Spatio-temporal scaling effects on longshore sediment transport pattern along the nearshore zone

Science.gov (United States)

Khorram, Saeed; Ergil, Mustafa

2018-03-01

A measure of uncertainties, entropy has been employed in such different applications as coastal engineering probability inferences. Entropy sediment transport integration theories present novel visions in coastal analyses/modeling the application and development of which are still far-reaching. Effort has been made in the present paper to propose a method that needs an entropy-power index for spatio-temporal patterns analyses. Results have shown that the index is suitable for marine/hydrological ecosystem components analyses based on a beach area case study. The method makes use of six Makran Coastal monthly data (1970-2015) and studies variables such as spatio-temporal patterns, LSTR (long-shore sediment transport rate), wind speed, and wave height all of which are time-dependent and play considerable roles in terrestrial coastal investigations; the mentioned variables show meaningful spatio-temporal variability most of the time, but explanation of their combined performance is not easy. Accordingly, the use of an entropy-power index can show considerable signals that facilitate the evaluation of water resources and will provide an insight regarding hydrological parameters' interactions at scales as large as beach areas. Results have revealed that an STDDPI (entropy based spatio-temporal disorder dynamics power index) can simulate wave, long-shore sediment transport rate, and wind when granulometry, concentration, and flow conditions vary.

Variation of longshore current and sediment transport along the south Maharashtra coast, west coast of India

Digital Repository Service at National Institute of Oceanography (India)

Chandramohan, P.; SanilKumar, V.; Nayak, B.U.; Pathak, K.C.

on the field measurements, the estimated longshore sediment transport rates at Ratnagiri, Ambolgarh and Vengurla were 1.19 x 10 super(5), 1.9 x 10 super(5) and 0.53 x 10 super(5) m super(3) y/1 respectively and the direction was southward. Significance of field...

Nearshore waves and longshore sediment transport along Rameshwaram Island off the east coast of India

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Rajamanickam Gowthaman

2015-11-01

Full Text Available Wave-induced Longshore Sediment Transport (LST play an important role in the dynamics of the Dhanushkodi sandspit located southeast of Rameshwaram. The LST along the Dhanushkodi coast is studied based on data collected simultaneously in Gulf of Mannar (GoM and Palk Bay (PB using directional waverider buoys. The numerical model REF/DIF1 was used to calculate the nearshore waves and the LST rate was estimated using three different formulae. The model validation was done based on the measured nearshore waves using InterOcean S4DW. Numerical model LITPACK was also used for simulating non-cohesive sediment transport and the LITLINE module was used to study the shoreline evolution over 5 years. Low net annual LST along PB (~0.01 × 106 m3 compared to the GoM region (0.3 × 106 m3 were due to the weak waves. Accretion in the region led to growth of the Dhanushkodi sandspit by 65 m during the period 2010-2015.

Longshore currents and associated sediment transport in the nearshore areas of Kerala and Goa, west coast of India

Digital Repository Service at National Institute of Oceanography (India)

Murty, C.S.; Veerayya, M.

The field observations on the longshore currents at selected locations along the coasts of Goa and Kerala on the western seaboard spanning over a period of five years revealed high variability in their direction and speed. The currents...

20 CFR 655.530 - Special provisions regarding the performance of longshore activities at locations in the State of...

Science.gov (United States)

2010-04-01

...' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TEMPORARY EMPLOYMENT OF FOREIGN WORKERS IN THE UNITED STATES Attestations by Employers Using Alien Crewmembers for Longshore Activities in... preponderance of the evidence which may be submitted by any interested party, that an attestation is required...

Post-monsoon equilibrium beach profiles and longshore sediment transport rates at Candolim, Miramar and Keri beaches of Goa, India.

Digital Repository Service at National Institute of Oceanography (India)

Jayakumar, S.; Yadhunath, E.M.; Jishad, M.; Gowthaman, R.; Rajasekaran, C; Pednekar, P.S.

) and the profile shape factor m, which are inversely proportional to each other, have been analysed for their application to the study site. Also, the variation of these two parameters with beach slope and grain size is studied. Longshore sediment...

A significant longshore transport divergence zone at the Northeastern Brazilian coast: implications on coastal Quaternary evolution

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ABÍLIO C.S.P. BITTENCOURT

2002-09-01

Full Text Available By using the mean directions of the wave-fronts approaching the Brazilian northeastern coastal stretch comprised between the localities of Real river (Sergipe State and Galinhos (Rio Grande do Norte State - coincident with those of the main winds occurring in the area - and their periods, we have defined a wave climate model based on the construction of refraction diagrams. The resulting model of sediment transport, as obtained by numerical modelling from the refraction diagrams, taking into consideration the angle of approach and waves heights along the 10-m isobath, was capable of reproducing the patterns of sediment dispersion provided by geomorphic indicators of the longshore drift. All this coastal region, approximately 900 km in length, is characterized by a significant divergence zone in the direction of net longshore drift of sediments, the potential intensity of which increases considerably in value, in almost its entire length, continuously toward downdrift, which might explain the greater or lesser long term susceptibility to erosion, during the Quaternary, along the coastal stretch studied.Utilizando-se as direções médias das principais frentes-de-onda que se aproximam do trecho costeiro do nordeste brasileiro compreendido entre as localidades de Rio Real (Sergipe e Galinhos (Rio Grande do Norte - coincidentes com aquelas dos principais ventos que ocorrem na área - e de seus períodos, nós definimos um modelo de clima de ondas baseado na construção de diagramas de refração. O modelo resultante de transporte de sedimentos, obtido por modelagem numérica feita a partir dos diagramas de refração, considerando o ângulo de aproximação e a altura das ondas ao longo da isóbata de 10m, foi capaz de reproduzir os padrões de dispersão de sedimentos fornecidos pelos indicadores geomórficos de deriva litorânea. Toda essa região costeira, com cerca de 900km de extensão, caracteriza-se por se constituir em uma grande zona de

Wave-induced current considering wave-tide interaction in Haeundae

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Lim, Hak Soo

2017-04-01

The Haeundae, located at the south eastern end of the Korean Peninsula, is a famous beach, which has an approximately 1.6 km long and 70 m wide coastline. The beach has been repeatedly eroded by the swell waves caused by typhoons in summer and high waves originating in the East Sea in winter. The Korean government conducted beach restoration projects including beach nourishment (620,000 m3) and construction of two submerged breakwaters near both ends of the beach. To prevent the beach erosion and to support the beach restoration project, the Korean government initiated a R&D project, the development of coastal erosion control technology since 2013. As a part of the project, we have been measuring waves and currents at a water depth of 22 m, 1.8 km away from the beach using an acoustic wave and current meter (AWAC) continuously for more than three years; we have also measured waves and currents intensively near the surf-zone in summer and winter. In this study, a numerical simulation using a wave and current coupled model (ROMS-SWAN) was conducted for determining the wave-induced current considering seasonal swell waves (Hs : 2.5 m, Tp: 12 s) and for better understanding of the coastal process near the surf-zone in Haeundae. By comparing the measured and simulated results, we found that cross-shore current during summer is mainly caused by the eddy produced by the wave-induced current near the beach, which in turn, is generated by the strong waves coming from the SSW and S directions. During other seasons, longshore wave-induced current is produced by the swell waves coming from the E and ESE directions. The longshore current heading west toward Dong-Back Island, west end of the beach, during all the seasons and eddy current toward Mipo-Port, east end of the beach, in summer which is well matched with the observed residual current. The wave-induced current with long-term measurement data is incorporated in simulation of sediment transport modeling for developing

Tunnel-induced Dipolar Resonances in a Double-well Potential.

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Schulz, Bruno; Saenz, Alejandro

2016-11-18

A system of two dipolar particles that are confined in a double-well potential and interact via a realistic isotropic interaction potential is investigated as a protoype for ultracold atoms with a magnetic dipole moment or ultracold dipolar heteronuclear diatomic molecules in double-well traps or in optical lattices. The resulting energy spectrum is discussed as a function of the dipole-dipole interaction strength. The variation of the strength of the dipole-dipole interaction is found to lead to various resonance phenomena. Among those are the previously discussed inelastic confinement-induced resonances as well as the dipole-induced resonances. It is found that the double-well potential gives rise to a new type of resonances, tunnel-induced dipolar ones. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Climate induced changes in beach morphology and sediment dynamics, Machilipatnam

Digital Repository Service at National Institute of Oceanography (India)

Chauhan, O.S.

The wave climate, littoral current patterns, monthly and seasonal longshore drift rates, beach profile changes, and sediment budget of the beach sediments were determined along Machilipatnam, Andhra Pradesh (India) for the NE, SW monsoons...

Morphine potentiates seizures induced by GABA antagonists and attenuates seizures induced by electroshock in the rat.

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Foote, F; Gale, K

1983-11-25

In a naloxone-reversible, dose-dependent manner, morphine (10-50 mg/kg i.p.) protected against seizures induced by maximal electroshock and increased the incidence and severity of seizures induced by bicuculline, in rats. Morphine also potentiated seizures induced by isoniazid and by picrotoxin. Thus, opiate activity influences the expression of seizures in contrasting ways depending upon the mode of seizure induction. Since morphine consistently potentiated seizures induced by interference with GABA transmission, it appears that GABAergic systems may be of particular significance for the elucidation of the varied effects of morphine on seizure susceptibility.

A model integrating longshore and cross-shore processes for predicting long-term shoreline response to climate change

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Vitousek, Sean; Barnard, Patrick; Limber, Patrick W.; Erikson, Li; Cole, Blake

2017-01-01

We present a shoreline change model for coastal hazard assessment and management planning. The model, CoSMoS-COAST (Coastal One-line Assimilated Simulation Tool), is a transect-based, one-line model that predicts short-term and long-term shoreline response to climate change in the 21st century. The proposed model represents a novel, modular synthesis of process-based models of coastline evolution due to longshore and cross-shore transport by waves and sea-level rise. Additionally, the model uses an extended Kalman filter for data assimilation of historical shoreline positions to improve estimates of model parameters and thereby improve confidence in long-term predictions. We apply CoSMoS-COAST to simulate sandy shoreline evolution along 500 km of coastline in Southern California, which hosts complex mixtures of beach settings variably backed by dunes, bluffs, cliffs, estuaries, river mouths, and urban infrastructure, providing applicability of the model to virtually any coastal setting. Aided by data assimilation, the model is able to reproduce the observed signal of seasonal shoreline change for the hindcast period of 1995-2010, showing excellent agreement between modeled and observed beach states. The skill of the model during the hindcast period improves confidence in the model's predictive capability when applied to the forecast period (2010-2100) driven by GCM-projected wave and sea-level conditions. Predictions of shoreline change with limited human intervention indicate that 31% to 67% of Southern California beaches may become completely eroded by 2100 under sea-level rise scenarios of 0.93 to 2.0 m.

Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

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Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

2018-08-01

Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Ultrasonically-induced electrical potentials in demineralized bovine cortical bone

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Mori, Shunki; Makino, Taiki; Koyama, Daisuke; Takayanagi, Shinji; Yanagitani, Takahiko; Matsukawa, Mami

2018-04-01

While the low-intensity pulsed ultrasound technique has proved useful for healing of bone fractures, the ultrasound healing mechanism is not yet understood. To understand the initial physical effects of the ultrasound irradiation process on bone, we have studied the anisotropic piezoelectric properties of bone in the MHz range. Bone is known to be composed of collagen and hydroxyapatite (HAp) and shows strong elastic anisotropy. In this study, the effects of HAp on the piezoelectricity were investigated experimentally. To remove the HAp crystallites from the bovine cortical bone, demineralization was performed using ethylene diamine tetra-acetic acid (EDTA) solutions. To investigate the piezoelectricity, we have fabricated ultrasound transducers using the cortical bone or demineralized cortical bone. The induced electrical potentials due to the piezoelectricity were observed as the output of these transducers under pulsed ultrasound irradiation in the MHz range. The cortical bone transducer (before mineralization) showed anisotropic piezoelectric behavior. When the ultrasound irradiation was applied normal to the transducer surface, the observed induced electrical potentials had minimum values. The potential increased under off-axis ultrasound irradiation with changes in polarization. In the demineralized bone transducer case, however, the anisotropic behavior was not observed in the induced electrical potentials. These results therefore indicate that the HAp crystallites affect the piezoelectric characteristics of bone.

A diachronic view of the net longshore sediment drift during the Late Holocene at the Jequitinhonha River delta, Brazil, using numerical modeling

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Abilio C.S.P. Bittencourt

2011-12-01

Full Text Available Using numerical modeling, this work estimates sediment dispersion patterns caused by the incidence of waves in five distinct coastline contours of the Jequitinhonha River delta plain during the Late Holocene. For this study, a wave cliate odel based on the construction of ave refraction diagras relative to the current boundary conditions as defined and assumed to be valid for the five coastlines. Numerical modeling from the refraction diagrams was carried out considering the angle of incidence and wave height along the coastline. This work has allowed us to reproduce past and current patterns of net longshore sediment drift defined by a conceptual model developed from the integration of sediment cores, aerial photograph interpretation, C14 datings and geomorphic indicators of longshore drift. These results show that, on average, current wave conditions in the east-northeastern Brazilian region seem to have remained characteristically the same from approximately 5100 years BP until the present time. This type of information can be important when attempting to simulate possible future situations in terms of the long-term general behavior of the east-northeastern Brazilian coastal region.O presente trabalho apresenta uma estimativa, por modelagem numérica, dos padrões de dispersão de sedimentos causados pela incidência de ondas em cinco distintos contornos de linhas de costa da planície deltaica do Rio Jequitinhonha durante o Holoceno Tardio. Para isso, um modelo de clima de ondas baseado na construção de diagramas de refração de onda, em função das condições de contorno atuais, foi definido e assumido ser válido para as cinco linhas de costa. A modelagem numérica, a partir dos diagramas de refração, foi feita considerando o ângulo de aproximação e a altura da onda ao longo da linha de costa. O trabalho permitiu reproduzir os padrões pretéritos e atuais da deriva litorânea efetiva de sedimentos, definidos por um modelo

Hindcast of breaking waves and its impact at an island sheltered coast, Karwar

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Dora, G. Udhaba; Kumar, V. Sanil

2018-01-01

Variability in the characteristics of depth-induced wave breakers along a non-uniform coastal topography and its impact on the morpho-sedimentary processes is examined at the island sheltered wave-dominated micro-tidal coast, Karwar, west coast of India. Waves are simulated using the coupled wind wave model, SWAN nested in WAVEWATCH III, forced by the reanalysis winds from different sources (NCEP/NCAR, ECMWF, and NCEP/CFSR). Impact of the wave breakers is evaluated through mean longshore current and sediment transport for various wave energy conditions across different coastal morphology. Study revealed that the NCEP/CFSR wind is comparatively reasonable in simulation of nearshore waves using the SWAN model nested by 2D wave spectra generated from WAVEWATCH III. The Galvin formula for estimating mean longshore current using the crest wave period and the Kamphuis approximation for longshore sediment transport is observed realistically at the sheltered coastal environment while the coast interacts with spilling and plunging breakers.

Studies on nearshore processes at Yarada beach (South of Visakhapatnam harbour) east coast of India

Digital Repository Service at National Institute of Oceanography (India)

Chandramohan, P.; Rao, T.V.N.; Rao, D.P.; Rao, B.P.

Influence of breakwaters on Yarada Beach, Andhra Pradesh, India (3.5 km length) stability and distribution on wave induced longshore currents in this region were studied. Monthly observations on variation in beach levels, distribution of wave...

Planar density of vacuum charge induced by a supercritical Coulomb potential

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V.R. Khalilov

2017-06-01

Full Text Available Analytical expressions for the planar density of an induced vacuum charge are obtained in a strong Coulomb potential in coordinate space. Treatment is based on a self-adjoint extension approach for constructing of the Green's function of a charged fermion in an external electromagnetic field. Induced vacuum charge density is calculated and analyzed in subcritical and supercritical Coulomb potentials for massless and massive fermions. We argue that the virtual and so-called real vacuum polarizations contribute in an induced vacuum charge in a supercritical Coulomb potential. The behavior of the polarization vacuum charge density is investigated at long and short distances from the Coulomb center. The induced vacuum charge has a screening sign. Screening of a Coulomb impurity in graphene is briefly discussed. The real vacuum polarization charge density that acquires the quantum electrodynamics vacuum in a supercritical Coulomb potential due to the real vacuum polarization is calculated. It is shown that the vacuum charge densities essentially differ in massive and massless cases. We expect that our results can, as a matter of principle, be tested in graphene with a supercritical Coulomb impurity.

Planar density of vacuum charge induced by a supercritical Coulomb potential

Energy Technology Data Exchange (ETDEWEB)

Khalilov, V.R., E-mail: khalilov@phys.msu.ru; Mamsurov, I.V.

2017-06-10

Analytical expressions for the planar density of an induced vacuum charge are obtained in a strong Coulomb potential in coordinate space. Treatment is based on a self-adjoint extension approach for constructing of the Green's function of a charged fermion in an external electromagnetic field. Induced vacuum charge density is calculated and analyzed in subcritical and supercritical Coulomb potentials for massless and massive fermions. We argue that the virtual and so-called real vacuum polarizations contribute in an induced vacuum charge in a supercritical Coulomb potential. The behavior of the polarization vacuum charge density is investigated at long and short distances from the Coulomb center. The induced vacuum charge has a screening sign. Screening of a Coulomb impurity in graphene is briefly discussed. The real vacuum polarization charge density that acquires the quantum electrodynamics vacuum in a supercritical Coulomb potential due to the real vacuum polarization is calculated. It is shown that the vacuum charge densities essentially differ in massive and massless cases. We expect that our results can, as a matter of principle, be tested in graphene with a supercritical Coulomb impurity.

Dihydrotestosterone Potentiates EGF-Induced ERK Activation by Inducing SRC in Fetal Lung Fibroblasts

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Smith, Susan M.; Murray, Sandy; Pham, Lucia D.; Minoo, Parviz; Nielsen, Heber C.

2014-01-01

Lung maturation is regulated by interactions between mesenchymal and epithelial cells, and is delayed by androgens. Fibroblast–Type II cell communications are dependent on extracellular signal-regulated kinases (ERK) 1/2 activation by the ErbB receptor ligands epidermal growth factor (EGF), transforming growth factor (TGF)-α, and neuregulin (Nrg). In other tissues, dihydrotestosterone (DHT) has been shown to activate SRC by a novel nontranscriptional mechanism, which phosphorylates EGF receptors to potentiate EGF-induced ERK1/2 activation. This study sought to determine if DHT potentiates EGFR signaling by a nontranscriptional mechanism. Embryonic day (E)17 fetal lung cells were isolated from dams treated with or without DHT since E12. Cells were exposed to 30 ng/ml DHT for periods of 30 minutes to 3 days before being stimulated with 100 ng/ml EGF, TGF-α, or Nrg for up to 30 minutes. Lysates were immunoblotted for ErbB and SRC pathway signaling intermediates. DHT increased ERK1/2 activation by EGF, TGF-α, and Nrg in fibroblasts and Type II cells. Characterization in fibroblasts showed that potentiation of the EGF pathway was significant after 60 minutes of DHT exposure and persisted in the presence of the translational inhibitor cycloheximide. SRC and EGF receptor phosphorylation was increased by DHT, as was EGF-induced SHC1 phosphorylation and subsequent association with GRB2. Finally, SRC silencing, SRC inhibition with PP2, and overexpression of a dominant-negative SRC each prevented DHT from increasing EGF-induced ERK1/2 phosphorylation. These results suggest that DHT activates SRC to potentiate the signaling pathway leading from the EGF receptor to ERK activation in primary fetal lung fibroblasts. PMID:24484548

HIGH PERCENTAGE OF RARE EARTH ELEMENT CONNECTION WITH THE ACCUMULATION SEDIMENT AS RESPONSE LONGSHORE CURRENTS IN THE BELITUNG WATERS

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Delyuzar Ilahude

2017-07-01

Full Text Available The study area is geographically located in the West coast of Belitung island at coordinates 105o48'00" - 106o06' 00" E and 06o46'00" - 06o50' 00" S. The beach and coastal area is influenced by wave energy from the West and North directions The purpose of this study is to analyze the relationship between the zone of sediment accumulation of empirical approaches on oceanography parameter containing rare earth elements. The approach used is to predict the shore wave energy using wave prediction curve deep waters to obtain the energy flux of the wave at each point of reference. Sediments containing rare earth elements tend to lead to the south as a result of the movement of longshore currents. Regional coastal area of the western part of the island of Belitung, especially in the southern part of the estuary of the river Tanjung Pandan is estimated to be a zone of sediment accumulation. The movement of sediment caused by wave energy from the north led to sedimentation evolved significantly in the south which is thought to contain rare earths minerals derived from land. This sedimentation process takes place on a seasonal basis, which allegedly took place in the west. The movement of sediment to the south of the mouth of the Cerucuk River it is predicted that rare earth elements were supplied from these rivers tend to settle in the southern part of the estuary Cerucuk throughout the year.

Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

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Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

2004-01-01

The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

Dirac gap-induced graphene quantum dot in an electrostatic potential

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Giavaras, G.; Nori, Franco

2011-04-01

A spatially modulated Dirac gap in a graphene sheet leads to charge confinement, thus enabling a graphene quantum dot to be formed without the application of external electric and magnetic fields [G. Giavaras and F. Nori, Appl. Phys. Lett. 97, 243106 (2010)]. This can be achieved provided the Dirac gap has a local minimum in which the states become localized. In this work, the physics of such a gap-induced dot is investigated in the continuum limit by solving the Dirac equation. It is shown that gap-induced confined states couple to the states introduced by an electrostatic quantum well potential. Hence the region in which the resulting hybridized states are localized can be tuned with the potential strength, an effect which involves Klein tunneling. The proposed quantum dot may be used to probe quasirelativistic effects in graphene, while the induced confined states may be useful for graphene-based nanostructures.

Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers

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Zhuoling An

2018-01-01

Full Text Available Metabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS analyses and multivariate statistics was implemented to identify potential biomarkers for hydrazine-induced hepatotoxicity. The global serum and urine metabolomics of 30 hydrazine-treated rats at 24 or 48 h postdosing and 24 healthy rats were characterized by a metabolomics approach. Multivariate statistical data analyses and receiver operating characteristic (ROC curves were performed to identify the most significantly altered metabolites. The 16 most significant potential biomarkers were identified to be closely related to hydrazine-induced liver injury. The combination of these biomarkers had an area under the curve (AUC > 0.85, with 100% specificity and sensitivity, respectively. This high-quality classification group included amino acids and their derivatives, glutathione metabolites, vitamins, fatty acids, intermediates of pyrimidine metabolism, and lipids. Additionally, metabolomics pathway analyses confirmed that phenylalanine, tyrosine, and tryptophan biosynthesis as well as tyrosine metabolism had great interactions with hydrazine-induced liver injury in rats. These discriminating metabolites might be useful in understanding the pathogenesis mechanisms of liver injury and provide good prospects for drug-induced liver injury diagnosis clinically.

Investigation Of The Microbial-Induced Corrosion Potential Of Soils ...

African Journals Online (AJOL)

Investigation of sulphate-reducing bacteria induced corrosion potential of soils along 18-inch 45km Tebidaba/Brass underground oil pipeline in Southern Ijaw LGA of Bayelsa State, Nigeria, is carried out experimentally. The analysis involves determination of some physico-chemical parameters of soils in the pipeline route, ...

Stress induces pain transition by potentiation of AMPA receptor phosphorylation.

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Li, Changsheng; Yang, Ya; Liu, Sufang; Fang, Huaqiang; Zhang, Yong; Furmanski, Orion; Skinner, John; Xing, Ying; Johns, Roger A; Huganir, Richard L; Tao, Feng

2014-10-08

Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition. Copyright © 2014 the authors 0270-6474/14/3413737-10$15.00/0.

Liu Jun Zi Tang—A Potential, Multi-Herbal Complementary Therapy for Chemotherapy-Induced Neurotoxicity

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Chun-Tang Chiou

2018-04-01

Full Text Available Liu Jun Zi Tang (LJZT has been used to treat functional dyspepsia and depression, suggesting its effects on gastrointestinal and neurological functions. LJZT is currently used as a complementary therapy to attenuate cisplatin-induced side effects, such as dyspepsia. However, its effect on chemotherapy-induced neuropathic pain or neurotoxicity has rarely been studied. Thus, we explored potential mechanisms underlying LJZT protection against cisplatin-induced neurotoxicity. We observed that LJZT attenuated cisplatin-induced thermal hyperalgesia in mice and apoptosis in human neuroblastoma SH-SY5Y cells. Furthermore, it also attenuated cisplatin-induced cytosolic and mitochondrial free radical formation, reversed the cisplatin-induced decrease in mitochondrial membrane potential, and increased the release of mitochondrial pro-apoptotic factors. LJZT not only activated the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α promoter region, but also attenuated the cisplatin-induced reduction of PGC-1α expression. Silencing of the PGC-1α gene counteracted the protection of LJZT. Taken together, LJZT mediated, through anti-oxidative effect and mitochondrial function regulation, to prevent cisplatin-induced neurotoxicity.

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

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Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

2016-01-01

MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

Glucocorticoid: A potential role in microgravity-induced bone loss

Science.gov (United States)

Yang, Jiancheng; Yang, Zhouqi; Li, Wenbin; Xue, Yanru; Xu, Huiyun; Li, Jingbao; Shang, Peng

2017-11-01

Exposure of animals and humans to conditions of microgravity, including actual spaceflight and simulated microgravity, results in numerous negative alterations to bone structure and mechanical properties. Although there are abundant researches on bone loss in microgravity, the explicit mechanism is not completely understood. At present, it is widely accepted that the absence of mechanical stimulus plays a predominant role in bone homeostasis disorders in conditions of weightlessness. However, aside from mechanical unloading, nonmechanical factors such as various hormones, cytokines, dietary nutrition, etc. are important as well in microgravity induced bone loss. The stress-induced increase in endogenous glucocorticoid (GC) levels is inevitable in microgravity environments. Moreover, it is well known that GCs have a detrimental effect to bone health at excess concentrations. Therefore, GC plays a potential role in microgravity-induced bone loss. This review summarizeds several studies and their prospective solutions to this hypothesis.

Patterns of Seismicity Associated with USGS Identified Areas of Potentially Induced Seismicity.

Science.gov (United States)

Barnes, Caitlin; Halihan, Todd

2018-03-13

A systematic review across U.S. Geological Survey (USGS) identified potentially induced seismic locations was conducted to discover seismic distance patterns and trends over time away from injection disposal wells. Previous research indicates a 10 km (6 miles) average where the majority of induced seismicity is expected to occur within individual locations, with some areas reporting a larger radius of 35 km (22 miles) to over 70 km (43 miles). This research analyzed earthquake occurrences within nine USGS locations where specified wells were identified as contributors to induced seismicity to determine distance patterns from disposal wells or outward seismic migration over time using established principles of hydrogeology. Results indicate a radius of 31.6 km (20 miles) where 90% of felt earthquakes occur among locations, with the closest proximal felt seismic events, on average, occurring 3 km (1.9 miles) away from injection disposal wells. The results of this research found distance trends across multiple locations of potentially induced seismicity. © 2018, National Ground Water Association.

Regorafenib Induces Apoptosis and Inhibits Metastatic Potential of Human Bladder Carcinoma Cells.

Science.gov (United States)

Hsu, Fei-Ting; Sun, Cho-Chin; Wu, Chia-Hsing; Lee, Yen-Ju; Chiang, Chih-Hung; Wang, Wei-Shu

2017-09-01

The aim of the present study was to verify the effects of regorafenib on apoptosis and metastatic potential in TSGH 8301 human bladder carcinoma cells in vitro. Cells were treated with different concentration of regorafenib for different periods of time. Effects of regorafenib on cell viability, apoptosis pathways, metastatic potential, and expression of metastatic and anti-apoptotic proteins were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, flow cytometry, cell migration and invasion assay, and western blotting. We found regorafenib significantly reduced cell viability, cell migration and invasion, and expression of metastatic and anti-apoptotic proteins. In addition, regorafenib significantly induced accumulation of sub-G 1 phase cells, loss of mitochondrial membrane potential, and expression of active caspase-3 and caspase-8. These results show that regorafenib not only induces apoptosis, but also inhibits metastatic potential in bladder cancer TSGH 8301 cells in vitro. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Beach Response to Wave Energy Converter Farms Acting as Coastal Defence

DEFF Research Database (Denmark)

Mendoza, Edgar; Silva, Rodolfo; Zanuttigh, Barbara

2014-01-01

of two beaches, i.e. the Bay of Santander in Spain and Las Glorias beach in Mexico, representing two different case studies where the long-shore sediment transport is dominant. The hydrodynamics induced by these devices is represented by means of a 2D elliptic modified mild-slope model that is calibrated...

Anti-glaucoma potential of Heliotropium indicum Linn in experimentally-induced glaucoma

OpenAIRE

Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Owusu-Afriyie, Osei

2015-01-01

Background Heliotropium indicum is used as a traditional remedy for hypertension in Ghana. The aim of the study was to evaluate the anti-glaucoma potential of an aqueous whole plant extract of H. indicum to manage experimentally-induced glaucoma. Methods The percentage change in intraocular pressure (IOP), after inducing acute glaucoma (15 mLkg?1 of 5?% dextrose, i.v.), in New Zealand White rabbits pretreated with Heliotropium indicum aqueous extract (HIE) (30?300 mgkg?1), acetazolamide (5 mg...

3,3'-diindolylmethane potentiates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of gastric cancer cells.

Science.gov (United States)

Ye, Yang; Miao, Shuhan; Wang, Yan; Zhou, Jianwei; Lu, Rongzhu

2015-05-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) specifically kills cancer cells without destroying the majority of healthy cells. However, numerous types of cancer cell, including gastric cancer cells, tend to be resistant to TRAIL. The bioactive product 3,3'-diindolylmethane (DIM), which is derived from cruciferous vegetables, is also currently recognized as a candidate anticancer agent. In the present study, a Cell Counting Kit 8 cell growth assay and an Annexin V-fluorescein isothiocyanate apoptosis assay were performed to investigate the potentiating effect of DIM on TRAIL-induced apoptosis in gastric cancer cells, and the possible mechanisms of this potentiation. The results obtained demonstrated that, compared with TRAIL or DIM treatment alone, co-treatment with TRAIL (25 or 50 ng/ml) and DIM (10 µmol/l) induced cytotoxic and apoptotic effects in BGC-823 and SGC-7901 gastric cancer cells. Furthermore, western blot analysis revealed that the protein expression levels of death receptor 5 (DR5), CCAAT/enhancer binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were upregulated in the co-treated gastric cancer cells. To the best of our knowledge, the present study is the first to provide evidence that DIM sensitizes TRAIL-induced inhibition of proliferation and apoptosis in gastric cancer cells, accompanied by the upregulated expression of DR5, CHOP and GRP78 proteins, which may be involved in endoplasmic reticulum stress mechanisms.

Exogenous glutamate induces short and long-term potentiation in the rat medial vestibular nuclei.

Science.gov (United States)

Grassi, S; Frondaroli, A; Pessia, M; Pettorossi, V E

2001-08-08

In rat brain stem slices, high concentrations of exogenous glutamate induce long-term potentiation (LTP) of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation. At low concentrations, glutamate can also induce short-term potentiation (STP), indicating that LTP and STP are separate events depending on the level of glutamatergic synapse activation. LTP and STP are prevented by blocking NMDA receptors and nitric oxide (NO) synthesis. Conversely, blocking platelet-activating factor (PAF) and group I metabotropic glutamate receptors only prevents the full development of LTP. Moreover, in the presence of blocking agents, glutamate causes transient inhibition, suggesting that when potentiation is impeded, exogenous glutamate can activate presynaptic mechanisms that reduce glutamate release.

Effect of sulfhydryls on potentiation of radiation-induced cell lethality by substituted anthraquinones

International Nuclear Information System (INIS)

Kimler, B.F.

1984-01-01

The effects of various substituted anthraquinones (SAQ's) and Adriamycin (ADR) were investigated in cultured Chinese hamster V79 cells. These drugs cause a potentiation of radiation-induced cell lethality, albeit by different mechanisms. One possibility is that these components operate through the production of free radicals which then produce DNA strand breaks and crosslinks. If so, then one should be able to change the degree of cell kill by modifying sulfhydryl (SH) levels such that free radical processes are altered. Diamide, buthionine-S, R-sulfoximine, and N-ethylmaleimide (NEM) were used to reduce intracellular SH levels. Cysteamine and dithiotheitol were used to increase SH levels. In general, altered SH levels did not affect SAQ-induced cytotoxicity at low drug concentrations. When drug-tested cells were also irradiated, survival levels were generally those predicted from assuming purely additive interactions. On the other hand, survival after treatment with high concentrations of ADR and one other SAQ were decreased by concomitant treatment with NEM. Since altered SH levels do not produce changes in the potentiation of radiation-induced cell lethality by SAQs, it is concluded that free radicals are not involved in this potentiation. A free radical-mediated process may be involved in the cytotoxicity induced by ADR and other SAQs; however, it is not a simple process

Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias.

Science.gov (United States)

Lu, H R; Hortigon-Vinagre, M P; Zamora, V; Kopljar, I; De Bondt, A; Gallacher, D J; Smith, G

2017-09-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were digitized at 10kHz and the records subsequently analyzed off-line. Cells were exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound) that were blinded to the investigating laboratory. Action potential parameters were measured, including rise time (T rise ) of the optical action potential duration (oAPD). Significant effects on oAPD were sensitively detected with 11 QT-prolonging drugs, while oAPD shortening was observed with I Ca -antagonists, I Kr -activator or ATP-sensitive K + channel (K ATP )-opener. Additionally, the assay detected varied effects induced by 6 different sodium channel blockers. The detection threshold for these drug effects was at or below the published values of free effective therapeutic plasma levels or effective concentrations by other studies. The results of this blinded study indicate that OAP is a sensitive method to accurately detect drug-induced effects (i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early after depolarizations) in hiPS-CMs; therefore, this technique will potentially be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

Science.gov (United States)

Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

2017-07-01

The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

Antioxidant Potential of Momordica Charantia in Ammonium Chloride-Induced Hyperammonemic Rats

Directory of Open Access Journals (Sweden)

A. Justin Thenmozhi

2011-01-01

Full Text Available The present study was aimed to investigate the antioxidant potential of Momordica charantia fruit extract (MCE in ammonium chloride-induced (AC hyperammonemic rats. Experimental hyperammonemia was induced in adult male Wistar rats (180–200 g by intraperitoneal injections of ammonium chloride (100 mg kg−1 body weight thrice a week. The effect of oral administration (thrice a week for 8 consecutive weeks of MCE (300 mg kg−1 body weight on blood ammonia, plasma urea, serum liver marker enzymes and oxidative stress biomarkers in normal and experimental animals was analyzed. Hyperammonemic rats showed a significant increase in the activities of thiobarbituric acid reactive substances, hydroperoxides and liver markers (alanine transaminase, aspartate transaminase and alkaline phosphatase, and the levels of glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione were decreased in the liver and brain tissues. Treatment with MCE normalized the above-mentioned changes in hyperammonemic rats by reversing the oxidant-antioxidant imbalance during AC-induced hyperammonemia, and offered protection against hyperammonemia. Our results indicate that MCE exerting the antioxidant potentials and maintaining the cellular integrity of the liver tissue could offer protection against AC-induced hyperammonemia. However, the exact underlying mechanism is yet to be investigated, and examination of the efficacy of the active constituents of the M. charantia on hyperammonemia is desirable.

Level shifts induced by a short-range potential

International Nuclear Information System (INIS)

Karnakov, B.M.; Mur, V.D.

1984-01-01

Formulas are derived which express the shifts of levels with energies Esub(n)sup((0)) << rsub(c)sup(-2) in a field Vsub(f)(r) induced by a short-range potential U(r) of radius rsub(c) in terms of the low energy scattering parameters (scattering length and effective radius) with a moment l in the potential. If the interaction between the particle and center is nonresonant, the method developed is identical to perturbation theory on the scattering length. The theory is extended to systems with random degeneracy (Vsub(f) is the Coulomb potential). Formulas describing quasi-intersection of terms are obtained for the case of resonance interaction with the center in a partial wave with l not equal to 0 when energetically close levels are present in both U and Vsub(f). Some features of the level shift are mentioned for the case when the level possesses an anomalously small coupling energy and its coresponding wave function becomes delocalized with decrease of the coupling energy to zero. The problem is discussed of the level shift when the potential Vsub(f) is a potential well surrounded by a weaklyt penetrable barrier. Some applications of the theory to a particle in the field of two short-range potentials or in the field of a short-range and Coulomb centers are considered. Formulas are also obtained for the shifts and widths of the Landau levels and of the shallow level with an arbitrary moment which perturbs the Landau levels

Multi-property isotropic intermolecular potentials and predicted spectral lineshapes of collision-induced absorption (CIA), collision-induced light scattering (CILS) and collision-induced hyper-Rayleigh scattering (CIHR) for H2sbnd Ne, -Kr and -Xe

Science.gov (United States)

El-Kader, M. S. A.; Godet, J.-L.; Gustafsson, M.; Maroulis, G.

2018-04-01

Quantum mechanical lineshapes of collision-induced absorption (CIA), collision-induced light scattering (CILS) and collision-induced hyper-Rayleigh scattering (CIHR) at room temperature (295 K) are computed for gaseous mixtures of molecular hydrogen with neon, krypton and xenon. The induced spectra are detected using theoretical values for induced dipole moment, pair-polarizability trace and anisotropy, hyper-polarizability and updated intermolecular potentials. Good agreement is observed for all spectra when the literature and the present potentials which are constructed from the transport and thermo-physical properties are used.

Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans

DEFF Research Database (Denmark)

Andersen, Hjalte H.; Melholt, Camilla; Hilborg, Sigurd D.

2017-01-01

A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists...... and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value....... (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical “cold-like” counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin...

RECEPTOR POTENTIAL AND LIGHT-INDUCED MITOCHONDRIAL ACTIVATION IN BLOWFLY PHOTORECEPTOR MUTANTS

NARCIS (Netherlands)

MOJET, MH; TINBERGEN, J; STAVENGA, DG

1991-01-01

1. Simultaneous measurements of the receptor potential and the light-induced mitochondrial activation were performed in white-eyed blowflies Calliphora vicina, mutant chalky, and Lucilia cuprina, mutants w(F) and w'nss. The intensity dependence and the temporal dynamics were investigated. 2. The

Correlation between passive film-induced stress and stress corrosion cracking of α-Ti in a methanol solution at various potentials

International Nuclear Information System (INIS)

Guo, X.Z.; Gao, K.W.; Chu, W.Y.; Qiao, L.J.

2003-01-01

The flow stress of a specimen of α-Ti before unloading is different with the yield stress of the same specimen after unloading and forming a passive film through immersing in a methanol solution at various constant potentials. The difference is the passive film-induced stress. The film-induced stress and susceptibility to stress corrosion cracking (SCC) in the methanol solution at various potentials were measured. At the stable open-circuit potential and under anodic polarization, both film-induced tensile stress σ p and susceptibility to SCC had a maximum value. The film-induced stress and SCC susceptibility, however, decreased steeply with a decrease in potential under cathodic polarization. When the potential V≤-280 mV SCE , the film-induced stress became compressive; correspondingly, susceptibility to SCC was zero. Therefore, the variation of film-induced stress with potential was consistent with that of susceptibility to SCC. A large film-induced tensile stress is the necessary condition for SCC of α-Ti in the methanol solution. The symbol and amount of the film-induced stress were related to the compositions of the passive film, which have been analyzed using the X-ray photoelectron spectrum (XPS)

Phorbol-ester-induced down-regulation of protein kinase C in mouse pancreatic islets. Potentiation of phase 1 and inhibition of phase 2 of glucose-induced insulin secretion

DEFF Research Database (Denmark)

Thams, P; Capito, K; Hedeskov, C J

1990-01-01

and potentiated phase 1 of glucose-induced secretion. Furthermore, perifusion of islets in the presence of staurosporine (1 microM), an inhibitor of protein kinase C, potentiated phase 1 and inhibited phase 2 of glucose-induced secretion. In addition, down-regulation of protein kinase C potentiated phase 1...

Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

International Nuclear Information System (INIS)

Montaigne, David; Marechal, Xavier; Baccouch, Riadh; Modine, Thomas; Preau, Sebastien; Zannis, Konstantinos; Marchetti, Philippe; Lancel, Steve; Neviere, Remi

2010-01-01

The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 μM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt max of 105 ± 8 mN/s in control hearts vs. 49 ± 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 ± 0.2 in control hearts vs. 2.2 ± 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 ± 1 μM cytochrome c/min/mg in control hearts vs. 14 ± 3 μM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.

MicroRNAs as Potential Mediators for Cigarette Smoking Induced Atherosclerosis

Directory of Open Access Journals (Sweden)

Yuka Yokoyama

2018-04-01

Full Text Available Smoking increases the risk of atherosclerosis-related events, such as myocardial infarction and ischemic stroke. Recent studies have examined the expression levels of altered microRNAs (miRNAs in various diseases. The profiles of tissue miRNAs can be potentially used in diagnosis or prognosis. However, there are limited studies on miRNAs following exposure to cigarette smoke (CS. The present study was designed to dissect the effects and cellular/molecular mechanisms of CS-induced atherosclerogenesis. Apolipoprotein E knockout (ApoE KO mice were exposed to CS for five days a week for two months at low (two puffs/min for 40 min/day or high dose (two puffs/min for 120 min/day. We measured the area of atherosclerotic plaques in the aorta, representing the expression of miRNAs after the exposure period. Two-month exposure to the high dose of CS significantly increased the plaque area in aortic arch, and significantly upregulated the expression of atherosclerotic markers (VCAM-1, ICAM-1, MCP1, p22phox, and gp91phox. Exposure to the high dose of CS also significantly upregulated the miRNA-155 level in the aortic tissues of ApoE KO mice. Moreover, the expression level of miR-126 tended to be downregulated and that of miR-21 tended to be upregulated in ApoE KO mice exposed to the high dose of CS, albeit statistically insignificant. The results suggest that CS induces atherosclerosis through increased vascular inflammation and NADPH oxidase expression and also emphasize the importance of miRNAs in the pathogenesis of CS-induced atherosclerosis. Our findings provide evidence for miRNAs as potential mediators of inflammation and atherosclerosis induced by CS.

Phenolic acids potentiate colistin-mediated killing of Acinetobacter baumannii by inducing redox imbalance.

Science.gov (United States)

Ajiboye, Taofeek O; Skiebe, Evelyn; Wilharm, Gottfried

2018-05-01

Phenolic acids with catechol groups are good prooxidants because of their low redox potential. In this study, we provided data showing that phenolic acids, caffeic acid, gallic acid and protocatechuic acid, enhanced colistin-mediated bacterial death by inducing redox imbalance. The minimum inhibitory concentrations of these phenolic acids against Acinetobacter baumannii AB5075 were considerably lowered for ΔsodB and ΔkatG mutants. Checkerboard assay shows synergistic interactions between colistin and phenolic acids. The phenolic acids exacerbated colistin-induced oxidative stress in A. baumannii AB5075 through increased superoxide anion generation, NAD + /NADH and ADP/ATP ratio. In parallel, the level of reduced glutathione was significantly lowered. We conclude that phenolic acids potentiate colistin-induced oxidative stress in A. baumannii AB5075 by increasing ROS generation, energy metabolism and electron transport chain activity with a concomitant decrease in glutathione. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cocaine potentiates ketamine-induced loss of the righting reflex and sleeping time in mice. Role of catecholamines.

Science.gov (United States)

Vanderwende, C; Spoerlein, M T; Lapollo, J

1982-07-01

Cocaine in graded doses potentiated ketamine-induced loss of the righting reflex and sleeping time. Potentiation of drug-induced sleep with cocaine was not a generalized phenomenon inasmuch as it had no effect on sleep induced by pentobarbital or hexobarbital and decreased sleep induced by phenobarbital. Pentylenetetrazole reduced ketamine sleep but d-amphetamine had a potentiative action. dl-alpha-Methyl-p-tyrosine methyl ester itself increased both the number losing the righting reflex and the sleeping time induced by ketamine. However, the effect cocaine on sleeping time was blocked 3 h after the dl-alpha-methyl-p-tyrosine methyl ester was given. The alpha and beta adrenergic blocking drugs, phenoxybenzamine and propranolol, increased the number of animals losing the righting reflex with ketamine, and phenoxybenzamine lengthened the sleeping time. Alpha and beta adrenergic agonists, l-phenylephrine and isoproterenol, increased the number of animals going to sleep with ketamine but did not significantly alter how long they would sleep. The agonists had no effect on the cocaine interaction with ketamine, whereas the antagonists blocked the effect of cocaine. Both stimulation and blockade of dopamine receptors led to increased loss of the righting reflex and sleeping time with ketamine but only receptor blockade antagonized the effect of cocaine on ketamine-induced sleep. Thus, both the noradrenergic and dopaminergic systems appear to be involved in the ability of cocaine to potentiate ketamine-induced sleep.

Enhanced photosynthetic capacity and antioxidant potential mediate brassinosteriod-induced phenanthrene stress tolerance in tomato

International Nuclear Information System (INIS)

Ahammed, Golam Jalal; Li, Xin; Xia, Xiao-Jian; Shi, Kai; Zhou, Yan-Hong; Yu, Jing-Quan

2015-01-01

Photosynthesis, the basal manufacturing process in the earth is habitually restricted by airborne micropollutants such as phenanthrene (PHE). Here, we show that 24-epibrassinolide (EBR), a bioactive plant steroid is able to keep higher photosynthetic capacity consistently for a long period under a shoot-imposed PHE stress in tomato. EBR-promoted photosynthetic capacity and efficiency eventually resulted in a 37.5% increase of biomass under PHE stress. As primary response, transcripts of antioxidant genes were remarkably induced by EBR in PHE-treated plants. Activities of antioxidant and detoxification enzymes were also enhanced by EBR. Notably, EBR-induced higher antioxidant potential was associated with reduced levels of H 2 O 2 and O 2 · — , resulting in a 32.7% decrease of content of malondialdehyde in the end of experiment and relatively healthy chloroplast ultrastructure in EBR + PHE treatment compared with PHE alone. These results indicate that EBR alleviates shoot-imposed PHE phytotoxicity by maintaining a consistently higher photosynthetic capacity and antioxidant potential in tomato. - Highlights: • PHE mist spray gradually inhibits photosynthesis and eventually reduces biomass. • EBR maintains a consistently higher photosynthesis even under PHE stress. • EBR upregulates expression of antioxidant genes as initial response to PHE stress. • EBR reduces oxidative stress by constantly activating strong antioxidant potential. • EBR-induced efficient neutralization of ROS protects chloroplast ultrastructure. - 24-epibrassinolide protects tomato plants from airborne phenanthrene-induced damages by maintaining a consistently higher photosynthetic capacity and antioxidant potential

Nrf2 deficiency potentiates methamphetamine-induced dopaminergic axonal damage and gliosis in the striatum.

Science.gov (United States)

Granado, Noelia; Lastres-Becker, Isabel; Ares-Santos, Sara; Oliva, Idaira; Martin, Eduardo; Cuadrado, Antonio; Moratalla, Rosario

2011-12-01

Oxidative stress that correlates with damage to nigrostriatal dopaminergic neurons and reactive gliosis in the basal ganglia is a hallmark of methamphetamine (METH) toxicity. In this study, we analyzed the protective role of the transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2), a master regulator of redox homeostasis, in METH-induced neurotoxicity. We found that Nrf2 deficiency exacerbated METH-induced damage to dopamine neurons, shown by an increase in loss of tyrosine hydroxylase (TH)- and dopamine transporter (DAT)-containing fibers in striatum. Consistent with these effects, Nrf2 deficiency potentiated glial activation, indicated by increased striatal expression of markers for microglia (Mac-1 and Iba-1) and astroglia (GFAP) one day after METH administration. At the same time, Nrf2 inactivation dramatically potentiated the increase in TNFα mRNA and IL-15 protein expression in GFAP+ cells in the striatum. In sharp contrast to the potentiation of striatal damage, Nrf2 deficiency did not affect METH-induced dopaminergic neuron death or expression of glial markers or proinflammatory molecules in the substantia nigra. This study uncovers a new role for Nrf2 in protection against METH-induced inflammatory and oxidative stress and striatal degeneration. Copyright © 2011 Wiley‐Liss, Inc.

Colloid electrochemistry of conducting polymer: towards potential-induced in-situ drug release

International Nuclear Information System (INIS)

Sankoh, Supannee; Vagin, Mikhail Yu.; Sekretaryova, Alina N.; Thavarungkul, Panote; Kanatharana, Proespichaya; Mak, Wing Cheung

2017-01-01

Highlights: • Pulsed electrode potential induced an in-situ drug release from dispersion of conducting polymer microcapsules. • Fast detection of the released drug within the colloid microenvironment. • Improved the efficiency of localized drug release at the electrode interface. - Abstract: Over the past decades, controlled drug delivery system remains as one of the most important area in medicine for various diseases. We have developed a new electrochemically controlled drug release system by combining colloid electrochemistry and electro-responsive microcapsules. The pulsed electrode potential modulation led to the appearance of two processes available for the time-resolved registration in colloid microenvironment: change of the electronic charge of microparticles (from 0.5 ms to 0.1 s) followed by the drug release associated with ionic equilibration (1–10 s). The dynamic electrochemical measurements allow the distinction of drug release associated with ionic relaxation and the change of electronic charge of conducting polymer colloid microparticles. The amount of released drug (methylene blue) could be controlled by modulating the applied potential. Our study demonstrated a surface-potential driven controlled drug release of dispersion of conducting polymer carrier at the electrode interfaces, while the bulk colloids dispersion away from the electrode remains as a reservoir to improve the efficiency of localized drug release. The developed new methodology creates a model platform for the investigations of surface potential-induced in-situ electrochemical drug release mechanism.

Van der Waals-like forces between hadrons induced by color confining potentials

International Nuclear Information System (INIS)

Gavela, M.B.; Yaouanc, A. le; Oliver, L.; Pene, O.; Raynal, J.C.; Sood, S.

1979-01-01

The London treatment of van der Waals forces is generalized to long-range forces induced by instantaneous confining potentials. Special attention is given to the problem of accounting for the intermediate colour-octet states. The result is in contradiciton with data on nucleon-nucleon phase shifts for any confining potential V(r) = -a(Σsub(A)lambdasup(A)lambda sup(A))rsup(α) for α > 0.1. (Auth.)

Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans.

Science.gov (United States)

Andersen, Hjalte H; Melholt, Camilla; Hilborg, Sigurd D; Jerwiarz, Anne; Randers, Amalie; Simoni, Amalie; Elberling, Jesper; Arendt-Nielsen, Lars

2017-01-04

A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists (trans-cinnamaldehyde/L-menthol, respectively), on histamine-induced itch, wheals and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-test lancets. Recorded outcome-parameters were itch intensity, wheal reactions, and neurogenic inflammation (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical "cold-like" counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin was used as a positive antipruritic control/comparator. Cold counter-irritation stimuli from 4°C to 22°C inhibited itch in a stimulus-intensity-dependent manner (p cold-like" counter-irritation with both L-menthol and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value.

Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

Science.gov (United States)

Qin, Si-Yong; Feng, Jun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Liu, Xiang-Ji; Luo, Guo-Feng; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2014-02-12

Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Equal-potential interpretation of electrically induced resonances in metamaterials

DEFF Research Database (Denmark)

Peng, Liang; Mortensen, N. Asger

2011-01-01

We propose a general description of electrically induced resonances (EIR) in metamaterials (MMs) comprising subwavelength unit cells. Based on classical electrodynamics, we found that EIR is governed by an equal-potential effect. Our theory accounts for the EIR phenomena and can give a renewed...... definition of the effective electric field and hence effective permittivity for MMs made of either dielectrics or metals as well as combinations thereof. The EIR, inherent to the periodic structures, may be the unifying origin of recently observed anomalous electromagnetic phenomena, e.g. the enhanced...

Potential role of coenzyme Q10 in facilitating recovery from statin-induced rhabdomyolysis.

Science.gov (United States)

Wang, L W; Jabbour, A; Hayward, C S; Furlong, T J; Girgis, L; Macdonald, P S; Keogh, A M

2015-04-01

Rhabdomyolysis is a rare, but serious complication of statin therapy, and represents the most severe end of the spectrum of statin-induced myotoxicity. We report a case where coenzyme Q10 facilitated recovery from statin-induced rhabdomyolysis and acute renal failure, which had initially persisted despite statin cessation and haemodialysis. This observation is biologically plausible due to the recognised importance of coenzyme Q10 in mitochondrial bioenergetics within myocytes, and the fact that statins inhibit farnesyl pyrophosphate production, a biochemical step crucial for coenzyme Q10 synthesis. Coenzyme Q10 is generally well tolerated, and may potentially benefit patients with statin-induced rhabdomyolysis. © 2015 Royal Australasian College of Physicians.

Hyperhomocysteinemia potentiates diabetes-impaired EDHF-induced vascular relaxation: Role of insufficient hydrogen sulfide

Directory of Open Access Journals (Sweden)

Zhongjian Cheng

2018-06-01

Full Text Available Insufficient hydrogen sulfide (H2S has been implicated in Type 2 diabetic mellitus (T2DM and hyperhomocysteinemia (HHcy-related cardiovascular complications. We investigated the role of H2S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA of db/db mice fed a high methionine (HM diet. HM diet (8 weeks induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively, and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF-induced endothelium-dependent relaxation to acetylcholine (ACh, determined by the presence of eNOS inhibitor N(ω-nitro-L-arginine methyl ester (L-NAME and prostacyclin (PGI2 inhibitor indomethacin (INDO, in SMA from db/db mice but not that from db/+ mice. A non-selective Ca2+-active potassium channel (KCa opener NS309 rescued T2DM/HHcy-impaired EDHF-mediated vascular relaxation to ACh. EDHF-induced relaxation to ACh was inhibited by a non-selective KCa blocker TEA and intermediate-conductance KCa blocker (IKCa Tram-34, but not by small-conductance KCa (SKCa blocker Apamin. HHcy potentiated the reduction of free sulfide, H2S and cystathionine γ-lyase protein, which converts L-cysteine to H2S, in SMA of db/db mice. Importantly, a stable H2S donor DATS diminished the enhanced O2- production in SMAs and lung endothelial cells of T2DM/HHcy mice. Antioxidant PEG-SOD and DATS improved T2DM/HHcy impaired relaxation to ACh. Moreover, HHcy increased hyperglycemia-induced IKCa tyrosine nitration in human micro-vascular endothelial cells. EDHF-induced vascular relaxation to L-cysteine was not altered, whereas such relaxation to NaHS was potentiated by HHcy in SMA of db/db mice which was abolished by ATP-sensitive potassium channel blocker Glycolamide but not by KCa blockers. Conclusions: Intermediate HHcy potentiated H2S reduction via CSE-downregulation in microvasculature of T2DM mice. H2S is justified as an EDHF. Insufficient H2S

YC-1 potentiates cAMP-induced CREB activation and nitric oxide production in alveolar macrophages

Energy Technology Data Exchange (ETDEWEB)

Hwang, Tsong-Long, E-mail: htl@mail.cgu.edu.tw [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan (China); Tang, Ming-Chi [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Kuo, Liang-Mou [Department of General Surgery, Chang Gung Memorial Hospital at Chia-Yi, Taiwan (China); Chang, Wen-De; Chung, Pei-Jen; Chang, Ya-Wen; Fang, Yao-Ching [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China)

2012-04-15

Alveolar macrophages play significant roles in the pathogenesis of several inflammatory lung diseases. Increases in exhaled nitric oxide (NO) are well documented to reflect disease severity in the airway. In this study, we investigated the effect of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), a known activator of soluble guanylyl cyclase, on prostaglandin (PG)E{sub 1} (a stable PGE{sub 2} analogue) and forskolin (a adenylate cyclase activator) induced NO production and inducible NO synthase (iNOS) expression in rat alveolar macrophages (NR8383). YC-1 did not directly cause NO production or iNOS expression, but drastically potentiated PGE{sub 1}- or forskolin-induced NO production and iNOS expression in NR8383 alveolar macrophages. Combination treatment with YC-1 and PGE{sub 1} significantly increased phosphorylation of the cAMP response element-binding protein (CREB), but not nuclear factor (NF)-κB activation. The combined effect on NO production, iNOS expression, and CREB phosphorylation was reversed by a protein kinase (PK)A inhibitor (H89), suggesting that the potentiating functions were mediated through a cAMP/PKA signaling pathway. Consistent with this, cAMP analogues, but not the cGMP analogue, caused NO release, iNOS expression, and CREB activation. YC-1 treatment induced an increase in PGE{sub 1}-induced cAMP formation, which occurred through the inhibition of cAMP-specific phosphodiesterase (PDE) activity. Furthermore, the combination of rolipram (an inhibitor of PDE4), but not milronone (an inhibitor of PDE3), and PGE{sub 1} also triggered NO production and iNOS expression. In summary, YC-1 potentiates PGE{sub 1}-induced NO production and iNOS expression in alveolar macrophages through inhibition of cAMP PDE activity and activation of the cAMP/PKA/CREB signaling pathway. Highlights: ► YC-1 potentiated PGE1-induced iNOS expression in alveolar macrophages. ► The combination of YC-1 and PGE1 increased CREB but not NFκB activation. �

Induced mitochondrial membrane potential for modeling solitonic conduction of electrotonic signals.

