ig) for 10 d and 21 d. Hepatotoxicity was assayed by plasma enzymes (sALT, sAST) and histopathological examinations. Hepatic CYP2E1 activity was measured by aniline hydroxylase (ANH), and CYP2E1 mRNA expression was determined by RT-PCR. Plasma hydrazine concentration was determined by RP-HPLC.RESULTS: For a 10 d INH-treatment, hepatic CYP2E1 level was increased to 3.7-fold over the control; liver impairment appeared after 21 d treatment, while CYP2E1 and plasma hydrazine were, respectively, increased to 4.6-fold and 1.7-fold. However, in INH-RFP group for 10 d, CYP2E1 and plasma hydrazine were, respectively,decreased by 13 % and 18 % over INH group; similarly, hepatic injury is equal to INH group appeared after 21 d,and CYP2E1 was further decreased by 26 %. Correlation analysis showed that sALT had a positive correlation with plasma hydrazine and with CYP2E1 activity; CYP2E1 activity was also markedly correlated with plasma hydrazine.And compared with control, there is no difference in changes of CYP2E1 mRNA expression in INH and INH-RFP treatment for 21 d. CONCLUSION: The metabolite of INH, hydrazine, plays an important role in INH-induced hepatotoxicity in rats. The induction of CYP2E1 by hydrazine is involved in the hepatotoxicity of INH. RFP does not exacerbate INH-induced hepatotoxicity in short term, which relates to down-regulation of CYP2E1.

  3. Altered protein S-glutathionylation identifies a potential mechanism of resistance to acetaminophen-induced hepatotoxicity.

    Science.gov (United States)

    McGarry, David J; Chakravarty, Probir; Wolf, C Roland; Henderson, Colin J

    2015-11-01

    Acetaminophen (APAP) is the most commonly used over-the-counter analgesic. However, hepatotoxicity induced by APAP is a major clinical issue, and the factors that define sensitivity to APAP remain unclear. We have previously demonstrated that mice nulled for glutathione S-transferase Pi (GSTP) are resistant to APAP-induced hepatotoxicity. This study aims to exploit this difference to delineate pathways of importance in APAP toxicity. We used mice nulled for GSTP and heme oxygenase-1 oxidative stress reporter mice, together with a novel nanoflow liquid chromatography-tandem mass spectrometry methodology to investigate the role of oxidative stress, cell signaling, and protein S-glutathionylation in APAP hepatotoxicity. We provide evidence that the sensitivity difference between wild-type and Gstp1/2(-/-) mice is unrelated to the ability of APAP to induce oxidative stress, despite observing significant increases in c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation in wild-type mice. The major difference in response to APAP was in the levels of protein S-glutathionylation: Gstp1/2(-/-) mice exhibited a significant increase in the number of S-glutathionylated proteins compared with wild-type animals. Remarkably, these S-glutathionylated proteins are involved in oxidative phosphorylation, respiratory complexes, drug metabolism, and mitochondrial apoptosis. Furthermore, we found that S-glutathionylation of the rate-limiting glutathione-synthesizing enzyme, glutamate cysteine ligase, was markedly increased in Gstp1/2(-/-) mice in response to APAP. The data demonstrate that S-glutathionylation provides an adaptive response to APAP and, as a consequence, suggest that this is an important determinant in APAP hepatotoxicity. This work identifies potential novel avenues associated with cell survival for the treatment of chemical-induced hepatotoxicity.

  4. Potential protective effect of etanercept and aminoguanidine in methotrexate-induced hepatotoxicity and nephrotoxicity in rats.

    Science.gov (United States)

    Hafez, Heba M; Ibrahim, Mohamed A; Ibrahim, Salwa A; Amin, Entesar F; Goma, Wafaey; Abdelrahman, Aly M

    2015-12-05

    Methotrexate (MTX), a chemotherapeutic and immunosuppressant drug, is generally well-tolerated by most patients. However, its cytotoxic nature contributes to life-threatening side effects including hepatotoxicity and nephrotoxicity. The present study investigated the possible role of tumor necrosis factor-alpha (TNF-α) inhibitor, etanercept and inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine, on MTX-induced hepatotoxicity and nephrotoxicity in rats. Rats were divided into 7 groups: control group, etanercept group, aminoguanidine group, MTX group, MTX+etanercept group, MTX+aminoguanidine group, and MTX+etanercept+aminoguanidine group. MTX caused hepatotoxicity and nephrotoxicity as evidenced biochemically by significant increase in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, respectively as well as by histopathological changes. Such effects were associated with significant changes in oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase, and glutathione (GSH)) as well as by upregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. Etanercept and aminoguanidine significantly attenuated MTX-hepatotoxicity and nephrotoxicity. The protective effect of either agent was associated with significant improvement in oxidative stress parameters as well as by downregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. The study suggested that inhibitors of either TNF-α and/or iNOS have protective effect in MTX-induced hepatotoxicity and nephrotoxicity. The protective effect of either agent relies, at least partially, on their antioxidant effects and decreased TNF-α, iNOS, and caspase-3 expressions.

  5. Efficacy of Rosmarinus officinalis leaves extract against cyclophosphamide-induced hepatotoxicity.

    Science.gov (United States)

    El-Naggar, Sabry A; Abdel-Farid, Ibrahim B; Germoush, Mousa O; Elgebaly, Hassan A; Alm-Eldeen, Abeer A

    2016-10-01

    Context Cyclophosphamide (CTX) is used to treat different cancer types, although it causes severe hepatotoxicity due to its oxidative stress effect. Rosmarinus officinalis, L. (Lamiaceae) has a therapeutic potential against hepatotoxicity due to its antioxidant activity. Objective The objective of this study is to investigate the phytochemical analysis of the methanol extract of Rosmarinus officianalis leaves (MEROL) and its efficacy against CTX-induced hepatotoxicity. Materials and methods The phytochemical analyses were assessed spectrophotometericaly. To assess the MEROL efficacy, 72 Swiss albino mice were divided into six groups. Group 1 was control, groups 2 and 3 included mice which were injected intraperitoneally (i.p.) with 100 or 200 mg/kg of MEROL at days 1, 4, 7, 10, 13 and 16; group 4 was injected (i.p.) with CTX (200 mg/kg) at day 17, groups 5 and 6 were injected (i.p.) with MEROL as groups 3 and 4 followed by 200 mg/kg CTX at day 17, respectively. At day 22, six mice from each group were sacrificed and the others were sacrificed at day 37. Results MEROL has a high content of total phenolics, saponins, total antioxidant capacity and DPPH radical scavenging activity. The median lethal dose (LD50) value of MEROL was 4.125 g/kg b.w. The inhibitory concentration 50 (IC50) value for DPPH radical scavenging was 55 μg/mL. Pretreatment with 100 mg/kg MEROL for 16 d ameliorated CTX-induced hepatotoxicity represented in lowering the levels of the aspartate aminotransferase (AST) and lipid profile and minimizing the histological damage. Conclusions Pretreatment with 100 mg/kg b.w. MEROL mitigated CTX-induced hepatotoxicity due to its antioxidant activity.

  6. 46 CFR 78.47-55 - Instructions for changing steering gear.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Instructions for changing steering gear. 78.47-55... OPERATIONS Markings for Fire and Emergency Equipment, Etc. § 78.47-55 Instructions for changing steering gear..., relating in order, the different steps to be taken in changing to the emergency steering gear. Each...

  7. 46 CFR 97.37-33 - Instructions for changing steering gear.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Instructions for changing steering gear. 97.37-33... steering gear. (a) Instructions in at least 1/2 inch letters and figures shall be posted in the steering... gear. Each clutch, gear, wheel, lever, valve, or switch which is used during the changeover shall...

  8. 46 CFR 130.140 - Steering on OSVs of 100 or more gross tons.

    Science.gov (United States)

    2010-10-01

    ... hydraulic-helm steering-system in paragraph (b) of this section. (b) Each hydraulic-helm steering-system... the vessel at every service speed without being damaged at maximum astern speed. (2) A hydraulic... stops. (6) Either— (i) Two steering pumps in accordance with § 130.130(c)(3) of this part; or (ii)...

  9. 7 CFR 59.103 - Mandatory weekly reporting for steers and heifers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Mandatory weekly reporting for steers and heifers. 59... (CONTINUED) LIVESTOCK MANDATORY REPORTING Cattle Reporting § 59.103 Mandatory weekly reporting for steers and heifers. (a) In general. The corporate officers or officially designated representatives of each steer...

  10. The Impact of Analog and Bang-Bang Steering Gear Control on Ship's Fuel Economy

    DEFF Research Database (Denmark)

    Nørtoft Thomsen, J. C.; Blanke, Mogens; Reid, R. E.

    1982-01-01

    it is found to be at least equally important regarding steering performance and fuel economy. The paper presents a comprehensive survey of steering gear principles commonly used, including relevant details of three analog steering gear servo principles, which have outperformed conventional designs. Control...

  11. Proportional directional valve based automatic steering system for tractors

    Institute of Scientific and Technical Information of China (English)

    Jin-yi LIU; Jing-quan TAN; En-rong MAO; Zheng-he SONG; Zhong-xiang ZHU‡

    2016-01-01

    Most automatic steering systems for large tractors are designed with hydraulic systems that run on either constant flow or constant pressure. Such designs are limited in adaptability and applicability. Moreover, their control valves can unload in the neutral position and eventually lead to serious hydraulic leakage over long operation periods. In response to the problems noted above, a multifunctional automatic hydraulic steering circuit is presented. The system design is composed of a 5-way-3-position proportional directional valve, two pilot-controlled check valves, a pressure-compensated directional valve, a pressure-compensated flow regulator valve, a load shuttle valve, and a check valve, among other components. It is adaptable to most open-center systems with constant flow supply and closed-center systems with load feedback. The design maintains the lowest pressure under load feedback and stays at the neutral position during unloading, thus meeting the requirements for steering. The steering controller is based on proportional-integral-derivative (PID) running on a 51-microcontroller-unit master control chip. An experimental platform is developed to establish the basic characteristics of the system subject to stepwise inputs and sinusoi-dal tracking. Test results show that the system design demonstrates excellent control accuracy, fast response, and negligible leak during long operation periods.

  12. Steering gameplay behavior in the interactive tag playground

    NARCIS (Netherlands)

    Delden, van Robby; Moreno, Alejandro; Poppe, Ronald; Reidsma, Dennis; Heylen, Dirk; Aarts, Emile; Ruyter, de Boris; Markopoulos, Panos; Loenen, van Evert; Wichert, Reiner; Schouten, Ben; Terken, Jacques; Kranenburg, van Rob; Ouden, den Elke; O'Hare, Gregory

    2014-01-01

    This paper deals with steering player behavior in the Interactive Tag Playground (ITP). The ITP, an ambient environment instrumented with contact-free sensor technology and ambient display capabilities, enhances the traditional game of tag by determining when a valid tag has been made and visualisin

  13. Steering Gameplay Behavior in the Interactive Tag Playground

    NARCIS (Netherlands)

    Van Delden, Robby; Moreno, Alejandro; Poppe, Ronald; Reidsma, Dennis; Heylen, Dirk K J

    2014-01-01

    This paper deals with steering player behavior in the Interactive Tag Playground (ITP). The ITP, an ambient environment instrumented with contact-free sensor technology and ambient display capabilities, enhances the traditional game of tag by determining when a valid tag has been made and visualisin

  14. Complex Education Systems: From Steering Change to Governance

    Science.gov (United States)

    Michel, Alain

    2016-01-01

    The theories and approaches of steering/monitoring a process of change within education systems have evolved over the last 20 years or so as a result of many factors such as globalisation and decentralisation, a faster pace of change, increasing expectations and demands from various stakeholders (parents, employers, teacher unions, etc.) and the…

  15. Analytic Steering: Inserting Context into the Information Dialog

    Energy Technology Data Exchange (ETDEWEB)

    Bohn, Shawn J.; Calapristi, Augustin J.; Brown, Shyretha D.; Nakamura, Grant C.

    2011-10-23

    An analyst’s intrinsic domain knowledge is a primary asset in almost any analysis task. Unstructured text analysis systems that apply un-supervised content analysis approaches can be more effective if they can leverage this domain knowledge in a manner that augments the information discovery process without obfuscating new or unexpected content. Current unsupervised approaches rely upon the prowess of the analyst to submit the right queries or observe generalized document and term relationships from ranked or visual results. We propose a new approach which allows the user to control or steer the analytic view within the unsupervised space. This process is controlled through the data characterization process via user supplied context in the form of a collection of key terms. We show that steering with an appropriate choice of key terms can provide better relevance to the analytic domain and still enable the analyst to uncover un-expected relationships; this paper discusses cases where various analytic steering approaches can provide enhanced analysis results and cases where analytic steering can have a negative impact on the analysis process.

  16. Threats and protection for electronically-steered array radars

    NARCIS (Netherlands)

    Janssen, J.P.B.; Monni, S.; Maas, A.P.M.; Vliet, F.E. van

    2008-01-01

    Front-end power overload protection is a vital issue in any electro-magnetic sensor. The issues around active electronically-steered arrays are more recent and pose new threats. Different categories of threats can damage the sensitive electronics in the phased-array radar, like hostile high power

  17. Image Processing In Laser-Beam-Steering Subsystem

    Science.gov (United States)

    Lesh, James R.; Ansari, Homayoon; Chen, Chien-Chung; Russell, Donald W.

    1996-01-01

    Conceptual design of image-processing circuitry developed for proposed tracking apparatus described in "Beam-Steering Subsystem For Laser Communication" (NPO-19069). In proposed system, desired frame rate achieved by "windowed" readout scheme in which only pixels containing and surrounding two spots read out and others skipped without being read. Image data processed rapidly and efficiently to achieve high frequency response.

  18. DSPIC BASED POWER ASSISTED STEERING USING BRUSHLESS DIRECT CURRENT MOTOR

    Directory of Open Access Journals (Sweden)

    G. R.P. Lakshmi

    2013-01-01

    Full Text Available This study illustrates the Electrically Assisted power Steering (EAS using BLDC motor for a vehicle. Earlier the Electrically Assisted power Steering (EAS was implemented with DSP. This study shows the usage of a dsPIC to control the BLDC motor with an encoder. The BLDC motor here is driven by dsPIC through a three phase inverter system. IRAMS type of inverter is used which is cost efficient and space efficient. The dsPIC supplied with the input of the steering. In its higher capacity the vehicles speed controller acts as the assistance level controller for steering effort. At the lower capacity, the torque controller gives the effort level control. In reality this can be realized as torque sensor and vehicle sensor interfaced in the dsPIC. For actual implementation in the system, a dsPIC-based BLDC motor controller with three-phase inverter module is used with Hall-effect sensor feedback. It is designed in such a way that the driver assistance can be varied at any time without any difficulty.

  19. The Analysis of The Fault of Electrical Power Steering

    Directory of Open Access Journals (Sweden)

    Zhang Li Wen

    2016-01-01

    Full Text Available This paper analysis the common fault types of primary Electrical Power Steering system, meanwhile classify every fault. It provides the basis for further troubleshooting and maintenance. At the same time this paper propose a practical working principle of fault-tolerant, in order to make the EPS system more security and durability.

  20. Mechanisms of ovipositor insertion and steering of a parasitic wasp.

    Science.gov (United States)

    Cerkvenik, Uroš; van de Straat, Bram; Gussekloo, Sander W S; van Leeuwen, Johan L

    2017-09-12

    Drilling into solid substrates with slender beam-like structures is a mechanical challenge, but is regularly done by female parasitic wasps. The wasp inserts her ovipositor into solid substrates to deposit eggs in hosts, and even seems capable of steering the ovipositor while drilling. The ovipositor generally consists of three longitudinally connected valves that can slide along each other. Alternative valve movements have been hypothesized to be involved in ovipositor damage avoidance and steering during drilling. However, none of the hypotheses have been tested in vivo. We used 3D and 2D motion analysis to quantify the probing behavior of the fruit-fly parasitoid Diachasmimorpha longicaudata (Braconidae) at the levels of the ovipositor and its individual valves. We show that the wasps can steer and curve their ovipositors in any direction relative to their body axis. In a soft substrate, the ovipositors can be inserted without reciprocal motion of the valves. In a stiff substrate, such motions were always observed. This is in agreement with the damage avoidance hypothesis of insertion, as they presumably limit the overall net pushing force. Steering can be achieved by varying the asymmetry of the distal part of the ovipositor by protracting one valve set with respect to the other. Tip asymmetry is enhanced by curving of ventral elements in the absence of an opposing force, possibly due to pretension. Our findings deepen the knowledge of the functioning and evolution of the ovipositor in hymenopterans and may help to improve man-made steerable probes.

  1. Multifunctional Converter Drive for Automotive Electric Power Steering Systems

    NARCIS (Netherlands)

    Hackner, T.J.

    2013-01-01

    In this thesis it is shown that in the case of an automotive electric power steering system, critical pulse power loads can be decoupled from the power net with a storage element and a multifunctional converter. A multifunctional converter system is proposed because it uses the motor drive system as

  2. Interagency Advanced Power Group -- Steering group meeting minutes

    Energy Technology Data Exchange (ETDEWEB)

    1993-11-18

    This document contains the draft meeting minutes of the Steering Group of the Interagency Advanced Power Group. Included are the discussions resulting from the presentation of working group reports and the results of a discussion of IAPG policies and procedures. In the appendix are the reports of the following working groups: Electrical, Mechanical, Solar, and Systems.

  3. Threats and protection for electronically-steered array radars

    NARCIS (Netherlands)

    Janssen, J.P.B.; Monni, S.; Maas, A.P.M.; Vliet, F.E. van

    2008-01-01

    Front-end power overload protection is a vital issue in any electro-magnetic sensor. The issues around active electronically-steered arrays are more recent and pose new threats. Different categories of threats can damage the sensitive electronics in the phased-array radar, like hostile high power el

  4. CLOSED FORM OF THE STEERED ELONGATED HERMITE-GAUSS WAVELETS

    NARCIS (Netherlands)

    Papari, Giuseppe; Campisi, Patrizio; Petkov, Nicolai

    2010-01-01

    We provide a closed form, both in the spatial and in the frequency domain, of a family of wavelets which arise from steering elongated Hermite-Gauss filters. These wavelets have interesting mathematical properties, as they form new dyadic families of eigenfunctions of the 2D Fourier transform, and

  5. The value of theoretical multiplicity for steering transitions towards sustainability

    NARCIS (Netherlands)

    Dewulf, A.; Termeer, C.J.A.M.; Pot, W.D.; Werkman, R.A.; Breeman, G.E.

    2009-01-01

    Transition management, as a theory of directing structural societal changes towards sustainable system innovations, has become a major topic in scientific research over the last years. In this paper we focus on the question how transitions towards sustainability can be steered, governed or managed,

  6. Mechanics of Flexible Needles Robotically Steered through Soft Tissue

    NARCIS (Netherlands)

    Misra, S.; Reed, K.B.; Schafer, B.W.; Ramesh, K.T.; Okamura, A.M.

    2010-01-01

    The tip asymmetry of a bevel-tip needle results in the needle naturally bending when it is inserted into soft tissue. This enables robotic needle steering, which can be used in medical procedures to reach subsurface targets inaccessible by straight-line trajectories. However, accurate path planning

  7. Effect of Lagenaria siceraria fruit extract (Bottle gourd on hepatotoxicity induced by antitubercular drugs in albino rats

    Directory of Open Access Journals (Sweden)

    Satyajeet K. Funde

    2013-12-01

    Conclusion: Ethanolic extract of Lagenaria siceraria fruit possesses significant hepatoprotective and antioxidant activity in antitubercular drugs induced hepatotoxicity. [Int J Basic Clin Pharmacol 2013; 2(6.000: 728-734

  8. GENE EXPRESSION PROFILING IN THE LIVER OF CD-1 MICE TO CHARACTERIZE THE HEPATOTOXICITY OF TRIAZOLE FUNGICIDES

    Science.gov (United States)

    Four triazole fungicides used in agricultural or pharmaceutical applications were examined for hepatotoxic effects in mouse liver. Besides organ weight, histopathology, and cytochrome P450 (CYP) enzyme induction, DNA microarrays were used to generate gene expression profiles and ...

  9. Modulatory effects of dietary inclusion of garlic (Allium sativum on gentamycin–induced hepatotoxicity and oxidative stress in rats

    Directory of Open Access Journals (Sweden)

    Adedayo O. Ademiluyi

    2013-06-01

    Conclusions: These results suggest that dietary inclusion of garlic powder could protect against gentamycin-induced hepatotoxicity, improve antioxidant status and modulate oxidative stress; a function attributed to their phenolic constituents.

  10. Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

    OpenAIRE

    Akbulut, Sami; Elbe, Hulya; Eris, Cengiz; Dogan, Zumrut; Toprak, Gulten; Otan, Emrah; Erdemli, Erman; Turkoz, Yusuf

    2014-01-01

    AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.

  11. Natural terpenes prevent mitochondrial dysfunction, oxidative stress and release of apoptotic proteins during nimesulide-hepatotoxicity in rats.

    Science.gov (United States)

    Singh, Brijesh Kumar; Tripathi, Madhulika; Chaudhari, Bhushan P; Pandey, Pramod K; Kakkar, Poonam

    2012-01-01

    Nimesulide, an anti-inflammatory and analgesic drug, is reported to cause severe hepatotoxicity. In this study, molecular mechanisms involved in deranged oxidant-antioxidant homeostasis and mitochondrial dysfunction during nimesulide-induced hepatotoxicity and its attenuation by plant derived terpenes, camphene and geraniol has been explored in male Sprague-Dawley rats. Hepatotoxicity due to nimesulide (80 mg/kg BW) was evident from elevated SGPT, SGOT, bilirubin and histo-pathological changes. Antioxidants and key redox enzymes (iNOS, mtNOS, Cu/Zn-SOD, Mn-SOD, GPx and GR) were altered significantly as assessed by their mRNA expression, Immunoblot analysis and enzyme activities. Redox imbalance along with oxidative stress was evident from decreased NAD(P)H and GSH (56% and 74% respectively; Pterpenes against nimesulide toxicity. Therefore CG, a combination of natural terpenes prevented nimesulide induced cellular damage and ensuing hepatotoxicity.

  12. Direct Protection Against Acetaminophen Hepatotoxicity by Propylthiouracil: IN VIVO AND IN VITRO STUDIES IN RATS AND MICE

    OpenAIRE

    1981-01-01

    Hepatotoxicity caused by acetaminophen can be prevented by enzyme-catalyzed conjugation of its reactive metabolite with glutathione (GSH). Since we have shown in previous studies that 6-N-propyl-2-thiouracil (PTU) can substitute for GSH as a substrate for the GSH S-transferases, we examined the possibility that PTU might also protect against acetaminophen hepatotoxicity by direct chemical interaction with the reactive metabolite of acetaminophen. In an in vitro system consisting of [3H]acetam...

  13. Effect of Lagenaria siceraria fruit extract (Bottle gourd) on hepatotoxicity induced by antitubercular drugs in albino rats

    OpenAIRE

    Satyajeet K. Funde; Jugalkishore B. Jaju; Shrikant C. Dharmadhikari; Ganesh R. Pawar

    2013-01-01

    Background: Anti TB drug induced hepatotoxicity has higher incidence in Indian population [11.5%] than western population [4.5%]. Antitubercular drug induced hepatotoxicity is mediated through oxidative and free radical damage to hepatocytes. Lagenaria siceraria [Bottle Gourd] is reported to have antioxidant and hepatoprotective activity. Hence in the present study we tested hepatoprotective and antioxidant activity of fruit extract of L. Siceraria in anti tubercular drug induced hepatotoxici...

  14. A study of effect of Nigella sativa oil in paracetamol induced hepatotoxicity in albino rats

    OpenAIRE

    Manik S. Ghadlinge; Jugalkishor B. Jaju; Rakhamaji D. Chandane; Rakesh R. Jadhav; Rama R. Bhosle

    2014-01-01

    Background: Acetaminophen (paracetamol) toxicity is a common cause of drug induced hepatotoxicity in children and adults. Specific treatment of paracetamol induced hepatitis is available in the form of N acetylcysteine only. Nigella sativa (NS) is used for the treatment of various ailments. Many studies have shown that NS plant has hepatoprotective potential. Hence, this study study was carried out to explore the prophylactic and therapeutic effect of NS oil against hepatotoxicity induced by ...

  15. Study on a New Steering Mechanism for Point-the-Bit Rotary Steerable System

    Directory of Open Access Journals (Sweden)

    Yuanzhi Li

    2014-02-01

    Full Text Available This paper presents a novel steering mechanism embedded in a point-the-bit rotary steerable system (RSS for oilfield exploitation. The new steering mechanism adopts a set of universal joints to alleviate the high alternative strain on drilling mandrel and employs a specially designed planetary gear small tooth number difference (PGSTD to achieve directional steering. Its principle and characteristics are explained and examined through a series of analyses. First, the eccentric displacement vector of the offset point on the drilling mandrel is formulated and kinematic solutions are established. Next, structural design for the new steering mechanism is addressed. Then, procedures and program architectures for simulating offset state of the drilling mandrel and motion trajectory of the whole steering mechanism are presented. After that, steering motion simulations of the new steering mechanism for both 2D and 3D well trajectories are then performed by combining LabVIEW and SolidWorks. Finally, experiments on the steering motion control of the new steering mechanism prototype are carried out. The simulations and experiments reveal that the steering performance of the new steering mechanism is satisfied. The research can provide good guidance for further research and engineering application of the point-the-bit RSS.

  16. Development of active rear steer actuator. Development of four wheel steer actuator for active safety; Active rear steer actuator no kaihatsu. Yobo anzen ni muketa 4WS actuator no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, T. [Aisin Seiki Co. Ltd., Aichi (Japan)

    1997-10-01

    Recently, ecology, energy saving and safety have become important issues. And Active Safety is spotlighted in vehicle control area. Many researches and developments on four wheel steer system have been done to improve vehicle stability. We have developed the Active Rear Steer system with electromechanical Actuator, which is mass-productive, compact, and high response and durable. 10 figs., 5 tabs.

  17. To Set Up a Logistic Regression Prediction Model for Hepatotoxicity of Chinese Herbal Medicines Based on Traditional Chinese Medicine Theory

    Science.gov (United States)

    Liu, Hongjie; Li, Tianhao; Zhan, Sha; Pan, Meilan; Ma, Zhiguo; Li, Chenghua

    2016-01-01

    Aims. To establish a logistic regression (LR) prediction model for hepatotoxicity of Chinese herbal medicines (HMs) based on traditional Chinese medicine (TCM) theory and to provide a statistical basis for predicting hepatotoxicity of HMs. Methods. The correlations of hepatotoxic and nonhepatotoxic Chinese HMs with four properties, five flavors, and channel tropism were analyzed with chi-square test for two-way unordered categorical data. LR prediction model was established and the accuracy of the prediction by this model was evaluated. Results. The hepatotoxic and nonhepatotoxic Chinese HMs were related with four properties (p flavors (p 0.05). There were totally 12 variables from four properties and five flavors for the LR. Four variables, warm and neutral of the four properties and pungent and salty of five flavors, were selected to establish the LR prediction model, with the cutoff value being 0.204. Conclusions. Warm and neutral of the four properties and pungent and salty of five flavors were the variables to affect the hepatotoxicity. Based on such results, the established LR prediction model had some predictive power for hepatotoxicity of Chinese HMs. PMID:27656240

  18. To Set Up a Logistic Regression Prediction Model for Hepatotoxicity of Chinese Herbal Medicines Based on Traditional Chinese Medicine Theory.

    Science.gov (United States)

    Liu, Hongjie; Li, Tianhao; Chen, Lingxiu; Zhan, Sha; Pan, Meilan; Ma, Zhiguo; Li, Chenghua; Zhang, Zhe

    2016-01-01

    Aims. To establish a logistic regression (LR) prediction model for hepatotoxicity of Chinese herbal medicines (HMs) based on traditional Chinese medicine (TCM) theory and to provide a statistical basis for predicting hepatotoxicity of HMs. Methods. The correlations of hepatotoxic and nonhepatotoxic Chinese HMs with four properties, five flavors, and channel tropism were analyzed with chi-square test for two-way unordered categorical data. LR prediction model was established and the accuracy of the prediction by this model was evaluated. Results. The hepatotoxic and nonhepatotoxic Chinese HMs were related with four properties (p 0.05). There were totally 12 variables from four properties and five flavors for the LR. Four variables, warm and neutral of the four properties and pungent and salty of five flavors, were selected to establish the LR prediction model, with the cutoff value being 0.204. Conclusions. Warm and neutral of the four properties and pungent and salty of five flavors were the variables to affect the hepatotoxicity. Based on such results, the established LR prediction model had some predictive power for hepatotoxicity of Chinese HMs.

  19. Mechanisms of halocarbon-induced hepatotoxicity in the mouse. Final report, 1 April 1989-31 March 1990

    Energy Technology Data Exchange (ETDEWEB)

    Smith, M.A.; Gandy, J.

    1990-05-30

    Previous studies have shown that high-dose exposure to the halocarbon bromobenzene resulted in hepatotoxicity and lethality that was substantially diminished by co-treatment with the alpha-adrenergic antagonist, phentolamine. The purpose of this study was to compare the hepatoxicity resulting from exposure to the related halocarbons, chlorobenzene, bromobenzene and iodobenzene, and to determine whether the resulting hepatotoxicity could be antagonized by phentolamine. Halobenzene-induced changes in hepatic glutathione concentrations and serum concentrations of catecholamines were determined as possible mediators of hepatic damage. Iodobenzene administration resulted in toxicities similar to that seen with bromobenzene. Administration of either iodobenzene or bromobenzene resulted in hepatotoxicity as measured by serum alanine aminotransferase (ALT) activity about 1000 fold above normal values. Chlorobenzene was also capable of producing hepatotoxicity, but not to the same extent as iodobenzene. Chlorobenzene-induced hepatotoxicity resulted in serum ALT values approximately 100 fold above normals. Chlorobenzene, bromobenzene or iodobenzene administration significantly decreased hepatic glutathione concentrations to approximately 20% of control concentrations. Phentolamine co-treatments significantly decreased serum ALT activity for all three compounds suggesting that hepatotoxicity might be mediated through an alpha-adrenergic system.