Directory of Open Access Journals (Sweden)

R R Poznanski

Full Text Available A cable model that includes polarization-induced capacitive current is derived for modeling the solitonic conduction of electrotonic potentials in neuronal branchlets with microstructure containing endoplasmic membranes. A solution of the nonlinear cable equation modified for fissured intracellular medium with a source term representing charge 'soakage' is used to show how intracellular capacitive effects of bound electrical charges within mitochondrial membranes can influence electrotonic signals expressed as solitary waves. The elastic collision resulting from a head-on collision of two solitary waves results in localized and non-dispersing electrical solitons created by the nonlinearity of the source term. It has been shown that solitons in neurons with mitochondrial membrane and quasi-electrostatic interactions of charges held by the microstructure (i.e., charge 'soakage' have a slower velocity of propagation compared with solitons in neurons with microstructure, but without endoplasmic membranes. When the equilibrium potential is a small deviation from rest, the nonohmic conductance acts as a leaky channel and the solitons are small compared when the equilibrium potential is large and the outer mitochondrial membrane acts as an amplifier, boosting the amplitude of the endogenously generated solitons. These findings demonstrate a functional role of quasi-electrostatic interactions of bound electrical charges held by microstructure for sustaining solitons with robust self-regulation in their amplitude through changes in the mitochondrial membrane equilibrium potential. The implication of our results indicate that a phenomenological description of ionic current can be successfully modeled with displacement current in Maxwell's equations as a conduction process involving quasi-electrostatic interactions without the inclusion of diffusive current. This is the first study in which solitonic conduction of electrotonic potentials are generated by

Induced gravity with Higgs potential. Elementary interactions and quantum processes

International Nuclear Information System (INIS)

Bezares Roder, Nils Manuel

2010-01-01

This work is intended to first serve as introduction in fundamental subjects of physics in order to be then able to review the mechanism of symmetry breakdown and its essential character in physics. It introduces the concept of scalar-tensor theories of gravity based on Bergmann-Wagoner models with a Higgs potential. The main physical context aimed is the problem of Dark Matter and Dark Energy. On the one hand, there is gravitation. Within this context, we have Dark Matter as an especially relevant concept. This work entails the following main contributions: - General features of Einstein's theory are introduced together with generalities of the different elementary interactions of physics from which the concepts of dark sectors and Higgs Mechanism are derived. - The concept of symmetry breaking and especially the Higgs Mechanism of mass generation are discussed in their relevance for the most different subjects of physics, especially in relation to the Standard Model of elementary particle physics with elementary Higgs fields. - Scalar-Tensor Theories are introduced in order to build in them the process of Higgs Mechanism. This is then fulfilled with a theory of induced gravity with a Higgs potential which seems renormalizable according to deWitt's power counting criterion, and with mass-generating Higgs fields which only couple gravitationally as well as with Higgs fields which act analogously to cosmon fields. - Further, the energy density of the gravitational field is derived for the specific model of induced gravity from an analogy to electrodynamics. It is shown that a nonvanishing value of pressure related to the scalar field is necessary in order to reproduce standard linear solar-relativistic dynamics. Within astrophysical considerations for flat rotation curves of galaxies, a possible dark-matter behavior is concluded within spherical symmetry. The scalar field and the dark-matter profile of total energy density are derived. An analogous relation between

Induced gravity with Higgs potential. Elementary interactions and quantum processes

Energy Technology Data Exchange (ETDEWEB)

Bezares Roder, Nils Manuel

2010-07-01

This work is intended to first serve as introduction in fundamental subjects of physics in order to be then able to review the mechanism of symmetry breakdown and its essential character in physics. It introduces the concept of scalar-tensor theories of gravity based on Bergmann-Wagoner models with a Higgs potential. The main physical context aimed is the problem of Dark Matter and Dark Energy. On the one hand, there is gravitation. Within this context, we have Dark Matter as an especially relevant concept. This work entails the following main contributions: - General features of Einstein's theory are introduced together with generalities of the different elementary interactions of physics from which the concepts of dark sectors and Higgs Mechanism are derived. - The concept of symmetry breaking and especially the Higgs Mechanism of mass generation are discussed in their relevance for the most different subjects of physics, especially in relation to the Standard Model of elementary particle physics with elementary Higgs fields. - Scalar-Tensor Theories are introduced in order to build in them the process of Higgs Mechanism. This is then fulfilled with a theory of induced gravity with a Higgs potential which seems renormalizable according to deWitt's power counting criterion, and with mass-generating Higgs fields which only couple gravitationally as well as with Higgs fields which act analogously to cosmon fields. - Further, the energy density of the gravitational field is derived for the specific model of induced gravity from an analogy to electrodynamics. It is shown that a nonvanishing value of pressure related to the scalar field is necessary in order to reproduce standard linear solar-relativistic dynamics. Within astrophysical considerations for flat rotation curves of galaxies, a possible dark-matter behavior is concluded within spherical symmetry. The scalar field and the dark-matter profile of total energy density are derived. An analogous

Basolateral amygdala inactivation impairs learning-induced long-term potentiation in the cerebellar cortex.

Directory of Open Access Journals (Sweden)

Lan Zhu

Full Text Available Learning to fear dangerous situations requires the participation of basolateral amygdala (BLA. In the present study, we provide evidence that BLA is necessary for the synaptic strengthening occurring during memory formation in the cerebellum in rats. In the cerebellar vermis the parallel fibers (PF to Purkinje cell (PC synapse is potentiated one day following fear learning. Pretraining BLA inactivation impaired such a learning-induced long-term potentiation (LTP. Similarly, cerebellar LTP is affected when BLA is blocked shortly, but not 6 h, after training. The latter result shows that the effects of BLA inactivation on cerebellar plasticity, when present, are specifically related to memory processes and not due to an interference with sensory or motor functions. These data indicate that fear memory induces cerebellar LTP provided that a heterosynaptic input coming from BLA sets the proper local conditions. Therefore, in the cerebellum, learning-induced plasticity is a heterosynaptic phenomenon that requires inputs from other regions. Studies employing the electrically-induced LTP in order to clarify the cellular mechanisms of memory should therefore take into account the inputs arriving from other brain sites, considering them as integrative units. Based on previous and the present findings, we proposed that BLA enables learning-related plasticity to be formed in the cerebellum in order to respond appropriately to new stimuli or situations.

Surf zone dynamics along the south Karnataka Coast between Bhatkal and Ullal, west coast of India

Digital Repository Service at National Institute of Oceanography (India)

Chandramohan, P.; SanilKumar, V.; Nayak, B.U.; Raju, N.S.N.

stronger in June, and relatively low and steady during the rest of the year. Coast between Padubidri and Ullal experienced relatively stronger longshore currents than the coast between Maravanthe and Malpe. Longshore sediment transport rate was relatively...

TMS-induced cortical potentiation during wakefulness locally increases slow wave activity during sleep.

Directory of Open Access Journals (Sweden)

Reto Huber

2007-03-01

Full Text Available Sleep slow wave activity (SWA is thought to reflect sleep need, increasing in proportion to the length of prior wakefulness and decreasing during sleep. However, the process responsible for SWA regulation is not known. We showed recently that SWA increases locally after a learning task involving a circumscribed brain region, suggesting that SWA may reflect plastic changes triggered by learning.To test this hypothesis directly, we used transcranial magnetic stimulation (TMS in conjunction with high-density EEG in humans. We show that 5-Hz TMS applied to motor cortex induces a localized potentiation of TMS-evoked cortical EEG responses. We then show that, in the sleep episode following 5-Hz TMS, SWA increases markedly (+39.1+/-17.4%, p<0.01, n = 10. Electrode coregistration with magnetic resonance images localized the increase in SWA to the same premotor site as the maximum TMS-induced potentiation during wakefulness. Moreover, the magnitude of potentiation during wakefulness predicts the local increase in SWA during sleep.These results provide direct evidence for a link between plastic changes and the local regulation of sleep need.

Asparaginase Potentiates Glucocorticoid-Induced Osteonecrosis in a Mouse Model.

Directory of Open Access Journals (Sweden)

Chengcheng Liu

Full Text Available Osteonecrosis is a common dose-limiting toxicity of glucocorticoids. Data from clinical trials suggest that other medications can increase the risk of glucocorticoid-induced osteonecrosis. Here we utilized a mouse model to study the effect of asparaginase treatment on dexamethasone-induced osteonecrosis. Mice receiving asparaginase along with dexamethasone had a higher rate of osteonecrosis than those receiving only dexamethasone after 6 weeks of treatment (44% vs. 10%, P = 0.006. Similarly, epiphyseal arteriopathy, which we have shown to be an initiating event for osteonecrosis, was observed in 58% of mice receiving asparaginase and dexamethasone compared to 17% of mice receiving dexamethasone only (P = 0.007. As in the clinic, greater exposure to asparaginase was associated with greater plasma exposure to dexamethasone (P = 0.0001. This model also recapitulated other clinical risk factors for osteonecrosis, including age at start of treatment, and association with the systemic exposure to dexamethasone (P = 0.027 and asparaginase (P = 0.036. We conclude that asparaginase can potentiate the osteonecrotic effect of glucocorticoids.

Effects of microstructure and water on the electrical potentials in bone induced by ultrasound irradiation

Energy Technology Data Exchange (ETDEWEB)

Tsuneda, H.; Matsukawa, S.; Takayanagi, S.; Matsukawa, M., E-mail: mmatsuka@mail.doshisha.ac.jp [Wave Electronics Research Center, Laboratory of Ultrasonic Electronics, Doshisha University, 1-3, Tatara Miyakodani, Kyotanabe, Kyoto 610-0321 (Japan); Mizuno, K. [Underwater Technology Collaborative Research Center, Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505 (Japan); Yanagitani, T. [Graduate School of Engineering, Nagoya Institute of Technology, Gokiso cho, Showa-ku, Nagoya 466-8555 (Japan)

2015-02-16

The healing mechanism of bone fractures by low intensity pulse ultrasound is yet to be fully understood. There have been many discussions regarding how the high frequency dynamic stress can stimulate numerous cell types through various pathways. As one possible initial process of this mechanism, we focus on the piezoelectricity of bone and demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. We have fabricated ultrasonic bone transducers using bovine cortical bone as the piezoelectric device. The ultrasonically induced electrical potentials in the transducers change as a function of time during immersed ultrasonic pulse measurements and become stable when the bone is fully wet. In addition, the magnitude of the induced electrical potentials changes owing to the microstructure in the cortical bone. The potentials of transducers with haversian structure bone are higher than those of plexiform structure bone, which informs about the effects of bone microstructure on the piezoelectricity.

Norepinephrine induces pathway-specific long-lasting potentiation and depression in the hippocampal dentate gyrus.

Science.gov (United States)

Dahl, D; Sarvey, J M

1989-01-01

The study presented here indicates that norepinephrine (NE) selectively induces long-lasting modifications of synaptically mediated responses in the dentate gyrus of the rat hippocampal slice. A low concentration of NE (1.0 microM; in the presence of 50 microM phentolamine, an alpha-adrenergic antagonist) or a 1.0 microM concentration of the specific beta-adrenergic agonist isoproterenol induced long-lasting pathway-specific alterations of granule cell electrophysiological responses. Excitatory postsynaptic potentials and population spikes evoked by stimulation of the medial perforant pathway (PP) were potentiated for more than 45 min. In contrast, responses to lateral PP stimulation were depressed for the same period. Both potentiation and depression were blocked by the beta-adrenergic antagonist propranolol (1.0 microM). These results indicate that NE can act differentially on projections to the dentate gyrus arising in the entorhinal cortex. Such selective persistent modifications of cortical circuits may be involved in processes in the mammalian brain underlying attention, learning, and memory. PMID:2734319

Induced-Charge Enhancement of the Diffusion Potential in Membranes with Polarizable Nanopores.

Science.gov (United States)

Ryzhkov, I I; Lebedev, D V; Solodovnichenko, V S; Shiverskiy, A V; Simunin, M M

2017-12-01

When a charged membrane separates two salt solutions of different concentrations, a potential difference appears due to interfacial Donnan equilibrium and the diffusion junction. Here, we report a new mechanism for the generation of a membrane potential in polarizable conductive membranes via an induced surface charge. It results from an electric field generated by the diffusion of ions with different mobilities. For uncharged membranes, this effect strongly enhances the diffusion potential and makes it highly sensitive to the ion mobilities ratio, electrolyte concentration, and pore size. Theoretical predictions on the basis of the space-charge model extended to polarizable nanopores fully agree with experimental measurements in KCl and NaCl aqueous solutions.

Transient Receptor Potential Vanilloid 1 Expression Mediates Capsaicin-Induced Cell Death

Directory of Open Access Journals (Sweden)

Ricardo Ramírez-Barrantes

2018-06-01

Full Text Available The transient receptor potential (TRP ion channel family consists of a broad variety of non-selective cation channels that integrate environmental physicochemical signals for dynamic homeostatic control. Involved in a variety of cellular physiological processes, TRP channels are fundamental to the control of the cell life cycle. TRP channels from the vanilloid (TRPV family have been directly implicated in cell death. TRPV1 is activated by pain-inducing stimuli, including inflammatory endovanilloids and pungent exovanilloids, such as capsaicin (CAP. TRPV1 activation by high doses of CAP (>10 μM leads to necrosis, but also exhibits apoptotic characteristics. However, CAP dose–response studies are lacking in order to determine whether CAP-induced cell death occurs preferentially via necrosis or apoptosis. In addition, it is not known whether cytosolic Ca2+ and mitochondrial dysfunction participates in CAP-induced TRPV1-mediated cell death. By using TRPV1-transfected HeLa cells, we investigated the underlying mechanisms involved in CAP-induced TRPV1-mediated cell death, the dependence of CAP dose, and the participation of mitochondrial dysfunction and cytosolic Ca2+ increase. Together, our results contribute to elucidate the pathophysiological steps that follow after TRPV1 stimulation with CAP. Low concentrations of CAP (1 μM induce cell death by a mechanism involving a TRPV1-mediated rapid and transient intracellular Ca2+ increase that stimulates plasma membrane depolarization, thereby compromising plasma membrane integrity and ultimately leading to cell death. Meanwhile, higher doses of CAP induce cell death via a TRPV1-independent mechanism, involving a slow and persistent intracellular Ca2+ increase that induces mitochondrial dysfunction, plasma membrane depolarization, plasma membrane loss of integrity, and ultimately, cell death.

Radiation induced dry eye: problem and potential remedies

International Nuclear Information System (INIS)

Vemuganti, Geeta K.; Tiwari, Shubha

2016-01-01

Advances in orbital radiotherapy have significantly increased therapeutic efficiency and reduced the side effects but a significant proportion of patients are still seen with ophthalmic complication like dry eye syndrome (DES). The treatment of DES involves temporary palliative therapies like ocular surface lubrication and rehydration. We aimed at establishing the human lacrimal gland cultures and evaluating for the presence of stem cells and secretory potential. Using human lacrimal gland tissues obtained from samples of therapeutic exenteration post-radiotherapy, we established a monolayer as well as 3D lacrispheres that show evidence of stem cells, secretory acinar cells, duct like formation and other cells like myoepithelial cells and duct like cells. The stem cells were identified as CD 117 positive that co-segregated with G0/G1 phase, ALDH high, label retaining cells and high clone forming ability. The most promising evidence of its secretory function was seen in the presence of tear substances like lysosymes, lactiferrin, and scIg A in the conditioned media of the lacrimal gland cultures. This novel development would pave way for development of a functionally competent 3D construct for potential clinical application in severe cases of radiation induced dry eye. (author)

Preliminary analysis of the potential for thermally-induced rock fracture around high-level waste containers

International Nuclear Information System (INIS)

Ratigan, J.L.

1976-01-01

The major results are: the development of parametric formulations relating the potential for thermally induced fracturing in the high-level radioactive waste repository concept to the elastic and thermal properties of the site rock and the depth of the excavation, and the recognition of a need to determine the actual ''failure envelope'' for any potential site rock in the laboratory and adjust the parametric relations appropriately. Analysis of five rock types indicated that none would experience elastic/brittle failure due to the thermal stresses induced by the introduction of a 5 kW heat source. However, the rock strengths and elastic properties are laboratory values and not in situ values

Evaluation of Delft3D Performance in Nearshore Flows

National Research Council Canada - National Science Library

Hsu, Y. L; Dykes, James D; Allard, Richard A; Kaihatu, James M

2006-01-01

.... All three bottom friction formulations, i.e., Chezy, White-Colebrook, and Manning, are evaluated and all can produce good longshore current results, if proper empirical bottom friction coefficient is used. The RMS error for longshore current is about 0.2 m/s.

20 CFR 701.301 - Definitions and use of terms.

Science.gov (United States)

2010-04-01

... employment, including: (A) Any longshore worker or other person engaged in longshoring operations; (B) Any... operation (meaning any recreational activity, including but not limited to scuba diving, commercial rafting... renting, leasing or chartering equipment to another for the latter's pleasure), restaurant, museum or...

Assessment of Quantitative Aftershock Productivity Potential in Mining-Induced Seismicity

Science.gov (United States)

Kozłowska, Maria; Orlecka-Sikora, Beata

2017-03-01

Strong mining-induced earthquakes exhibit various aftershock patterns. The aftershock productivity is governed by the geomechanical properties of rock in the seismogenic zone, mining-induced stress and coseismic stress changes related to the main shock's magnitude, source geometry and focal mechanism. In order to assess the quantitative aftershock productivity potential in the mining environment we apply a forecast model based on natural seismicity properties, namely constant tectonic loading and the Gutenberg-Richter frequency-magnitude distribution. Although previous studies proved that mining-induced seismicity does not obey the simple power law, here we apply it as an approximation of seismicity distribution to resolve the number of aftershocks, not considering their magnitudes. The model used forecasts the aftershock productivity based on the background seismicity level estimated from an average seismic moment released per earthquake and static stress changes caused by a main shock. Thus it accounts only for aftershocks directly triggered by coseismic process. In this study we use data from three different mines, Mponeng (South Africa), Rudna and Bobrek (Poland), representing different geology, exploitation methods and aftershock patterns. Each studied case is treated with individual parameterization adjusted to the data specifics. We propose the modification of the original model, i.e. including the non-uniformity of M 0, resulting from spatial correlation of mining-induced seismicity with exploitation. The results show that, even when simplified seismicity distribution parameters are applied, the modified model predicts the number of aftershocks for each analyzed case well and accounts for variations between these values. Such results are thus another example showing that coseismic processes of mining-induced seismicity reflect features of natural seismicity and that similar models can be applied to study the aftershock rate in both the natural and the

Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Zamansky, G B

1986-08-01

The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells.

Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

International Nuclear Information System (INIS)

Zamansky, G.B.

1986-01-01

The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells. (author)

Potential of mechanical metamaterials to induce their own global rotational motion

Science.gov (United States)

Dudek, K. K.; Wojciechowski, K. W.; Dudek, M. R.; Gatt, R.; Mizzi, L.; Grima, J. N.

2018-05-01

The potential of several classes of mechanical metamaterials to induce their own overall rotational motion through the individual rotation of their subunits is examined. Using a theoretical approach, we confirm that for various rotating rigid unit systems, if by design the sum of angular momentum of subunits rotating in different directions is made to be unequal, then the system will experience an overall rotation, the extent of which may be controlled through careful choice of the geometric parameters defining these systems. This phenomenon of self-induced rotation is also confirmed experimentally. Furthermore, we discuss how these systems can be designed in a special way so as to permit extended rotations which allows them to overcome geometric lockage and the relevance of this concept in applications ranging from satellites to spacecraft and telescopes employed in space.

Kindling-induced potentiation of excitatory and inhibitory inputs to hippocampal dentate granule cells. II. Effects of the NMDA antagonist MK-801.

LENUS (Irish Health Repository)

Robinson, G B

1991-10-18

The effect of the non-competitive N-methyl-D-aspartate antagonist MK-801 on the early development of kindling-induced potentiation was examined in the rabbit hippocampal dentate gyrus. MK-801 (0.5 mg\\/kg) was administered 2 h before each daily kindling stimulation was applied to the perforant path. This treatment continued for the first 10 days of kindling. MK-801 depressed the growth of the afterdischarge duration and suppressed development of behavioral seizures. MK-801 did not block kindling-induced potentiation of either the perforant path-dentate granule cell population spike or excitatory postsynaptic potential. Random impulse train stimulation and non-linear systems analytic techniques were used to examine kindling-induced potentiation of presumed GABAergic recurrent inhibitory circuits. Both the magnitude and duration of kindling-induced response inhibition, to the second of each pair of impulses within the train, were reduced in rabbits pretreated with MK-801. These results suggest that MK-801 differentially affects kindling-induced potentiation of excitatory and inhibitory circuits within the rabbit hippocampal dentate gyrus.

Use of PRIM code to analyze potential radiation-induced genetic and somatic effects to man from Jackpile-Paguate mines

International Nuclear Information System (INIS)

Momeni, M.H.

1983-01-01

Potential radiation-induced effects from inhalation and ingestion of land external exposure to radioactive materials at the Jackpile-Paguate uranium mine complex near Paguate, New Mexico, were analyzed. The Uranium Dispersion and Dosimetry (UDAD) computer code developed at Argonne National Laboratory was used to calculate the dose rates and the time-integrated doses to tissues at risk as a function of age and time for the population within 80 km of the mines. The ANL computer code Potential Radiation-Induced Biological Effects on Man (PRIM) then was used to calculate the potential radiation-induced somatic and genetic effects among the same population on the basis of absolute and relative risk models as a function of duration of exposure and age at time of exposure. The analyses were based on the recommendations in BEIR II and WASH-1400 and the lifetable method. The death rates were calculated for radiation exposure from the mines and for naturally induced effects for 19 age cohorts, 20 time intervals, and for each sex. The results indicated that under present conditions of the radiation environment at the mines, the number of potential fatal radiation-induced neoplasms that could occur among the regional population over the next 85 years would be 95 using the absolute risk model, and 243 using the relative risk model. Over the same period, there would be less than two radiation-induced genetic effects (dominant and multifactorials). After decommissioning f the mine site, these risks would decrease to less than 1 and less than 3 potential radiation-induced deaths under the relative and absolute risk models, respectively, and 0.001 genetic disorders. Because of various sources of error, the uncertainty in these predicted risks could be a factor of five

Phonon-mediated decay of an atom in a surface-induced potential

International Nuclear Information System (INIS)

Kien, Fam Le; Hakuta, K.; Dutta Gupta, S.

2007-01-01

We study phonon-mediated transitions between translational levels of an atom in a surface-induced potential. We present a general master equation governing the dynamics of the translational states of the atom. In the framework of the Debye model, we derive compact expressions for the rates for both upward and downward transitions. Numerical calculations for the transition rates are performed for a deep silica-induced potential allowing for a large number of bound levels as well as free states of a cesium atom. The total absorption rate is shown to be determined mainly by the bound-to-bound transitions for deep bound levels and by bound-to-free transitions for shallow bound levels. Moreover, the phonon emission and absorption processes can be orders of magnitude larger for deep bound levels as compared to the shallow bound ones. We also study various types of transitions from free states. We show that, for thermal atomic cesium with a temperature in the range from 100 μK to 400 μK in the vicinity of a silica surface with a temperature of 300 K, the adsorption (free-to-bound decay) rate is about two times larger than the heating (free-to-free upward decay) rate, while the cooling (free-to-free downward decay) rate is negligible

Nearshore processes along Tikkavanipalem Beach, Visakhapatnam, India

Digital Repository Service at National Institute of Oceanography (India)

SanilKumar, V.; AshokKumar, K.; Raju, N.S.N.

on theoretical and measured longshore currents. The ratio of spectral energy at first and second spectral peaks show that the energy at second peak was more than fifty percent of the energy at first peak in 35% of the data collected. The longshore current speed...

Potentiating Effects of Lactuca sativa on Pentobarbital-Induced Sleep.

Science.gov (United States)

Ghorbani, Ahmad; Rakhshandeh, Hassan; Sadeghnia, Hamid Reza

2013-01-01

Traditionally, Lactuca sativa (lettuce) has been recommended for its hypnotic property. The present study was planned to investigate sleep-prolonging effect of this plant. The hydro-alcoholic extract (HAE) of lettuce and its water fraction (WF), ethyl acetate fraction (EAF), and n-butanol fraction (NBF) were administrated (IP) to mice 30 min before the pentobarbital injection. Moreover, both in-vivo and in-vitro toxicity of the extracts were determined. The quality of HAE and NBF was also evaluated using HPLC fingerprint. The HAE prolonged the pentobarbital-induced sleep duration at dose of 400 mg/Kg. The NBF was the only fraction which could increase the sleep duration and decrease sleep latency. The effects of NBF were comparable to those of induced by diazepam. The LD50-value for HAE was found to be 4.8 g/Kg. No neurotoxic effect was observed either by HAE or by its fractions in cultured PC12 neuron-like cells. The results suggest that lettuce potentiates pentobarbital hypnosis without major toxic effect. The main component(s) responsible for this effect is most likely to be non-polar agent(s) which found in NBF of this plant.

Exploring the potential effect of Ocimum sanctum in vincristine-induced neuropathic pain in rats

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Jaggi Amteshwar

2010-01-01

Full Text Available Abstract The present study was designed to investigate the ameliorative potential of Ocimum sanctum and its saponin rich fraction in vincristine-induced peripheral neuropathic pain in rats. Peripheral neuropathy was induced in rats by administration of vincristine sulfate (50 μg/kg i.p. for 10 consecutive days. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species (TBARS, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Vincristine administration was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia. Furthermore, vincristine administration was also associated with an increase in oxidative stress and calcium levels. However, administration of Ocimum sanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated vincristine-induced neuropathic pain along with decrease in oxidative stress and calcium levels. It may be concluded that Ocimum sanctum has ameliorative potential in attenuating chemotherapy induced-painful neuropathic state, which may be attributed to decrease in oxidative stress and calcium levels. Furthermore, saponin rich fraction of Ocimum sanctum may be responsible for its noted beneficial effect in neuropathic pain in rats.

Simulation of wake potentials induced by relativistic proton bunches in electron clouds

Energy Technology Data Exchange (ETDEWEB)

Petrov, Fedor; Boine-Frankenheim, Oliver; Weiland, Thomas [Technische Universitaet Darmstadt (Germany). Institut fuer Theorie Elektromagnetischer Felder (TEMF)

2012-07-01

Electron clouds limit the intensity of modern high intensity hadron accelerators. Presently electron clouds are the main limiting factor for the LHC operation with 25 ns bunch trains. The bunches passing through an electron cloud induce a wake field. When the electron cloud density exceeds a certain threshold beam instabilities occur. The presence of electron clouds results in a shift of the synchronous phase, which increases if the bunch spacing is reduced. For LHC and SPS conditions we compare the longitudinal electron cloud wake potentials and stopping powers obtained using a simplified 2D electrostatic Particle-in-Cell code with fully electromagnetic simulations using VORPAL. In addition we analyze the wake fields induced by displaced or tilted bunches.

Acute total sleep deprivation potentiates amphetamine-induced locomotor-stimulant effects and behavioral sensitization in mice.

Science.gov (United States)

Saito, Luis P; Fukushiro, Daniela F; Hollais, André W; Mári-Kawamoto, Elisa; Costa, Jacqueline M; Berro, Laís F; Aramini, Tatiana C F; Wuo-Silva, Raphael; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

2014-02-01

It has been demonstrated that a prolonged period (48 h) of paradoxical sleep deprivation (PSD) potentiates amphetamine (AMP)-induced behavioral sensitization, an animal model of addiction-related neuroadaptations. In the present study, we examined the effects of an acute short-term deprivation of total sleep (TSD) (6h) on AMP-induced behavioral sensitization in mice and compared them to the effects of short-term PSD (6 h). Three-month-old male C57BL/6J mice underwent TSD (experiment 1-gentle handling method) or PSD (experiment 2-multiple platforms method) for 6 h. Immediately after the sleep deprivation period, mice were tested in the open field for 10 min under the effects of saline or 2.0 mg/kg AMP. Seven days later, to assess behavioral sensitization, all of the mice received a challenge injection of 2.0 mg/kg AMP and were tested in the open field for 10 min. Total, peripheral, and central locomotion, and grooming duration were measured. TSD, but not PSD, potentiated the hyperlocomotion induced by an acute injection of AMP and this effect was due to an increased locomotion in the central squares of the apparatus. Similarly, TSD facilitated the development of AMP-induced sensitization, but only in the central locomotion parameter. The data indicate that an acute period of TSD may exacerbate the behavioral effects of AMP in mice. Because sleep architecture is composed of paradoxical and slow wave sleep, and 6-h PSD had no effects on AMP-induced hyperlocomotion or sensitization, our data suggest that the deprivation of slow wave sleep plays a critical role in the mechanisms that underlie the potentiating effects of TSD on both the acute and sensitized addiction-related responses to AMP. Copyright © 2013 Elsevier Inc. All rights reserved.

Coastal Changes due to the Construction of Artificial Harbour Entrances and Practical Solutions, including Beach Replenishment

NARCIS (Netherlands)

Bijker, E.W.; Van der Leijé, J.P.; Pilon, J.J.; Svasek, J.N.; In 't Veld, J.K.; Verhagen, H.J.

1981-01-01

When longshore sediment transport is interrupted by a construction along a coast, e.g harbour moles or a dredged approach channel, the equilibrium of the coastline may be disturbed. When the disruption is caused by breakwaters, the longshore transport that is held back will cause accretion updrift

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

Science.gov (United States)

2012-01-01

Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted. PMID:22891821

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

Directory of Open Access Journals (Sweden)

Ebdrup Bjørn H

2012-08-01

Full Text Available Abstract Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1. Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted.

Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

Science.gov (United States)

Lu, Siyuan; Madhukar, Anupam

2013-02-01

Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

Resting potential, oncogene-induced tumorigenesis, and metastasis: the bioelectric basis of cancer in vivo

Science.gov (United States)

Lobikin, Maria; Chernet, Brook; Lobo, Daniel; Levin, Michael

2012-12-01

Cancer may result from localized failure of instructive cues that normally orchestrate cell behaviors toward the patterning needs of the organism. Steady-state gradients of transmembrane voltage (Vmem) in non-neural cells are instructive, epigenetic signals that regulate pattern formation during embryogenesis and morphostatic repair. Here, we review molecular data on the role of bioelectric cues in cancer and present new findings in the Xenopus laevis model on how the microenvironment's biophysical properties contribute to cancer in vivo. First, we investigated the melanoma-like phenotype arising from serotonergic signaling by ‘instructor’ cells—a cell population that is able to induce a metastatic phenotype in normal melanocytes. We show that when these instructor cells are depolarized, blood vessel patterning is disrupted in addition to the metastatic phenotype induced in melanocytes. Surprisingly, very few instructor cells need to be depolarized for the hyperpigmentation phenotype to occur; we present a model of antagonistic signaling by serotonin receptors that explains the unusual all-or-none nature of this effect. In addition to the body-wide depolarization-induced metastatic phenotype, we investigated the bioelectrical properties of tumor-like structures induced by canonical oncogenes and cancer-causing compounds. Exposure to carcinogen 4-nitroquinoline 1-oxide (4NQO) induces localized tumors, but has a broad (and variable) effect on the bioelectric properties of the whole body. Tumors induced by oncogenes show aberrantly high sodium content, representing a non-invasive diagnostic modality. Importantly, depolarized transmembrane potential is not only a marker of cancer but is functionally instructive: susceptibility to oncogene-induced tumorigenesis is significantly reduced by forced prior expression of hyperpolarizing ion channels. Importantly, the same effect can be achieved by pharmacological manipulation of endogenous chloride channels, suggesting

Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments.

Science.gov (United States)

Jin, Faguang; Li, Congcong

2017-06-01

Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration.

Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments

Science.gov (United States)

Jin, Faguang; Li, Congcong

2017-01-01

Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration. PMID:28587319

Potential for parasite-induced biases in aquatic invertebrate population studies

Science.gov (United States)

Fisher, Justin D.L.; Mushet, David M.; Stockwell, Craig A.

2014-01-01

Recent studies highlight the need to include estimates of detection/capture probability in population studies. This need is particularly important in studies where detection and/or capture probability is influenced by parasite-induced behavioral alterations. We assessed potential biases associated with sampling a population of the amphipod Gammarus lacustris in the presence of Polymorphus spp. acanthocephalan parasites shown to increase positive phototaxis in their amphipod hosts. We trapped G. lacustris at two water depths (benthic and surface) and compared number of captures and number of parasitized individuals at each depth. While we captured the greatest number of G. lacustris individuals in benthic traps, parasitized individuals were captured most often in surface traps. These results reflect the phototaxic movement of infected individuals from benthic locations to sunlit surface waters. We then explored the influence of varying infection rates on a simulated population held at a constant level of abundance. Simulations resulted in increasingly biased abundance estimates as infection rates increased. Our results highlight the need to consider parasite-induced biases when quantifying detection and/or capture probability in studies of aquatic invertebrate populations.

Effect of a two-dimensional potential on the rate of thermally induced escape over the potential barrier

International Nuclear Information System (INIS)

Han, S.; Lapointe, J.; Lukens, J.E.

1992-01-01

The thermally induced escape rate of a particle trapped in a two-dimensional (2D) potential well has been investigated through experiment and numerical simulations. The measurements were performed on a special type of superconducting quantum interference device (SQUID) which has 2 degrees of freedom. The energies associated with the motion perpendicular to (transverse) and along (longitudinal) the escape direction are quite different: the ratio between the transverse and longitudinal small oscillation frequencies is ω t /ω l ∼7. The SQUID's parameters, which were used to determine the potential shape and energy scales were all independently determined. All data were obtained under conditions for which the 2D thermal activation (TA) model is expected to be valid. The results were found in good agreement with the theoretical prediction. The measured thermal activation energy is found to be the same as the barrier height calculated from the independently determined potential parameters. No evidence of apparent potential barrier enhancement recently reported in a similar system was found. In addition, the results of our numerical simulations suggest that the region in which the 2D thermal activation model is applicable may be extended to barriers as low as ΔU∼k BT

β2-Adrenergic Receptor Activation Suppresses the Rat Phenethylamine Hallucinogen-Induced Head Twitch Response: Hallucinogen-Induced Excitatory Post-synaptic Potentials as a Potential Substrate

Science.gov (United States)

Marek, Gerard J.; Ramos, Brian P.

2018-01-01

5-Hydroxytryptamine2A (5-HT2A) receptors are enriched in layers I and Va of the rat prefrontal cortex and neocortex and their activation increases the frequency of glutamatergic excitatory post-synaptic potentials/currents (EPSP/Cs) onto layer V pyramidal cells. A number of other G-protein coupled receptors (GPCRs) are also enriched in cortical layers I and Va and either induce (α1-adrenergic and orexin2) or suppress (metabotropic glutamate2 [mGlu2], adenosine A1, μ-opioid) both 5-HT-induced EPSCs and head twitches or head shakes induced by the phenethylamine hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Another neurotransmitter receptor also localized to apparent thalamocortical afferents to layers I and Va of the rat prefrontal cortex and neocortex is the β2-adrenergic receptor. Therefore, we conducted preliminary electrophysiological experiments with rat brain slices examining the effects of epinephrine on electrically-evoked EPSPs following bath application of DOI (3 μM). Epinephrine (0.3–10 μM) suppressed the late EPSPs produced by electrical stimulation and DOI. The selective β2-adrenergic receptor antagonist ICI-118,551 (300 nM) resulted in a rightward shift of the epinephrine concentration-response relationship. We also tested the selective β2-adrenergic receptor agonist clenbuterol and the antagonist ICI-118,551 on DOI-induced head twitches. Clenbuterol (0.3–3 mg/kg, i.p.) suppressed DOI (1.25 mg/kg, i.p.)-induced head twitches. This clenbuterol effect appeared to be at least partially reversed by the selective β2-adrenergic receptor antagonist ICI-118,553 (0.01–1 mg/kg, i.p.), with significant reversal at doses of 0.1 and 1 mg/kg. Thus, β2-adrenergic receptor activation reverses the effects of phenethylamine hallucinogens in the rat prefrontal cortex. While Gi/Go-coupled GPCRs have previously been shown to suppress both the electrophysiological and behavioral effects of 5-HT2A receptor activation in the mPFC, the present work appears

Pilot Study on Potential Impacts of Fisheries-Induced Changes in Zooplankton Mortality on Marine Biogeochemistry

Science.gov (United States)

Getzlaff, Julia; Oschlies, Andreas

2017-11-01

In this pilot study we link the yield of industrial fisheries to changes in the zooplankton mortality in an idealized way accounting for different target species (planktivorous fish—decreased zooplankton mortality; large predators—increased zooplankton mortality). This indirect approach is used in a global coupled biogeochemistry circulation model to estimate the range of the potential impact of industrial fisheries on marine biogeochemistry. The simulated globally integrated response on phytoplankton and primary production is in line with expectations—a high (low) zooplankton mortality results in a decrease (increase) of zooplankton and an increase (decrease) of phytoplankton. In contrast, the local response of zooplankton and phytoplankton depends on the region under consideration: In nutrient-limited regions, an increase (decrease) in zooplankton mortality leads to a decrease (increase) in both zooplankton and phytoplankton biomass. In contrast, in nutrient-replete regions, such as upwelling regions, we find an opposing response: an increase (decrease) of the zooplankton mortality leads to an increase (decrease) in both zooplankton and phytoplankton biomass. The results are further evaluated by relating the potential fisheries-induced changes in zooplankton mortality to those driven by CO2 emissions in a business-as-usual 21st century emission scenario. In our idealized case, the potential fisheries-induced impact can be of similar size as warming-induced changes in marine biogeochemistry.

Calcium-Induced calcium release during action potential firing in developing inner hair cells.

Science.gov (United States)

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

2015-03-10

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages.

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Ulrike Kuebler

Full Text Available BACKGROUND: Psychological stress delays wound healing but the precise underlying mechanisms are unclear. Macrophages play an important role in wound healing, in particular by killing microbes. We hypothesized that (a acute psychological stress reduces wound-induced activation of microbicidal potential of human monocyte-derived macrophages (HMDM, and (b that these reductions are modulated by stress hormone release. METHODS: Fourty-one healthy men (mean age 35 ± 13 years were randomly assigned to either a stress or stress-control group. While the stress group underwent a standardized short-term psychological stress task after catheter-induced wound infliction, stress-controls did not. Catheter insertion was controlled. Assessing the microbicidal potential, we investigated PMA-activated superoxide anion production by HMDM immediately before and 1, 10 and 60 min after stress/rest. Moreover, plasma norepinephrine and epinephrine and salivary cortisol were repeatedly measured. In subsequent in vitro studies, whole blood was incubated with norepinephrine in the presence or absence of phentolamine (norepinephrine blocker before assessing HMDM microbicidal potential. RESULTS: Compared with stress-controls, HMDM of the stressed subjects displayed decreased superoxide anion-responses after stress (p's <.05. Higher plasma norepinephrine levels statistically mediated lower amounts of superoxide anion-responses (indirect effect 95% CI: 4.14-44.72. Norepinephrine-treated HMDM showed reduced superoxide anion-production (p<.001. This effect was blocked by prior incubation with phentolamine. CONCLUSIONS: Our results suggest that acute psychological stress reduces wound-induced activation of microbicidal potential of HMDM and that this reduction is mediated by norepinephrine. This might have implications for stress-induced impairment in wound healing.

Automated Data Collection for Determining Statistical Distributions of Module Power Undergoing Potential-Induced Degradation

DEFF Research Database (Denmark)

Hacke, Peter; Spataru, Sergiu

We propose a method for increasing the frequency of data collection and reducing the time and cost of accelerated lifetime testing of photovoltaic modules undergoing potential-induced degradation (PID). This consists of in-situ measurements of dark current-voltage curves of the modules at elevate...

Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells

Directory of Open Access Journals (Sweden)

Tang XJ

2016-10-01

Full Text Available Xiang-Jun Tang,1,* Kuan-Ming Huang,1,* Hui Gui,1,* Jun-Jie Wang,2 Jun-Ti Lu,1 Long-Jun Dai,1,3 Li Zhang,1 Gang Wang2 1Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan, 2Department of Pharmaceutics, Shanghai Eighth People’s Hospital, Jiangsu University, Shanghai, People’s Republic of China; 3Department of Surgery, University of British Columbia, Vancouver, BC, Canada *These authors contributed equally to this work Abstract: As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viability was assessed using a methylthiazol tetrazolium assay and a real-time cell analyzer. Immunoblotting and quantitative reverse transcriptase polymerase chain reaction techniques were used for determining the expression levels of related molecules in protein and mRNA. The results indicated that myricetin-induced cytotoxicity was highly potentiated by the encapsulation of myricetin. Mitochondrial apoptotic pathway was demonstrated to be involved in myricetin-induced glioblastoma cell death. The epidermal growth factor receptor (EGFR/PI3K/Akt pathway located in the plasma membrane and cytosol and the RAS-ERK pathway located in mitochondria served as upstream and downstream targets, respectively, in myricetin-induced apoptosis. MiR-21 inhibitors interrupted the expression of EGFR, p-Akt, and K-Ras in the same fashion as myricetin-loaded mixed micelles (MYR-MCs and miR-21 expression were dose-dependently inhibited by MYR-MCs, indicating the interaction of miR-21 with MYR-MCs. This study provided evidence

Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

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GURPREET KAUR

2015-03-01

Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

8 CFR 258.3 - Action upon arrival.

Science.gov (United States)

2010-01-01

..., docks, or real estate; possible environmental contamination; or possible injury or death to a person, a... OF LONGSHORE WORK BY ALIEN CREWMEN § 258.3 Action upon arrival. (a) The master or agent of the vessel... so. (b) If nonimmigrant crewmen will perform longshore work, the master or agent of the vessel shall...

Electrostatic potential fluctuation induced by charge discreteness in a nanoscale trench

International Nuclear Information System (INIS)

Lee, Taesang; Kim, S. S.; Jho, Y. S.; Park, Gunyoung; Chang, C. S.

2007-01-01

A simplified two-dimensional Monte Carlo simulation is performed to estimate the charging potential fluctuations caused by strong binary Coulomb interactions between discrete charged particles in nanometer scale trenches. It is found that the discrete charge effect can be an important part of the nanoscale trench research, inducing scattering of ion trajectories in a nanoscale trench by a fluctuating electric field. The effect can enhance the ion deposition on the side walls and disperse the material contact energy of the incident ions, among others

Disorder-induced trapping versus Anderson localization in Bose-Einstein condensates expanding in disordered potentials

International Nuclear Information System (INIS)

Sanchez-Palencia, L; Clement, D; Lugan, P; Bouyer, P; Aspect, A

2008-01-01

We theoretically investigate the localization of an expanding Bose-Einstein condensate (BEC) with repulsive atom-atom interactions in a disordered potential. We focus on the regime where the initial inter-atomic interactions dominate over the kinetic energy and the disorder. At equilibrium in a trapping potential and for the considered small disorder, the condensate shows a Thomas-Fermi shape modified by the disorder. When the condensate is released from the trap, a strong suppression of the expansion is obtained in contrast to the situation in a periodic potential with similar characteristics. This effect crucially depends on both the momentum distribution of the expanding BEC and the strength of the disorder. For strong disorder as in the experiments reported by Clement et al 2005 Phys. Rev. Lett. 95 170409 and Fort et al 2005 Phys. Rev. Lett. 95 170410, the suppression of the expansion results from the fragmentation of the core of the condensate and from classical reflections from large modulations of the disordered potential in the tails of the condensate. We identify the corresponding disorder-induced trapping scenario for which large atom-atom interactions and strong reflections from single modulations of the disordered potential play central roles. For weak disorder, the suppression of the expansion signals the onset of Anderson localization, which is due to multiple scattering from the modulations of the disordered potential. We compute analytically the localized density profile of the condensate and show that the localization crucially depends on the correlation function of the disorder. In particular, for speckle potentials the long-range correlations induce an effective mobility edge in 1D finite systems. Numerical calculations performed in the mean-field approximation support our analysis for both strong and weak disorder

Potential of high pressure homogenization to induce autolysis of wine yeasts.

Science.gov (United States)

Comuzzo, Piergiorgio; Calligaris, Sonia; Iacumin, Lucilla; Ginaldi, Federica; Palacios Paz, Anthony Efrain; Zironi, Roberto

2015-10-15

High pressure homogenization (HPH) was tested for inducing autolysis in a commercial strain of Saccharomyces bayanus for winemaking. The effects on cell viability, the release of soluble proteins, glucidic colloids and amino acids in wine-like medium and the volatile composition of the autolysates were investigated after processing, in comparison with thermolysis. HPH seemed a promising technique for inducing autolysis of wine yeasts. One pass at 150 MPa was the best operating conditions. Soluble colloids, proteins and free amino acids were similar after HPH and thermolysis, but the former gave a more interesting volatile composition after processing, with higher concentrations of ethyl esters (fruity odors) and lower fatty acids (potential off-flavors). This might allow different winemaking applications for HPH, such as the production of yeast derivatives for wine ageing. In the conditions tested, HPH did not allow the complete inactivation of yeast cells; the treatment shall be optimized before winemaking use. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electromechanical Assessment of Human Knee Articular Cartilage with Compression-Induced Streaming Potentials.

Science.gov (United States)

Becher, Christoph; Ricklefs, Marcel; Willbold, Elmar; Hurschler, Christof; Abedian, Reza

2016-01-01

To assess the electromechanical properties of human knee articular cartilage with compression-induced streaming potentials for reliability among users and correlation with macroscopic and histological evaluation tools and sulfated glycosaminoglycan (sGAG) content. Streaming potentials are induced in cartilage in response to loading when mobile positive ions in the interstitial fluid temporarily move away from negatively charged proteoglycans. Streaming potential integrals (SPIs) were measured with an indentation probe on femoral condyles of 10 human knee specimens according to a standardized location scheme. Interobserver reliability was measured using an interclass correlation coefficient (ICC). The learning curves of 3 observers were evaluated by regression analysis. At each SPI measurement location the degradation level of the tissue was determined by means of the International Cartilage Repair Society (ICRS) score, Mankin score, and sGAG content. The computed ICC was 0.77 (0.70-0.83) indicating good to excellent linear agreement of SPI values among the 3 users. A significant positive linear correlation of the learning index values was observed for 2 of the 3 users. Statistically significant negative correlations between SPI and both ICRS and Mankin scores were observed (r = 0.502, P < 0.001, and r = 0.255, P = 0.02, respectively). No correlation was observed between SPI and sGAG content (r = 0.004, P = 0.973). SPI values may be used as a quantitative means of cartilage evaluation with sufficient reliability among users. Due to the significant learning curve, adequate training should be absolved before routine use of the technique.

Detection of Potential Induced Degradation in c-Si PV Panels Using Electrical Impedance Spectroscopy

DEFF Research Database (Denmark)

Oprea, Matei-lon; Spataru, Sergiu; Sera, Dezso

2016-01-01

This work, for the first time, investigates an Impedance Spectroscopy (IS) based method for detecting potential-induced degradation (PID) in crystalline silicon photovoltaic (c-Si PV) panels. The method has been experimentally tested on a set of panels that were confirmed to be affected by PID...

ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes

Directory of Open Access Journals (Sweden)

Guodong Pan

2016-01-01

Full Text Available Aldehyde dehydrogenase (ALDH gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress. H9C2 cardiomyocyte cell lines were pretreated with 10 μM disulfiram (DSF, an inhibitor of ALDH2 or vehicle (DMSO for 2 hours, and then subjected to high glucose stress {33 mM D-glucose (HG or 33 mM D-mannitol as an osmotic control (Ctrl} for 24 hrs. The decrease in ALDH2 activity with DSF pretreatment was higher in HG group when compared to Ctrl group. Increased 4HNE adduct formation with DSF pretreatment was higher in HG group compared to Ctrl group. Pretreatment with DSF leads to potentiated HG-induced cell death in cultured H9C2 cardiomyocytes by lowering mitochondrial membrane potential. Our results indicate that ALDH2 activity is important in preventing high glucose induced cellular dysfunction.

Rosewood oil induces sedation and inhibits compound action potential in rodents.

Science.gov (United States)

de Almeida, Reinaldo Nóbrega; Araújo, Demétrius Antonio Machado; Gonçalves, Juan Carlos Ramos; Montenegro, Fabrícia Costa; de Sousa, Damião Pergentino; Leite, José Roberto; Mattei, Rita; Benedito, Marco Antonio Campana; de Carvalho, José Gilberto Barbosa; Cruz, Jader Santos; Maia, José Guilherme Soares

2009-07-30

Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

River delta shoreline reworking and erosion in the Mediterranean and Black Seas: the potential roles of fluvial sediment starvation and other factors

Directory of Open Access Journals (Sweden)

Manon Besset

2017-09-01

Full Text Available The Mediterranean basin (including the Black Sea is characterized by a plethora of deltas that have developed in a wave-influenced setting. Many of these deltas are sourced in sediments by river catchments that have been variably dammed. The vulnerability status of a selection of ten deltas subject to different levels of reduction in fluvial sediment supply following damming was analysed by quantifying changes in delta protrusion area and protrusion angle over the last 30 years. The rationale for choosing these two metrics, which do not require tricky calculations of longshore bedload transport volumes and river ‘influence’, is that as sediment supply wanes, increasing relative efficiency of waves leads to longshore redistribution of reworked sediments and progressive ‘flattening’ of the delta protrusion. The results show that eight of the ten deltas (Nile, Rhône, Ebro, Ceyhan, Arno, Ombrone, Moulouya, Medjerda are in erosion, whereas two (Danube, Po show stability, but the statistical relationship between change in delta protrusion area and sediment flux reduction is poor, thus suggesting that the role of dams in causing delta shoreline erosion may have been over-estimated. But this poor relationship could also be due to a long temporal lag between dam construction and bedload removal and transport to the coast downstream of dams, and, where the delta protrusion is being eroded, to bedload trapping by shoreline engineering structures and by elongating delta-flank spits. Other potential influential factors in shoreline change include subsidence, sea-level rise, storminess, exceptional river floods, and managed sediment releases downstream of dams. A longer observation period and high-resolution sediment-budget studies will be necessary to determine more definitively to which extent continued trapping of sediment behind dams will impact overall delta stability in the Mediterranean and Black Seas. Mitigation of delta erosion is likely to

In vitro growth potential of fibroblasts isolated from pigs with radiation-induced fibrosis

International Nuclear Information System (INIS)

Martin, M.; Remy, J.; Daburon, F.

1986-01-01

Degenerative processes were studied in pig muscles irradiated with single doses of 30 or 40 Gy. Damaged muscle was gradually replaced by an invasive fibrotic tissue. As a control, surgical muscle exeresis was performed of the same size as the radiation-induced lesions at the same anatomical site. Primary cultures were set up comprising cells freshly extracted from normal dermis, or from tissue exhibiting either normal wound fibrosis or radiation-induced fibrosis. The growth potential of cells taken from the latter region far exceeded that of the two other types; attachment efficiency was higher, and fibronectin was detected early by immunofluorescence. These in vivo and in vitro observations imply that a pathological repair process occurs after localized irradiation. (author)

Antigenotoxic potential of Asparagus racemosus root extract against electron beam radiation induced micronuclei formation in Swiss albino mice

International Nuclear Information System (INIS)

Bhandary, B. Satheesh Kumar; Sharmila, K.P.; Suchetha Kumari, N.; Bhat, Vadish S.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.; Fernandes, Ronald

2016-01-01

To evaluate the antigenotoxic potential of Asparagus Racemosus Root ethanolic extract (ARE) against electron beam radiation induced micronuclei formation in Swiss albino mice. Micronucleus assay was performed in the bone marrow of Swiss albino mice according to the method of Hosseinimehr et al., 2003. The experimental animals were orally administered 200 mg/kg body weight of ARE once daily for 15 consecutive days. At the end of experimental period, the animals were euthanized and the bone marrow was collected from the femur. Control (C), Radiation control (RC) and drug control (DC) group was also maintained. The number of radiation induced Micronucleated Polychromatic Erythrocytes (MnPCE) and Micronucleated Normochromatic Erythrocytes were decreased in the ARE treated mice which was statistically significant (p<0.05) compared to radiation control group. Present findings demonstrate the antigenotoxic potential of ARE against electron beam radiation induced micronuclei formation which may be attributed to scavenging of radiation-induced free radicals

Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation.

Science.gov (United States)

Michael, G; Dempster, J; Kane, K A; Coker, S J

2007-12-01

Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether IKs blockade or enhancement of INa could potentiate TdP induced by IKr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. Experiments were performed in open-chest, pentobarbital-anaesthetized, alpha 1-adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the IKr blocker E-4031 (1, 3 and 10 nmol kg(-1) min(-1)), the IKs blocker HMR1556 (25, 75 and 250 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. In a second study rabbits received either the same doses of E-4031, the INa enhancer, ATX-II (0.4, 1.2 and 4.0 nmol kg(-1)) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded. HMR1556 alone did not cause TdP but increased E-4031-induced TdP from 25 to 80%. ATX-II alone caused TdP in 38% of rabbits, as did E-4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred. Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP.

Chronic alcohol feeding potentiates hormone-induced calcium signalling in hepatocytes.

Science.gov (United States)

Bartlett, Paula J; Antony, Anil Noronha; Agarwal, Amit; Hilly, Mauricette; Prince, Victoria L; Combettes, Laurent; Hoek, Jan B; Gaspers, Lawrence D

2017-05-15

Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined. We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca 2+ -mobilizing hormones resulting in a leftward shift in the concentration-response relationship and the transition from oscillatory to more sustained and prolonged Ca 2+ increases. Our data demonstrate that alcohol-dependent adaptation in the Ca 2+ signalling pathway occurs at the level of hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) production and does not involve changes in the sensitivity of the IP 3 receptor or size of internal Ca 2+ stores. We suggest that prolonged and aberrant hormone-evoked Ca 2+ increases may stimulate the production of mitochondrial reactive oxygen species and contribute to alcohol-induced hepatocyte injury. ABSTRACT: 'Adaptive' responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide-dependent cytosolic calcium ([Ca 2+ ] i ) increases, which can adversely affect mitochondrial Ca 2+ levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose-response for Ca 2+ -mobilizing hormones resulting in more sustained and prolonged [Ca 2+ ] i increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca 2+ increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. Acute alcohol treatment (25 mm) completely inhibited hormone-induced calcium increases in control livers, but not after chronic alcohol-feeding, suggesting desensitization to the inhibitory actions of ethanol. Hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) accumulation and phospholipase C

Evaluation of the Potential of Brazilian Propolis against UV-Induced Oxidative Stress

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Yris Maria Fonseca

2011-01-01

Full Text Available This study investigated the potential use of topically and orally administered propolis extracts to prevent UV irradiation-induced oxidative stress in skin. The results illustrated that green propolis extract (GPE contained greater amounts of polyphenols, coumaric acid, drupanin, baccharin and artepillin C than did brown propolis extract (BPE. GPE showed higher antioxidant activity than BPE when the IC50 (concentration that caused 50% inhibition values were compared. Interesting, the oral treatment of hairless mice demonstrated a recovery of 30.0% for GPE and 22.8% for BPE with respect to UV irradiation-induced GSH depletion. The topical pretreatment of animals with both propolis extract solutions recovered around 14.0% of the depleted GSH. However, the employed treatments did not inhibit the increase of cutaneous proteinase secretion/activity caused by irradiation. These findings indicate that despite differences in composition and antioxidant properties, GPE and BPE both successfully prevent UV-induced GSH depletion in vivo and are both promising antioxidant systems against oxidative stress in skin. Based on these findings, complementary studies should be performed to enhance our understanding of the protective effects of propolis extracts in skin.

Anticancer Potential of Nutraceutical Formulations in MNU-induced Mammary Cancer in Sprague Dawley Rats.

Science.gov (United States)

Pitchaiah, Gummalla; Akula, Annapurna; Chandi, Vishala

2017-01-01

Nutraceuticals help in combating some of the major health problems of the century including cancer, and 'nutraceutical formulations' have led to the new era of medicine and health. To develop different nutraceutical formulations and to assess the anticancer potential of nutraceutical formulations in N-methyl-N-nitrosourea (MNU)-induced mammary cancer in Sprague Dawley rats. Different nutraceutical formulations were prepared using fine powders of amla, apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed. The anticancer potential of nutraceutical formulations was evaluated against MNU-induced mammary cancer in female Sprague Dawley rats. Improvement in total phenolic content was significant ( P safe to use in animals. Microbial load was within the limits. Significant longer tumor-free days ( P apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed. The anticancer potential of nutraceutical formulations was evaluated against MNU-induced mammary cancer in female Sprague Dawley rats. Improvement in total phenolic content was observed after self-fortification process. Toxicity studies showed that the nutraceutical formulations were safe to use in animals. Microbial load was within the limits. Longer tumor-free days, lower tumor incidence, lower tumor multiplicity and tumor burden were observed for nutraceutical formulation-treated groups. This suggests that combination of whole food-based nutraceuticals acted synergistically in the prevention of mammary cancer. Further, the process of fortification enhanced the anticancer potential of nutraceutical formulations. Abbreviations used: HMNU: N-methyl-N-nitrosourea, CAM: Complementary and Alternative Medicine, NF: Nutraceutical

Spectral induced polarization and electrodic potential monitoring of microbially mediated iron sulfide transformations

Energy Technology Data Exchange (ETDEWEB)

Hubbard, Susan; Personna, Y.R.; Ntarlagiannis, D.; Slater, L.; Yee, N.; O' Brien, M.; Hubbard, S.

2008-02-15

Stimulated sulfate-reduction is a bioremediation technique utilized for the sequestration of heavy metals in the subsurface.We performed laboratory column experiments to investigate the geoelectrical response of iron sulfide transformations by Desulfo vibriovulgaris. Two geoelectrical methods, (1) spectral induced polarization (SIP), and (2) electrodic potential measurements, were investigated. Aqueous geochemistry (sulfate, lactate, sulfide, and acetate), observations of precipitates (identified from electron microscopy as iron sulfide), and electrodic potentials on bisulfide ion (HS) sensitive silver-silver chloride (Ag-AgCl) electrodes (630 mV) were diagnostic of induced transitions between an aerobic iron sulfide forming conditions and aerobic conditions promoting iron sulfide dissolution. The SIP data showed 10m rad anomalies during iron sulfide mineralization accompanying microbial activity under an anaerobic transition. These anomalies disappeared during iron sulfide dissolution under the subsequent aerobic transition. SIP model parameters based on a Cole-Cole relaxation model of the polarization at the mineral-fluid interface were converted to (1) estimated biomineral surface area to pore volume (Sp), and (2) an equivalent polarizable sphere diameter (d) controlling the relaxation time. The temporal variation in these model parameters is consistent with filling and emptying of pores by iron sulfide biofilms, as the system transitions between anaerobic (pore filling) and aerobic (pore emptying) conditions. The results suggest that combined SIP and electrodic potential measurements might be used to monitor spatiotemporal variability in microbial iron sulfide transformations in the field.

Therapeutic potential of alpha-ketoglutarate against acetaminophen-induced hepatotoxicity in rats

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Lalita Mehra

2016-01-01

Full Text Available Objective: Alpha-ketoglutarate (α-KG is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP induced toxicity in rats. Materials and Methods: Animals were divided into three groups of six animals each. Group I (Vehicle control: Normal Saline, Group II (APAP: A single intraperitoneal injection of 0.6 g/kg, Group III (APAP + α-KG: APAP as in Group II with α-KG treatment at a dose of 2 g/kg, orally for 5 days. Then the levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP with oxidative stress markers including malondialdehyde (MDA, reduced glutathione (GSH, superoxide dismutase (SOD, catalase (CAT, and histopathology were analyzed. Results: The results indicate that APAP caused significant elevations in ALT, AST, ALP, and MDA levels, while GSH, SOD, and CAT were significantly depleted while co-administration of α-KG showed a significant (P < 0.05 reduction in the severity of these damages. Histologically, the liver showed inflammation and necrosis after APAP treatment, which were significantly restored with co-administration of α-KG. Conclusion: These results indicate the possible therapeutic potential of α-KG in protecting liver damage by APAP in rats.

Urban stress-induced biogenic VOC emissions and SOA-forming potentials in Beijing

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A. Ghirardo

2016-03-01

Full Text Available Trees can significantly impact the urban air chemistry by the uptake and emission of reactive biogenic volatile organic compounds (BVOCs, which are involved in ozone and particle formation. Here we present the emission potentials of "constitutive" (cBVOCs and "stress-induced" BVOCs (sBVOCs from the dominant broadleaf woody plant species in the megacity of Beijing. Based on the municipal tree census and cuvette BVOC measurements on leaf level, we built an inventory of BVOC emissions, and assessed the potential impact of BVOCs on secondary organic aerosol (SOA formation in 2005 and 2010, i.e., before and after realizing the large tree-planting program for the 2008 Olympic Games. We found that sBVOCs, such as fatty acid derivatives, benzenoids, and sesquiterpenes, constituted a significant fraction ( ∼  40 % of the total annual BVOC emissions, and we estimated that the overall annual BVOC budget may have doubled from  ∼  4.8  ×  109 g C year−1 in 2005 to  ∼  10.3  ×  109 g C year−1 in 2010 due to the increase in urban greening, while at the same time the emission of anthropogenic VOCs (AVOCs decreased by 24 %. Based on the BVOC emission assessment, we estimated the biological impact on SOA mass formation potential in Beijing. Constitutive and stress-induced BVOCs might produce similar amounts of secondary aerosol in Beijing. However, the main contributors of SOA-mass formations originated from anthropogenic sources (> 90 %. This study demonstrates the general importance to include sBVOCs when studying BVOC emissions. Although the main problems regarding air quality in Beijing still originate from anthropogenic activities, the present survey suggests that in urban plantation programs, the selection of low-emitting plant species has some potential beneficial effects on urban air quality.

Channel Dredging and Geomorphic Response at and Adjacent to Mobile Pass, Alabama

Science.gov (United States)

2010-09-01

Aug 3 Gulf Shores, AL 1 974 80 Erin 1995 Oct 4 Perdido Key, FL 3 938 110 Opal 1997 Jul 19 Mobile Pass, AL 1 987 65 Danny 1998 Sept 28 Ship Island...study evaluating the potential impacts of offshore sand mining on coastal change. Overall, many authors discuss the effect of hurricanes on...longshore sand transport rate for the ocean fronting portion of Dauphin Island. As such, potential uncertainty calculations can be deter- mined relative

The potential of virus-induced gene silencing for speeding up functional characterization of plant genes

NARCIS (Netherlands)

Benedito, V.A.; Visser, P.B.; Angenent, G.C.; Krens, F.A.

2004-01-01

Virus-induced gene silencing (VIGS) has been shown to be of great potential in plant reverse genetics. Advantages of VIGS over other approaches, such as T-DNA or transposon tagging, include the circumvention of plant transformation, methodological simplicity and robustness, and speedy results. These

Appropriate bare potentials for studying fusion induced by 6He

International Nuclear Information System (INIS)

Crema, E; Chamon, L.C; Gomes, P.R.S.

2007-01-01

best way to constrain the choice of the bare potential to be used, since their heights and shapes should be reproduced by the calculations. However, great experimental work is demanded to obtain the barrier distribution, and so far this was not achieved with low-intensity radioactive beams. In order to overcome these difficulties, we have shown recently [3] that the parameter-free Sao Paulo potential (SPP) [4, 5] is a reliable bare interaction for studying fusion of systems involving stable weakly-bound nuclei in situations in which experimental barrier distributions cannot be obtained. As it is deduced from fundamental grounds, the SPP does not contain the limitations discussed above and does not contain any adjustable parameter. In this seminar we will show that the SPP is an appropriate bare potential in the study of fusion reactions induced by the radioactive weakly-bound nucleus 6 He. (Author)

Hepatoprotective Potential of Propolis toward Hepar Injury Rats (Rattus norvegicus Induced by Carbon Tetrachloride

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Diah Krisnansari

2016-09-01

Full Text Available Introduction: The prevalence of chronic liver disease continues to increase. One potentially hepatotoxic substances that cause chronic liver disease is carbon tetrachloride. The process of liver damage can be prevented by the antioxidant role of propolis. The aims of this research was to study the hepatoprotective potential of propolis toward hepar injury rats induced by carbon tetrachlorida. Method: This was an experimental study with pre-post test. Twenty five male Wistar rats aged 12–16 week old, weighing 125–200 gr were allocated into 5 groups. Group I: standard meal + aquadest-gavage; group II: standard meal + CCl4 1% 1 mL + aquadest-gavage, group III: standard meal + CCl4 1% 1 mL + 0,054 gr propolis-gavage, group IV: standard meal + CCl4 1% 1 mL + 0,108 gr propolis-gavage and group V: standard meal + CCl4 1% 1 mL + sylimarin 50 mg/kg-gavage. IL-6, SOD, NAS score+fibrotic were measured after treatment. Analysed of IL-6 and NAS score+fibrotic with Kruskal Wallis to Mann Whitney and analysed of SOD with One-Way ANOVA to LSD. Results: The study showed that there were significant differences in IL-6, SOD and NAS score + fibrotic between groups. Discussion: Provision of 0,054 gr and 0,108 gr have hepatoprotective potential toward hepar injury rats induced by carbon tetrachlorida. Further research need to identify antioxidants and hepatoprotective potential of propolis on human with liver disease. Keywords: IL-6, SOD, fibrotic, propolis

Nuclear Spiral Shocks and Induced Gas Inflows in Weak Oval Potentials

Energy Technology Data Exchange (ETDEWEB)

Kim, Woong-Tae [Department of Physics and Astronomy, Seoul National University, Seoul 151-742 (Korea, Republic of); Elmegreen, Bruce G., E-mail: wkim@astro.snu.ac.kr, E-mail: bge@us.ibm.com [IBM T. J. Watson Research Center, 1101 Kitchawan Road, Yorktown Heights, NY 10598 (United States)

2017-05-20

Nuclear spirals are ubiquitous in galaxy centers. They exist not only in strong barred galaxies but also in galaxies without noticeable bars. We use high-resolution hydrodynamic simulations to study the properties of nuclear gas spirals driven by weak bar-like and oval potentials. The amplitude of the spirals increases toward the center by a geometric effect, readily developing into shocks at small radii even for very weak potentials. The shape of the spirals and shocks depends rather sensitively on the background shear. When shear is low, the nuclear spirals are loosely wound and the shocks are almost straight, resulting in large mass inflows toward the center. When shear is high, on the other hand, the spirals are tightly wound and the shocks are oblique, forming a circumnuclear disk through which gas flows inward at a relatively lower rate. The induced mass inflow rates are enough to power black hole accretion in various types of Seyfert galaxies as well as to drive supersonic turbulence at small radii.

Implication of microRNAs in the development and potential treatment of radiation-induced heart disease.

Science.gov (United States)

Kura, Branislav; Babal, Pavel; Slezak, Jan

2017-10-01

Radiotherapy is the most commonly used methodology to treat oncological disease, one of the most widespread causes of death worldwide. Oncological patients cured by radiotherapy applied to the mediastinal area have been shown to suffer from cardiovascular disease. The increase in the prevalence of radiation-induced heart disease has emphasized the need to seek new therapeutic targets to mitigate the negative impact of radiation on the heart. In this regard, microRNAs (miRNAs) have received considerable interest. miRNAs regulate post-transcriptional gene expression by their ability to target various mRNA sequences because of their imperfect pairing with mRNAs. It has been recognized that miRNAs modulate a diverse spectrum of cardiac functions with developmental, pathophysiological, and clinical implications. This makes them promising potential targets for diagnosis and treatment. This review summarizes the recent findings about the possible involvement of miRNAs in radiation-induced heart disease and their potential use as diagnostic or treatment targets in this respect.

Influence of the external conditions on salt retention and pressure-induced electrical potential measured across a composite membrane

DEFF Research Database (Denmark)

Benavente, Juana; Jonsson, Gunnar Eigil

1999-01-01

Transport on single electrolyte solutions (NaCl and MgCl2) due to pressure gradients across a commercial reverse osmosis membrane was studied by measuring volume flux (J(v)), salt rejection (S) and pressure induced electrical potential (Delta E) in a crossflow cell. The influence on these paramet......Transport on single electrolyte solutions (NaCl and MgCl2) due to pressure gradients across a commercial reverse osmosis membrane was studied by measuring volume flux (J(v)), salt rejection (S) and pressure induced electrical potential (Delta E) in a crossflow cell. The influence......, r = 1, 0.5 and 0.1), respectively. Results show that J(v), S and Delta E values slightly increase when the velocity of the feed solution increases, but the mixed electrolytes strongly affect both salt rejection and pressure-induced electrical potential. A change in the sign of both parameters...... with respect to the value determined with single electrolytes at the same concentration was obtained, which is attributed to a strong coupling among the fluxes of individual ions and their distribution in the membrane when transport of mixed salt is studied. (C) 1999 Elsevier Science B.V. All rights reserved....

A population genetic analysis of the potential for a crude oil spill to induce heritable mutations and impact natural populations

Energy Technology Data Exchange (ETDEWEB)

Cronin, M.A. [LGL Alaska Research Associates Inc., Anchorage, AK (United States); Bickham, J.W. [Texas A and M University, College Station, TX (United States). Dept. of Wildlife and Fisheries Sciences; LGL Ecological Genetics Inc., Bryan, TX (United States)

1998-07-01

The primary environmental impact following an oil spill typically is acute toxicity to fish and wildlife. However, multigenerational effects through toxicant-induced heritable mutations might also occur. Some polycyclic aromatic hydrocarbon (PAH) components of crude oil are potentially mutagenic, although specific components and doses that induce mutations are poorly known. We applied population genetics concepts to assess the extent of mortality and the persistence of deleterious heritable mutations resulting from exposure to potential mutagens, such as crude oil. If lethal mutations are induced, the population will experience some mortality, but the mutations are quickly removed or reduced to low frequency by natural selection. This occurs within one or a few generations when mutations are dominant or partially recessive. Totally recessive alleles persist in low frequency for many generations, but result in relatively little impact on the population, depending on the number of mutated loci. We also applied population genetics concepts to assess the potential for heritable mutations induced by the Exxon Valdez oil spill in Prince William Sound, Alaska, to affect pink salmon populations. We stress that breeding units (e.g., streams with distinct spawning populations of salmon) must be considered individually to assess heritable genetic effects. For several streams impacted by the oil spill, there is inconsistency between observed egg mortality and that expected if lethal heritable mutations had been induced by exposure to crude oil. Observed mortality was either higher or lower than expected depending on the spawning population, year, and cohort considered. Any potential subtle effect of lethal mutations induced by the Exxon Valdez oil spill is overridden by natural environmental variation among spawning areas. We discuss the need to focus on population-level effects in toxicological assessments because fish and wildlife management focuses on populations, not

Pipeline grounding condition: A control of pipe-to-soil potential for AC interference induced corrosion reduction

CSIR Research Space (South Africa)

Adedeji, KB

2017-02-01

Full Text Available The interference effect from high voltage overhead lines on nearby metallic pipelines is a major challenge for utility owners due to the induced AC potentials on metallic pipelines. Nevertheless, numerous mitigation techniques have been proposed...

Improved single particle potential for transport model simulations of nuclear reactions induced by rare isotope beams

International Nuclear Information System (INIS)

Xu Chang; Li Baoan

2010-01-01

Taking into account more accurately the isospin dependence of nucleon-nucleon interactions in the in-medium many-body force term of the Gogny effective interaction, new expressions for the single-nucleon potential and the symmetry energy are derived. Effects of both the spin (isospin) and the density dependence of nuclear effective interactions on the symmetry potential and the symmetry energy are examined. It is shown that they both play a crucial role in determining the symmetry potential and the symmetry energy at suprasaturation densities. The improved single-nucleon potential will be useful for more accurate simulation of nuclear reactions induced by rare-isotope beams within transport models.

Apoptosis induced by low-intensity ultrasound in vitro: Alteration of protein profile and potential molecular mechanism

Science.gov (United States)

Feng, Yi; Wan, Mingxi

2017-03-01

To analyze the potential mechanism related to the apoptosis induced by low intensity focused ultrasound, comparative proteomic method was introduced in the study. After ultrasound irradiation (3.0 W/cm2, 1 minute, 6 hours incubation post-irradiation), the human SMMC-7721 hepatocarcinoma cells were stained by trypan blue to detect the morphologic changes, and then the percentage of early apoptosis were tested by the flow cytometry with double staining of FITC-labelled Annexin V/Propidium iodide. Two-dimensional SDS polyacrylamide gel electrophoresis was used to get the protein profile and some proteins differently expressed after ultrasound irradiation were identified by MALDI-TOF mass spectrometry. It's proved early apoptosis of cells were induced by low intentisy focused ultrasound. After ultrasound irradiation, the expressing characteristics of several proteins changed, in which protein p53 and heat shock proteins are associated with apoptosis initiation. It is suggested that the low-intensity ultrasound-induced apoptotic cancer therapy has the potential application via understanding its relevant molecular signaling and key proteins. Moreover, the comparative proteomic method is proved to be useful to supply information about the protein expression to analyze the metabolic processes related to bio-effects of biomedical ultrasound.

The potential of induced pluripotent stem cell derived hepatocytes.

Science.gov (United States)

Hannoun, Zara; Steichen, Clara; Dianat, Noushin; Weber, Anne; Dubart-Kupperschmitt, Anne

2016-07-01

Orthotopic liver transplantation remains the only curative treatment for liver disease. However, the number of patients who die while on the waiting list (15%) has increased in recent years as a result of severe organ shortages; furthermore the incidence of liver disease is increasing worldwide. Clinical trials involving hepatocyte transplantation have provided encouraging results. However, transplanted cell function appears to often decline after several months, necessitating liver transplantation. The precise aetiology of the loss of cell function is not clear, but poor engraftment and immune-mediated loss appear to be important factors. Also, primary human hepatocytes (PHH) are not readily available, de-differentiate, and die rapidly in culture. Hepatocytes are available from other sources, such as tumour-derived human hepatocyte cell lines and immortalised human hepatocyte cell lines or porcine hepatocytes. However, all these cells suffer from various limitations such as reduced or differences in functions or risk of zoonotic infections. Due to their significant potential, one possible inexhaustible source of hepatocytes is through the directed differentiation of human induced pluripotent stem cells (hiPSCs). This review will discuss the potential applications and existing limitations of hiPSC-derived hepatocytes in regenerative medicine, drug screening, in vitro disease modelling and bioartificial livers. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Involvement of microglia activation in the lead induced long-term potentiation impairment.

Directory of Open Access Journals (Sweden)

Ming-Chao Liu

Full Text Available Exposure of Lead (Pb, a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α, interleukin-1β (IL-1β and inducible nitric oxide synthase (iNOS in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits.

Tunneling and traversal of ultracold three-level atoms through vacuum-induced potentials

Energy Technology Data Exchange (ETDEWEB)

Badshah, Fazal; Irfan, Muhammad; Qamar, Shahid [Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences, Nilore, Islamabad 45650 (Pakistan); Qamar, Sajid [Department of Physics, COMSATS Institute of Information Technology, Islamabad (Pakistan)

2011-09-15

The passage of ultracold three-level atoms through the potential induced by the vacuum cavity mode is discussed using cascade atomic configuration. We study the tunneling or traversal time of the ultracold atoms via a bimodal high-Q cavity. It is found that the phase time, which may be considered as a measure for the time required to traverse the cavity, exhibits superclassical and subclassical behaviors. Further, the dark states and interference effects in cascade atomic configuration may influence the passage time of the atom through the cavity.

Tunneling and traversal of ultracold three-level atoms through vacuum-induced potentials

International Nuclear Information System (INIS)

Badshah, Fazal; Irfan, Muhammad; Qamar, Shahid; Qamar, Sajid

2011-01-01

The passage of ultracold three-level atoms through the potential induced by the vacuum cavity mode is discussed using cascade atomic configuration. We study the tunneling or traversal time of the ultracold atoms via a bimodal high-Q cavity. It is found that the phase time, which may be considered as a measure for the time required to traverse the cavity, exhibits superclassical and subclassical behaviors. Further, the dark states and interference effects in cascade atomic configuration may influence the passage time of the atom through the cavity.

Effects of momentum-dependent symmetry potential on heavy-ion collisions induced by neutron-rich nuclei

International Nuclear Information System (INIS)

Li Baoan; Das, Champak B.; Das Gupta, Subal; Gale, Charles

2004-01-01

Using an isospin- and momentum-dependent transport model we study effects of the momentum-dependent symmetry potential on heavy-ion collisions induced by neutron-rich nuclei. It is found that symmetry potentials with and without the momentum-dependence but corresponding to the same density-dependent symmetry energy E sym (ρ) lead to significantly different predictions on several E sym (ρ)-sensitive experimental observables especially for energetic nucleons. The momentum- and density-dependence of the symmetry potential have to be determined simultaneously in order to extract the E sym (ρ) accurately. The isospin asymmetry of midrapidity nucleons at high transverse momenta is particularly sensitive to the momentum-dependence of the symmetry potential. It is thus very useful for investigating accurately the equation of state of dense neutron-rich matter

Assessment of Rainfall-induced Landslide Potential and Spatial Distribution

Science.gov (United States)

Chen, Yie-Ruey; Tsai, Kuang-Jung; Chen, Jing-Wen; Chiang, Jie-Lun; Hsieh, Shun-Chieh; Chue, Yung-Sheng

2016-04-01

Recently, due to the global climate change, most of the time the rainfall in Taiwan is of short duration but with high intensity. Due to Taiwan's steep terrain, rainfall-induced landslides often occur and lead to human causalities and properties loss. Taiwan's government has invested huge reconstruction funds to the affected areas. However, after rehabilitation they still face the risk of secondary sediment disasters. Therefore, this study assesses rainfall-induced (secondary) landslide potential and spatial distribution in watershed of Southern Taiwan under extreme climate change. The study areas in this research are Baolai and Jianshan villages in the watershed of the Laonongxi River Basin in the Southern Taiwan. This study focused on the 3 years after Typhoon Morakot (2009 to 2011). During this period, the study area experienced six heavy rainfall events including five typhoons and one heavy rainfall. The genetic adaptive neural network, texture analysis and GIS were implemented in the analysis techniques for the interpretation of satellite images and to obtain surface information and hazard log data and to analyze land use change. A multivariate hazards evaluation method was applied to quantitatively analyze the weights of various natural environmental and slope development hazard factors. Furthermore, this study established a slope landslide potential assessment model and depicted a slope landslide potential diagram by using the GIS platform. The interaction between (secondary) landslide mechanism, scale, and location was analyzed using association analysis of landslide historical data and regional environmental characteristics. The results of image classification before and after six heavy rainfall events show that the values of coefficient of agreement are at medium-high level. By multivariate hazards evaluation method, geology and the effective accumulative rainfall (EAR) are the most important factors. Slope, distance from fault, aspect, land disturbance

PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications.

Science.gov (United States)

Barreiro, Esther; Gea, Joaquim

2018-01-26

Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic inhibition of PARP activity attenuated the deleterious effects seen on depleted muscles in mouse models of oncologic cachexia. In the present minireview the mechanisms whereby PARP activity inhibition may improve muscle mass and performance in models of cancer-induced cachexia are discussed. Specifically, the beneficial effects of inhibition of PARP activity on attenuation of increased oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial content and epigenetic modulation of muscle phenotype are reviewed in this article. Finally, the potential therapeutic strategies of pharmacological PARP activity inhibition for the treatment of cancer-induced cachexia are also being described in this review.

Prediction of phospholipidosis-inducing potential of drugs by in vitro biochemical and physicochemical assays followed by multivariate analysis.

Science.gov (United States)

Kuroda, Yukihiro; Saito, Madoka

2010-03-01

An in vitro method to predict phospholipidosis-inducing potential of cationic amphiphilic drugs (CADs) was developed using biochemical and physicochemical assays. The following parameters were applied to principal component analysis, as well as physicochemical parameters: pK(a) and clogP; dissociation constant of CADs from phospholipid, inhibition of enzymatic phospholipid degradation, and metabolic stability of CADs. In the score plot, phospholipidosis-inducing drugs (amiodarone, propranolol, imipramine, chloroquine) were plotted locally forming the subspace for positive CADs; while non-inducing drugs (chlorpromazine, chloramphenicol, disopyramide, lidocaine) were placed scattering out of the subspace, allowing a clear discrimination between both classes of CADs. CADs that often produce false results by conventional physicochemical or cell-based assay methods were accurately determined by our method. Basic and lipophilic disopyramide could be accurately predicted as a nonphospholipidogenic drug. Moreover, chlorpromazine, which is often falsely predicted as a phospholipidosis-inducing drug by in vitro methods, could be accurately determined. Because this method uses the pharmacokinetic parameters pK(a), clogP, and metabolic stability, which are usually obtained in the early stages of drug development, the method newly requires only the two parameters, binding to phospholipid, and inhibition of lipid degradation enzyme. Therefore, this method provides a cost-effective approach to predict phospholipidosis-inducing potential of a drug. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Anti-glaucoma potential of Heliotropium indicum Linn in experimentally-induced glaucoma.

Science.gov (United States)

Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Owusu-Afriyie, Osei

2015-01-01

Heliotropium indicum is used as a traditional remedy for hypertension in Ghana. The aim of the study was to evaluate the anti-glaucoma potential of an aqueous whole plant extract of H. indicum to manage experimentally-induced glaucoma. The percentage change in intraocular pressure (IOP), after inducing acute glaucoma (15 mLkg(-1) of 5 % dextrose, i.v.), in New Zealand White rabbits pretreated with Heliotropium indicum aqueous extract (HIE) (30-300 mgkg(-1)), acetazolamide (5 mgkg(-1)), and normal saline (10 mLkg(-1)) per os were measured. IOPs were also monitored in chronic glaucoma in rabbits (induced by 1 % prednisolone acetate drops, 12 hourly for 21 days) after treatments with the same doses of HIE, acetazolamide, and normal saline for 2 weeks. The anti-oxidant property of the extract was assessed by assaying for glutathione levels in the aqueous humour. Glutamate concentration in the vitreous humour was also determined using ELISA technique. Histopathological assessment of the ciliary bodies was made. The extract significantly reduced intraocular pressure (p ≤ 0.05-0.001) in acute and chronic glaucoma, preserved glutathione levels and glutamate concentration (p ≤ 0.01-0.001). Histological assessment of the ciliary body showed a decrease in inflammatory infiltration in the extract and acetazolamide-treated group compared with the normal saline-treated group. The aqueous whole plant extract of Heliotropium indicum has ocular hypotensive, anti-oxidant and possible neuro-protective effects, which therefore underscore its plausible utility as an anti-glaucoma drug with further investigation.

Potential role of an antimicrobial peptide, KLK in inhibiting lipopolysaccharide-induced macrophage inflammation.

Directory of Open Access Journals (Sweden)

Pornpimon Jantaruk

Full Text Available Antimicrobial peptides (AMPs are attractive alternatives to antibiotics. Due to their immune modulatory properties, AMPs are at present emerging as promising agents for controlling inflammatory-mediated diseases. In this study, anti-inflammatory potential of an antimicrobial peptide, KLK (KLKLLLLLKLK and its analogs was evaluated in lipopolysaccharide (LPS-induced RAW 264.7 macrophages. The results herein demonstrated that KLK peptide as well as its analogs significantly inhibited the pro-inflammatory mediator nitric oxide (NO, interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α production in LPS-stimulated RAW 264.7 macrophages in dose-dependent manners, and such inhibitory effects were not due to direct cytotoxicity. When considering inhibition potency, KLK among the test peptides exhibited the most effective activity. The inhibitory activity of KLK peptide also extended to include suppression of LPS-induced production of prostaglandin E2 (PGE2. KLK significantly decreased mRNA and protein expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 as well as mRNA expression of IL-1β and TNF-α. Moreover, KLK inhibited nuclear translocation of nuclear factor-κB (NF-κB p65 and blocked degradation and phosphorylation of inhibitor of κB (IκB. Taken together, these results suggested that the KLK peptide inhibited inflammatory response through the down-regulation of NF-κB mediated activation in macrophages. Since peptide analogs with different amino acid sequences and arrangement were investigated for their anti-inflammatory activities, the residues/structures required for activity were also discussed. Our findings therefore proved anti-inflammatory potential of the KLK peptide and provide direct evidence for therapeutic application of KLK as a novel anti-inflammatory agent.

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

International Nuclear Information System (INIS)

Fang, Zhong-Ze; Zhang, Dunfang; Cao, Yun-Feng; Xie, Cen; Lu, Dan; Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao; Chen, Qianming; Chen, Yu; Wang, Haina; Gonzalez, Frank J.

2016-01-01

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4 + naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4 + naive T cells.

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

Energy Technology Data Exchange (ETDEWEB)

Fang, Zhong-Ze [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin (China); Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian (China); Zhang, Dunfang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu (China); Cao, Yun-Feng [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian (China); Xie, Cen [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Lu, Dan [Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin (China); Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Chen, Qianming; Chen, Yu [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu (China); Wang, Haina [School of Pharmaceutical Sciences, Shandong University, Jinan (China); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)

2016-01-15

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.

Protective property of mulberry digest against oxidative stress - A potential approach to ameliorate dietary acrylamide-induced cytotoxicity.

Science.gov (United States)

Zhang, Linxia; Xu, Yang; Li, Yuting; Bao, Tao; Gowd, Vemana; Chen, Wei

2017-09-01

The aim of this study was investigating the protective effect of mulberry digest (MBD) on acrylamide-induced oxidative stress. Composition analysis of MBD revealed that it contained six major phenolic compounds (quercetin-3-O-rutinoside, quercetin hexoside, quercetin rhamnosylhexoside hexoside, kaempferol rhamnosylhexoside, cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside). After in vitro digestion, the contents of two anthocyanins were both decreased significantly, while the contents of four flavonoid glycosides were all increased. In addition, MBD was found to successfully suppress acrylamide-induced ROS overproduction, restore the mitochondrial membrane potential, and inhibit the mitochondrial membrane lipid peroxidation and glutathione depletion. More interestingly, the protective effect of MBD against acrylamide-induced oxidative damage was enhanced compared with mulberry fruits without digestion (MBE). Further study revealed that MBD enhanced the cell resistance capacity to acrylamide-induced oxidative stress, rather than its direct reaction with acrylamide. Overall, our results indicate that MBD provides a potent protection against acrylamide-induced oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

Science.gov (United States)

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

2012-01-01

BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

Potential candidate genomic biomarkers of drug induced vascular injury in the rat

International Nuclear Information System (INIS)

Dalmas, Deidre A.; Scicchitano, Marshall S.; Mullins, David; Hughes-Earle, Angela; Tatsuoka, Kay; Magid-Slav, Michal; Frazier, Kendall S.; Thomas, Heath C.

2011-01-01

Drug-induced vascular injury is frequently observed in rats but the relevance and translation to humans present a hurdle for drug development. Numerous structurally diverse pharmacologic agents have been shown to induce mesenteric arterial medial necrosis in rats, but no consistent biomarkers have been identified. To address this need, a novel strategy was developed in rats to identify genes associated with the development of drug-induced mesenteric arterial medial necrosis. Separate groups (n = 6/group) of male rats were given 28 different toxicants (30 different treatments) for 1 or 4 days with each toxicant given at 3 different doses (low, mid and high) plus corresponding vehicle (912 total rats). Mesentery was collected, frozen and endothelial and vascular smooth muscle cells were microdissected from each artery. RNA was isolated, amplified and Affymetrix GeneChip® analysis was performed on selectively enriched samples and a novel panel of genes representing those which showed a dose responsive pattern for all treatments in which mesenteric arterial medial necrosis was histologically observed, was developed and verified in individual endothelial cell- and vascular smooth muscle cell-enriched samples. Data were confirmed in samples containing mesentery using quantitative real-time RT-PCR (TaqMan™) gene expression profiling. In addition, the performance of the panel was also confirmed using similarly collected samples obtained from a timecourse study in rats given a well established vascular toxicant (Fenoldopam). Although further validation is still required, a novel gene panel has been developed that represents a strategic opportunity that can potentially be used to help predict the occurrence of drug-induced mesenteric arterial medial necrosis in rats at an early stage in drug development. -- Highlights: ► A gene panel was developed to help predict rat drug-induced mesenteric MAN. ► A gene panel was identified following treatment of rats with 28

Accelerated Testing and Modeling of Potential-Induced Degradation as a Function of Temperature and Relative Humidity

DEFF Research Database (Denmark)

Hacke, Peter; Spataru, Sergiu; Terwilliger, Kent

2015-01-01

An acceleration model based on the Peck equation was applied to power performance of crystalline silicon cell modules as a function of time and of temperature and humidity, which are the two main environmental stress factors that promote potential-induced degradation (PID). This model was derived...

Accelerated Testing and Modeling of Potential-Induced Degradation as a Function of Temperature and Relative Humidity

DEFF Research Database (Denmark)

Hacke, Peter; Spataru, Sergiu; Terwilliger, Kent

2015-01-01

An acceleration model based on the Peck equation was applied to power performance of crystalline silicon cell modules as a function of time and of temperature and humidity, the two main environmental stress factors that promote potential-induced degradation. This model was derived from module pow...

Anticancer Potential of Nutraceutical Formulations in MNU-induced Mammary Cancer in Sprague Dawley Rats

OpenAIRE

Pitchaiah, Gummalla; Akula, Annapurna; Chandi, Vishala

2017-01-01

Background: Nutraceuticals help in combating some of the major health problems of the century including cancer, and ?nutraceutical formulations? have led to the new era of medicine and health. Objective: To develop different nutraceutical formulations and to assess the anticancer potential of nutraceutical formulations in N-methyl-N-nitrosourea (MNU)-induced mammary cancer in Sprague Dawley rats. Materials and Methods: Different nutraceutical formulations were prepared using fine powders of a...

A preliminary census of engineering activities located in Sicily (Southern Italy) which may "potentially" induce seismicity

Science.gov (United States)

Aloisi, Marco; Briffa, Emanuela; Cannata, Andrea; Cannavò, Flavio; Gambino, Salvatore; Maiolino, Vincenza; Maugeri, Roberto; Palano, Mimmo; Privitera, Eugenio; Scaltrito, Antonio; Spampinato, Salvatore; Ursino, Andrea; Velardita, Rosanna

2015-04-01

The seismic events caused by human engineering activities are commonly termed as "triggered" and "induced". This class of earthquakes, though characterized by low-to-moderate magnitude, have significant social and economical implications since they occur close to the engineering activity responsible for triggering/inducing them and can be felt by the inhabitants living nearby, and may even produce damage. One of the first well-documented examples of induced seismicity was observed in 1932 in Algeria, when a shallow magnitude 3.0 earthquake occurred close to the Oued Fodda Dam. By the continuous global improvement of seismic monitoring networks, numerous other examples of human-induced earthquakes have been identified. Induced earthquakes occur at shallow depths and are related to a number of human activities, such as fluid injection under high pressure (e.g. waste-water disposal in deep wells, hydrofracturing activities in enhanced geothermal systems and oil recovery, shale-gas fracking, natural and CO2 gas storage), hydrocarbon exploitation, groundwater extraction, deep underground mining, large water impoundments and underground nuclear tests. In Italy, induced/triggered seismicity is suspected to have contributed to the disaster of the Vajont dam in 1963. Despite this suspected case and the presence in the Italian territory of a large amount of engineering activities "capable" of inducing seismicity, no extensive researches on this topic have been conducted to date. Hence, in order to improve knowledge and correctly assess the potential hazard at a specific location in the future, here we started a preliminary study on the entire range of engineering activities currently located in Sicily (Southern Italy) which may "potentially" induce seismicity. To this end, we performed: • a preliminary census of all engineering activities located in the study area by collecting all the useful information coming from available on-line catalogues; • a detailed compilation

Manipulation of resonant tunneling by substrate-induced inhomogeneous energy band gaps in graphene with square superlattice potentials

International Nuclear Information System (INIS)

Li, Guanqiang; Chen, Guangde; Peng, Ping; Cao, Zhenzhou; Ye, Honggang

2013-01-01

We investigate the resonant transmission of Dirac electrons through inhomogeneous band gap graphene with square superlattice potentials by transfer matrix method. The effects of the incident angle of the electrons, Fermi energy and substrate-induced Dirac gaps on the transmission are considered. It is found that the Dirac gap of graphene adds another degree of freedom with respect to the incident angle, the Fermi energy and the parameters of periodic superlattice potentials (i.e., the number, width and height of the barriers) for the transmission. In particular, the inhomogeneous Dirac gap induced by staggered substrates can be used to manipulate the transmission. The properties of the conductance and Fano factor at the resonant peaks are found to be affected by the gaps significantly. The results may be helpful for the practical application of graphene-based electronic devices

The potential biological mechanisms of arsenic-induced diabetes mellitus

International Nuclear Information System (INIS)

Tseng, C.-H.

2004-01-01

Although epidemiologic studies carried out in Taiwan, Bangladesh, and Sweden have demonstrated a diabetogenic effect of arsenic, the mechanisms remain unclear and require further investigation. This paper reviewed the potential biological mechanisms of arsenic-induced diabetes mellitus based on the current knowledge of the biochemical properties of arsenic. Arsenate can substitute phosphate in the formation of adenosine triphosphate (ATP) and other phosphate intermediates involved in glucose metabolism, which could theoretically slow down the normal metabolism of glucose, interrupt the production of energy, and interfere with the ATP-dependent insulin secretion. However, the concentration of arsenate required for such reaction is high and not physiologically relevant, and these effects may only happen in acute intoxication and may not be effective in subjects chronically exposed to low-dose arsenic. On the other hand, arsenite has high affinity for sulfhydryl groups and thus can form covalent bonds with the disulfide bridges in the molecules of insulin, insulin receptors, glucose transporters (GLUTs), and enzymes involved in glucose metabolism (e.g., pyruvate dehydrogenase and α-ketoglutarate dehydrogenase). As a result, the normal functions of these molecules can be hampered. However, a direct effect on these molecules caused by arsenite at physiologically relevant concentrations seems unlikely. Recent evidence has shown that treatment of arsenite at lower and physiologically relevant concentrations can stimulate glucose transport, in contrary to an inhibitory effect exerted by phenylarsine oxide (PAO) or by higher doses of arsenite. Induction of oxidative stress and interferences in signal transduction or gene expression by arsenic or by its methylated metabolites are the most possible causes to arsenic-induced diabetes mellitus through mechanisms of induction of insulin resistance and β cell dysfunction. Recent studies have shown that, in subjects with chronic

Biological dosimetry: the potential use of radiation-induced apoptosis in human T-lymphocytes

International Nuclear Information System (INIS)

Menz, R.; Andres, R.; Larsson, B.; Ozsahin, M.; Crompton, N.E.A.; Trott, K.

1997-01-01

An assay for biological dosimetry based on the induction of apoptosis in human T-lymphocytes is described. Radiation-induced apoptosis was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation. CD4 and CD8 T-lymphocytes were analysed. They were recognized on the basis of their cell-surface antigens. Four parameters were measured for both cell types: cell size, granularity, antigen immunofluorescence and DNA content. Apoptosis was quantified as the fraction of CD4-, or CD8-positive cells with a characteristic reduction of cell size and DNA content. At doses below 1 Gy, levels of radiation-induced apoptosis increased for up to 5 days after irradiation. Optimal dose discrimination was observed 4 days after irradiation, at which time the dose-response curves were linear, with a slope of 8% ± 0.5% per 0.1 Gy. In controlled, dose-response experiments the lowest dose level at which the radiation-induced apoptosis frequency was still significantly above control was 0.05 Gy. After 5 days post-irradiation incubation, intra- and interdonor variations were measured and found to be similar; thus, apoptotic levels depend more on the dose than on the donor. The results demonstrate the potential of this assay as a biological dosimeter. (orig.)

Glucosylceramide and Lysophosphatidylcholines as Potential Blood Biomarkers for Drug-Induced Hepatic Phospholipidosis

Science.gov (United States)

Saito, Kosuke; Maekawa, Keiko; Ishikawa, Masaki; Senoo, Yuya; Urata, Masayo; Murayama, Mayumi; Nakatsu, Noriyuki; Yamada, Hiroshi; Saito, Yoshiro

2014-01-01

Drug-induced phospholipidosis is one of the major concerns in drug development and clinical treatment. The present study involved the use of a nontargeting lipidomic analysis with liquid chromatography-mass spectrometry to explore noninvasive blood biomarkers for hepatic phospholipidosis from rat plasma. We used three tricyclic antidepressants (clomipramine [CPM], imipramine [IMI], and amitriptyline [AMT]) for the model of phospholipidosis in hepatocytes and ketoconazole (KC) for the model of phospholipidosis in cholangiocytes and administered treatment for 3 and 28 days each. Total plasma lipids were extracted and measured. Lipid molecules contributing to the separation of control and drug-treated rat plasma in a multivariate orthogonal partial least squares discriminant analysis were identified. Four lysophosphatidylcholines (LPCs) (16:1, 18:1, 18:2, and 20:4) and 42:1 hexosylceramide (HexCer) were identified as molecules separating control and drug-treated rats in all models of phospholipidosis in hepatocytes. In addition, 16:1, 18:2, and 20:4 LPCs and 42:1 HexCer were identified in a model of hepatic phospholipidosis in cholangiocytes, although LPCs were identified only in the case of 3-day treatment with KC. The levels of LPCs were decreased by drug-induced phospholipidosis, whereas those of 42:1 HexCer were increased. The increase in 42:1 HexCer was much higher in the case of IMI and AMT than in the case of CPM; moreover, the increase induced by IMI was dose-dependent. Structural characterization determining long-chain base and hexose delineated that 42:1 HexCer was d18:1/24:0 glucosylceramide (GluCer). In summary, our study demonstrated that d18:1/24:0 GluCer and LPCs are potential novel biomarkers for drug-induced hepatic phospholipidosis. PMID:24980264

Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

Directory of Open Access Journals (Sweden)

Heera Ram

2014-01-01

Full Text Available Acacia senegal L. (Fabaceae seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil for 15 days. Circulating total cholesterol (TC, HDL-cholesterol (HDL-C, LDL-cholesterol (LDL-C, triglycerides, and VLDL-cholesterol (VLDL-C levels; atherogenic index (AI; cardiac lipid peroxidation (LPO; planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34±0.72 and increased lumen volume (51.65±3.66, administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o. for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics.

Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin.

Science.gov (United States)

Waseem, Mohammad; Parvez, Suhel

2016-03-01

Peripheral neurotoxicity is one of the serious dose-limiting side effects of oxaliplatin (Oxa) when used in the treatment of malignant conditions. It is documented that it elicits major side effects specifically neurotoxicity due to oxidative stress forcing the patients to limit its clinical use in long-term treatment. Oxidative stress has been proven to be involved in Oxa-induced toxicity including neurotoxicity. The mitochondria have recently emerged as targets for anticancer drugs in various kinds of toxicity including neurotoxicity that can lead to neoplastic disease. However, there is paucity of literature involving the role of the mitochondria in mediating Oxa-induced neurotoxicity and its underlying mechanism is still debatable. The purpose of this study was to investigate the dose-dependent damage caused by Oxa on isolated brain mitochondria under in vitro conditions. The study was also designed to investigate the neuroprotective effects of nutraceuticals, curcumin (CMN), and quercetin (QR) on Oxa-induced mitochondrial oxidative stress and respiratory chain complexes in the brain of rats. Oxidative stress biomarkers, levels of nonenzymatic antioxidants, activities of enzymatic antioxidants, and mitochondrial complexes were evaluated against the neurotoxicity induced by Oxa. Pretreatment with CMN and QR significantly replenished the mitochondrial lipid peroxidation levels and protein carbonyl content induced by Oxa. CMN and QR ameliorated altered nonenzymatic and enzymatic antioxidants and complex enzymes of mitochondria. We conclude that CMN and QR, by attenuating oxidative stress as evident by mitochondrial dysfunction, hold promise as agents that can potentially reduce Oxa-induced adverse effects in the brain.

Environmentally induced epigenetic toxicity: potential public health concerns.

Science.gov (United States)

Marczylo, Emma L; Jacobs, Miriam N; Gant, Timothy W

2016-09-01

Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory in vivo high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection.

Large potential change induced by pellet injection in JIPP T-IIU tokamak plasmas

International Nuclear Information System (INIS)

Hamada, Y.; Sato, K.N.; Sakakita, H.

1995-05-01

A large, rapid change in the local plasma potential is found to be induced by off-axis hydrogen ice-pellet injection into a tokamak plasma. The polarity of the rapid change is reversed when the pellet is injected into the upper and lower halves of the poloidal plasma cross-section. This change can be interpreted as being due to the gradient-B drift of particles in the high-density plasmas of the pellet cloud, before the increase of the plasma density due to the ablation becomes uniform on the magnetic surface. (author)

Potentiation of lead-induced cell death in PC12 cells by glutamate: Protection by N-acetylcysteine amide (NACA), a novel thiol antioxidant

International Nuclear Information System (INIS)

Penugonda, Suman; Mare, Suneetha; Lutz, P.; Banks, William A.; Ercal, Nuran

2006-01-01

Oxidative stress has been implicated as an important factor in many neurological diseases. Oxidative toxicity in a number of these conditions is induced by excessive glutamate release and subsequent glutamatergic neuronal stimulation. This, in turn, causes increased generation of reactive oxygen species (ROS), oxidative stress, excitotoxicity, and neuronal damage. Recent studies indicate that the glutamatergic neurotransmitter system is involved in lead-induced neurotoxicity. Therefore, this study aimed to (1) investigate the potential effects of glutamate on lead-induced PC12 cell death and (2) elucidate whether the novel thiol antioxidant N-acetylcysteine amide (NACA) had any protective abilities against such cytotoxicity. Our results suggest that glutamate (1 mM) potentiates lead-induced cytotoxicity by increased generation of ROS, decreased proliferation (MTS), decreased glutathione (GSH) levels, and depletion of cellular adenosine-triphosphate (ATP). Consistent with its ability to decrease ATP levels and induce cell death, lead also increased caspase-3 activity, an effect potentiated by glutamate. Exposure to glutamate and lead elevated the cellular malondialdehyde (MDA) levels and phospholipase-A 2 (PLA 2 ) activity and diminished the glutamine synthetase (GS) activity. NACA protected PC12 cells from the cytotoxic effects of glutamate plus lead, as evaluated by MTS assay. NACA reduced the decrease in the cellular ATP levels and restored the intracellular GSH levels. The increased levels of ROS and MDA in glutamate-lead treated cells were significantly decreased by NACA. In conclusion, our data showed that glutamate potentiated the effects of lead-induced PC12 cell death by a mechanism involving mitochondrial dysfunction (ATP depletion) and oxidative stress. NACA had a protective role against the combined toxic effects of glutamate and lead by inhibiting lipid peroxidation and scavenging ROS, thus preserving intracellular GSH

Nonlinear dynamics in a trapped atomic Bose-Einstein condensate induced by an oscillating Gaussian potential

International Nuclear Information System (INIS)

Fujimoto, Kazuya; Tsubota, Makoto

2011-01-01

We consider a trapped atomic Bose-Einstein condensate penetrated by a repulsive Gaussian potential and theoretically investigate the dynamics induced by oscillating the Gaussian potential. Our study is based on the numerical calculation of the two-dimensional Gross-Pitaevskii equation. Our calculation reveals the dependence of the characteristic behavior of the condensate on the amplitude and frequency of the oscillating potential. These dynamics are deeply related to the nucleation and dynamics of quantized vortices and solitons. When the potential oscillates with a large amplitude, it nucleates many vortex pairs that move away from the potential. When the amplitude of the oscillation is small, it nucleates solitons through an annihilation of vortex pairs. We discuss three issues concerning the nucleation of vortices. The first is the phase diagram for the nucleation of vortices and solitons near the oscillating potential. The second is the mechanism and critical velocity of the nucleation. The critical velocity of the nucleation is an important issue in quantum fluids, and we propose an expression for the velocity containing both the coherence length and the size of the potential. The third is the divergence of the nucleation time, which is the time it takes for the potential to nucleate vortices, near the critical parameters for vortex nucleation.

Serotonin‐induced bistability of turtle motoneurones caused by a nifedipine‐sensitive calcium plateau potential

DEFF Research Database (Denmark)

Hounsgaard, J.; Kiehn, O.

1989-01-01

1. The effect of serotonin on the firing properties of motoneurones was studied in transverse sections of the adult turtle spinal cord in vitro with intracellular recording techniques. 2. In normal medium, turtle motoneurones adapt from an initial high frequency to a low steady firing during...... of the frequency jump was shortened as the amplitude of the activation pulse was increased. From a positive holding potential the after‐depolarization exceeded spike threshold and its duration increased with an increase in steady bias current. The effect of serotonin on turtle motoneurones could be blocked....... It is concluded that serotonin induces a Ca2+‐dependent and nifedipine‐sensitive plateau potential in turtle motoneurones primarily by reducing a K+‐current responsible for the slow after‐hyperpolarization....

Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

OpenAIRE

Bielecka, Magdalena K.; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E.; Christodoulides, Myron

2014-01-01

A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human protein...

Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

Science.gov (United States)

Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

2017-11-01

Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Blockade of Adrenal Medulla-Derived Epinephrine Potentiates Bee Venom-Induced Antinociception in the Mouse Formalin Test: Involvement of Peripheral β-Adrenoceptors

Directory of Open Access Journals (Sweden)

Suk-Yun Kang

2013-01-01

Full Text Available The injection of diluted bee venom (DBV into an acupoint has been used traditionally in eastern medicine to treat a variety of inflammatory chronic pain conditions. We have previously shown that DBV had a potent antinociceptive efficacy in several rodent pain models. However, the peripheral mechanisms underlying DBV-induced antinociception remain unclear. The present study was designed to investigate the role of peripheral epinephrine on the DBV-induced antinociceptive effect in the mouse formalin assay. Adrenalectomy significantly enhanced the antinociceptive effect of DBV during the late phase of the formalin test, while chemical sympathectomy had no effect. Intraperitoneal injection of epinephrine blocked this adrenalectomy-induced enhancement of the DBV-induced antinociceptive effect. Moreover, injection of a phenylethanolamine N-methyltransferase (PNMT inhibitor enhanced the DBV-induced antinociceptive effect. Administration of nonselective β-adrenergic antagonists also significantly potentiated this DBV-induced antinociception, in a manner similar to adrenalectomy. These results demonstrate that the antinociceptive effect of DBV treatment can be significantly enhanced by modulation of adrenal medulla-derived epinephrine and this effect is mediated by peripheral β-adrenoceptors. Thus, DBV acupoint stimulation in combination with inhibition of peripheral β-adrenoceptors could be a potentially novel strategy for the management of inflammatory pain.

Source Parameters from Full Moment Tensor Inversions of Potentially Induced Earthquakes in Western Canada

Science.gov (United States)

Wang, R.; Gu, Y. J.; Schultz, R.; Kim, A.; Chen, Y.

2015-12-01

During the past four years, the number of earthquakes with magnitudes greater than three has substantially increased in the southern section of Western Canada Sedimentary Basin (WCSB). While some of these events are likely associated with tectonic forces, especially along the foothills of the Canadian Rockies, a significant fraction occurred in previously quiescent regions and has been linked to waste water disposal or hydraulic fracturing. A proper assessment of the origin and source properties of these 'induced earthquakes' requires careful analyses and modeling of regional broadband data, which steadily improved during the past 8 years due to recent establishments of regional broadband seismic networks such as CRANE, RAVEN and TD. Several earthquakes, especially those close to fracking activities (e.g. Fox creek town, Alberta) are analyzed. Our preliminary full moment tensor inversion results show maximum horizontal compressional orientations (P-axis) along the northeast-southwest orientation, which agree with the regional stress directions from borehole breakout data and the P-axis of historical events. The decomposition of those moment tensors shows evidence of strike-slip mechanism with near vertical fault plane solutions, which are comparable to the focal mechanisms of injection induced earthquakes in Oklahoma. Minimal isotropic components have been observed, while a modest percentage of compensated-linear-vector-dipole (CLVD) components, which have been linked to fluid migraition, may be required to match the waveforms. To further evaluate the non-double-couple components, we compare the outcomes of full, deviatoric and pure double couple (DC) inversions using multiple frequency ranges and phases. Improved location and depth information from a novel grid search greatly assists the identification and classification of earthquakes in potential connection with fluid injection or extraction. Overall, a systematic comparison of the source attributes of

High potential oxidation-reduction titration of absorbance changes induced by pulsed laser and continuous light in chromatophores of photosynthesizing bacteria Rhodospirillum rubrum and Ectothiorhodospira shaposhnikovii

International Nuclear Information System (INIS)

Remennikov, S.M.; Chamorovsky, S.K.; Kononenko, A.A.; Venediktov, P.S.; Rubin, A.B.

1975-01-01

The photoreactions, activated both by pulsed laser and continuous light were studied in the membranes of isolated bacterial chromatophores poised at different oxidation-reduction potentials over a range of +200 mV to +500 mV. In Rhodospirillum rubrum a midpoint potential of oxidation-reduction curves for the laser-induced positive absorbance changes centred around 430 nm and carotenoid red shifts coincides with that for continuous light-induced absorbance changes, bleaching at 865 nm and blue shift at 800 nm, of the photosynthetic reaction centre bacteriochlorophyll. In Ectothiorhodospira shaposhnikovii the photosynthetic reaction centre bacteriochlorophyll, its photooxidation can be seen as light-induced absorbance changes, bleaching at 890 nm, blue shift at 800 nm and broad band appearance near 440 nm, has a midpoint oxidation-reduction potential of +390 mV at pH 7.4. The analysis of the oxidation-reduction titration curves for the high-potential c-type cytochrome absorbance changes induced both by pulsed laser and continuous light allowed to show that at least two haems of this cytochrome with a midpoint potential of +290 mV (pH 7.4), associated with each reaction centre bacteriochlorophyll, can donate electrons to the oxidized pigment directly

Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats

International Nuclear Information System (INIS)

Pouyatos, BenoIt; Gearhart, Caroline A.; Fechter, Laurence D.