  20. Time of daily supplementation for steers grazing dormant intermediate wheatgrass pasture.

    Science.gov (United States)

    Barton, R K; Krysl, L J; Judkins, M B; Holcombe, D W; Broesder, J T; Gunter, S A; Beam, S W

    1992-02-01

    To compare the effects of time of daily protein supplementation on grazing behavior, forage intake, digesta kinetics, ruminal fermentation, and serum hormones and metabolites, 12 ruminally cannulated Holstein steers (449 and 378 kg average initial and final BW, respectively) were allotted to three groups. Treatments consisted of CON = no supplement, AM = cottonseed meal (.25% of BW) at 0600, and PM = cottonseed meal (.25% of BW) at 1200. Steers grazed a dormant (1.1% N) intermediate wheatgrass (Thinopyrum intermedium Host) pasture. Sampling trials occurred in December, January, and February. Supplementation altered (P = .01) time spent grazing; CON steers grazed approximately 1.5 h longer than supplemented steers. Supplemented steers lost less (P = .02) BW (-40 kg) than CON steers (-75 kg) did. Supplementation did not alter (P greater than .15) forage OM intake; however, total OM intake was greater (P = .01) for supplemented steers (22.3 g/kg of BW) than for CON (18.4 g/kg of BW) steers. Supplementation did not affect (P greater than .15) digesta kinetics. Extent of in situ NDF (96 h) and rate (%/h) of disappearance for supplemented steers was greater (P = .01) than for CON steers. Across all periods, ruminal NH3 N and total VFA concentrations were lower (P = .01) for CON steers than for supplemented steers. Serum insulin (ng/mL) concentration was lower (P = .03) and concentration of serum growth hormone (ng/mL) was higher (P = .02) for CON steers than for supplemented steers. Cottonseed meal supplementation enhanced utilization of intermediate wheatgrass; however, supplementation time had minimal effects on the variables measured.

  1. Protective role of food supplement Spirulina fusiformis in chemical induced hepatotoxicity: A Bromobenzene model in rats

    Directory of Open Access Journals (Sweden)

    Evan Prince Sabina

    2014-03-01

    Full Text Available The present study evaluated the efficacy of Spirulina fusiformis in protecting against chemical induced hepatotoxicity in rats using Bromobenzene as the candidate toxin. A single oral dose of bromobenzene (BB (10mmol/kg b.w. resulted in significant (p< 0.05 decrease in antioxidant levels (catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidese, total reduced glutathione and total protein, and significant (p< 0.05 increase in the levels of serum bilirubin, liver enzymes (alanine transaminase, aspartate transaminase and alkaline phosphatase indicating the induction of hepatotoxicity. Spirulina fusiformis (400 mg/kg b.w was orally administered for 8 days prior to the administration of BB and was seen to protect the above parameters from significant changes upon challenge with bromobenzene. This was also confirmed by the histological examination of liver tissues after sacrifice. The protective effect of Spirulina fusiformis was comparable to that of the standard hepatoprotective drug sylimarin.

  2. Hepatotoxic effect of 1-bromopropane and its conjugation with glutathione in male ICR mice.

    Science.gov (United States)

    Lee, Sang Kyu; Jo, Sang Wook; Jeon, Tae Won; Jun, In Hye; Jin, Chun Hua; Kim, Ghee Hwan; Lee, Dong Ju; Kim, Tae-Oh; Lee, Eung-Seok; Jeong, Tae Cheon

    2005-10-01

    The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of 1-BP in corn oil to mice significantly increased serum activities of alanine aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In addition, 1-BP treatment dose-dependently increased levels of S-propyl GSH conjugate at 12 h after treatment, as measured by liquid chromatography-electrospray ionization tandem mass spectrometry. The GSH conjugate was maximally increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel depletion of hepatic GSH content. Finally, 1-BP induced the production of malondialdehyde in liver. The present results suggest that 1-BP might cause hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the formation of GSH conjugates in male ICR mice.

  3. Scientific and Regulatory Perspectives in Herbal and Dietary Supplement Associated Hepatotoxicity in the United States

    Directory of Open Access Journals (Sweden)

    Mark I. Avigan

    2016-03-01

    Full Text Available In the United States (US, the risk of hepatotoxicity linked to the widespread use of certain herbal products has gained increased attention among regulatory scientists. Based on current US law, all dietary supplements sold domestically, including botanical supplements, are regulated by the Food and Drug Administration (FDA as a special category of foods. Under this designation, regulatory scientists do not routinely evaluate the efficacy of these products prior to their marketing, despite the content variability and phytochemical complexity that often characterizes them. Nonetheless, there has been notable progress in the development of advanced scientific methods to qualitatively and quantitatively measure ingredients and screen for contaminants and adulterants in botanical products when hepatotoxicity is recognized.

  4. HEPATOPROTECTIVE ACTIVITY OF ALSTONIA SCHOLARIS FRUITS AGAINST CARBON TETRACHLORIDE-INDUCED HEPATOTOXICITY IN RATS

    Directory of Open Access Journals (Sweden)

    K. RAVI SHANKAR, A. LAKSHMANA RAO, L. KALYANI

    2013-09-01

    Full Text Available The hepatoprotective activity of ethanolic extract of fruits of Alstonia scholaris was evaluated by carbon tetrachloride (CCL4-induced hepatotoxicity in rats. The toxicant CCL4 was used to induce hepatotoxicity at a dose of 2 ml/kg as 1:1 mixture with olive oil. The ethanolic extract of fruits of Alstonia scholaris was administered in the dose of 150 and 300 mg/kg/day orally for 5 days. Silymarin (50 mg/kg was used as standard drug. The hepatoprotective effect of the ethanolic extract was evaluated by the assessment of biochemical parameters such as SGOT, SGPT, SALKP, total bilirubin and histopathological studies of the liver. Treatment of animals with the ethanolic extract significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver as indicated by lower levels of serum bilirubin as compared with the normal and silymarin treated groups.

  5. Protective effect of alcoholic extract of Entada pursaetha DC. against CCl4-induced hepatotoxicity in rats.

    Science.gov (United States)

    Gupta, Gaurav; More, Amar Sunil; Kumari, Rashmi Rekha; Lingaraju, Madhu Cholenahalli; Kumar, Dhirendra; Kumar, Dinesh; Mishra, Santosh Kumar; Tandan, Surender Kumar

    2014-03-01

    The alcoholic extract of stem of E. pursaetha (PSE, 30, 100, 300 mg/kg body weight, po for 7 days) showed hepatoprotective activity against CCl4 (2 mL/kg body weight, ip)-induced hepatotoxicity. The extract exhibited a significant dose-dependent hepatoprotective effect comparable to standard drug silymarin, by preventing increase in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and total bilirubin, lactate dehydrogenase; by lowering hepatic levels of malonaldehyde, nitrate-nitrite, myeloperoxidase activity; enhancing activities of antioxidant enzymes, superoxide dismutase, catalase and increasing reduced glutathione levels in liver, which suggests the antioxidant property of PSE. Histopathological studies also supported the above biochemical parameters. The results suggested that alcoholic extract of E. pursaetha possesses significant hepatoprotective activity in CCl4-induced acute hepatotoxicity in rats and this is likely to be mediated through its antioxidant activities.

  6. Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats

    Directory of Open Access Journals (Sweden)

    Daniela Rodrigues

    2012-12-01

    Full Text Available CONTEXT: Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. OBJECTIVE: The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. METHODS: Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x10(7 hepatocytes or phosphate buffered saline through the portal vein or into the spleen and were sacrificed after 48 hours. RESULTS: Alanine aminotransferase levels measured within the experiment did not differ between groups at any time point. Molecular analysis and histology showed presence of hepatocytes in liver of transplanted animals injected either through portal vein or spleen. CONCLUSION: These data demonstrate the feasibility and efficacy of hepatocyte transplantation in the liver or spleen in a mild acetaminophen-induced hepatotoxicity model.

  7. Enoxaparin-induced hepatotoxicity: an under-recognised complication of enoxaparin therapy.

    Science.gov (United States)

    Pivarnik, Katie Ann; Schiffman, Fred; Sullivan, James; Finn, Arkadiy

    2016-09-23

    Low-molecular-weight heparins including enoxaparin are commonly used for anticoagulation as prophylaxis and treatment for deep vein thrombosis (DVT). Prescribers of enoxaparin monitor for common side effects, such as bleeding and thrombocytopenia, but hepatotoxicity, a less common and under-reported adverse effect, may be overlooked. This report describes a case of enoxaparin-induced hepatotoxicity in a 57-year-old man who was started on the drug for a DVT. Within 3 days of taking enoxaparin, elevated transaminases were noted, and the drug was discontinued after 6 days. Similar to other published reports, the patient's transaminases peaked 1 day after discontinuation of the drug and then trended down to normal over 32 days.

  8. Protective effect of stem bark of Ceiba pentandra linn. against paracetamol-induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Nirmal K Bairwa

    2010-01-01

    Full Text Available The present study reports protective activity of ethyl acetate fraction of methanol extract of stem bark of Ceiba pentandra against paracetamol-induced liver damage in rats. The ethyl acetate fraction (400 mg/kg was administered orally to the rats with hepatotoxicity induced by paracetamol (3 gm/kg. Silymarin (100 mg/kg was used as positive control. High performance thin layer chromatography (HPTLC fingerprinting of ethyl acetate fraction revealed presence of its major chemical constituents. A significant (P < 0.05 reduction in serum enzymes GOT (ALT, aspartate aminotransferase (AST, GPT alkaline phosphatase (ALP, total bilirubin content and histopathological screening in the rats treated gave indication that ethyl acetate fraction of methanolic extract of Ceiba pentandra possesses hepatoprotective potential against paracetamol-induced hepatotoxicity in rats.

  9. Hepatoprotective effect of leaves of aqueous ethanol extract of Cestrum nocturnum against paracetamol-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    M. Imran Qadir

    2014-06-01

    Full Text Available The hepatoprotective activities of Cestrum nocturnum (Queen of Night was evaluated against the paracetamol induced hepatotoxicity in the mice. Aqueous ethanol (30:70 extract of plant was obtained by maceration. Results showed that aqueous ethanol extract of C. nocturnum (250 mg/kg and 500 mg/kg produced significant (p<0.05 hepatoprotective activities against paracetamol induced liver injury in Swiss albino mice. Histopathalogical studied of liver further supported the hepatoprotective effects of C. notrunum. Phyto-chemical screening showed the presence of alkaloids, flavonoids, saponins, terpenes, phenolic compounds, carbohydrates and volatile oils. Most of the flavonoids have hepatoprotective activity. Therefore, the hepatoprotective activity of C. nocturnum may be due to the presence of flavonoids and phenolic components. It was concluded from the present study that aqueous ethanol extract of leaves of C. nocturnum has hepatoprotective activity against the paracetamol-induced hepatotoxicity in albino mice.

  10. Hepatotoxicity associated with microcystin/ Hepatotoxicidade associada à microcistina

    Directory of Open Access Journals (Sweden)

    Ana Paula Frederico Rodrigues Loureiro Bracarense

    2008-08-01

    Full Text Available Urban and industrial discharges, intense agricultural exploitation and fisheries have been causing the eutrophication in both drinking and recreational waters. A frequent consequence of eutrophication in waters is the massive development of cyanobacteria. The occurrence of these blooms induces a severe problem, as Microcystis aeruginosa, the most widespread distributed cyanobacteria, can produce microcystins (MC. Toxic effects of MC have been described in liver, lungs, stomach, and intestine. Deaths in wildlife, livestock and human beings were also associated with MC exposition. MC exposition can occurs directly by ingestion, inhalation, contact, intravenous inoculation of contaminated water (hemodialysis or indirectly, by the consumption of animals, as fish and mollusks, the majors ingestors of cyanobacteria and its toxins. The most toxic MC, an also the most common is microcystin-LR (MC-LR, that has the liver as the main target organ. Microcystin is taken up specifically into the liver by bile acid transporters and, after entering the cytoplasm, inhibit protein phosphatases 1 and 2A, which leads to the increase in protein phosphorylation. This effect has two main consequences: the destruction of cytoskeleton directly causing cytotoxic effects, and deregulation of cell division, leading to tumor-promoting activity. Acute exposition to MC induces severe intrahepatic hemorrhage, necrosis and apoptosis, while chronic exposure can cause hepatic or intestinal neoplasia. It has been documented that MC hepatotoxicity is closely associated with intracellular reactive oxygen species formation. Natural degradation of microcystins depends on the solar radiation and bacteria. If degradation is insufficient, MC will persist in the freshwater food chain. Microcystin contamination of waters is therefore a hazard to human and animal health, so efforts to avoid eutrophication of waters sources are essential, in order to minimize the risks to public health

  11. Hydrogen sulfide attenuates carbon tetrachloride-induced hepatotoxicity, liver cirrhosis and portal hypertension in rats.

    Directory of Open Access Journals (Sweden)

    Gang Tan

    Full Text Available BACKGROUND: Hydrogen sulfide (H(2S displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H(2S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H(2S in carbon tetrachloride (CCl(4-induced hepatotoxicity, cirrhosis and portal hypertension. METHODS AND FINDINGS: Sodium hydrosulfide (NaHS, a donor of H(2S, and DL-propargylglycine (PAG, an irreversible inhibitor of cystathionine γ-lyase (CSE, were applied to the rats to investigate the effects of H(2S on CCl(4-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H(2S, hepatic H(2S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl(4 significantly reduced serum levels of H(2S, hepatic H(2S production and CSE expression. NaHS attenuated CCl(4-induced acute hepatotoxicity by supplementing exogenous H(2S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, hyaluronic acid (HA, albumin, tumor necrosis factor (TNF-α, interleukin (IL-1β, IL-6 and soluble intercellular adhesion molecule (ICAM-1, liver histology, hepatic hydroxyproline content and α-smooth muscle actin (SMA expression. PAG showed opposing effects to NaHS on most of the above parameters. CONCLUSIONS: Exogenous H(2S attenuates CCl(4-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H(2S may present a promising approach, particularly for its prophylactic effects, against liver

  12. Increased susceptibility of Nrf2-null mice to 1-bromopropane-induced hepatotoxicity.

    Science.gov (United States)

    Liu, Fang; Ichihara, Sahoko; Valentine, William M; Itoh, Ken; Yamamoto, Masayuki; Sheik Mohideen, Sahabudeen; Kitoh, Junzoh; Ichihara, Gaku

    2010-06-01

    1-Bromopropane (1-BP) was introduced as an alternative to ozone-depleting solvents. However, it was found to exhibit neurotoxicity, reproductive toxicity, and hepatotoxicity in rodents and neurotoxicity in human. However, the mechanisms underlying the toxicities of 1-BP remain elusive. The present study investigated the role of oxidative stress in 1-BP-induced hepatotoxicity using nuclear factor erythroid 2-related factor 2 (Nrf2)-null mice. Groups of 24 male Nrf2-null mice and 24 male wild-type (WT) C57BL/6J mice were each divided into three groups of eight and exposed to 1-BP at 0, 100, or 300 ppm for 8 h/day for 28 days by inhalation. Liver histopathology showed significantly larger area of necrosis in Nrf2-null mice relative to WT mice at the same exposure level. Nrf2-null mice also had greater malondialdehyde (MDA) levels, higher ratio of oxidized glutathione/reduced form of glutathione, and lower total glutathione content. The constitutive level and the increase in ratio per exposure level of glutathione S-transferase (GST) activity were lower in the liver of Nrf2-null mice than WT mice. Exposure to 1-BP at 300 ppm increased the messenger RNA levels of heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GcLm), glutamate-cysteine synthetase (GcLc), glutathione reductase, and NAD(P)H: quinone oxidoreductase 1 (NQO1) in WT mice but not in Nrf2-null mice except for GST Yc2. Nrf2-null mice were more susceptible to 1-BP-induced hepatotoxicity. That oxidative stress plays a role in 1-BP hepatotoxicity is deduced from the low expression levels and activities of antioxidant enzymes and high MDA levels in Nrf2-null mice.

  13. Clinical and Laboratory Findings of Lead Hepatotoxicity in the Workers of a Car Battery Manufacturing Factory

    Directory of Open Access Journals (Sweden)

    Bita Dadpour

    2016-02-01

    Full Text Available Background: Occupational lead poisoning is common in workers of some industries, but lead hepatotoxicity has rarely been reported. Several animal studies have revealed lead induced liver damage but clinical studies concerning the manifestations of lead induced liver toxicity in humans are scares. This study was designed to investigate the clinical manifestations and pathological parameters of hepatic dysfunction and its relationship with blood and urine lead concentrations in a car battery-manufacturing workers. Methods: This cross sectional study was carried out in Mashhad, Iran, during April-June 2011. One hundred and twelve workers underwent blood and urine sampling for determination of lead concentrations and liver function tests. Clinical signs and symptoms of possible lead hepatotoxicity were investigated. Results: Mean (±SD age of the workers was 28.78 (±5.17 yr with a daytime work of 8.67 (±1.41 h and mean work duration of 3.89 (±2.40 yr. Mean blood lead concentration (BLC and urine lead concentration (ULC were 398.95 (±177.41 µg/l and 83.67(±50 μg/l, respectively. We found no correlation between the clinical findings and BLC or ULC. A weak correlation (R: 0.27, P=0.087 between serum alkaline phosphatase concentration and BLC was obtained. No significant relationship was found between other liver function tests and BLC or ULC. Conclusion: We found no specific clinical and laboratory abnormalities of liver in the workers of car battery manufacturer who had chronic lead toxicity. Further investigations with more specific laboratory tests such as LDH5 and gamma glutamyl transferase (GGT as well as novel biomarkers of metal induced hepatotoxicity might be helpful in evaluating lead hepatotoxicity.

  14. Clinical and Laboratory Findings of Lead Hepatotoxicity in the Workers of a Car Battery Manufacturing Factory

    OpenAIRE

    Bita Dadpour; Reza Afshari; Seyed Reza Mousavi; Sina Kianoush; Mohamad Reza Keramati; Vali Allah Moradi; Mahmood Sadeghi; Faezeh Madani Sani; Mahdi Balali Mood

    2016-01-01

    Background: Occupational lead poisoning is common in workers of some industries, but lead hepatotoxicity has rarely been reported. Several animal studies have revealed lead induced liver damage but clinical studies concerning the manifestations of lead induced liver toxicity in humans are scares. This study was designed to investigate the clinical manifestations and pathological parameters of hepatic dysfunction and its relationship with blood and urine lead concentrations in a car battery-ma...

  15. Effect of Mallotus Philippensis Muell.-Arg leaves against hepatotoxicity of Carbon tetrachloride in rats

    OpenAIRE

    Ramakrishna S; Geetha K.M,; Bhaskar gopal P.V.V.S,; Ranjit kumar P; Charan Madav. P,; Umachandar. L

    2011-01-01

    Liver Toxicity is a major health problem of worldwide proportions. Herbal medicines derived from plant extracts are being increasingly utilized to treat a wide variety of clinical diseases. In the present study MEMP leaves is used to screen the hepatoprotective activity. Hepatotoxicity was induced in experimental animals by administration of carbon tetra chloride (CCl4) (25ml/kg, i.p.). Silymarin (25 mg/kg, p.o.) was used as the standard. Functional parameters like onset of sleep and duration...

  16. Preventive effect of zinc toward the hepatotoxicity of nickel in rats

    OpenAIRE

    Kechrid, Zine

    2013-01-01

    We studied the effect of zinc treatment on nickel sulphate-induced hepatotoxicity in male albino rats. Liver dysfunction parameters represented by aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), blood glucose, serum total protein and serum albumin were estimated. Liver glutathione level, catalase and GPx activities were also determined in liver as indicators of oxidative damage. Exposure of rats to nickel caused a significant a decrease in body weight and...

  17. Hepatoprotective potential of ethanolic extract of Pandanus odoratissimus root against paracetamol-induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Garima Mishra

    2015-01-01

    Full Text Available Background: Pandanus odoratissimus (Pandanaceae is popular in the indigenous system of medicines like Ayurveda, Siddha, Unani and Homoeopathy. In the traditional system of medicine various plant parts such as leaves, root, flowers, and oils are used as anthelmintic, tonic, stomachic, digestive and in the treatment of jaundice and various liver disorders. Objective: The aim was to investigate the hepatoprotective activity of ethanolic extract of the root of P. odoratissimus against paracetamol (PCM induced hepatotoxicity in rats. Materials and Methods: Hepatotoxicity was induced in male Wistar rat by PCM (2 g/kg b.w. p.o. for 7 days. The ethanolic extract of P. odoratissimus root was administered at the dose level of 200 mg/kg and 400 mg/kg b.w. orally for 7 days and silymarin (100 mg/kg b.w. p.o. as standard drug was administered once daily for a week. The hepatoprotective effect of ethanolic extract was evaluated by assessment of biochemical parameters such as serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase, serum alkaline phosphatase, total and direct bilirubin and triglycerides. Histopathological study of rat liver was also done. Results: Experimental findings revealed that the extract at dose level of 200 mg/kg and 400 mg/kg of b.w. showed dose dependant hepatoprotective effect against PCM induced hepatotoxicity by significantly restoring the levels of serum enzymes to normal that was comparable to that of silymarin, but the extract at dose level of 400 mg/kg was found to be more potent when compared to that of 200 mg/kg. Besides, the results obtained from histopathological study also support the study. Conclusion: From the results, it can be concluded that ethanolic extract of the root of P. odoratissimus afforded significant protection against PCM induced hepatotoxicity in rats.

  18. Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity

    Science.gov (United States)

    Massart, Julie; Begriche, Karima; Moreau, Caroline; Fromenty, Bernard

    2017-01-01

    Background Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. Aim The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity. For this purpose, we performed a data-mining analysis using different queries including drug-induced liver injury (or DILI), drug-induced hepatotoxicity, fatty liver, nonalcoholic fatty liver disease (or NAFLD), steatosis and obesity. The main data from the collected articles are reported in this review and when available, some pathophysiological hypotheses are put forward. Relevance for patients Drugs that could pose a potential risk in obese patients include compounds belonging to different pharmacological classes such as acetaminophen, halothane, methotrexate, rosiglitazone, stavudine and tamoxifen. For some of these drugs, experimental investigations in obese rodents confirmed the clinical observations and unveiled different pathophysiological mechanisms which could explain why these pharmaceuticals are particularly hepatotoxic in obesity and NAFLD. Other drugs such as pentoxifylline, phenobarbital and omeprazole might also pose a risk but more investigations are required to determine whether this risk is significant or not. Because obese people often take several drugs for the treatment of different obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary heart disease, it is urgent to identify the main pharmaceuticals that can cause acute hepatitis on a fatty liver background or induce NAFLD worsening

  19. A multiple endpoint approach to predict the hepatotoxicity of pharmaceuticals in vitro

    OpenAIRE

    Truisi, Germaine Loredana

    2014-01-01

    A new approach was evaluated to predict the hepatotoxic potential of pharmaceuticals. For this purpose, primary rat and human hepatocytes cultured in an optimised sandwich configuration were used; thus, allowing the long-term, repeat-dosing of drugs. The strategy based on the evaluation of multiple endpoints, including cytotoxicity, biokinetic profiling, transcriptomics and proteomics. Pharmaceuticals with known toxicities and pharmacokinetic properties were used as model compounds.

  20. The thermostable direct hemolysin from Grimontia hollisae causes acute hepatotoxicity in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Yan-Ren Lin

    Full Text Available BACKGROUND: G. hollisae thermostable direct hemolysin (Gh-TDH is produced by most strains of G. hollisae. This toxin has been reported to be absorbed in the intestines in humans. Secondary liver injury might be caused by venous return of the toxin through the portal system. We aimed to firstly analyze the in vitro and in vivo hepatotoxicity of Gh-TDH. METHODS: Liver cells (primary human non-cancer cell and FL83B mouse cells were treated and mice (BALB/c were fed with this toxin to investigate its hepatotoxicity. Morphological examination and cytotoxicity assays using liver cells were also performed. Fluorescein isothiocyanate-conjugated toxin was used to analyze the localization of this protein in liver cells. Mice were subjected to liver function measurements and liver biopsies following toxin treatment and wild-type bacterial infection. PET (positron emission tomography/CT (computed tomography images were taken to assess liver metabolism during acute injury and recovery. RESULTS: The effect of hepatotoxicity was dose and time dependent. Cellular localization showed that the toxin was initially located around the cellular margins and subsequently entered the nucleus. Liver function measurements and liver biopsies of the mice following treatment with toxin or infection with wild-type Grimontia hollisae showed elevated levels of transaminases and damage to the periportal area, respectively. The PET/CT images revealed that the reconstruction of the liver continued for at least one week after exposure to a single dose of the toxin or bacterial infection. CONCLUSIONS: The hepatotoxicity of Gh-TDH was firstly demonstrated. The damage was located in the periportal area of the liver, and the liver became functionally insufficient.

  1. Etiopathogenesis of Nonalcoholic Steatohepatitis: Role of Obesity, Insulin Resistance and Mechanisms of Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Praveen Guturu

    2012-01-01

    Full Text Available Incidence of nonalcoholic fatty liver disease is increasing with an estimated prevalence of 20–30% in developed nations. This is leading to increased incidence of chronic liver disease, cirrhosis, and hepatocellular cancer. It is critical to understand the etiology and pathogenesis of any disease to create therapeutic targets and develop new treatments. In this paper we discuss the etiology and pathogenesis of nonalcoholic steatohepatitis with special focus on obesity, role of insulin resistance, and molecular mechanisms of hepatotoxicity.

  2. Amelioration of carbon tetrachloride induced hepatotoxicity in rats by standardized Feronia limonia. Linn leaf extracts

    OpenAIRE

    Devkar, Ranjitsinh V; Jadeja, Ravirajsinh N.; Jain, Mahendra; Kapadia, Rakhee; Mishra, S. H.; Menaka C. Thounaojam

    2012-01-01

    The hepatoprotective potential of standardized Feronia limonia (Family, Rutaceae) methanolic extract (FL-7) and chloroform soluble fraction (FL-9) were assessed against carbon tetrachloride (CCl4) induced oxidative stress and hepatotoxicity in rats. Rats treated with CCl4 recorded significant elevation in plasma markers of hepatic injury, alteration in hepatic antioxidant status and histopathological damages. However, rats pretreated with FL-7 (200 or 400 mg/kg, p.o.) and FL-9 (100 or 200 mg/...

  3. Salidroside Protects against Cadmium-Induced Hepatotoxicity in Rats via GJIC and MAPK Pathways.

    Science.gov (United States)

    Zou, Hui; Liu, Xuezhong; Han, Tao; Hu, Di; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Zhu, Jiaqiao; Liu, Zong-ping

    2015-01-01

    It is known that cadmium (Cd) induces cytotoxicity in hepatocytes; however, the underlying mechanism is unclear. Here, we studied the molecular mechanisms of Cd-induced hepatotoxicity in rat liver cells (BRL 3A) and in vivo. We observed that Cd treatment was associated with a time- and concentration-dependent decrease in the cell index (CI) of BRL 3A cells and cellular organelle ultrastructure injury in the rat liver. Meanwhile, Cd treatment resulted in the inhibition of gap junction intercellular communication (GJIC) and activation of mitogen-activated protein kinase (MAPK) pathways. Gap junction blocker 18-β-glycyrrhetinic acid (GA), administered in combination with Cd, exacerbated cytotoxic injury in BRL 3A cells; however, GA had a protective effect on healthy cells co-cultured with Cd-exposed cells in a co-culture system. Cd-induced cytotoxic injury could be attenuated by co-treatment with an extracellular signal-regulated kinase (ERK) inhibitor (U0126) and a p38 inhibitor (SB202190) but was not affected by co-treatment with a c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results indicate that ERK and p38 play critical roles in Cd-induced hepatotoxicity and mediate the function of gap junctions. Moreover, MAPKs induce changes in GJIC by controlling connexin gene expression, while GJIC has little effect on the Cd-induced activation of MAPK pathways. Collectively, our study has identified a possible mechanistic pathway of Cd-induced hepatotoxicity in vitro and in vivo, and identified the participation of GJIC and MAPK-mediated pathways in Cd-induced hepatotoxicity. Furthermore, we have shown that salidroside may be a functional chemopreventative agent that ameliorates the negative effects of Cd via GJIC and MAPK pathways.