2005-01-01

The diversity of chemical and drugs that can potentiate noise-induced hearing loss (NIHL) has impeded efforts to predict such interactions. We have hypothesized that chemical contaminants that disrupt intrinsic antioxidant defenses hold significant risk for potentiating NIHL. If this is true, then acrylonitrile (ACN) would be expected to potentiate NIHL. ACN, one of the 50 most commonly used chemicals in the United States, is metabolized via two pathways that are likely to disrupt intrinsic reactive oxygen species (ROS) buffering systems: (1) it conjugates glutathione, depleting this important antioxidant rapidly; (2) a second pathway involves the formation of cyanide, which can inhibit superoxide dismutase. We hypothesized that moderate noise exposure, that does not produce permanent hearing loss by itself, could initiate oxidative stress and that ACN could render the inner ear more sensitive to noise by disrupting intrinsic antioxidant defenses. Temporary and persistent effects of ACN alone (50 mg/kg, sc 5 days), noise alone (95 or 97 dB octave band noise, 4 h/day for 5 days), or ACN in combination with noise were determined using distortion product otoacoustic emissions (DPOAEs) and compound action potential (CAP) amplitudes. Histopathological damage to hair cells resulting from these treatments was also investigated using surface preparations of the organ of Corti. Individually, neither ACN nor noise exposures caused any permanent hearing or hair cell loss; only a reversible temporary threshold shift was measured in noise-exposed animals. However, when given in combination, ACN and noise induced permanent threshold shifts (13-16 dB between 7 and 40 kHz) and a decrease in DPOAE amplitudes (up to 25 dB at 19 kHz), as well as significant outer hair cell (OHC) loss (up to 20% in the first row between 13 and 47 kHz). This investigation demonstrates that ACN can potentiate NIHL at noise levels that are realistic in terms of human exposure, and that the OHCs are the

Inhibition of Autophagy Potentiates Atorvastatin-Induced Apoptotic Cell Death in Human Bladder Cancer Cells in Vitro

Science.gov (United States)

Kang, Minyong; Jeong, Chang Wook; Ku, Ja Hyeon; Kwak, Cheol; Kim, Hyeon Hoe

2014-01-01

Statins are cholesterol reduction agents that exhibit anti-cancer activity in several human cancers. Because autophagy is a crucial survival mechanism for cancer cells under stress conditions, cooperative inhibition of autophagy acts synergistically with other anti-cancer drugs. Thus, this study investigates whether combined treatment of atorvastatin and autophagy inhibitors results in enhancing the cytotoxic effects of atorvastatin, upon human bladder cancer cells, T24 and J82, in vitro. To measure cell viability, we performed the EZ-Cytox cell viability assay. We examined apoptosis by flow cytometry using annexin-V/propidium iodide (PI and western blot using procaspase-3 and poly (ADP-ribose) polymerase (PARP) antibodies. To examine autophagy activation, we evaluated the co-localization of LC3 and LysoTracker by immunocytochemistry, as well as the expression of LC3 and p62/sequestosome-1 (SQSTM1) by western blot. In addition, we assessed the survival and proliferation of T24 and J82 cells by a clonogenic assay. We found that atorvastatin reduced the cell viability of T24 and J82 cells via apoptotic cell death and induced autophagy activation, shown by the co-localization of LC3 and LysoTracker. Moreover, pharmacologic inhibition of autophagy significantly enhanced atorvastatin-induced apoptosis in T24 and J82 cells. In sum, inhibition of autophagy potentiates atorvastatin-induced apoptotic cell death in human bladder cancer cells in vitro, providing a potential therapeutic approach to treat bladder cancer. PMID:24815071

Potential-Induced Degradation-Delamination Mode in Crystalline Silicon Modules: Preprint

Energy Technology Data Exchange (ETDEWEB)

Hacke, Peter L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kempe, Michael D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Wohlgemuth, John [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Li, Jichao [SunPower Corporation; Shen, Yu-Chen [SunPower Corporation

2018-03-21

A test sequence producing potential-induced degradation-delamination (PID-d) in crystalline silicon modules has been tested and found comparable under visual inspection to cell/encapsulant delamination seen in some fielded modules. Four commercial modules were put through this sequence, 85 degrees C, 85%, 1000 h damp heat, followed by an intensive PID stress sequence of 72 degrees C, 95% RH, and -1000 V, with the module face grounded using a metal foil. The 60 cell c-Si modules exhibiting the highest current transfer (4.4 center dot 10-4 A) exhibited PID-d at the first inspection after 156 h of PID stress. Effects promoting PID-d are reduced adhesion caused by damp heat, sodium migration further reducing adhesion to the cells, and gaseous products of electrochemical reactions driven by the applied system voltage. A new work item proposal for an IEC test standard to evaluate for PID-d is anticipated.

Circulating MicroRNAs as Potential Biomarkers for Traumatic Brain Injury-Induced Hypopituitarism.

Science.gov (United States)

Taheri, Serpil; Tanriverdi, Fatih; Zararsiz, Gokmen; Elbuken, Gulsah; Ulutabanca, Halil; Karaca, Zuleyha; Selcuklu, Ahmet; Unluhizarci, Kursad; Tanriverdi, Kahraman; Kelestimur, Fahrettin

2016-10-15

Traumatic brain injury (TBI), a worldwide public health problem, has recently been recognized as a common cause of pituitary dysfunction. Circulating microRNAs (miRNAs) present in the sera are characteristically altered in many pathological conditions and have been used as diagnostic markers for specific diseases. It is with this goal that we planned to study miRNA expression in patients with TBI-induced hypopituitarism. Thirty-eight patients (27 male, 11 female; mean age, 43 ± 18 years) who had been admitted to the neurosurgery intensive care unit due to TBI were included in the acute phase of the study. In the chronic phase, miRNA expression profile blood samples were drawn from 25 patients who had suffered TBI 5 years ago. In the acute phase (on Days 1, 7, and 28), a substantial amount of patients (26%, 40%, and 53%; respectively) had hypopituitarism (acute adrenocorticotropic hormone deficiency). In the chronic phase eight of 25 patients (32%) had TBI-induced-hypopituitarism. Forty-seven age-gender-similar healthy controls (25 male, 22 female, mean age: 41 ± 14 years) were included in the study. In order to identify potential candidate miRNA/miRNAs whose levels had been altered in response to TBI-induced hypopituitarism, 740 miRNA expression analyses were performed in the sera of TBI patients by high throughput real-time polymerase chain reaction. Statistical analyses showed that miRNA-126-3p (miR-126-3p) and miRNA-3610 (miR-3610) were detected in the sera of patients who developed hypopituitarism on the 1st, 7th, and 28th days, and in the 5th year following TBI. In addition, miRNA-3907 showed statistically significant and constant dynamic changes on the 1st, 7th, and 28th days, and in the 5th year in the patients with TBI. Our results indicated that altered expression of miR-126-3p and miR-3610 may play an important role in the development of TBI-induced hypopituitarism.

Acute Elevated Glucose Promotes Abnormal Action Potential-Induced Ca2+ Transients in Cultured Skeletal Muscle Fibers

Directory of Open Access Journals (Sweden)

Erick O. Hernández-Ochoa

2017-01-01

Full Text Available A common comorbidity of diabetes is skeletal muscle dysfunction, which leads to compromised physical function. Previous studies of diabetes in skeletal muscle have shown alterations in excitation-contraction coupling (ECC—the sequential link between action potentials (AP, intracellular Ca2+ release, and the contractile machinery. Yet, little is known about the impact of acute elevated glucose on the temporal properties of AP-induced Ca2+ transients and ionic underlying mechanisms that lead to muscle dysfunction. Here, we used high-speed confocal Ca2+ imaging to investigate the temporal properties of AP-induced Ca2+ transients, an intermediate step of ECC, using an acute in cellulo model of uncontrolled hyperglycemia (25 mM, 48 h.. Control and elevated glucose-exposed muscle fibers cultured for five days displayed four distinct patterns of AP-induced Ca2+ transients (phasic, biphasic, phasic-delayed, and phasic-slow decay; most control muscle fibers show phasic AP-induced Ca2+ transients, while most fibers exposed to elevated D-glucose displayed biphasic Ca2+ transients upon single field stimulation. We hypothesize that these changes in the temporal profile of the AP-induced Ca2+ transients are due to changes in the intrinsic excitable properties of the muscle fibers. We propose that these changes accompany early stages of diabetic myopathy.

Bauhinia forficata prevents vacuous chewing movements induced by haloperidol in rats and has antioxidant potential in vitro.

Science.gov (United States)

Peroza, Luis Ricardo; Busanello, Alcindo; Leal, Caroline Queiroz; Röpke, Jivago; Boligon, Aline Augusti; Meinerz, Daiane; Libardoni, Milena; Athayde, Margareth Linde; Fachinetto, Roselei

2013-04-01

Classical antipsychotics can produce motor disturbances like tardive dyskinesia in humans and orofacial dyskinesia in rodents. These motor side effects have been associated with oxidative stress production in specific brain areas. Thus, some studies have proposed the use of natural compounds with antioxidant properties against involuntary movements induced by antipsychotics. Here, we examined the possible antioxidant activity of Bauhinia forficata (B. forficata), a plant used in folk medicine as a hypoglycemic, on brain lipid peroxidation induced by different pro-oxidants. B. forficata prevented the formation of lipid peroxidation induced by both pro-oxidants tested. However, it was effective against lipid peroxidation induced by sodium nitroprusside (IC50 = 12.08 μg/mL) and Fe(2+)/EDTA (IC50 = 41.19 μg/mL). Moreover, the effects of B. forficata were analyzed on an animal model of orofacial dyskinesia induced by long-term treatment with haloperidol, where rats received haloperidol each 28 days (38 mg/kg) and/or B. forficata decoction daily (2.5 g/L) for 16 weeks. Vacuous chewing movements (VCMs), locomotor and exploratory activities were evaluated. Haloperidol treatment induced VCMs, and co-treatment with B. forficata partially prevented this effect. Haloperidol reduced the locomotor and exploratory activities of animals in the open field test, which was not modified by B. forficata treatment. Our present data showed that B. forficata has antioxidant potential and partially protects against VCMs induced by haloperidol in rats. Taken together, our data suggest the protection by natural compounds against VCMs induced by haloperidol in rats.

Analysis of potential radiation-induced genetic and somatic effects to man from milling of uranium

International Nuclear Information System (INIS)

Momeni, M.H.

1984-01-01

Potential mortality from natural causes and from radiation exposure conditions typical of those in the vicinity of uranium mills in the western USA was calculated. The exposure conditions were those assumed to exist in the vicinity of a hypothetical model mill. Dose rates to organs at risk were calculated as a function of time using the Uranium Dispersion and Dosimetry Code (Momeni et al. 1979). The changes in population size, birth rates, and radiation-induced and natural mortalities were calculated using the PRIM code (Momeni 1983). The population of the region within a radius of 80 km from the model mill is projected to increase from 57 428 to 75 638.6 during the 85 years of this analysis. Within the same period, the average birth rates for five-year periods increase from 5067.8 to 7436.1. The cumulative deaths within the five-year periods increase from 724 and 3501.8 from spontaneously induced neoplasms and all causes, respectively, to 1538.2 and 6718.2. In comparison to natural causes, radiation-induced mortality is negligible. The highest rate of death from radiation in any five-year period is only 0.2, compared with 1538.2 deaths attributable to spontaneous incidence. The total radiation-induced genetic disorders were much less than unity for the 85-year period of analysis, in contrast with the 10.7% natural incidence of these disorders

The potential protective role of Physalis peruviana L. fruit in cadmium-induced hepatotoxicity and nephrotoxicity.

Science.gov (United States)

Dkhil, Mohamed A; Al-Quraishy, Saleh; Diab, Marwa M S; Othman, Mohamed S; Aref, Ahmed M; Abdel Moneim, Ahmed E

2014-12-01

This study aimed to investigate the potential protective role of Physalis peruviana L. (family Solanaceae) against cadmium-induced hepatorenal toxicity in Wistar rats. Herein, cadmium chloride (CdCl2) (6.5 mg/kg bwt/day) was intraperitoneally injected for 5 days, and methanolic extract of physalis (MEPh) was pre-administered to a group of Cd-treated rats by an oral administration at a daily dose of 200 mg/kg bwt for 5 days. The findings revealed that CdCl2 injection induced significant decreases in kidney weight and kidney index. Cadmium intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of uric acid, urea and creatinine were increased in the serum. The pre-administration of MEPh alleviated hepatorenal toxicity in Cd-treated rats. Physalis was noted to play a good hepatorenal protective role, reducing lipid peroxidation, nitric oxide, and enhancing enzymatic activities and non-enzymatic antioxidant molecule, glutathione, in hepatic and renal tissues of Cd-treated rats. Moreover, physalis treatment was able to reverse the histopathological changes in liver and kidney tissues and also increased the expression of Bcl-2 protein in liver and kidney of rats. Overall, the results showed that MEPh can induce antioxidant and anti-apoptotic effects and also exerts beneficial effects for the treatment of Cd-induced hepatorenal toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor

Energy Technology Data Exchange (ETDEWEB)

Isales, Gregory M.; Hipszer, Rachel A.; Raftery, Tara D. [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States); Chen, Albert; Stapleton, Heather M. [Division of Environmental Sciences and Policy, Nicholas School of the Environment, Duke University, Durham, NC (United States); Volz, David C., E-mail: volz@mailbox.sc.edu [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States)

2015-04-15

Highlights: • Triphenyl phosphate-induced toxicity in zebrafish embryos is enhanced in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate uptake or metabolism within zebrafish embryos is not altered in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate decreases expression of cytochrome P450 26a1 in zebrafish embryos. • Triphenyl phosphate inhibits retinoic acid-induced activation of human retinoic acid receptors. - Abstract: Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5–72 h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) – a primary TPP metabolite – were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) – a major target gene for RA-induced RAR activation in zebrafish – and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may

Cyclopentenone prostaglandins as potential inducers of phase II detoxification enzymes. 15-deoxy-delta(12,14)-prostaglandin j2-induced expression of glutathione S-transferases.

Science.gov (United States)

Kawamoto, Y; Nakamura, Y; Naito, Y; Torii, Y; Kumagai, T; Osawa, T; Ohigashi, H; Satoh, K; Imagawa, M; Uchida, K

2000-04-14

Exposure of cells to a wide variety of chemoprotective compounds confers resistance to a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of protective enzymes, such as glutathione S-transferases (GSTs). In the present study, we developed a cell culture system that potently responds to phenolic antioxidants and found that antitumor prostaglandins (PGs) are potential inducers of GSTs. We screened primary hepatocytes and multiple cell lines for inducing GST activity upon incubation with the phenolic antioxidant (tert-butylhydroquinone) and found that rat liver epithelial RL34 cells most potently responded. Based on an extensive screening of diverse chemical agents on the induction of GST activity in RL34 cells, the J2 series of PGs, 15-deoxy-Delta(12,14)-prostaglandin J2 (15-deoxy-Delta(12,14)-PGJ2) in particular, were found to be potential inducers of GST. Enhanced gene expression of Class pi GST isozyme (GSTP1) by 15-deoxy-Delta(12,14)-PGJ2 was evident as a drastic elevation of the mRNA level. Hence, we examined the molecular mechanism underlying the 15-deoxy-Delta(12, 14)-PGJ2-induced GSTP1 gene expression. From functional analysis of various deletion mutant genes, we found that the 15-deoxy-Delta(12, 14)-PGJ2 reponse element was localized in a region containing a GSTP1 enhancer I (GPEI) that consists of two imperfect phorbol 12-O-tetradecanoylphorbol-13-acetate response elements. When the GPEI was combined with the minimum GSTP1 promoter, the element indeed showed an enhancer activity in response to 15-deoxy-Delta(12, 14)-PGJ2. Point mutations of either of the two imperfect 12-O-tetradecanoylphorbol-13-acetate response elements in GPEI completely abolished the enhancer activity. Gel mobility shift assays demonstrated that 15-deoxy-Delta(12,14)-PGJ2 specifically stimulated the binding of nuclear proteins including the transcription factor c-Jun, but not Nrf2, to GPEI. These results

Analysis of Light-Induced Transmembrane Ion Gradients and Membrane Potential in Photosystem I Proteoliposomes

International Nuclear Information System (INIS)

Pennisi, Cristian P.; Greenbaum, Elias; Yoshida, Ken

2010-01-01

Photosystem I (PSI) complexes can support a light-driven electrochemical gradient for protons, which is the driving force for energy-conserving reactions across biological membranes. In this work, a computational model that enables a quantitative description of the light-induced proton gradients across the membrane of PSI proteoliposomes is presented. Using a set of electrodiffusion equations, a compartmental model of a vesicle suspended in aqueous medium was studied. The light-mediated proton movement was modeled as a single proton pumping step with backpressure of the electric potential. The model fits determinations of pH obtained from PSI proteoliposomes illuminated in the presence of mediators of cyclic electron transport. The model also allows analysis of the proton gradients in relation to the transmembrane ion fluxes and electric potential. Sensitivity analysis enabled a determination of the parameters that have greater influence on steady-state levels and onset/decay rates of transmembrane pH and electric potential. This model could be used as a tool for optimizing PSI proteoliposomes for photo-electrochemical applications.

The availability of hydrogeologic data associated with areas identified by the US Geological Survey as experiencing potentially induced seismicity resulting from subsurface injection

Science.gov (United States)

Barnes, Caitlin; Halihan, Todd

2018-05-01

A critical need exists for site-specific hydrogeologic data in order to determine potential hazards of induced seismicity and to manage risk. By 2015, the United States Geological Survey (USGS) had identified 17 locations in the USA that are experiencing an increase in seismicity, which may be potentially induced through industrial subsurface injection. These locations span across seven states, which vary in geological setting, industrial exposure and seismic history. Comparing the research across the 17 locations revealed patterns for addressing induced seismicity concerns, despite the differences between geographical locations. Most induced seismicity studies evaluate geologic structure and seismic data from areas experiencing changes in seismic activity levels, but the inherent triggering mechanism is the transmission of hydraulic pressure pulses. This research conducted a systematic review of whether data are available in these locations to generate accurate hydrogeologic predictions, which could aid in managing seismicity. After analyzing peer-reviewed research within the 17 locations, this research confirms a lack of site-specific hydrogeologic data availability for at-risk areas. Commonly, formation geology data are available for these sites, but hydraulic parameters for the seismically active injection and basement zones are not available to researchers conducting peer-reviewed research. Obtaining hydrogeologic data would lead to better risk management for injection areas and provide additional scientific evidential support for determining a potentially induced seismic area.

Numerical and experimental study of the effect of the induced electric potential in Lorentz force velocimetry

Science.gov (United States)

Hernández, Daniel; Boeck, Thomas; Karcher, Christian; Wondrak, Thomas

2018-01-01

Lorentz force velocimetry (LFV) is a contactless velocity measurement technique for electrically conducting fluids. When a liquid metal or a molten glass flows through an externally applied magnetic field, eddy currents and a flow-braking force are generated inside the liquid. This force is proportional to the velocity or flow rate of the fluid and, due to Newton’s third law, a force of the same magnitude but in opposite direction acts on the source of the applied magnetic field which in our case are permanent magnets. According to Ohm’s law for moving conductors at low magnetic Reynolds numbers, an electric potential is induced which ensures charge conservation. In this paper, we analyze the contribution of the induced electric potential to the total Lorentz force by considering two different scenarios: conducting walls of finite thickness and aspect ratio variation of the cross-section of the flow. In both the cases, the force component generated by the electric potential is always in the opposite direction to the total Lorentz force. This force component is sensitive to the electric boundary conditions of the flow of which insulating and perfectly conducting walls are the two limiting cases. In the latter case, the overall electric resistance of the system is minimized, resulting in a considerable increase in the measured Lorentz force. Additionally, this force originating from the electric potential also decays when the aspect ratio of the cross-section of the flow is changed. Hence, the sensitivity of the measurement technique is enhanced by either increasing wall conductivity or optimizing the aspect ratio of the cross-section of the flow.

Integrated Application of Remote Sensing, GIS and Hydrological Modeling to Estimate the Potential Impact Area of Earthquake-Induced Dammed Lakes

OpenAIRE

Bo Cao; Shengmei Yang; Song Ye

2017-01-01

Dammed lakes are an important secondary hazard caused by earthquakes. They can induce further damage to nearby humans. Current hydrology calculation research on dammed lakes usually lacks spatial expressive ability and cannot accurately conduct impact assessment without the support of remote sensing, which obtains important characteristic information of dammed lakes. The current study aims to address the issues of the potential impact area estimate of earthquake-induced dammed lakes by combin...

Induced pluripotent stem cells for the treatment of stroke: the potential and the pitfalls.

Science.gov (United States)

Yu, Fenggang; Li, Yingying; Morshead, Cindi M

2013-09-01

The extraordinary discovery of induced pluripotent stem cells (iPSCs) has led to the very real possibility that patient-specific cell therapy can be realized. The potential to develop cell replacement therapies outside the ethical and legal limitations, has initiated a new era of hope for regenerative strategies to treat human neurological disease including stroke. In this article, we will review and compare the current approaches to derive iPSCs from different somatic cells, and the induction into neuronal phenotypes, considering the advantages and disadvantages to the methodologies of derivation. We will highlight the work relating to the use of iPSC-based therapies in models of stroke and their potential use in clinical trials. Finally, we will consider future directions and areas of exploration which may promote the realization of iPSC-based cell replacement strategies for the treatment of stroke.

Induced seismicity and the potential for liability under U.S. law

Science.gov (United States)

Cypser, Darlene A.; Davis, Scott D.

1998-04-01

Research by seismologists over the past 30+ years has firmly established that some human activities induce seismicity. Sometimes induced seismicity causes injuries to people or property. The activities which induce seismicity generally involve extraction of energy, or natural resources, or the disposal of wastes. As the human population increases these extraction and disposal activities will increase in number of sites and intensity of effort as the demands become greater and the resources scarcer. With these increases the number and severity of damaging induced earthquakes is likely to increase. Induced seismicity may cause injuries by vibrations or by seismically induced ground failure. In either case compensation for injuries caused by induced seismicity should be paid for by the inducer. In the United States the inducer of damaging seismicity can be made to pay for the harm caused. Liability for damage caused by vibrations can be based on several legal theories: trespass, strict liability, negligence and nuisance. Our research revealed no cases in which an appellate court has upheld or rejected the application of tort liability to an induced earthquake situation. However, there are numerous analogous cases that support the application of these legal theories to induced seismicity. Vibrations or concussions due to blasting or heavy machinery are sometimes viewed as a `trespass' analogous to a physical invasion. In some states activities which induce earthquakes might be considered `abnormally dangerous' activities that require companies engaged in them to pay for injuries the quakes cause regardless of how careful the inducers were. In some circumstances, a court may find that an inducer was negligent in its site selection or in maintenance of the project. If induced seismicity interferes with the use or enjoyment of another's land, then the inducing activity may be a legal nuisance, even if the seismicity causes little physical damage. In most states of the

Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

Science.gov (United States)

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

2012-10-01

Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity

Directory of Open Access Journals (Sweden)

Hozeifa M. Hassan

2018-03-01

Full Text Available Tuberculosis (TB is one of the oldest infectious diseases that affected humankind and remains one of the world’s deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS potentially enhanced INH toxicity. These enhancing activities ranged between augmenting the inflammatory stress, oxidative stress, alteration of bile acid homeostasis, and CYP2E1 over-expression. Although pre-treatment with dexamethasone (DEX helped overcome both inflammatory and oxidative stress which ended-up in alleviation of LPS augmenting effects, but still minor toxicities were being detected, alongside with CYP2E1 over expression. This finding positively indicated the corner-stone role played by CYP2E1 in the pathogenesis of INH/LPS-induced liver damage. Therefore, we examined whether INH/LPS co-treatment with CYP2E1 inhibitor diallyl sulfide (DAS and DEX can protect against the INH/LPS-induced hepatotoxicity. Our results showed that pre-administration of both DAS and DEX caused significant reduction in serum TBA, TBil, and gamma-glutamyl transferase levels. Furthermore, the histopathological analysis showed that DAS and DEX could effectively reverse the liver lesions seen following INH/LPS treatment and protect against hepatic steatosis as indicated by absence of lipid accumulation. Pre-treatment with DAS alone could not completely block the CYP2E1 protein expression following INH/LPS treatment, as appeared in the immunoblotting and immunohistochemistry results. This is probably due to the fact that the combined enhancement activities of both INH and LPS on CYP2E1 protein expression

Participation of intracellular and extracellular pH changes in photosynthetic response development induced by variation potential in pumpkin seedlings.

Science.gov (United States)

Sherstneva, O N; Vodeneev, V A; Katicheva, L A; Surova, L M; Sukhov, V S

2015-06-01

Electrical signals presented in plants by action potential and by variation potential (VP) can induce a reversible inactivation of photosynthesis. Changes in the intracellular and extracellular pH during VP generation are a potential mechanism of photosynthetic response induction; however, this hypothesis requires additional experimental investigation. The purpose of the present work was to analyze the influence of pH changes on induction of the photosynthetic response in pumpkin. It was shown that a burning of the cotyledon induced VP propagation into true leaves of pumpkin seedlings inducing a decrease in the photosynthetic CO2 assimilation and an increase in non-photochemical quenching of fluorescence, whereas respiration was activated insignificantly. The photosynthetic response magnitude depended linearly on the VP amplitude. The intracellular and extracellular concentrations of protons were analyzed using pH-sensitive fluorescent probes, and the VP generation was shown to be accompanied by apoplast alkalization (0.4 pH unit) and cytoplasm acidification (0.3 pH unit). The influence of changes in the incubation medium pH on the non-photochemical quenching of fluorescence of isolated chloroplasts was also investigated. It was found that acidification of the medium stimulated the non-photochemical quenching, and the magnitude of this increase depended on the decrease in pH. Our results confirm the contribution of changes in intracellular and extracellular pH to induction of the photosynthetic response caused by VP. Possible mechanisms of the influence of pH changes on photosynthesis are discussed.

Protective role of Nrf2 against mechanical-stretch-induced apoptosis in mouse fibroblasts: a potential therapeutic target of mechanical-trauma-induced stress urinary incontinence.

Science.gov (United States)

Li, Qiannan; Li, Bingshu; Liu, Cheng; Wang, Linlin; Tang, Jianming; Hong, Li

2018-01-10

We investigated the protective effect and underlying molecular mechanism of nuclear factor-E2-related factor 2 (Nrf2) against mechanical-stretch-induced apoptosis in mouse fibroblasts. Normal cells, Nrf2 silencing cells, and Nrf2 overexpressing cells were respectively divided into two groups-nonintervention and cyclic mechanical strain (CMS)-subjected to CMS of 5333 μ (1.0 Hz for 4 h), six groups in total (control, CMS, shNfe212, shNfe212 + CMS, LV-shNfe212, and LV-shNfe212 + CMS). After treatment, cell apoptosis; cell-cycle distribution; expressions of Nrf2, Bax, Bcl-2, Cyt-C, caspase-3, caspase-9, cleaved-caspase-3, and cleaved-caspase-9; mitochondrial membrane potential (ΔΨm); reactive oxygen species (ROS); and malondialdehyde (MDA) levels were measured. Thirty virgin female C57BL/6 mice were divided into two groups: control (without intervention) and vaginal distension (VD) groups, which underwent VD for 1 h with an 8-mm dilator (0.3 ml saline). Leak-point pressure (LPP) was tested on day 7 after VD; Nrf2 expression, apoptosis, and MDA levels were then measured in urethra and anterior vaginal wall. Mechanical stretch decreased Nrf2 messenger RNA (mRNA) and protein expressions. Overexpression of Nrf2 alleviated mechanical-stretch-induced cell apoptosis; S-phase arrest of cell cycle; up-regulation of Bax, cytochrome C (Cyt-C), ROS, MDA, ratio of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9; and exacerbated the decrease of Bcl2 and ΔΨm in L929 cells. On the contrary, silencing of Nrf2 showed opposite effects. Besides, VD reduced LPP levels and Nrf2 expression and increased cell apoptosis and MDA generation in the urethra and anterior vaginal wall. Nrf2 exhibits a protective role against mechanical-stretch -induced apoptosis on mouse fibroblasts, which might indicate a potential therapeutic target of mechanical-trauma-induced stress urinary incontinence (SUI).

Hepatocurative potential of sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride induced liver toxicity in mice.

Science.gov (United States)

Mahesh, A; Jeyachandran, R; Cindrella, L; Thangadurai, D; Veerapur, V P; Muralidhara Rao, D

2010-06-01

The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl 4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CCl 4 . The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CCl 4 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method.

Potential for ion-induced nucleation of volatile organic compounds by radon decay in indoor environments

International Nuclear Information System (INIS)

Daisey, J.M.

1991-11-01

There is considerable interest in the ''unattached'' fraction of radon progeny in indoor air because of its significance to the estimation of the risks of radon exposure. Because of its high mobility in air, the unattached fraction is more efficiently deposited in the respiratory tract. Variation in the diameter of the ''unattached'' fraction and in its diffusion coefficient can be due to clustering of other atmospheric species around the 218 PoO 2 + ion. The purpose of this study was to investigate the potential for the formation of clusters of vapor phase organic compounds, found in indoor air, around the 218 PoO 2 + ion and to determine which were most likely to form clusters. A secondary purpose was to provide a compilation of measurements of indoor organic compounds for future experiments and theoretical calculations by the radon research community. The classical charged liquid droplet theory (Thomson equation) was used to estimate the Gibbs free energy of ion-induced nucleation and to provide an indication of the indoor organic compounds most likely to undergo ion-induced nucleation. Forty-four volatile and semi-volatile organic compounds out of the more than 300 which have been reported in indoor air were investigated. Water vapor was included for comparison. The results indicate that there is a potential for the formation of clusters of organic compounds around the 218 PoO 2 + ion. The compounds with the greatest potential for cluster formation are the volatile oxidized hydrocarbons (e.g., n-butanol, phenol, hexanal, nonanal, benzaldehyde, the ketones and the acetates) and the semi-volatile organic compounds (pentachlorophenol, nicotine, chlordane, chlorpyrifos)

Potential chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis in rats: myrrh (Commiphora molmol) vs. turmeric (Curcuma longa).

Science.gov (United States)

El-Shahat, Mohamed; El-Abd, Sabah; Alkafafy, Mohamed; El-Khatib, Gamal

2012-09-01

The aim of the present study was to assess the potential chemopreventive effects of myrrh (Commiphora molmol) vs. turmeric (Curcuma longa) in hepatocarcinogenic rats induced by a single intraperitoneal injection of diethylnitrosamine (DENA) (200 mg/kg body weight). Ninety male Wistar rats used in this study were randomly divided into six equal groups (n=15). Group 1 rats served as negative controls; group 2 received a single i.p. injection of DENA and served as positive controls. Rats in both groups were fed on basal diet. Group 3 rats were fed a diet containing 5% turmeric, whereas group 4 rats were fed a diet containing 2% myrrh. Rats in groups 5 and 6 received a single i.p. injection of DENA and were fed diets containing 5% turmeric and 2% myrrh, respectively. The study demonstrated that DENA caused a significant increase in serum indices of liver enzymes and also severe histological and immunohistochemical changes in hepatic tissues. These included disorganized hepatic parenchyma, appearance of pseudoacinar and trabecular arrays of hepatocytes and alterations in CD10-immunoreactivity. Dietary supplementation of turmeric relatively improved the biochemical parameters to values approximating those of the negative controls and delayed the initiation of carcinogenesis. In contrast, myrrh did not improve the biochemical parameters or delay the hepatocarcinogenesis. Both turmeric and myrrh induced significant biochemical and histological changes in non-treated rats. In conclusion, DENA significantly changes the biological enzymatic activities in serum and the integrity of hepatic tissues. Phytochemicals with potential hepatoprotective effects must be applied cautiously owing to their potential hepatotoxicity. Copyright © 2011 Elsevier GmbH. All rights reserved.

Potential mechanisms behind contrast medium-induced nephropathy

African Journals Online (AJOL)

How contrast medium-induced nephropathy (CIN) comes about is poorly understood, although CIN is a common cause of acute renal failure. Hitherto, the various studies performed have led to different interpretations and partially contradictory conclusions. This article aimed to review the mechanisms underlying CIN and to ...

Paired-Associative Stimulation-Induced Long-term Potentiation-Like Motor Cortex Plasticity in Healthy Adolescents

Directory of Open Access Journals (Sweden)

Jonathan C. Lee

2017-05-01

Full Text Available ObjectiveThe objective of this study was to evaluate the feasibility of using paired-associative stimulation (PAS to study excitatory and inhibitory plasticity in adolescents while examining variables that may moderate plasticity (such as sex and environment.MethodsWe recruited 34 healthy adolescents (aged 13–19, 13 males, 21 females. To evaluate excitatory plasticity, we compared mean motor-evoked potentials (MEPs elicited by single-pulse transcranial magnetic stimulation (TMS before and after PAS at 0, 15, and 30 min. To evaluate inhibitory plasticity, we evaluated the cortical silent period (CSP elicited by single-pulse TMS in the contracted hand before and after PAS at 0, 15, and 30 min.ResultsAll participants completed PAS procedures. No adverse events occurred. PAS was well tolerated. PAS-induced significant increases in the ratio of post-PAS MEP to pre-PAS MEP amplitudes (p < 0.01 at all post-PAS intervals. Neither socioeconomic status nor sex was associated with post-PAS MEP changes. PAS induced significant CSP lengthening in males but not females.ConclusionPAS is a feasible, safe, and well-tolerated index of adolescent motor cortical plasticity. Gender may influence PAS-induced changes in cortical inhibition. PAS is safe and well tolerated by healthy adolescents and may be a novel tool with which to study adolescent neuroplasticity.

The Therapeutic Potential of Monocyte/Macrophage Manipulation in the Treatment of Chemotherapy-Induced Painful Neuropathy

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Karli Montague

2017-11-01

Full Text Available In cancer treatments a dose-limiting side-effect of chemotherapeutic agents is the development of neuropathic pain, which is poorly managed by clinically available drugs at present. Chemotherapy-induced painful neuropathy (CIPN is a major cause of premature cessation of treatment and so a greater understanding of the underlying mechanisms and the development of novel, more effective therapies, is greatly needed. In some cases, only a weak correlation between chemotherapy-induced pain and neuronal damage is observed both clinically and preclinically. As such, a critical role for non-neuronal cells, such as immune cells, and their communication with neurons in CIPN has recently been appreciated. In this mini-review, we will discuss preclinical evidence for the role of monocytes/macrophages in the periphery in CIPN, with a focus on that which is associated with the chemotherapeutic agents vincristine and paclitaxel. In addition we will discuss the potential mechanisms that regulate monocyte/macrophage–neuron crosstalk in this context. Informed by preclinical data, we will also consider the value of monocytes/macrophages as therapeutic targets for the treatment of CIPN clinically. Approaches that manipulate the signaling pathways discussed in this review show both promise and potential pitfalls. Nonetheless, they are emerging as innovative therapeutic targets with CX3CL1/R1-regulation of monocyte/macrophage–neuron communication currently emerging as a promising front-runner.

Activation of Transient Receptor Potential Melastatin Subtype 8 Attenuates Cold-Induced Hypertension Through Ameliorating Vascular Mitochondrial Dysfunction.

Science.gov (United States)

Xiong, Shiqiang; Wang, Bin; Lin, Shaoyang; Zhang, Hexuan; Li, Yingsha; Wei, Xing; Cui, Yuanting; Wei, Xiao; Lu, Zongshi; Gao, Peng; Li, Li; Zhao, Zhigang; Liu, Daoyan; Zhu, Zhiming

2017-08-02

Environmental cold-induced hypertension is common, but how to treat cold-induced hypertension remains an obstacle. Transient receptor potential melastatin subtype 8 (TRPM8) is a mild cold-sensing nonselective cation channel that is activated by menthol. Little is known about the effect of TRPM8 activation by menthol on mitochondrial Ca 2+ homeostasis and the vascular function in cold-induced hypertension. Primary vascular smooth muscle cells from wild-type or Trpm8 -/- mice were cultured. In vitro, we confirmed that sarcoplasmic reticulum-resident TRPM8 participated in the regulation of cellular and mitochondrial Ca 2+ homeostasis in the vascular smooth muscle cells. TRPM8 activation by menthol antagonized angiotensin II induced mitochondrial respiratory dysfunction and excess reactive oxygen species generation by preserving pyruvate dehydrogenase activity, which hindered reactive oxygen species-triggered Ca 2+ influx and the activation of RhoA/Rho kinase pathway. In vivo, long-term noxious cold stimulation dramatically increased vasoconstriction and blood pressure. The activation of TRPM8 by dietary menthol inhibited vascular reactive oxygen species generation, vasoconstriction, and lowered blood pressure through attenuating excessive mitochondrial reactive oxygen species mediated the activation of RhoA/Rho kinase in a TRPM8-dependent manner. These effects of menthol were further validated in angiotensin II-induced hypertensive mice. Long-term dietary menthol treatment targeting and preserving mitochondrial function may represent a nonpharmaceutical measure for environmental noxious cold-induced hypertension. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Rosmarinic acid potentiates carnosic acid induced apoptosis in lung fibroblasts.

Directory of Open Access Journals (Sweden)

Sana Bahri

Full Text Available Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA and rosmarinic acid (RA was reported to cure bleomycin-(BLM-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11.70±1.46 μM, indicating synergic action. TGFβ-transformed HLF, rat lung fibroblasts and L929 cells presented similar sensitivity to CA and CA+RA (20μM+100μM, respectively treatment. Rat alveolar epithelial cells died only under CA+RA treatment, while A549 cells were not affected. Annexin V staining and DNA quantification suggested that HLF are arrested in G0/G1 cell cycle phase and undergo apoptosis. CA caused sustained activation of phospho-Akt and phospho-p38 expression and inhibition of p21 protein.Addition of RA potentiated these effects, while RA added alone had no action.Only triple combination of inhibitors (MAPK-p38, pan-caspase, PI3K/Akt/autophagy partially attenuated apoptosis; this suggests that cytotoxicity of CA+RA treatment has a complex mechanism involving several parallel signaling pathways. The in vivo antifibrotic effect of CA and RA was compared with that of Vitamine-E in BLM-induced fibrosis model in rats. We found comparable reduction in fibrosis score by CA, RA and CA+RA, attenuation of collagen deposition and normalization of oxidative stress markers. In conclusion, antifibrotic effect of CA+RA is due to synergistic pro-apoptotic action on lung fibroblasts and myofibroblasts.

Dipolar-induced interplay between inter-level physics and macroscopic phase transitions in triple-well potentials

International Nuclear Information System (INIS)

Zhang Aixia; Xue Jukui

2012-01-01

We propose a scheme to reveal the interplay between dipole–dipole interaction (DDI), inter-level coupling and macroscopic phase transitions in dipolar condensates. By considering a macroscopic sample of dipolar bosons in triple-well potentials, DDI-induced coupling between the inter-level physics and the macroscopic phase transitions is presented. When the DDI exceeds certain thresholds, the degeneracy of the two lowest energy levels and the excitation of new eigenstates occur, respectively. Interestingly, these thresholds give the boundaries of various quantum phase transitions. That is, the quantum phase transitions are the consequence of the levels' degeneracy and the new eigenstates' excitation. Furthermore, DDI-induced long-range macroscopic Josephson oscillations are observed and long-range coherent quantum transportation is achieved. Our results give clear proof of the interplay between the multi-level physics and quantum phase transitions, and also provide a way for designing the long-range coherent quantum transportation. (paper)

Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

International Nuclear Information System (INIS)

Nozaki, Yumiko; Honda, Yayoi; Tsujimoto, Shinji; Watanabe, Hitoshi; Kunimatsu, Takeshi; Funabashi, Hitoshi

2014-01-01

Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K + channel and Ca 2+ channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I Kr and I Ks blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca 2+ channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I Kr blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans

Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

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Nozaki, Yumiko, E-mail: yumiko-nozaki@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Honda, Yayoi, E-mail: yayoi-honda@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Tsujimoto, Shinji, E-mail: shinji-tsujimoto@ds-pharma.co.jp [Regenerative and Cellular Medicine Office, Dainippon Sumitomo Pharma. Co., Ltd., Chuo-ku, Tokyo 104-0031 (Japan); Watanabe, Hitoshi, E-mail: hitoshi-1-watanabe@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Kunimatsu, Takeshi, E-mail: takeshi-kunimatsu@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Funabashi, Hitoshi, E-mail: hitoshi-funabashi@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan)

2014-07-01

Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.

Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.

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Tamaki Ishima

Full Text Available In addition to both the α1 adrenergic receptor and N-methyl-D-aspartate (NMDA receptor antagonists, ifenprodil binds to the sigma receptor subtypes 1 and 2. In this study, we examined the effects of ifenprodil on nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Ifenprodil significantly potentiated NGF-induced neurite outgrowth, in a concentration-dependent manner. In contrast, the α1 adrenergic receptor antagonist, prazosin and the NMDA receptor NR2B antagonist, Ro 25-6981 did not alter NGF-induced neurite outgrowth. Potentiation of NGF-induced neurite outgrowth mediated by ifenprodil was significantly antagonized by co-administration of the selective sigma-1 receptor antagonist, NE-100, but not the sigma-2 receptor antagonist, SM-21. Similarly, ifenprodil enhanced NGF-induced neurite outgrowth was again significantly reduced by the inositol 1,4,5-triphosphate (IP(3 receptor antagonists, xestospongin C and 2-aminoethoxydiphenyl borate (2-APB treatment. Furthermore, BAPTA-AM, a chelator of intracellular Ca(2+, blocked the effects of ifenprodil on NGF-induced neurite outgrowth, indicating the role of intracellular Ca(2+ in the neurite outgrowth. These findings suggest that activation at sigma-1 receptors and subsequent interaction with IP(3 receptors may mediate the pharmacological effects of ifenprodil on neurite outgrowth.

Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death.

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Itakura, Masanori; Nakajima, Hidemitsu; Semi, Yuko; Higashida, Shusaku; Azuma, Yasu-Taka; Takeuchi, Tadayoshi

2015-11-13

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple functions, including mediating oxidative stress-induced neuronal cell death. This process is associated with disulfide-bonded GAPDH aggregation. Some reports suggest a link between GAPDH and the pathogenesis of several oxidative stress-related diseases. However, the pathological significance of GAPDH aggregation in disease pathogenesis remains unclear due to the lack of an effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH aggregation inhibitor (GAI) peptide and evaluated its biological profile. The decapeptide GAI specifically inhibited GAPDH aggregation in a concentration-dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic activity or cell viability. The GAI peptide also exerted a protective effect against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could potentially serve as a tool to investigate GAPDH aggregation-related neurodegenerative and neuropsychiatric disorders and as a possible therapy for diseases associated with oxidative stress-induced cell death. Copyright © 2015 Elsevier Inc. All rights reserved.

Butachlor induced dissipation of mitochondrial membrane potential, oxidative DNA damage and necrosis in human peripheral blood mononuclear cells

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Dwivedi, Sourabh; Saquib, Quaiser; Al-Khedhairy, Abdulaziz A.; Musarrat, Javed

2012-01-01

Highlights: ► Butachlor exhibited strong binding affinity with DNA and produced 8-oxodG adducts. ► Butachlor induced DNA strand breaks and micronuclei formation in PBMN cells. ► Butachlor induced ROS and dissipation of mitochondrial membrane potential in cells. ► Butachlor resulted in cell cycle arrest and eventually caused cellular necrosis. -- Abstract: Butachlor is a systemic herbicide widely applied on rice, tea, wheat, beans and other crops; however, it concurrently exerts toxic effects on beneficial organisms like earthworms, aquatic invertebrates and other non-target animals including humans. Owing to the associated risk to humans, this chloroacetanilide class of herbicide was investigated with the aim to assess its potential for the (i) interaction with DNA, (ii) mitochondria membrane damage and DNA strand breaks and (iii) cell cycle arrest and necrosis in butachlor treated human peripheral blood mononuclear (PBMN) cells. Fluorescence quenching data revealed the binding constant (Ka = 1.2 × 10 4 M −1 ) and binding capacity (n = 1.02) of butachlor with ctDNA. The oxidative potential of butachlor was ascertained based on its capacity of inducing reactive oxygen species (ROS) and substantial amounts of promutagenic 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) adducts in DNA. Also, the discernible butachlor dose-dependent reduction in fluorescence intensity of a cationic dye rhodamine (Rh-123) and increased fluorescence intensity of 2′,7′-dichlorodihydro fluorescein diacetate (DCFH-DA) in treated cells signifies decreased mitochondrial membrane potential (ΔΨm) due to intracellular ROS generation. The comet data revealed significantly greater Olive tail moment (OTM) values in butachlor treated PBMN cells vs untreated and DMSO controls. Treatment of cultured PBMN cells for 24 h resulted in significantly increased number of binucleated micronucleated (BNMN) cells with a dose dependent reduction in the nuclear division index (NDI). The flow

Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

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Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

2012-01-01

Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

The Non-structural Protein of Crimean-Congo Hemorrhagic Fever Virus Disrupts the Mitochondrial Membrane Potential and Induces Apoptosis*

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Barnwal, Bhaskar; Karlberg, Helen; Mirazimi, Ali; Tan, Yee-Joo

2016-01-01

Viruses have developed distinct strategies to overcome the host defense system. Regulation of apoptosis in response to viral infection is important for virus survival and dissemination. Like other viruses, Crimean-Congo hemorrhagic fever virus (CCHFV) is known to regulate apoptosis. This study, for the first time, suggests that the non-structural protein NSs of CCHFV, a member of the genus Nairovirus, induces apoptosis. In this report, we demonstrated the expression of CCHFV NSs, which contains 150 amino acid residues, in CCHFV-infected cells. CCHFV NSs undergoes active degradation during infection. We further demonstrated that ectopic expression of CCHFV NSs induces apoptosis, as reflected by caspase-3/7 activity and cleaved poly(ADP-ribose) polymerase, in different cell lines that support CCHFV replication. Using specific inhibitors, we showed that CCHFV NSs induces apoptosis via both intrinsic and extrinsic pathways. The minimal active region of the CCHFV NSs protein was determined to be 93–140 amino acid residues. Using alanine scanning, we demonstrated that Leu-127 and Leu-135 are the key residues for NSs-induced apoptosis. Interestingly, CCHFV NSs co-localizes in mitochondria and also disrupts the mitochondrial membrane potential. We also demonstrated that Leu-127 and Leu-135 are important residues for disruption of the mitochondrial membrane potential by NSs. Therefore, these results indicate that the C terminus of CCHFV NSs triggers mitochondrial membrane permeabilization, leading to activation of caspases, which, ultimately, leads to apoptosis. Given that multiple factors contribute to apoptosis during CCHFV infection, further studies are needed to define the involvement of CCHFV NSs in regulating apoptosis in infected cells. PMID:26574543

Induced fermion number, phase-shift flip, and the axial anomaly in the Aharonov-Bohm potential

International Nuclear Information System (INIS)

Moroz, A.

1994-01-01

The spectral properties of the Dirac and the Klein-Gordon equations in the Aharonov-Bohm potential are discussed. The density of states for different self-adjoint extensions is calculated. The presence of the bound state manifests itself by asymmetric differential scattering cross sections. The results are applied to several physical quantities: the total energy, induced fermion-number, and the axial anomaly. The predictions of a persistent current in the presence of a cosmic string and a gravitational vortex are made. (author) 41 refs.; 1 fig

An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures

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Dugbartey, George J.; Peppone, Luke J.; de Graaf, Inge A.M.

2017-01-01

Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide. PMID:27717837

Salinity induced oxidative stress enhanced biofuel production potential of microalgae Scenedesmus sp. CCNM 1077.

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Pancha, Imran; Chokshi, Kaumeel; Maurya, Rahulkumar; Trivedi, Khanjan; Patidar, Shailesh Kumar; Ghosh, Arup; Mishra, Sandhya

2015-01-01

Microalgal biomass is considered as potential feedstock for biofuel production. Enhancement of biomass, lipid and carbohydrate contents in microalgae is important for the commercialization of microalgal biofuels. In the present study, salinity stress induced physiological and biochemical changes in microalgae Scenedesmus sp. CCNM 1077 were studied. During single stage cultivation, 33.13% lipid and 35.91% carbohydrate content was found in 400 mM NaCl grown culture. During two stage cultivation, salinity stress of 400 mM for 3 days resulted in 24.77% lipid (containing 74.87% neutral lipid) along with higher biomass compared to single stage, making it an efficient strategy to enhance biofuel production potential of Scenedesmus sp. CCNM 1077. Apart from biochemical content, stress biomarkers like hydrogen peroxide, lipid peroxidation, ascorbate peroxidase, proline and mineral contents were also studied to understand the role of reactive oxygen species (ROS) mediated lipid accumulation in microalgae Scenedesmus sp. CCNM 1077. Copyright © 2015 Elsevier Ltd. All rights reserved.

The potential for vault-induced seismicity in nuclear fuel waste disposal: experience from Canadian mines

International Nuclear Information System (INIS)

Martin, C.D.; Chandler, N.A.

1996-12-01

A seismic event which causes damage to an underground opening is called a rockburst. Practical experience indicates that these damaging seismic events are associated with deep mines where extraction ratios are greater than 0.6. For the arrangement being considered by AECL for nuclear fuel waste disposal vaults, extraction ratios, for the room and pillar design, will be less than 0.3. At this extraction ratio the stress magnitudes will not be sufficient to induce seismic events that can damage the underground openings. Documented world-wide experience shows that unless the underground opening is very close to the source of a naturally occurring seismic event, such as an earthquake, the opening will also not experience any significant damage. Backfilling a disposal vault will improve its resistance to earthquake damage. Backfilling a disposal vault will also reduce the total convergence of the openings caused by thermal loads and hence minimize the potential for thermally-induced seismic events. (author)

Ameliorating potential of Equisetum arvense against the Cyclophosphamide induced genotoxic damage in mice

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Jasbir Kour

2017-10-01

Full Text Available Medicinal plants have always been on the vanguard whether regarding the treatment of a number of ailments or even cancer. It has been suggested that the use of antimutagens/anticarcinogens in everyday life can be the most effective way to avert human cancer and genetic diseases. Equisetum arvense, commonly known as the field horsetail or common horsetail (Sehetband or Brahmgund locally in Kashmir, is a very common, bushy perennial herb native to the northern hemisphere and rich in secondary metabolites. In the present study, we evaluated the potential of the plant E. arvense against the cytotoxic and mutagenic effects induced by cyclophosphamide (chemotherapeutic agent in the bone marrow cells of mice using the Chromosome assay (CA and Mitotic index (MI in vivo as the biomarkers. E. arvense was subjected to extraction with hexane, ethanol and aqueous solvents. Screening for antimutagenic activity was carried out using albino mice as the model organism. Toxicological study was performed following 3 protocols: pre-treatment, simultaneous treatment and post-treatment with the three extracts of the plant and the mutagen. In order to find out the phytocomponents responsible for showing the highest antimutagenic activity, phytochemical analysis was also carried out using GC-MS. The present study was focused on evaluating the mutagenic/antimutagenic potential of the plant Equisetum arvense which exhibited potent antimutagenic activity against the cyclophosphamide induced mutations. Chromosomal aberrations and mitotic index were used as biomarkers to assess the mutations. In the present study mice treated with CPA showed significant increase in aberrant metaphases, CAs (including and excluding gaps, while decreased cellular proliferation rate (MI compared to the control group. The plant extracts were not cytotoxic or mutagenic to the animal. The highest antimutagenic activity (98% was shown by the ethanolic extract. The analysis of the effect of

Integrated Application of Remote Sensing, GIS and Hydrological Modeling to Estimate the Potential Impact Area of Earthquake-Induced Dammed Lakes

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Bo Cao

2017-10-01

Full Text Available Dammed lakes are an important secondary hazard caused by earthquakes. They can induce further damage to nearby humans. Current hydrology calculation research on dammed lakes usually lacks spatial expressive ability and cannot accurately conduct impact assessment without the support of remote sensing, which obtains important characteristic information of dammed lakes. The current study aims to address the issues of the potential impact area estimate of earthquake-induced dammed lakes by combining remote sensing (RS, a geographic information system (GIS, and hydrological modeling. The Tangjiashan dammed lake induced by the Wenchuan earthquake was selected as the case for study. The elevation-versus-reservoir capacity curve was first calculated using the seed-growing algorithm based on digital elevation model (DEM data. The simulated annealing algorithm was applied to train the hydrological modeling parameters according to the historical hydrologic data. Then, the downstream water elevation variational process under different collapse capacity conditions was performed based on the obtained parameters. Finally, the downstream potential impact area was estimated by the highest water elevation values at different hydrologic sections. Results show that a flood with a collapse elevation of at least 680 m will impact the entire downstream region of Beichuan town. We conclude that spatial information technology combined with hydrological modeling can accurately predict and demonstrate the potential impact area with limited data resources. This paper provides a better guide for future immediate responses to dammed lake hazard mitigation.

The anorexic agents, sibutramine and fenfluramine, depress GABAB-induced inhibitory postsynaptic potentials in rat mesencephalic dopaminergic cells

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Ledonne, Ada; Sebastianelli, Luca; Federici, Mauro; Bernardi, Giorgio; Mercuri, Nicola Biagio

2009-01-01

Background and purpose Nutrition is the result of a complex interaction among environmental, homeostatic and reward-related processes. Accumulating evidence supports key roles for the dopaminergic neurons of the ventral midbrain in regulating feeding behaviour. For this reason, in the present study, we have investigated the electrophysiological effects of two centrally acting anorexic agents, fenfluramine and sibutramine, on these cells. Experimental approach Rat midbrain slices were used to make intracellular recordings from dopaminergic neurons of the substantia nigra and the ventral tegmental area. Gamma-aminobutyric acid (GABA)-mediated synaptic transmission was assessed from the inhibitory postsynaptic potentials (IPSPs) mediated by GABAA and GABAB receptors. Key results Fenfluramine and sibutramine reduced, concentration-dependently, the GABAB IPSPs, without affecting the GABAA-mediated potentials. This effect is presynaptic, as postsynaptic membrane responses induced by application of a GABAB receptor agonist, baclofen, were not affected by the two drugs. Furthermore, the selective 5-hydroxytriptamine 1B (5-HT1B) receptor antagonist, SB216641, blocked the reduction of GABAB IPSPs caused by fenfluramine and sibutramine, indicating that the receptor mediating this effect is 5-HT1B. Conclusions and implications Two anorexic agents, fenfluramine and sibutramine, induced the activation of 5-HT1B receptors located on presynaptic GABAergic terminals, thus reducing the release of GABA. This action can alter the strength of synaptic afferents that modify the activity of dopaminergic neurons, inducing neuronal excitation. Our results reveal an additional mechanism of action for fenfluramine and sibutramine that might contribute to reducing food intake, by influencing the pleasurable and motor aspects of feeding behaviour. PMID:19298257

Intermittent Hypoxia-Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation

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Esteban A. Moya

2016-01-01

Full Text Available Oxidative stress is involved in the development of carotid body (CB chemosensory potentiation and systemic hypertension induced by chronic intermittent hypoxia (CIH, the main feature of obstructive sleep apnea. We tested whether peroxynitrite (ONOO−, a highly reactive nitrogen species, is involved in the enhanced CB oxygen chemosensitivity and the hypertension during CIH. Accordingly, we studied effects of Ebselen, an ONOO− scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir in the CB, the CB chemosensory discharge, and arterial blood pressure (BP in rats exposed to CIH. Male Sprague-Dawley rats were exposed to CIH (5% O2, 12 times/h, 8 h/day for 7 days. Ebselen (10 mg/kg/day was administrated using osmotic minipumps and BP measured with radiotelemetry. Compared to the sham animals, CIH-treated rats showed increased 3-NT-ir within the CB, enhanced CB chemosensory responses to hypoxia, increased BP response to acute hypoxia, and hypertension. Rats treated with Ebselen and exposed to CIH displayed a significant reduction in 3-NT-ir levels (60.8 ± 14.9 versus 22.9 ± 4.2 a.u., reduced CB chemosensory response to 5% O2 (266.5 ± 13.4 versus 168.6 ± 16.8 Hz, and decreased mean BP (116.9 ± 13.2 versus 82.1 ± 5.1 mmHg. Our results suggest that CIH-induced CB chemosensory potentiation and hypertension are critically dependent on ONOO− formation.

Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations.

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Kometer, Michael; Schmidt, André; Jäncke, Lutz; Vollenweider, Franz X

2013-06-19

Visual illusions and hallucinations are hallmarks of serotonergic hallucinogen-induced altered states of consciousness. Although the serotonergic hallucinogen psilocybin activates multiple serotonin (5-HT) receptors, recent evidence suggests that activation of 5-HT2A receptors may lead to the formation of visual hallucinations by increasing cortical excitability and altering visual-evoked cortical responses. To address this hypothesis, we assessed the effects of psilocybin (215 μg/kg vs placebo) on both α oscillations that regulate cortical excitability and early visual-evoked P1 and N170 potentials in healthy human subjects. To further disentangle the specific contributions of 5-HT2A receptors, subjects were additionally pretreated with the preferential 5-HT2A receptor antagonist ketanserin (50 mg vs placebo). We found that psilocybin strongly decreased prestimulus parieto-occipital α power values, thus precluding a subsequent stimulus-induced α power decrease. Furthermore, psilocybin strongly decreased N170 potentials associated with the appearance of visual perceptual alterations, including visual hallucinations. All of these effects were blocked by pretreatment with the 5-HT2A antagonist ketanserin, indicating that activation of 5-HT2A receptors by psilocybin profoundly modulates the neurophysiological and phenomenological indices of visual processing. Specifically, activation of 5-HT2A receptors may induce a processing mode in which stimulus-driven cortical excitation is overwhelmed by spontaneous neuronal excitation through the modulation of α oscillations. Furthermore, the observed reduction of N170 visual-evoked potentials may be a key mechanism underlying 5-HT2A receptor-mediated visual hallucinations. This change in N170 potentials may be important not only for psilocybin-induced states but also for understanding acute hallucinatory states seen in psychiatric disorders, such as schizophrenia and Parkinson's disease.

Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

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Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

2017-04-01

Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

Quantum tunneling time of a Bose-Einstein condensate traversing through a laser-induced potential barrier

International Nuclear Information System (INIS)

Duan Zhenglu; Fan Bixuan; Yuan Chunhua; Zhang Weiping; Cheng Jing; Zhu Shiyao

2010-01-01

We theoretically study the effect of atomic nonlinearity on the tunneling time in the case of an atomic Bose-Einstein condensate (BEC) traversing the laser-induced potential barrier. The atomic nonlinearity is controlled to appear only in the region of the barrier by employing the Feshbach resonance technique to tune interatomic interaction in the tunneling process. Numerical simulation shows that the atomic nonlinear effect dramatically changes the tunneling behavior of the BEC matter wave packet and results in the violation of the Hartman effect and the occurrence of negative tunneling time.

Protective effects of Arctium lappa L. roots against hydrogen peroxide-induced cell injury and potential mechanisms in SH-SY5Y cells.

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Tian, Xing; Guo, Li-Ping; Hu, Xiao-Long; Huang, Jin; Fan, Yan-Hua; Ren, Tian-Shu; Zhao, Qing-Chun

2015-04-01

Accumulated evidence has shown that excessive reactive oxygen species (ROS) have been implicated in neuronal cell death related with various chronic neurodegenerative disorders. This study was designed to explore neuroprotective effects of ethyl acetate extract of Arctium lappa L. roots (EAL) on hydrogen peroxide (H2O2)-induced cell injury in human SH-SY5Y neuroblastoma cells. The cell viability was significantly decreased after exposure to 200 μM H2O2, whereas pretreatment with different concentrations of EAL attenuated the H2O2-induced cytotoxicity. Hoechst 33342 staining indicated that EAL reversed nuclear condensation in H2O2-treated cells. Meanwhile, TUNEL assay with DAPI staining showed that EAL attenuated apoptosis was induced by H2O2. Pretreatment with EAL also markedly elevated activities of antioxidant enzyme (GSH-Px and SOD), reduced lipid peroxidation (MDA) production, prevented ROS formation, and the decrease of mitochondrial membrane potential. In addition, EAL showed strong radical scavenging ability in 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assays. Furthermore, EAL inhibited H2O2-induced apoptosis by increases in the Bcl-2/Bax ratio, decreases in cytochrome c release, and attenuation of caspase-3, caspase-9 activities, and expressions. These findings suggest that EAL may be regarded as a potential antioxidant agent and possess potent neuroprotective activity against H2O2-induced injury.

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

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VENKATA R.K. THIAGARAJAN

2014-09-01

Full Text Available The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS, reduced glutathione (GSH and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

Forsythoside A exerts antipyretic effect on yeast-induced pyrexia mice via inhibiting transient receptor potential vanilloid 1 function

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Liu, Cuiling; Su, Hongchang; Wan, Hongye; Qin, Qingxia; Wu, Xuan; Kong, Xiangying; Lin, Na

2017-01-01

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel gated by noxious heat, playing major roles in thermoregulation. Forsythoside A (FT-A) is the most abundant phenylethanoid glycosides in Fructus Forsythiae, which has been prescribed as a medicinal herb for treating fever in China for a long history. However, how FT-A affects pyrexia and what is the underlying molecular mechanism remain largely unknown. Here we found that FT-A exerted apparent antipyretic effect through decreasing the levels of prostaglandin E2 (PGE2) and interleukin 8 (IL-8) in a dose-dependent fashion on the yeast induced pyrexia mice. Interestingly, FT-A significantly downregulated TRPV1 expression in the hypothalamus and dorsal root ganglion (DRG) of the yeast induced pyrexia mice. Moreover, FT-A inhibited IL-8 and PGE2 secretions, and calcium influx in the HEK 293T-TRPV1 cells after stimulated with capsaicin, the specific TRPV1 agonist. Further investigation of the molecular mechanisms revealed that FT-A treatment rapidly inhibited phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 in both yeast induced pyrexia mice and HEK 293T-TRPV1 cells. These results suggest that FT-A may serve as a potential antipyretic agent and the therapeutic action of Fructus Forsythiae on pyretic related disease is, in part, due to the FT-A activities. PMID:28123347

Radioprotective potential of Decalepis hamiltonii: a study on gamma radiation-induced oxidative stress and toxicity in Drosophila melanogaster

International Nuclear Information System (INIS)

Pasha, Muzeer; Shivanandappa, T.; Ramesh, S.R.; Sanjeev, Ganesh

2016-01-01

Radiation-induced damage to normal tissues restricts the therapeutic use of radiation in clinical application for cancer treatment and thereby limits the efficacy of the treatment. The use of chemical compounds as radioprotectors is a desirable strategy to improve the therapeutic index of radiotherapy. However, most of the synthetic radioprotective compounds studied have shown to have undesirable properties of toxicity. There is a need for safer, natural radioprotective agents without compromising efficacy of the treatment. We have investigated the radioprotective potential of Decalepis hamiltonii (Dh) root extract which is rich in natural antioxidants by employing Drosophila melanogaster as a model. Irradiation of Drosophila with 100, 200, and 400 Gy of gamma radiation induced dose-dependent mortality. Elevation in the levels of thiobarbituric acid reactive substances (TBARS), the activities of catalase (CAT) and superoxide dismutase (SOD), and depletion of glutathione (GSH) content suggested radiation-induced oxidative stress. Pretreatment of flies with Dh root extract protected them from radiation-induced mortality and oxidative stress as evidenced by reduction in TBARS and restoration of the antioxidant enzymes, SOD and CAT, and GSH to control levels. This is the first report of radioprotective action of Dh root extract in D. melanogaster. (author)

The Potential Therapeutic Effect of Curcumin on the Adjuvant-induced Arthritis in Irradiated Rats

International Nuclear Information System (INIS)

El-Ghazaly, M.A.; Nada, A.S.; Hegazy, M.E.; Kenawy, S.A.

2010-01-01

Naturalistic that provide medical or health benefits, including prevention and treatment of diseases. They may be advantageous in inflammation and exposure to radiation. The study was conducted to investigate curcumin potential to modulate, counteract or prevent the inflammatory response induced in arthritic irradiated and non-irradiated rats using the adjuvant-induced arthritis model. Diclofenac was used as a reference standard non-steroidal anti-inflammatory drug (NSAID). Results indicated that exposure of rats to single dose of gamma-radiation (6 Gy) before induction of inflammation increased production of prostaglandin E2 (PGE2), tumour necrosis factor-gamma (TNF-gamma) and malondialdehyde (MDA) levels in serum. Blood glutathione (GSH) was shown to be reduced in irradiated animals. Curcumin suppressed the elevated levels of TNF-gamma, PGE2 and MDA and was able to restore blood GSH level. Reduction in liver contents of copper (Cu), zinc (Zn), selenium (Se) and iron (Fe) was recorded in animals irradiated before induction of inflammation. In addition, curcumin restored the hepatic contents of these trace elements. The present results suggest that irradiation of rats caused marked changes in the inflammatory response, while curcumin suppressed the inflammatory response in both irradiated and normal rats

Enhancing repair of radiation-induced strand breaks in cellular DNA as a radiotherapeutic potential

International Nuclear Information System (INIS)

Nair, C.K.K.

2014-01-01

Protection of mammalian organisms including man from deleterious effects of ionizing radiation is of paramount importance and development of effective approaches to combat radiation damages using non-toxic radioprotectors is of considerable interest for defence, nuclear industries, radiation accidents, space travels, etc., besides the protection of normal tissues during radiotherapy of tumours. Many synthetic as well as natural compounds have been investigated in the recent past for their efficacy to protect the biological systems from radiation induced damages. They include sulfhydryl compounds, antioxidants, plant extracts, immune-modulators, and other agents. However, the inherent toxicity of many of the synthetic agents at the effective radio-protective concentration warranted further search for safer and more effective radio-protectors. In this context, therapeutic radioprotectors which are effective on post irradiation administration are of special relevance. One of the property that can be applied while screening for such radiation protective therapeutics is their ability to enhance repair of radiation-induced lesions in cellular DNA in terms of cellular repair index based on the parameters of the DNA following comet assay. Post irradiation administration of some natural and synthetic agents have shown their potential to enhance repair of radiation-induced strand breaks in cellular DNA in mice. These include phytoceuticals such as gallic acid, sesamol etc., extracts of medicinal plants such as Andrographis panniculata, and a few synthetic compounds such as tocopherol-mono-glucoside. The talk will give an overview of the work on DNA repair enhancement by a few natural and synthetic agents. (author)

Shakuyakukanzoto attenuates oxaliplatin-induced cold dysesthesia by inhibiting the expression of transient receptor potential melastatin 8 in mice

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Tsugunobu Andoh

2017-01-01

Full Text Available Oxaliplatin-induced peripheral neuropathy characterized especially as cold dysesthesia is a major dose-limiting side effect of the drug and is very difficult to control. In the present study, we examined whether the traditional herbal formulation Shakuyakukanzoto (SKT: 芍藥甘草湯Sháo Yào Gān Cǎo Tāng could relieve oxaliplatin-induced cold dysesthesia in mice. The inhibitory mechanisms were also investigated. Repetitive administration of SKT (0.1–1.0 g/kg starting from the day after oxaliplatin injection inhibited cold dysesthesia in a dose-dependent manner. Our previous report has shown that the mRNA expression of transient receptor potential melastatin 8 (TRPM8, characterized as a cold-sensing cation channel, is increased in the dorsal root ganglia of mice treated with oxaliplatin. In addition, TRPM8 antagonist TC-I 2014 (10 and 30 mg/kg also attenuated cold dysesthesia in oxaliplatin-treated mice. Taken together, it is suggested that TRPM8 is involved in the cold dysesthesia induced by oxaliplatin. Repetitive administration of SKT inhibited the mRNA expression of TRPM8 induced by oxaliplatin in the dorsal root ganglia. These results suggested that prophylactic repetitive administration of SKT is effective in preventing the exacerbation of oxaliplatin-induced cold dysesthesia by inhibiting the mRNA expression of TRPM8 in the dorsal root ganglia.

Potential-induced structural transitions of DL-homocysteine monolayers on Au(111) electrode surfaces

International Nuclear Information System (INIS)

Zhang Jingdong; Demetriou, Anna; Welinder, Anne Christina; Albrecht, Tim; Nichols, Richard J.; Ulstrup, Jens

2005-01-01

Monolayers of homocysteine on Au(111)-surfaces have been investigated by voltammetry, in situ scanning tunnelling microscopy (STM) and subtractively normalised interfacial Fourier transform spectroscopy (SNIFTIRS). A pair of sharp voltammetric peaks build up in the potential range 0 to -0.1V (vs. SCE) in phosphate buffer pH 7.7. The peak half-widths are about 25mV at a scan rate of 10mVs -1 . This is much smaller than for a one-electron Faradaic process (90.6mV) under similar conditions. The coverage of homocysteine is 6.1 (+/-0.2)x10 -10 molcm -2 , or 5.9x10 -5 Ccm -2 , from Au-S reductive desorption at -0.8V (SCE) in 0.1M NaOH, while the charge is only about 8x10 -6 Ccm -2 (pH 7.7) for the 0 to -0.1V peak. This suggests a capacitive origin. The peak potential and shape depend on pH. At pH 7.7 both cathodic and anodic peak currents reach a maximum, but drop at both higher and lower pH. The midpoint potential shows biphasic behaviour, decreasing linearly with increasing pH until pH 10.4 towards a constant value at higher pH. The cathodic and anodic peak charges decay at pH both higher and lower than 7.7. The homocysteine monolayer was investigated by in situ STM at different potentials at pH 7.7. The molecules pack into highly ordered domains around the peak potential. High-resolution in situ STM reveals a (√3x5) R30 deg. lattice with three homocysteine molecules in each unit cell. The adlayer changes into disordered structures on either side of the peak potential. This process is reversible. We propose that the voltammetric peaks are capacitive. The ordered domains are formed only around the potential of zero charge (pzc) and dissipate at potentials on either side of the peak, inducing mirror charge flow in the metallic electrode as the charged -COO - and -NH 3 + groups approach the surface. No bands for carboxylate coordinated to the surface were observed in SNIFTIRS implying more subtle orientation changes of the charged groups on transcending the voltammetric

Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: A potential model to study carpal tunnel syndrome?

NARCIS (Netherlands)

Oh, S.; Ettema, A.M.; Zhao, C.; Zobitz, M.E.; Wold, L.E.; An, K.N.; Amadio, P.C.

2008-01-01

In this pilot study, hypertonic dextrose solution was used to induce fibrosis of the subsynovial connective tissue (SSCT) and create an animal model of potential use in the study of carpal tunnel syndrome (CTS). The SSCT of the carpal tunnel in 15 New Zealand white rabbits were injected with 0.05 ml

Potential and Challenges of Induced Pluripotent Stem Cells in Liver Diseases Treatment

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Yue Yu

2014-09-01

Full Text Available Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from cell therapy involving living metabolically active cells, either by treatment of their liver disease, or by prevention of their disease phenotype. Cell therapies, including hepatocyte transplantation and bioartificial liver (BAL devices, have been proposed as therapeutic alternatives to the shortage of transplantable livers. Both BAL and hepatocyte transplantation are cellular therapies that avoid use of a whole liver. Hepatocytes are also widely used in drug screening and liver disease modelling. However, the demand for human hepatocytes, heavily outweighs their availability by conventional means. Induced pluripotent stem cells (iPSCs technology brings together the potential benefits of embryonic stem cells (ESCs (i.e., self-renewal, pluripotency and addresses the major ethical and scientific concerns of ESCs: embryo destruction and immune-incompatibility. It has been shown that hepatocyte-like cells (HLCs can be generated from iPSCs. Furthermore, human iPSCs (hiPSCs can provide an unlimited source of human hepatocytes and hold great promise for applications in regenerative medicine, drug screening and liver diseases modelling. Despite steady progress, there are still several major obstacles that need to be overcome before iPSCs will reach the bedside. This review will focus on the current state of efforts to derive hiPSCs for potential use in modelling and treatment of liver disease.

Honey potentiates the gastric protection effects of sucralfate against ammonia-induced gastric lesions in rats.

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Ali, Abu Taib Mohammad Mobarok; Al Swayeh, Othman Abdullah

2003-09-01

Natural honey is widely used all over the world as a complementary and alternative medicine in various disorders including gastrointestinal lesions. To evaluate the effects of combination of low dosage of honey (0.312 g/kg) and sucralfate (0.125 or 0.250 g /kg) on gastric protection and to determine any potentiating interactions between them against ammonia-induced gastric lesions in rats. Twenty-four hours fasted rats were given I ml of ammonium hydroxide 1 % intragastrically and they were killed one hour later under deep ether anesthesia. The gastric lesion index was calculated according to the method of Takaishi et al 1998. Non protein sulthydryls level was determined spectrophotometrically as described by Sedlak and Lindsay 1968. Administration of ammonium hydroxide produced red and black linear lesions and significant depletion of gastric nonprotein sulthydryls level. Oral administration of honey (0.312g/kg) or sucralfate (0.125 and 0.250 g/kg) 30 min before ammonium hydroxide reduced the severity of gastric mucosal lesions by 1 I or 18 and 42 % respectively, and has shown the changes in nonprotein sulfhydryls level induced by ammonium hydroxide. Furthermore, pretreatment with a combination of a low dose of honey (0.312 g /kg) and sucralfate (0.125 g or 0.250 g/kg) afforded significantly greater protection (58 and 77 %) than that obtained with either of them administered alone. The present results suggest potentiation of gastric protection effect of sucralfate by honey and this may have a clinical value in the treatment of peptic ulcer diseases in Helicobacter pylori positive patients.

Anesthetic-Induced Oxidative Stress and Potential Protection

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Cheng Wang

2010-01-01

Full Text Available Prolonged exposure of developing mammals to general anesthetics affects the N-methyl-D-aspartate (NMDA–type glutamate or γ-aminobutyric acid (GABA receptor systems and enhances neuronal toxicity. Stimulation of immature neurons by NMDA antagonists or GABA agonists is thought to increase overall nervous system excitability and may contribute to abnormal neuronal cell death during development. Although the precise mechanisms by which NMDA antagonists or GABA agonists cause neuronal cell death are still not completely understood, up-regulation of the NMDA receptor subunit NR1 may be an initiative factor in neuronal cell death. It is increasingly apparent that mitochondria lie at the center of the cell death regulation process. Evidence for the role of oxidative stress in anesthetic-induced neurotoxicity has been generated in studies that apply oxidative stress blockers. Prevention of neuronal death by catalase and superoxide dismutase in vitro, or by M40403 (superoxide dismutase mimetic in vivo, supports the contention that the involvement of reactive oxygen species (ROS and the nature of neuronal cell death in rodents is mainly apoptotic. However, more evidence is necessary to in order verify the role of the NMDA receptor subunit NR1 and ROS in anesthetic-induced neurodegeneration.

Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

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Daniel Minge

Full Text Available Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP dynamics immediately following status epilepticus (SE in mice. SE was induced by intraperitoneal (i.p. injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV. No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP, was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP-induced Ca(2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+ and K(+ current components.

Valproic acid-induced hyperammonemic encephalopathy - a potentially fatal adverse drug reaction.

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Sousa, Carla

2013-12-01

A patient with an early diagnosed epilepsy Valproic acid is one of the most widely used antiepileptic drugs. Hyperammonemic encephalopathy is a rare, but potentially fatal, adverse drug reaction to valproic acid. A patient with an early diagnosed epilepsy, treated with valproic acid, experienced an altered mental state after 10 days of treatment. Valproic acid serum levels were within limits, hepatic function tests were normal but ammonia levels were above the normal range. Valproic acid was stopped and the hyperammonemic encephalopathy was treated with lactulose 15 ml twice daily, metronidazole 250 mg four times daily and L-carnitine 1 g twice daily. Monitoring liver function and ammonia levels should be recommended in patients taking valproic acid. The constraints of the pharmaceutical market had to be taken into consideration and limited the pharmacological options for this patient's treatment. Idiosyncratic symptomatic hyperammonemic encephalopathy is completely reversible, but can induce coma and even death, if not timely detected. Clinical pharmacists can help detecting adverse drug reactions and provide evidence based information for the treatment.

Transient thermal driven bubble's surface and its potential ultrasound-induced damage

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Movahed, Pooya; Freund, Jonathan B.

2017-11-01

Ultrasound-induced bubble activity in soft tissues is well-known to be a potential injury mechanism in therapeutic ultrasound treatments. We consider damage by transient thermal effects, including a hypothetical mechanism based on transient thermal phenomena, including viscous dissipation. A spherically symmetric compressible Navier-Stokes discretization is developed to solve the full governing equations, both inside and outside of the bubble, without the usual simplifications in the Rayleigh-Plesset bubble dynamics approach. Equations are solved in the Lagrangian framework, which provides a sharp and accurate representation of the interface as well as the viscous dissipation and thermal transport effects, which preclude reduction to the usual Rayleigh-Plesset ordinary differential equation. This method is used to study transient thermal effects at different frequencies and pressure amplitudes relevant to therapeutic ultrasound treatments. High temperatures achieved in the surrounding medium during the violent bubble collapse phase due to the viscous dissipation in the surrounding medium and thermal conduction from the bubble are expected to cause damage. This work was supported by NIH NIDDK Grant P01-DK043881.

Potential protective effect of honey against paracetamol-induced hepatotoxicity.

Science.gov (United States)

Galal, Reem M; Zaki, Hala F; Seif El-Nasr, Mona M; Agha, Azza M

2012-11-01

Paracetamol overdose causes severe hepatotoxicity that leads to liver failure in both humans and experimental animals. The present study investigates the protective effect of honey against paracetamol-induced hepatotoxicity in Wistar albino rats. We have used silymarin as a standard reference hepatoprotective drug. Hepatoprotective activity was assessed by measuring biochemical parameters such as the liver function enzymes, serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST). Equally, comparative effects of honey on oxidative stress biomarkers such as malondialdyhyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were also evaluated in the rat liver homogenates.  We estimated the effect of honey on serum levels and hepatic content of interleukin-1beta (IL-1β) because the initial event in paracetamol-induced hepatotoxicity has been shown to be a toxic-metabolic injury that leads to hepatocyte death, activation of the innate immune response and upregulation of inflammatory cytokines. Paracetamol caused marked liver damage as noted by significant increased activities of serum AST and ALT as well as the level of Il-1β. Paracetamol also resulted in a significant decrease in liver GSH content and GPx activity which paralleled an increase in Il-1β and MDA levels. Pretreatment with honey and silymarin prior to the administration of paracetamol significantly prevented the increase in the serum levels of hepatic enzyme markers, and reduced both oxidative stress and inflammatory cytokines. Histopathological evaluation of the livers also revealed that honey reduced the incidence of paracetamol-induced liver lesions. Honey can be used as an effective hepatoprotective agent against paracetamol-induced liver damage.

Microstructure and fracture toughness of irradiated stainless steel retrieved from the field: the potential role of radiation-induced clusters

International Nuclear Information System (INIS)

Chou, P.; Soneda, N.; Nishida, K.; Dohi, K.; Marquis, E.A.; Chen, Y.

2015-01-01

The microstructures of six material/fluence combinations of stainless steels retrieved from BWR components (top guide and control rods) have been examined by atom probe tomography; the irradiated microstructure had been already characterized by transmission electron microscopy (TEM). The fracture toughness of two material/fluence combinations had been previously measured. The aggregate results strongly suggest that radiation-induced clusters play a significant role in the degradation of fracture toughness that occurs at fluences below ∼ 13 dpa. Because TEM has not been able to consistently identify and quantify the nano-sized clusters in this fluence range, it has not highlighted the potential role of radiation-induced clusters. (authors)

Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

International Nuclear Information System (INIS)

Stoilov, L.M.; Mullenders, L.H.F.; Natarajan, A.T.

1994-01-01

The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations

Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

Energy Technology Data Exchange (ETDEWEB)

Stoilov, L.M. (Department of Molecular Genetics, Institute of Genetics, Sofia (Bulgaria)); Mullenders, L.H.F.; Natarajan, A.T. (J.A. Cohen Institute, Interuniversity Research Institute for Radiopathology and Radiation Protection, Leiden (Netherlands))

1994-12-01

The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations.

Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.

Science.gov (United States)

Palmeri, Agostino; Ricciarelli, Roberta; Gulisano, Walter; Rivera, Daniela; Rebosio, Claudia; Calcagno, Elisa; Tropea, Maria Rosaria; Conti, Silvia; Das, Utpal; Roy, Subhojit; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto; Puzzo, Daniela

2017-07-19

High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking Aβ function, by using anti-murine Aβ antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates Aβ levels in the healthy brain which, in turn, boosts synaptic plasticity and memory. SIGNIFICANCE STATEMENT Amyloid-β (Aβ) is a key pathogenetic factor in Alzheimer's disease. However, low concentrations of endogenous Aβ, mimicking levels of the peptide in the healthy brain, enhance hippocampal long-term potentiation (LTP) and memory. Because the second messenger cGMP exerts a central role in LTP mechanisms, here we studied whether cGMP affects Aβ levels and function during LTP. We show that cGMP enhances Aβ production by increasing the APP/BACE-1 convergence in endolysosomal compartments. Moreover, the cGMP-induced enhancement of LTP and memory was disrupted by blockade of Aβ, suggesting that the physiological effect of the cyclic nucleotide on LTP and memory is dependent upon Aβ. Copyright © 2017 the authors 0270-6474/17/376926-12$15.00/0.

Electrophysiological Characteristics of Human iPSC-Derived Cardiomyocytes for the Assessment of Drug-Induced Proarrhythmic Potential.

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Wataru Yamamoto

Full Text Available The aims of this study were to (1 characterize basic electrophysiological elements of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs that correspond to clinical properties such as QT-RR relationship, (2 determine the applicability of QT correction and analysis methods, and (3 determine if and how these in-vitro parameters could be used in risk assessment for adverse drug-induced effects such as Torsades de pointes (TdP. Field potential recordings were obtained from commercially available hiPSC-CMs using multi-electrode array (MEA platform with and without ion channel antagonists in the recording solution. Under control conditions, MEA-measured interspike interval and field potential duration (FPD ranged widely from 1049 to 1635 ms and from 334 to 527 ms, respectively and provided positive linear regression coefficients similar to native QT-RR plots obtained from human electrocardiogram (ECG analyses in the ongoing cardiovascular-based Framingham Heart Study. Similar to minimizing the effect of heart rate on the QT interval, Fridericia's and Bazett's corrections reduced the influence of beat rate on hiPSC-CM FPD. In the presence of E-4031 and cisapride, inhibitors of the rapid delayed rectifier potassium current, hiPSC-CMs showed reverse use-dependent FPD prolongation. Categorical analysis, which is usually applied to clinical QT studies, was applicable to hiPSC-CMs for evaluating torsadogenic risks with FPD and/or corrected FPD. Together, this results of this study links hiPSC-CM electrophysiological endpoints to native ECG endpoints, demonstrates the appropriateness of clinical analytical practices as applied to hiPSC-CMs, and suggests that hiPSC-CMs are a reliable models for assessing the arrhythmogenic potential of drug candidates in human.

Radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (Family: Poaceae), against radiation-induced cytogenetic damage

International Nuclear Information System (INIS)

Satish Rao, B.S.; Upadhya, D.; Adiga, S.K.

2007-01-01

The exposure of humans to ionizing radiations may be advertently by routine diagnostic and therapeutic purposes or inadvertently during natural, occupational and nuclear accident situations. Therefore, in order to overcome the deleterious biological effects of radiation several chemical agents have been studied for their radioprotective potential. The medicinal plants being one of the resources for such clinically important natural agents, used extensively in several drug discovery related research. Here the radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (Family: Poaceae), against radiation-induced cytogenetic damage was analyzed using Chinese hamster fibroblast cells (V79) and human peripheral blood lymphocytes (HPBLs) growing in vitro is reported

Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242.

Science.gov (United States)

Ranganathan, M; DeMartinis, N; Huguenel, B; Gaudreault, F; Bednar, M M; Shaffer, C L; Gupta, S; Cahill, J; Sherif, M A; Mancuso, J; Zumpano, L; D'Souza, D C

2017-11-01

There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine. The current study assessed whether the AMPAR potentiator PF-04958242 would attenuate ketamine-induced deficits in verbal learning and memory in humans. Healthy male subjects (n=29) participated in two randomized treatment periods of daily placebo or PF-04958242 for 5 days separated by a washout period. On day 5 of each treatment period, subjects underwent a ketamine infusion for 75 min during which the effects of PF-04958242/placebo were assessed on ketamine-induced: (1) impairments in verbal learning and recall measured by the Hopkins Verbal Learning Test; (2) impairments in working memory on a CogState battery; and (3) psychotomimetic effects measured by the Positive and Negative Syndrome Scale and Clinician-Administered Dissociative Symptoms Scale. PF-04958242 significantly reduced ketamine-induced impairments in immediate recall and the 2-Back and spatial working memory tasks (CogState Battery), without significantly attenuating ketamine-induced psychotomimetic effects. There were no pharmacokinetic interactions between PF-04958242 and ketamine. Furthermore, PF-04958242 was well tolerated. 'High-impact' AMPAR potentiators like PF-04958242 may have a role in the treatment of the cognitive symptoms, but not the positive or negative symptoms, associated with schizophrenia. The excellent concordance between the

The nonsteroidal anti-inflammatory drug indomethacin induces heterogeneity in lipid membranes: potential implication for its diverse biological action.

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Yong Zhou

2010-01-01

Full Text Available The nonsteroidal anti-inflammatory drug (NSAID, indomethacin (Indo, has a large number of divergent biological effects, the molecular mechanism(s for which have yet to be fully elucidated. Interestingly, Indo is highly amphiphilic and associates strongly with lipid membranes, which influence localization, structure and function of membrane-associating proteins and actively regulate cell signaling events. Thus, it is possible that Indo regulates diverse cell functions by altering micro-environments within the membrane. Here we explored the effect of Indo on the nature of the segregated domains in a mixed model membrane composed of dipalmitoyl phosphatidyl-choline (di16:0 PC, or DPPC and dioleoyl phosphatidyl-choline (di18:1 PC or DOPC and cholesterol that mimics biomembranes.Using a series of fluorescent probes in a fluorescence resonance energy transfer (FRET study, we found that Indo induced separation between gel domains and fluid domains in the mixed model membrane, possibly by enhancing the formation of gel-phase domains. This effect originated from the ability of Indo to specifically target the ordered domains in the mixed membrane. These findings were further confirmed by measuring the ability of Indo to affect the fluidity-dependent fluorescence quenching and the level of detergent resistance of membranes.Because the tested lipids are the main lipid constituents in cell membranes, the observed formation of gel phase domains induced by Indo potentially occurs in biomembranes. This marked Indo-induced change in phase behavior potentially alters membrane protein functions, which contribute to the wide variety of biological activities of Indo and other NSAIDs.

Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

Science.gov (United States)

Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

2013-01-01

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Immunotoxicity and allergic potential induced by topical application of dimethyl carbonate (DMC) in a murine model

Science.gov (United States)

Anderson, Stacey E.; Franko, Jennifer; Anderson, Katie L.; Munson, Albert E.; Lukomska, Ewa; Meade, B. Jean

2015-01-01

Dimethyl carbonate (DMC) is an industrial chemical, used as a paint and adhesive solvent, with the potential for significant increases in production. Using select immune function assays, the purpose of these studies was to evaluate the immunotoxicity of DMC following dermal exposure using a murine model. Following a 28-day exposure, DMC produced a significant decrease in thymus weight at concentrations of 75% and greater. No effects on body weight, hematological parameters (erythrocytes, leukocytes, and their differentials), or immune cell phenotyping (B-cells, T-cells, and T-cell sub-sets) were identified. The IgM antibody response to sheep red blood cell (SRBC) was significantly reduced in the spleen but not the serum. DMC was not identified to be an irritant and evaluation of the sensitization potential, conducted using the local lymph node assay (LLNA) at concentrations ranging from 50–100%, did not identify increases in lymphocyte proliferation. These results demonstrate that dermal exposure to DMC induces immune suppression in a murine model and raise concern about potential human exposure and the need for occupational exposure regulations. PMID:22953780

Serotonin potentiates transforming growth factor-beta3 induced biomechanical remodeling in avian embryonic atrioventricular valves.

Directory of Open Access Journals (Sweden)

Philip R Buskohl

Full Text Available Embryonic heart valve primordia (cushions maintain unidirectional blood flow during development despite an increasingly demanding mechanical environment. Recent studies demonstrate that atrioventricular (AV cushions stiffen over gestation, but the molecular mechanisms of this process are unknown. Transforming growth factor-beta (TGFβ and serotonin (5-HT signaling modulate tissue biomechanics of postnatal valves, but less is known of their role in the biomechanical remodeling of embryonic valves. In this study, we demonstrate that exogenous TGFβ3 increases AV cushion biomechanical stiffness and residual stress, but paradoxically reduces matrix compaction. We then show that TGFβ3 induces contractile gene expression (RhoA, aSMA and extracellular matrix expression (col1α2 in cushion mesenchyme, while simultaneously stimulating a two-fold increase in proliferation. Local compaction increased due to an elevated contractile phenotype, but global compaction appeared reduced due to proliferation and ECM synthesis. Blockade of TGFβ type I receptors via SB431542 inhibited the TGFβ3 effects. We next showed that exogenous 5-HT does not influence cushion stiffness by itself, but synergistically increases cushion stiffness with TGFβ3 co-treatment. 5-HT increased TGFβ3 gene expression and also potentiated TGFβ3 induced gene expression in a dose-dependent manner. Blockade of the 5HT2b receptor, but not 5-HT2a receptor or serotonin transporter (SERT, resulted in complete cessation of TGFβ3 induced mechanical strengthening. Finally, systemic 5-HT administration in ovo induced cushion remodeling related defects, including thinned/atretic AV valves, ventricular septal defects, and outflow rotation defects. Elevated 5-HT in ovo resulted in elevated remodeling gene expression and increased TGFβ signaling activity, supporting our ex-vivo findings. Collectively, these results highlight TGFβ/5-HT signaling as a potent mechanism for control of biomechanical

Arctigenin, a Potential Anti-Arrhythmic Agent, Inhibits Aconitine-Induced Arrhythmia by Regulating Multi-Ion Channels

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Zhenying Zhao

2013-11-01

Full Text Available Background/Aims: Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. Methods: A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD, sodium current (INa, L-type calcium current (ICa, L and transient outward potassium current (Ito were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Results: Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90 were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited INa and ICa,L and attenuated the aconitine-increased INa and ICa,L by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine. Conclusions: Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, INa, ICa, L, and Ito may be multiple targets of arctigenin, leading to its antiarrhythmic effect.

Inducing magneto-electric response in topological insulator

International Nuclear Information System (INIS)

Zeng, Lunwu; Song, Runxia; Zeng, Jing

2013-01-01

Utilizing electric potential and magnetic scalar potential formulas, which contain zero-order Bessel functions of the first kind and the constitutive relations of topological insulators, we obtained the induced magnetic scalar potentials and induced magnetic monopole charges which are induced by a point charge in topological insulators. The results show that infinite image magnetic monopole charges are generated by a point electric charge. The magnitude of the induced magnetic monopole charges are determined not only by the point electric charge, but also by the material parameters. - Highlights: ► Electric potential and magnetic scalar potential which contain zero-order Bessel function of the first kind were derived. ► Boundary conditions of topological insulator were built. ► Induced monopole charges were worked out.

Evaluation of ameliorative potential of supranutritional selenium on enrofloxacin-induced testicular toxicity.

Science.gov (United States)

Rungsung, Soya; Khan, Adil Mehraj; Sood, Naresh Kumar; Rampal, Satyavan; Singh Saini, Simrat Pal

2016-05-25

The study was designed to assess the ameliorative potential of selenium (Se) on enrofloxacin-induced testicular toxicity in rats. There was a significant decrease in body weight and non-significant decrease in mean testicular weight of enrofloxacin treated rats. In enrofloxacin treated rats, total sperm count and viability decreased where as sperm abnormalities increased. Testicular histopathology revealed dose dependent dysregulation of spermatogenesis and presence of necrotic debris in seminiferous tubules which was marginally improved with Se. Enrofloxacin also produced a dose dependent decrease in testosterone level. The activity of testicular antioxidant enzymes decreased where as lipid peroxidation increased in a dose-dependent manner. Se supplementation partially restored oxidative stress and sperm damage and did not affect the plasma concentrations of enrofloxacin or ciprofloxacain. The results indicate that enrofloxacin produces a dose-dependent testicular toxicity in rats that is moderately ameliorated with supranutritional Se. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.

Science.gov (United States)

Philippar, Ulrike; Roussos, Evanthia T; Oser, Matthew; Yamaguchi, Hideki; Kim, Hyung-Do; Giampieri, Silvia; Wang, Yarong; Goswami, Sumanta; Wyckoff, Jeffrey B; Lauffenburger, Douglas A; Sahai, Erik; Condeelis, John S; Gertler, Frank B

2008-12-01

The spread of cancer during metastatic disease requires that tumor cells subvert normal regulatory networks governing cell motility to invade surrounding tissues and migrate toward blood and lymphatic vessels. Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) proteins regulate cell motility by controlling the geometry of assembling actin networks. Mena, an Ena/VASP protein, is upregulated in the invasive subpopulation of breast cancer cells. In addition, Mena is alternately spliced to produce an invasion isoform, Mena(INV). Here we show that Mena and Mena(INV) promote carcinoma cell motility and invasiveness in vivo and in vitro, and increase lung metastasis. Mena and Mena(INV) potentiate epidermal growth factor (EGF)-induced membrane protrusion and increase the matrix degradation activity of tumor cells. Interestingly, Mena(INV) is significantly more effective than Mena in driving metastases and sensitizing cells to EGF-dependent invasion and protrusion. Upregulation of Mena(INV) could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels.

Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials.

Science.gov (United States)

La Cesa, S; Di Stefano, G; Leone, C; Pepe, A; Galosi, E; Alu, F; Fasolino, A; Cruccu, G; Valeriani, M; Truini, A

2018-01-01

In the neurophysiological assessment of patients with neuropathic pain, laser evoked potentials (LEPs), contact heat evoked potentials (CHEPs) and the evoked potentials by the intraepidermal electrical stimulation via concentric needle electrode are widely agreed as nociceptive specific responses; conversely, the nociceptive specificity of evoked potentials by surface concentric electrode (SE-PREPs) is still debated. In this neurophysiological study we aimed at verifying the nociceptive specificity of SE-PREPs. We recorded LEPs, CHEPs and SE-PREPs in eleven healthy participants, before and after epidermal denervation produced by prolonged capsaicin application. We also used skin biopsy to verify the capsaicin-induced nociceptive nerve fibre loss in the epidermis. We found that whereas LEPs and CHEPs were suppressed after capsaicin-induced epidermal denervation, the surface concentric electrode stimulation of the same denervated skin area yielded unchanged SE-PREPs. The suppression of LEPs and CHEPs after nociceptive nerve fibre loss in the epidermis indicates that these techniques are selectively mediated by nociceptive system. Conversely, the lack of SE-PREP changes suggests that SE-PREPs do not provide selective information on nociceptive system function. Capsaicin-induced epidermal denervation abolishes laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs), but leaves unaffected pain-related evoked potentials by surface concentric electrode (SE-PREPs). These findings suggest that unlike LEPs and CHEPs, SE-PREPs are not selectively mediated by nociceptive system. © 2017 European Pain Federation - EFIC®.

Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells

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Kim, Kitai; Zhao, Rui; Doi, Akiko; Ng, Kitwa; Unternaehrer, Juli; Cahan, Patrick; Hongguang, Huo; Loh, Yuin-Han; Aryee, Martin J.; Lensch, M. William; Li, Hu; Collins, James J.; Feinberg, Andrew P.; Daley, George Q.

2012-01-01

We compared bona-fide human induced pluripotent stem cells (iPSC) derived from umbilical cord blood (CB) and neonatal keratinocytes (K). As a consequence of both incomplete erasure of tissue-specific methylation and aberrant de novo methylation, CB-iPSC and K-iPSC are distinct in genome-wide DNA methylation profiles and differentiation potential. Extended passage of some iPSC clones in culture didn't improve their epigenetic resemblance to ESC, implying that some human iPSC retain a residual “epigenetic memory” of their tissue of origin. PMID:22119740

Computer-aided designing of immunosuppressive peptides based on IL-10 inducing potential

Science.gov (United States)

Nagpal, Gandharva; Usmani, Salman Sadullah; Dhanda, Sandeep Kumar; Kaur, Harpreet; Singh, Sandeep; Sharma, Meenu; Raghava, Gajendra P. S.

2017-01-01

In the past, numerous methods have been developed to predict MHC class II binders or T-helper epitopes for designing the epitope-based vaccines against pathogens. In contrast, limited attempts have been made to develop methods for predicting T-helper epitopes/peptides that can induce a specific type of cytokine. This paper describes a method, developed for predicting interleukin-10 (IL-10) inducing peptides, a cytokine responsible for suppressing the immune system. All models were trained and tested on experimentally validated 394 IL-10 inducing and 848 non-inducing peptides. It was observed that certain types of residues and motifs are more frequent in IL-10 inducing peptides than in non-inducing peptides. Based on this analysis, we developed composition-based models using various machine-learning techniques. Random Forest-based model achieved the maximum Matthews’s Correlation Coefficient (MCC) value of 0.59 with an accuracy of 81.24% developed using dipeptide composition. In order to facilitate the community, we developed a web server “IL-10pred”, standalone packages and a mobile app for designing IL-10 inducing peptides (http://crdd.osdd.net/raghava/IL-10pred/). PMID:28211521

Override of the radiation-induced mitotic block in human tumour cells by methylxanthines and its relationship to the potentiation of cytotoxicity

International Nuclear Information System (INIS)

Musk, S.R.R.; Steel, G.G.

1990-01-01

Caffeine, theophylline, theobromine and paraxanthine, were tested for ability to override mitotic block induced by ionizing radiation in the human bladder carcinoma cell line RT112. All were found to partially override the block, at a concentration of 1mM in the order caffeine > theophylline > theobromine = paraxanthine. At a concentration of 1 mM only caffeine was found to potentiate cell killing as well as causing block override; at higher concentrations all had a significant effect on survival but little or no further influence on the degree of block override. It is concluded that override of a mitotic block is not in itself sufficient to cause increased killing when irradiated cells are incubated in the presence of caffeine, and that caffeine exerts its potentiating effect by directly inhibiting repair of damage in DNA or by causing override of radiation-induced inhibition of DNA synthesis. (author)

Override of the radiation-induced mitotic block in human tumour cells by methylxanthines and its relationship to the potentiation of cytotoxicity

Energy Technology Data Exchange (ETDEWEB)

Musk, S.R.R.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

1990-06-01

Caffeine, theophylline, theobromine and paraxanthine, were tested for ability to override mitotic block induced by ionizing radiation in the human bladder carcinoma cell line RT112. All were found to partially override the block, at a concentration of 1mM in the order caffeine > theophylline > theobromine = paraxanthine. At a concentration of 1 mM only caffeine was found to potentiate cell killing as well as causing block override; at higher concentrations all had a significant effect on survival but little or no further influence on the degree of block override. It is concluded that override of a mitotic block is not in itself sufficient to cause increased killing when irradiated cells are incubated in the presence of caffeine, and that caffeine exerts its potentiating effect by directly inhibiting repair of damage in DNA or by causing override of radiation-induced inhibition of DNA synthesis. (author).

Protective potentials of wild rice (Zizania latifolia (Griseb) Turcz) against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats.

Science.gov (United States)

Han, Shu-Fen; Zhang, Hong; Zhai, Cheng-Kai

2012-07-01

The study evaluates the protective potentials of wild rice against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats. In addition to the rats of low-fat diet group, others animals were exposed to a high-fat/cholesterol diet condition for 8 weeks. The city diet (CD) is based on the diet consumed by urban residents in modern China, which is rich in fat/cholesterol and high in carbohydrates from white rice and processed wheat starch. The chief source of dietary carbohydrates of wild rice diet (WRD) is from Chinese wild rice and other compositions are the same with CD. Rats fed CD showed elevated body and liver organ weights, lipid profiles, free fatty acids (FFA) and leptin comparable with rats fed high-fat/cholesterol diet (HFD) known to induce obesity and hyperlipidaemia in this species. However, rats consuming WRD suppressed the increase of lipid droplets accumulation, FFA, and leptin, and the decrease of lipoprotein lipase and adipose triglyceride lipase. Meanwhile, WRD prevented high-fat/cholesterol diet-induced elevation in protein expression of sterol-regulatory element binding protein-1c, and gene expression of fatty acid synthase and acetyl-CoA carboxylase. These findings indicate that wild rice as a natural food has the potentials of preventing obesity and liver lipotoxicity induced by a high-fat/cholesterol diet in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

Science.gov (United States)

Hirata, Riki; Togashi, Hiroko; Matsumoto, Machiko; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro

2008-08-21

Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

Inducing magneto-electric response in topological insulator

Energy Technology Data Exchange (ETDEWEB)

Zeng, Lunwu, E-mail: 163.sin@163.com [Jiangsu Key Laboratory for Intelligent Agricultural Equipment, College of Engineering, Nanjing Agricultural University, Nanjing 210031 (China); Song, Runxia [Jiangsu Key Laboratory for Intelligent Agricultural Equipment, College of Engineering, Nanjing Agricultural University, Nanjing 210031 (China); Zeng, Jing [Faculty of Business and Economics, Macquarie University, NSW 2122 (Australia)

2013-02-15

Utilizing electric potential and magnetic scalar potential formulas, which contain zero-order Bessel functions of the first kind and the constitutive relations of topological insulators, we obtained the induced magnetic scalar potentials and induced magnetic monopole charges which are induced by a point charge in topological insulators. The results show that infinite image magnetic monopole charges are generated by a point electric charge. The magnitude of the induced magnetic monopole charges are determined not only by the point electric charge, but also by the material parameters. - Highlights: Black-Right-Pointing-Pointer Electric potential and magnetic scalar potential which contain zero-order Bessel function of the first kind were derived. Black-Right-Pointing-Pointer Boundary conditions of topological insulator were built. Black-Right-Pointing-Pointer Induced monopole charges were worked out.

Potential of Induced Pluripotent Stem Cells (iPSCs for Treating Age-Related Macular Degeneration (AMD

Directory of Open Access Journals (Sweden)

Mark Fields

2016-12-01

Full Text Available The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD, Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD).

Science.gov (United States)

Fields, Mark; Cai, Hui; Gong, Jie; Del Priore, Lucian

2016-12-08

The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

Potential influence of climate-induced vegetation shifts on future land use and associated land carbon fluxes in Northern Eurasia

International Nuclear Information System (INIS)

Kicklighter, D W; Melillo, J M; Lu, X; Cai, Y; Paltsev, S; Sokolov, A P; Reilly, J M; Zhuang, Q; Parfenova, E I; Tchebakova, N M

2014-01-01

Climate change will alter ecosystem metabolism and may lead to a redistribution of vegetation and changes in fire regimes in Northern Eurasia over the 21st century. Land management decisions will interact with these climate-driven changes to reshape the region’s landscape. Here we present an assessment of the potential consequences of climate change on land use and associated land carbon sink activity for Northern Eurasia in the context of climate-induced vegetation shifts. Under a ‘business-as-usual’ scenario, climate-induced vegetation shifts allow expansion of areas devoted to food crop production (15%) and pastures (39%) over the 21st century. Under a climate stabilization scenario, climate-induced vegetation shifts permit expansion of areas devoted to cellulosic biofuel production (25%) and pastures (21%), but reduce the expansion of areas devoted to food crop production by 10%. In both climate scenarios, vegetation shifts further reduce the areas devoted to timber production by 6–8% over this same time period. Fire associated with climate-induced vegetation shifts causes the region to become more of a carbon source than if no vegetation shifts occur. Consideration of the interactions between climate-induced vegetation shifts and human activities through a modeling framework has provided clues to how humans may be able to adapt to a changing world and identified the trade-offs, including unintended consequences, associated with proposed climate/energy policies. (paper)

Estradiol-induced increase in the magnitude of long-term potentiation is prevented by blocking NR2B-containing receptors.

Science.gov (United States)

Smith, Caroline C; McMahon, Lori L

2006-08-16

Estradiol, through activation of genomic estrogen receptors, induces changes in synaptic morphology and function in hippocampus, a brain region important for memory acquisition. Specifically, this hormone increases CA1 pyramidal cell dendritic spine density, NMDA receptor (NMDAR)-mediated transmission, and the magnitude of long-term potentiation (LTP) at CA3-CA1 synapses. We recently reported that the estradiol-induced increase in LTP magnitude occurs only when there is a simultaneous increase in the fractional contribution of NMDAR-mediated transmission relative to AMPA receptor transmission, suggesting a direct role for the increase in NMDAR transmission to the heightened LTP magnitude. Estradiol has been shown to increase expression of the NMDAR subunit NR2B, but whether this translates into an increase in function of NR2B-containing receptors remains to be determined. Here we show that not only is the estradiol-induced increase in NMDAR transmission mediated by NR2B-containing receptors, but blocking these receptors using RO25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol] (0.5 microM), an NR2B selective antagonist, prevents the estradiol-induced increase in LTP magnitude. Thus, our data show a causal link between the estradiol-induced increase in transmission mediated by NR2B-containing NMDARs and the increase in LTP magnitude.

First-principles assessment of potential ultrafast laser-induced structural transition in Ni

Energy Technology Data Exchange (ETDEWEB)

Bévillon, E.; Colombier, J.P., E-mail: jean.philippe.colombier@univ-st-etienne.fr; Stoian, R.

2016-06-30

Highlights: • First-principles theory calculations in nonequilibrium conditions. • Electronic temperatures fully and consistently taken into account. • Evaluation of an ultrafast laser-induced solid-to-solid transition in Ni. • Relative energies, phonon spectra and energy path are evaluated. • Discussion on the generation of non-thermal forces in metals. - Abstract: The possibility to trigger ultrafast solid-to-solid transitions in transition metals under femtosecond laser irradiation is investigated by means of first-principles calculations. Electronic heating can drastically modify screening, charge distribution and atomic binding features, potentially determining new structural relaxation paths in the solid phase, before thermodynamic solid-to-liquid transformations set in. Consequently, we evaluate here the effect of electronic excitation on structural stability and conditions for structural transitions. Ni is chosen as a case study for the probability of a solid transition, and the stability of its FCC phase is compared to the non-standard HCP structure while accounting for the heating of the electronic subsystem. From a phonon spectra analysis, we show that the thermodynamic stability order reverses at an electronic temperature of around 10{sup 4} K. Both structures exhibit a dynamic stability, indicating they present a metastability depending on the heating. However, the general hardening of phonon modes with the increase of the electronic temperature points out that no transformation will occur, as confirmed by the study of a typical FCC to HCP diffusionless transformation path, showing an increasing energy barrier. Finally, based on electronic density of states interpretation, the tendency of different metal categories to undergo or not an ultrafast laser-induced structural transition is discussed.

[Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

Science.gov (United States)

Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

2009-08-18

It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a

Radiation-induced bystander effect: The important part of ionizing radiation response. Potential clinical implications

Directory of Open Access Journals (Sweden)

Maria Wideł

2009-08-01

Full Text Available It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the “bystander effect” or “radiation-induced bystander effect” (RIBE. This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy, but also after conventional irradiation (X-rays, gamma rays at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not defi nitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effectmay have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation fi eld and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The

Potential-induced degradation of Cu(In,Ga)Se2 photovoltaic modules

Science.gov (United States)

Yamaguchi, Seira; Jonai, Sachiko; Hara, Kohjiro; Komaki, Hironori; Shimizu-Kamikawa, Yukiko; Shibata, Hajime; Niki, Shigeru; Kawakami, Yuji; Masuda, Atsushi

2015-08-01

Potential-induced degradation (PID) of Cu(In,Ga)Se2 (CIGS) photovoltaic (PV) modules fabricated from integrated submodules is investigated. PID tests were performed by applying a voltage of -1000 V to connected submodule interconnector ribbons at 85 °C. The normalized energy conversion efficiency of a standard module decreases to 0.2 after the PID test for 14 days. This reveals that CIGS modules suffer PID under this experimental condition. In contrast, a module with non-alkali glass shows no degradation, which implies that the degradation occurs owing to alkali metal ions, e.g., Na+, migrating from the cover glass. The results of dynamic secondary ion mass spectrometry show Na accumulation in the n-ZnO transparent conductive oxide layer of the degraded module. A CIGS PV module with an ionomer (IO) encapsulant instead of a copolymer of ethylene and vinyl acetate shows no degradation. This reveals that the IO encapsulant can prevent PID of CIGS modules. A degraded module can recover from its performance losses by applying +1000 V to connected submodule interconnector ribbons from an Al plate placed on the test module.

Anti obese potential of Cucurbita maxima seeds oil: effect on lipid profile and histoarchitecture in high fat diet induced obese rats.

Science.gov (United States)

Kalaivani, A; Sathibabu Uddandrao, V V; Brahmanaidu, P; Saravanan, Ganapathy; Nivedha, P R; Tamilmani, P; Swapna, K; Vadivukkarasi, Sasikumar

2017-10-19

In this study, we made an attempt to evaluate the potential of Cucurbita maxima seeds oil (CSO) against high-fat diet (HFD)-induced obesity in rats. We investigated the effect of CSO (100 mg/kg body weight) supplementation over 30 days on the changes of HFD-induced obese rats in body weight, biochemical parameters and lipid profile as well as investigated the effects of CSO on the histopathological changes. Oral administration with CSO revealed significant diminution in body weight gain, glucose and insulin levels, which altered the activity of lipid profile and restored the pathological alterations. It demonstrated that CSO had considerably altered these parameters when evaluated with HFD control rats. In conclusion, this study established that CSO prevents the HFD-induced obesity by altering the markers important to lipid metabolism.

Arctigenin, a potential anti-arrhythmic agent, inhibits aconitine-induced arrhythmia by regulating multi-ion channels.

Science.gov (United States)

Zhao, Zhenying; Yin, Yongqiang; Wu, Hong; Jiang, Min; Lou, Jianshi; Bai, Gang; Luo, Guo'an

2013-01-01

Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I(Na)), L-type calcium current (I(Ca, L)) and transient outward potassium current (I(to)) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited I(Na) and I(Ca,L) and attenuated the aconitine-increased I(Na) and I(Ca,L) by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine. Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I(Na), I(Ca, L), and I(to) may be multiple targets of arctigenin, leading to its antiarrhythmic effect. © 2013 S. Karger AG, Basel.

Asarone from Acori Tatarinowii Rhizoma Potentiates the Nerve Growth Factor-Induced Neuronal Differentiation in Cultured PC12 Cells: A Signaling Mediated by Protein Kinase A.

Directory of Open Access Journals (Sweden)

Kelly Y C Lam

Full Text Available Acori Tatarinowii Rhizoma (ATR, the rhizome of Acorus tatarinowii Schott, is being used clinically to treat neurological disorders. The volatile oil of ATR is being considered as an active ingredient. Here, α-asarone and β-asarone, accounting about 95% of ATR oil, were evaluated for its function in stimulating neurogenesis. In cultured PC12 cells, application of ATR volatile oil, α-asarone or β-asarone, stimulated the expression of neurofilaments, a bio-marker for neurite outgrowth, in a concentration-dependent manner. The co-treatment of ATR volatile oil, α-asarone or β-asarone, with low concentration of nerve growth factor (NGF potentiated the NGF-induced neuronal differentiation in cultured PC12 cells. In addition, application of protein kinase A inhibitors, H89 and KT5720, in cultures blocked the ATR-induced neurofilament expression, as well as the phosphorylation of cAMP-responsive element binding protein (CREB. In the potentiation of NGF-induced signaling in cultured PC12 cells, α-asarone and β-asarone showed synergistic effects. These results proposed the neurite-promoting asarone, or ATR volatile oil, could be useful in finding potential drugs for treating various neurodegenerative diseases, in which neurotrophin deficiency is normally involved.

Local field potentials in the ventral tegmental area during cocaine-induced locomotor activation: Measurements in freely moving rats.

Science.gov (United States)

Harris Bozer, Amber L; Li, Ai-Ling; Sibi, Jiny E; Bobzean, Samara A M; Peng, Yuan B; Perrotti, Linda I

2016-03-01

The ventral tegmental area (VTA) has been established as a critical nucleus for processing behavioral changes that occur during psychostimulant use. Although it is known that cocaine induced locomotor activity is initiated in the VTA, not much is known about the electrical activity in real time. The use of our custom-designed wireless module for recording local field potential (LFP) activity provides an opportunity to confirm and identify changes in neuronal activity within the VTA of freely moving rats. The purpose of this study was to investigate the changes in VTA LFP activity in real time that underlie cocaine induced changes in locomotor behavior. Recording electrodes were implanted in the VTA of rats. Locomotor behavior and LFP activity were simultaneously recorded at baseline, and after saline and cocaine injections. Results indicate that cocaine treatment caused increases in both locomotor behavior and LFP activity in the VTA. Specifically, LFP activity was highest during the first 30 min following the cocaine injection and was most robust in Delta and Theta frequency bands; indicating the role of low frequency VTA activity in the initiation of acute stimulant-induced locomotor behavior. Our results suggest that LFP recording in freely moving animals can be used in the future to provide valuable information pertaining to drug induced changes in neural activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of the potential-drop method to measurements of hydrogen-induced sub-critical crack growth in zirconium-2.5 wt% niobium

International Nuclear Information System (INIS)

Simpson, L.A.; Clarke, C.F.