  4. Aggravation of clozapine-induced hepatotoxicity by glycyrrhetinic acid in rats.

    Science.gov (United States)

    Jia, Ling-ling; Zhong, Ze-yu; Li, Feng; Ling, Zhao-li; Chen, Yang; Zhao, Wei-man; Li, Ying; Jiang, Shu-wen; Xu, Ping; Yang, Yang; Hu, Meng-yue; Liu, Li; Liu, Xiao-dong

    2014-01-01

    Clozapine (CLZ) was reported to be associated with hepatotoxicity. Glycyrrhetinic acid (GA) has a liver protective effect. Our preliminary experiments showed that GA aggravated rather than attenuated CLZ-induced hepatotoxicity in primary cultured rat hepatocytes. The study aimed to describe the enhancing effect of GA on CLZ-induced hepatotoxicity in vivo and in vitro. Data from primary cultured rat hepatocytes showed the decreased formation of metabolites demethylclozapine (nor-CLZ) and clozapine N-oxide (CLZ N-oxide). The results in vivo showed that 7-day CLZ treatment led to marked accumulation of triglyceride (TG) and increase in γ-glutamyl transpeptidase (γ-GT) activity, liver weight, and serum AST in rats. Co-administration of GA enhanced the increases in hepatic TG, γ-GT, liver weight, and serum total cholesterol induced by CLZ. GA decreased plasma concentrations of nor-CLZ and CLZ N-oxide. Compared with control rats, hepatic microsomes of GA rats exhibited the decreased formations of nor-CLZ and CLZ N-oxide, accompanied by decreases in activities of CYP2C11 and CYP2C19 and increased activity of CYP1A2. QT-PCR analysis demonstrated that GA enhanced expression of CYP1A2, but suppressed expression of CYP2C11 and CYP2C13. All these results support the conclusion that GA aggravated CLZ-induced hepatotoxicity, which was partly via inhibiting CYP2C11 and CYP2C13 or inducing CYP1A2.

  5. Protective effect of stem bark of Ceiba pentandra linn. against paracetamol-induced hepatotoxicity in rats

    OpenAIRE

    Bairwa, Nirmal K.; Sethiya, Neeraj K.; Mishra, S. H.

    2010-01-01

    The present study reports protective activity of ethyl acetate fraction of methanol extract of stem bark of Ceiba pentandra against paracetamol-induced liver damage in rats. The ethyl acetate fraction (400 mg/kg) was administered orally to the rats with hepatotoxicity induced by paracetamol (3 gm/kg). Silymarin (100 mg/kg) was used as positive control. High performance thin layer chromatography (HPTLC) fingerprinting of ethyl acetate fraction revealed presence of its major chemical constituen...

  6. Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats

    OpenAIRE

    Daniela Rodrigues; Themis Reverbel Da Silveira; Ursula Matte

    2012-01-01

    CONTEXT: Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. OBJECTIVE: The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. METHODS: Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x10(7) ...

  7. Salidroside Protects against Cadmium-Induced Hepatotoxicity in Rats via GJIC and MAPK Pathways.

    Directory of Open Access Journals (Sweden)

    Hui Zou

    Full Text Available It is known that cadmium (Cd induces cytotoxicity in hepatocytes; however, the underlying mechanism is unclear. Here, we studied the molecular mechanisms of Cd-induced hepatotoxicity in rat liver cells (BRL 3A and in vivo. We observed that Cd treatment was associated with a time- and concentration-dependent decrease in the cell index (CI of BRL 3A cells and cellular organelle ultrastructure injury in the rat liver. Meanwhile, Cd treatment resulted in the inhibition of gap junction intercellular communication (GJIC and activation of mitogen-activated protein kinase (MAPK pathways. Gap junction blocker 18-β-glycyrrhetinic acid (GA, administered in combination with Cd, exacerbated cytotoxic injury in BRL 3A cells; however, GA had a protective effect on healthy cells co-cultured with Cd-exposed cells in a co-culture system. Cd-induced cytotoxic injury could be attenuated by co-treatment with an extracellular signal-regulated kinase (ERK inhibitor (U0126 and a p38 inhibitor (SB202190 but was not affected by co-treatment with a c-Jun N-terminal kinase (JNK inhibitor (SP600125. These results indicate that ERK and p38 play critical roles in Cd-induced hepatotoxicity and mediate the function of gap junctions. Moreover, MAPKs induce changes in GJIC by controlling connexin gene expression, while GJIC has little effect on the Cd-induced activation of MAPK pathways. Collectively, our study has identified a possible mechanistic pathway of Cd-induced hepatotoxicity in vitro and in vivo, and identified the participation of GJIC and MAPK-mediated pathways in Cd-induced hepatotoxicity. Furthermore, we have shown that salidroside may be a functional chemopreventative agent that ameliorates the negative effects of Cd via GJIC and MAPK pathways.

  8. Salidroside Protects against Cadmium-Induced Hepatotoxicity in Rats via GJIC and MAPK Pathways

    Science.gov (United States)

    Han, Tao; Hu, Di; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Zhu, Jiaqiao; Liu, Zong-ping

    2015-01-01

    It is known that cadmium (Cd) induces cytotoxicity in hepatocytes; however, the underlying mechanism is unclear. Here, we studied the molecular mechanisms of Cd-induced hepatotoxicity in rat liver cells (BRL 3A) and in vivo. We observed that Cd treatment was associated with a time- and concentration-dependent decrease in the cell index (CI) of BRL 3A cells and cellular organelle ultrastructure injury in the rat liver. Meanwhile, Cd treatment resulted in the inhibition of gap junction intercellular communication (GJIC) and activation of mitogen-activated protein kinase (MAPK) pathways. Gap junction blocker 18-β-glycyrrhetinic acid (GA), administered in combination with Cd, exacerbated cytotoxic injury in BRL 3A cells; however, GA had a protective effect on healthy cells co-cultured with Cd-exposed cells in a co-culture system. Cd-induced cytotoxic injury could be attenuated by co-treatment with an extracellular signal-regulated kinase (ERK) inhibitor (U0126) and a p38 inhibitor (SB202190) but was not affected by co-treatment with a c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results indicate that ERK and p38 play critical roles in Cd-induced hepatotoxicity and mediate the function of gap junctions. Moreover, MAPKs induce changes in GJIC by controlling connexin gene expression, while GJIC has little effect on the Cd-induced activation of MAPK pathways. Collectively, our study has identified a possible mechanistic pathway of Cd-induced hepatotoxicity in vitro and in vivo, and identified the participation of GJIC and MAPK-mediated pathways in Cd-induced hepatotoxicity. Furthermore, we have shown that salidroside may be a functional chemopreventative agent that ameliorates the negative effects of Cd via GJIC and MAPK pathways. PMID:26070151

  9. Ipomoea aquatica Extract Shows Protective Action Against Thioacetamide-Induced Hepatotoxicity

    OpenAIRE

    Hadi, A. Hamid A.; Siddig Ibrahim Abdelwahab; Suzy Munir Salama; Salim Said Alkiyumi; Mahmood Ameen Abdullah; Ahmed Salim Alrashdi

    2012-01-01

    In the Indian system of traditional medicine (Ayurveda) it is recommended to consume Ipomoea aquatica to mitigate disorders like jaundice. In this study, the protective effects of ethanol extract of I. aquatica against liver damage were evaluated in thioacetamide (TAA)-induced chronic hepatotoxicity in rats. There was no sign of toxicity in the acute toxicity study, in which Sprague-Dawley (SD) rats were orally fed with ...

  10. Use of Arctium lappa Extract Against Acetaminophen-Induced Hepatotoxicity in Rats

    OpenAIRE

    Attalla Farag El-Kott, PhD; Mashael Mohammed Bin-Meferij, PhD

    2015-01-01

    Background: Severe destructive hepatic injuries can be induced by acetaminophen overdose and may lead to acute hepatic failure. Objective: To investigate the ameliorative effects of Arctium lappa root extract on acetaminophen-induced hepatotoxicity. Methods: Rats were divided into 4 groups: normal control group, Arctium lappa extract group, acetaminophen-injected group, and acetaminophen treated with Arctium lappa extract group. Results: The treatment with Arctium lappa extract reduc...

  11. Steering of Educational Processes in a Digital Medium Environment

    DEFF Research Database (Denmark)

    Tække, Jesper; Paulsen, Michael

    2015-01-01

    This paper is about challenges to steering and leadership of educational interaction in classrooms provided by the new medium environment that comes with digital media. In the new medium environment, the old way of steering what is going on in the classroom appears not to work since...... it was developed in the image of the industrial society and based on a closed classroom. Now with the digital media and wireless networks the classroom is opened and the old way of organizing teaching has become inadequate: The students are disturbed by the new media, instead of learning through them. Inspired...... by systems theory we outline a more adequate way of teaching in the new medium environment – a teaching that can manage the new situation and use the new possibilities provided by the digital media. The argumentation builds on empirical findings from the action research project Socio Media Education (SME...

  12. Detailed field test of yaw-based wake steering

    Science.gov (United States)

    Fleming, P.; Churchfield, M.; Scholbrock, A.; Clifton, A.; Schreck, S.; Johnson, K.; Wright, A.; Gebraad, P.; Annoni, J.; Naughton, B.; Berg, J.; Herges, T.; White, J.; Mikkelsen, T.; Sjöholm, M.; Angelou, N.

    2016-09-01

    This paper describes a detailed field-test campaign to investigate yaw-based wake steering. In yaw-based wake steering, an upstream turbine intentionally misaligns its yaw with respect to the inflow to deflect its wake away from a downstream turbine, with the goal of increasing total power production. In the first phase, a nacelle-mounted scanning lidar was used to verify wake deflection of a misaligned turbine and calibrate wake deflection models. In the second phase, these models were used within a yaw controller to achieve a desired wake deflection. This paper details the experimental design and setup. All data collected as part of this field experiment will be archived and made available to the public via the U.S. Department of Energy's Atmosphere to Electrons Data Archive and Portal.

  13. Mechanics of Thin Strip Steering in Hot Rolling

    Science.gov (United States)

    Jiang, Zhengyi; Tieu, Kiet A.

    2004-06-01

    The hot rolling of thin strip can result in several problems in hot rolling, for instance, the control of strip steering, strip shape and flatness and surface roughness etc. Therefore, the hot rolling of thin strip brings out a requirement of innovative technologies such as the extended control of shape and flatness, steering control and reduction of load by roll gap lubrication. In this paper, the authors focus on the analysis of thin strip snaking movement, as well as solve the related problems such as the shape and flatness due to a larger reduction applied when the strip is thinner. A finite element method was used to simulate this nonsymmetricity rolling considering the non-uniform reduction along the strip width. The calculated spread is compared with the measured values obtained from the rolling mill in laboratory and the friction effect is also discussed.

  14. Robust autopilot with wave filter for ship steering

    Institute of Scientific and Technical Information of China (English)

    WANG Xian-zhou; XU Han-zhen

    2006-01-01

    Research was done to overcome traditional problems associated with automatic steering systems of a ship in a seaway. A ship's dynamic model with wave disturbances was built and a wave filter was designed by means of an extended states observer (ESO). The model estimated the low frequency motion component from a heading measurement corrupted by colorednoise, so back-and-forth steering caused by high frequency wave disturbances was avoided. At the same time, a robust autopilot system,designed by variable structure control theory, was presented. Simulation results achieved in dangerous sea status show that the wave filter works very well and the autopilot has strong robustness to environmental disturbances and model perturbation, and more importantly, the frequency of rudder adjustments is reduced noticeably.

  15. Predictive control and identification: Applications to steering dynamics

    DEFF Research Database (Denmark)

    Hansen, Anca Daniela

    1996-01-01

    The main objective of the present thesis is to enhance insight into predictive controller design and identification in connection with steering dynamics. In Chapter 2, the dynamics of ship steering are reviewed. Models of different complexity, suitable for control systems design are presented....... The influence of wind, waves and currents on the chip motions are also discussed. Chapter 3 deals with the model reduction problem. Some basic concepts are explained, due to their role in the reduction of the dynamic models. Two model reductions techniques, based on singular values, are described....... The theoretical properties of these methods are studied and their performance is examined via simulation on a stochastic linear Mariner Class Vessel model. In Chapter 4, the attention is focused on the derivation of an extended GPC. This extended strategy implies a generalization of the model structure...

  16. Steering of Educational Processes in a Digital Medium Environment

    DEFF Research Database (Denmark)

    Tække, Jesper; Paulsen, Michael Eric

    2016-01-01

    it was developed in the image of the industrial society and based on a closed classroom. Now with the digital media and wireless networks the classroom is opened and the old way of organizing teaching has become inadequate: The students are disturbed by the new media, instead of learning through them. Inspired......This paper is about challenges to steering and leadership of educational interaction in classrooms provided by the new medium environment that comes with digital media. In the new medium environment, the old way of steering what is going on in the classroom appears not to work since...... by systems theory we outline a more adequate way of teaching in the new medium environment – a teaching that can manage the new situation and use the new possibilities provided by the digital media. The argumentation builds on empirical findings from the action research project Socio Media Education (SME...

  17. Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats

    Science.gov (United States)

    Ncube, Denver

    2017-01-01

    Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p = 0.0017) and AST levels (p = 0.0008) than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (p fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.

  18. Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats.

    Science.gov (United States)

    Mathews, Varghese V; Paul, Mv Sauganth; Abhilash, M; Manju, Alex; Abhilash, S; Nair, R Harikumaran

    2014-10-01

    Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As(2)O(3)-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As(2)O(3) was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As(2)O(3). Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As(2)O(3). In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As(2)O(3) offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As(2)O(3)-induced hepatotoxicity. © The Author(s) 2012.

  19. Protective effects of 2,4-dihydroxybenzophenone against acetaminophen-induced hepatotoxicity in mice

    Institute of Scientific and Technical Information of China (English)

    Yue-Ying He; Bao-Xu Zhang; Feng-Lan Jia

    2011-01-01

    AIM: To examine the effects of 2,4-dihydroxybenzophenone (BP-1), a benzophenone derivative used as an ultraviolet light absorbent, on acetaminophen (APAP)- induced hepatotoxicity in C57BL/6J mice. METHODS: Mice were administered orally with BP-1 at doses of 200, 400 and 800 mg/kg body weight respectively every morning for 4 d before a hepatotoxic dose of APAP (350 mg/kg body weight) was given subcutaneously. Twenty four hours after APAP intoxication, the serum enzyme including serum alaine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were measured and liver histopathologic changes were examined. RESULTS: BP-1 administration dramatically reduced serum ALT, AST and LDH levels. Liver histopathological examination showed that BP-1 administration antagonized APAP-induced liver pathological damage in a dose-dependent manner. Further tests showed that APAP-induced hepatic lipid peroxidation was reduced significantly by BP-1 pretreatment, and glutathione depletion was ameliorated obviously. CONCLUSION: BP-1 can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity, and reduction of oxidative stress might be part of the protection mechanism.

  20. Suspected Greater Celandine hepatotoxicity: liver-specific causality evaluation of published case reports from Europe.

    Science.gov (United States)

    Teschke, Rolf; Glass, Xaver; Schulze, Johannes; Eickhoff, Axel

    2012-03-01

    In 21 published case reports, the use of the herb Greater Celandine (GC) (Chelidonium majus L.) has been causally related to liver injury, but a variety of confounding variables were evident that might have offset causality. This study reanalyses causality levels in these cases with a liver-specific causality evaluation method. All 21 cases were submitted to the liver-specific, standardized, structured, quantitative and updated scale of the Council for International Organizations of Medical Sciences. This scale considers, among other items, latency period, course of alanine aminotransferase after treatment discontinuation, risk factors, comedication and alternative causes. Using this method for assessment, causality for GC was highly probable in two and probable in six cases, with lower causality grading in the remaining 13 cases. In these patients, causality for GC was possible in 10 cases and excluded in three cases. On the basis of the eight cases with highly probable and probable causality gradings, GC hepatotoxicity represents an idiosyncratic reaction of the metabolic type, whereas immunologic or obligatory hepatotoxic features are lacking. In some cases, alternative diagnoses and poor data quality were confounding variables that reduced causality levels. Confounding variables reduced causality levels for GC in reported cases of liver injury, but there is still striking evidence for herb-induced liver injury by GC with high causality gradings. GC hepatotoxicity is caused by an idiosyncratic reaction of the metabolic form, but there is uncertainty with respect to its culprit(s).

  1. [Component analysis and acute hepatotoxicity of volatile oils from argy wormwood leaf extracted by different methods].

    Science.gov (United States)

    Liu, Hongjie; Bai, Yang; Hong, Yanlong; Zhang, Xun

    2010-06-01

    To analyze the chemical composition and compare acute hepatotoxicity of essential oils extracted from argy wormwood leaf in Guangdong by four different methods. Four extraction methods, including hydrodistillation extraction, supercritical fluid CO2 extraction, petroleum ether ultrasonic extraction and petroleum ether microwave extraction, were employed to prepare essential oil from argy wormwood leaf in Guangdong. The products were analyzed qualitatively and quantitatively using GC-MS and GC-FID. Sixty mice were divided into 5 groups according to different essential oils and took the same dose orally, then after 5 hours, hepatic functional parameters in serum were detected such as alanine aminotransferase (ALT) and so on, and morphologic change of hepatic tissues was observed. The extraction rate of the four methods and identified compounds was 1.02%, 80 (hydrodistillation extraction), 2.46%, 56 (supercritical fluid CO2 extraction), 3.17%, 45 (petroleum ether ultrasonic extraction) and 3.32%, 78 (petroleum ether microwave extraction) respectively. Totally 153 compounds were identified from those essential oils. Compared with that of the control group, some hepatic functional parameters of hydrodistillation and supercritical fluid CO2 extraction groups rose significantly (P extracted from argy wormwood leaf by different methods may have not only different chemical composition, but also different acute hepatotoxicity, and monoterpenes and benzenes in the essential oils might induce acute hepatotoxicity.

  2. FDA proposals to limit the hepatotoxicity of paracetamol (acetaminophen): are they reasonable?

    Science.gov (United States)

    Graham, Garry G; Day, Richard O; Graudins, Andis; Mohamudally, Anthoulla

    2010-04-01

    Hepatotoxicity from paracetamol is of great concern because of the considerable number of patients who develop severe toxicity from this drug. A group of senior medical practitioners, academics and scientists were brought together on June 29 and 30, 2009 by the Food and Drug Administration of USA (FDA) with the aim of providing advice on how to limit the number of cases of hepatotoxicity due to paracetamol in USA. The most contentious recommendations were the reduction in the dose of paracetamol to 650 mg and the elimination of prescription combination products of paracetamol and opiates. The first recommendation indicates that many members of the committee consider, despite much evidence to the contrary, that therapeutic doses of paracetamol (up to 4 g daily) are associated with a significant incidence of hepatotoxicity. The second recommendation, if accepted by FDA, will require major changes in the therapeutic use of paracetamol and opiates. Adoption of these two recommendations may lead to the increased use of NSAIDs with the potential of increasing incidence of NSAIDs-related adverse reactions.

  3. The Ameliorative Effects of L-2-Oxothiazolidine-4-Carboxylate on Acetaminophen-Induced Hepatotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    Jun Ho Shin

    2013-03-01

    Full Text Available The aim of the study was to investigate the ameliorative effects and the mechanism of action of L-2-oxothiazolidine-4-carboxylate (OTC on acetaminophen (APAP-induced hepatotoxicity in mice. Mice were randomly divided into six groups: normal control group, APAP only treated group, APAP + 25 mg/kg OTC, APAP + 50 mg/kg OTC, APAP + 100 mg/kg OTC, and APAP + 100 mg/kg N-acetylcysteine (NAC as a reference control group. OTC treatment significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels in a dose dependent manner. OTC treatment was markedly increased glutathione (GSH production and glutathione peroxidase (GSH-px activity in a dose dependent manner. The contents of malondialdehyde and 4-hydroxynonenal in liver tissues were significantly decreased by administration of OTC and the inhibitory effect of OTC was similar to that of NAC. Moreover, OTC treatment on APAP-induced hepatotoxicity significantly reduced the formation of nitrotyrosin and terminal deoxynucleotidyl transferase dUTP nick end labeling positive areas of liver tissues in a dose dependent manner. Furthermore, the activity of caspase-3 in liver tissues was reduced by administration of OTC in a dose dependent manner. The ameliorative effects of OTC on APAP-induced liver damage in mice was similar to that of NAC. These results suggest that OTC has ameliorative effects on APAP-induced hepatotoxicity in mice through anti-oxidative stress and anti-apoptotic processes.

  4. A critical analysis of the hepatotoxicity cases described in the literature related to Herbalife (r products

    Directory of Open Access Journals (Sweden)

    Flávio Ailton Duque Zambrone

    2015-12-01

    Full Text Available Abstract The aim of this study was to assess the hepatotoxicity cases described in the literature, attributed to the consumption of Herbalife(r products, and to determine whether a causal relationship exists between the reported cases of liver injury and the use of these products. A literature search was performed on the PubMed, LILACS and PAHO databases. Seven publications reporting a total of 53 cases of hepatotoxicity linked to the use of Herbalife(r products were retrieved. All of the studies lacked sufficient information to some degree, whether related to patients' history, concomitant use of medication and/or other compounds (including alcohol, observations on interrupted use (dechallenge, results found with markers, viral serology and autoantibodies or observations concerning re-exposure to the products. In addition to these items, the lack of clear information on the type of products evaluated and their respective composition is an important factor to be considered. Furthermore, data quality was also questionable due to the presence of confounding factors, absence of proper exclusion of alternative explanations, and the use of questionable methods for attributing causality. Hence, an association between hepatotoxicity and consumption of these products cannot be proven based on the data collected and rigorous scientific analysis.

  5. In silico models for the prediction of dose-dependent human hepatotoxicity

    Science.gov (United States)

    Cheng, Ailan; Dixon, Steven L.

    2003-12-01

    The liver is extremely vulnerable to the effects of xenobiotics due to its critical role in metabolism. Drug-induced hepatotoxicity may involve any number of different liver injuries, some of which lead to organ failure and, ultimately, patient death. Understandably, liver toxicity is one of the most important dose-limiting considerations in the drug development cycle, yet there remains a serious shortage of methods to predict hepatotoxicity from chemical structure. We discuss our latest findings in this area and present a new, fully general in silico model which is able to predict the occurrence of dose-dependent human hepatotoxicity with greater than 80% accuracy. Utilizing an ensemble recursive partitioning approach, the model classifies compounds as toxic or non-toxic and provides a confidence level to indicate which predictions are most likely to be correct. Only 2D structural information is required and predictions can be made quite rapidly, so this approach is entirely appropriate for data mining applications and for profiling large synthetic and/or virtual libraries.

  6. Sirtuin 1 modulation in rat model of acetaminophen-induced hepatotoxicity.

    Science.gov (United States)

    Wojnarová, L; Kutinová Canová, N; Farghali, H; Kučera, T

    2015-01-01

    Sirtuin 1 (SIRT1) is involved in important biological processes such as energy metabolism and regulatory functions of the cell cycle, apoptosis, and inflammation. Our previous studies have shown hepatoprotective effect of polyphenolic compound resveratrol, which is also an activator of SIRT1. Therefore, the aim of our present study was to clarify the role of SIRT1 in process of hepatoprotection in animal model of drug-induced liver damage. Male Wistar rats were used for both in vivo and in vitro studies. Hepatotoxicity was induced by single dose of acetaminophen (APAP). Some rats and hepatocytes were treated by resveratrol or synthetic selective activator of sirtuin 1 (CAY10591). The degree of hepatotoxicity, the activity and expression of the SIRT1 were determined by biochemical, histological and molecular-biological assessments of gained samples (plasma, liver tissue, culture media and hepatocytes). Resveratrol and CAY attenuated APAP-induced hepatotoxicity in vivo and in vitro. Moreover, both drugs enhanced APAP-reduced SIRT1 activity. Our results show that modulation of the SIRT1 activity plays a role in hepatoprotection. Synthetic activators of SIRT1 would help in understanding the role of SIRT1 and are therefore a major boost towards the search for specific treatment of liver disease.

  7. Hepatoprotective activity of quercetin against acrylonitrile-induced hepatotoxicity in rats.

    Science.gov (United States)

    Abo-Salem, Osama M; Abd-Ellah, Mohamed F; Ghonaim, Mabrouk M

    2011-01-01

    Acrylonitrile is a potent hepatotoxic, mutagen, and carcinogen. A role for free radical-mediated lipid peroxidation in the toxicity of acrylonitrile has been suggested. The present study was designed to assess the hepatoprotective effect of quercetin against acrylonitrile-induced hepatotoxicity in rats. Liver damage was induced by oral administration of acrylonitrile (50 mg/kg/day/5 weeks). Acrylonitrile produced a significant elevation of malondialdehyde (138.9%) with a marked decrease in reduced glutathione (72.4%), and enzymatic antioxidants; superoxide dismutase (81%), and glutathione peroxidase (53.2%) in the liver. Serum aspartate aminotransferase, alanine aminotransferases, direct bilirubin, and total bilirubin showed a significant increase in acrylonitrile alone treated rats (115.5%, 110.8%, 1006.8%, and 1000.8%, respectively). Pretreatment with quercetin (70 mg/kg/day/6 weeks) and its coadministration with acrylonitrile prevented acrylonitrile-induced alterations in hepatic lipid peroxides and enzymatic antioxidants as well as serum aminotransferases and bilirubin. Histopathological findings supported the biochemical results. We suggest that querectin possess hepatoprotective effect against acrylonitrile-induced hepatotoxicity through its antioxidant activity.

  8. Inhibition of Glycogen Synthase Kinase 3 Accelerated Liver Regeneration after Acetaminophen-Induced Hepatotoxicity in Mice.

    Science.gov (United States)

    Bhushan, Bharat; Poudel, Samikshya; Manley, Michael W; Roy, Nairita; Apte, Udayan

    2017-03-01

    Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. Timely initiation of compensatory liver regeneration after APAP hepatotoxicity is critical for final recovery, but the mechanisms of liver regeneration after APAP-induced ALF have not been extensively explored yet. Previous studies from our laboratory have demonstrated that activation of β-catenin signaling after APAP overdose is associated with timely liver regeneration. Herein, we investigated the role of glycogen synthase kinase 3 (GSK3) in liver regeneration after APAP hepatotoxicity using a pharmacological inhibition strategy in mice. Treatment with specific GSK3 inhibitor (L803-mts), starting from 4 hours after 600 mg/kg dose of APAP, resulted in early initiation of liver regeneration in a dose-dependent manner, without modifying the peak regenerative response. Acceleration of liver regeneration was not secondary to alteration of APAP-induced hepatotoxicity, which remained unchanged after GSK3 inhibition. Early cell cycle initiation in hepatocytes after GSK3 inhibition was because of rapid induction of cyclin D1 and phosphorylation of retinoblastoma protein. This was associated with increased activation of β-catenin signaling after GSK3 inhibition. Taken together, our study has revealed a novel role of GSK3 in liver regeneration after APAP overdose and identified GSK3 as a potential therapeutic target to improve liver regeneration after APAP-induced ALF. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Therapeutic potential of carfilzomib, an irreversible proteasome inhibitor, against acetaminophen-induced hepatotoxicity in mice.

    Science.gov (United States)

    Alanazi, Abdulrazaq; Algfeley, Saleh G; Al-Hosaini, Khaled A; Korashy, Hesham M; Imam, Faisal; Nagi, Mahmoud N

    2017-04-01

    Overdose of acetaminophen (APAP) is often associated with hepatotoxicity. Carfilzomib (CFZ) shows multiple pharmacological activities including anti-inflammatory potential. Therefore, this study was undertaken to evaluate the possible therapeutic effects of CFZ against APAP-induced hepatotoxicity. Hepatotoxicity was induced by administration of APAP (350 mg/kg, intraperitoneal). Mice were given CFZ (0.125, 0.25, or 0.5 mg/kg, intraperitoneal) 1.5 h after APAP administration. Animals were sacrificed on 6 h and blood and liver tissue samples were collected for analysis. In CFZ-post-treated group, there was significant and dose-dependent decrease in serum alanine aminotransferase levels. The level of tumor necrosis factor-α (TNF-α), reactive oxygen species, and NO decreased, whereas glutathione increased significantly by CFZ post-treatment. Upregulated mRNA expression of COX-II and iNOS were significantly downregulated by CFZ post-treatment. CFZ may exert its hepatoprotective action by alleviating inflammatory, oxidative, and nitrosative stress via inhibition of TNF-α, COX-II, and iNOS. © 2016 Wiley Periodicals, Inc.

  10. Effects of ebselen on radiocontrast media-induced hepatotoxicity in rats.

    Science.gov (United States)

    Basarslan, Fatmagul; Yilmaz, Nigar; Davarci, Isil; Akin, Mustafa; Ozgur, Mustafa; Yilmaz, Cahide; Ulutas, Kemal Turker

    2013-09-01

    Oxidative stress is accepted as a potential responsible mechanism in the pathogenesis of radiocontrast media (RCM)-induced hepatotoxicity. Therefore, we aimed to investigate the protective effects of ebselen against RCM-induced hepatotoxicity by measuring tissue oxidant/antioxidant parameters and histological changes in rats. Wistar albino rats were randomly separated into four groups consisting of eight rats per group. Normal saline was given to the rats in control group (group 1). RCM was given to the rats in group 2, and both RCM and ebselen were given to the rats in group 3. Only ebselen was given to the rats in group 4. Liver sections of the killed animals were analyzed to measure the levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as histopathological changes. In RCM group, SOD and CAT levels were found increased. In RCM-ebselen group, MDA, SOD and CAT levels were found decreased. In RCM-ebselen group, however, GSH-Px activities of liver tissue increased. All these results indicated that ebselen produced a protective mechanism against RCM-induced hepatotoxicity and took part in oxidative stress.

  11. Carvacrol suppresses the expression of inflammatory marker genes in D-galactosamine-hepatotoxic rats

    Institute of Scientific and Technical Information of China (English)

    Balakrishnan Aristatile; Abdullah H Al-Assaf; Kodukkur Viswanathan Pugalendi

    2013-01-01

    Objective:To unravel the mechanism of anti-inflammatory activity of carvacrol in D-galactosamine(D-GalN)-induced hepatotoxic rats.Methods:The mRNA and protein expression levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2) and nuclear factor kappa-B(NF-κB) were assayed by semi-quantitative reverse transcriptase polymerase chain reaction(RTPCR) and western blot analysis.Results:We found that the mRNA and protein expressions ofTNF-α, IL-6, iNOS,COX-2 andNF-κB were significantly up-regulated inD-galactosamine induced hepatotoxic rats and treatment with carvacrol significantly down-regulated the expressions of these genes showing the mechanism behind the anti-inflammatory activity of carvacrol. Conclusions:All above results reveal that the carvacrol well known anti-inflammatory activities inD-galactosamine induced hepatotoxic rats.