1977-10-01

Adaptation of the potential-drop method of crack-following to the problem of hydrogen-induced sub-critical crack growth in Zr-2.5% Nb is described. Reasons for non-linearity in the calibration of crack extension against potential drop in compact tension specimens are discussed. It is shown that despite non-linearities, careful comparison of fractographic features with the potential-drop record can lead to a continuous plot of crack velocity against time or stress intensity factor. Procedures for correcting data through temperature and load changes are also described. The application of the technique to studies of the mechanism of hydrogen crack growth is illustrated with several examples. (author)

Evaluation of the oxidative potential of urban Pm and its relation to in vitro induced DNA damage: a spatial and temporal comparison

Energy Technology Data Exchange (ETDEWEB)

Quintana B, R. O.; Alfaro M, E.; Garcia C, C. M.; Vazquez L, I. [Instituto Nacional de Cancerologia, Laboratorio de Toxicologia Ambiental, Av. San Fernando No. 22, Col. Seccion 16, 14080 Mexico D. F. (Mexico); Rosas P, I. [UNAM, Centro de Ciencias de la Atmosfera, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Gomez V, V.; Salmon S, M. de J. [UNAM, Instituto de Quimica, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Osornio V, A. R., E-mail: qbro@hotmail.com [University of Alberta, Edmonton Clinic Health Academy, 11405 87 Avenue, Edmonton, Alberta T6G 1C9 (Canada)

2015-07-01

Some toxic effects of particulate matter (Pm) are related to the oxidative potential (Op) of the particles. The electron paramagnetic resonance (EPR) technique was used to evaluate the intensity of paramagnetic species (Ps) and EPR plus spin trapping, to evaluate the Op of Pm. We evaluated, in parallel, the DNA degradation potential of PM{sub 10} and PM{sub 2.5} collected from three regions of Mexico City in 1991 and 2003. Each region had different sources of pollution; industrial, commercial or residential. Both techniques evaluated Fenton-type reactions in the presence and absence of deferoxamine. PM{sub 10} samples from the industrial region presented similar high Op, independently of sampling year. PM{sub 10} and PM{sub 2.5} collected in the commercial and residential regions in 2003 had similarly low Op. The Op induced by PM{sub 10} from the industrial region was completely inhibited by Dfo, and Dfo partially inhibited the Op induced by PM{sub 10} from other regions. PM{sub 2.5} Op was not inhibited by Dfo. Pm from the industrial region was the most potent inductor of DNA degradation, while Pm from residential region was the least potent, correlating with the Op. Dfo inhibited the degradation of DNA induced by Pm. The Op of Pm collected in the industrial and residential region correlated with the DNA degradation. The region, size and year of Pm collection are linked to observed Op variations and DNA degradation induced by Pm. (Author)

Antioxidant Potential of Spirulina platensis Mitigates Oxidative Stress and Reprotoxicity Induced by Sodium Arsenite in Male Rats

Directory of Open Access Journals (Sweden)

Samir A. E. Bashandy

2016-01-01

Full Text Available The present study aimed to examine the protective role of Spirulina platensis (S. platensis against arsenic-induced testicular oxidative damage in rats. Arsenic (in the form of NaAsO2 at a dose of 6.3 mg/kg body weight for 8 weeks caused a significant accumulation of arsenic in testicular tissues as well as a decrease in the levels of testicular superoxide dismutase (SOD, catalase (CAT, reduced glutathione, and zinc. Moreover, it significantly decreased plasma testosterone, luteinizing hormone (LH, triiodothyronine (T3, and thyroxine (T4 levels and reduced sperm motility and sperm count. Arsenic (AS led to a significant increase in testicular malondialdehyde (MDA, tumour necrosis factor alpha (TNF-α, nitric oxide (NO, and sperm abnormalities. S. platensis at a dose of 300 mg/kg was found to attenuate As-induced oxidative stress, testicular damage, and sperm abnormalities by its potent antioxidant activity. S. platensis may represent a potential therapeutic option to protect the testicular tissue from arsenic intoxication.

Antioxidant Potential of Spirulina platensis Mitigates Oxidative Stress and Reprotoxicity Induced by Sodium Arsenite in Male Rats

Science.gov (United States)

Bashandy, Samir A. E.; El Awdan, Sally A.; Ebaid, Hossam; Alhazza, Ibrahim M.

2016-01-01

The present study aimed to examine the protective role of Spirulina platensis (S. platensis) against arsenic-induced testicular oxidative damage in rats. Arsenic (in the form of NaAsO2 at a dose of 6.3 mg/kg body weight for 8 weeks) caused a significant accumulation of arsenic in testicular tissues as well as a decrease in the levels of testicular superoxide dismutase (SOD), catalase (CAT), reduced glutathione, and zinc. Moreover, it significantly decreased plasma testosterone, luteinizing hormone (LH), triiodothyronine (T3), and thyroxine (T4) levels and reduced sperm motility and sperm count. Arsenic (AS) led to a significant increase in testicular malondialdehyde (MDA), tumour necrosis factor alpha (TNF-α), nitric oxide (NO), and sperm abnormalities. S. platensis at a dose of 300 mg/kg was found to attenuate As-induced oxidative stress, testicular damage, and sperm abnormalities by its potent antioxidant activity. S. platensis may represent a potential therapeutic option to protect the testicular tissue from arsenic intoxication. PMID:26881036

Amorphization induced by chemical disorder in crystalline NiZr2: A molecular-dynamics study based on an n-body potential

International Nuclear Information System (INIS)

Massobrio, C.; Pontikis, V.; Martin, G.

1989-01-01

We present the first molecular-dynamics study of the amorphization of a crystalline alloy (NiZr 2 ) induced by chemical disorder. We used a n-body potential in conjunction with isobaric-isothermal molecular dynamics. The behavior of the pair distribution function suggests that the instability leading to the amorphous state is a first-order phase transformation

Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

International Nuclear Information System (INIS)

Martirosyan, Anna; Clendening, James W; Goard, Carolyn A; Penn, Linda Z

2010-01-01

Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes

Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory.

Science.gov (United States)

Tamano, Haruna; Fukura, Kotaro; Suzuki, Miki; Sakamoto, Kazuhiro; Yokogoshi, Hidehiko; Takeda, Atsushi

2013-06-01

Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after birth on mild stress-induced attenuation of hippocamapal CA1 long-term potentiation (LTP), the present study evaluated the effect of theanine intake after weaning on stress-induced impairments of LTP and recognition memory. Young rats were fed water containing 0.3% theanine for 3 weeks after weaning and subjected to water immersion stress for 30min, which was more severe than tail suspension stress for 30s used previously. Serum corticosterone levels were lower in theanine-administered rats than in the control rats even after exposure to stress. CA1 LTP induced by a 100-Hz tetanus for 1s was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, in hippocampal slices from the control rats and was attenuated by water immersion stress. In contrast, CA1 LTP was not significantly inhibited in the presence of APV in hippocampal slices from theanine-administered rats and was not attenuated by the stress. Furthermore, object recognition memory was impaired in the control rats, but not in theanine-administered rats. The present study indicates the preventive effect of theanine intake after weaning on stress-induced impairments of hippocampal LTP and recognition memory. It is likely that the modification of corticosterone secretion after theanine intake is involved in the preventive effect. Copyright © 2013 Elsevier Inc. All rights reserved.

Patch behaviour and predictability properties of modelled finite-amplitude sand ridges on the inner shelf

Directory of Open Access Journals (Sweden)

N. C. Vis-Star

2008-12-01

Full Text Available The long-term evolution of shoreface-connected sand ridges is investigated with a nonlinear spectral model which governs the dynamics of waves, currents, sediment transport and the bed level on the inner shelf. Wave variables are calculated with a shoaling-refraction model instead of using a parameterisation. The spectral model describes the time evolution of amplitudes of known eigenmodes of the linearised system. Bottom pattern formation occurs if the transverse bottom slope of the inner shelf, β, exceeds a critical value β_c. For fixed model parameters the sensitivity of the properties of modelled sand ridges to changes in the number (N−1 of resolved subharmonics (of the initially fastest growing mode is investigated. For any N the model shows the growth and subsequent saturation of the height of the sand ridges. The saturation time scale is several thousands of years, which suggests that observed sand ridges have not reached their saturated stage yet. The migration speed of the ridges and the average longshore spacing between successive crests in the saturated state differ from those in the initial state. Analysis of the potential energy balance of the ridges reveals that bed slope-induced sediment transport is crucial for the saturation process. In the transient stage the shoreface-connected ridges occur in patches. The overall characteristics of the bedforms (saturation time, final maximum height, average longshore spacing, migration speed hardly vary with N. However, individual time series of modal amplitudes and bottom patterns strongly depend on N, thereby implying that the detailed evolution of sand ridges can only be predicted over a limited time interval. Additional experiments show that the critical bed slope β_c increases with larger offshore angles of wave incidence, larger offshore wave heights and longer wave periods, and that the corresponding maximum height of the ridges

Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

International Nuclear Information System (INIS)

Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman

2013-01-01

Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano

Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

Energy Technology Data Exchange (ETDEWEB)

Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman, E-mail: prof_arkb@yahoo.co.in

2013-02-15

Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano

Influence of jasmonic acid as potential activator of induced ...

Indian Academy of Sciences (India)

MADU

seed vigor and reduction in market acceptability of the produce. ... effect prior to the challenge of infection and induces defense against KB probably by maintaining a critical balance ..... could be a strategy to combat KB infection through.

Potentiation of radiation-induced cell kill by synthetic metalloporphyrins

International Nuclear Information System (INIS)

O'Hara, J.A.; Douple, E.B.; Abrams, M.J.; Picker, D.J.; Giandomenico, C.M.; Vollano, J.F.

1989-01-01

The effects of the combination of several meso-substituted, water soluble metalloporphyrins with ionizing radiation on hypoxic and oxic monolayers of Chinese hamster fibroblast (V79N) cells were studied. The metalloporphyrins tested included a series of cationic metalloporphyrins complexed with Co(III), Zn(II), Fe(III), Cu(II), Pd(II) or Mn(III) and a series of anionic porphyrins chelated with Co(III), Fe(III), Cu(II), Rh(III), Mn(III) or Sn(IV). Both cationic and anionic free porphyrins were also tested. Cationic ligands were tetrakis(4N-methylpyridyl)porphine [TMPyP], tetrakis(4N-trimethylamino phenyl)porphine [TMAP], tetrakis(4N-butylpyridyl)porphine [TBPyP] and tetrakis(3N-methylpyridyl)porphine [3TMPyP]. Anionic ligands tested were tetrakis(4-sulfonato phenyl)porphine [TPPS], tetrakis(biphenyl)porphine sulfonate [TBPS] and tetrakis(4-carboxyphenyl)porphine [TCPP]. SER calculated from survival curves and SFR from one radiation dose were used to assess the relative effectiveness of this class as non-cytotoxic hypoxic and oxic cell-kill potentiators. Comparisons were made at 100 microM, which was essentially non-toxic (greater than 70% survival) for all porphyrins tested except for Co[TMPyP] (approximately 50% survival after 1 hour at 37 degrees C under oxic conditions). The greatest effects on radiation-induced cell kill were achieved with Co[TPPS] and Co[TMPyP] with SER values of 2.3 and 2.4 respectively. Porphyrin analogs with no coordinated metal were found to be less active than the same compound with metal. The overall charge on the molecule did not systematically relate to the biological activity of the compounds tested

A fibroblast/macrophage co-culture model to evaluate the biocompatibility of an electrospun Dextran/PLGA scaffold and its potential to induce inflammatory responses

International Nuclear Information System (INIS)

Pan Hui; Kantharia, Sarah; Jiang Hongliang; Chen Weiliam

2011-01-01

Fibroblasts and macrophages are the two major types of cells responding to implanted biomaterials. They play crucial roles in inflammatory responses, host-material interactions and tissue remodeling. However, the synergistic interactions of these two cell types with biomaterials are not fully understood. In this investigation, an in vitro fibroblast/macrophage co-culture system was utilized to examine the biocompatibility and the potential to induce inflammatory responses of an electrospun Dextran/PLGA scaffold. The scaffold did not affect the morphologies, attachments, proliferations and viabilities of both the fibroblasts and macrophages, cultured separately or together. Moreover, it only activated a small subset of the macrophages implicating a low potential to induce either severe acute or chronic inflammatory response. Additionally, fibroblasts played a role in prolonging macrophage activation in the presence of the scaffolds. Using antibody arrays, IL-10, SDF-1, MIP-1 gamma and RANTES were found to be up-regulated when the cells were incubated with the scaffolds. The results of subdermal implantation of the Dextran/PLGA scaffolds confirmed its biocompatibility and low inflammatory potential.

A fibroblast/macrophage co-culture model to evaluate the biocompatibility of an electrospun Dextran/PLGA scaffold and its potential to induce inflammatory responses

Energy Technology Data Exchange (ETDEWEB)

Pan Hui; Kantharia, Sarah [Department of Biomedical Engineering, State University of New York-Stony Brook, Stony Brook, NY 11794-2580 (United States); Jiang Hongliang [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Chen Weiliam, E-mail: weiliam.chen@nyumc.org [Division of Wound Healing and Regenerative Medicine, Department of Surgery, New York University School of Medicine, New York, NY 10016 (United States)

2011-12-15

Fibroblasts and macrophages are the two major types of cells responding to implanted biomaterials. They play crucial roles in inflammatory responses, host-material interactions and tissue remodeling. However, the synergistic interactions of these two cell types with biomaterials are not fully understood. In this investigation, an in vitro fibroblast/macrophage co-culture system was utilized to examine the biocompatibility and the potential to induce inflammatory responses of an electrospun Dextran/PLGA scaffold. The scaffold did not affect the morphologies, attachments, proliferations and viabilities of both the fibroblasts and macrophages, cultured separately or together. Moreover, it only activated a small subset of the macrophages implicating a low potential to induce either severe acute or chronic inflammatory response. Additionally, fibroblasts played a role in prolonging macrophage activation in the presence of the scaffolds. Using antibody arrays, IL-10, SDF-1, MIP-1 gamma and RANTES were found to be up-regulated when the cells were incubated with the scaffolds. The results of subdermal implantation of the Dextran/PLGA scaffolds confirmed its biocompatibility and low inflammatory potential.

Potential of Laser Induced Breakdown Spectroscopy for analyzing the quality of unroasted and ground coffee

Science.gov (United States)

Silva, Tiago Varão; Hubinger, Silviane Zanni; Gomes Neto, José Anchieta; Milori, Débora Marcondes Bastos Pereira; Ferreira, Ednaldo José; Ferreira, Edilene Cristina

2017-09-01

Coffee is an important commodity and a very popular beverage around the world. Its economic value as well as beverage quality are strongly dependent of the quality of beans. The presence of defective beans in coffee blends has caused a negative impact on the beverage Global Quality (GQ) assessed by cupping tests. The main defective beans observed in the productive chain has been those Blacks, Greens and Sours (BGS). Chemical composition of BGS has a damaging impact on beverage GQ. That is why analytical tools are needed for monitoring and controlling the GQ in coffee agro-industry. Near Infrared Spectroscopy (NIRS) has been successfully applied for assessment of coffee quality. Another potential technique for direct, clean and fast measurement of coffee GQ is Laser Induced Breakdown Spectroscopy (LIBS). Elements and diatomic molecules commonly present in organic compounds (structure) can be assessed by using LIBS. In this article is reported an evaluation of LIBS for the main interferents of GQ (BGS defects). Results confirm the great potential of LIBS for discriminating good beans from those with BGS defects by using emission lines of C, CN, C2 and N. Most importantly, some emission lines presented strong linear correlation (r > 0.9) with NIRS absorption bands assigned to proteins, lipids, sugar and carboxylic acids, suggesting LIBS potential to estimate these compounds in unroasted and ground coffee samples.

Macrophage specific MRI imaging for antigen induced arthritides. A potential new strategy for the diagnosis of rheumatoid arthritis

International Nuclear Information System (INIS)

Simon, G.H.; Rummeny, E.J.; Daldrup-Link, H.E.

2007-01-01

The present work describes the potential of iron oxides for the detection of macrophages in synovitis in experimental, antigen-induced arthritis. The pivotal role of macrophages in rheumatoid arthritis (RA) in humans and in antigen-induced arthritis (AIA) in animal models is discussed. The latter appear to be very similar in many aspects to the human RA. We show the potential for iron oxide-enhanced magnetic resonance imaging (MRI) to determine the macrophage content in the arthritic synovial membranes. The results of our own research, as well as those of other research groups, are presented and discussed. MRI after the intravenous (i.v.) administration of iron oxides enables the depiction of macrophage content in arthritic synovial membranes in AIA through the effects of the intracellular compartmentalisation of iron oxide particles. These effects can be demonstrated in 24-h delayed images after i.v. contrast application, on T2-weighted spin-echo or turbo-spin-echo sequences, and especially on T2 * -weighted gradient-echo sequences. The signal effects are not only apparent in high field strength (4.7 Tesla) but also on 1.5 Tesla clinical scanners. The use of iron oxides enables the determination of the macrophage content in synovitis in animals with AIA. This parameter represents a potential marker to determine disease activity, and possibly represents a marker to evaluate the effectiveness of specific therapies in human RA. Current knowledge of iron oxide-enhanced MRI is limited to animal models. The clinical evaluation of this new method in patients with RA has not yet been performed. However, based on the considerations presented here, significant progress in the diagnostic work-up of RA can be expected

A study on induced current focusing potential drop (ICFPD) technique. Examination of the sizing accuracy of defects and its frequency dependence

International Nuclear Information System (INIS)

Kim, Hoon; Shoji, Tetsuo

1994-01-01

Aiming at nondestructive detection and size prediction of defects with high accuracy and resolution, an Induced Current Focusing Potential Drop (ICFPD) technique has been developed. This technique can be applied for determining the location and size of defects in components with not only simple shape such as plain surface but also more complex shape and geometry such as curved surface and dissimilar joint. This paper describes the basic principle of ICFPD and its probe development. In this ICFPD, current was induced in a conductive material by a straight induction wire, which is electrically isolated, placed on it. The benefits of this new technique compared with the conventional ACPD are: (1) Current is induced and focused only at an explorating region. (2) Applicable to defect detection by scanning the sensor probe in an explorating region. (3) Applicable to defect detection in a weld joint of austenitic stainless steel. As the results of the innovation in instrumentation and the improvement in evaluation procedure by use of suitable parameters, the existence of defects is clearly observed as the variation of potential drops, and the nondimensional parameter (V c,max. /V avg. ) has a direct correlation with crack depth. Especially, for the depth less than 5 mm, the ICFPD shows higher sensitivity than the conventional ACPD at the frequencies of 3, 10 and 30 kHz. (author)

Temperature-dependency analysis and correction methods of in-situ power-loss estimation for crystalline silicon modules undergoing potential-induced degradation stress testing

DEFF Research Database (Denmark)

Spataru, Sergiu; Hacke, Peter; Sera, Dezso

2015-01-01

We propose a method of in-situ characterization of the photovoltaic module power at standard test conditions using superposition of the dark current-voltage (I-V) curve measured at elevated stress temperature during potential-induced degradation (PID) testing. PID chamber studies were performed o...

Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

Directory of Open Access Journals (Sweden)

Teresa de Souza Fernandez

2013-01-01

Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

Potential of laryngeal muscle regeneration using induced pluripotent stem cell-derived skeletal muscle cells.

Science.gov (United States)

Dirja, Bayu Tirta; Yoshie, Susumu; Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Nakamura, Ryosuke; Otsuki, Koshi; Nomoto, Yukio; Wada, Ikuo; Hazama, Akihiro; Omori, Koichi

2016-01-01

Conclusion Induced pluripotent stem (iPS) cells may be a new potential cell source for laryngeal muscle regeneration in the treatment of vocal fold atrophy after recurrent laryngeal nerve paralysis. Objectives Unilateral vocal fold paralysis can lead to degeneration, atrophy, and loss of force of the thyroarytenoid muscle. At present, there are some treatments such as thyroplasty, arytenoid adduction, and vocal fold injection. However, such treatments cannot restore reduced mass of the thyroarytenoid muscle. iPS cells have been recognized as supplying a potential resource for cell transplantation. The aim of this study was to assess the effectiveness of the use of iPS cells for the regeneration of laryngeal muscle through the evaluation of both in vitro and in vivo experiments. Methods Skeletal muscle cells were generated from tdTomato-labeled iPS cells using embryoid body formation. Differentiation into skeletal muscle cells was analyzed by gene expression and immunocytochemistry. The tdTomato-labeled iPS cell-derived skeletal muscle cells were transplanted into the left atrophied thyroarytenoid muscle. To evaluate the engraftment of these cells after transplantation, immunohistochemistry was performed. Results The tdTomato-labeled iPS cells were successfully differentiated into skeletal muscle cells through an in vitro experiment. These cells survived in the atrophied thyroarytenoid muscle after transplantation.

Minoxidil is a potential neuroprotective drug for paclitaxel-induced peripheral neuropathy

Science.gov (United States)

Chen, Yi-Fan; Chen, Li-Hsien; Yeh, Yu-Min; Wu, Pei-Ying; Chen, Yih-Fung; Chang, Lian-Yun; Chang, Jang-Yang; Shen, Meng-Ru

2017-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. No medication has been shown to be effective in the treatment of CIPN. This study aims to integrate the image-based high-content screening, mouse behavior models and mechanistic cell-based assays to discover potential neuroprotective drugs. Among screened compounds, minoxidil showed the most potent neuroprotective effect against paclitaxel, with regard to neurite outgrowth of dorsal root ganglia (DRG). Minoxidil protected mice from thermal insensitivity and alleviated mechanical allodynia in paclitaxel-treated mice. The ultrastructure and quantified G-ratio of myelin integrity of sciatic nerve tissues supported the observations in mouse behavioral tests. The mechanistic study on DRG neurons suggested that minoxidil suppressed neuroinflammation and remodeled the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, minoxidil showed a synergistic anti-tumor effect with paclitaxel both in tumor xenograft models of cervical and breast cancer. Interestingly, the quantitative assays on hair length and hair growth both exhibited that minoxidil significantly improved the hair quality after chemotherapy. Since minoxidil is a drug approved by the Food and Drug Administration (FDA), the safety and biocompatibility are well documented. The immediate next step is to launch an early-stage clinical trial intending to prevent CIPN by minoxidil. PMID:28349969

Instanton-induced scalar potential for the universal hypermultiplet

International Nuclear Information System (INIS)

Ketov, Sergei V.

2003-01-01

We calculate the scalar potential in the gauged N=2 supergravity with a single hypermultiplet, whose generic quaternionic moduli space metric has an Abelian isometry. This isometry is gauged by the use of a graviphoton gauge field. The hypermultiplet metric and the scalar potential are both governed by the single real potential that is a solution to the 3d (integrable) continuous Toda equation. An explicit solution, controlled by the Eisenstein series E 3/2 , is found in the case of the D-instanton-corrected universal hypermultiplet moduli space metric having an U(1)xU(1) isometry, with one of the isometries being gauged

Instanton-induced scalar potential for the universal hypermultiplet

Energy Technology Data Exchange (ETDEWEB)

Ketov, Sergei V. E-mail: ketov@comp.metro-u.ac.jp

2003-04-21

We calculate the scalar potential in the gauged N=2 supergravity with a single hypermultiplet, whose generic quaternionic moduli space metric has an Abelian isometry. This isometry is gauged by the use of a graviphoton gauge field. The hypermultiplet metric and the scalar potential are both governed by the single real potential that is a solution to the 3d (integrable) continuous Toda equation. An explicit solution, controlled by the Eisenstein series E{sub 3/2}, is found in the case of the D-instanton-corrected universal hypermultiplet moduli space metric having an U(1)xU(1) isometry, with one of the isometries being gauged.

2D potential structures induced by RF sheaths coupled with transverse currents in front of ICRH antenna

International Nuclear Information System (INIS)

Faudot, E.; Heuraux, S.; Colas, L.

2004-01-01

Sheaths are space charge regions at the plasma-wall. They are induced by the differential inertia between ions and electrons, and without external perturbation, they create a floating potential between the neutral plasma and the walls. In Tokamaks, these sheaths are locally enhanced by the RF (radiofrequency) electric field generated by the ICRF (ion cyclotron resonance frequency) antennas used to heat magnetic fusion plasmas at very high temperature. RF sheaths are located at the connection points of magnetic field lines to the wall, or to the bumpers which protect the antenna or to any part of the antenna structure. The asymmetric behaviour of these oscillating sheaths rectifies RF potentials in the plasma in front of antenna, to finally create nonlinearly a DC potential which can be much higher than the floating potential. We study specifically how the space-time distribution of these RF and DC rectified potentials is modified when nearby flux tubes are allowed to exchange perpendicular polarization current. To simulate that, a 2-dimensional (2D) fluid code has been implemented to compute the 2D RF potential map in a plane perpendicular to magnetic lines, and within the flute approximation the whole 3-dimensional potential map is deduced. In simulation, we consider a homogeneous transverse conductivity and use a 'test' potential map having, in absence of transverse currents, a Gaussian shape characterized by its width r 0 and its amplitude φ 0 . As a function of these 2 parameters (normalized respectively to a characteristic length for transverse transport and to the local temperature), we can estimate the peaking and the smoothing of the potential structure in the presence of polarization current. So, we are able to determine, for typical plasmas, the amplitude of DC potential peaks, particularly on antenna's corners, where hot spots appear during a shot. In Tore-supra conditions near antenna corners, potential structures that are shorter than 1 centimeter are

2D potential structures induced by RF sheaths coupled with transverse currents in front of ICRH antenna

International Nuclear Information System (INIS)

Faudot, E.; Heuraux, S.; Colas, L.

2004-01-01

Sheaths are space charge regions at the plasma-wall. They are induced by the differential inertia between ions and electrons, and without external perturbation, they create a floating potential between the neutral plasma and the walls. In tokamaks, these sheaths are locally enhanced by the RF (radiofrequency) electric field generated by the ICRF (ion cyclotron resonance frequency) antennas used to heat magnetic fusion plasmas at very high temperature. RF sheaths are located at the connection points of magnetic field lines to the wall, or to the bumpers which protect the antenna or to any part of the antenna structure. The asymmetric behaviour of these oscillating sheaths rectifies RF potentials in the plasma in front of antenna, to finally create nonlinearly a DC potential which can be much higher than the floating potential. We study specifically how the space-time distribution of these RF and DC rectified potentials is modified when nearby flux tubes are allowed to exchange perpendicular polarization current. To simulate that, a 2D (2-dimensional) fluid code has been implemented to compute the 2D RF potential map in a plane perpendicular to magnetic lines, and within the flute approximation the whole 3-dimensional potential map is deduced. In simulation, we consider a homogeneous transverse conductivity and use a 'test' potential map having, in absence of transverse currents, a Gaussian shape characterized by its width r0 and its amplitude φ 0 . As a function of these 2 parameters (normalized respectively to a characteristic length for transverse transport and to the local temperature), we can estimate the peaking and the smoothing of the potential structure in the presence of polarization current. So, we are able to determine, for typical plasmas, the amplitude of DC potential peaks, particularly on antenna's corners, where hot spots appear during a shot. In typical Tore Supra conditions near antenna corners potential structures less than centimetric are

Theoretical potential for low energy consumption phase change memory utilizing electrostatically-induced structural phase transitions in 2D materials

Science.gov (United States)

Rehn, Daniel A.; Li, Yao; Pop, Eric; Reed, Evan J.

2018-01-01

Structural phase-change materials are of great importance for applications in information storage devices. Thermally driven structural phase transitions are employed in phase-change memory to achieve lower programming voltages and potentially lower energy consumption than mainstream nonvolatile memory technologies. However, the waste heat generated by such thermal mechanisms is often not optimized, and could present a limiting factor to widespread use. The potential for electrostatically driven structural phase transitions has recently been predicted and subsequently reported in some two-dimensional materials, providing an athermal mechanism to dynamically control properties of these materials in a nonvolatile fashion while achieving potentially lower energy consumption. In this work, we employ DFT-based calculations to make theoretical comparisons of the energy required to drive electrostatically-induced and thermally-induced phase transitions. Determining theoretical limits in monolayer MoTe2 and thin films of Ge2Sb2Te5, we find that the energy consumption per unit volume of the electrostatically driven phase transition in monolayer MoTe2 at room temperature is 9% of the adiabatic lower limit of the thermally driven phase transition in Ge2Sb2Te5. Furthermore, experimentally reported phase change energy consumption of Ge2Sb2Te5 is 100-10,000 times larger than the adiabatic lower limit due to waste heat flow out of the material, leaving the possibility for energy consumption in monolayer MoTe2-based devices to be orders of magnitude smaller than Ge2Sb2Te5-based devices.

Chronic ethanol feeding promotes azoxymethane and dextran sulfate sodium-induced colonic tumorigenesis potentially by enhancing mucosal inflammation

International Nuclear Information System (INIS)

Shukla, Pradeep K.; Chaudhry, Kamaljit K.; Mir, Hina; Gangwar, Ruchika; Yadav, Nikki; Manda, Bhargavi; Meena, Avtar S.; Rao, RadhaKrishna

2016-01-01

Alcohol consumption is one of the major risk factors for colorectal cancer. However, the mechanism involved in this effect of alcohol is unknown. We evaluated the effect of chronic ethanol feeding on azoxymethane and dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in mouse colon. Inflammation in colonic mucosa was assessed at a precancerous stage by evaluating mucosal infiltration of neutrophils and macrophages, and analysis of cytokine and chemokine gene expression. Chronic ethanol feeding significantly increased the number and size of polyps in colon of AOM/DSS treated mice. Confocal microscopic and immunoblot analyses showed a significant elevation of phospho-Smad, VEGF and HIF1α in the colonic mucosa. RT-PCR analysis at a precancerous stage indicated that ethanol significantly increases the expression of cytokines IL-1α, IL-6 and TNFα, and the chemokines CCL5/RANTES, CXCL9/MIG and CXCL10/IP-10 in the colonic mucosa of AOM/DSS treated mice. Confocal microscopy showed that ethanol feeding induces a dramatic elevation of myeloperoxidase, Gr1 and CD68-positive cells in the colonic mucosa of AOM/DSS-treated mice. Ethanol feeding enhanced AOM/DSS-induced suppression of tight junction protein expression and elevated cell proliferation marker, Ki-67 in the colonic epithelium. This study demonstrates that chronic ethanol feeding promotes colonic tumorigenesis potentially by enhancing inflammation and elevation of proinflammatory cytokines and chemokines

Potential nephrotoxic effects produced by steroidal saponins from hydro alcoholic extract of Tribulus terrestris in STZ-induced diabetic rats.

Science.gov (United States)

Gandhi, Sonia; Srinivasan, B P; Akarte, Atul S

2013-09-01

Chronic hyperglycemia leads to the development of microvascular complications like diabetic nephropathy. The present study investigated the potential effects of the hydroalcoholic extract of Tribulus terrestris, a plant of Zygophyllaceae family, on the renal complications in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by administering STZ (90 mg/kg) to the 2-days old neonates. After 6 weeks of induction, diabetic rats were treated with 50 mg/kg hydroalcoholic extract of T. terrestris for 8 weeks. The anti-hyperglycaemic nature was confirmed by reduction in blood glucose and improvement in insulin levels. Diabetic renal injury associated with decrease in total proteins and albumin levels was observed to be improved by T. terrestris extract. Glomerular filtration rate along with inflammatory and growth factors, adiponectin and erythropoietin were also improved by the treatment, though the findings were not significant. However, the beneficial antidiabetic effects of T. terrestris extract in plasma were not observed in kidney histopathology. This was confirmed by the quantitative estimation of unhydrolyzed fraction of saponins (major component: protodioscin) in plasma and kidney samples of normal and diabetic rats. Hence, it can be concluded that 8 weeks treatment with T. terrestris extract produces potential toxic effects in kidney, which are independent of its anti-diabetic action.

Potentiation of glucose-induced insulin release in islets by desHis1[Glu9]glucagon amide

DEFF Research Database (Denmark)

Kofod, Hans; Unson, C G; Merrifield, R B

1988-01-01

Glucagon and secretin and some of their hybrid analogs potentiate glucose-induced release of insulin from isolated mouse pancreatic islets. It was recently shown that the synthetic glucagon analog, desHis1[Glu9]glucagon amide, does not stimulate the formation of cyclic adenosine monophosphate...... in the rat hepatocyte membrane, but binds well to the glucagon receptor and is a good competitive antagonist of glucagon. In the present study the effect of this analog on isolated islets was examined. desHis1-[Glu9]glucagon amide at 3 x 10(-7) M, in the presence of 0.01 M D-glucose, increased the release...

Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

Science.gov (United States)

Bielecka, Magdalena K.; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E.

2014-01-01

A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human proteins, we immunized mice with recombinant truncated type I rMIP proteins that lacked the globular domain and the signal leader peptide (LP) signal sequence (amino acids 1 to 22) and contained the His purification tag at either the N or C terminus (C-term). The immunogenicity of truncated rMIP proteins was compared to that of full (i.e., full-length) rMIP proteins (containing the globular domain) with either an N- or C-terminal His tag and with or without the LP sequence. By comparing the functional murine antibody responses to these various constructs, we determined that C-term His truncated rMIP (−LP) delivered in liposomes induced high levels of antibodies that bound to the surface of wild-type but not Δmip mutant meningococci and showed bactericidal activity against homologous type I MIP (median titers of 128 to 256) and heterologous type II and III (median titers of 256 to 512) strains, thereby providing at least 82% serogroup B strain coverage. In contrast, in constructs lacking the LP, placement of the His tag at the N terminus appeared to abrogate bactericidal activity. The strategy used in this study would obviate any potential concerns regarding the use of MIP antigens for inclusion in bacterial vaccines. PMID:25452551

Recombinant protein truncation strategy for inducing bactericidal antibodies to the macrophage infectivity potentiator protein of Neisseria meningitidis and circumventing potential cross-reactivity with human FK506-binding proteins.

Science.gov (United States)

Bielecka, Magdalena K; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E; Christodoulides, Myron

2015-02-01

A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human proteins, we immunized mice with recombinant truncated type I rMIP proteins that lacked the globular domain and the signal leader peptide (LP) signal sequence (amino acids 1 to 22) and contained the His purification tag at either the N or C terminus (C-term). The immunogenicity of truncated rMIP proteins was compared to that of full (i.e., full-length) rMIP proteins (containing the globular domain) with either an N- or C-terminal His tag and with or without the LP sequence. By comparing the functional murine antibody responses to these various constructs, we determined that C-term His truncated rMIP (-LP) delivered in liposomes induced high levels of antibodies that bound to the surface of wild-type but not Δmip mutant meningococci and showed bactericidal activity against homologous type I MIP (median titers of 128 to 256) and heterologous type II and III (median titers of 256 to 512) strains, thereby providing at least 82% serogroup B strain coverage. In contrast, in constructs lacking the LP, placement of the His tag at the N terminus appeared to abrogate bactericidal activity. The strategy used in this study would obviate any potential concerns regarding the use of MIP antigens for inclusion in bacterial vaccines. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in human lymphocyte death induced by nickel carbonate hydroxide in vitro

Energy Technology Data Exchange (ETDEWEB)

M' Bemba-Meka, Prosper [Faculty of Medicine, Universite de Montreal, QC (Canada); University of Louisville, Department of Pharmacology and Toxicology, Center for Genetics and Molecular Medicine, Louisville, KY (United States); Lemieux, Nicole [Universite de Montreal, Department of Pathology and Cellular Biology, Main Station, P.O. Box 6128, Montreal, QC (Canada); Chakrabarti, Saroj K. [Faculty of Medicine, Universite de Montreal, QC (Canada)

2006-07-15

When isolated human lymphocytes were treated in vitro with various concentrations of soluble form of nickel carbonate hydroxide (NiCH) (0-1 mM), at 37 C for 4 h, both concentration- and time-dependent effects of NiCH on lymphocyte death were observed. Increased generation of hydrogen peroxide (H{sub 2}O{sub 2}), superoxide anion (O{sub 2} {sup -}), depletion of both no protein (NP-) and protein (P-) sulfhydryl (SH) contents and lipid peroxidation (LPO) were induced by NiCH. Pretreatment of lymphocytes with either catalase (H{sub 2}O{sub 2} scavenger), or deferoxamine (DFO) (iron chelator), or excess glutathione (GSH) (an antioxidant) not only significantly reduced the NiCH-induced generation of H{sub 2}O{sub 2} and LPO, but also increased the NP-SH and P-SH contents initially reduced by NiCH. NiCH-induced generation of excess O{sub 2} {sup -} but not excess LPO was significantly reduced by pretreatment with superoxide dismutase (SOD). NiCH-induced lymphocyte death was significantly prevented by pre-treatment with either catalase, or dimethylthiourea/mannitol (hydroxyl radical scavengers), or DFO, or excess GSH/N-acetylcysteine. NiCH-induced lymphocyte death was also significantly prevented by pretreatment with excess SOD. Thus, various types of oxidative stresses play an important role in NiCH-induced lymphocyte death. Cotreatment with cyclosporin A, a specific inhibitor of alteration in mitochondrial membrane potential ({delta}{psi}{sub m}), not only inhibited NiCH-induced alteration in {delta}{psi}{sub m}, but also significantly prevented Ni-compound-induced lymphocyte death. Furthermore, NiCH-induced destabilization of cellular calcium homeostasis. As such, NiCH-induced lymphocyte death was significantly prevented by modulating intracellular calcium fluxes such as Ca{sup 2+} channel blockers and intracellular Ca{sup 2+} antagonist. Thus, the mechanism of NiCH (soluble form)-induced activation of lymphocyte death signalling pathways involves not only the excess

Vortex lattice matching effects in a washboard pinning potential induced by Co nanostripe arrays

International Nuclear Information System (INIS)

Dobrovolskiy, Oleksandr V.; Begun, Evgeniya; Huth, Michael; Shklovskij, Valerij A.; Tsindlekht, Menachem I.

2011-01-01

We furnish superconducting Nb thin films with linearly-extended uniaxial pinning nanostructures. An array of Co stripes is deposited by focused electron beam-induced deposition. Nanostructures are designed to be commensurate with the vortex lattice at small magnetic fields. We investigate vortex lattice matching effects by magneto-transport measurements. Drops in ρ(B) are observed only when the vortex lattice parameter matches the nanostructure period. No matching effects corresponding to the Co stripe width have been observed. Drops in ρ(B) are more pronounced for the vortex motion perpendicular to the Co stripes. An advanced mask-less nanofabrication technique, focused electron beam-induced deposition (FEBID), has been employed on epitaxial Nb thin films to prepare ferromagnetic decorations in the form of an array of Co stripes. These substantially modify the non-patterned films' superconducting properties, providing a washboard-like pinning potential landscape for the vortex motion. At small magnetic fields B ≤ 0.1 T, vortex lattice matching effects have been investigated by magneto-transport measurements. Step-like drops in the field dependencies of the films resistivity ρ(B) have been observed in particular for the vortex motion perpendicular to the Co stripes. The field values, corresponding to the middle points of these drops in ρ(B), meet the vortex lattice parameter matching the pinning structure's period. These disagree with the results of Jaque et al. (2002) , who observed matching effects corresponding to the stripe width in Nb films grown on periodically distributed submicrometric lines of Ni.

Does ozone enhance the remineralizing potential of nanohydroxyapatite on artificially demineralized enamel? A laser induced fluorescence study

Science.gov (United States)

Srinivasan, Samuelraj; Prabhu, Vijendra; Chandra, Subhash; Koshy, Shalini; Acharya, Shashidhar; Mahato, Krishna K.

2014-02-01

The present era of minimal invasive dentistry emphasizes the early detection and remineralization of initial enamel caries. Ozone has been shown to reverse the initial demineralization before the integrity of the enamel surface is lost. Nano-hydroxyapatite is a proven remineralizing agent for early enamel caries. In the present study, the effect of ozone in enhancing the remineralizing potential of nano-hydroxyapatite on artificially demineralized enamel was investigated using laser induced fluorescence. Thirty five sound human premolars were collected from healthy subjects undergoing orthodontic treatment. Fluorescence was recorded by exciting the mesial surfaces using 325 nm He-Cd laser with 2 mW power. Tooth specimens were subjected to demineralization to create initial enamel caries. Following which the specimens were divided into three groups, i.e ozone (ozonated water for 2 min), without ozone and artificial saliva. Remineralization regimen was followed for 3 weeks. The fluorescence spectra of the specimens were recorded from all the three experimental groups at baseline, after demineralization and remineralization. The average spectrum for each experimental group was used for statistical analysis. Fluorescence intensities of Ozone treated specimens following remineralization were higher than that of artificial saliva, and this difference was found to be statistically significant (P<0.0001). In a nutshell, ozone enhanced the remineralizing potential of nanohydroxyapatite, and laser induced fluorescence was found to be effective in assessing the surface mineral changes in enamel. Ozone can be considered an effective agent in reversing the initial enamel caries there by preventing the tooth from entering into the repetitive restorative cycle.

Therapeutic Potential of Date Palm Pollen for Testicular Dysfunction Induced by Thyroid Disorders in Male Rats.

Directory of Open Access Journals (Sweden)

Akram M El-Kashlan

Full Text Available Hyper- or hypothyroidism can impair testicular function leading to infertility. The present study was designed to examine the protective effect of date palm pollen (DPP extract on thyroid disorder-induced testicular dysfunction. Rats were divided into six groups. Group I was normal control. Group II received oral DPP extract (150 mg kg(-1, group III (hyperthyroid group received intraperitoneal injection of L-thyroxine (L-T4, 300 μg kg(-1; i.p., group IV received L-T4 plus DPP extract, group V (hypothyroid group received propylthiouracil (PTU, 10 mg kg(-1; i.p. and group VI received PTU plus DPP extract. All treatments were given every day for 56 days. L-T4 or PTU lowered genital sex organs weight, sperm count and motility, serum levels of luteinizing hormone (LH, follicle stimulating hormone (FSH and testosterone (T, testicular function markers and activities of testicular 3β-hydroxysteroid dehydrogenase (3β-HSD and 17β-hydroxysteroid dehydrogenase (17β-HSD. Moreover, L-T4 or PTU increased estradiol (E2 serum level, testicular oxidative stress, DNA damage and apoptotic markers. Morphometric and histopathologic studies backed these observations. Treatment with DPP extract prevented LT4- or PTU induced changes. In addition, supplementation of DPP extract to normal rats augmented sperm count and motility, serum levels of LH, T and E2 paralleled with increased activities of 3β-HSD and 17β-HSD as well as testicular antioxidant status. These results provide evidence that DPP extract may have potential protective effects on testicular dysfunction induced by altered thyroid hormones.

New Insights into Potential Prevention and Management Options for Chemotherapy-Induced Peripheral Neuropathy

Directory of Open Access Journals (Sweden)

Janet Schloss

2016-01-01

Full Text Available Objective: Neurological complications such as chemotherapy-induced peripheral neuropathy (CIPN and neuropathic pain are frequent side effects of neurotoxic chemotherapy agents. An increasing survival rate and frequent administration of adjuvant chemotherapy treatments involving neurotoxic agents makes it imperative that accurate diagnosis, prevention, and treatment of these neurological complications be implemented. Methods: A consideration was undertaken of the current options regarding protective and treatment interventions for patients undergoing chemotherapy with neurotoxic chemotherapy agent or experience with CIPN. Current knowledge on the mechanism of action has also been identified. The following databases PubMed, the Cochrane Library, Science Direct, Scopus, EMBASE, MEDLINE, CINAHL, CNKI, and Google Scholar were searched for relevant article retrieval. Results: A range of pharmaceutical, nutraceutical, and herbal medicine treatments were identified that either showed efficacy or had some evidence of efficacy. Duloxetine was the most effective pharmaceutical agent for the treatment of CIPN. Vitamin E demonstrated potential for the prevention of cisplatin-IPN. Intravenous glutathione for oxaliplatin, Vitamin B6 for both oxaliplatin and cisplatin, and omega 3 fatty acids for paclitaxel have shown protection for CIPN. Acetyl-L-carnitine may provide some relief as a treatment option. Acupuncture may be of benefit for some patients and Gosha-jinki-gan may be of benefit for protection from adverse effects of oxaliplatin induced peripheral neuropathy. Conclusions: Clinicians and researchers acknowledge that there are numerous challenges involved in understanding, preventing, and treating peripheral neuropathy caused by chemotherapeutic agents. New insights into mechanisms of action from chemotherapy agents may facilitate the development of novel preventative and treatment options, thereby enabling medical staff to better support patients by

Study of the potential effect of selenium on gamma-radiation induced ovarian failure

International Nuclear Information System (INIS)

Said, R.S.M.

2012-01-01

Radiotherapy is a major factor contributing to female infertility by inducing premature ovarian failure (POF). Therefore, the need for an effective radioprotective agent is evident. The present study investigated the mechanism of potential radioprotective effect of sodium selenite on radiation-induced ovarian failure and whether sodium selenite can stimulate in vivo follicular development in experimental rats. Immature female Sprague-Dawely rats were either exposed to gamma radiation (3.2 Gy, LD 20 ), once and/or treated with sodium selenite (0.5 mg/kg), once daily for one week before irradiation. Follicular and oocyte development, apoptotic markers, proliferation marker as well as oxidative stress markers were assessed 24-h after irradiation. In addition, fertility assessment was performed after female rats became completely mature at two months of age. Sodium selenite significantly enhanced follicular development as compared to the irradiated group. Sodium selenite significantly reversed the oxidative stress effects of radiation that was evidenced by increasing in lipid peroxide level and decreasing in glutathione level, and glutathione peroxidase (GPx) activity. Assessment of apoptosis and cell proliferation markers revealed that caspase 3 and cytochrome c expressions markedly-increased, whereas, PCNA expression markedly-decreased in the irradiated group; in contrast, sodium selenite treatment prevented these alterations. Histopathological examination further confirmed the radioprotective efficacy of sodium selenite and its in-vivo effect on ovarian follicles’ maturation. In conclusion, sodium selenite showed a radioprotective effect and improved folliculogenesis through increasing ovarian granulosa cells proliferation, estradiol and FSH secretion, and GPx activity, whilst decreasing lipid peroxidation and oxidative stress, leading to inhibition of the apoptosis pathway through decreasing the expressions of caspase 3 and cytochrome c.

Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells.

Science.gov (United States)

Inayat-Hussain, S H; Annuar, B O; Din, L B; Ali, A M; Ross, D

2003-08-01

Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

Interferon Potentiates Toll-Like Receptor-Induced Prostaglandin D2 Production through Positive Feedback Regulation between Signal Transducer and Activators of Transcription 1 and Reactive Oxygen Species

Directory of Open Access Journals (Sweden)

Ji-Yun Kim

2017-12-01

Full Text Available Prostaglandin D2 (PGD2 is a potent lipid mediator that controls inflammation, and its dysregulation has been implicated in diverse inflammatory disorders. Despite significant progress made in understanding the role of PGD2 as a key regulator of immune responses, the molecular mechanism underlying PGD2 production remains unclear, particularly upon challenge with different and multiple inflammatory stimuli. Interferons (IFNs potentiate macrophage activation and act in concert with exogenous inflammatory mediators such as toll-like receptor (TLR ligands to amplify inflammatory responses. A recent study found that IFN-γ enhanced lipopolysaccharide-induced PGD2 production, indicating a role of IFNs in PGD2 regulation. Here, we demonstrate that TLR-induced PGD2 production by macrophages was significantly potentiated by signaling common to IFN-β and IFN-γ in a signal transducer and activators of transcription (STAT1-dependent mechanism. Such potentiation by IFNs was also observed for PGE2 production, despite the differential regulation of PGD synthase and PGE synthase isoforms mediating PGD2 and PGE2 production under inflammatory conditions. Mechanistic analysis revealed that the generation of intracellular reactive oxygen species (ROS was remarkably potentiated by IFNs and required for PGD2 production, but was nullified by STAT1 deficiency. Conversely, the regulation of STAT1 level and activity by IFNs was largely dependent on ROS levels. Using a model of zymosan-induced peritonitis, the relevance of this finding in vivo was supported by marked inhibition of PGD2 and ROS produced in peritoneal exudate cells by STAT1 deficiency. Collectively, our findings suggest that IFNs, although not activating on their own, are potent amplifiers of TLR-induced PGD2 production via positive-feedback regulation between STAT1 and ROS.

Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE.

Science.gov (United States)

Casciola-Rosen, L; Rosen, A

1997-01-01

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease which is characterized clinically by pleiotropy and periodicity. The immune features which accompany the characteristic flares of the disease have strongly suggested that the autoimmune response is driven by self antigen, and is T cell-dependent. These features have prompted the search for potential initiating process(es) which induce the release of self-antigens in a form which causes T cell tolerance to those self molecules to be broken. We review here several recent observations which implicate apoptotic cells as an important potential source of clustered and concentrated autoantigens in SLE, and present our current model whereby the novel autoantigen fragments generated in apoptotic surface blebs initiate and drive the autoimmune response in this disease.

Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems

Directory of Open Access Journals (Sweden)

Elham A. Afify

2017-11-01

Full Text Available Tolerance to the analgesic effect of morphine is a major clinical problem which can be managed by co-administration of another drug. This study investigated the ability of propranolol to potentiate the antinociceptive action of morphine and the possible mechanisms underlying this effect. Antinociception was assessed in three nociceptive tests (thermal, hot plate, (visceral, acetic acid, and (inflammatory, formalin test in mice and quantified by measuring the percent maximum possible effect, the percent inhibition of acetic acid-evoked writhing response, and the area under the curve values of number of flinches for treated mice, respectively. The study revealed that propranolol (0.25–20 mg/Kg, IP administration did not produce analgesia in mice. However, 10 mg/Kg propranolol, enhanced the antinociceptive effect of sub-analgesic doses of morphine (0.2, 1, and 2 mg/Kg, IP in the three nociceptive tests. It also shifted the dose response curve of morphine to the left. The combined effect of propranolol and morphine was attenuated by haloperidol (D2 receptor antagonist, 1.5 mg/Kg, IP, and bicuculline (GABAA receptor antagonist, 2 mg/Kg, IP. Repeated daily administration of propranolol (10 mg/Kg, IP did not alter the nociceptive responses in the three pain tests, but it significantly potentiated morphine-induced antinociception in the hot plate, acetic acid-evoked writhing, and in the second phase of formalin tests. Together, the data suggest that a cross-talk exists between the opioidergic and adrenergic systems and implicate dopamine and GABA systems in this synergistic effect of morphine-propranolol combination. Propranolol may serve as an adjuvant therapy to potentiate the effect of opioid analgesics.

Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.

Science.gov (United States)

Farshori, Nida Nayyar; Al-Sheddi, Ebtsam S; Al-Oqail, Mai M; Hassan, Wafaa H B; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Siddiqui, Maqsood A

2015-08-01

The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 μg/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia. © The Author(s) 2013.

29 CFR 1917.27 - Personnel.

Science.gov (United States)

2010-07-01

... operations involved. 3 3 The following are recommended topics: (i) Safety responsibility and authority; (ii) elements of accident prevention; (iii) attitudes, leadership and motivation; (iv) hazards of longshoring...

Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine.

Science.gov (United States)

Shtrichman, R; Germanguz, I; Itskovitz-Eldor, J

2013-06-01

Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biological characteristics of iPSCs are not yet fully understood and their similarity to human embryonic stem cells (hESCs) is still unresolved. Variations among iPSCs, resulting from their original tissue or cell source, and from the experimental protocols used for their derivation, significantly affect epigenetic properties and differentiation potential. Here we review the potential of iPSCs for regenerative and personalized medicine, and assess their expression pattern, epigenetic memory and differentiation capabilities in relation to their parental tissue source. We also summarize the patient-specific iPSCs that have been derived for applications in biological research and drug discovery; and review risks that must be overcome in order to use iPSC technology for clinical applications.

Allergic Potential and Immunotoxicity Induced by Topical Application of 1-Chloro-4-(Trifluoromethyl)Benzene (PCBTF) in a Murine Model

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Franko, Jennifer; Jackson, Laurel G.; Meade, B. Jean; Anderson, Stacey E.

2011-01-01

The purpose of the studies in this paper was to evaluate the allergic potential, immunotoxicity, and irritancy of the occupationally relevant chemical, 1-chloro-4-(trifluoromethyl)benzene, also known as parachlorobenzotrifluoride (PCBTF), following dermal exposure in a murine model. Evaluation of the sensitization potential, conducted using the local lymph node assay (LLNA) at concentrations ranging from 50% to 100%, identified a dose-dependent increase in lymphocyte proliferation with a calculated EC3 value of 53.1%. While no elevations in total or specific IgE were observed after exposure to any concentration of the chemical, significant increases in IFN-γ protein production by stimulated draining lymphoid cells were observed, indicating a T-cell-mediated response. Dermal exposure to PCBTF was not found to alter the immune response to a T-cell-dependant antigen. These results demonstrate that PCBTF has the potential to induce allergic sensitization following dermal exposure and based on LLNA results would be classified as a weak sensitizer. PMID:21747864

Exercise-Induced Anaphylaxis: A Case Report and Review of the Diagnosis and Treatment of a Rare but Potentially Life-Threatening Syndrome

Directory of Open Access Journals (Sweden)

Nathan T. Jaqua

2013-01-01

Full Text Available A 24-year-old male Marine with an uncomplicated medical history and a long history of strenuous, daily exercise presented to the emergency department after experiencing anaphylactic shock while running. Symptoms resolved following administration of intramuscular diphenhydramine, ranitidine, intravenous methylprednisolone, and intravenous fluids. On followup in the allergy clinic, a meticulous clinical history was obtained which elucidated a picture consistent with exercise-induced anaphylaxis. He had experienced diffuse pruritus and urticaria while exercising on multiple occasions over the last three years. His symptoms would usually increase as exercise continued. Prior to the first episode, he regularly exercised without symptoms. Exercise-induced anaphylaxis is a rare but potentially life-threatening syndrome that requires a careful clinical history and is a diagnosis of exclusion. Treatment is primarily exercise avoidance. Prophylactic mediations are inconsistently effective but are empirically used. Successful treatment with omalizumab was recently reported in a case of refractory exercise-induced anaphylaxis.

Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride.

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Lin, Song-Chow; Lin, Chia-Hsien; Lin, Chun-Ching; Lin, Yun-Ho; Chen, Chin-Fa; Chen, I-Cheng; Wang, Li-Ya

2002-01-01

Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s). Copyright 2002 National Science Council, ROC and S. Karger AG, Basel

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis

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Arzu Tatar

Full Text Available Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione and an oxidative product (malondialdehyde were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

Negative induced mood influences word production: An event-related potentials study with a covert picture naming task.

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Hinojosa, J A; Fernández-Folgueiras, U; Albert, J; Santaniello, G; Pozo, M A; Capilla, A

2017-01-27

The present event-related potentials (ERPs) study investigated the effects of mood on phonological encoding processes involved in word generation. For this purpose, negative, positive and neutral affective states were induced in participants during three different recording sessions using short film clips. After the mood induction procedure, participants performed a covert picture naming task in which they searched letters. The negative compared to the neutral mood condition elicited more negative amplitudes in a component peaking around 290ms. Furthermore, results from source localization analyses suggested that this activity was potentially generated in the left prefrontal cortex. In contrast, no differences were found in the comparison between positive and neutral moods. Overall, current data suggest that processes involved in the retrieval of phonological information during speech generation are impaired when participants are in a negative mood. The mechanisms underlying these effects were discussed in relation to linguistic and attentional processes, as well as in terms of the use of heuristics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Missing ozone-induced potential aerosol formation in a suburban deciduous forest

Science.gov (United States)

Nakayama, T.; Kuruma, Y.; Matsumi, Y.; Morino, Y.; Sato, K.; Tsurumaru, H.; Ramasamy, S.; Sakamoto, Y.; Kato, S.; Miyazaki, Y.; Mochizuki, T.; Kawamura, K.; Sadanaga, Y.; Nakashima, Y.; Matsuda, K.; Kajii, Y.

2017-12-01

As a new approach to investigating formation processes of secondary organic aerosol (SOA) in the atmosphere, ozone-induced potential aerosol formation was measured in summer at a suburban forest site surrounded by deciduous trees, near Tokyo, Japan. After passage through a reactor containing high concentrations of ozone, increases in total particle volume (average of 1.4 × 109 nm3/cm3, which corresponds to 17% that of pre-existing particles) were observed, especially during daytime. The observed aerosol formations were compared with the results of box model simulations using simultaneously measured concentrations of gaseous and particulate species. According to the model, the relative contributions of isoprene, monoterpene, and aromatic hydrocarbon oxidation to SOA formation in the reactor were 24, 21, and 55%, respectively. However, the model could explain, on average, only ∼40% of the observed particle formation, and large discrepancies between the observations and model were found, especially around noon and in the afternoon when the concentrations of isoprene and oxygenated volatile organic compounds were high. The results suggest a significant contribution of missing (unaccounted-for) SOA formation processes from identified and/or unidentified volatile organic compounds, especially those emitted during daytime. Further efforts should be made to explore and parameterize this missing SOA formation to assist in the improvement of atmospheric chemistry and climate models.