  12. Attenuation of anti-tuberculosis therapy induced hepatotoxicity by Spirulina fusiformis, a candidate food supplement.

    Science.gov (United States)

    Martin, Sherry Joseph; Baskaran, Udhaya Lavinya; Vedi, Mahima; Sabina, Evan Prince

    2014-12-01

    Therapy using Isoniazid (INH) and Rifampicin (RIF) leads to induction of hepatotoxicity in some individuals undergoing anti-tuberculosis treatment. In this study, we assessed the effect of Spirulina fusiformis on INH and RIF induced hepatotoxicity in rats compared with hepatoprotective drug Silymarin. Induction of hepatotoxicity was measured by changes in the liver marker enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase). The antioxidant status was also analyzed in liver tissue homogenate and plasma by measurement of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and lipid peroxidation levels. We also aimed to study the binding and interactions of the transcription factors Pregnane X Receptor (PXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of Spirulina fusiformis by in silico methods. The administration of INH and RIF resulted in significant (p Spirulina fusiformis was seen to protect the parameters from significant changes upon challenge with INH and RIF in a dose-dependent manner. This was corroborated by histological examination of the liver. The results of the in silico analyses further support the wet lab results.

  13. A fatal case of bupropion (Zyban hepatotoxicity with autoimmune features: Case report

    Directory of Open Access Journals (Sweden)

    Humayun Fawwaz

    2007-09-01

    Full Text Available Abstract Background Bupropion is approved for the treatment of mood disorders and as an adjuvant medication for smoking cessation. Bupropion is generally well tolerated and considered safe. Two randomized controlled trials of bupropion therapy for smoking cessation did not report any hepatic adverse events. However, there are three reports of severe but non-fatal bupropion hepatotoxicity published in the literature. Case Presentation We present the case of a 55-year old man who presented with jaundice and severe hepatic injury approximately 6 months after starting bupropion for smoking cessation. Laboratory evaluation demonstrated a mixed picture of hepatocellular injury and cholestasis. Liver biopsy demonstrated findings consistent with severe hepatotoxic injury due to drug induced liver injury. Laboratory testing was also notable for positive autoimmune markers. The patient initially had clinical improvement with steroid therapy but eventually died of infectious complications. Conclusion This report represents the first fatal report of bupropion related hepatotoxicity and the second case of bupropion related liver injury demonstrating autoimmune features. The common use of this medication for multiple indications makes it important for physicians to consider this medication as an etiologic agent in patients with otherwise unexplained hepatocellular jaundice.

  14. Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin

    Directory of Open Access Journals (Sweden)

    Xin Che

    2016-07-01

    Full Text Available Geniposide (GE is the main bioactive component of Gardeniae Fructus. The hepatotoxicity of geniposide limited clinical application. In order to get a new geniposide derivative that has less hepatotoxicity and still possesses the antidepressant activity, a new C-1 hydroxyl methylation derivative named methyl genipin (MG was synthesized from geniposide. In the present study, we demonstrated that MG did not increase the liver index, alanine aminotransferase (ALT and aspirate aminotransferase (AST. Histopathological examination suggested that no toxic damages were observed in rats treated orally with MG (0.72 mmol/kg. More importantly, a 7-day treatment with MG at 0.13, 0.26, and 0.52 mmol/kg/day could reduce the duration of immobility. It showed that the antidepressant-like effects of MG were similar to GE in the tail suspension test and the forced swim test. Furthermore, we found MG could be detected in the brain homogenate of mice treated orally with MG 0.52 mmol/kg/day for 1 day by HPLC. The area under the curve (AUC of MG in the brain homogenate was enhanced to 21.7 times that of GE. The brain amount and distribution speed of MG were improved significantly after oral administration. This study demonstrated that MG possessed the antidepressant effects and could cross the blood–brain barrier, but had less hepatotoxicity.

  15. Planning analysis and political steering with New Public Management

    DEFF Research Database (Denmark)

    Sager, Tore Øivin; Sørensen, Claus Hedegaard

    2011-01-01

    of interviews sheds light on the apparent paradox that parliamentarians accept delegation of highway investment decisions despite their profound scepticism to the cost-benefit analyses and impact calculations that are essential to management by objectives and results, which was to give them continued political...... by the Government. The political concentration on strategic steering, the concomitant delegation, and management by objectives and results are central components of New Public Management....

  16. Low-Absorption Liquid Crystals for Infrared Beam Steering

    Science.gov (United States)

    2015-09-30

    absorption coefficient and d is the LC layer thickness . Let us take a~!0/cm as an example. For a 10-|j,m- thick LC layer, ad=0.01 and the transmittance...remains 99%. However, if the LC layer thickness (or effective optical path length) increases, then the absorption will increase exponentially, as Eq. (1...weight-and-power, 2) increasing mean-time-between- failure, and 3) reducing system complexity. Beam steering based on liquid crystal ( LC ) optical phase

  17. Quadrupole Law and Steering Options in the Linac4 DTL

    CERN Document Server

    Stovall, J

    2009-01-01

    The Linac4 drift-tube linac (DTL) reference design has been modified to reduce the power consumption in tank 1 by adjusting the accelerating field and phase laws. In this note we investigate three options for the transverse focusing lattice, quadrupole law, and two options for beam steering. We use acceptance, sensitivity to alignment errors and the probabiity of beam loss as figures of merit for evaluating each option.

  18. Modeling the behavior of the helmsman steering a ship

    Science.gov (United States)

    Veldhuyzen, W.; Stassen, H. G.

    1973-01-01

    A supertanker is considered as a nonlinear system which responds very slowly to changes in the rudder position. Moreover this type of ship is often unstable in loaded condition. In order to model the helmsman's behavior, a number of tests were performed using a ship maneuvering simulator. The trained subjects had to steer a 200,000 tons tanker along a varying course. The results obtained from these trials are presented.

  19. Planning analysis and political steering with New Public Management

    DEFF Research Database (Denmark)

    Sager, Tore Øivin; Sørensen, Claus Hedegaard

    2011-01-01

    of interviews sheds light on the apparent paradox that parliamentarians accept delegation of highway investment decisions despite their profound scepticism to the cost-benefit analyses and impact calculations that are essential to management by objectives and results, which was to give them continued political...... by the Government. The political concentration on strategic steering, the concomitant delegation, and management by objectives and results are central components of New Public Management....

  20. Erasmus Darwin's improved design for steering carriages and cars.

    Science.gov (United States)

    King-Hele, Desmond

    2002-01-01

    Carriage journeys in England during the eighteenth century were notoriously dangerous. Rutted and pot-holed roads exacerbated the deficiencies in steering, springing and stability. In 1758 the young Dr. Erasmus Darwin (1731-1802; F. R. S. 1761) was travelling about 10,000 miles a year in visits to patients from his house at Lichfield. To alleviate the danger and discomfort of his journey, he developed a design for improved carriage steering and stability, which he road-tested over 20,000 miles on two carriages. In 1765 Richard Lovell Edgeworth (1744-1817; F. R. S. 1718) heard about Darwin's design, urged the Society of Arts to enquire about it, and then visited Darwin himself. With the aid of manuscripts from the Archive of the Royal Society of Arts and elsewhere, I offer a reconstruction of Darwin's improved method of steering, which relies on four jointed rods, initially in the form of an isosceles trapezium. The mechanism was reinvented more than 50 years later, and came to be used widely in early modern cars.

  1. Optimization of Steering Elements in the RIA Driver Linac

    CERN Document Server

    SchnirmanLessner, Eliane; Ostroumov, Peter

    2005-01-01

    The driver linac of the projected RIA facility is a versatile accelerator, a 1.4-GV, CW superconducting linac designed to simultaneously accelerate several heavy-ion charge states, providing beams from protons at about 1 GeV to uranium at 400 MeV/u at power levels at a minimum of 100 kW and up to 400 kW for most beams. Acceleration of multiple-charge-state uranium beams places stringent requirements on the linac design. A steering algorithm was derived that fulfilled the driver’s real estate requirements, such as placement of steering dipole coils on SC solenoids and of beam position monitors outside cryostats, and beam-dynamics requirements, such as coupling effects induced by the focusing solenoids.* The algorithm has been fully integrated in the tracking code TRACK** and is used to study and optimize the number and position of steering elements that minimize the multiple-beam centroid oscillations and preserve the beam emittance under misalignments of accelerating and transverse focusing elements...

  2. Volume monogamy of quantum steering ellipsoids for multiqubit systems

    Science.gov (United States)

    Cheng, Shuming; Milne, Antony; Hall, Michael J. W.; Wiseman, Howard M.

    2016-10-01

    The quantum steering ellipsoid can be used to visualize 2-qubit states, and thus provides a generalization of the Bloch picture for the single qubit. Recently, a monogamy relation for the volumes of steering ellipsoids has been derived for pure 3-qubit states and shown to be stronger than the celebrated Coffman-Kundu-Wootters inequality. We first demonstrate the close connection between this volume monogamy relation and the classification of pure 3-qubit states under stochastic local operations and classical communication. We then show that this monogamy relation does not hold for general mixed 3-qubit states and derive a weaker monogamy relation that does hold for such states. We also prove a volume monogamy relation for pure 4-qubit states (further conjectured to hold for the mixed case), and generalize our 3-qubit inequality to n qubits. Finally, we study the effect of noise on the quantum steering ellipsoid and find that the volume of any 2-qubit state is nonincreasing when the state is exposed to arbitrary local noise. This implies that any volume monogamy relation for a given class of multiqubit states remains valid under the addition of local noise. We investigate this quantitatively for the experimentally relevant example of isotropic noise.

  3. Imperfection Insensitivity Analyses of Advanced Composite Tow-Steered Shells

    Science.gov (United States)

    Wu, K. Chauncey; Farrokh, Babak; Stanford, Bret K.; Weaver, Paul M.

    2016-01-01

    Two advanced composite tow-steered shells, one with tow overlaps and another without overlaps, were previously designed, fabricated and tested in end compression, both without cutouts, and with small and large cutouts. In each case, good agreement was observed between experimental buckling loads and supporting linear bifurcation buckling analyses. However, previous buckling tests and analyses have shown historically poor correlation, perhaps due to the presence of geometric imperfections that serve as failure initiators. For the tow-steered shells, their circumferential variation in axial stiffness may have suppressed this sensitivity to imperfections, leading to the agreement noted between tests and analyses. To investigate this further, a numerical investigation was performed in this study using geometric imperfections measured from both shells. Finite element models of both shells were analyzed first without, and then, with measured imperfections that were then, superposed in different orientations around the shell longitudinal axis. Small variations in both the axial prebuckling stiffness and global buckling load were observed for the range of imperfections studied here, which suggests that the tow steering, and resulting circumferentially varying axial stiffness, may result in the test-analysis correlation observed for these shells.

  4. PERFORMANCE ANALYSIS OF AZIMUTH ELECTRONIC BEAM STEERING MODE SPACEBORNE SAR

    Institute of Scientific and Technical Information of China (English)

    Han Xiaodong; Xu Wei; Han Xiaolei

    2013-01-01

    Pointing angle and pattern of the antenna can be changed swiftly to actualize the azimuth beam scanning by using electronic beam steering,which makes the Synthetic Aperture Radar (SAR)system more flexible and achieve a high resolution or cover a long strip within short time span.When the pointing angle is steered away from boresight,some aberrations may appear on the antenna pattern,e.g.,the grating lobe appears,the main lobe gain decrease,and antenna pattern broadens,e.g.,the aberrations result in the worsening of system performance,and complicate the corresponding performance analysis method.Conventional computation methods of performance parameters do not account for the rapid change of the antenna pattern.It introduces remarkable errors when the scanning angle is large.In this paper,a method of calculating performance parameters is proposed for the beam steering mode,which achieves the parameters by the energy accumulation in time domain.Actually,the proposed method simulates the working process of SAR and obtains accurate performance parameters.Furthermore,we analyze the effects of the grating lobe on the Azimuth Ambiguity to Signal Ratio (AASR),and present the generic Pulse Repetition Frequency (PRF) choosing principle which can also prevent the ambiguous area from weighting by the grating lobe.Finally,the effect of the antenna configuration on the performance parameters is analyzed by a system example.

  5. Visual-Motor Control of Steering and Awareness of Performance

    Directory of Open Access Journals (Sweden)

    Callum Mole

    2012-05-01

    Full Text Available In order to carry out skilled, visually guided actions, humans need to be able to use feedback to monitor and adjust performance. Such feedback can be relatively low level, with some motor commands being recalibrated rapidly based on visual feedback with little cognitive awareness (eg, Mon-Williams and Murray 2000. In tasks such as driving, however, awareness of performance could be important for making strategic adjustments in order to respond to road conditions. To investigate whether participants could accurately gauge steering performance, we used a simulated driving scenario. Participants (n=30 were required to steer around a series of bends and stay within a central marked zone. In order to alter the task demands, the speed of travel (fast/slow and the width of the zone (narrow/wide were manipulated. After each bend the participants made an explicit percentage judgment of time spent within the required zone. The mean group steering results showed that performance was worst for faster speeds and narrower zones, and this pattern was matched in the awareness judgements. Closer inspection of the data, however, showed that at an individual level these judgements often failed to capture trial performance and were often merely influenced by the visible task characteristics (eg, fast and narrow trial. This suggests that participants may erroneously rely on salient cues about task characteristics to assess performance if direct feedback is weak. This has important implications for driving since individuals may be failing to respond to situation characteristics that actually make performance worse.

  6. Postweaning performance and carcass merit of F1 steers sired by Brahman and alternative subtropically adapted breeds.

    Science.gov (United States)

    Franke, D E

    1997-10-01

    Comparisons were made among F1 steers sired by Brahman and alternative subtropically adapted breeds of bulls for feedlot and carcass traits when steers were produced from Angus- and Hereford-type dams. Brahman-derivative breeds included Brangus, Beefmaster, and Santa Gertrudis. Brangus- and Beefmaster-sired steers weighed less at slaughter, whereas carcasses of Brangus- and Santa Gertrudis-sired steers had more marbling than those of Brahman-sired steers. Brahman-sired steer carcasses had greater longissimus muscle area than carcasses of Santa Gertrudis-sired steers. Other Zebu breeds compared to Brahman were Boran, Gir, Indu-Brazil, Nellore, Red Brahman, and Sahiwal. Steers by Brahman sires had higher slaughter weights than steers by Boran, Gir, Nellore, or Sahiwal sires. Hot carcass weights of Brahman-sired steers were also higher than those of Boran- and Sahiwal-sired steers. Steer carcasses by Brahman sires had greater longissimus muscle area than those of steers by Sahiwal sires. Non-Zebu breeds included Tuli and Senepol. Steers by Tuli sires grew slower, had lower slaughter weights, and their carcasses weighed less than those of Brahman-sired steers. Brahman-sired steer carcasses had greater longissimus muscle area but less marbling than carcasses of Tuli-sired steers. These data suggest that steers by Brahman sires have an advantage for slaughter weight over steers by Brangus, Beefmaster, Boran, Gir, Nellore, Sahiwal, and Tuli sires, but their carcasses are at a disadvantage for marbling score compared with those by Brangus, Boran, Nellore, and Tuli sires.

  7. The Relation between Hepatotoxicity and the Total Coumarin Intake from Traditional Japanese Medicines Containing Cinnamon Bark.

    Science.gov (United States)

    Iwata, Naohiro; Kainuma, Mosaburo; Kobayashi, Daisuke; Kubota, Toshio; Sugawara, Naoko; Uchida, Aiko; Ozono, Sahoko; Yamamuro, Yuki; Furusyo, Norihiro; Ueda, Koso; Tahara, Eiichi; Shimazoe, Takao

    2016-01-01

    Cinnamon bark is commonly used in traditional Japanese herbal medicines (Kampo medicines). The coumarin contained in cinnamon is known to be hepatotoxic, and a tolerable daily intake (TDI) of 0.1 mg/kg/day, has been quantified and used in Europe to insure safety. Risk assessments for hepatotoxicity by the cinnamon contained in foods have been reported. However, no such assessment of cinnamon bark has been reported and the coumarin content of Kampo medicines derived from cinnamon bark is not yet known. To assess the risk for hepatotoxicity by Kampo medicines, we evaluated the daily coumarin intake of patients who were prescribed Kampo medicines and investigated the relation between hepatotoxicity and the coumarin intake. The clinical data of 129 outpatients (18 male and 111 female, median age 58 years) who had been prescribed keishibukuryogankayokuinin (TJ-125) between April 2008 and March 2013 was retrospectively investigated. Concurrent Kampo medicines and liver function were also surveyed. In addition to TJ-125, the patients took some of the other 32 Kampo preparations and 22 decoctions that include cinnamon bark. The coumarin content of these Kampo medicines was determined by high performance liquid chromatography (HPLC). TJ-125 had the highest daily content of coumarin (5.63 mg/day), calculated from the daily cinnamon bark dosage reported in the information leaflet inserted in each package of Kampo medicine. The coumarin content in 1g cinnamon bark decoction was 3.0 mg. The daily coumarin intake of the patients was 0.113 (0.049-0.541) mg/kg/day, with 98 patients (76.0%) exceeding the TDI. Twenty-three patients had an abnormal change in liver function test value, but no significant difference was found in the incidence of abnormal change between the group consuming less than the TDI value (6/31, 19.4%) and the group consuming equal to or greater than the TDI value (17/98, 17.3%). In addition, no abnormal change related to cinnamon bark was found for individual

  8. The Relation between Hepatotoxicity and the Total Coumarin Intake from Traditional Japanese Medicines Containing Cinnamon Bark

    Science.gov (United States)

    Iwata, Naohiro; Kainuma, Mosaburo; Kobayashi, Daisuke; Kubota, Toshio; Sugawara, Naoko; Uchida, Aiko; Ozono, Sahoko; Yamamuro, Yuki; Furusyo, Norihiro; Ueda, Koso; Tahara, Eiichi; Shimazoe, Takao

    2016-01-01

    Cinnamon bark is commonly used in traditional Japanese herbal medicines (Kampo medicines). The coumarin contained in cinnamon is known to be hepatotoxic, and a tolerable daily intake (TDI) of 0.1 mg/kg/day, has been quantified and used in Europe to insure safety. Risk assessments for hepatotoxicity by the cinnamon contained in foods have been reported. However, no such assessment of cinnamon bark has been reported and the coumarin content of Kampo medicines derived from cinnamon bark is not yet known. To assess the risk for hepatotoxicity by Kampo medicines, we evaluated the daily coumarin intake of patients who were prescribed Kampo medicines and investigated the relation between hepatotoxicity and the coumarin intake. The clinical data of 129 outpatients (18 male and 111 female, median age 58 years) who had been prescribed keishibukuryogankayokuinin (TJ-125) between April 2008 and March 2013 was retrospectively investigated. Concurrent Kampo medicines and liver function were also surveyed. In addition to TJ-125, the patients took some of the other 32 Kampo preparations and 22 decoctions that include cinnamon bark. The coumarin content of these Kampo medicines was determined by high performance liquid chromatography (HPLC). TJ-125 had the highest daily content of coumarin (5.63 mg/day), calculated from the daily cinnamon bark dosage reported in the information leaflet inserted in each package of Kampo medicine. The coumarin content in 1g cinnamon bark decoction was 3.0 mg. The daily coumarin intake of the patients was 0.113 (0.049–0.541) mg/kg/day, with 98 patients (76.0%) exceeding the TDI. Twenty-three patients had an abnormal change in liver function test value, but no significant difference was found in the incidence of abnormal change between the group consuming less than the TDI value (6/31, 19.4%) and the group consuming equal to or greater than the TDI value (17/98, 17.3%). In addition, no abnormal change related to cinnamon bark was found for individual

  9. A review of the evidence concerning hepatic glutathione depletion and susceptibility to hepatotoxicity after paracetamol overdose

    Directory of Open Access Journals (Sweden)

    Kalsi SS

    2011-12-01

    Full Text Available Sarbjeet S Kalsi1,2, Paul I Dargan2–4, W Stephen Waring5, David M Wood2–41Emergency Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 2Clinical Toxicology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 3King’s Health Partners, London, UK; 4King’s College London, London, UK; 5York Teaching Hospital NHS Foundation Trust, York, UKAbstract: Paracetamol (acetaminophen poisoning is common throughout the world. The management of nonstaggered (acute paracetamol overdose is based on the plasma paracetamol concentration plotted on a treatment nomogram. In the UK there are two treatment lines on this nomogram, with the lower treatment line used for individuals felt to be at ‘high risk’ of paracetamol-related hepatotoxicity either as a result of induction of cytochrome P450 isoenzymes or reduction of intrahepatic glutathione. In this article we review the risk factors that, in current guidelines, are felt to increase risk due to a reduction in intrahepatic glutathione concentrations. Based on our review of the published literature, we feel that cystic fibrosis, acute viral illness, malnutrition, and eating disorders such as anorexia nervosa are likely to be associated with reduction in intrahepatic glutathione concentrations, and that this risk is likely to be related to malnutrition secondary to the disease. Chronic hepatitis C infection is also associated with reduced glutathione concentrations, although this appears to be independent of any associated malnutrition. Ageing and acute fasting are not associated with an increased risk of paracetamol-related hepatotoxicity due to reductions in glutathione concentrations. Finally, the evidence for HIV infection is inconclusive, particularly as the majority of studies were conducted in the pre-anti-viral treatment (HAART era; however it is likely that patients with symptomatic HIV/AIDS have reduced glutathione concentrations due to associated malnutrition. Although

  10. Chlorpromazine-induced hepatotoxicity during inflammation is mediated by TIRAP-dependent signaling pathway in mice

    Energy Technology Data Exchange (ETDEWEB)

    Gandhi, Adarsh, E-mail: adarsh.gandhi@nih.gov [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Guo, Tao, E-mail: tguo4@jhu.edu [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Shah, Pranav [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Baylor College of Medicine, Department of Pediatrics, 1102 Bates Avenue, Suite 530, Houston, TX 77030 (United States); Ghose, Romi, E-mail: rghose@uh.edu [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States)

    2013-02-01

    Inflammation is a major component of idiosyncratic adverse drug reactions (IADRs). To understand the molecular mechanism of inflammation-mediated IADRs, we determined the role of the Toll-like receptor (TLR) signaling pathway in idiosyncratic hepatotoxicity of the anti-psychotic drug, chlorpromazine (CPZ). Activation of TLRs recruits the first adaptor protein, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) to the TIR domain of TLRs leading to the activation of the downstream kinase, c-Jun-N-terminal kinase (JNK). Prolonged activation of JNK leads to cell-death. We hypothesized that activation of TLR2 by lipoteichoic acid (LTA) or TLR4 by lipopolysaccharide (LPS) will augment the hepatotoxicity of CPZ by TIRAP-dependent mechanism involving prolonged activation of JNK. Adult male C57BL/6, TIRAP{sup +/+} and TIRAP{sup −/−} mice were pretreated with saline, LPS (2 mg/kg) or LTA (6 mg/kg) for 30 min or 16 h followed by CPZ (5 mg/kg) or saline (vehicle) up to 24 h. We found that treatment of mice with CPZ in presence of LPS or LTA leads to ∼ 3–4 fold increase in serum ALT levels, a marked reduction in hepatic glycogen content, significant induction of serum tumor necrosis factor (TNF) α and prolonged JNK activation, compared to LPS or LTA alone. Similar results were observed in TIRAP{sup +/+} mice, whereas the effects of LPS or LTA on CPZ-induced hepatotoxicity were attenuated in TIRAP{sup −/−} mice. For the first time, we show that inflammation-mediated hepatotoxicity of CPZ is dependent on TIRAP, and involves prolonged JNK activation in vivo. Thus, TIRAP-dependent pathways may be targeted to predict and prevent inflammation-mediated IADRs. -- Highlights: ► Inflammation augments the toxicity of an idiosyncratic hepatotoxin chlorpromazine. ► Activation of Toll-like receptors by LPS or LTA induces chlorpromazine toxicity. ► Sustained stress kinase (JNK) activation is associated with chlorpromazine toxicity. ► These studies

  11. Data transfer through beam steering using agile lensing

    Science.gov (United States)

    Arshad, Muhammad Assad; Reza, Syed Azer; Muhammad, Ahsan

    2016-04-01

    This paper presents a data transfer scheme using multi-focus tunable lenses. The design involves the use of a standard laser source and a variable focus agile lens to steer to the laser beam that passes through the lens. In our proposed system, the beam steer angle depends on an input electrical signal which drives the tunable lens. Therefore the beam steer angle is made to follow the variations in the input electrical drive signal. This is extremely interesting for data transfer applications as the data signal can be used as the input drive signal to the lens. The laser beam is steered according to the input data voltage levels and when the beam is incident on a photo-detector of a finite size, only a fraction of its total incident optical power is received by the photo-detector. This power contribution is proportional to the fraction of the total number of photons per unit area which are incident on the active area of the detector. The remaining photons which are not incident on the photo-detector do not contribute to the received power at the photo-detector. We present the theory of beam steering through a tunable lens and present a theoretical framework which governs data transfer through the proposed method. We also present the transfer function of the proposed system which helps us to calculate its essential theoretical performance parameters such as modulation depth and bit error rates. We also present experimental results to demonstrate efficient data transfer through the proposed method. As tunable lenses are primarily deployed in motion-free multi-focus cameras hence most of the modern portable devices such as cellphones and tablets use these lenses to operate the in-built variable focus cameras that are part of these devices. Because tunable lenses are commonly present in several different portable devices, the proposed method of data transfer between two devices is highly promising as it expands the use of the already deployed tunable lenses with

  12. Multiobjective Optimization of Steering Mechanism for Rotary Steering System Using Modified NSGA-II and Fuzzy Set Theory

    Directory of Open Access Journals (Sweden)

    Hongtao Li

    2015-01-01

    Full Text Available Due to the complicated design process of gear train, optimization is a significant approach to improve design efficiency. However, the design of gear train is a complex multiobjective optimization with mixed continuous-discrete variables under numerous nonlinear constraints, and conventional optimization algorithms are not suitable to deal with such optimization problems. In this paper, based on the established dynamic model of steering mechanism for rotary steering system, the key component of which is a planetary gear set with teeth number difference, the optimization problem of steering mechanism is formulated to achieve minimum dynamic responses and outer diameter by optimizing structural parameters under geometric, kinematic, and strength constraints. An optimization procedure based on modified NSGA-II by incorporating dynamic crowding distance strategies and fuzzy set theory is applied to the multiobjective optimization. For comparative purpose, NSGA-II is also employed to obtain Pareto optimal set, and dynamic responses of original and optimized designs are compared. The results show the optimized design has better dynamic responses with minimum outer diameter and the response decay decreases faster. The optimization procedure is feasible to the design of gear train, and this study can provide guidance for designer at the preliminary design phase of mechanical structures with gear train.

  13. Effects of saponin extracts on air emissions from steers.

    Science.gov (United States)

    Li, W; Powers, W

    2012-11-01

    A series of experiments were conducted to quantify the effects of saponin extracts from Quillaja saponaria Molina (QS), Yucca schidigera Roezl ex Ortgies (YS), and Camellia sinensis (L.) Kuntze (TS) on gaseous emissions from steers (Bos taurus). During Exp. 1, a control diet [C1, corn (Zea mays L.) and corn silage basal diet] was compared with YS1 (C1 + 0.64% dietary DM of YS) and QS1 (C1 + 1.5% dietary DM of QS), with 4 replicates per treatment. During Exp. 2, the control diet (C2, corn and corn silage basal diet) was compared with TS2 (C2 + 0.25% dietary DM of TS). Product inclusion levels were established to provide the same concentration of saponin compounds across studies for Exp. 1 and 2. Experiment 3 compared C3 (corn and corn silage basal diet), QS3 (C3 + 1.5% QS), YS3 (C3 + 1.5% YS), and TS3 (C3 + 0.5% TS). Holstein steers (n = 12) at initial BW of 354 ± 10 kg (Exp. 1), 429 ± 10 kg (Exp. 2), 382 ± 16 kg (Period 1, Exp. 3) and 400 ± 12 kg (Period 2, Exp. 3) were individually housed in environmental rooms for 22 d per study. Gaseous emissions including methane (CH(4)), ammonia (NH(3)), and nitrous oxide (N(2)O) were monitored in room exhaust air. No differences in DMI (7.54 ± 0.09 kg) and ADG (1.16 ± 0.19 kg) were observed in Exp. 1 (P > 0.05). Adding TS2 to the diet improved DMI in Exp. 2 (8.94 kg in TS2 vs. 8.53 in C2; P < 0.01), whereas ADG was not affected by diet. During Exp. 3, steers fed the TS3 diet ate less (6.36 kg/d) and gained less BW (0.31 kg/d) compared with the other 3 treatments. Saponin inclusion did not alter daily CH(4) emission per unit DMI (13.17, 10.90, and 13.21 g/kg DMI, for Exp. 1, 2, and 3, respectively). Emissions of NH(3) per unit N intake were not affected by diets in Exp. 1 (134.89 mg/g N consumed) and Exp. 3 (134.99 mg/g N consumed). Feeding TS2 reduced NH(3) emission per unit of N consumed by 30% compared with C2 (P < 0.01). Feeding up to 0.5% of TS failed to reduce CH(4) emissions without impairing steer growth. Nitrous

  14. Electronic differential control of 2WD electric vehicle considering steering stability

    Science.gov (United States)

    Hua, Yiding; Jiang, Haobin; Geng, Guoqing

    2017-03-01

    Aiming at the steering wheel differential steering control technology of rear wheel independent driving electric wheel, considering the assisting effect of electronic differential control on vehicle steering, based on the high speed steering characteristic of electric wheel car, the electronic differential speed of auxiliary wheel steering is also studied. A yaw moment control strategy is applied to the vehicle at high speed. Based on the vehicle stability reference value, yaw rate is used to design the fuzzy controller to distribute the driving wheel torque. The simulation results show that the basic electronic differential speed function is realized based on the yaw moment control strategy, while the vehicle stability control is improved and the driving safety is enhanced. On the other hand, the torque control strategy can also assist steering of vehicle.

  15. Robust Adaptive Beamforming Based on Steering Vector Estimation via Semidefinite Programming Relaxation

    CERN Document Server

    Khabbazibasmenj, Arash; Hassanien, Aboulnasr

    2010-01-01

    We develop a new approach to robust adaptive beamforming in the presence of signal steering vector errors. Since the signal steering vector is known imprecisely, its presumed (prior) value is used to find a more accurate estimate of the actual steering vector, which then is used for obtaining the optimal beamforming weight vector. The objective for finding such an estimate of the actual signal steering vector is the maximization of the beamformer output power, while the constraints are the normalization condition and the requirement that the estimate of the steering vector does not converge to an interference steering vector. Our objective and constraints are free of any design parameters of non-unique choice. The resulting optimization problem is a non-convex quadratically constrained quadratic program, which is NP hard in general. However, for our problem we show that an efficient solution can be found using the semi-definite relaxation technique. Moreover, the strong duality holds for the proposed problem ...

  16. Repositioning and steering laser beam power via coherent combination of multiple Airy beams.

    Science.gov (United States)

    Zhang, Ze; Ye, Zhuoyi; Song, Daohong; Zhang, Peng; Chen, Zhigang

    2013-12-10

    We study numerically and experimentally laser coherent combination (LCC) with multiple one- or two-dimensional Airy beams. It is shown that the method of LCC using Airy beams leads to a higher combining efficiency and a better feature of propagation than that using conventional Gaussian beams. Based on such coherent Airy beams combination, we propose a laser steering approach that could achieve large-angle beam steering (over 0.6°) without the need of using any mechanical steering component.

  17. Cycling around a curve: the effect of cycling speed on steering and gaze behavior.

    Directory of Open Access Journals (Sweden)

    Pieter Vansteenkiste

    Full Text Available Although it is generally accepted that visual information guides steering, it is still unclear whether a curvature matching strategy or a 'look where you are going' strategy is used while steering through a curved road. The current experiment investigated to what extent the existing models for curve driving also apply to cycling around a curve, and tested the influence of cycling speed on steering and gaze behavior. Twenty-five participants were asked to cycle through a semicircular lane three consecutive times at three different speeds while staying in the center of the lane. The observed steering behavior suggests that an anticipatory steering strategy was used at curve entrance and a compensatory strategy was used to steer through the actual bend of the curve. A shift of gaze from the center to the inside edge of the lane indicates that at low cycling speed, the 'look where you are going' strategy was preferred, while at higher cycling speeds participants seemed to prefer the curvature matching strategy. Authors suggest that visual information from both steering strategies contributes to the steering system and can be used in a flexible way. Based on a familiarization effect, it can be assumed that steering is not only guided by vision but that a short-term learning component should also be taken into account.

  18. Cycling around a curve: the effect of cycling speed on steering and gaze behavior.

    Science.gov (United States)

    Vansteenkiste, Pieter; Van Hamme, David; Veelaert, Peter; Philippaerts, Renaat; Cardon, Greet; Lenoir, Matthieu

    2014-01-01

    Although it is generally accepted that visual information guides steering, it is still unclear whether a curvature matching strategy or a 'look where you are going' strategy is used while steering through a curved road. The current experiment investigated to what extent the existing models for curve driving also apply to cycling around a curve, and tested the influence of cycling speed on steering and gaze behavior. Twenty-five participants were asked to cycle through a semicircular lane three consecutive times at three different speeds while staying in the center of the lane. The observed steering behavior suggests that an anticipatory steering strategy was used at curve entrance and a compensatory strategy was used to steer through the actual bend of the curve. A shift of gaze from the center to the inside edge of the lane indicates that at low cycling speed, the 'look where you are going' strategy was preferred, while at higher cycling speeds participants seemed to prefer the curvature matching strategy. Authors suggest that visual information from both steering strategies contributes to the steering system and can be used in a flexible way. Based on a familiarization effect, it can be assumed that steering is not only guided by vision but that a short-term learning component should also be taken into account.

  19. Theoretical modeling on the laser induced effect of liquid crystal optical phased beam steering

    Science.gov (United States)

    He, Xiaoxian; Wang, Xiangru; Wu, Liang; Tan, Qinggui; Li, Man; Shang, Jiyang; Wu, Shuanghong; Huang, Ziqiang

    2017-01-01

    Non-mechanical laser beam steering has been reported previously in liquid crystal array devices. To be one of the most promising candidates to be practical non-mechanical laser deflector, its laser induced effect still has few theoretical model. In this paper, we propose a theoretical model to analyze this laser induced effect of LC-OPA to evaluate the deterioration on phased beam steering. The model has three parts: laser induced thermal distribution; temperature dependence of material parameters and beam steering deterioration. After these three steps, the far field of laser beam is obtained to demonstrate the steering performance with the respect to the incident laser beam power and beam waist.

  20. Modeling, Validation, and Control of Electronically Actuated Pitman Arm Steering for Armored Vehicle

    Directory of Open Access Journals (Sweden)

    Vimal Rau Aparow

    2016-01-01

    Full Text Available In this study, 2 DOF mathematical models of Pitman arm steering system are derived using Newton’s law of motion and modeled in MATLAB/SIMULINK software. The developed steering model is included with a DC motor model which is directly attached to the steering column. The Pitman arm steering model is then validated with actual Pitman arm steering test rig using various lateral inputs such as double lane change, step steer, and slalom test. Meanwhile, a position tracking control method has been used in order to evaluate the effectiveness of the validated model to be implemented in active safety system of a heavy vehicle. The similar method has been used to test the actual Pitman arm steering mechanism using hardware-in-the-loop simulation (HILS technique. Additional friction compensation is added in the HILS technique in order to minimize the frictional effects that occur in the mechanical configuration of the DC motor and Pitman arm steering. The performance of the electronically actuated Pitman arm steering system can be used to develop a firing-on-the-move actuator (FOMA for an armored vehicle. The FOMA can be used as an active safety system to reject unwanted yaw motion due to the firing force.

  1. EVALUATION OF A CONCEPTUAL VEHICLE STEERING SYSTEM FOR INDEPENDENT WHEEL CONTROL

    Directory of Open Access Journals (Sweden)

    Ryszard BUCHALIK

    2017-03-01

    Full Text Available This paper presents a brief description of an unconventional steering system involving electronic stability control and its influence on vehicle motion. The proposed configuration enables individual changes in steering angle for each single wheel, in contrast to the mechanical linkage solution. An analysis of vehicle behaviour during emergency braking on a heterogeneous surface is conducted, especially with regard to the undesirable rotation of the vehicle body. The benefits of using this active steering system, implemented in the steer-by-wire mode, are characterized, while the problems for further consideration and the potential benefits of such a solution are described.

  2. Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts.

    Science.gov (United States)

    Burel, Sebastien A; Hart, Christopher E; Cauntay, Patrick; Hsiao, Jill; Machemer, Todd; Katz, Melanie; Watt, Andy; Bui, Huynh-Hoa; Younis, Husam; Sabripour, Mahyar; Freier, Susan M; Hung, Gene; Dan, Amy; Prakash, T P; Seth, Punit P; Swayze, Eric E; Bennett, C Frank; Crooke, Stanley T; Henry, Scott P

    2016-03-18

    High affinity antisense oligonucleotides (ASOs) containing bicylic modifications (BNA) such as locked nucleic acid (LNA) designed to induce target RNA cleavage have been shown to have enhanced potency along with a higher propensity to cause hepatotoxicity. In order to understand the mechanism of this hepatotoxicity, transcriptional profiles were collected from the livers of mice treated with a panel of highly efficacious hepatotoxic or non-hepatotoxic LNA ASOs. We observed highly selective transcript knockdown in mice treated with non-hepatotoxic LNA ASOs, while the levels of many unintended transcripts were reduced in mice treated with hepatotoxic LNA ASOs. This transcriptional signature was concurrent with on-target RNA reduction and preceded transaminitis. Remarkably, the mRNA transcripts commonly reduced by toxic LNA ASOs were generally not strongly associated with any particular biological process, cellular component or functional group. However, they tended to have much longer pre-mRNA transcripts. We also demonstrate that the off-target RNA knockdown and hepatotoxicity is attenuated by RNase H1 knockdown, and that this effect can be generalized to high affinity modifications beyond LNA. This suggests that for a certain set of ASOs containing high affinity modifications such as LNA, hepatotoxicity can occur as a result of unintended off-target RNase H1 dependent RNA degradation. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Architectural evaluation of beam-steered shuffle optical interconnect

    Science.gov (United States)

    Murdocca, Miles J.; Batchu, Ravi V.; Dennison, Michael

    1996-06-01

    We report on a reconfigurable optical interconnection approach in which static communication graphs are extracted from high level programs and are mapped onto a two stage optical beam-steered/perfect shuffle interconnect. An array of processing elements (PEs) is partitioned into functional units of equal size that are served by one optical input/output (I/O) port per PE. PEs within a functional unit can use any of the optical I/O ports served by that functional unit. An optical beam-steering mechanism in conjunction with an optical perfect shuffle interconnects the functional units. At the highest level, computer programs are written in the Id dataflow programming language. At the next level, dataflow graphs (communication graphs that represent the natural parallelism in a computation) are automatically extracted from the high-level programs. At the lowest level, the dataflow graphs are mapped onto the optical beam-steered/perfect shuffle interconnect. This mapping step is facilitated by a mechanism that redirects optical beams to that the physical interconnect takes the form of the dataflow graph. An intended application is to create low latency realizations of specialized hardware on-the-fly, such as for rapid prototyping. An advantage of this approach over competing all-electronic or static free-space optical interconnection approaches is that the optical interconnect has low depth (two stages) with low fan-out (typically 1 to 3). In previous work, the behaviors of the mappings are studied for randomly generated dataflow graphs. In the work reported here, the behaviors of the mappings are studied for extracted dataflow graphs. We conclude that this interconnection approach is effective for extracted dataflow graphs, using only a single pass through the network, if the interconnect is augmented with a small crossbar within each functional unit.

  4. Frequency-dependent optical steering from subwavelength plasmonic structures.

    Science.gov (United States)

    Djalalian-Assl, A; Gómez, D E; Roberts, A; Davis, T J

    2012-10-15

    We show theoretically and with numerical simulations that the direction of the in-plane scattering from a subwavelength optical antenna system can be controlled by the frequency of the incident light. This optical steering effect does not rely on propagation phase shifts or diffraction but arises from phase shifts in the localized surface plasmon modes of the antenna. An analytical model is developed to optimize the parameters for the configuration, showing good agreement with a rigorous numerical simulation. The simulation predicts a 25° angular shift in the direction of the light scattered from two gold nanorods for a wavelength change of 12 nm.

  5. Hierarchical Visual Analysis and Steering Framework for Astrophysical Simulations

    Institute of Scientific and Technical Information of China (English)

    肖健; 张加万; 原野; 周鑫; 纪丽; 孙济洲

    2015-01-01

    A framework for accelerating modern long-running astrophysical simulations is presented, which is based on a hierarchical architecture where computational steering in the high-resolution run is performed under the guide of knowledge obtained in the gradually refined ensemble analyses. Several visualization schemes for facilitating ensem-ble management, error analysis, parameter grouping and tuning are also integrated owing to the pluggable modular design. The proposed approach is prototyped based on the Flash code, and it can be extended by introducing user-defined visualization for specific requirements. Two real-world simulations, i.e., stellar wind and supernova remnant, are carried out to verify the proposed approach.

  6. AN ALGORITHM FOR STEERING CONTROL WITH SIMULATION RESULTS

    OpenAIRE

    Apeksha V. Sakhare,; Prof. Dr. V. M. Thakare; Prof. R. V. Dharaskar

    2010-01-01

    The idea behind the paper was channelization of human thoughts to automated realization. It is decided to implement the theme of automatic maneuvering of vehicles and the unanimous choice of sensor was touch screen. It was started with the thought of being able to replace the steering of a car completely by a touch screen. It is drawn on the experience of driving to reach at the choice of touch screen as a drive interface. Another innovation was the touch screen controller being wireless. The...

  7. Adaptive feedback linearization applied to steering of ships

    Directory of Open Access Journals (Sweden)

    Thor I. Fossen

    1993-10-01

    Full Text Available This paper describes the application of feedback linearization to automatic steering of ships. The flexibility of the design procedure allows the autopilot to be optimized for both course-keeping and course-changing manoeuvres. Direct adaptive versions of both the course-keeping and turning controller are derived. The advantages of the adaptive controllers are improved performance and reduced fuel consumption. The application of nonlinear control theory also allows the designer in a systematic manner to compensate for nonlinearities in the control design.

  8. Correlation steering in the angularly multimode Raman atomic memory.

    Science.gov (United States)

    Mazelanik, Mateusz; Dąbrowski, Michał; Wasilewski, Wojciech

    2016-09-19

    We present the possibility of steering the direction of correlations between the off-resonant Raman scattered photons from the angularly multimode atomic memory based on warm rubidium vapors. Using acousto-optic deflectors (AOD) driven by different modulation frequencies, we experimentally change the angle of incidence of the laser beams on the atomic ensemble. By performing correlation measurements for various deflection angles, we verify that we can choose the anti-Stokes light propagation direction independently of the correlated Stokes scattered light in a continuous way. As a result we can select the spatial mode of photons retrieved from the memory, which may be important for future development of quantum information processing.

  9. Superdirective dielectric nanoantennas with effect of light steering

    CERN Document Server

    Krasnok, Alexander; Slobozhanyuk, Alexey; Simovski, Constantin; Belov, Pavel; Kivshar, Yuri

    2013-01-01

    We introduce a novel concept of superdirective antennas based on the generation of higher-order optically-induced magnetic multipole modes. All-dielectric nanoantenna can be realized as an optically small spherical dielectric nanoparticle with a notch excited by a point source (e.g. a quantum dot) located in the notch. The superdirectivity effect is not associated with high dissipative losses. For these dielectric nanoantennas we predict the effect of the beam steering at the nanoscale characterized by a subwavelength sensitivity of the beam radiation direction to the source position. We confirm the predicted effects experimentally through the scaling to the microwave frequency range.

  10. Effect of captopril and telmisartan on methotrexate-induced hepatotoxicity in rats: impact of oxidative stress, inflammation and apoptosis.

    Science.gov (United States)

    Kelleni, Mina T; Ibrahim, Salwa A; Abdelrahman, Aly M

    2016-06-01

    Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid drug whose efficacy is limited by its hepatotoxicity. The aim of this study was to investigate the possible protective role of captopril (100 mg/kg/day, p.o. for seven days), an angiotensin converting enzyme inhibitor, and telmisartan (10 mg/kg/day p.o. for seven days), an angiotensin II receptor blocker with peroxisome proliferative receptor gamma (PPARγ) agonism, in a model of MTX (single dose 20 mg/kg i.p. at the fifth day) induced hepatotoxicity in rats. Results of the present study revealed MTX-induced hepatotoxicity as demonstrated by increased level of liver enzymes and confirmed by histopathology. Pretreatment with captopril or telmisartan produced a significant hepatic protection manifested as a significant (p captopril/Telmisartan, if tolerated and not contraindicated, as preferable antihypertensive agents in patients receiving MTX in their chemotherapy protocols.

  11. Effect of methanol extract of Cuscuta reflexa aerial parts on hepatotoxicity induced by antitubercular drugs in rats

    Directory of Open Access Journals (Sweden)

    B R Balakrishnan

    2010-03-01

    Full Text Available Abstract: Evaluation of hepatoprotective activity of extracts of Cuscuta reflexa (Convolvulaceae on Isoniazid (INH and Rifambicin (RIF induced hepatotoxicity rats. Hepatotoxicity was observed by biochemical measurments: Serum alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP activities, ﻻ- GT the levels of total bilirubin were evaluated. There was a significant decrease in serum parameters in extract and standard drug treated groups. Histopathological changes were also observed in livers of animals that received extract and standard drug. Industrial relevance: The data generated in this study suggest that Cuscuta reflexa, could be very useful in the management of hepatoprotection on INH and RIF induced hepatotoxicity. Further studies will still be required at identifying the active hypoglycaemic phytoconstituents and their possible mechanism.

  12. Growth, carcass characteristics, and profitability of organic versus conventional dairy beef steers.

    Science.gov (United States)

    Bjorklund, E A; Heins, B J; Dicostanzo, A; Chester-Jones, H

    2014-03-01

    Bull calves (n=49), born at the University of Minnesota West Central Research and Outreach Center (Morris) between March and May 2011, were used to compare growth measurements and profitability of conventional and organic dairy steers. Calves were assigned to 1 of 3 replicated groups at birth: conventional (CONV; n=16), organic (pasture and concentrate; ORG; n=16), or organic grass only (GRS; n=17), and analysis of variables was on a pen basis. Breed groups of calves were Holstein (HO; n=9); Holsteins (n=11) maintained at 1964 breed average level; crossbreds (n=19) including combinations of HO, Montbéliarde, and Swedish Red; and crossbreds (n=10) including combinations of HO, Jersey, Swedish Red, and Normande. The CONV steers were fed a diet of 80% concentrate and 20% forage. The ORG steers were fed a diet of organic corn, organic corn silage, and at least 30% of their diet consisted of organic pasture during the grazing season. The GRS steers grazed pasture during the grazing season and were fed high-quality hay or hay silage during the nongrazing season. Intakes of a total mixed ration were recorded daily with herd management software. A profit function was defined to include revenues and expenses for beef value, feed intake, pasture intake, health cost, and yardage. The GRS (358.6 kg) steers had lesser total gains from birth to slaughter than ORG (429.6 kg) and CONV (534.5 kg) steers. Furthermore, the GRS (0.61 kg/d) steers had lesser average daily gain from birth compared with ORG (0.81 kg/d) and CONV (1.1 kg/d) steers. The GRS and ORG steers had smaller rib eye area (49.5 and 65.8 cm(2), respectively) compared with CONV (75.4 cm(2)) steers. For profitability, GRS steers had 43% greater profit than CONV steers due to organic beef price premiums and lower feed costs. On the other hand, ORG steers had substantially less profit than CONV steers. The higher cost of production for the ORG steers is due to the extreme high value of organic corn. The results of the

  13. Evaluation of Potential Usage of Incremental-Type Rotary Encoder Application for Angle Sensing in Steering System

    Directory of Open Access Journals (Sweden)

    Sunarto Kaleg

    2014-12-01

    Full Text Available The main target of a steering system is that the driver can change vehicle trajectory in accordance with the desired direction.  Power steering has become a standard feature in automobile.  It provides assisting power when the driver turns the steering wheel. The well-known power steering types include; Hydraulic Power Steering (HPS, Electro - Hydraulic Power Steering (EHPS, and Electric Power Steering (EPS. EHPS or EPS uses an Electronic Control Unit (ECU which is specific for each vehicle. The ECU should be able to regulate power of electric motor to provide corresponding assisting power for the steering wheel. Therefore ECU requires input signals, one of which is vehicle wheel angle that can be indicated from the vehicle steering wheel angle. Incremental type of Rotary Encoder (RE is used in steering angle sensor on a minibus. RE specification used was 60 pulses per rotation and the minibus steering transmission specification is 3.5 round of right wheel off angle to the left wheel off angle. So we get the RE angular resolution 6ºper pulse and 105 number of pulses to half of the steering transmission ratio. Repeatability then tested against to a steering angle counter module. Testing is done with a test cycle consisting of 3 repetitions: condition center of the steering wheel, the steering wheel is turned to full right, then to the full left, then back to the right up to the steering wheel center. The results obtained 2 pulses deviation, or equivalent to 12º of steering angle.

  14. Herbal hepatotoxicity by Greater Celandine (Chelidonium majus): causality assessment of 22 spontaneous reports.

    Science.gov (United States)

    Teschke, Rolf; Glass, Xaver; Schulze, Johannes

    2011-12-01

    Toxic liver injury due to the herb Greater Celandine (GC) (Chelidonium majus L.) has been assumed in patients originating from various European countries and created concern. Based on regulatory and liver unspecific ad hoc causality assessments in 22 spontaneous cases of Germany, causality levels for GC were considered probable in 16 and possible in 6 cases. We now analyzed the data of these 22 cases regarding their causality levels employing the liver specific, standardized, structured and quantitative assessment method of the updated scale of CIOMS (Council for International Organizations of Medical Sciences). Causality for GC was found highly probable (n=2), probable (n=6), possible (n=10), unlikely (n=1), and excluded (n=3). Thus, causality could be upgraded in 2 cases to a highly probable causality level, but had to be down graded to excluded, unlikely, or possible causality levels in 3, 1, or 9 cases, respectively. GC hepatotoxicity shows a hepatocellular pattern of liver injury with female gender predominance. On average, age of the patients was 56.4 years, treatment 36.4 days, and latency period until first symptoms and jaundice 29.8 and 35.6 days, respectively. This analysis therefore provides further evidence for the existence of GC hepatotoxicity as a distinct form of herb induced liver injury, but due to poor data quality the causal association between GC use and liver injury is less strong than hitherto assumed. We propose replacement of the regulatory organ unspecific by a liver specific causality assessment method in cases of herb induced liver injury as well as stricter pharmacovigilance strategies towards improvements of data quality. Toxicological studies are now warranted to elucidate the mechanism(s) of human GC hepatotoxicity that represents a European issue. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Prevention of hepatotoxicity due to anti tuberculosis treatment: A novel integrative approach

    Institute of Scientific and Technical Information of China (English)

    Meghna R Adhvaryu; Narsimha M Reddy; Bhasker C Vakharia

    2008-01-01

    AIM: To evaluate the ability of Curcuma longa (CL) and Tinospora cordifolia (TC) formulation to prevent anti-tuberculosis (TB) treatment (ATT) induced hepatotoxicity.METHODS: Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation.Isoniazid,rifampicin,pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment.Curcumin enriched (25%) CL and a hydro-ethanolic extract enriched (50%) TC 1 g each divided in two doses comprised the herbal adjuvant.Hemogram,bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result.RESULTS: Incidence and severity of hepatotoxicity was significantly lower in trial group (incidence: 27/192 vs 2/316,P < 0.0001).Mean aspartate transaminase (AST) (195.93 ± 108.74 vs 85 ± 4.24,P < 0.0001),alanine transaminase (ALT) (75.74 ± 26.54 vs 41 ±1.41,P < 0.0001) and serum bilirubin (5.4 ± 3.38 vs 1.5± 0.42,P < 0.0001).A lesser sputum positivity ratio at the end of 4 wk (10/67 vs 4/137,P = 0.0068) and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment (9/152 vs 2/278,P = 0.0037) was observed.Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group (P < 0.0001).CONCLUSION: The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects.

  16. The Role of RAAS Inhibition by Aliskiren on Paracetamol-Induced Hepatotoxicity Model in Rats.

    Science.gov (United States)

    Karcioglu, Saliha Sena; Palabiyik, Saziye Sezin; Bayir, Yasin; Karakus, Emre; Mercantepe, Tolga; Halici, Zekai; Albayrak, Abdulmecit

    2016-03-01

    Paracetamol is one of the most popular and widely used analgesic and antipyretic agents, but an overdose can cause hepatotoxicity and lead to acute liver failure. Aliskiren directly inhibits renin which downregulates the renin-angiotensin-aldosterone system (RAAS). Recent findings suggest that RAAS system takes part in the pathogenesis of liver fibrosis. We aimed to reveal the relationship between hepatotoxicity and the RAAS by examining paracetamol induced hepatotoxicity. Rats were separated into five groups as follows: control, 100 mg/kg aliskiren (p.o.), 2 g/kg paracetamol (per os (p.o.)), 2 g/kg paracetamol + 50mg/kg aliskiren (p.o.), and 2 g/kg paracetamol + 100 mg/kg aliskiren(p.o.). Samples were analyzed at the biochemical, molecular, and histopathological levels. Paracetamol toxicity increased alanine aminotransferases (ALT), aspartate aminotransferases (AST), renin, and angiotensin II levels in the serum samples. In addition, the SOD activity and glutathione (GSH) levels decreased while Lipid Peroxidation (MDA) levels increased in the livers of the rats treated with paracetamol. Paracetamol toxicity caused a significant increase in TNF-α and TGF-β. Both aliskiren doses showed an improvement in ALT, AST, oxidative parameters, angiotensin II, and inflammatory cytokines. Only renin levels increased in aliskiren treatment groups due to its pharmacological effect. A histopathological examination of the liver showed that aliskiren administration ameliorated the paracetamol-induced liver damage. In immunohistochemical staining, the expression of TNF-α in the cytoplasm of the hepatocytes was increased in the paracetamol group but not in other treatment groups when compared to the control group. In light of these observations, we suggest that the therapeutic administration of aliskiren prevented oxidative stress and cytokine changes and also protected liver tissues during paracetamol toxicity by inhibiting the RAAS.

  17. Ameliorative effect of vitamin C against hepatotoxicity induced by emamectin benzoate in rats.

    Science.gov (United States)

    Khaldoun Oularbi, H; Richeval, C; Lebaili, N; Zerrouki-Daoudi, N; Baha, M; Djennas, N; Allorge, D

    2016-07-26

    In the present study, we aimed to assess the potential protective effect of ascorbic acid (AA) against emamectin benzoate (EMB)-induced hepatotoxicity. For this purpose, biochemical, histopathological and analytical investigations were performed. Male Wistar rats were distributed into three groups, that is, a control group, an EMB group given 10 mg EMB/kg body weight (BW) by gavage and an EMB + AA group given 10 mg EMB/kg BW and vitamin C intraperitoneally (200 mg/kg). The duration of the treatment was 28 days and the duration of the study was 42 days. There was a statistically significant increase of all hepatic biomarkers, that is, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase activities, and glycemia, in EMB-treated group when compared with the control group. Light microscopic observations revealed variable signs of hepatotoxicity in the EMB group, which were represented by alteration of normal hepatic architecture, inflammatory cell infiltration, hepatocellular steatosis and foci of necrosis at 28 and 42 days post-treatment. However, co-treatment with vitamin C reduced EMB-related liver toxicity and diminished the abnormal biochemical and architectural damage. Emamectin B1a and B1b residues were detectable in all plasma samples of treated rats at 14, 21 and 28 days of treatment. The drug liver tissue concentration was significantly lower in EMB + AA group compared with EMB group at 28 and 42 days. In conclusion, the findings of the present study clearly indicate a significant protective action of vitamin C against EMB hepatotoxicity.

  18. Repression of acetaminophen-induced hepatotoxicity by a combination of celastrol and brilliant blue G.

    Science.gov (United States)

    Abdelaziz, Heba A; Shaker, Mohamed E; Hamed, Mohamed F; Gameil, Nariman M

    2017-06-05

    The sterile inflammatory response is an eminent contributor to acetaminophen (APAP)-hepatotoxicity in humans. Recent advances unraveled an axial role of the NLRP3-inflammasome in APAP-post injury inflammation. Nevertheless, the role of signaling events preceded the NLRP3-inflammasome activation, like the transcription factor NF-κB and the purinergic receptor P2X7, is still unclear and needs further elucidation. Here, we investigated the pharmacological inhibition of these upstream signaling molecules by celastrol and brilliant blue G (BBG) (separately or simultaneously) in APAP-hepatotoxicity in mice. The results indicated that both celastrol and BBG pretreatments, especially when combined together, curbed APAP-induced hepatocellular injury (ALT, AST and LDH) and death (necrosis and apoptosis). The underlying mechanisms of protection of such combination against APAP-challenge were attributed to their efficient cooperation in: i) preventing the consumption of hepatic antioxidants (reduced glutathione and superoxide dismutase); ii) limiting the overproduction of lipid peroxidation aldehydes (malondialdehyde and 4-hydroxynonenal) and total nitrate/nitrite products; iii) attenuating the inflammatory cells accumulation in the liver, as evidenced by reducing the number of F4/80 positive cells/field in immunostaining and myeloperoxidase activity; iv) reversing the dysregulation in production of pro-inflammatory (TNF-α, IL-17A and IL-23) and anti-inflammatory (IL-10) cytokines; and v) enhancing the reparative capacity of injured hepatocytes, as demonstrated by increasing the percentage of PCNA positive hepatocytes per field of immunostaining. In conclusion, this murine study elicits a potential clinical applicability and therapeutic utility of celastrol and BBG combination in human cases of APAP-overdose hepatotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Improved Hepatoprotective Effect of Liposome-Encapsulated Astaxanthin in Lipopolysaccharide-Induced Acute Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Chun-Hung Chiu

    2016-07-01

    Full Text Available Lipopolysaccharide (LPS-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST, a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10 for seven days and then were LPS-challenged (i.p., 5 mg/kg. The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT, glutamic oxaloacetic transaminase (GOT, blood urea nitrogen (BUN, creatinine (CRE, hepatic malondialdehyde (MDA and glutathione peroxidase (GSH-Px, IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS, suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day. Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity.

  20. Effect of imidacloprid on hepatotoxicity and nephrotoxicity in male albino mice

    Directory of Open Access Journals (Sweden)

    Yasir Arfat

    2014-01-01

    Full Text Available Imidacloprid (IC is a systemic insecticide related to the tobacco toxin nicotine. IC is a toxic substance frequently used into combat insects, rodents and plants pests and other creatures that can pose problems for agriculture. We, therefore, planned this study to assess risk factors, biochemical and histological alterations associated with hepatotoxicity and nephrotoxicity. Forty-eight adult male albino mice were divided into four groups of 12 animals each. All the animals were given standard synthetic pellet diet. One group served as control, and the other three were served as experimental groups. Decrease in the body weight of the high dose group was observed at 15 mg/kg/day, and no mortality occurred during the treatment period. High dose of imidacloprid caused a significant elevation of serum clinical chemistry parameters, serum glutamic oxaloacetic transaminase (SGOT, serum glutamic pyruvate kinase (SGPT, alkaline phosphatase (ALP and total bilirubin (TBIL. Histology of liver and kidney indicates hepatotoxicity and nephrotoxicity at a high dose of imidacloprid. Based on the morphological, biochemical and histopathological analysis, it is evident that imidacloprid induced toxicological effects at 15 mg/kg/day to mice. The results of the present study demonstrate that IC had significant effects on body weight, liver functions and kidney (p < 0.05 at a dose of 15 mg/kg body weight. IC treatment 5 and 10 mg/kg/day may be considered as no observed adverse effect level (NOAEL for mice. It was concluded that IC can cause hepatotoxicity and nephrotoxicity at a dose much lower than the LD50 (131 mg/kg body weight in mice.

  1. Improved Hepatoprotective Effect of Liposome-Encapsulated Astaxanthin in Lipopolysaccharide-Induced Acute Hepatotoxicity.

    Science.gov (United States)

    Chiu, Chun-Hung; Chang, Chun-Chao; Lin, Shiang-Ting; Chyau, Charng-Cherng; Peng, Robert Y

    2016-07-14

    Lipopolysaccharide (LPS)-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST), a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA) apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group) were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10) for seven days and then were LPS-challenged (i.p., 5 mg/kg). The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), creatinine (CRE), hepatic malondialdehyde (MDA) and glutathione peroxidase (GSH-Px), IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS), suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day). Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity.

  2. Antioxidant and anti-inflammatory role of zingerone in ethanol-induced hepatotoxicity.

    Science.gov (United States)

    Mani, Vijay; Arivalagan, Sivaranjani; Siddique, Aktarul Islam; Namasivayam, Nalini

    2016-10-01

    Alcoholic liver disease is a direct result of alcohol-induced hepatotoxicity coupled with impaired hepatic regenerative activity. Our aim of the study was to investigate the beneficial effect of zingerone on hepatic oxidative stress and inflammation induced by ethanol in experimental rats. Male albino Wistar rats were divided into four groups. Rats of groups 1 and 2 received isocaloric glucose and dimethyl sulfoxide (2 % DMSO). Hepatotoxicity was induced in groups 3 and 4 by supplementing 30 % ethanol post orally for 60 days. Rats of groups 2 and 4 received zingerone (20 mg/kg body weight in 2 % DMSO p.o) daily during the final 30 days of the experimental period. Ethanol alone administered rats showed significant increase in the plasma and tissue lipid peroxidation markers such as thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes, and a significant decrease in the activities of plasma and tissue enzymic and non-enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione, vitamin C, and vitamin E. Moreover, the presence of mast cells and increase in the expressions of inflammatory markers such as NF-κB, COX-2, TNF-α, and IL-6 and decrease in the expression of Nrf2 in the liver was observed in ethanol-fed rats. Supplementation with zingerone to ethanol-fed rats reversed the changes induced by ethanol in the experimental rats. Thus, zingerone, through its antioxidant and anti-inflammatory effects, may represent a therapeutic option to protect against ethanol-induced hepatotoxicity.

  3. The role of infliximab on paracetamol-induced hepatotoxicity in rats.

    Science.gov (United States)

    Ferah, Irmak; Halici, Zekai; Bayir, Yasin; Demirci, Elif; Unal, Bunyami; Cadirci, Elif

    2013-06-01

    Paracetamol has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Infliximab is tumor necrosis factor alpha (TNF-α) inhibitor agent, which has been developed as a therapeutic agent for TNF-α-mediated disease. It acts by binding and neutralizing TNF. The aim of our study was to evaluate the hepatoprotective activity of infliximab on paracetamol-induced hepatotoxicity and to understand the relationship between the TNF-α and paracetamol-induced liver injury. Fifty-six rats were divided into eight groups as each composed of seven rats: (1) intact, (2) 7 mg/kg infliximab, (3) 140 mg/kg NAC, (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 3 mg/kg infliximab, (7) 2 g/kg paracetamol + 5 mg/kg infliximab and (8) 2 g/kg paracetamol + 7 mg/kg infliximab groups. Liver function tests including lipid peroxidation levels were analyzed and histopathological changes of liver were also observed. There were statistically significant increases in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), levels of TNF-α and malondialdehyde (MDA) and decreases in the activity of superoxide dismutase (SOD) and level of glutathione (GSH) in the group treated with paracetamol. Infliximab administration dramatically reduced serum ALT, AST and TNF-α level. Also, it restored GSH, SOD and decreased MDA levels in liver. Liver histopathological examination showed that infliximab administration antagonized paracetamol-induced liver pathological damage. The results of present study suggest that infliximab has significant hepatoprotective activity on paracetamol-induced hepatotoxicity.

  4. Effects of platelet-rich plasma on liver regeneration in CCl4-induced hepatotoxicity model.

    Science.gov (United States)

    Mafi, Afsaneh; Dehghani, Farzaneh; Moghadam, Abbas; Noorafshan, Ali; Vojdani, Zahra; Talaei-Khozani, Tahereh

    2016-12-01

    Numerous bioactive growth factors and cytokines in platelet-rich plasma (PRP) have recently made it an attractive biomaterial for therapeutic purposes. These growth factors have the potential to regenerate the injured tissues. The aim of this study was to investigate the therapeutic effects of PRP in hepatotoxic animal model. Hepatotoxicity was induced in rats by oral administration of 4 mL/kg/week of CCl4 diluted 1:1 in corn oil for 10 weeks. To confirm the hepatotoxicity, 24 h after the last CCl4 administration, blood samples were collected via cardiac puncture to assess the serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein, and total bilirubin. Twenty-four hours after blood collection, the experimental animals received a single injection of PRP (1 mL) via the anterior mesenteric vein. One week later, all biochemical tests were performed again, and the rats were scarified and their livers were removed, prepared histologically, and stained. The stereological analyses were performed to evaluate the effects of PRP on histopathological features of CCl4-treated livers. The results were compared statistically with the corresponding control and CCl4+normal saline (NS)-treated animals. A significant decrease in the number and volume of hepatocytes (p = 0.01), and also a reduction in the volume of sinusoids (p = 0.001) and connective tissue (p = 0.04), were observed in the PRP-treated animals compared with the CCl4+NS-treated ones. Our findings demonstrated that application of PRP had beneficial effects on CCl4-induced fibrosis; however, it had detrimental effects on the total number of hepatocytes and the volume of hepatocytes and sinusoidal spaces.

  5. Detecting mRNA Predictors of Acetaminophen-Induced Hepatotoxicity in Mouse Blood Using Quantitative Real-Time PCR.

    Science.gov (United States)

    Kanno, Syu-ichi; Tomizawa, Ayako; Yomogida, Shin

    2016-01-01

    Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. Drug-induced liver injury from agents such as APAP is known to vary between individuals within a species. To avoid liver injury and ensure the proper use of pharmaceutical products, it is important to be able to predict such risks using genetic information. This study evaluated the use of quantitative real-time polymerase chain reaction (RT-qPCR) to identify mRNAs (carried in the blood of male ddY mice) capable of predicting susceptibility to APAP-induced hepatotoxicity. Screening was performed on samples obtained at 18 h after treatment from mice that had been orally treated with 500 mg/kg APAP. APAP-induced hepatotoxicity was seen in 60% of the mice, and the mortality rate was 12%. Blood APAP concentration did not differ significantly between mice with and without APAP-induced hepatotoxicity. We compared blood mRNA expression levels between mice with (positive, serious or lethal injury) and without hepatotoxicity in the APAP-treated group. The transcript levels of interleukin-encoding loci Il1β, Il10, and tumor necrosis factor (Tnf) were increased in the lethal injury group. Transcripts of the loci encoding transthyretin (Ttr) and metallothionein 1 (Mt1) showed increases in the liver injury group, while those of the glutathione peroxidase 3-encoding locus (Gpx3) were decreased. APAP hepatotoxicity was potentiated in fasted animals, although fasting did not appear to affect the level of expression of these genes. These results indicate that mRNA expression of Il1β, Il10, Tnf, Ttr, Mt1, and Gpx3 in mouse blood may provide useful surrogate markers of APAP-induced hepatotoxicity.

  6. A Systematic Strategy for Screening and Application of Specific Biomarkers in Hepatotoxicity Using Metabolomics Combined With ROC Curves and SVMs.

    Science.gov (United States)

    Li, Yubo; Wang, Lei; Ju, Liang; Deng, Haoyue; Zhang, Zhenzhu; Hou, Zhiguo; Xie, Jiabin; Wang, Yuming; Zhang, Yanjun

    2016-04-01

    Current studies that evaluate toxicity based on metabolomics have primarily focused on the screening of biomarkers while largely neglecting further verification and biomarker applications. For this reason, we used drug-induced hepatotoxicity as an example to establish a systematic strategy for screening specific biomarkers and applied these biomarkers to evaluate whether the drugs have potential hepatotoxicity toxicity. Carbon tetrachloride (5 ml/kg), acetaminophen (1500 mg/kg), and atorvastatin (5 mg/kg) are established as rat hepatotoxicity models. Fifteen common biomarkers were screened by multivariate statistical analysis and integration analysis-based metabolomics data. The receiver operating characteristic curve was used to evaluate the sensitivity and specificity of the biomarkers. We obtained 10 specific biomarker candidates with an area under the curve greater than 0.7. Then, a support vector machine model was established by extracting specific biomarker candidate data from the hepatotoxic drugs and nonhepatotoxic drugs; the accuracy of the model was 94.90% (92.86% sensitivity and 92.59% specificity) and the results demonstrated that those ten biomarkers are specific. 6 drugs were used to predict the hepatotoxicity by the support vector machines model; the prediction results were consistent with the biochemical and histopathological results, demonstrating that the model was reliable. Thus, this support vector machine model can be applied to discriminate the between the hepatic or nonhepatic toxicity of drugs. This approach not only presents a new strategy for screening-specific biomarkers with greater diagnostic significance but also provides a new evaluation pattern for hepatotoxicity, and it will be a highly useful tool in toxicity estimation and disease diagnoses.

  7. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Henninger, Christian [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf (Germany); Huelsenbeck, Johannes; Huelsenbeck, Stefanie [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Grösch, Sabine [Institute of Clinical Pharmacology, Johann Wolfgang Goethe University Frankfurt, Theodor Stern Kai 7, D-60590 Frankfurt/Main (Germany); Schad, Arno [Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Lackner, Karl J. [Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Kaina, Bernd [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Fritz, Gerhard, E-mail: fritz@uni-duesseldorf.de [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf (Germany)

    2012-05-15

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline

  8. Evaluation of hepatotoxicity and clastogenicity of carbofuran in male Wistar rats.

    Science.gov (United States)

    Gbadegesin, Michael A; Owumi, Solomon E; Akinseye, Victor; Odunola, Oyeronke A

    2014-03-01

    Carbofuran based pesticides have gained wide usage in Nigeria recently. Consequently, animals and human populations are exposed to them in the environment. Information on in vivo toxicity of carbofuran in experimental models is scanty. The present study therefore examined the hepatotoxicity and clastogenic effects of carbofuran in rats. Male Wistar rats were exposed to carbofuran (p.o) at 0-5mg/kg bw for 5weeks. Carbofuran induced significant (prats. It therefore may constitute an environmental health risks in individuals so exposed.

  9. Ketoconazole hepatotoxicity in a patient treated for environmental illness and systemic candidiasis

    Energy Technology Data Exchange (ETDEWEB)

    Brusko, C.S.; Marten, J.T. (Purdue University School of Pharmacy and Pharmacal Sciences, Lafayette, IN (United States))

    1991-12-01

    Environmental illness, a hypothesized disease caused by exposure to substances such as combustion products, pesticides, food additives, and Candida albicans, is discussed. The case of a patient with environmental illness and systemic candidiasis for six weeks with ketoconazole, liver enzyme concentrations increased. One month after discontinuation of ketoconazole, the liver enzyme concentrations decreased; however, over the next five months, liver enzymes and bilirubin increased. The patient developed encephalopathy and eventually was transferred to a medical center for possible liver transplant. A review of the literature pertaining to ketoconazole hepatotoxicity is also presented.16 references.

  10. Evaluation of Prophylactic and Therapeutic Effects of Silymarin on Diazepam-Induced Hepatotoxicity in Cats

    OpenAIRE

    Bahman Mosallanejad; Reza Avizeh; Hossien Najafzadeh

    2011-01-01

    Problem statement: Diazepam is commonly administered for seizure control and appetite stimulant in cats. Cats may develop acute fatal hepatic necrosis after receiving oral diazepam for several days. The aim of this study was to detect the protective action of silymarin on diazepam-induced hepatotoxicity in cats. Approach: About 25 healthy cats were randomly allotted to five equal groups. Animals in Group A were given diazepam (repeated dose 2.5 mg kg-1, p.o. q 12 h for 4 days); Group B consis...

  11. Hydroxycut hepatotoxicity: A case series and review of liver toxicity from herbal weight loss supplements

    Institute of Scientific and Technical Information of China (English)

    Lily Dare; Jennifer Hewett; Joseph Kartaik Lim

    2008-01-01

    Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxiciLy, although the individual chemical components underlying liver injury remain poorly understood. We report two cases of acute hepatitis in the seLLing of Hydroxycut exposure and describe possible mechanisms of liver injury. We also comprehensively review and summarize the existing literature on commonly used weight loss supplements,and their individual components which have demonstrated potential for liver toxicity. An increased effort to screen for and educate patients and physicians about supplement-associated hepatotoxicity is warranted.

  12. Interaction between nitric oxide synthase and cyclooxygenase in the development of acetaminophen-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Meltem Kolgazi

    2015-03-01

    Results: AG and KET prevented the increase in liver malondialdehyde levels due to APAP toxicity. Decreased liver glutathione in APAP group was prevented by all treatments except NIM. Stimulated liver myeloperoxidase activity in APAP group was attenuated by all treatments except INDO and NIM. Elevation of liver chemiluminescence, nuclear factor (NF- and #61547;B expression and serum alanine transferase level due to APAP overdose were also suppressed by all treatments. Conclusions: NOS and COX pathways interact in the development of hepatotoxicity due to APAP overdose. [J Exp Integr Med 2015; 5(1.000: 16-22

  13. Hepatotoxicity of anti-inflammatory and analgesic drugs:ultrastructural aspects

    Institute of Scientific and Technical Information of China (English)

    Irena MANOV; Helen MOTANIS; Idan FRUMIN; Theodore C IANCU

    2006-01-01

    With the increasing incidence of drug-induced liver disease,attempts are being made to better understand the mechanisms behind these frequently life-endangering reactions.Analgesics and anti-inflammatory drugs are a major group exhibiting hepatotoxicity.We review research relating to these reactions,focusing on ultrastructural findings,which may contribute to the comprehension and possible avoidance of drug-induced liver disease.We also present some original observations on clinical material and cultured cells exposed to acetaminophen alone or in combination with the antioxidant N-acetylcysteine or the P-glycoprotein inhibitor verapamil.

  14. Amiodarone-induced exudative bullous lesion and hepatotoxicity in a patient with ventricular tachycardia

    Directory of Open Access Journals (Sweden)

    Ahmet Karakurt

    2015-09-01

    Full Text Available Amiodarone is a potent, iodine rich, highly lipophilic class III antiarrhythmic drug widely used for the management of both supraventricular and ventricular arrhythmias. It tends to concentrate in tissues including fat, lung, liver cornea and skin. Several side effects have been reported in patients taking amiodarone. The mechanisms of amiodarone-induced side effects are poorly understood. Accumulation of amiodarone in tissues and organs has been suggested as a possible mechanism. The most frequent dermatologic side effects are photosensitivity, skin discoloration and erythema. This article presents the case of a patient who developed amiodarone-induced bullous skin lesions and hepatotoxicity.

  15. Feeding behavior of steers fed a complete mixed ration.

    Science.gov (United States)

    Chase, L E; Wangsness, P J; Baumgardt, B R

    1976-11-01

    Feeding behavior of five Holstein steers fed a complete mixed ration was studied by use of individual, electronically controlled feeding behavior units. Both individual meal and daily behavioral parameters were measured. Number of meals, size of each individual meal, time spent eating, and intervals between meals were measured. Eating rates were then calculated. Diurnal feeding patterns were observed with 60.9% of the meals occurring between 0600 and 1800 h. For individual meals, body weight accounted for less than 30% of the variation in meal size. Average meal size was 414.5 g. Respective means for overall meal duration, actual meal duration, overall eating rate, and actual eating rate were 20.3 min, 13.7 min, 23.1 g/min, and 30.0 g/min. Meal size per body weight (g/kg or g/kg.75) was relatively constant during observation. Both increased eating rate and increased meal length were associated with larger meals. However, eating rate tended to plateau while meal length continued to increase with larger meals. Steers consumed 10.01 meals per day while total daily overall meal duration and actual meal duration were 220.9 and 156.4 min.

  16. Stability Simulation of a Vehicle with Wheel Active Steering

    Directory of Open Access Journals (Sweden)

    Brabec Pavel

    2016-01-01

    Full Text Available This paper deals with the possibility of increasing the vehicle driving stability at a higher speed. One of the ways how to achieve higher stability is using the 4WS system. Mathematical description of vehicle general movement is a very complex task. For simulation, models which are aptly simplified are used. For the first approach, so-called single-truck vehicle model (often linear is usually used. For the simulation, we have chosen to extend the model into a two-truck one, which includes the possibility to input more vehicle parameters. Considering the 4WS system, it is possible to use a number of potential regulations. In our simulation model, the regulation system with compound coupling was used. This type of regulation turns the rear wheels depending on the input parameters of the system (steering angle of the front wheels and depending on the output moving quantities of the vehicle, most frequently the yaw rate. Criterion for compensation of lateral deflection centre of gravity angle is its zero value, or more precisely the zero value of its first-order derivative. Parameters and set-up of the simulation model were done in conjunction with the dSAPACE software. Reference performances of the vehicle simulation model were made through the defined manoeuvres. But the simulation results indicate that the rear-wheels steering can have a positive effect on the vehicle movement stability, especially when changing the driving direction at high speed.

  17. Needle Steering in 3-D Via Rapid Replanning.

    Science.gov (United States)

    Patil, Sachin; Burgner, Jessica; Webster, Robert J; Alterovitz, Ron

    2014-08-01

    Steerable needles have the potential to improve the effectiveness of needle-based clinical procedures such as biopsy and drug delivery by improving targeting accuracy and reaching previously inaccessible targets that are behind sensitive or impenetrable anatomical regions. We present a new needle steering system capable of automatically reaching targets in 3-D environments while avoiding obstacles and compensating for real-world uncertainties. Given a specification of anatomical obstacles and a clinical target (e.g., from preoperative medical images), our system plans and controls needle motion in a closed-loop fashion under sensory feedback to optimize a clinical metric. We unify planning and control using a new fast algorithm that continuously replans the needle motion. Our rapid replanning approach is enabled by an efficient sampling-based rapidly exploring random tree (RRT) planner that achieves orders-of-magnitude reduction in computation time compared with prior 3-D approaches by incorporating variable curvature kinematics and a novel distance metric for planning. Our system uses an electromagnetic tracking system to sense the state of the needle tip during the procedure. We experimentally evaluate our needle steering system using tissue phantoms and animal tissue ex vivo. We demonstrate that our rapid replanning strategy successfully guides the needle around obstacles to desired 3-D targets with an average error of less than 3 mm.

  18. Reducing supplementation frequency for Nellore beef steers grazing tropical pastures

    Directory of Open Access Journals (Sweden)

    Roberta Carrilho Canesin

    2014-04-01

    Full Text Available Reduced supplementation frequency is a broadly applied management practice. Ruminants consuming low quality forages/pastures, supplemented less than once daily are able to maintain body weight gain (BWG, efficiency of use of dry matter, nitrogen and other nutrients, as compared with animals supplemented once daily. We evaluated the feeding behavior, dry matter intake (DMI, dry matter and organic matter digestibility (DMD and OMD, BWG, Longissimus muscle area and backfat depth of Nellore steers raised on Brachiaria brizantha cv. Marandu pastures during the dry season, with different supplementation patterns. Thirty six animals (338 ± 40.7 kg were distributed over nine paddocks according to a completely randomized design. Treatments were based on supplementation frequency: once daily (OD, once daily except Saturdays and Sundays (SS, or on alternate days (AD, at 1.0 %, 1.4 % and 2.0 % BW, respectively. Average total DMI accounted for 1.6 % BW day-1, with no effect of supplementation frequency. Supplementation frequency had no effect on BWG or grazing time during the day. There was no difference in Longissimus muscle area animals supplemented daily, SS and AD. The backfat depth was thinner in animals supplemented AD, but even in this case, it was within the standards considered satisfactory for a finishing steer. Reducing supplementation frequency seems a good option to lower labor costs without affecting feed efficiency or carcass quality in beef cattle grazing tropical pastures.

  19. Research on the Steering Strategy for Hydrogen Maser

    Science.gov (United States)

    Yin, D. S.; Zhao, S. H.; Gao, Y. P.

    2016-07-01

    In the master clock system, the local standard time UTC(k) with a better short-term stability will be generated, if the hydrogen maser is set as a frequency source of the master clock. But the hydrogen maser always exhibits an apparent frequency drift, thus its long-term stability gets poor with time, therefore the stability and accuracy of UTC(k) become worse. To solve this problem, we compare the performance of hydrogen maser with cesium clocks, and modify the time scale algorithm when the hydrogen maser is involved, we also propose a new steering strategy when hydrogen maser is used as the frequency source of master clock. We set up an experiment system and write programs, and finally the new steering strategy is testified with the laboratory data. Results show that when the hydrogen maser is involved in the atomic time scale calculation, the short-term frequency stability of reference time scale will be improved. Meanwhile, the local time UTC(k) has a better short-term frequency stability when the frequency source of the master clock uses hydrogen maser instead of cesium clock.

  20. Needle Steering in 3-D Via Rapid Replanning

    Science.gov (United States)

    Patil, Sachin; Burgner, Jessica; Webster, Robert J.; Alterovitz, Ron

    2014-01-01

    Steerable needles have the potential to improve the effectiveness of needle-based clinical procedures such as biopsy and drug delivery by improving targeting accuracy and reaching previously inaccessible targets that are behind sensitive or impenetrable anatomical regions. We present a new needle steering system capable of automatically reaching targets in 3-D environments while avoiding obstacles and compensating for real-world uncertainties. Given a specification of anatomical obstacles and a clinical target (e.g., from preoperative medical images), our system plans and controls needle motion in a closed-loop fashion under sensory feedback to optimize a clinical metric. We unify planning and control using a new fast algorithm that continuously replans the needle motion. Our rapid replanning approach is enabled by an efficient sampling-based rapidly exploring random tree (RRT) planner that achieves orders-of-magnitude reduction in computation time compared with prior 3-D approaches by incorporating variable curvature kinematics and a novel distance metric for planning. Our system uses an electromagnetic tracking system to sense the state of the needle tip during the procedure. We experimentally evaluate our needle steering system using tissue phantoms and animal tissue ex vivo. We demonstrate that our rapid replanning strategy successfully guides the needle around obstacles to desired 3-D targets with an average error of less than 3 mm. PMID:25435829

  1. Electronically-Controlled Beam-Steering through Vanadium Dioxide Metasurfaces

    Science.gov (United States)

    Hashemi, Mohammed Reza M.; Yang, Shang-Hua; Wang, Tongyu; Sepúlveda, Nelson; Jarrahi, Mona

    2016-10-01

    Engineered metamaterials offer unique functionalities for manipulating the spectral and spatial properties of electromagnetic waves in unconventional ways. Here, we report a novel approach for making reconfigurable metasurfaces capable of deflecting electromagnetic waves in an electronically controllable fashion. This is accomplished by tilting the phase front of waves through a two-dimensional array of resonant metasurface unit-cells with electronically-controlled phase-change materials embedded inside. Such metasurfaces can be placed at the output facet of any electromagnetic radiation source to deflect electromagnetic waves at a desired frequency, ranging from millimeter-wave to far-infrared frequencies. Our design does not use any mechanical elements, external light sources, or reflectarrays, creating, for the first time, a highly robust and fully-integrated beam-steering device solution. We demonstrate a proof-of-concept beam-steering metasurface optimized for operation at 100 GHz, offering up to 44° beam deflection in both horizontal and vertical directions. Dynamic control of electromagnetic wave propagation direction through this unique platform could be transformative for various imaging, sensing, and communication applications, among others.

  2. Electronically-Controlled Beam-Steering through Vanadium Dioxide Metasurfaces

    Science.gov (United States)

    Hashemi, Mohammed Reza M.; Yang, Shang-Hua; Wang, Tongyu; Sepúlveda, Nelson; Jarrahi, Mona

    2016-01-01

    Engineered metamaterials offer unique functionalities for manipulating the spectral and spatial properties of electromagnetic waves in unconventional ways. Here, we report a novel approach for making reconfigurable metasurfaces capable of deflecting electromagnetic waves in an electronically controllable fashion. This is accomplished by tilting the phase front of waves through a two-dimensional array of resonant metasurface unit-cells with electronically-controlled phase-change materials embedded inside. Such metasurfaces can be placed at the output facet of any electromagnetic radiation source to deflect electromagnetic waves at a desired frequency, ranging from millimeter-wave to far-infrared frequencies. Our design does not use any mechanical elements, external light sources, or reflectarrays, creating, for the first time, a highly robust and fully-integrated beam-steering device solution. We demonstrate a proof-of-concept beam-steering metasurface optimized for operation at 100 GHz, offering up to 44° beam deflection in both horizontal and vertical directions. Dynamic control of electromagnetic wave propagation direction through this unique platform could be transformative for various imaging, sensing, and communication applications, among others. PMID:27739471

  3. Aeronautical satellite antenna steering using magnetic field sensors

    Science.gov (United States)

    Sydor, John; Dufour, Martial

    1993-01-01

    Designers of aeronautical satellite terminals are often faced with the problem of steering a directive antenna from an airplane or helicopter. This problem is usually solved by using aircraft orientation information derived from inertial sensors on-board the aircraft in combination with satellite ephemeris information calculated from geographic coordinates. This procedure works well but relies heavily on avionics that are external to the terminal. For the majority of small aircraft and helicopters which will form the bulk of future aeronautical satcom users, such avionics either do not exist or are difficult for the satellite terminal to interface with. At the Communications Research Center (CRC), work has been undertaken to develop techniques that use the geomagnetic field and satellite antenna pointing vectors (both of which are stationary in a local geographical area) to track the position of a satellite relative to a moving platform such as an aircraft. The performance of this technique is examined and a mathematical steering transformation is developed within this paper. Details are given regarding the experimental program that will be undertaken to test the concepts proposed herein.

  4. Motion Synthesis of a Self-Steered Mobile Robot

    Science.gov (United States)

    Roseborrough, Michael; Phillips, Keith

    1987-02-01

    Until the late 1950's there was an almost exclusive use of graphical methods in the kinematic analysis and synthesis of mechanisms. With the increasing availability of high-speed digital computers there was a major reawakening of interest in a field con-sidered by many to be mature and dormant. Today the birth of advanced robotic systems has heightened the interest in applications of kinematic analysis and synthesis. This paper discusses the application of kinematics to the path planning model of a three wheeled, self-steering, mobile robot. The problem is formulated through a kinematic analysis of the path curvature and the synthesis of a set of equivalent linkages. The equivalent linkages facilitate a direct relationship between the path and the robot steering control mechanism. This is accomplished through the kinematic param-eters displacement, velocity and acceleration. The mathematical model is presented in a generalized format with the robot represented as a rigid body. Examples are shown which solve the problem of moving the robot through a crowded environment and arriving at its destination in a predetermined orientation.

  5. Monitoring and Steering of Large-Scale Distributed Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Geist, G.A.; Kohl, J.A.

    1999-09-01

    Oak Ridge National Laboratory is developing a state-of-the-art parallel application development system called CUMULVS, which allows scientists to easily incorporate interactive visualization, computational steering and fault tolerance into distributed software applications. The system is a valuable tool for many large scientific applications because it enables the scientist to visually monitor large data fields and remotely control parameters inside a running application. Collaborative monitoring is provided by allowing multiple researchers to simultaneously attach to a simulation, each controlling their own view of the same or different data fields within the simulation. By supporting steering of a simulation while it is running, CUMULVS provides the opportunity to accelerate the process of scientific discovery. CUMULVS also provides a simple mechanism to incorporate automatic checkpointing and heterogeneous task migration into large applications so that simulations can continue to run for weeks unattended. This paper will give an overview of the CUMULVS system and its capabilities, including several case histories. The status of the project is described with instructions on how to obtain the software.

  6. Defining Value in Cancer Care: AVBCC 2013 Steering Committee Report.

    Science.gov (United States)

    Zweigenhaft, Burt; Bosserman, Linda; Kenney, James T; Lawless, Grant D; Marsland, Thomas A; Deligdish, Craig K; Burgoyne, Douglas S; Knopf, Kevin B; Long, Douglas M; McKercher, Patrick; Owens, Gary M; Hennessy, John E; Lang, James R; Malin, Jennifer; Natelson, Leonard; Palmgren, Matthew C; Slotnik, Jayson; Shockney, Lillie D; Vogenberg, F Randy

    2013-07-01

    The AVBCC Annual Meeting experiences exponential growth in attendance and participation as oncologists, payers, employers, managed care executives, patient advocates, and drug manufacturers convened in Hollywood, FL, on May 2-5, 2013, for the Third Annual Conference of the Association for Value-Based Cancer Care (AVBCC). The conference presented an all-inclusive open forum for stakeholder dialogue and integration across the cancer care continuum, facilitating an open dialogue among the various healthcare stakeholders to align their perspectives around the urgent need to address value in cancer care, costs, patient education, safety, outcomes, and quality. The AVBCC 2013 Steering Committee was held on the first day of the conference to define value in cancer care. The committee was divided into 7 groups, each representing a key stakeholder in oncology. The goal of the Steering Committee was to define value from the particular point of view of each of the stakeholder groups and to suggest how that particular perspective can contribute to the value proposition in oncology, by balancing cost, quality, and access to care to improve overall patient outcomes. The following summary highlights the major points addressed by each group.

  7. Biogas production from steer manures in Vietnam: Effects of feed supplements and tannin contents.

    Science.gov (United States)

    Pham, Cuong H; Saggar, Surinder; Vu, Cuong C; Tate, Kevin R; Tran, Thao T T; Luu, Thi T; Ha, Hanh T; Nguyen, Huong L T; Sommer, Sven G

    2017-08-05

    In developing countries, the simple biogas digesters installed underground without heating or stirring are seen as a 'green' technology to convert animal waste into biogas, a source of bio-energy. However, quantitative estimates of biogas production of manures from steers fed local feed diets at actual incubation temperatures have yet to be carried out. The aim of this study was to determine the methane (CH4) production potential of manures from steers in Vietnam offered traditional feed rations or supplemental diets. Biochemical CH4 production (BMP) was measured in batch tests at 30°C using manures collected from two different experiments of steers fed diets containing feed supplements. BMP was 110.1 (NLkg(-1)VS) for manure from steers receiving a control diet, significantly lower 79.0 (NL kg(-1)VS) for manure from steers fed a diet containing 0.3% tannin (%DM), but then showed an increasing trend to 90.9 and 91.2 (NL kg(-1)VS) for manures from steers receiving 0.4 and 0.5% tannin (%DM) supplements, respectively. Similarly, the CH4 production (NL kg(-1)VS) of manure from steers was 174 for control, 142 for control supplemented concentrate (C), 143 for control added rice straw treated with urea (R), and 127 for control supplemented C and R. Our results show there was a decrease in CH4 emissions from steer manures through using supplemented rations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Genetic effects on carcass quantity, quality, and palatability traits in straightbred and crossbred Romosinuano steers

    Science.gov (United States)

    The objectives of this work were to estimate heterosis and breed genetic effects for carcass quantity, quality, and palatability traits of steers (Bos spp.) produced from matings of Romosinuano, Brahman, and Angus cattle. Steers (n = 464) were weaned at 7 mo of age and transported to the Southern G...

  9. Application of washed rumen technique for rapid determination of fasting heat production in steers

    Science.gov (United States)

    Two experiments were conducted to evaluate the use of a washed rumen technique as an alternative approach for determining fasting HP in cattle. In Exp. 1, 8 Holstein steers (322±30 kg) were adapted to a cubed alfalfa-based diet (1.5xNEm) for 10 d. After which steers were placed into individual hea...

  10. Two dimensional thermo-optic beam steering using a silicon photonic optical phased array

    Science.gov (United States)

    Mahon, Rita; Preussner, Marcel W.; Rabinovich, William S.; Goetz, Peter G.; Kozak, Dmitry A.; Ferraro, Mike S.; Murphy, James L.

    2016-03-01

    Components for free space optical communication terminals such as lasers, amplifiers, and receivers have all seen substantial reduction in both size and power consumption over the past several decades. However, pointing systems, such as fast steering mirrors and gimbals, have remained large, slow and power-hungry. Optical phased arrays provide a possible solution for non-mechanical beam steering devices that can be compact and lower in power. Silicon photonics is a promising technology for phased arrays because it has the potential to scale to many elements and may be compatible with CMOS technology thereby enabling batch fabrication. For most free space optical communication applications, two-dimensional beam steering is needed. To date, silicon photonic phased arrays have achieved two-dimensional steering by combining thermo-optic steering, in-plane, with wavelength tuning by means of an output grating to give angular tuning, out-of-plane. While this architecture might work for certain static communication links, it would be difficult to implement for moving platforms. Other approaches have required N2 controls for an NxN element phased array, which leads to complexity. Hence, in this work we demonstrate steering using the thermo-optic effect for both dimensions with a simplified steering mechanism requiring only two control signals, one for each steering dimension.

  11. Design and Development of Labview Based Steering Wheel Angle Sensor System

    Directory of Open Access Journals (Sweden)

    Tony George

    2015-04-01

    Full Text Available Conventional angle sensors can measure only 360°,but passenger car steering wheel turns through +/-720o (a total of 4 complete turns. In this paper we describe iGMR based steering wheel angle sensor implementation which can be used as a rotation sensor to measure +/- 720°.

  12. Does pedalling on a recumbent bicycle influence the cyclist’s steering behaviour?

    NARCIS (Netherlands)

    Boon, K.M.; Klap, P.; Van Lanen, J.A.; Letsoin, G.J.; Jansen, A.J.

    2014-01-01

    The paper presents the answer to the question how pedalling on a specific recumbent bicycle, such as the VeloX3, influences a cyclist’s ability to steer the bicycle. The research aims to find the correlation between pedalling and the undesired steering movements it creates. To test this assumption a

  13. Alteration in gene expression in the jejunum mucosa of Angus steers with divergent ADG

    Science.gov (United States)

    The objective of this study was to determine the association of differentially expressed genes in the jejunum of steers with average DMI and high or low ADG. Feed intake and growth were measured in a cohort of 144 commercial Angus steers consuming a finishing ration containing (on a DM basis) 67.8% ...

  14. Reducing Digging Losses by Using Automated Steering to Plant and Invert Peanuts

    Directory of Open Access Journals (Sweden)

    George Vellidis

    2014-07-01

    Full Text Available GPS guidance of farm machinery has been increasingly adopted by farmers because of the perceived gains in efficiency that it provides. In the southeastern USA one of the reasons farmers adopt GPS guidance, and specifically automated steering (auto-steer, is that it can theoretically result in large yield gains when used to plant and invert peanuts—one of the region’s most important crops. The goal of our study was to quantify the yield benefit of using real time kinematic (RTK-based auto-steer to plant and invert peanuts under a variety of terrain conditions. Yield benefits result from reduced digging losses. The study was conducted for two consecutive years (2010 and 2011 on a private farm in Georgia, USA. When all data are grouped together, auto-steer outperformed conventional by 579 kg/ha in 2010 and 451 kg/ha in 2011. We also evaluated the performance of auto-steer under different curvature conditions using low, medium, and high curvature rows. The results showed that auto-steer outperformed conventional under all curvature by a minimum of 338 kg/ha. Finally, we evaluated passive implement guidance in combination with auto-steer and found that it holds tremendous potential for further reducing digging losses. In many cases, auto-steer will pay for itself within a year.

  15. Integrating deflection models and image feedback for real-time flexible needle steering

    NARCIS (Netherlands)

    Abayazid, Momen; Roesthuis, Roy; Reilink, Rob; Misra, Sarthak

    2013-01-01

    Needle insertion procedures are commonly used for diagnostic and therapeutic purposes. In this paper, an image- guided control system is developed to robotically steer flexible nee- dles with an asymmetric tip. Knowledge about needle deflection is required for accurate steering. Two different models

  16. Integrating deflection models and image feedback for real-time flexible needle steering

    NARCIS (Netherlands)

    Abayazid, Momen; Roesthuis, Roy J.; Reilink, Rob; Misra, Sarthak

    2012-01-01

    Needle insertion procedures are commonly used for diagnostic and therapeutic purposes. In this paper, an image- guided control system is developed to robotically steer flexible nee- dles with an asymmetric tip. Knowledge about needle deflection is required for accurate steering. Two different models

  17. Dynamic Modeling of Hydraulic Power Steering System with Variable Ratio Rack and Pinion Gear

    Science.gov (United States)

    Zhang, Nong; Wang, Miao

    A comprehensive mathematical model of a typical hydraulic power steering system equipped with variable ratio rack and pinion gear is developed. The steering system’s dynamic characteristics are investigated and its forced vibrations are compared with those obtained from a counterpart system with a constant ratio rack and pinion gear. The modeling details of the mechanism subsystem, hydraulic supply lines subsystem and the rotary spool valve subsystem are provided and included in the integrated steering system model. The numerical simulations are conducted to investigate the dynamics of the nonlinear parametric steering system. From the comparison between simulated results and the experimental ones, it is shown that the model accurately integrates the boost characteristics of the rotary spool valve which is the key component of hydraulic power steering system. The variable ratio rack-pinion gear behaviors significantly differently from its constant ratio counterpart does. It significantly affects not only the system natural frequencies but also reduces vibrations under constant rate and ramp torque steering inputs. The developed steering model produces valid predictions of the system’s behavior and therfore could assist engineers in the design and analysis of integrated steering systems.

  18. Modulation of the acute phase response in feedlot steers supplemented with Saccharomyces cerevisiae

    Science.gov (United States)

    This study was designed to determine the effect of supplementing feedlot steers with Saccharomyces cerevisiae CNCM I-1079 (SC) on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 266 ± 4 kilograms body weight) were separated into three treatment groups (n = 6/treatm...

  19. Relationship of leptin concentrations with feed intake, growth, and efficiency in finishing beef steers

    Science.gov (United States)

    The objective of this experiment was to determine the association of serum leptin concentrations with production measures including DMI, ADG, G:F as well as carcass characteristics in genetically diverse finishing beef steers. Three cohorts of steers (n = 473 total) were individually fed a finishin...

  20. Differential acute phase immune responses by Angus and Romosinuano steers following an endotoxin challenge

    Science.gov (United States)

    Our primary objective was to evaluate potential genetic differences between two diverse Bos taurus breeds (Angus (AG) and Romosinuano (RO)) in response to an endotoxin. The RO is a tropically adaptive Bos taurus breed developed in the Sinú valley of northern Colombia. Eighteen steers (n = 9 steers/b...

  1. Exogenous administration of lipids to steers alters aspects of the innate immune response to endotoxin challenge

    Science.gov (United States)

    Limitations in energy availability are known to impede the efficiency of the immune response to endotoxemia. Therefore, this study examined the effects of increasing energy availability on the pro-inflammatory response to LPS in Holstein steers. Steers were randomly assigned to 1 of 3 groups (n = 7 ...

  2. Effects of clay on fat necrosis and carcass characteristics in Japanese Black steers

    National Research Council Canada - National Science Library

    Oka, Akio; Iwamoto, Eiji; Tatsuda, Ken

    2015-01-01

    Twenty 10‐month‐old J apanese B lack steers were used to evaluate the effects of clay on fat necrosis and carcass characteristics. Ten steers ( C lay group) were fed the clay (50 g/day) during 10–30 months of age...

  3. Effects of steering demand on lane keeping behaviour, self-reports, and physiology : A simulator study

    NARCIS (Netherlands)

    Dijksterhuis, Chris; Brookhuis, Karel A.; De Waard, Dick

    2011-01-01

    In this study a driving simulator was used to determine changes in mental effort in response to manipulations of steering demand. Changes in mental effort were assessed by using subjective effort ratings, physiology, and the standard deviation of the lateral position. Steering demand was increased b

  4. 46 CFR 130.130 - Steering on OSVs of less than 100 gross tons.

    Science.gov (United States)

    2010-10-01

    ... must be installed in the pilothouse to indicate operation of the power units. (e) The auxiliary means... 46 Shipping 4 2010-10-01 2010-10-01 false Steering on OSVs of less than 100 gross tons. 130.130... VESSEL CONTROL, AND MISCELLANEOUS EQUIPMENT AND SYSTEMS Vessel Control § 130.130 Steering on OSVs of...

  5. Beam steering for circular switched parasitic arrays using a combinational approach

    CSIR Research Space (South Africa)

    Mofolo, ROM

    2011-09-01

    Full Text Available In this paper, the authors present a method of electronic beam steering for circular switched parasitic array (SPA) antennas. In circular SPA antennas, one achieves azimuth beam steering by open-circuiting and short-circuiting different parasitic...

  6. Optimized detection of steering via linear criteria for arbitrary-dimensional states

    Science.gov (United States)

    Zheng, Yu-Lin; Zhen, Yi-Zheng; Cao, Wen-Fei; Li, Li; Chen, Zeng-Bing; Liu, Nai-Le; Chen, Kai

    2017-03-01

    Einstein-Podolsky-Rosen (EPR) steering, as a new form of nonlocality, stands between entanglement and Bell nonlocality, implying promising applications for quantum information tasks. The problem of detecting EPR steering plays an important role in characterization of quantum nonlocality. Despite some significant progress, one still faces a practical issue: how to detect EPR steering in an experimentally friendly fashion. Resorting to an EPR steering inequality, one is required to apply a strategy as efficiently as possible for any selected measurement settings on the two subsystems, one of which may not be trusted. Inspired by the recent powerful linear criteria proposed by Saunders et al. [D. J. Saunders, S. J. Jones, H. M. Wiseman, and G. J. Pryde, Nat. Phys. 6, 845 (2010)., 10.1038/nphys1766], we present an optimized method of certifying steering for an arbitrary-dimensional state in a cost-effective manner. We provide a practical way to signify steering via only a few settings to optimally violate the steering inequality. Our method leads to steering detections in a highly efficient way, and can be performed with any number of settings, for an arbitrary bipartite mixed state, which can reduce experimental overheads significantly.

  7. Carcass characteristics and composition of Brahman, angus and Brahman x Angus steers fed for different times-on-feed.

    Science.gov (United States)

    Lunt, D K; Smith, G C; Murphey, C E; Savell, J W; Carpenter, Z L; Petersen, H D

    1985-01-01

    Twenty-five steers of each of three breedtypes (Angus, Brahman and F(1) Brahman x Angus) were sorted by frame size and muscle thickness, assigned to groups (five steers of each breedtype) to be fed for 0, 56, 112, 168 or 224 days, slaughtered and compared for various carcass traits. Steers of each breedtype had similar dressing percentages. Carcasses from all three breedtypes merited similar USDA quality and yield grades; breedtypes differences in quality grade were slight. Differences were found in the fat deposition patterns exhibited by the three breedtypes. Brahman steers tended to deposit more of their total fat as subcutaneous fat early in the feeding period. Angus steers had more (P carcass weight at all five feeding periods and more (P Brahman steers. Brahman steers had a higher percentage of their separable lean in the muscles of the round than did steers of the other breedtypes.

  8. Comparative stress responses to short transport and related events in Hereford and Brahman steers.

    Science.gov (United States)

    Browning, R; Leite-Browning, M L

    2013-02-01

    Three summer experiments compared responses to transportation-related events in 2- to 4-yr-old Brahman (Bos indicus) and Hereford (B. taurus) steers. In Exp. 1, steers were hauled round-trip (4 h) or fasted in holding pens. Transport transiently increased (P Brahman across treatments. Steers in Exp. 2 were hauled to a new farm for a 1-wk relocation period or hauled round-trip an equal time (0.67 h) and returned to the home station. Both treatments similarly experienced transport-day BW shrink and increased (P Brahman. Relocation did not elicit (P Brahman steers were not more sensitive than Herefords. Hereford steers were susceptible to greater transport BW shrink than Brahman under the summer conditions.

  9. The Design of a Controller for the Steer-by-Wire System

    Science.gov (United States)

    Oh, Se-Wook; Chae, Ho-Chol; Yun, Seok-Chan; Han, Chang-Soo

    Drive-by-Wire (DBW) technologies improve conventional vehicle performance and a Steer-by-Wire (SBW) system is one of the DBW technologies. The control algorithm of the SBW system was designed in this paper. To verify the control algorithm, the SBW system is modeled using the bond graph method. The first aim of the control algorithm is controlling the steering wheel assist motor to make the real vehicle's steering feel and for a vehicle designer to adjust the steering feel as he finds necessary. Therefore, torque map is designed to determine the steering wheel reactive torque. The second aim is controlling the front wheel assist motor to improve vehicle's maneuverability and stability by using understeer and oversteer propensity of a vehicle. Furthermore, high performance control algorithm is proposed in this paper and Active Roll Stability Control (ARSC) method is designed as one of the high performance control algorithm.

  10. Robust PID Steering Control in Parameter Space for Highly Automated Driving

    Directory of Open Access Journals (Sweden)

    Mümin Tolga Emirler

    2014-01-01

    Full Text Available This paper is on the design of a parameter space based robust PID steering controller. This controller is used for automated steering in automated path following of a midsized sedan. Linear and nonlinear models of this midsized sedan are presented in the paper. Experimental results are used to validate the longitudinal and lateral dynamic models of this vehicle. This paper is on automated steering control and concentrates on the lateral direction of motion. The linear model is used to design a PID steering controller in parameter space that satisfies D-stability. The PID steering controller that is designed is used in a simulation study to illustrate the effectiveness of the proposed method. Simulation results for a circular trajectory and for a curved trajectory are presented and discussed in detail. This study is part of a larger research effort aimed at implementing highly automated driving in a midsized sedan.

  11. Analysis of Steering Knuckle of All Terrain Vehicles (ATV) Using Finite Element Analysis

    Science.gov (United States)

    Dusane, S. V.; Dipke, M. K.; Kumbhalkar, M. A.

    2016-09-01

    Steering knuckle is the most stress sustaining and critical component of All Terrain Vehicle (ATV). Steering knuckle is the pivot point of the steering and suspension system, which allows the front wheels to turn and also allow the movement of suspension arms motion. The light weight and high strength component is always in demanding for racecar application. Lightweight and optimized design of steering knuckle is proposed to use for a BAJA SAE INDIA off road racecar. Due to the failure in knuckle in terrain vehicle after some instances, it has to be modified for better performance. The 3D CAD model created by using CATIA V5 and static as well as model analysis carried out in ANSYS 12 to understand its behavior under operating conditions. All test for frame was carried out on aluminum alloys 6061-T6 & for spindle EN8. The paper discusses the FE analysis of existing and modified Steering Knuckle.

  12. High speed, high power one-dimensional beam steering from a 6-element optical phased array.

    Science.gov (United States)

    Huang, W Ronny; Montoya, Juan; Kansky, Jan E; Redmond, Shawn M; Turner, George W; Sanchez-Rubio, Antonio

    2012-07-30

    Beam steering at high speed and high power is demonstrated from a 6-element optical phased array using coherent beam combining (CBC) techniques. The steering speed, defined as the inverse of the time to required to sweep the beam across the steering range, is 40 MHz and the total power is 396 mW. The measured central lobe FWHM width is 565 μrad. High on-axis intensity is maintained periodically by phase-locking the array via a stochastic-parallel-gradient-descent (SPGD) algorithm. A master-oscillator-power-amplifier (MOPA) configuration is used where the amplifier array elements are semiconductor slab-coupled-optical-waveguide-amplifiers (SCOWAs). The beam steering is achieved by LiNbO(3) phase modulators; the phase-locking occurs by current adjustment of the SCOWAs. The system can be readily scaled to GHz steering speed and multiwatt-class output.

  13. One-way steering of optical fields via dissipation of an atomic reservoir

    Science.gov (United States)

    Rao, Shi; Hu, Xiangming; Li, Lingchao; Xu, Jun

    2016-11-01

    Einstein-Podolsky-Rosen (EPR) steering as a form of quantum correlation lies between entanglement and Bell nonlocality and exhibits an inherent asymmetry between two observers. We study EPR steering of two fields, which are generated via four-wave mixing processes and are entangled with each other due to the dissipation of the atomic reservoir. It is shown that the one-way steering happens from one mode to the other for different cavity decay rates and not too small cooperation parameters. Depending on the adiabatic and nonadiabatic conditions, the one-way steering occurs in a different detuning region when the cooperation parameters are relatively small. An increase in the cooperation parameters leads to an increase both in the parameter region and in the degree for the one-way steering. Finally we generalize the present scheme to the cases of the bright and/or collective fields.

  14. Effect of abomasal infusion of aspartate on nitrogen balance and plasma amino acids in Holstein steers.

    Science.gov (United States)

    Wessels, R H; Titgemeyer, E C

    1998-01-01

    We investigated the effect of abomasally infused aspartate (Asp) on N balance and plasma amino acids in steers. Four ruminally cannulated Holstein steers (180 kg) housed in metabolism crates were used in an experiment designed as a 4 x 3 Youden square. Steers received continuous abomasal infusions of water or water containing 40 or 80 g Asp/d. Steers were fed twice daily a diet containing 473 g/kg corn, 463 g/kg alfalfa hay and 52 g/kg soybean meal at levels near ad libitum intake. Abomasally infused Asp had no effect on N balance. Infusion of 80 g Asp/d increased (P < 0.05) plasma concentrations of Asp, glutamate and alanine. Metabolism of Asp by gut tissues probably prevented the large change in plasma concentration of Asp that seems necessary to trigger hormonal responses. We conclude that abomasal supplementation of steers with up to 80 g/d of Asp does not enhance performance.

  15. Performance Analyses of the Radio Orbital Angular Momentum Steering Technique Based on Ka-Band Antenna

    Directory of Open Access Journals (Sweden)

    Mingtuan Lin

    2017-01-01

    Full Text Available The misalignment in the orbital angular momentum- (OAM- based system would distort the radiation patterns of twisted beams carrying OAM, consequently making the OAM-based communication infeasible. To tackle the misalignment problem, a radio OAM steering technique based on a uniform circular array (UCA is illustrated. Subsequently, simulations are conducted to explore the influence of the OAM steering on the OAM mode quality and transmission performance. Furthermore, UCAs working at Ka-band with formulated feeding networks are designed and fabricated to analyze the performance of the OAM steering. The influences of OAM steering on mode quality and orthogonality are then evaluated in the experiment. Overall, the analyses of OAM steering technique are beneficial for the development of radio OAM study.

  16. Postgraze assessment of toxicosis symptoms for steers grazed on toxic endophyte-infected tall fescue pasture.

    Science.gov (United States)

    Aiken, G E; Klotz, J L; Johnson, J M; Strickland, J R; Schrick, F N

    2013-12-01

    A 2-yr pen experiment was conducted using 12 different crossbred Angus steers each year to determine if short-term changes in prolactin concentrations, body temperature, and vasoconstriction reflect recovery from fescue toxicosis after steers that previously grazed toxic endophyte (Neotyphodium coenophialum)-infected Kentucky 31 tall fescue [Lolium arundinaceum (Schreb.) Darbysh] are placed on nontoxic feed. Groups of 6 steers from toxic endophyte-infected and endophyte-free tall fescue grazing treatments were blocked by BW for assignment to pens as a randomized complete block design with 2 replications. Two environments were implemented by initiating the experiment on 18 August in yr 1 and on 8 September in yr 2 for durations of 30 and 21 d, respectively. Rectal temperatures were recorded, jugular blood was collected for assaying serum prolactin, and cross sections of the caudal artery were ultrasonically imaged at selected time points to evaluate temporal changes in the response variables. Rectal temperatures in steers on the toxic endophyte pasture treatment declined (P 0.10) to those on endophyte-free treatment on d 30 in yr 1 and by d 15 in yr 2. Prolactin concentrations in steers on the toxic endophyte pasture treatment showed curvilinear increases (P 0.10) to steers on the endophyte-free treatment by d 15 in yr 1 and by d 10 in yr 2. Luminal areas of the caudal artery in toxic endophyte steers were less (P endophyte-free steers across all dates in both years. Results indicated that rectal temperatures in steers after they are removed from toxic fescue may decrease over time, but temporal changes in rectal temperatures could be affected more by prevailing ambient temperatures than by actual mitigation of fescue toxicosis. Prolactin concentrations in steers after they are removed from toxic endophyte tall fescue can increase and stabilize in less than 2 wk, but alkaloid-induced vasoconstriction that causes a vulnerability to severe heat stress is not

  17. Sida rhombifolia ssp. retusa seed extract inhibits DEN induced murine hepatic preneoplasia and carbon tetrachloride hepatotoxicity.

    Science.gov (United States)

    Poojari, Radhika; Gupta, Sanjay; Maru, Girish; Khade, Bharat; Bhagwat, Sanjay

    2009-01-01

    Sida rhombifolia ssp. retusa is a well established drug in the Ayurvedic system of medicine used for antirheumatism and antiasthmatism. Inhibitory effects of S. rhombifolia ssp. retusa seed extract on DEN induced hepatocellular preneoplastic foci and carbon tetrachloride (CCl4) induced hepatotoxicity was investigated in rats. Rats received DEN, 1ppm/g b.w. in drinking water for 6 weeks or CCl(4), 0.7 ml/kg i.p. once a week for 4 weeks and seed extract 50 mg, 100 mg/kg b.w. orally prior, during and after exposure to DEN/CCl4 for 20 or 5 weeks, respectively. Treatment with seed extract significantly inhibited the increase in DEN/CCl(4) induced activities of pre-cancerous marker enzymes; gamma-glutamyl transpeptidase, glutathione-S-transferase, hepatotoxicity marker enzymes; glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and alkaline phosphatase as well as lipid peroxidase. Depleted glutathione, protein and albumin levels were restored. Also, histopathological and transmission electron microscopic studies showed prevention of cellular degenerative changes. The chemopreventive and hepatoprotective potentials of seed extract are due to free radical scavenging activity and restoration of cellular structural integrity.

  18. Can hyperbaric oxygenation decrease doxorubicin hepatotoxicity and improve regeneration in the injured liver?

    Science.gov (United States)

    Firat, Ozgur; Kirdok, Ozgur; Makay, Ozer; Caliskan, Cemil; Yilmaz, Funda; Ilgezdi, Savas; Karabulut, Bulent; Coker, Ahmet; Zeytunlu, Murat

    2009-01-01

    Portal vein embolization is used in the treatment of hepatocellular cancer, with the purpose of enhancing resectability. However, regeneration is restricted due to hepatocellular injury following chemotherapeutics (e.g. doxorubicin). The aim of this study was to investigate whether hyperbaric oxygenation (HBO) can alleviate the hepatotoxicity of chemotherapy and improve regeneration in the injured liver. Rats were allocated to four experimental groups. Group I rats were subjected to right portal vein ligation (RPVL); rats in groups II and III were administered doxorubicin prior to RPVL, with group III rats being additionally exposed to HBO sessions postoperatively; group IV rats was sham-operated. All rats were sacrificed on postoperative day 7, and liver injury was assessed by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Protein synthetic ability was determined based albumin levels and liver regeneration by the mitotic index (MI). The AST and ALT values of group II rats were significantly higher than those of group I, but not those of group III. Rats treated with doxorubicin and HBO (groups II and III) showed slightly but not significant differences in albumin levels than those subjected to only RPVL or sham-operated. The MI was significantly increased in groups I, II, and III, with the MI of group III rats significantly higher than those of group I rats. Based on our results, we conclude that HBO treatment has the potential to diminish doxorubicin-related hepatotoxicity and improve regeneration in the injured liver.

  19. Metabolomics evaluation of the effects of green tea extract on acetaminophen-induced hepatotoxicity in mice.

    Science.gov (United States)

    Lu, Yihong; Sun, Jinchun; Petrova, Katya; Yang, Xi; Greenhaw, James; Salminen, William F; Beger, Richard D; Schnackenberg, Laura K

    2013-12-01

    Green tea has been purported to have beneficial health effects including protective effects against oxidative stress. Acetaminophen (APAP) is a widely used analgesic drug that can cause acute liver injury in overdose situations. These studies explored the effects of green tea extract (GTE) on APAP-induced hepatotoxicity in liver tissue extracts using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry and nuclear magnetic resonance spectroscopy. Mice were orally administered GTE, APAP or GTE and APAP under three scenarios. APAP alone caused a high degree of hepatocyte necrosis associated with increases in serum transaminases and alterations in multiple metabolic pathways. The time of GTE oral administration relative to APAP either protected against or potentiated the APAP-induced hepatotoxicity. Dose dependent decreases in histopathology scores and serum transaminases were noted when GTE was administered prior to APAP; whereas, the opposite occurred when GTE was administered after APAP. Similarly, metabolites altered by APAP alone were less changed when GTE was given prior to APAP. Significantly altered pathways included fatty acid metabolism, glycerophospholipid metabolism, glutathione metabolism, and energy pathways. These studies demonstrate the complex interaction between GTE and APAP and the need to employ novel analytical strategies to understand the effects of dietary supplements on pharmaceutical compounds.

  20. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity.

    Science.gov (United States)

    Beger, Richard D; Sun, Jinchun; Schnackenberg, Laura K

    2010-03-01

    Hepatotoxicity and nephrotoxicity are two major reasons that drugs are withdrawn post-market, and hence it is of major concern to both the FDA and pharmaceutical companies. The number of cases of serious adverse effects (SAEs) in marketed drugs has climbed faster than the number of total drug prescriptions issued. In some cases, preclinical animal studies fail to identify the potential toxicity of a new chemical entity (NCE) under development. The current clinical chemistry biomarkers of liver and kidney injury are inadequate in terms of sensitivity and/or specificity, prompting the need to discover new translational specific biomarkers of organ injury. Metabolomics along with genomics and proteomics technologies have the capability of providing translational diagnostic and prognostic biomarkers specific for early stages of liver and kidney injury. Metabolomics has several advantages over the other omics platforms such as ease of sample preparation, data acquisition and use of biofluids collected through minimally invasive procedures in preclinical and clinical studies. The metabolomics platform is reviewed with particular emphasis on applications involving drug-induced hepatotoxicity and nephrotoxicity. Analytical platforms for metabolomics, chemometrics for mining metabolomics data and the applications of the metabolomics technologies are covered in detail with emphasis on recent work in the field.

  1. Vitamin E and selenium treatment of monocrotaline induced hepatotoxicity in rats.

    Science.gov (United States)

    Cuce, G; Canbaz, H T; Sozen, M E; Yerlikaya, F H; Kalkan, S

    2017-01-01

    Monocrotaline (MCT) is a hepatotoxic pyrrolizidine alkaloid that is derived from plants; exposure may occur by consumption of contaminated grains, herbal teas and medicines. MCT can cause liver damage. We investigated the antioxidant effects of selenium (Se) and vitamin E against the toxic effects of MCT. Female Wistar albino rats were divided into four groups: a control group, an MCT group, an MCT + Se group, and an MCT + vitamin E group. Liver tissues were harvested, fixed, processed to paraffin and sections were cut. Anti-von Willebrand factor (vWF) immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL), and hematoxylin and eosin staining were performed. Serum and liver tissue glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx) levels were measured. Histopathological and TUNEL data showed significantly increased liver damage in the MCT group compared to controls. Histopathological and TUNEL staining indicated significant improvements in the MCT + vitamin E and MCT + Se groups compared to the MCT group. MCT significantly reduced the serum GSH level and GPx activity, and liver GPx activity. Biochemical data indicated a significant improvement in serum GSH level in the MCT + vitamin E group compared to the MCT group. We suggest that vitamin E and Se afford limited protection against MCT hepatotoxicity.

  2. Hematological, antioxidant and protective performance of Usnea longissima on chemical induced hepatotoxicity in experimental animals

    Directory of Open Access Journals (Sweden)

    Pritt Verma

    2017-05-01

    Full Text Available Objective: To investigated the hematological, antioxidant and protective performance of Usnea longissima (U. longissima on CCl4 induced hepatotoxicity in experimental animals. Methods: Hepatotoxicity was induced by CCl4 (1 mL/kg body weigt 1:1 CCl4 i.p., ethanolic U. longissima extracts at a doses (200 and 400 mg/kg body weigt were administered to and compared with Silymarin (25 mg/kg body weigt and hematological, antioxidant and enzymatic, non-enzymatic parameters were assessed through the liver functions test. All the observation was also supplemented with histopathological examination of liver sections. Results: Phytochemical investigation showed that ethanolic extract contains poly phenolic compounds tannins, flavonoids, alkaloids and saponins and acute toxicity study shows that ethanolic extract was safe up to 2 000 mg/kg body weight. The toxicant induced a rise in the plasma enzyme levels of ALT, AST, ALP and total bilirubin level. This increased level was significantly decreased by the extract at 400 mg/kg body weight than 200 mg/kg body weight. The animals were prevented (partly or fully which was showed in the histopathological changes using ethonolic U. longissima extract. Conclusions: The outcome of this study reveals that, there is a powerful antioxidant and hepatoprotective activity of U. longissima. It is believed that the present constituents are responsible for courting the hepatic disease and alternative components have the power to act as free radical scavenging properties.

  3. Ameliorative Influence of Green Tea Extract on Copper Nanoparticle-Induced Hepatotoxicity in Rats

    Science.gov (United States)

    Ibrahim, Marwa A.; Khalaf, A. A.; Galal, Mona K.; Ogaly, Hanan A.; H. M. Hassan, Azza

    2015-09-01

    The potential toxicity of copper nanoparticles (CNPs) to the human health and environment remains a critical issue. In the present study, we investigated the protective influence of an aqueous extract of green tea leaves (GTE) against CNPs-induced (20-30 nm) hepatotoxicity. Four different groups of rats were used: group I was the control, group II received CNPs (40 mg/kg BW), group III received CNPs plus GTE, and group IV received GTE alone. We highlighted the hepatoprotective effect of GTE against CNPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, histopathological alterations, and DNA damage evaluation. The rats that were given CNPs only had a highly significant elevation in liver enzymes, alteration in oxidant-antioxidant balance, and severe pathological changes. In addition, we detected a significant elevation of DNA fragmentation percentage, marked DNA laddering, and significance over expression of both caspase-3 and Bax proteins. The findings for group III clarify the efficacy of GTE as a hepatoprotectant on CNPs through improving the liver enzyme activity, antioxidant status, as well as suppressing DNA fragmentation and the expression of the caspase-3 and Bax proteins. In conclusion, GTE was proved to be a potential hepatoprotective additive as it significantly ameliorates the hepatotoxicity and apoptosis induced by CNPs.

  4. Hepatotoxic effects of polidocanol in a model of autologously perfused porcine livers.

    Science.gov (United States)

    Grosse-Siestrup, Christian; Unger, Volker; Pfeffer, Jeanette; Dinh, Q Thai; Nagel, Stefan; Springer, Jochen; Witt, Christian; Wussow, Anke; Groneberg, David A

    2004-12-01

    Polidocanol is an effective sclerosing agent that consists of 95% hydroxypolyethoxydodecane and 5% ethyl alcohol and is known to have a low risk of complications. However, since the compound has been proposed for the local treatment of liver diseases, the potential for topical hepatic side effects should be examined. Therefore, the new model of normothermic-hemoperfused isolated porcine slaughterhouse livers was used to examine polidocanol-hepatotoxicity encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. Polidocanol was administered via the hepatic artery and portal vein and the effects of the sclerosant on organ function parameters were compared with those in an untreated control group. In contrast to the untreated control organs, significant differences were found in the polidocanol group for parameters such as alanine aminotransferase or organ weight after perfusion. The most striking differences were found for hepatic bile flow, which dropped in the polidocanol group to 0.24+/-0.02 ml/min per 1000 g after administration of the compound compared with 3.80+/-1.08 ml/min per 1000 g in the control group. In summary, the present observations indicate a risk of hepatotoxic effects of polidocanol. Clinicians should be aware of this problem and the use of polidocanol for intrahepatic sclerosing should be restricted to specialized centers.

  5. Hepatoprotective effect of Rosa canina fruit extract against carbon tetrachloride induced hepatotoxicity in rat

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    Heibatollah Sadeghi

    2016-03-01

    Full Text Available Objective: The present study was conducted to investigate the hepatoprotective activity of hydro-ethanolic fruit extract of Rosa canina (R. canina against carbon tetrachloride (CCl4-induced hepatotoxicity in rats. Methods: Male Wistar albino rats were randomly divided into six groups of 8 animals of each, including control, toxic (CCl4, R. canina 250, 500, and 750 mg/kg + CCl4 and R. canina 750 mg/kg alone. R. canina (p.o., daily and CCl4 (1 ml/kg twice a week, 50% v/v in olive oil, i.p. were administered to animals for six weeks. Serum analysis was performed to assay the levels of aspartate aminotransferase (AST, alanine amino transaminase (ALT, alkaline phosphatase (ALP, albumin (ALB, total protein (TP and malondialdehyde (MDA. Biochemical observations were also supplemented with histopathological examination (haematoxylin and eosin staining of liver section.Results: Hepatotoxicity was evidenced by considerable increase in serum levels of AST, ALT, ALP, and lipid peroxidation (MDA and decrease in levels of ALB and TP. Injection of CCL4 also induced congestion in central vein, and lymphocyte infiltration. Treatment with hydro-alcoholic fruit extract of R. canina at doses of 500 and 750 mg/kg significantly reduced CCl4-elevated levels of ALT, AST, ALP and MDA (p

  6. Chelidonium majus 30C and 200C in induced hepato-toxicity in rats.

    Science.gov (United States)

    Banerjee, Antara; Pathak, Surajit; Biswas, Surjyo Jyoti; Roy-Karmakar, Susanta; Boujedaini, Naoual; Belon, Philippe; Khuda-Bukhsh, Anisur Rahman

    2010-07-01

    Homeopathy is a popular form of complementary and alternative medicine and is used to treat for certain liver ailments. To analyze the efficacy of homeopathic Chelidonium majus (Chel) 30C and 200C in amelioration of experimentally induced hepato-toxicity in rats. Rats were randomized into six sub-groups: negative control; negative control+EtOH; positive control; positive control+EtOH group; Chel 30; Chel 200. Rats were sacrificed at day 30, 60, 90 and 120; various toxicity biomarkers and pathological parameters were evaluated. Gelatin zymography for determination of metalloproteinases activity and Western blot of p53 and Bcl-2 proteins were also employed. All analyses were observer blind. Chronic feeding of p-dimethyl amino azo benzene (p-DAB) and phenobarbital (PB) elevated the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), triglyceride, cholesterol, creatinine and bilirubin and lowered the levels of glutathione (GSH), glucose-6-phosphate dehydrogenase (G-6-PD), catalase and HDL-cholesterol. There were statistically significant modulations of these parameters in the treated animals, compared to positive controls. In both treated groups, there was downregulation of metalloproteinases, p53 and Bcl-2 proteins compared to over-expression in the positive control groups. Both the potencies of Chel exhibited anti-tumor and anti-oxidative stress potential against artificially induced hepatic tumors and hepato-toxicity in rats. More studies are warranted. 2010 Elsevier Ltd. All rights reserved.

  7. Chelidonium majus is not hepatotoxic in Wistar rats, in a 4 weeks feeding experiment.

    Science.gov (United States)

    Mazzanti, Gabriela; Di Sotto, Antonella; Franchitto, Antonio; Mammola, Caterina Loredana; Mariani, Paola; Mastrangelo, Sabina; Menniti-Ippolito, Francesca; Vitalone, Annabella

    2009-12-10

    Aerial parts of Chelidonium majus L. (Papaveraceae family) are traditionally used in the treatment of gallstones and dyspepsia, however several cases of hepatotoxicity are reported. In this work we evaluated the effects on liver function of a C. majus extract, obtained from the herbal material responsible for one case of hepatotoxicity. Experiments were performed in Wistar rats, after oral administration of doses corresponding to 1.5 and 3g/(kg day) of herbal drug, for 2 or 4 weeks. Blood samples were collected to perform biochemical analysis, whereas liver samples were used for histomorphological and immunohistochemical examination along with the determination of oxidative stress parameters. No significant modification in animal body weight, food consumption, enzyme activities, hepatic histomorphology and MDA formation, at either time or dosage level. Conversely, C. majus induced a slight but significant decrease of GSH levels and SOD activity, especially at the high dose. Our study suggests that C. majus, at doses about 50 and 100 times higher than those generally used in humans, does not alter hepatic function. However, the reduction in GSH levels and SOD activity suggests particular attention in use of C. majus or its preparations in situations (pharmacological treatments, physio-pathological conditions, etc.) that can compromise liver function.

  8. Metabolism by conjugation appears to confer resistance to paracetamol (acetaminophen) hepatotoxicity in the cynomolgus monkey.

    Science.gov (United States)

    Yu, Hong; Barrass, Nigel; Gales, Sonya; Lenz, Eva; Parry, Tony; Powell, Helen; Thurman, Dale; Hutchison, Michael; Wilson, Ian D; Bi, Luke; Qiao, Junwen; Qin, Qiuping; Ren, Jin

    2015-03-01

    1. Paracetamol overdose remains the leading cause of acute liver failure in humans. This study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. No adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. Only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals were observed, with no clear dose response. 3. Toxicokinetic analysis showed good plasma exposure, albeit with less than proportional rises in Cmax and AUC, with increasing dose. The Cmax values in monkey were up to 3.5 times those associated with human liver toxicity and the AUC approx. 1000 times those associated with liver enzyme changes in 31-44% of human subjects. 4. Metabolite profiling of urine by (1)H NMR spectroscopy revealed paracetamol and its glucuronide and sulphate metabolites. Glutathione-derived metabolites, e.g. the cysteinyl conjugate, were only present in very low concentrations whilst the mercapturate was not detected. 5. These in vivo observations demonstrated that the cynomolgus monkey is remarkably resistant to paracetamol-induced toxicity and a poor model for investigating paracetamol-related hepatotoxicity in humans.

  9. Characterization of rat or human hepatocytes cultured in microphysiological systems (MPS) to identify hepatotoxicity.

    Science.gov (United States)

    Chang, Shih-Yu; Voellinger, Jenna L; Van Ness, Kirk P; Chapron, Brian; Shaffer, Rachel M; Neumann, Thomas; White, Collin C; Kavanagh, Terrance J; Kelly, Edward J; Eaton, David L

    2017-04-01

    The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc.) that can utilize primary liver cells from multiple species (e.g., rat and human). Compared to conventional monolayer cell culture, which typically survives for 5-7days or less, primary rat or human hepatocytes in an MPS exhibited higher viability and improved hepatic functions, such as albumin production, expression of hepatocyte marker HNF4α and canaliculi structure, for up to 14days. Additionally, induction of Cytochrome P450 (CYP) 1A and 3A4 in cryopreserved human hepatocytes was observed in the MPS. The acute cytotoxicity of the potent hepatotoxic and hepatocarcinogen, aflatoxin B1, was evaluated in human hepatocytes cultured in an MPS, demonstrating the utility of this model for acute hepatotoxicity assessment. These results indicate that MPS-cultured hepatocytes provide a promising approach for evaluating chemical toxicity in vitro. Copyright © 2017. Published by Elsevier Ltd.

  10. The pericarp extract of Prunus persica attenuates chemotherapy-induced acute nephrotoxicity and hepatotoxicity in mice.

    Science.gov (United States)

    Lee, Chang Ki; Park, Kwang-Kyun; Hwang, Jae-Kwan; Lee, Sang Kook; Chung, Won-Yoon

    2008-06-01

    The fruit of Prunus persica L. (peach) is one of the common fruits. Its seed is well known as a traditional medicine (Persicae Semen) in Japan, China, and other Asian countries. However, the biological activities of P. persica fruit except its seed are poorly understood. This study was aimed at evaluating the protective effect of the pericarp extract of P. persica (PPE) against cisplatin-induced acute toxicity in mice. PPE (500 mg/kg, p.o.) showed a significant protection against the acute nephrotoxicity and hepatotoxicity induced by a single administration of cisplatin (45 mg/kg, i.p.) over a 16-hour period in mice. Its protective effect was evaluated by serum and tissue biochemical parameters. The pretreatment with PPE for 7 days prevented the cisplatin-induced decrease in the kidney and liver weights as a percentage of the total body weight. PPE significantly inhibited both the cisplatin-induced elevation in serum blood urea nitrogen and creatinine levels caused by kidney damage and the cisplatin-induced increase in serum alanine aminotransferase and aspartate aminotransferase levels by the liver damage. In addition, the administration of PPE caused recovery of the cisplatin-mediated changes in levels of serum nitric oxide and tissue lipid peroxidation, and reduced glutathione content returned to control levels. These results suggest that PPE protects against cisplatin-induced nephrotoxicity and hepatotoxicity by reducing cisplatin-induced oxidative stress in mice.

  11. The chronic hepatotoxicity assessment of the herbal formula Zishen Yutai pill.

    Science.gov (United States)

    Xing, Xiaoyan; Deng, Xuehong; Shi, Jinjin; Zhang, Meishuang; Sun, Guibo; Tang, Shimin; Huang, Qiuling; Sun, Xiaobo

    2017-02-01

    Zishen Yutai pill (ZYP) is an oriental herbal formula, while hepatotoxicity assessment of ZYP was rarely evaluated. Therefore, our aim is to re-evaluate its hepatotoxicity in both normal and carbon tetrachloride (CCl4) induced chronic liver injury rats. In the normal model, two doses of ZYP (1.575 and 9.450 g kg(-1) d(-1); i.e. 1 × , 6 × clinical doses) were given orally to rats for 24 weeks. In the chronic liver injury model, 10% CCl4 was administered to rats abdominally twice a week at a dose of 5 mL kg(-1) for 12 consecutive weeks. Administration time started from 4 weeks after the beginning of CCl4 treatment. Toxicological parameters included mortality, body weight, food consumption, clinical signs, biochemical parameters, gross observation, organ weight, necropsy findings and histopathology were monitored. In the normal model, we found no any mortality or abnormality in clinical signs, relative liver weight, biochemical parameters and histopathology in ZYP treatment groups. In the chronic liver injury model, liver damage related parameter such as ALT was elevated at the high dose of ZYP treatment in contrast to the CCl4-treated group (P rats and 9.450 g kg(-1) d(-1) ZYP in the injury rats.

  12. Effect of fenugreek seed extract on adriamycin-induced hepatotoxicity and oxidative stress in albino rats.

    Science.gov (United States)

    Sakr, Saber A; Abo-El-Yazid, Samah M

    2012-11-01

    The purpose of this work was to evaluate the effect of aqueous extract of fenugreek seeds against hepatotoxicity induced in albino rats by the anticancer drug adriamycin (ADR). Animals were given single dose of ADR (10 mg/kg body weight) and were killed after 2 and 4 weeks. Liver of ADR-treated animals showed histopathological and biochemical alterations. The histopathological changes include hepatic tissue impairment, cytoplasmic vacuolization of the hepatocytes, congestion of blood vessels, leucocytic infiltrations and fatty infiltration. Moreover, the expression of proliferating cell nuclear antigen was increased in ADR-treated rats. The liver enzymes, aspartate aminotransferase (ALT) and alanine aminotransferase (AST) were increased in the sera of treated rats. Moreover, ADR significantly increased the concentration of malondialdehyde (MDA) and decreased the activities of superoxide dismutase (SOD) and catalase (CAT) in hepatic tissue. Treating animals with ADR and aqueous extract of fenugreek (0.4 g/kg body weight) seeds led to an improvement in histological and biochemical alterations induced by ADR. The biochemical results showed that AST and ALT appeared normal together with reduction in the level of MDA (lipid peroxidation marker) and increase in SOD and CAT activities. It was concluded from this study that the aqueous extract fenugreek seeds has a beneficial impact on ADR-induced hepatotoxicity due to its antioxidant effect in albino rats.

  13. An antibody of TNF-alpha did not prevent thioacetamide-induced hepatotoxicity in rats.

    Science.gov (United States)

    Demirel, Ulvi; Harputluoglu, Murat M M; Seckin, Yuksel; Ciralik, Harun; Temel, Ismail; Ozyalin, Fatma; Otlu, Baris; Yilmaz, Bilgic; Dincturk, Mehmet Sarp; Aladag, Hulya

    2011-07-01

    Tumor necrosis factor (TNF)-α antibodies have been shown to reduce liver damage in different models. We investigated the effects of infliximab (a TNF-α antibody) on liver damage in thioacetamide (TAA)-induced hepatotoxicity in rats. Group 1 (n = 8) was the control group. In group 2 (n = 8), the TAA group, the rats received 300 mg/kg intraperitoneal (ip) TAA daily for 2 days. In group 3 (n = 8), the TAA + Infliximab (INF) group, infliximab (5 mg/kg ip daily) was administered 48 hours before the first dose of TAA daily for 2 days and was maintained for 4 consecutive days. In group 4 (n = 8), the INF group, the rats received only ip infliximab (5 mg/kg) daily. Livers were excised for histopathological and biochemical tests (thiobarbituric-acid-reactive substances [TBARS], and myeloperoxidase [MPO]). Serum ammonia, aspartate transaminase (AST), alanine transaminase (ALT), TNF-α, liver TBARS and MPO levels, and liver necrosis and inflammation scores in the TAA group were significantly higher than in the control and INF groups (all p induced hepatotoxicity, and infliximab does not improve oxidative liver damage.

  14. Hepatoprotective potential of ethanolic extract of Aquilaria agallocha leaves against paracetamol induced hepatotoxicity in SD rats.

    Science.gov (United States)

    Alam, Janey; Mujahid, Md; Badruddeen; Jahan, Yasmeen; Bagga, Paramdeep; Rahman, Md Azizur

    2017-01-01

    Many traditional systems of medicines employ herbal drugs for the hepatoprotection. Aim of the study was designed to evaluate the hepatoprotective potential of 'ethanolic extract of Aquilaria agallocha ( Chen Xiang) leaves' (AAE) against paracetamol (PCM) induced hepatotoxicity in SD rats. Group I animals were treated with 1% CMC for 8 days. Group II, III, IV and V animals were first treated with '1% CMC' 1 ml/kg/day, AAE 200 mg/kg/day, AAE 400 mg/kg/day and silymarin 100 mg/kg/day respectively for 7 days and then, orally administered with PCM 3 g/kg b. wt. on 8th day in a single dose. 24 h after the last dosing by PCM, the blood was obtained through the retro-orbital plexus under light anesthesia and the animals were sacrificed. Hepatoprotective potential was assessed by various biochemical parameters such as ALT, AST, ALP, LDH, bilirubin, cholesterol, TP and ALB. Group IV rats showed significant (p rats. Hepatoprotective potential of AAE 400 mg/kg/day was comparable to that of standard drug silymarin 100 mg/kg/day. Results of the study were well supported by the histopathological observations. This study confirms that AAE possesses hepatoprotective potential comparable to that of standard drug silymarin as it exhibited comparable protective potential against PCM induced hepatotoxicity in SD rats.

  15. Syzygium Cumini (L. Seeds Extract Ameliorates Cisplatin Induced Hepatotoxicity in Male Wistar Rats

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    R.Maheswari

    2015-02-01

    Full Text Available The discovery of cisplatin, cis-[Pt(II(NH(3(2Cl(2] ([PtCl2(NH32] or CDDP, was a corner stone which triggered the interest in platinum(II-and other metal-containing compounds as potential anticancer drugs. Cisplatin, is one of the most potent chemotherapy drugs widely used for cancer treatment. In our present study, an attempt has been made to study the effect of Cisplatin on biochemical and histopathological parameters and ameliorating effects of the Syzygium cumini (L. aqueous seeds extract or Eugena Jambolana in male wistar rats. Adult male wistar rats were divided into four different groups. Group I Served as vehicle treated normal saline (Control, Group II Rats received single intra-peritoneal (Ip injection of cisplatin (7mg/kg bw, Group III received Syzygium cumini (L. aqueous seeds extract 400mg/kg/bw orally for 7 days beginning one day prior to cisplatin (CP injection. Group IV Rats received alone Syzygium cumini (L. aqueous seeds extract (400mg/kg bw treated. Cisplatin exposure leads to adverse effects on hematological, hepatotoxic parameters including Erythrocytes (RBCs. Cisplatin induction leads to reduction in the levels of Enzymic and Non-Enzymic antioxidants levels. However, on treatment with Syzygium cumini (L. aqueous seeds extract normalized the levels of all the biochemical and hematological parameters. These findings highlight the efficacy of Syzygium cumini (L. aqueous seeds extract as protective effects Cisplatin induced hepatotoxicity.

  16. Protective effect of Etlingera elatior (torch ginger) extract on lead acetate--induced hepatotoxicity in rats.

    Science.gov (United States)

    Haleagrahara, Nagaraja; Jackie, Tan; Chakravarthi, Srikumar; Rao, Mallikarjuna; Kulur, Anupama

    2010-10-01

    Lead is known to disrupt the biological systems by altering the molecular interactions, cell signaling, and cellular function. Exposure to even low levels of lead may have potential hazardous effects on brain, liver, kidneys and testes. The efficacy of Etlingera elatior (torch ginger) to protect hepatotoxicity induced by lead acetate was evaluated experimentally in male Sprague - Dawley rats. Rats were exposed to lead acetate in drinking water (500 ppm) for 21 days and the effects of concurrent treatment with extract of E. elatior on hepatic lipid hydroperoxides (LPO), protein carbonyl content (PCC), total antioxidants (TA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione S- Transferase (GST) levels and histopathological changes in liver were evaluated. There was a significant decrease in TA and other antioxidant enzymes (p induced changes in hepatic architecture. E. elatior has also reduced the blood lead levels (BLL). Thus, there has been extensive biochemical and structural alterations indicative of liver toxicity with exposure to lead and E. elatior treatment significantly reduced these oxidative damage. Our results suggest that E. elatior has a powerful antioxidant effect against lead-induced hepatotoxicity.

  17. Protective effect of Pisonia aculeata on thioacetamide induced hepatotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Anbarasu C; Rajkapoor B; Bhat KS; John Giridharan; A Arul Amuthan; Satish K

    2012-01-01

    Objective:To evaluate the protective effect of Pisonia aculeata (P. aculeata) on thioacetamide induced hepatotoxicity in rats. Methods:Male Wistar rats were administered 250 or 500 mg/kg p.o. of P. aculeata extract for 21 days and simultaneously administered thioacetamide (TAA) 50 mg/kg bw s.c. 1 h after the respective assigned treatments every 72 h. At the end of all experimental methods, all the animals were sacrificed by cervical decapitation. Blood samples were collected. Serum was separated and analyzed for various biochemical parameters. Results: TAA induced a significant rise in aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO) with a reduction of total protein, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione S-transferase (GST). Treatment of rats with different doses of plant extract (250 and 500 mg/kg) significantly (P<0.001) altered serum marker enzymes and antioxidant levels to near normal against TAA treated rats. The activity of the extract at a dose of 300 mg/kg was comparable to the standard drug, silymarin (50 mg/kg, p.o.). Conclusions:It can be concluded that P. aculeata extract possesses a remarkable hepatoprotective and antioxidant activity against TAA induced hepatotoxicity. More research is required to derive an optimal therapeutic dose.

  18. Effects of selenium on chromium (VI)-induced hepatotoxicity in adult rats.

    Science.gov (United States)

    Soudani, Nejla; Ben Amara, Ibtissem; Sefi, Mediha; Boudawara, Tahia; Zeghal, Najiba

    2011-09-01

    Chromium, a major environmental pollutant, is known for its wide toxic manifestations. The present experiment pertains to the protective role of selenium (Se) against K(2)Cr(2)O(7)-induced hepatotoxicity. Female Wistar rats were divided into four groups of six each: group I served as controls which received standard diet; group II received in drinking water K(2)Cr(2)O(7) alone (700 ppm); group III received both K(2)Cr(2)O(7) and Se (0.5 Na(2)SeO(3) mg/kg of diet); group IV received Se (0.5 mg/kg of diet) for 3 weeks. Exposure of rats to chromium promoted oxidative stress with an increase in malondialdehyde (MDA) and a decrease in glutathione (GSH) levels. A decrease in glutathione peroxidase (GPx) and an increase in superoxide dismutase (SOD) and catalase (CAT) activities were observed. Se supplementation to the diet of group III improved all the parameters cited above. Yet, plasma transaminases (AST and ALT), lactate dehydrogenase (LDH) activities, cholesterol, triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels increased, while high density lipoprotein-cholesterol (HDL-C) decreased. Co-administration of Se to the diet of group III restored hepatic markers to near-normal values. The biochemical results confirmed the histopathological findings. Therefore, our investigation revealed that Se was effective in preventing K(2)Cr(2)O(7)-induced hepatotoxicity.

  19. Therapeutic effects of Cassia angustifolia in a cadmium induced hepatotoxicity assay conducted in male albino rats

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    Muhammad Tahir Haidry

    2016-06-01

    Full Text Available The present study aims to investigate the therapeutic effects of Senna plant (Cassia angustifolia L. in a cadmium induced hepatotoxicity assay by evaluating the activity of alanine transaminase (ALT, aspartate transaminase (AST, alkaline phosphatase (ALP and total protein (TP in the albino rats’ serum. A total of 30 white albino rats were taken and divided into three groups; each group comprising ten rats. The group A was taken as a control group; group B was given cadmium chloride concentration of 5 mg/kg (body weight for 42 days; and group C was given cadmium chloride 5 mg/kg body weight for first 21 days and then extract of C. angustifolia 100 mg/kg (body weight was given for remaining 21 days. The analysis were performed twice i.e., on 21st day and 42nd day. Results illustrated that the concentration of cadmium was significantly elevated (P<0.05 at the levels of serum biochemical markers namely ALT, AST, ALP which lowered the protein levels in albino rats. Moreover, treatment with the standard extracts of C. angustifolia observed to reverse the effects of the cadmium significantly (P<0.05. It is concluded that the C. angustifolia had hepatoprotective effects and therapeutic potential against the cadmium induced hepatotoxicity in albino rats.

  20. Hepatoprotective potential of ethanolic extract of Caesalpenia crista leaves against paracetamol induced hepatotoxicity in rats

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    Garima Mishra

    2015-01-01

    Full Text Available Objective: To investigate the hepatoprotective activity of ethanolic extract of leaves of Caesalpenia crista (C. crista against paracetamol induced hepatotoxicity in rats. Methods: Paracetamol (2 g/kg body weight was used to induce hepatotoxicity in albino rats. Ethanolic extract of leaves of C. crista was administered at the dose levels of 200 and 400 mg/kg body weight orally for 7 d. Silymarin (100 mg/kg was used as standard drug. The hepatoprotective effect of ethanolic extract was evaluated by assessment of biochemical parameters such as serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, serum alkaline phosphatase, bilirubin (total and direct, and triglycerides content. Histopathological study of rat liver was also done. Results: Administration of ethanolic extract at doses 200 mg/kg and 400 mg/kg body weight exhibited significant reduction in elevated level of serum marker enzymes, bilirubin (total and direct and triglycerides when compared to positive control group. Conclusions: It is concluded that the ethanolic extract of C. crista leaves seems to justify the promising hepatoprotective effect on paracetamol induced liver damage in rats.