Screening of Pesticides with the Potential of Inducing DSB and Successive Recombinational Repair

Directory of Open Access Journals (Sweden)

Karen Suárez-Larios

2017-01-01

Full Text Available A study was realized to ascertain whether eight selected pesticides would induce double strand breaks (DSB in lymphocyte cultures and whether this damage would induce greater levels of proteins Rad51 participating in homologous recombination or of p-Ku80 participating in nonhomologous end joining. Only five pesticides were found to induce DSB of which only glyphosate and paraoxon induced a significant increase of p-Ku80 protein, indicating that nonhomologous end joining recombinational DNA repair system would be activated. The type of gamma-H2AX foci observed was comparable to that induced by etoposide at similar concentrations. These results are of importance since these effects occurred at low concentrations in the micromolar range, in acute treatments to the cells. Effects over longer exposures in actual environmental settings are expected to produce cumulative damage if repeated events of recombination take place over time.

The oxidative potential and biological effects induced by PM10 obtained in Mexico City and at a receptor site during the MILAGRO Campaign

International Nuclear Information System (INIS)

Quintana, Raul; Serrano, Jesus; Gomez, Virginia; Foy, Benjamin de; Miranda, Javier; Garcia-Cuellar, Claudia; Vega, Elizabeth; Vazquez-Lopez, Ines; Molina, Luisa T.; Manzano-Leon, Natalia; Rosas, Irma; Osornio-Vargas, Alvaro R.

2011-01-01

As part of a field campaign that studied the impact of Mexico City pollution plume at the local, sub-regional and regional levels, we studied transport-related changes in PM 10 composition, oxidative potential and in vitro toxicological patterns (hemolysis, DNA degradation). We collected PM 10 in Mexico City (T 0 ) and at a suburban-receptor site (T 1 ), pooled according to two observed ventilation patterns (T 0 → T 1 influence and non-influence). T 0 samples contained more Cu, Zn, and carbon whereas; T 1 samples contained more of Al, Si, P, S, and K (p 4 -2 increased in T 1 during the influence periods. Oxidative potential correlated with Cu/Zn content (r = 0.74; p 1 PM 10 induced greater hemolysis and T 0 PM 10 induced greater DNA degradation. Influence/non-influence did not affect oxidative potential nor biological effects. Results indicate that ventilation patterns had little effect on intrinsic PM 10 composition and toxicological potential, which suggests a significant involvement of local sources. - Highlights: → Transport-related changes in PM 10 composition, oxidative potential and in vitro toxicity were studied. → Cu, Zn, and carbon levels were predominant in urban PM 10 ; receptor site PM 10 was rich in soil elements. → SO 4 -2 was the only component increased in PM 10 from the receptor during the influence periods. → PM 10 oxidative potential correlates with Cu/Zn content but not with studied biological effects. → Ventilation patterns had little effect on PM 10 composition and toxicity. - Mexico City ventilation patterns had little effect on the intrinsic PM 10 composition and toxicological potential, which suggests a significant involvement of local sources as opposed to downwind transport.

Effects of mode profile on tunneling and traversal of ultracold atoms through vacuum-induced potentials

Science.gov (United States)

Badshah, Fazal; Irfan, Muhammad; Qamar, Sajid; Qamar, Shahid

2016-04-01

We consider the resonant interaction of an ultracold two-level atom with an electromagnetic field inside a high-Q micromaser cavity. In particular, we study the tunneling and traversal of ultracold atoms through vacuum-induced potentials for secant hyperbolic square and sinusoidal cavity mode functions. The phase time which may be considered as an appropriate measure of the time required for the atoms to cross the cavity, significantly modifies with the change of cavity mode profile. For example, switching between the sub and superclassical behaviors in phase time can occur due to the mode function. Similarly, negative phase time appears for the transmission of the two-level atoms in both excited and ground states for secant hyperbolic square mode function which is in contrast to the mesa mode case.

A new infusion pathway monitoring system utilizing electrostatic induced potential.

Science.gov (United States)

Maki, Hiromichi; Yonezawa, Yoshiharu; Ogawa, Hidekuni; Ninomiya, Ishio; Sada, Kouji; Hamada, Shingo; Hahn, Alien W; Caldwell, W Morton

2006-01-01

We have developed a new infusion pathway monitoring system employing linear integrated circuits and a low-power 8-bit single chip microcomputer. The system is available for hospital and home use and it constantly monitors the intactness of the pathway. The sensor is an electro-conductive polymer electrode wrapped around the infusion polyvinyl chloride infusion tube. This records an AC (alternating current) voltage induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltage and alerts the nursing station, via the nurse call system or PHS (personal handy phone System).

Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity.

Science.gov (United States)

Wu, Yu-Ching; Chang, Chao-Yuan; Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

2015-01-01

Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression.

Hypoxia-Inducible Factor-1α: A Potential Factor for the Enhancement of Osseointegration between Dental Implants and Tissue-Engineered Bone

Directory of Open Access Journals (Sweden)

Duohong Zou

2011-07-01

Full Text Available Introduction: Tissue-engineered bones are widely utilized to protect healthy tissue, reduce pain, and increase the success rate of dental implants. one of the most challenging obstacles lies in obtaining effective os-seointegration between dental implants and tissue-engineered structures. Deficiencies in vascularization, osteogenic factors, oxygen, and other nutrients inside the tissue-engineered bone during the early stages following implantation all inhibit effective osseointe-gration. Oxygen is required for aerobic metabolism in bone and blood vessel tissues, but oxygen levels inside tissue-engineered bone are not suf-ficient for cell proliferation. HIF-1α is a pivotal regulator of hypoxic and ischemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and osteogenesis.The hypothesis: Hypoxia-Inducible Factor-1α seems a potential factor for the enhancement of osseointegration between dental implants and tissue-engineered bone.Evaluation of the hypothesis: Enhancement of HIF-1α protein expression is recognized as the most promising approach for angiogenesis, because it can induce multiple angiogenic targets in a coordinated manner. Therefore, it will be a novel potential therapeutic methods targeting HIF-1α expression to enhance osseointegration be-tween dental implants and tissue-engineered bone.

Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

Science.gov (United States)

Meredith, Rhiannon M.; van Ooyen, Arjen

2012-01-01

CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

L-arginine and Arginase Products Potentiate Dexmedetomidine-induced Contractions in the Rat Aorta.

Science.gov (United States)

Wong, Emily S W; Man, Ricky Y K; Ng, Kwok F J; Leung, Susan W S; Vanhoutte, Paul M

2018-03-01

The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. L-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of L-arginine in modulating the overall vascular response to dexmedetomidine. Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, N-nitro-L-arginine methyl ester hydrochloride (L-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), L-arginine, (S)-(2-boronethyl)-L-cysteine hydrochloride (arginase inhibitor), N-hydroxy-L-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed. Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with L-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous L-arginine augmented the dexmedetomidine-induced contractions in the presence of L-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-L-cysteine hydrochloride (Emax 16 ± 4%) and N-hydroxy-L-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as L-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by L-arginine treatment in the presence of L-NAME (N = 4). These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of

High-fat diet-induced insulin resistance does not increase plasma anandamide levels or potentiate anandamide insulinotropic effect in isolated canine islets.

Science.gov (United States)

Woolcott, Orison O; Richey, Joyce M; Kabir, Morvarid; Chow, Robert H; Iyer, Malini S; Kirkman, Erlinda L; Stefanovski, Darko; Lottati, Maya; Kim, Stella P; Harrison, L Nicole; Ionut, Viorica; Zheng, Dan; Hsu, Isabel R; Catalano, Karyn J; Chiu, Jenny D; Bradshaw, Heather; Wu, Qiang; Kolka, Cathryn M; Bergman, Richard N

2015-01-01

Obesity has been associated with elevated plasma anandamide levels. In addition, anandamide has been shown to stimulate insulin secretion in vitro, suggesting that anandamide might be linked to hyperinsulinemia. To determine whether high-fat diet-induced insulin resistance increases anandamide levels and potentiates the insulinotropic effect of anandamide in isolated pancreatic islets. Dogs were fed a high-fat diet (n = 9) for 22 weeks. Abdominal fat depot was quantified by MRI. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp. Fasting plasma endocannabinoid levels were analyzed by liquid chromatography-mass spectrometry. All metabolic assessments were performed before and after fat diet regimen. At the end of the study, pancreatic islets were isolated prior to euthanasia to test the in vitro effect of anandamide on islet hormones. mRNA expression of cannabinoid receptors was determined in intact islets. The findings in vitro were compared with those from animals fed a control diet (n = 7). Prolonged fat feeding increased abdominal fat content by 81.3±21.6% (mean±S.E.M, Pcanines, high-fat diet-induced insulin resistance does not alter plasma anandamide levels or further potentiate the insulinotropic effect of anandamide in vitro.

Longshore sediment transport along the Indian coast

Digital Repository Service at National Institute of Oceanography (India)

Chandramohan, P.; Nayak, B.U.

Coast. Maharashtra Coast and the part between Pondicherry and Point Calimere in Tamilnadu, show negligible order of annual net transport. Annual net transport along the east coast is in north and along the west coast in south but for South Gujarat Coast....

Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human—Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans-

Science.gov (United States)

Goda, Keisuke; Kobayashi, Akio; Takahashi, Akemi; Takahashi, Tadakazu; Saito, Kosuke; Maekawa, Keiko; Saito, Yoshiro; Sugai, Shoichiro

2017-01-01

In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans. We conducted in vivo and in vitro exploratory studies for this purpose. In vivo lipidomics analysis was conducted to investigate the relationships between alteration of the hepatic lipids and mitochondrial dysfunction. In the liver of rats treated with compound X, triglycerides containing long-chain fatty acids, which are the main energy source of the mitochondria, accumulated. Accumulation of these triglycerides was considered to be related to the inhibition of mitochondrial respiration based on the results of in vitro mitochondria toxicity studies. In conclusion, fatty change of the hepatocytes (steatosis) in non-clinical toxicity studies of drug candidates can be regarded as a critical finding for the estimation of their potential risk to induce DILI in humans when the fatty change is induced by mitochondrial dysfunction. PMID:28417920

Doubling the Spectrum of Time-Domain Induced Polarization: Removal of Harmonic Noise and Self-Potential Drift

Science.gov (United States)

Fiandaca, G.; Olsson, P. I.; Auken, E.; Larsen, J. J.; Maurya, P. K.; Dahlin, T.

2015-12-01

The extraction of spectral information in the inversion process of time-domain (TD) induced polarization (IP) data is changing the use of the IP method. Data interpretation is evolving from a qualitative description of the soil, able only to discriminate the presence of contrasts in chargeability parameters, towards a quantitative analysis of the investigated media, which allows soil-type characterization. Two major limitations restrict the extraction of the spectral information of TDIP data in the field: i) the difficulty of acquiring reliable early-time measurements, in the millisecond range and ii) the self-potential drift in the measured potentials distorting the shape of the late time IP decays, in the second range. For measuring at early-times, we developed a new method for removing the powerline noise contained in the data through a model-based approach, localizing the fundamental frequency of the powerline signal in the full-waveform IP recordings. By this, we cancel both the fundamental signal and its harmonics. This noise cancellation allows the use of earlier and narrower gates, down to a few milliseconds after the current turn-off. Even earlier gates can be measured but they will be inductively "contaminated" which we at present want to avoid. A proper removal of the self-potential drift present between the potential electrodes is essential for preserving the shape of the TD decays, especially for late times. Usually constant or linear drift-removal algorithms are used, but these algorithms fail in removing the background potentials due to the polarization of the electrodes previously used for current injection. We developed a drift-removal scheme that model the polarization effect and efficiently allows for preserving the shape of the IP decays. The removal of both the harmonic noise and self-potential drift allows for doubling the usable range of TDIP data to more than three decades in time (corresponding to three decays in frequency), and will

Involvement of near-UV-induced synthesis of serotonin in photoprotection and in potentiation of far UV lethality in the yeast Candida guilliermondii

International Nuclear Information System (INIS)

Fraikin, G.Y.; Strakhovskaya, M.G.; Rubin, L.B.

1981-01-01

Mechanisms of near-UV (334 nm) induced photoprotection as well as potentiation of far-UV (254 nm) lethality are considered in Candida guilliermondii. Using exogenous precursors of serotonin, it appears that the above two mechanisms involve photoactivated synthesis of serotonin. It has been postulated that the serotonin effect could take place by binding to DNA. (author)

Synthesis of new heterocyclic compounds based on pyrazolopyridine scaffold and evaluation of their neuroprotective potential in MPP+-induced neurodegeneration.

Science.gov (United States)

Jouha, Jabrane; Loubidi, Mohammed; Bouali, Jamila; Hamri, Salha; Hafid, Abderrafia; Suzenet, Franck; Guillaumet, Gérald; Dagcı, Taner; Khouili, Mostafa; Aydın, Fadime; Saso, Luciano; Armagan, Güliz

2017-03-31

Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP + -induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique. Based on the cell viability results obtained by MTT assay, the percentage of neuroprotection-induced by compounds against MPP + -induced neurotoxicity in SH-SY5Y cells was between 20% and 30% at 5 μM concentrations of all synthesized compounds. Moreover, the downregulation in pro-apoptotic proteins including bax and caspase-3 were found following the novel synthesized compounds treatments and these effects were observed in a dose-dependent manner. Our results provide an evidence that these heterocyclic compounds based on pyrazolopyridine derivatives may have a role on dopaminergic neuroprotection via antiapoptotic pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

DEFF Research Database (Denmark)

Fosgerau, Keld; Weber, Uno J; Gotfredsen, Jacob W

2010-01-01

Background  The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feas......Background  The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated...... the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. Methods First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies...... was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Conclusions Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining...

Studies on sediment transport along Kerala Coast, south west coast of India

Digital Repository Service at National Institute of Oceanography (India)

Sajeev, R.; Chandramohan, P.; Josanto, V.; Sanakaranarayanan, V.N.

Longshore sediment transport characteristics of the Kerala Coast have been examined to delineate various physical processes affecting the different coastal environments. Monthly averages of the daily LEO (Littoral Environmental Observation) data...

Propionyl-L-carnitine as a potential protective agent against radiation-induced cardiotoxicity

International Nuclear Information System (INIS)

Ramadan, L.A.

2003-01-01

In this study, propiony-L-carnitine (PLC); a natural short-chain derivative of L-carnitine, has been tested as a potential protective agent against radiation-induced cardio-toxicity. Cardiotoxicity was assessed in the homo-genate of the heart by measuring the plasma levels of creatine phosphokinase (CPK), lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST), as well as malon-dialdehyde (MDA), glutathione content (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), adenosine triphosphate (ATP) and nitric oxide (NO) production, whole body gamma-irradiation (2 and 6Gy ) of rats significantly increased CPK, LDH, AST,MDA, and NO and significantly decreased GSH,GSH-PX, SOD and ATP. Daily administration (one week) of PLC before whole body irradiation caused significant recovery for the serum enzyme CPK, LDH, AST and MDA, GSH, GSH-PX, SOD, ATP and NO levels in cardiac tissue. The protective effect PLC was attributed to it's antioxidant properties. Radiation therapy, likewise, is a valuable method of treatment for a variety of intrathoracic neoplasms. During radiotherapy of thoracic tumorus, the heart is often included in the primary treatment volume and chronic impairment of myocadial function occurs (cilliers and lochner, 1993; benderitter et al., 1995). Irradiation causes numerous changes in different metabolic reactions within the cardiac cells with major adverse undersirable effects that involve cardiotoxicity

Deliberate total parathyroidectomy: a potentially novel therapy for tumor-induced hypophosphatemic osteomalacia.

Science.gov (United States)

Bhadada, Sanjay K; Palnitkar, Saroj; Qiu, Shijing; Parikh, Nayana; Talpos, Gary B; Rao, Sudhaker D

2013-11-01

Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic metabolic bone disorder that can be cured by removing or ablating the offending tumor. However, when the tumor cannot be localized, lifelong therapy with oral phosphate and calcitriol or cinacalcet with close monitoring is required. A 56-year-old man was diagnosed with TIO in 1990. Initial therapy consisted of oral phosphate and calcitriol with symptomatic and biochemical improvement and healing of osteomalacia. Eight years later, hypercalcemic hyperparathyroidism developed, requiring subtotal parathyroidectomy with a transient increase in serum phosphate and normalization of serum calcium and PTH. Recurrent hypercalcemic hyperparathyroidism developed after 10 years of medical therapy. A deliberate total parathyroidectomy produced a prompt rise in serum phosphate into the normal range > 3.0 mg/dL and remained normal during the next 4 years of follow-up, despite continued very high serum fibroblast growth factor-23 levels throughout the 23-year follow-up. We report an unusual case of a TIO patient with long-term follow-up who developed recurrent hypercalcemic hyperparathyroidism on long-term oral phosphate therapy. Deliberate total parathyroidectomy normalized serum phosphate despite persistently elevated fibroblast growth factor-23 levels. Total parathyroidectomy offers a potentially novel therapy in some patients with TIO in whom medical therapy is not feasible or the tumor is unresectable.

Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice

Energy Technology Data Exchange (ETDEWEB)

Guenancia, Charles [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Li, Na [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Hachet, Olivier [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Rigal, Eve [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cottin, Yves [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Dutartre, Patrick; Rochette, Luc [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Vergely, Catherine, E-mail: cvergely@u-bourgogne.fr [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France)

2015-04-15

Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran–iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran–iron (15 mg/kg) for 3 weeks (D0–D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6 mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran–iron (125–1000 μg/mL) in combination with DOX, paradoxically limited cytotoxicity in H9c2 and increased it in EMT-6. In mice, IO alone resulted in cardiac hypertrophy (+ 22%) and up-regulation of brain natriuretic peptide and β-myosin heavy-chain (β-MHC) expression, as well as an increase in cardiac nitro-oxidative stress revealed by electron spin resonance spectroscopy. In DOX-treated mice, there was a significant decrease in left-ventricular ejection fraction (LVEF) and an up-regulation of cardiac β-MHC and atrial natriuretic peptide (ANP) expression. However, prior IO did not exacerbate the DOX-induced fall in LVEF and there was no increase in ANP expression. IO did not impair the capacity of DOX to decrease cancer cell viability and could even prevent some aspects of DOX cardiotoxicity in cardiomyocytes and in mice. - Highlights: • The effects of iron on cardiomyocytes were opposite to those on cancer cell lines. • In our model, iron overload did not potentiate anthracycline cardiotoxicity. • Chronic oxidative stress induced by iron could mitigate doxorubicin cardiotoxicity. • The role of iron in

Transmembrane voltage: Potential to induce lateral microdomains.

Czech Academy of Sciences Publication Activity Database

Malínský, Jan; Tanner, W.; Opekarová, Miroslava

2016-01-01

Roč. 1861, č. 8 (2016), s. 806-811 ISSN 1388-1981 R&D Projects: GA ČR(CZ) GA15-10641S Institutional support: RVO:68378041 Keywords : membrane microdomain * membrane potential * fluorescence spectroscopy * membrane structure * fluorescence microscopy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.547, year: 2016

Brazilian Red Propolis Induces Apoptosis-Like Cell Death and Decreases Migration Potential in Bladder Cancer Cells

Directory of Open Access Journals (Sweden)

Karine Rech Begnini

2014-01-01

Full Text Available Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL. Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment.

Brazilian red propolis induces apoptosis-like cell death and decreases migration potential in bladder cancer cells.

Science.gov (United States)

Begnini, Karine Rech; Moura de Leon, Priscila Marques; Thurow, Helena; Schultze, Eduarda; Campos, Vinicius Farias; Martins Rodrigues, Fernanda; Borsuk, Sibele; Dellagostin, Odir Antônio; Savegnago, Lucielli; Roesch-Ely, Mariana; Moura, Sidnei; Padilha, Francine F; Collares, Tiago; Pêgas Henriques, João Antonio; Seixas, Fabiana Kömmling

2014-01-01

Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP) on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL) on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay) assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL). Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment.

A spatial modeling framework to evaluate domestic biofuel-induced potential land use changed and emissions

Science.gov (United States)

Elliot, Joshua; Sharma, Bhavna; Best, Neil; Glotter, Michael; Dunn, Jennifer B.; Foster, Ian; Miguez, Fernando; Mueller, Steffen; Wang, Michael

2014-01-01

We present a novel bottom-up approach to estimate biofuel-induced land-use change (LUC) and resulting CO2 emissions in the U.S. from 2010 to 2022, based on a consistent methodology across four essential components: land availability, land suitability, LUC decision-making, and induced CO2 emissions. Using highresolution geospatial data and modeling, we construct probabilistic assessments of county-, state-, and national-level LUC and emissions for macroeconomic scenarios. We use the Cropland Data Layer and the Protected Areas Database to characterize availability of land for biofuel crop cultivation, and the CERES-Maize and BioCro biophysical crop growth models to estimate the suitability (yield potential) of available lands for biofuel crops. For LUC decisionmaking, we use a county-level stochastic partial-equilibrium modeling framework and consider five scenarios involving annual ethanol production scaling to 15, 22, and 29 BG, respectively, in 2022, with corn providing feedstock for the first 15 BG and the remainder coming from one of two dedicated energy crops. Finally, we derive high-resolution above-ground carbon factors from the National Biomass and Carbon Data set to estimate emissions from each LUC pathway. Based on these inputs, we obtain estimates for average total LUC emissions of 6.1, 2.2, 1.0, 2.2, and 2.4 gCO2e/MJ for Corn-15 Billion gallons (BG), Miscanthus × giganteus (MxG)-7 BG, Switchgrass (SG)-7 BG, MxG-14 BG, and SG-14 BG scenarios, respectively.

Baby universes with induced gravity

International Nuclear Information System (INIS)

Gao Yihong; Gao Hongbo

1989-01-01

In this paper some quantum effects of baby universes with induced gravity are discussed. It is proved that the interactions between the baby-parent universes are non-local, and argue that the induced low-energy cosmological constant is zero. This argument does not depend on the detail of the induced potential

Synthesis, Characterization and In Vitro Anticancer Activity of C-5 Curcumin Analogues with Potential to Inhibit TNF-α-Induced NF-κB Activation

Directory of Open Access Journals (Sweden)

Amit Anthwal

2014-01-01

Full Text Available In a search of new compounds active against cancer, synthesis of a series of C-5 curcumin analogues was carried out. The new compounds demonstrated good cytotoxicity against chronic myeloid leukemia (KBM5 and colon cancer (HCT116 cell lines. Further, these compounds were found to have better potential to inhibit TNF-α-induced NF-κB activation in comparison to curcumin, which show their potential to act as anti-inflammatory agents. Some compounds were found to show higher cytotoxicity against cancer cell lines in comparison to curcumin used as standard.

Cross-shore redistribution of nourished sand near a breaker bar

DEFF Research Database (Denmark)

Jacobsen, Niels Gjøl; Fredsøe, Jørgen

2014-01-01

the Engelund and Fredsøe deterministic concept. The methodology is as follows: a Dean/Bruun equilibrium profile is exposed to regular waves (chosen as H = 1.3 m and T = 4.8 s). These waves will form bars on the Dean/Bruun equilibrium profile, and the wave impact is continued until a quasi-steady behavior...... over the profile is consider as a means of imposing the net recirculation resulting from longshore nonuniformities or the impact of wind-induced shear stresses. The impact of wave height, irregularity in incident waves, and the size of the sediment grains on the cross-shore distribution of suspended...... bar can have both destructive and protective impacts on the original shoreward-located cross-shore profile....

A dispersive optical model potential for nucleon induced reactions on 238U and 232Th nuclei with full coupling

Directory of Open Access Journals (Sweden)

Chiba Satoshi

2013-03-01

Full Text Available A dispersive coupled-channel optical model potential (DCCOMP that couples the ground-state rotational and low-lying vibrational bands of 238U and 232Th nuclei is studied. The derived DCCOMP couples almost all excited levels below 1 MeV of excitation energy of the corresponding even-even actinides. The ground state, octupole, beta, gamma, and non-axial bands are coupled. The first two isobar analogue states (IAS populated in the quasi-elastic (p,n reaction are also coupled in the proton induced calculation, making the potential approximately Lane consistent. The coupled-channel potential is based on a soft-rotor description of the target nucleus structure, where dynamic vibrations are considered as perturbations of the rigid rotor underlying structure. Matrix elements required to use the proposed structure model in Tamura coupled-channel scheme are derived. Calculated ratio R(U238/Th232 of the total cross-section difference to the averaged σT for 238U and 232Th nuclei is shown to be in excellent agreement with measured data.

Anandamide induces matrix metalloproteinase-2 production through cannabinoid-1 receptor and transient receptor potential vanilloid-1 in human dental pulp cells in culture.

Science.gov (United States)

Miyashita, Keiko; Oyama, Tohru; Sakuta, Tetsuya; Tokuda, Masayuki; Torii, Mitsuo

2012-06-01

Anandamide (N-arachidonoylethanolamine [AEA]) is one of the main endocannabinoids. Endocannabinoids are implicated in various physiological and pathologic functions, inducing not only nociception but also regeneration and inflammation. The role of the endocannabinoid system in peripheral organs was recently described. The aim of this study was to investigate the effect of AEA on matrix metalloproteinase (MMP)-2 induction in human dental pulp cells (HPC). We examined AEA-induced MMP-2 production and the expression of AEA receptors (cannabinoid [CB] receptor-1, CB2, and transient receptor potential vanilloid-1 [TRPV1]) in HPC by Western blot. MMP-2 concentrations in supernatants were determined by enzyme-linked immunosorbent assay. We then investigated the role of the AEA receptors and mitogen-activated protein kinase in AEA-induced MMP-2 production in HPC. AEA significantly induced MMP-2 production in HPC. HPC expressed all 3 types of AEA receptor (CB1, CB2, and TRPV1). AEA-induced MMP-2 production was blocked by CB1 or TRPV1 antagonists and by small interfering RNA for CB1 or TRPV1. Furthermore, c-Jun N-terminal kinase inhibitor also reduced MMP-2 production. We demonstrated for the first time that AEA induced MMP-2 production via CB1 and TRPV1 in HPC. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

29 CFR 1918.88 - Log operations.

Science.gov (United States)

2010-07-01

...) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.88 Log operations. (a) Working in..., the employer shall ensure that employees remain clear of areas where logs being dumped could strike...

IN VITRO MODELS TO EVALUATE DRUG-INDUCED HYPERSENSITIVITY: POTENTIAL TEST BASED ON ACTIVATION OF DENDRITIC CELLS

Directory of Open Access Journals (Sweden)

Valentina Galbiati

2016-07-01

Full Text Available Hypersensitivity drug reactions (HDRs are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated ('allergic' and non immune-mediated ('pseudo allergic' reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon.We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells.

Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human?Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans-

OpenAIRE

Goda, Keisuke; Kobayashi, Akio; Takahashi, Akemi; Takahashi, Tadakazu; Saito, Kosuke; Maekawa, Keiko; Saito, Yoshiro; Sugai, Shoichiro

2017-01-01

In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury...

Ozone and sulphur dioxide effects on leaf water potential of Petunia

Energy Technology Data Exchange (ETDEWEB)

Elkiey, T.; Ormrod, D.P.

1979-01-01

Three cultivars of Petunia hydrida Vilm., of differing ozone visible injury sensitivity, were exposed to 40 parts per hundred million (pphm) ozone and/or 80 pphm SO/sub 2/ for 4 h to study the relationships of leaf water potential, pollutant exposure, and cultivar sensitivity. Ozone substantially decreased leaf water potential in cv White Cascade but not in cv Capri or White Magic. Sulphur dioxide did not affect leaf water potential but delayed ozone-induced changes. Cultivar sensitivity to ozone-induced changes in leaf water potential was not related to cultivar sensitivity to ozone-induced visible injury.

Fluctuation induced critical behavior at nonzero temperature and chemical potential

International Nuclear Information System (INIS)

Splittorff, K.; Lenaghan, J.T.; Wirstam, J.

2003-01-01

We discuss phase transitions in relativistic systems as a function of both the chemical potential and temperature. The presence of a chemical potential explicitly breaks Lorentz invariance and may additionally break other internal symmetries. This introduces new subtleties in the determination of the critical properties. We discuss separately three characteristic effects of a nonzero chemical potential. First, we consider only the explicit breaking of Lorentz invariance using a scalar field theory with a global U(1) symmetry. Second, we study the explicit breaking of an internal symmetry in addition to Lorentz invariance using two-color QCD at nonzero baryonic chemical potential. Finally, we consider the spontaneous breaking of a symmetry using three-color QCD at nonzero baryonic and isospin chemical potential. For each case, we derive the appropriate three-dimensional effective theory at criticality and study the effect of the chemical potential on the fixed point structure of the β functions. We find that the order of the phase transition is not affected by the explicit breaking of Lorentz invariance but is sensitive to the breaking of additional symmetries by the chemical potential

A synthetic coumarin (4-methyl-7 hydroxy coumarin) has anti-cancer potentials against DMBA-induced skin cancer in mice.

Science.gov (United States)

Bhattacharyya, Soumya S; Paul, Saili; Mandal, Sushil K; Banerjee, Antara; Boujedaini, Naoual; Khuda-Bukhsh, Anisur R

2009-07-01

Scopoletin, an alkaloid separated from ethanolic extract of the medicinal plant, Gelsemium sempervirens (Fam: Loganiaceae) has been reported to have anti-cancer potentials. The synthetic coumarin (4-Methyl-7 hydroxy coumarin) derived from resorcinol and ethyl aceto-acetate in presence of concentrated sulphuric acid is structurally close to scopoletin, being a coumarin derivative. Whether this synthetic compound also has anti-cancer potentials has been evaluated in vivo on DMBA (7,12-Dimethylbenz[a]anthracene) induced skin cancer in mice by analyzing results of several cytogenetic endpoints, Comet assay, and fluorescence activated cell sorting (FACS). Further, expressions of signal proteins like Aryl hydrocarbon receptor , p53, PCNA, Akt, Bcl-2, Bcl-xL, Bad, Bax, NF-kappaB Apaf, IL-6, Cytochrome-c, Caspase-3 and Caspase-9 were studied by immunoblot analysis along with histology of skin and immuno-histochemical localization of Aryl hydrocarbon receptor and PCNA in DMBA treated mice vis-a-vis carcinogen treated synthetic coumarin fed mice. Feeding of this synthetic coumarin induced positive modulations in expression of all biomarkers in DMBA administered mice, giving clues on its possible signaling pathway(s) - primarily through down-regulation of Aryl hydrocarbon receptor and PCNA and up-regulation of apoptotic proteins like Bax, Bad, Cytochrome c, Apaf, Caspase-3 and Caspase-9, resulting in an appreciable reduction in growth of papilloma in mice. Therefore, this synthetic coumarin shows promise for use in cancer therapy, particularly in skin cancer.

Myostatin expression, lymphocyte population, and potential cytokine production correlate with predisposition to high-fat diet induced obesity in mice.

Directory of Open Access Journals (Sweden)

Jeri-Anne Lyons

2010-09-01

Full Text Available A strong relationship exists between increased inflammatory cytokines and muscle insulin resistance in obesity. This study focused on identifying a relationship between metabolic propensity and myostatin expression in muscle and spleen cells in response to high-fat diet intake. Using a comparative approach, we analyzed the effects of high-fat diet intake on myostatin and follistatin expression, spleen cell composition, and potential cytokine expression in high-fat diet induced obesity (HFDIO resistant (SWR/J and susceptible (C57BL/6 mice models. Results demonstrated overall increased myostatin expression in muscle following high-fat diet intake in HFDIO-susceptible mice, while myostatin expression levels decreased initially in muscle from high-fat diet fed resistant mice. In HFDIO-resistant mice, myostatin expression decreased in spleen, while myostatin increased in spleen tissue from HFDIO-susceptible mice. Proinflammatory cytokine (IL-17, IL-1β, and IFNγ potential increased in splenocytes from HFDIO-susceptible mice. In comparison, C57BL/6 mice fed a high-fat diet exhibited higher frequencies of CD4(+/CD44(hi and CD8(+/CD44(hi cells in the spleen compared to control fed mice. Together, these results suggest that susceptibility to high-fat diet induced obesity could be influenced by local myostatin activity in a tissue-specific manner and that splenocytes exhibit differential cytokine production in a strain-dependent manner. This study sets the stage for future investigations into the interactions between growth, inflammation, and metabolism.

Effectiveness of ketogenic diet in pentylenetetrazol-induced and kindling rats as well as its potential mechanisms.

Science.gov (United States)

Wang, Shan; Ding, Yao; Ding, Xiao-Yan; Liu, Zhi-Rong; Shen, Chun-Hong; Jin, Bo; Guo, Yi; Wang, Shuang; Ding, Mei-Ping

2016-02-12

The effects and mechanisms of ketogenic diets (KD) are unclear. In this study, we aimed to reveal electrographic and behavioral thresholds in responses to the KD in pentylenetetrazol (PTZ)-induced seizures, as well as its antiepileptogenic effects on PTZ-kindling rats. Additionally, we investigated the potential link between KD and expression levels of two cation chloride co-transporters: K(+)-Cl(-) co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1). The KD group had significantly higher electrographic thresholds than the control (ND) group for the first spike-and-wave, subcontinuous spike-and-wave, high amplitude spike-and-wave, and polyspikes both in the cortex and hippocampus. Compared to the ND group, the KD group had higher behavioral thresholds for behavioral absence, first jerk, first overt myoclonia, and generalized seizures. In the PTZ-kindling model, KD not only prolonged the latency of myoclonic and clonic convulsions, but shortened clonic and generalized duration. In addition, KD rats had higher KCC2 protein expression before kindling, during myoclonic jerks, and GTCS compared with ND rats. There were no significant differences in NKCC1 protein levels between both groups following the four-week dietary intervention without PTZ exposure (before kindling). Moreover, KD inhibited the upregulation of NKCC1 expression induced by kindling in myoclonic jerks and GTCS. Therefore, our findings demonstrated that KD had antiepileptic features in elevating thresholds to most electrographic and behavioral seizure patterns in PTZ-induced rats, as well as delaying the progression and alleviating the severity of seizure in PTZ-kindling model. The antiepileptogenic effects of KD may be attributed to its regulatory properties on KCC2 and NKCC1 protein expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress: potential role in obesity.

Science.gov (United States)

Martínez-Martínez, Ernesto; Jurado-López, Raquel; Valero-Muñoz, María; Bartolomé, María Visitación; Ballesteros, Sandra; Luaces, María; Briones, Ana María; López-Andrés, Natalia; Miana, María; Cachofeiro, Victoria

2014-05-01

Leptin acts as a cardiac profibrotic factor. However, the mechanisms underlying this effect are unclear. Therefore, we sought to elucidate the mediators involved in this process and the potential role of leptin in cardiac fibrosis associated with obesity. Male Wistar rats were fed either a high-fat diet (HFD; 33.5% fat), or a standard diet (3.5% fat) for 6 weeks. HFD animals show cardiac hypertrophy, fibrosis and an increase in O2- production as evaluated by dihydroethidium. Echocardiographic parameters of cardiac structure and systolic function were similar in both groups. Cardiac levels of leptin, collagen I, galectin-3 and transforming growth factor β (TGF-β) were higher in HFD than in controls. In cardiac myofibroblasts, leptin (10-100 ng/ml) increased O2-, collagen I, galectin-3, TGF-β and connective tissue growth factor production (CTGF). These effects were prevented by the presence of either melatonin (10 mmol/l) or the inhibitor of mTOR, rapamycin (10 mmol/l). Blockage of galectin-3 activity by N-acetyllactosamine (LacNac 10 mmol/l) reduced both collagen I and O2(*-) production induced by leptin. The p70S6 kinase activation/phosphorylation, the downstream mediator of mTOR, induced by leptin was not modified by melatonin. Leptin reduced the metalloproteinase (MMP) 2 activity and the presence of melatonin, rapamycin or LacNac were unable to prevent it. The data suggest that leptin locally produced in the heart could participate in the fibrosis observed in HFD by affecting collagen turnover. Collagen synthesis induced by leptin seems to be mediated by the production of galectin-3, TGF-β and CTGF through oxidative stress increased by activation of mTOR pathway.

A comparative study of the potentiating effect of caffeine and poly-D-lysine on chromosome damage induced by X-rays in plant cells

Energy Technology Data Exchange (ETDEWEB)

Mateos, S.; Panneerselvam, N.; Cortes, F. (Sevilla University, Faculty of Biology (Spain). Department of Cell Biology); Mateos, J.C. (Centro Regional de Oncologia ' Duque del Infantado' , Sevilla (Spain))

1992-04-01

X-ray-induced chromosomal aberrations (CA) were potentiated by post-treatments in G{sub 2} with either caffeine (caff) or poly-D-lysine (PDL) in root-tip cells of Allium cepa. The enhancement of the yield of CA was concomittant with an increase in the frequency of mitosis. The results seem to support the idea of a direct relationship between radiation-induced G{sub 2} delay and repair of chromosome damage. Similarities between caff and PDL are reported in both decreasing G{sub 2} delay and enhancing chromatid aberration yield. The possible molecular mechanism(s) of action responsible for the cytogenetic effects observed are discussed. (author). 20 refs.; 2 tabs.

One nuclear calcium transient induced by a single burst of action potentials represents the minimum signal strength in activity-dependent transcription in hippocampal neurons.

Science.gov (United States)

Yu, Yan; Oberlaender, Kristin; Bengtson, C Peter; Bading, Hilmar

2017-07-01

Neurons undergo dramatic changes in their gene expression profiles in response to synaptic stimulation. The coupling of neuronal excitation to gene transcription is well studied and is mediated by signaling pathways activated by cytoplasmic and nuclear calcium transients. Despite this, the minimum synaptic activity required to induce gene expression remains unknown. To address this, we used cultured hippocampal neurons and cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH) that allows detection of nascent transcripts in the cell nucleus. We found that a single burst of action potentials, consisting of 24.4±5.1 action potentials during a 6.7±1.9s depolarization of 19.5±2.0mV causing a 9.3±0.9s somatic calcium transient, is sufficient to activate transcription of the immediate early gene arc (also known as Arg3.1). The total arc mRNA yield produced after a single burst-induced nuclear calcium transient was very small and, compared to unstimulated control neurons, did not lead to a significant increase in arc mRNA levels measured using quantitative reverse transcriptase PCR (qRT-PCR) of cell lysates. Significantly increased arc mRNA levels became detectable in hippocampal neurons that had undergone 5-8 consecutive burst-induced nuclear calcium transients at 0.05-0.15Hz. These results indicate that a single burst-induced nuclear calcium transient can activate gene expression and that transcription is rapidly shut off after synaptic stimulation has ceased. Copyright © 2017 Elsevier Ltd. All rights reserved.

Asperity-Type Potential Foreshock Sources Driven by Nucleation-Induced Creep within a Rate-and-State Fault Model

Science.gov (United States)

Higgins, N.; Lapusta, N.

2016-12-01

What physical mechanism drives the occurrence of foreshocks? Many studies have suggested that slow slip from the mainshock nucleation is a necessary ingredient for explaining foreshock observations. We explore this view, investigating asperity-type foreshock sources driven by nucleation-induced creep using rate-and-state fault models, and numerically simulatie their behavior over many rupture cycles. Inspired by the unique laboratory experiments of earthquake nucleation and rupture conducted on a meter-scale slab of granite by McLaskey and colleagues, we model potential foreshock sources as "bumps" on the fault interface by assigning a significantly higher normal compression and, in some cases, increased smoothness (lower characteristic slip) over small patches within a seismogenic fault. In order to study the mechanics of isolated patch-induced seismic events preceding the mainshock, we separate these patches sufficiently in space. The simulation results show that our rate-and-state fault model with patches of locally different properties driven by the slow nucleation of the mainshock is indeed able to produce isolated microseismicity before the mainshock. Remarkably, the stress drops of these precursory events are compatible with observations and approximately independent of the patch compression, despite the wide range of the elevated patch compression used in different simulations. We find that this unexpected property of stress drops for this type of model is due to two factors. Firstly, failure of stronger patches results in rupture further into the surrounding fault, keeping the average stress drop down. Secondly, patches close to their local nucleation size relieve a significant amount of stress via aseismic pre-slip, which also helps to keep the stress drop down. Our current work is directed towards investigating the seismic signature of such events and the potential differences with other types of microseismicity.

Characterization of the apoptotic response induced by the cyanine dye D112: a potentially selective anti-cancer compound.

Directory of Open Access Journals (Sweden)

Ning Yang

Full Text Available Chemotherapeutic drugs that are used in anti-cancer treatments often cause the death of both cancerous and noncancerous cells. This non-selective toxicity is the root cause of untoward side effects that limits the effectiveness of therapy. In order to improve chemotherapeutic options for cancer patients, there is a need to identify novel compounds with higher discrimination for cancer cells. In the past, methine dyes that increase the sensitivity of photographic emulsions have been investigated for anti-cancer properties. In the 1970's, Kodak Laboratories initiated a screen of approximately 7000 dye structural variants for selective toxicity. Among these, D112 was identified as a promising compound with elevated toxicity against a colon cancer cell line in comparison to a non-transformed cell line. Despite these results changing industry priorities led to a halt in further studies on D112. We decided to revive investigations on D112 and have further characterized D112-induced cellular toxicity. We identified that in response to D112 treatment, the T-cell leukemia cell line Jurkat showed caspase activation, mitochondrial depolarization, and phosphatidylserine externalization, all of which are hallmarks of apoptosis. Chemical inhibition of caspase enzymatic activity and blockade of the mitochondrial pathway through Bcl-2 expression inhibited D112-induced apoptosis. At lower concentrations, D112 induced growth arrest. To gain insight into the molecular mechanism of D112 induced mitochondrial dysfunction, we analyzed the intracellular localization of D112, and found that D112 associated with mitochondria. Interestingly, in the cell lines that we tested, D112 showed increased toxicity toward transformed versus non-transformed cells. Results from this work identify D112 as a potentially interesting molecule warranting further investigation.

Reassessment of liquefaction potential and estimation of earthquake- induced settlements at Paducah Gaseous Diffusion Plant, Paducah, Kentucky. Final report

International Nuclear Information System (INIS)

Sykora, D.W.; Yule, D.E.

1996-04-01

This report documents a reassessment of liquefaction potential and estimation of earthquake-induced settlements for the U.S. Department of Energy (DOE), Paducah Gaseous Diffusion Plant (PGDP), located southwest of Paducah, KY. The U.S. Army Engineer Waterways Experiment Station (WES) was authorized to conduct this study from FY91 to FY94 by the DOE, Oak Ridge Operations (ORO), Oak Ridge, TN, through Inter- Agency Agreement (IAG) No. DE-AI05-91OR21971. The study was conducted under the Gaseous Diffusion Plant Safety Analysis Report (GDP SAR) Program

Local establishment of repetitive long-term potentiation-induced synaptic enhancement in cultured hippocampal slices with divided input pathways.

Science.gov (United States)

Oe, Yuki; Tominaga-Yoshino, Keiko; Ogura, Akihiko

2011-09-01

Long-term potentiation (LTP) in the rodent hippocampus is a popular model for synaptic plasticity, which is considered the cellular basis for brain memory. Because most LTP analysis involves acutely prepared brain slices, however, the longevity of single LTP has not been well documented. Using stable hippocampal slice cultures for long-term examination, we previously found that single LTP disappeared within 1 day. In contrast, repeated induction of LTP led to the development of a distinct type of plasticity that lasted for more than 3 weeks and was accompanied by the formation of new synapses. Naming this novel plastic phenomenon repetitive LTP-induced synaptic enhancement (RISE), we proposed it as a model for the cellular processes involved in long-term memory formation. However, because in those experiments LTP was induced pharmacologically in the whole slice, it is not known whether RISE has input-pathway specificity, an essential property for memory. In this study, we divided the input pathway of CA1 pyramidal neurons by a knife cut and induced LTP three times, the third by tetanic stimulation in one of the divided pathways to express RISE specifically. Voltage-sensitive dye imaging and Golgi-staining performed 2 weeks after the three LTP inductions revealed both enhanced synaptic strength and increased dendritic spine density confined to the tetanized region. These results demonstrate that RISE is a feasible cellular model for long-term memory. Copyright © 2011 Wiley-Liss, Inc.

Essential role of transient receptor potential M8 (TRPM8) in a model of acute cold-induced urinary urgency.

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Uvin, Pieter; Franken, Jan; Pinto, Silvia; Rietjens, Roma; Grammet, Luc; Deruyver, Yves; Alpizar, Yeranddy A; Talavera, Karel; Vennekens, Rudi; Everaerts, Wouter; De Ridder, Dirk; Voets, Thomas

2015-10-01

Acute exposure of part of the skin to cold stimuli can evoke urinary urgency, a phenomenon termed acute cold-induced urgency (ACIU). Despite its high prevalence, particularly in patients with overactive bladder, little is known about the mechanisms that induce ACIU. To develop an animal model of ACIU and test the involvement of cold-activated ion channels transient receptor potential (TRP) M8 and TRPA1. Intravesical pressure and micturition were monitored in female mice (wild-type C57BL/6J, Trpa1(-/-), Trpm8(+/+), and Trpm8(-/-)) and Sprague Dawley rats. An intravesical catheter was implanted. Localized cooling of the skin was achieved using a stream of air or topical acetone. The TRPM8 antagonist (N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide (AMTB) or vehicle was injected intraperitoneally. Frequencies of bladder contractions and voids in response to sensory stimuli were compared using the Mann-Whitney or Kruskal-Wallis test. Brief, innocuously cold stimuli applied to different parts of the skin evoked rapid bladder contractions and voids in anesthetized mice and rats. These responses were strongly attenuated in Trpm8(-/-) mice and in rats treated with AMTB. As rodent bladder physiology differs from that of humans, it is difficult to directly extrapolate our findings to human patients. Our findings indicate that ACIU is an evolutionarily conserved reflex rather than subconscious conditioning, and provide a useful in vivo model for further investigation of the underlying mechanisms. Pharmacological inhibition of TRPM8 may be useful for treating ACIU symptoms in patients. Brief cold stimuli applied to the skin can evoke a sudden desire to urinate, which can be highly bothersome in patients with overactive bladder. We developed an animal model to study this phenomenon, and found that it depends on a specific molecular cold sensor, transient receptor potential M8 (TRPM8). Pharmacological inhibition of TRPM8 may alleviate acute cold-induced

Limiting the Magnitude of Potential Injection-Induced Seismicity Associated With Waste-Water Disposal, Hydraulic Fracturing and CO2 Sequestration

Science.gov (United States)

Zoback, Mark

2017-04-01

In this talk, I will address the likelihood for fault slip to occur in response to fluid injection and the likely magnitude of potentially induced earthquakes. First, I will review a methodology that applies Quantitative Risk Assessment to calculate the probability of a fault exceeding Mohr-Coulomb slip criteria. The methodology utilizes information about the local state of stress, fault strike and dip and the estimated pore pressure perturbation to predict the probability of the fault slip as a function of time. Uncertainties in the input parameters are utilized to assess the probability of slip on known faults due to the predictable pore pressure perturbations. Application to known faults in Oklahoma has been presented by Walsh and Zoback (Geology, 2016). This has been updated with application to the previously unknown faults associated with M >5 earthquakes in the state. Second, I will discuss two geologic factors that limit the magnitudes of earthquakes (either natural or induced) in sedimentary sequences. Fundamentally, the layered nature of sedimentary rocks means that seismogenic fault slip will be limited by i) the velocity strengthening frictional properties of clay- and carbonate-rich rock sequences (Kohli and Zoback, JGR, 2013; in prep) and ii) viscoplastic stress relaxation in rocks with similar composition (Sone and Zoback, Geophysics, 2013a, b; IJRM, 2014; Rassouli and Zoback, in prep). In the former case, if fault slip is triggered in these types of rocks, it would likely be aseismic due the velocity strengthening behavior of faults. In the latter case, the stress relaxation could result in rupture termination in viscoplastic formations. In both cases, the stratified nature of sedimentary rock sequences could limit the magnitude of potentially induced earthquakes. Moreover, even when injection into sedimentary rocks initiates fault slip, earthquakes large enough to cause damage will usually require slip on faults sufficiently large that they extend

Potentially induced earthquakes during the early twentieth century in the Los Angeles Basin

Science.gov (United States)

Hough, Susan E.; Page, Morgan T.

2016-01-01

Recent studies have presented evidence that early to mid‐twentieth‐century earthquakes in Oklahoma and Texas were likely induced by fossil fuel production and/or injection of wastewater (Hough and Page, 2015; Frohlich et al., 2016). Considering seismicity from 1935 onward, Hauksson et al. (2015) concluded that there is no evidence for significant induced activity in the greater Los Angeles region between 1935 and the present. To explore a possible association between earthquakes prior to 1935 and oil and gas production, we first revisit the historical catalog and then review contemporary oil industry activities. Although early industry activities did not induce large numbers of earthquakes, we present evidence for an association between the initial oil boom in the greater Los Angeles area and earthquakes between 1915 and 1932, including the damaging 22 June 1920 Inglewood and 8 July 1929 Whittier earthquakes. We further consider whether the 1933 Mw 6.4 Long Beach earthquake might have been induced, and show some evidence that points to a causative relationship between the earthquake and activities in the Huntington Beach oil field. The hypothesis that the Long Beach earthquake was either induced or triggered by an foreshock cannot be ruled out. Our results suggest that significant earthquakes in southern California during the early twentieth century might have been associated with industry practices that are no longer employed (i.e., production without water reinjection), and do not necessarily imply a high likelihood of induced earthquakes at the present time.

Supersymmetry breaking and α'-corrections to flux induced potentials

International Nuclear Information System (INIS)

Becker, Katrin; Becker, Melanie; Haack, Michael; Louis, Jan

2002-01-01

We obtain the vacuum solutions for M-theory compactified on eight-manifolds with non-vanishing four-form flux by analyzing the scalar potential appearing in the three-dimensional theory. Many of these vacua are not supersymmetric and yet have a vanishing three-dimensional cosmological constant.We show that in the context of type-IIB compactifications on Calabi-Yau threefolds with fluxes and external brane sources α'-corrections generate a correction to the supergravity potential proportional to the Euler number of the internal manifold which spoils the no-scale structure appearing in the classical potential. This indicates that α'-corrections may indeed lead to a stabilization of the radial modulus appearing in these compactifications. (author)

Modeling of Shoreline Changes of Tulamben Coast, Bali Indonesia

Science.gov (United States)

Yuanita, Nita; Pratama, Roka; Husrin, Semeidi

2015-04-01

Modeling of Shoreline Changes of Tulamben Coast, Bali Indonesia Tulamben coast is located in Lombok Strait on the northeastern coast of Bali island, Indonesia, as part of Karang Asem district. Severe erosion along the coastline has long been occurred in Karang Asem area and threatening houses, religious buildings (Hindu temples), and a national heritage site. As one of most popular diving site in Bali Island, Tulamben attracted many local and international tourist since 1980. The main attraction of Tulamben diving site is the USAT Liberty ship that was shipwrecked in Tulamben beach in 1942, after attacked by Japanese torpedo in Lombok Strait. Currently about 150 diver visit Tulamben per day. Due to physical changes of coastal environmental such as coastal erosion, sliding, and scouring, the shipwreck is vulnerable. It had been slipped off the beach several times and is predicted would be moved to deeper offshore floor if it is not protected. Coastal erosion in Karang Asem district is occurred probably due to interaction between cross-shore and long-shore wave-generated current and river sand supply decreasing after sand mining activities. In this study, the effect of cross-shore and longshore transport to coastal erosion in Tulamben is analyzed by doing numerical model. Numerical simulation of shoreline changes is performed by using Beach Processes Module of CEDAS (Coastal Engineering Design and Analysis System) consists of SBEACH and GENESIS. The model domain is covered Karang Asem coastline about 60 km length and wave data is calculated from hourly wind data (10 years). Simulated shoreline is calibrated using shoreline data from 1972 to 2013. Using calibrated model, then the simulation is performed from 2003 - 2013. From the simulation it is determined that longshore current and longshore sediment contribute to coastal erosion in Tulamben. Based on model results, several alternatives of general layout and configuration of coastal protection structures is proposed

MEK-ERK inhibition potentiates WAY-600-induced anti-cancer efficiency in preclinical hepatocellular carcinoma (HCC) models

Energy Technology Data Exchange (ETDEWEB)

Wang, Kaifeng, E-mail: kaifeng_wangdr@sina.com [Cancer center, the Affiliated Hospital of Hangzhou Normal University, Hangzhou (China); Fan, Yaohua [Oncology Department, No. 1 Hospital of Jiaxing, Zhejiang Province, Jiaxing (China); Chen, Gongying [Oncology Department, The Affiliated Hospital Hangzhou Normal University, Hangzhou (China); Wang, Zhengrong [Taizhou Hospital, Zhejiang Province, Taizhou (China); Kong, Dexin; Zhang, Peng [Oncology Department, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou (China)

2016-05-27

The search for novel anti-hepatocellular carcinoma (HCC) agents is important. Mammalian target of rapamycin (mTOR) hyper-activation plays a pivotal role in promoting HCC tumorigenesis and chemoresistance. The current preclinical study evaluated the potential anti-HCC activity by a potent mTOR kinase inhibitor, WAY-600. We showed that WAY-600 inhibited survival and proliferation of HCC cell lines (HepG2 and Huh7) and primary human HCC cells. Caspase-dependent apoptosis was activated by WAY-600 in above HCC cells. Reversely, caspase inhibitors largely attenuated WAY-600's lethality against HCC cells. At the signaling level, WAY-600 blocked mTOR complex 1/2 (mTORC1/2) assemble and activation, yet activated MEK-ERK pathway in HCC cells. MEK-ERK inhibitors, PD-98059 and MEK-162, or MEK1/2 shRNA significantly potentiated WAY-600's cytotoxicity in HCC cells. Further studies showed that WAY-600 intraperitoneal (i.p.) administration in nude mice inhibited p-AKT Ser-473 and displayed significant anti-cancer activity against HepG2 xenografts. Remarkably, co-administration of MEK-162 further potentiated WAY-600's anti-HCC activity in vivo. These preclinical results demonstrate the potent anti-HCC activity by WAY-600, either alone or with MEK-ERK inhibitors. -- Highlights: •WAY-600 inhibits HCC cell survival and proliferation in vitro. •WAY-600 activates caspase-dependent apoptosis in HCC cells. •WAY-600 blocks mTORC1/2 activation, but activates MEK-ERK in HCC cells. •MEK-ERK inhibitors or MEK1/2 shRNA enhances WAY-600's cytotoxicity against HCC cells. •MEK-162 co-administration potentiates WAY-600-induced the anti-HepG2 tumor efficacy.

Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage

International Nuclear Information System (INIS)

Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu; Li, Xiu-Miao; Jiang, Qin; Yan, Biao

2013-01-01

Highlights: •UVB irradiation induces RPE autophagy. •EGCG treatment represses UVB-mediated autophagy. •EGCG regulates UVB-mediated autophagy through mTOR signaling pathway. •EGCG sensitizes RPE cells to UVB-induced damage in an autophagy-dependent manner. -- Abstract: Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy

Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage

Energy Technology Data Exchange (ETDEWEB)

Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu; Li, Xiu-Miao; Jiang, Qin, E-mail: jqin710@vip.sina.com; Yan, Biao, E-mail: yanbiao1982@hotmail.com

2013-09-06

Highlights: •UVB irradiation induces RPE autophagy. •EGCG treatment represses UVB-mediated autophagy. •EGCG regulates UVB-mediated autophagy through mTOR signaling pathway. •EGCG sensitizes RPE cells to UVB-induced damage in an autophagy-dependent manner. -- Abstract: Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy.

Heuningnes (CSW19)

CSIR Research Space (South Africa)

Bickerton, IB

1984-02-01

Full Text Available on the longshore drift and run-off conditions. The recommendations in this report concerning increased tidal exchange through the forestry causeway should help to solve the management problem at the mouth....

Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

International Nuclear Information System (INIS)

Wu Chuanyun; Liu Bing; Wang Huili; Ruan Diyun

2011-01-01

Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T 4 ) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T 3 ) and tetraiodothyronine (T 4 ) levels accompanied by a dramatic decrease of TSH and application of L-T 4 restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T 4 treatment. L-T 4 treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T 4 relieves chronic Pb exposure-induced impairment of synaptic plasticity. - Highlights: → Lead may interfere with thyroid hormone homeostasis and induce hypothyroidism. → Levothyroxine decreases the hippocampal and blood Pb concentration. → Levothyroxine amends the T 3 , T 4 and TSH levels in blood. → Levothyroxine rescues the impaired LTP in CA1.

A new venous infusion path monitoring system utilizing electrostatic induced potential.

Science.gov (United States)

Ogawa, Hidekuni; Yonezawa, Yoshiharu; Maki, Hiromichi; Caldwell, W Morton

2008-01-01

A new venous infusion pathway monitoring system has been developed for hospital and home use. The system consists of linear and digital integrated circuits and a low-power 8-bit single chip microcomputer which constantly monitors the infusion pathway intactness. A 330 kHz AC voltage, which is induced on the patient's body by electrostatic coupling from a 330 kHz pulse oscillator, can be recorded by main and reference electrodes wrapped around the infusion polyvinyl chloride tube. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltages and alerts the nursing station, via the nurse call system or PHS (personal handy phone system).

Tris-hydroxymethyl-aminomethane enhances capsaicin-induced intracellular Ca2+ influx through transient receptor potential V1 (TRPV1 channels

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Satoshi Murakami

2016-02-01

Full Text Available Non-selective transient receptor potential vanilloid (TRPV cation channels are activated by various insults, including exposure to heat, acidity, and the compound capsaicin, resulting in sensations of pain in the skin, visceral organs, and oral cavity. Recently, TRPV1 activation was also demonstrated in response to basic pH elicited by ammonia and intracellular alkalization. Tris-hydroxymethyl aminomethane (THAM is widely used as an alkalizing agent; however, the effects of THAM on TRPV1 channels have not been defined. In this study, we characterized the effects of THAM-induced TRPV1 channel activation in baby hamster kidney cells expressing human TRPV1 (hTRPV1 and the Ca2+-sensitive fluorescent sensor GCaMP2 by real-time confocal microscopy. Notably, both capsaicin (1 μM and pH 6.5 buffer elicited steep increases in the intracellular Ca2+ concentration ([Ca2+]i, while treatment with THAM (pH 8.5 alone had no effect. However, treatment with THAM (pH 8.5 following capsaicin application elicited a profound, long-lasting increase in [Ca2+]i that was completely inhibited by the TRPV1 antagonist capsazepine. Taken together, these results suggest that hTRPV1 pre-activation is required to provoke enhanced, THAM-induced [Ca2+]i increases, which could be a mechanism underlying pain induced by basic pH.

Stress- and glucocorticoid-induced priming of neuroinflammatory responses: potential mechanisms of stress-induced vulnerability to drugs of abuse.

Science.gov (United States)

Frank, Matthew G; Watkins, Linda R; Maier, Steven F

2011-06-01

Stress and stress-induced glucocorticoids (GCs) sensitize drug abuse behavior as well as the neuroinflammatory response to a subsequent pro-inflammatory challenge. Stress also predisposes or sensitizes individuals to develop substance abuse. There is an emerging evidence that glia and glia-derived neuroinflammatory mediators play key roles in the development of drug abuse. Drugs of abuse such as opioids, psychostimulants, and alcohol induce neuroinflammatory mediators such as pro-inflammatory cytokines (e.g. interleukin (IL)-1β), which modulate drug reward, dependence, and tolerance as well as analgesic properties. Drugs of abuse may directly activate microglial and astroglial cells via ligation of Toll-like receptors (TLRs), which mediate the innate immune response to pathogens as well as xenobiotic agents (e.g. drugs of abuse). The present review focuses on understanding the immunologic mechanism(s) whereby stress primes or sensitizes the neuroinflammatory response to drugs of abuse and explores whether stress- and GC-induced sensitization of neuroimmune processes predisposes individuals to drug abuse liability and the role of neuroinflammatory mediators in the development of drug addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

Arsenic-induced nutrient uptake in As-hyperaccumulator Pteris vittata and their potential role to enhance plant growth.

Science.gov (United States)

Liu, Xue; Feng, Hua-Yuan; Fu, Jing-Wei; Chen, Yanshan; Liu, Yungen; Ma, Lena Q

2018-05-01

It is known that arsenic (As) promotes growth of As-hyperaccumulator Pteris vittata (PV), however, the associated mechanisms are unclear. Here we examined As-induced nutrient uptake in P. vittata and their potential role to enhance plant growth in sterile agar by excluding microbial effects. As-hyperaccumulator P. multifida (PM) and non-hyperaccumulator P. ensiformis (PE) belonging to the Pteris genus were used as comparisons. The results showed that, after 40 d of growth, As induced biomass increase in hyperaccumulators PV and PM by 5.2-9.4 fold whereas it caused 63% decline in PE. The data suggested that As played a beneficial role in promoting hyperaccumulator growth. In addition, hyperaccumulators PV and PM accumulated 7.5-13, 1.4-3.6, and 1.8-4.4 fold more As, Fe, and P than the non-hyperaccumulator PE. In addition, nutrient contents such as K and Zn were also increased while Ca, Mg, and Mn decreased or unaffected under As treatment. This study demonstrated that As promoted growth in hyperaccumulators and enhanced Fe, P, K, and Zn uptake. Different plant growth responses to As among hyperaccumulators PV and PM and non-hyperaccumulator PE may help to better understand why hyperaccumulators grow better under As-stress. Published by Elsevier Ltd.

In vivo antidiabetic and antioxidant potential of Helichrysum plicatum ssp. plicatum capitulums in streptozotocin-induced-diabetic rats.

Science.gov (United States)

Aslan, Mustafa; Deliorman Orhan, Didem; Orhan, Nilüfer; Sezik, Ekrem; Yesilada, Erdem

2007-01-03

Helichrysum species (Asteraceae) are widely found in Anatolia. Decoction prepared from the capitulums of Helichrysum plicatum ssp. plicatum is used to alleviate the symptoms of diabetes mellitus in folk medicine. In the present study, the hypoglycaemic and antioxidant potential of Helichrysum plicatum ssp. plicatum was evaluated by using in vivo methods in normal and streptozotocin-induced-diabetic rats. After the oral administration of water and ethanolic extracts at doses of 500mg/kg body weight prepared from the capitulums of plant, blood glucose levels were monitored at specific intervals. Tolbutamide was used as a reference drug at a dose of 100mg/kg. The experimental data indicated that water and ethanol extracts of capitulums demonstrate significant antihyperglycaemic and antioxidant activity in streptozotocin-induced rats which confirmed the folkloric utilization. In order to assess the role of polyphenolic components in the relevant activity, phenolic and flavonoid contents of each extract were also determined in terms of total phenols: 113.5+/-8.6mg (gallic acid equivalent/1g extract) and total flavanoids 50.5+/-1.9mg (quercetin equivalent/1g extract) for ethanol extract, total phenols: 75.9+/-3.7, flavonoids: 31.5+/-2.3 for water extract using Folin-Ciocalteu reagent.

Potential immunotoxic effects of trichloroethylene-induced IV allergic reaction in renal impairment

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Jun-Feng Yu

2017-08-01

Full Text Available Trichloroethylene (TCE is known to induce allergic contact dermatitis and subsequent occupational medicamentosa-like dermatitis (OMLD with multi-system injuries, including liver, kidney, and skin injuries. However, the mechanisms underlying immune system dysfunction that result in organ injury have not yet been clearly elucidated. In the present study, we measured the levels of secreted cytokines by effect or T cells in TCE-treated guinea pigs to better understand the contribution of allergic disorders in renal injuries. We immunized guinea pigs with trichloroethylene using the Guinea Pig Maximization Test (GPMT and scored the inflammation on the guinea pigs’ skin. The kidney function and ultra-structural changes in the kidneys were detected using biochemical methods and electron microscopy. The deposition of cytokines was determined using immunohistochemistry. The sensitization rate was 63.16% in the TCE-sensitized groups. The electron microscopy results showed tubular epithelial cell mitochondrial swelling, vacuolar degeneration, and atrophy of the microvillus in the sensitized groups. A high degree of cytokine deposition was observed in the renal tubular proximal epithelial cells in the TCE-sensitized groups. As observed in this study, the variation in the level of immune system activation not only indicates that TCE can largely magnify the immune reaction but also suggests a potential role of immune dysfunction in renal impairment.

Stress potentiates decision biases: A stress induced deliberation-to-intuition (SIDI model

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Rongjun Yu

2016-06-01

Full Text Available Humans often make decisions in stressful situations, for example when the stakes are high and the potential consequences severe, or when the clock is ticking and the task demand is overwhelming. In response, a whole train of biological responses to stress has evolved to allow organisms to make a fight-or-flight response. When under stress, fast and effortless heuristics may dominate over slow and demanding deliberation in making decisions under uncertainty. Here, I review evidence from behavioral studies and neuroimaging research on decision making under stress and propose that stress elicits a switch from an analytic reasoning system to intuitive processes, and predict that this switch is associated with diminished activity in the prefrontal executive control regions and exaggerated activity in subcortical reactive emotion brain areas. Previous studies have shown that when stressed, individuals tend to make more habitual responses than goal-directed choices, be less likely to adjust their initial judgment, and rely more on gut feelings in social situations. It is possible that stress influences the arbitration between the emotion responses in subcortical regions and deliberative processes in the prefrontal cortex, so that final decisions are based on unexamined innate responses. Future research may further test this ‘stress induced deliberation-to-intuition’ (SIDI model and examine its underlying neural mechanisms.

Anti-Cataract Potential of Heliotropium indicum Linn on Galactose-Induced Cataract in Sprague-Dawley Rats.

Science.gov (United States)

Kyei, Samuel; Koffuor, George A; Ramkissoon, Paul; Abu, Emmanuel K; Sarpong, Josephine F

2017-03-01

To evaluate the anti-cataract potential of an aqueous whole plant extract of Heliotropium indicum (HIE) on galactose-induced cataract in Sprague-Dawley rats. Cataract scores were recorded in 3-week-old Sprague-Dawley rats in which cataract was being induced by an oral administration of 1500 mgkg -1 galactose twice daily for 4 weeks, and concurrently being treated with 30, 100, or 300 mgkg -1 HIE daily over the induction period. Fasting blood glucose was monitored at weekly intervals. Changes in body weight as well as total lens protein, lens glutathione, and superoxide dismutase (SOD) were determined initially, and at the end of the experimental period. Crystalline lens weight-to-body-weight ratio was also determined for the various treatment groups at the end of the experimental period. Preliminary phytochemical screening, total antioxidant capacity, and reducing power assays were conducted on HIE. The 30 and 100 mgkg -1 HIE-treated rats recorded significantly lower (p ≤ 0.05-0.001) cataract scores (indicating very significant delays in cataractogenesis by the 3 rd and 4 th weeks of treatment) and blood glucose levels. Rats with delayed cataractogenesis also exhibited significant (p ≤ 0.05-0.001) weight gain, and reduction in lens weight. Total lens proteins glutathione and SOD levels in the crystalline lens were also significantly preserved (p ≤ 0.01-0.001). HIE showed substantial antioxidant capacity and reducing power. The aqueous whole plant extract of Heliotropium indicum delays cataractogenesis at an optimum dose of 30 mgkg -1 in Sprague-Dawley rats.

A Network-Based Pharmacology Study of the Herb-Induced Liver Injury Potential of Traditional Hepatoprotective Chinese Herbal Medicines.

Science.gov (United States)

Hong, Ming; Li, Sha; Tan, Hor Yue; Cheung, Fan; Wang, Ning; Huang, Jihan; Feng, Yibin

2017-04-14

Herbal medicines are widely used for treating liver diseases and generally regarded as safe due to their extensive use in Traditional Chinese Medicine practice for thousands of years. However, in recent years, there have been increased concerns regarding the long-term risk of Herb-Induced Liver Injury (HILI) in patients with liver dysfunction. Herein, two representative Chinese herbal medicines: one-Xiao-Chai-Hu-Tang (XCHT)-a composite formula, and the other- Radix Polygoni Multiflori (Heshouwu) -a single herb, were analyzed by network pharmacology study. Based on the network pharmacology framework, we exploited the potential HILI effects of XCHT and Heshouwu by predicting the molecular mechanisms of HILI and identified the potential hepatotoxic ingredients in XCHT and Heshouwu . According to our network results, kaempferol and thymol in XCHT and rhein in Heshouwu exhibit the largest number of liver injury target connections, whereby CASP3, PPARG and MCL1 may be potential liver injury targets for these herbal medicines. This network pharmacology assay might serve as a useful tool to explore the underlying molecular mechanism of HILI. Based on the theoretical predictions, further experimental verification should be performed to validate the accuracy of the predicted interactions between herbal ingredients and protein targets in the future.

Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor.

Directory of Open Access Journals (Sweden)

Suguru Fukushima

Full Text Available Malignant peripheral nerve sheath tumor (MPNST is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1 plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1α in MPNSTs is unclear.The expression of HIF-1α was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1α-specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1α.The nuclear expression of HIF-1α was positive in 75.6% of MPNST samples (62/82 cases. Positivity for HIF-1α was a significant poor prognostic factor both in univariate (P = 0.048 and multivariate (P ≤ 0.0001 analyses. HIF-1α knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1α, effectively inhibited the growth of MPNST cells and induced their apoptosis.Inhibition of HIF-1α signaling is a potential treatment option for MPNSTs.

Potential Lipid-Lowering Effects of Eleusine indica (L) Gaertn. Extract on High-Fat-Diet-Induced Hyperlipidemic Rats.

Science.gov (United States)

Ong, Siew Ling; Nalamolu, Koteswara Rao; Lai, How Yee

2017-01-01

To date, anti-obesity agents based on natural products are tested for their potential using lipase inhibition assay through the interference of hydrolysis of fat by lipase resulting in reduced fat absorption without altering the central mechanisms. Previous screening study had indicated strong anti-obesity potential in Eleusine indica ( E. indica ), but to date, no pharmacologic studies have been reported so far. This study was performed to investigate the lipid-lowering effects of E. indica using both in vitro and in vivo models. The crude methanolic extract of E. indica was fractionated using hexane (H-Ei), dichloromethane (DCM-Ei), ethyl acetate (EA-Ei), butanol (B-Ei), and water (W-Ei). All the extracts were tested for antilipase activity using porcine pancreatic lipase. Because H-Ei showed the highest inhibition, it was further subjected to chemical profiling using high-performance liquid chromatography. Subsequently, oral toxicity analysis of H-Ei was performed [Organization for Economic Cooperation and Development guidelines using fixed dose procedure (No. 420)]; efficacy analysis was performed using high-fat diet (HFD)-induced hyperlipidemic female Sprague-Dawley rats. According to the toxicity and efficacy analyses, H-Ei did not demonstrate any noticeable biochemical toxicity or physiologic abnormalities and did not cause any tissue damage as per histologic analysis. Furthermore, H-Ei significantly reduced body weight and improved serum profile and did not show hepatotoxicity and nephrotoxicity based on the serum profile. Moreover, H-Ei alleviated HFD-induced hepatosteatosis and ameliorated induced adiposity in both visceral and subcutaneous adipose tissue. Our results demonstrate that H-Ei effectively improved hyperlipidemia. Further studies to explore its possibility as an alternative pharmacologic agent to treat obesity are warranted. Hexane extract of Eleusine indica (H-Ei) showed strong potential in the inhibition of porcine pancreatic lipase (27.01 �

Coastal Morphology and Coastal Protection

NARCIS (Netherlands)

Van de Graaff, J.

2009-01-01

Lecture notes ct5309. Tides, currents and water; coastal problems; sediment transport processes; coastal transport modes; longshore transport; cross-shore transport; fundamentals of mud; channels and trenches; coastal protection; application of structures; application of nourishments.

Gel-free proteomics reveal potential biomarkers of priming-induced salt tolerance in durum wheat.

Science.gov (United States)

Fercha, Azzedine; Capriotti, Anna Laura; Caruso, Giuseppe; Cavaliere, Chiara; Gherroucha, Hocine; Samperi, Roberto; Stampachiacchiere, Serena; Lagana, Aldo

2013-10-08

Seed priming has been successfully demonstrated to be an efficient method to improve crop productivity under stressful conditions. As a first step toward better understanding of the mechanisms underlying the priming-induced salt stress tolerance in durum wheat, and to overcome the limitations of the gel-based approach, a comparative gel-free proteomic analysis was conducted with durum wheat seed samples of varying vigor as generated by hydro- and ascorbate-priming treatments. Results indicate that hydro-priming was accompanied by significant changes of 72 proteins, most of which are involved in proteolysis, protein synthesis, metabolism and disease/defense response. Ascorbate-priming was, however, accompanied by significant changes of 83 proteins, which are mainly involved in protein metabolism, antioxidant protection, repair processes and, interestingly, in methionine-related metabolism. The present study provides new information for understanding how 'priming-memory' invokes seed stress tolerance. The current work describes the first study in which gel-free shotgun proteomics were used to investigate the metabolic seed protein fraction in durum wheat. A combined approach of protein fractionation, hydrogel nanoparticle enrichment technique, and gel-free shotgun proteomic analysis allowed us to identify over 380 proteins exhibiting greater molecular weight diversity (ranging from 7 to 258kDa). Accordingly, we propose that this approach could be useful to acquire a wider perspective and a better understanding of the seed proteome. In the present work, we employed this method to investigate the potential biomarkers of priming-induced salt tolerance in durum wheat. In this way, we identified several previously unrecognized proteins which were never been reported before, particularly for the ascorbate-priming treatment. These findings could provide new avenues for improving crop productivity, particularly under unfavorable environmental conditions. © 2013.

Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-alpha in monocyte-derived macrophages.

Science.gov (United States)

Kim, Sung-Jo

2010-06-01

In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production in differentiated THP-1 cells, a human monocytic cell line. LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-alpha and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Leptin enhanced P. intermedia LPS-induced TNF-alpha production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-alpha expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-alpha production was not mediated by the leptin receptor. The ability of leptin to enhance P. intermedia LPS-induced TNF-alpha production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

High-fat diet-induced insulin resistance does not increase plasma anandamide levels or potentiate anandamide insulinotropic effect in isolated canine islets.

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Orison O Woolcott

Full Text Available Obesity has been associated with elevated plasma anandamide levels. In addition, anandamide has been shown to stimulate insulin secretion in vitro, suggesting that anandamide might be linked to hyperinsulinemia.To determine whether high-fat diet-induced insulin resistance increases anandamide levels and potentiates the insulinotropic effect of anandamide in isolated pancreatic islets.Dogs were fed a high-fat diet (n = 9 for 22 weeks. Abdominal fat depot was quantified by MRI. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp. Fasting plasma endocannabinoid levels were analyzed by liquid chromatography-mass spectrometry. All metabolic assessments were performed before and after fat diet regimen. At the end of the study, pancreatic islets were isolated prior to euthanasia to test the in vitro effect of anandamide on islet hormones. mRNA expression of cannabinoid receptors was determined in intact islets. The findings in vitro were compared with those from animals fed a control diet (n = 7.Prolonged fat feeding increased abdominal fat content by 81.3±21.6% (mean±S.E.M, P<0.01. In vivo insulin sensitivity decreased by 31.3±12.1% (P<0.05, concomitant with a decrease in plasma 2-arachidonoyl glycerol (from 39.1±5.2 to 15.7±2.0 nmol/L but not anandamide, oleoyl ethanolamide, linoleoyl ethanolamide, or palmitoyl ethanolamide. In control-diet animals (body weight: 28.8±1.0 kg, islets incubated with anandamide had a higher basal and glucose-stimulated insulin secretion as compared with no treatment. Islets from fat-fed animals (34.5±1.3 kg; P<0.05 versus control did not exhibit further potentiation of anandamide-induced insulin secretion as compared with control-diet animals. Glucagon but not somatostatin secretion in vitro was also increased in response to anandamide, but there was no difference between groups (P = 0.705. No differences in gene expression of CB1R or CB2R between groups were found.In canines, high-fat diet-induced

Orofacial neuropathic pain induced by oxaliplatin: downregulation of KCNQ2 channels in V2 trigeminal ganglion neurons and treatment by the KCNQ2 channel potentiator retigabine.

Science.gov (United States)

Ling, Jennifer; Erol, Ferhat; Viatchenko-Karpinski, Viacheslav; Kanda, Hirosato; Gu, Jianguo G

2017-01-01

Neuropathic pain induced by chemotherapy drugs such as oxaliplatin is a dose-limiting side effect in cancer treatment. The mechanisms underlying chemotherapy-induced neuropathic pain are not fully understood. KCNQ2 channels are low-threshold voltage-gated K+ channels that play a role in controlling neuronal excitability. Downregulation of KCNQ2 channels has been proposed to be an underlying mechanism of sensory hypersensitivity that leads to neuropathic pain. However, it is currently unknown whether KCNQ channels may be downregulated by chemotherapy drugs in trigeminal ganglion neurons to contribute to the pathogenesis of chemotherapy-induced orofacial neuropathic pain. In the present study, mechanical sensitivity in orofacial regions is measured using the operant behavioral test in rats treated with oxaliplatin. Operant behaviors in these animals show the gradual development of orofacial neuropathic pain that manifests with orofacial mechanical allodynia. Immunostaining shows strong KCNQ2 immunoreactivity in small-sized V2 trigeminal ganglion neurons in controls, and the numbers of KCNQ2 immunoreactivity positive V2 trigeminal ganglion neurons are significantly reduced in oxaliplatin-treated animals. Immunostaining is also performed in brainstem and shows strong KCNQ2 immunoreactivity at the trigeminal afferent central terminals innervating the caudal spinal trigeminal nucleus (Vc) in controls, but the KCNQ2 immunoreactivity intensity is significantly reduced in oxaliplatin-treated animals. We further show with the operant behavioral test that oxaliplatin-induced orofacial mechanical allodynia can be alleviated by the KCNQ2 potentiator retigabine. Taken together, these findings suggest that KCNQ2 downregulation may be a cause of oxaliplatin-induced orofacial neuropathic pain and KCNQ2 potentiators may be useful for alleviating the neuropathic pain.

Assessing the potential of spectral induced polarization to detect in situ changes in iron reduction

Science.gov (United States)

Rosier, C. L.; Price, A.; Sharma, S.; Atekwana, E. A.

2016-12-01

The near surface geophysical technique Spectral Induced Polarization (SIP), provides promise as an effective method measuring in situ biofilm formation/development. Yet, potential mechanisms responsible for observed shifts in SIP response due to biofilm are not clearly understood. In order to address possible mechanisms we assessed the influence of Shewanella oneidensis (MR1) cell density (colony forming units; CFU), biofilm production (Bradford assay) and iron reduction metabolism (colorimetric assay) on SIP response. Laboratory measurements were collected over three months on columns packed with either iron-coated or iron-free sands and amended with artificial ground water and acetate in order to stimulate biofilm production and microbial iron reduction. Additionally, scanning electron microscopy (SEM) was used to confirm the presence of S. oneidensis cells and biofilm. Our results suggest that during early/initial stage (75 days) of column incubation, SIP measurements revealed that phase and imaginary conductivity responses decreased as the concentration of reduced iron decreased below 2.0 mM. In contrast, we observed only a moderate increase in phase and imaginary conductivity ( 30%) within iron-free columns as a result of increases in S. oneidensis cells (CFU 1.5 x 1011) and biofilm production (7.0 mg ml-1). SEM analysis confirmed the presence of biofilm and cells within both iron-coated and iron-free columns. We hypothesize that the production of microbial metabolic byproducts is a potential mechanism explaining large phase shits observed in previous studies ( 50 mrads) rather than the conductivity of cells or biofilm. Our findings provide support for the following: i) ratio of cells to biofilm production only moderately influences both phase and imaginary conductivity response and ii) largest phase and imaginary conductivity response resulted from microbial metabolism (i.e. iron reduction) and potentially biofilm trapping of conductive materials (i

Valproic acid potentiates curcumin-mediated neuroprotection in Lipopolysaccharide induced rats

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Amira eZaky

2014-10-01

Full Text Available The etiology of neuroinflammation is complex and comprises multifactorial, involving both genetic and environmental factors during which diverse genetic and epigenetic modulations are implicated. Curcumin (Cur, and valproic acid (VPA, histone deacetylase 1 inhibitor, have neuroprotective effects. The present study was designed with an aim to investigate the ability of co-treatment of both compounds (Cur or VPA (200mg/kg for four weeks to augment neuroprotection and enhance brain recovery from intra-peritoneal (IP injection of (250 µg/kg lipopolysaccharide (LPS-stimulated neuroinflammatory condition on rat brain cortex. Cortex activation and the effects of combined treatment and production of proinflammatory mediators, COX-2, APE1 and nitric oxide/iNOS were investigated. Neuroinflammation development was assessed by histological analyses and by investigating associated indices (BACE1, APP, PSEN-1 and PSEN-2. Furthermore we measured the expression profile of let-7 miRNAs members a, b, c, e and f in all groups, a highly abundant regulator of gene expression in the CNS. Protein and mRNA levels of neuroinflammation markers COX-2, BACE1, APP and iNOS were also attenuated by combined therapy. On the other hand, assessment of the indicated five let-7 members, showed distinct expression profile pattern in the different groups. Let-7 a, b and c disappeared in the induced group, an effect that was partially suppressed by co-addition of either Cur or VPA. These data suggest that the combined treatment induced significantly the expression of the five members when compared to rats treated with Cur or VPA only as well as to self-recovery group, which indicates a possible benefit from the synergistic effect of Cur-VPA combination as therapeutic agents for neuroinflammation and its associated disorders. The mechanism elucidated here highlights the particular drug-induced expression profile of let-7 family as new targets for future pharmacological development.

Neural network-genetic programming for sediment transport

Digital Repository Service at National Institute of Oceanography (India)

Singh, A.K.; Deo, M.C.; SanilKumar, V.

The planning, operation, design and maintenance of almost all harbour and coastal engineering facilities call for an estimation of the longshore sediment transport rate. This is currently and popularly done with the help of empirical equations...

Daily beach profiles and littoral environmental observations off Baga, Calangute and Miramar beaches during November-December 1999

Digital Repository Service at National Institute of Oceanography (India)

Jayakumar, S.; Raju, N.S.N.; Gowthaman, R.; AshokKumar, K.; Anand, N.M.

16th November-15th December 1999, are as follows: (1) daily beach profiles, (2) daily littoral environmental observations and (3) beach sediment samples for grain size distribution. Longshore sediment transport rate is estimated theoretically based...

Capecitabine induced hypertriglyceridaemia: An underreported and potentially severe side effect

OpenAIRE

Tabchi S; Joseph K

2014-01-01

A 57 year-old-woman, with no previous history of dyslipedemia, developed severe hypertriglyceridemia while being treated with capecitabine for metastatic breast cancer. Capecitabine was not discontinued and serum triglyceride levels were normalized after 4 weeks of treatment with fenofibrate. Capecitabine induced hypertriglyceridemia, as a rare drug-related side effect, seems to be often overlooked by clinicians.

Nearshore waves and longshore sediment transport along Rameshwaram Island off the east coast of India

Digital Repository Service at National Institute of Oceanography (India)

Gowthaman, R.; SanilKumar, V.; Dwarakish, G.S.; Shanas, P.R.; Jena, B.K.; Singh, J.

changing. The accurate demarcation and monitoring of a shoreline are necessary for understanding coastal processes (Natesan, 2008). Remote sensing technology is commonly used to map the shoreline and offers the potential of updating maps frequently (Frihy... influence is less at 2 m water depth may be due to the frictional dissipation and breaking. Fig. 5 indicates that the numerical model will not give good results during tropical storm/depression. During the study period, the breaking wave height varied...

The oxidative potential and biological effects induced by PM{sub 10} obtained in Mexico City and at a receptor site during the MILAGRO Campaign

Energy Technology Data Exchange (ETDEWEB)

Quintana, Raul [Instituto Nacional de Cancerologia, Mexico City (Mexico); Serrano, Jesus [Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Mexico City (Mexico); Gomez, Virginia [Instituto de Quimica, Universidad Nacional Autonoma de Mexico, Mexico City (Mexico); Foy, Benjamin de [Earth and Atmospheric Sciences, Saint Louis University, St. Louis, MO (United States); Miranda, Javier [Instituto de Fisica, Universidad Nacional Autonoma de Mexico, Mexico City (Mexico); Garcia-Cuellar, Claudia [Instituto Nacional de Cancerologia, Mexico City (Mexico); Vega, Elizabeth [Instituto Mexicano del Petroleo, Mexico City (Mexico); Vazquez-Lopez, Ines [Instituto Nacional de Cancerologia, Mexico City (Mexico); Molina, Luisa T. [Molina Center for Energy and the Environment, CA (United States); Massachusetts Institute of Technology, Cambridge, MA (United States); Manzano-Leon, Natalia [Instituto Nacional de Cancerologia, Mexico City (Mexico); Rosas, Irma [Centro de Ciencias de la Atmosfera, Universidad Nacional Autonoma de Mexico, Mexico City (Mexico); Osornio-Vargas, Alvaro R., E-mail: osornio@ualberta.ca [Instituto Nacional de Cancerologia, Mexico City (Mexico); Department of Paediatrics, University of Alberta, 1048 RTF, 8308 114 St, Edmonton, AB T6G 2V2 (Canada)

2011-12-15

As part of a field campaign that studied the impact of Mexico City pollution plume at the local, sub-regional and regional levels, we studied transport-related changes in PM{sub 10} composition, oxidative potential and in vitro toxicological patterns (hemolysis, DNA degradation). We collected PM{sub 10} in Mexico City (T{sub 0}) and at a suburban-receptor site (T{sub 1}), pooled according to two observed ventilation patterns (T{sub 0} {yields} T{sub 1} influence and non-influence). T{sub 0} samples contained more Cu, Zn, and carbon whereas; T{sub 1} samples contained more of Al, Si, P, S, and K (p < 0.05). Only SO{sub 4}{sup -2} increased in T{sub 1} during the influence periods. Oxidative potential correlated with Cu/Zn content (r = 0.74; p < 0.05) but not with biological effects. T{sub 1} PM{sub 10} induced greater hemolysis and T{sub 0} PM{sub 10} induced greater DNA degradation. Influence/non-influence did not affect oxidative potential nor biological effects. Results indicate that ventilation patterns had little effect on intrinsic PM{sub 10} composition and toxicological potential, which suggests a significant involvement of local sources. - Highlights: > Transport-related changes in PM{sub 10} composition, oxidative potential and in vitro toxicity were studied. > Cu, Zn, and carbon levels were predominant in urban PM{sub 10}; receptor site PM{sub 10} was rich in soil elements. > SO{sub 4}{sup -2} was the only component increased in PM{sub 10} from the receptor during the influence periods. > PM{sub 10} oxidative potential correlates with Cu/Zn content but not with studied biological effects. > Ventilation patterns had little effect on PM{sub 10} composition and toxicity. - Mexico City ventilation patterns had little effect on the intrinsic PM{sub 10} composition and toxicological potential, which suggests a significant involvement of local sources as opposed to downwind transport.

Time-response characteristic and potential biomarker identification of heavy metal induced toxicity in zebrafish.

Science.gov (United States)

Yin, Jian; Wang, Ai-Ping; Li, Wan-Fang; Shi, Rui; Jin, Hong-Tao; Wei, Jin-Feng

2018-01-01

The present work aims to explore the time-response (from 24 h to 96 h) characteristic and identify early potential sensitive biomarkers of copper (Cu) (as copper chloride dihydrate), cadmium (Cd) (as cadmium acetate), lead (Pb) (as lead nitrate) and chromium (Cr) (as potassium dichromate) exposure in adult zebrafish, focusing on reactive oxygen species (ROS), SOD activity, lipid peroxidation and gene expression related to oxidative stress and inflammatory response. Furthermore, the survival rate decreased apparently by a concentration-dependent manner after Cu, Cr, Cd and Pb exposure, and we selected non-lethal concentrations 0.05 mg/L for Cu, 15 mg/L for Cr, 3 mg/L for Cd and 93.75μg/L for Pb to test the effect on the following biological indicators. Under non-lethal concentration, the four heavy metals have no apparent histological change in adult zebrafish gills. Similar trends in ROS production, MDA level and SOD activity were up-regulated by the four heavy metals, while MDA level responded more sensitive to Pb by time-dependent manner than the other three heavy metals. In addition, mRNA levels related to antioxidant system (SOD1, SOD2 and Nrf2) were up-regulated by non-lethal concentration Cu, Cr, Cd and Pb exposure. MDA level and SOD1 gene have a more delayed response to heavy metals. Genes related to immunotoxicity were increased significantly after heavy metals exposure at non-lethal concentrations. TNF-α and IL-1β gene have similar sensibility to the four heavy metals, while IL-8 gene was more responsive to Cr, Cd and Pb exposure at 48 h groups and IFN-γ gene showed more sensitivity to Cu at 48 h groups than the other heavy metals. In conclusion, the present works have suggested that the IFN-γ gene may applied as early sensitive biomarker to identify Cu-induced toxicity, while MDA content and IL-8 gene may use as early sensitive biomarkers for evaluating the risk of Pb exposure. Moreover, IL-8 and IFN-γ gene were more responsive to heavy

Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration

Directory of Open Access Journals (Sweden)

Daniel J. Liput

2017-11-01

Full Text Available Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs. The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs, and then evaluated the efficacy of fatty acid amide hydrolase (FAAH inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in [3H]-CP-55,940 binding in the entorhinal cortex and hippocampus following two days, but not four days, of treatment. Furthermore, binge alcohol treatment did not change the tissue content of the three NAEs quantified, including the endocannabinoid and anandamide. In a separate study, the FAAH inhibitor, URB597 was administered to rats during alcohol treatment and neuroprotection was assessed by FluoroJade B (FJB staining. The administration of URB597 during binge treatment did not significantly reduce FJB+ cells in the entorhinal cortex or hippocampus, however, a follow up “target engagement” study found that NAE augmentation by URB597 was impaired in alcohol intoxicated rats. Thus, potential alcohol induced alterations in URB597 pharmacodynamics may have contributed to the lack of neuroprotection by FAAH inhibition.

Circulation, mixing, and transport in nearshore Lake Erie in the vicinity of Villa Angela Beach and Euclid Creek, Cleveland, Ohio, September 11-12, 2012

Science.gov (United States)

Jackson, P. Ryan

2013-01-01

Villa Angela Beach, on the Lake Erie lakeshore near Cleveland, Ohio, is adjacent to the mouth of Euclid Creek, a small, flashy stream draining approximately 23 square miles and susceptible to periodic contamination from combined sewer overflows (CSOs) (97 and 163 CSO events in 2010 and 2011, respectively). Concerns over high concentrations of Escherichia coli (E. coli) in water samples taken along this beach and frequent beach closures led to the collection of synoptic data in the nearshore area in an attempt to gain insights into mixing processes, circulation, and the potential for transport of bacteria and other CSO-related pollutants from various sources in Euclid Creek and along the lakefront. An integrated synoptic survey was completed by the U.S. Geological Survey on September 11–12, 2012, during low-flow conditions on Euclid Creek, which followed rain-induced high flows in the creek on September 8–9, 2012. Data-collection methods included deployment of an autonomous underwater vehicle and use of a manned boat equipped with an acoustic Doppler current profiler. Spatial distributions of water-quality measures and nearshore currents indicated that the mixing zone encompassing the mouth of Euclid Creek and Villa Angela Beach is dynamic and highly variable in extent, but can exhibit a large zone of recirculation that can, at times, be decoupled from local wind forcing. Observed circulation patterns during September 2012 indicated that pollutants from CSOs in Euclid Creek and water discharged from three shoreline CSO points within 2,000 feet of the beach could be trapped along Villa Angela Beach by interaction of nearshore currents and shoreline structures. In spite of observed coastal downwelling, denser water from Euclid Creek is shown to mix to the surface via offshore turbulent structures that span the full depth of flow. While the southwesterly longshore currents driving the recirculation pattern along the beach front were observed during the 2011–12

An in vitro model to test relative antioxidant potential: Ultraviolet-induced lipid peroxidation in liposomes

International Nuclear Information System (INIS)

Pelle, E.; Maes, D.; Padulo, G.A.; Kim, E.K.; Smith, W.P.

1990-01-01

Since antioxidants have been shown to play a major role in preventing some of the effects of aging and photoaging in skin, it is important to study this phenomenon in a controlled manner. This was accomplished by developing a simple and reliable in vitro technique to assay antioxidant efficacy. Inhibition of peroxidation by antioxidants was used as a measure of relative antioxidant potential. Liposomes, high in polyunsaturated fatty acids (PUFA), were dispersed in buffer and irradiated with ultraviolet (UV) light. Irradiated liposomes exhibited a significantly higher amount of hydroperoxides than liposomes containing antioxidants in a dose- and concentration-dependent manner. Lipid peroxidation was determined spectrophotometrically by an increase in thiobarbituric acid reacting substances. To further substantiate the production of lipid peroxides, gas chromatography was used to measure a decrease in PUFA substrate. In order of decreasing antioxidant effectiveness, the following results were found among lipophilic antioxidants: BHA greater than catechin greater than BHT greater than alpha-tocopherol greater than chlorogenic acid. Among hydrophilic antioxidants, ascorbic acid and dithiothreitol were effective while glutathione was ineffective. In addition, ascorbic acid was observed to act synergistically with alpha-tocopherol, which is in agreement with other published reports on the interaction of these two antioxidants. Although peroxyl radical scavengers seem to be at a selective advantage in this liposomal/UV system, these results demonstrate the validity of this technique as an assay for measuring an antioxidant's potential to inhibit UV-induced peroxidation

Effect of Pre-Gamma Irradiation Induction of Metallothionein on potentially Radiation-Induced Toxic Heavy Metals Ions In Rats

International Nuclear Information System (INIS)

El-Shamy, El.

2004-01-01

Metallothionein, which is a cystein-rich metal binding protein, can act as free radical scavenger and involved in resistance to heavy metal toxicity. The induction of synthesis has been shown to protect organs from the toxic effect of radiation. This study aimed to stud the effects of pre-irradiation induction of by heavy metal (Zinc sulfate) on potentially gamma radiation-induced toxic heavy metals ions in rate liver and kidney tissues. Forty eight albino rats were included in this study. They were divided into eight groups each of six animals. Two control groups injected with saline. Two Zinc sulfate-treated groups injected with zinc sulfate, two Irradiated groups exposed to a single dose level (7 Gy) of whole body gamma irradiation and two combined zinc sulfate and irradiation groups injected with zinc sulfate and exposed to whole body gamma irradiation (at dose 7 Gy). Animals of all groups were sacrificed 24 and 48 hours after last either zinc sulfate dose or irradiation. Samples of liver and kidney's tissues were subjected to the following investigations: Estimation of tissue heavy Metals (Zinc, Iron and Copper), and tissue (MT). After irradiation, liver and kidney MT were increased approximately 10-fold and 2-fold respectively after irradiation. Accumulation of zinc and iron in both liver and kidney tissues were detected, while accumulation of copper only in the liver tissues. The pre-irradiation treatment with zinc sulfate (Zn SO4) resulted in highly significant decrease in zinc, iron, and copper levels in both liver and kidney tissues in comparison with irradiation groups. Conclusion, it can be supposed that pre-irradiation injection of ZnSO 4 exerted protective effect against the potentially radiation-induced toxic heavy metals ions through MT induction

Troglitazone induced apoptosis via PPARγ activated POX-induced ROS formation in HT29 cells.

Science.gov (United States)

Wang, Jing; Lv, XiaoWen; Shi, JiePing; Hu, XiaoSong; DU, YuGuo

2011-08-01

In order to investigate the potential mechanisms in troglitazone-induced apoptosis in HT29 cells, the effects of PPARγ and POX-induced ROS were explored. [3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, Annexin V and PI staining using FACS, plasmid transfection, ROS formation detected by DCFH staining, RNA interference, RT-PCR & RT-QPCR, and Western blotting analyses were employed to investigate the apoptotic effect of troglitazone and the potential role of PPARγ pathway and POX-induced ROS formation in HT29 cells. Troglitazone was found to inhibit the growth of HT29 cells by induction of apoptosis. During this process, mitochondria related pathways including ROS formation, POX expression and cytochrome c release increased, which were inhibited by pretreatment with GW9662, a specific antagonist of PPARγ. These results illustrated that POX upregulation and ROS formation in apoptosis induced by troglitazone was modulated in PPARγ-dependent pattern. Furthermore, the inhibition of ROS and apoptosis after POX siRNA used in troglitazone-treated HT29 cells indicated that POX be essential in the ROS formation and PPARγ-dependent apoptosis induced by troglitazone. The findings from this study showed that troglitazone-induced apoptosis was mediated by POX-induced ROS formation, at least partly, via PPARγ activation. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Modulation of ceramide metabolism in T-leukemia cell lines potentiates apoptosis induced by the cationic antimicrobial peptide bovine lactoferricin.

Science.gov (United States)

Furlong, Suzanne J; Ridgway, Neale D; Hoskin, David W

2008-03-01

Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that selectively induces apoptosis in several different types of human cancer cells. However, the potential use of LfcinB as an anticancer agent is presently limited by the need for relatively high concentrations of the peptide to trigger apoptosis. Ceramide is a membrane sphingolipid that is believed to function as a second messenger during apoptosis. In this study, we investigated the role of ceramide in LfcinB-induced apoptosis in CCRF-CEM and Jurkat T-leukemia cell lines. Exposure to LfcinB caused nuclear condensation and fragmentation, poly(ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation in CCRF-CEM and Jurkat T-cell acute lymphoblastic leukemia cell lines. Treatment with C6 ceramide, a cell-permeable, short-chain ceramide analog, also induced apoptotic nuclear morphology, PARP cleavage, and DNA fragmentation in T-leukemia cells. Although LfcinB treatment did not cause ceramide to accumulate in CCRF-CEM or Jurkat cells, the addition of C6 ceramide to LfcinB-treated T-leukemia cells resulted in increased DNA fragmentation. Furthermore, modulation of cellular ceramide metabolism either by inhibiting ceramidases with D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol or N-oleoylethanolamine, or by blocking glucosylceramide synthase activity with 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, enhanced the ability of LfcinB to trigger apoptosis in both Jurkat and CCRF-CEM cells. In addition, LfcinB-induced apoptosis of T-leukemia cells was enhanced in the presence of the antiestrogen tamoxifen, which has multiple effects on cancer cells, including inhibition of glucosylceramide synthase activity. We conclude that manipulation of cellular ceramide levels in combination with LfcinB therapy warrants further investigation as a novel strategy for the treatment of T cell-derived leukemias.

Nearshore processes along north Karnataka coast

Digital Repository Service at National Institute of Oceanography (India)

SanilKumar, V.; Raju, N.S.N.; Pathak, K.C.; Anand, N.M.

Ten base stations were established along the shoreline between Karwar and Bhatkal and monthly beach profiles, breaking wave characteristics and longshore currents were measured for a period of one year. The lowest beach levels were observed during...

Hypocholesterolemic and Antiatherosclerotic Potential of Basella alba Leaf Extract in Hypercholesterolemia-Induced Rabbits

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Gunasekaran Baskaran

2015-01-01

Full Text Available Hypercholesterolemia is the major risk factor that leads to atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and antiatherosclerotic effects of Basella alba (B. alba using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD, 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and triglycerides and increased HDL and antioxidant enzymes (SOD and GPx levels. The elevated levels of liver enzymes (AST and ALT and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.

Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

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Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

2017-09-01

Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

Apoptosis of leukemia K562 and Molt-4 cells induced by emamectin benzoate involving mitochondrial membrane potential loss and intracellular Ca2+ modulation.

Science.gov (United States)

Yun, Xinming; Rao, Wenbing; Xiao, Ciying; Huang, Qingchun

2017-06-01

Leukemia threatens millions of people's health and lives, and the pesticide-induced leukemia has been increasingly concerned because of the etiologic exposure. In this paper, cytotoxic effect of emamectin benzoate (EMB), an excellent natural-product insecticide, was evaluated through monitoring cell viability, cell apoptosis, mitochondrial membrane potential and intracellular Ca 2+ concentration ([Ca 2+ ] i ) in leukemia K562 and Molt-4 cells. Following the exposure to EMB, cell viability was decreased and positive apoptosis of K562 and Molt-4 cells was increased in a concentration- and time- dependent fashion. In the treatment of 10μM EMB, apoptotic cells accounted for 93.0% to K562 cells and 98.9% to Molt-4 cells based on the control, meanwhile, 63.47% of K562 cells and 81.15% of Molt-4 cells exhibited late apoptotic and necrotic features with damaged cytoplasmic membrane. 48h exposure to 10μM EMB increased significantly the great number of cells with mitochondrial membrane potential (MMP) loss, and the elevation of [Ca 2+ ] i level was peaked and persisted within 70s in K562 cells whilst 50s in Molt-4 cells. Moreover, a stronger cytotoxicity of EMB was further observed than that of imatinib. The results authenticate the efficacious effect of EMB as a potential anti-leukemia agent and an inconsistency with regard to insecticide-induced leukemia. Copyright © 2017 Elsevier B.V. All rights reserved.

Capecitabine induced hypertriglyceridaemia: An underreported and potentially severe side effect

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Tabchi S

2014-05-01

Full Text Available A 57 year-old-woman, with no previous history of dyslipedemia, developed severe hypertriglyceridemia while being treated with capecitabine for metastatic breast cancer. Capecitabine was not discontinued and serum triglyceride levels were normalized after 4 weeks of treatment with fenofibrate. Capecitabine induced hypertriglyceridemia, as a rare drug-related side effect, seems to be often overlooked by clinicians.

Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles.

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Santos, Tiago; Ferreira, Raquel; Quartin, Emanuel; Boto, Carlos; Saraiva, Cláudia; Bragança, José; Peça, João; Rodrigues, Cecília; Ferreira, Lino; Bernardino, Liliana

2017-09-01

Neurogenic niches constitute a powerful endogenous source of new neurons that can be used for brain repair strategies. Neuronal differentiation of these cells can be regulated by molecules such as retinoic acid (RA) or by mild levels of reactive oxygen species (ROS) that are also known to upregulate RA receptor alpha (RARα) levels. Data showed that neural stem cells from the subventricular zone (SVZ) exposed to blue light (405nm laser) transiently induced NADPH oxidase-dependent ROS, resulting in β-catenin activation and neuronal differentiation, and increased RARα levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis both in vitro and in vivo, while offering a temporal and spatial control of RA release. In conclusion, this combinatory treatment offers great advantages to potentiate neuronal differentiation, and provides an innovative and efficient application for brain regenerative therapies. Controlling the differentiation of stem cells would support the development of promising brain regenerative therapies. Blue light transiently increased reactive oxygen species, resulting in neuronal differentiation and increased retinoic acid receptor (RARα) levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis, while offering a temporal and spatial control of RA release. In this sense, our approach relying on the modulation of endogenous stem cells for the generation of new neurons may support the development of novel clinical therapies. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cadmium-Induced Toxicity and the Hepatoprotective Potentials of Aqueous Extract of Jessiaea Nervosa Leaf

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Ama Udu Ibiam

2013-08-01

Full Text Available Purpose: Hepatoprotective potentials of Jussiaea nervosa leaf extract against Cadmium-induced hepatotoxicity were investigated. Methods: Forty albino rats were randomly assigned into groups A-G with 4 rats in each of the groups A-F. Group A served as control and were given feed only while rats in groups B-F were orally exposed to varying concentrations of cadmium for six weeks. Effects of cadmium were most significant at 12 mg/Kg body weight (BW, and this dose was used for subsequent test involving oral administration of Jussiaea nervosa leaf extracts. In this segment, group G (n= 16 was sub-divided into four: G1-G4, with each sub-group containing four rats. Rats in sub-group G1 were given cadmium and feed only and served as positive control. Rats in sub-groups G2, G3, and G4 were given cadmium and 20, 50 and 100g/kg BW of Jussiaea nervosa extract, respectively, for six weeks. Blood and liver were analysed using standard laboratory techniques and methods. Results: Liver function parameters (ALT, AST, ALP, bilirubin were significantly (p<0.05 elevated in exposed rats in comparison to the controls, except for total protein and albumin, which were significantly decreased. Histopathological assessment reveals renal pathology in exposed rats in sharp contrast with the controls. Jussiaea nervosa extract however lowered the values of liver function parameters with 100mg/Kg BW dose producing the highest ameliorative effects. Similarly, the serum albumin and total protein significantly (p<0.05 improved with normal liver architecture. Conclusion: The results show the hepatoprotective potentials of Jussiaea nervosa extract against Cd toxicity.

Human Umbilical Cord Blood Serum Has Higher Potential in Inducing Proliferation of Fibroblast than Fetal Bovine Serum

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Ferry Sandra

2017-09-01

Full Text Available Background: Cytokines and growth factors were reported to play an important role in stimulating fibroblast proliferation. In vitro culture, fibroblast is mostly culture in medium containing fetal bovine serum (FBS.  Human umbilical cord blood (hUCB has been reported to have low immunogenic property and potential in wound healing, so therefore hUCB serum (hUCBS could be potential and were investigated in current study. Materials and Methods: Five hUCBs were collected from healthy volunteers with normal delivering procedure. hUCB was ex utero immediately collected from umbilical vein in vacutainers and processed. NIH3T3 cells were cultured in DMEM with 10% FBS or 5-20% hUCBS for 48 hours. Cells were then quantified using MTT assay. Protein concentration of FBS and hUCBS were quantified using Bradford assay. Results: NIH3T3 cells density grown in DMEM with 10% FBS was the lowest. NIH3T3 cells densities were increased along with the increment of hUCBS concentrations. MTT results showed that average number of NIH3T3 cells grown in DMEM with 10% FBS was 6,185±1,243. Meanwhile average numbers of NIH3T3 cells grown in DMEM with 5%, 10% and 20% hUCBS were 8,126±628, 9,685±313 and 12,200±304, respectively. Average numbers of NIH3T3 cells grown in DMEM with 5% hUCBS were significantly higher than the ones with 10% FBS (p=0.000. Bradford results showed that concentration of hUCBS was significantly higher than the one of FBS (p=0.000. Conclusion: hUCBS could induce higher proliferation rate of NIH3T3 cells than FBS. Hence hUCBS could be suggested as an alternate of FBS in inducing fibroblast. Keywords: NIH3T3, fibroblast, UCB, serum, FBS, proliferation

The coastal current off western India during the northeast monsoon

Digital Repository Service at National Institute of Oceanography (India)

Shetye, S.R.; Gouveia, A.D.; Shenoi, S.S.C.; Michael, G.S.; Sundar, D.; Almeida, A.M.; Santanam, K.

, temperature and dynamic topography. To understand the driving mechanism of the current, the annual cycle of the contribution of the longshore pressure gradient and that of the winds to the near-surface momentum balance was examined using available...

FBSAD Reef Fish-Habitat Quadrat Surveys at Hawaii Island (Big Island), Main Hawaiian Islands, 2005 (NODC Accession 0046935)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Habitat quadrats were surveyed at 8-13 m depths using shore-based transects swum at 3 longshore sites on the leeward coast (North and South Kohala districts) of the...

Beach processes between Mulgund and Shiroda, west coast of India

Digital Repository Service at National Institute of Oceanography (India)

Chandramohan, P.; Nayak, B.U.; Sanilkumar, V.; Pathak, K.C.

Study on beach processes for an year shows seasonal changes without annual net erosion. The beaches are stable and regain the maximum profiles during February to April. Distribution of longshore current direction is not uniform along the study...

Fishery Biology and Stock Assessment Division (FBSAD) Recruit Reef Fish Belt Transect and Habitat Quadrat Surveys at Hawaii Island (Big Island), Main Hawaiian Islands, 2005 (NODC Accession 0046935)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt transects were conducted at 8-13 m depths at 3 longshore sites on the leeward coast (North and South Kohala districts) of the Big Island (Hawaii...

FBSAD Recruit Reef Fish Belt Transect Survey at Hawaii Island (Big Island), Main Hawaiian Islands, 2005 (NODC Accession 0046935)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt transects were conducted at 8-13 m depths at 3 longshore sites on the leeward coast (North and South Kohala districts) of the Big Island (Hawaii...

Hydrogen sulfide potentiates interleukin-1β-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells

International Nuclear Information System (INIS)

Jeong, Sun-Oh; Pae, Hyun-Ock; Oh, Gi-Su; Jeong, Gil-Saeng; Lee, Bok-Soo; Lee, Seoul; Kim, Du Yong; Rhew, Hyun Yul; Lee, Kang-Min; Chung, Hun-Taeg

2006-01-01

Hydrogen sulfide (H 2 S) and nitric oxide (NO) are endogenously synthesized from L-cysteine and L-arginine, respectively. They might constitute a cooperative network to regulate their effects. In this study, we investigated whether H 2 S could affect NO production in rat vascular smooth muscle cells (VSMCs) stimulated with interleukin-1β (IL-1β). Although H 2 S by itself showed no effect on NO production, it augmented IL-β-induced NO production and this effect was associated with increased expression of inducible NO synthase (iNOS) and activation of nuclear factor (NF)-κB. IL-1β activated the extracellular signal-regulated kinase 1/2 (ERK1/2), and this activation was also enhanced by H 2 S. Inhibition of ERK1/2 activation by the selective inhibitor U0126 inhibited IL-1β-induced NF-κB activation, iNOS expression, and NO production either in the absence or presence of H 2 S. Our findings suggest that H 2 S enhances NO production and iNOS expression by potentiating IL-1β-induced NF-κB activation through a mechanism involving ERK1/2 signaling cascade in rat VSMCs

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

OpenAIRE

Ebdrup Bjørn H; Knop Filip K; Ishøy Pelle L; Rostrup Egill; Fagerlund Birgitte; Lublin Henrik; Glenthøj Birte

2012-01-01

Abstract Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the g...

The indirect global warming potential and global temperature change potential due to methane oxidation

International Nuclear Information System (INIS)

Boucher, Olivier; Collins, Bill; Friedlingstein, Pierre; Shine, Keith P

2009-01-01

Methane is the second most important anthropogenic greenhouse gas in the atmosphere next to carbon dioxide. Its global warming potential (GWP) for a time horizon of 100 years is 25, which makes it an attractive target for climate mitigation policies. Although the methane GWP traditionally includes the methane indirect effects on the concentrations of ozone and stratospheric water vapour, it does not take into account the production of carbon dioxide from methane oxidation. We argue here that this CO 2 -induced effect should be included for fossil sources of methane, which results in slightly larger GWP values for all time horizons. If the global temperature change potential is used as an alternative climate metric, then the impact of the CO 2 -induced effect is proportionally much larger. We also discuss what the correction term should be for methane from anthropogenic biogenic sources.

Sediment transport near the Peninsular tip of India

Digital Repository Service at National Institute of Oceanography (India)

Jena, B.K.; Chandramohan, P.

Studies were undertaken at Kolachel on the western side of the Peninsular tip from April 1995 to April 1996, for a period of one year. Monthly measurements were made on littoral environment observations (LEO) and beach level variations. Longshore...

Fisheries Biology and Stock Assessment Division (FBSAD) Recruit and Predator Reef Fish Belt Transect and Habitat Quadrat Surveys at Hawaii Island (Big Island), Main Hawaiian Islands, 2008; and Midway Atoll, Northwestern Hawaiian Islands (NWHI), 2008 (NODC Accession 0067519)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt transects were conducted and habitat quadrats were surveyed using transects at 1 to ~ 5 m depths at a total four (4) sites: at (1-2) 2 longshore...

Hydrogen sulfide, a potential novel drug, attenuates concanavalin A-induced hepatitis

Directory of Open Access Journals (Sweden)

Cheng P

2014-09-01

Full Text Available Ping Cheng,* Kan Chen,* Yujing Xia, Weiqi Dai, Fan Wang, Miao Shen, Chengfen Wang, Jing Yang, Rong Zhu, Huawei Zhang, Jingjing Li, Yuanyuan Zheng, Junshan Wang, Yan Zhang, Jie Lu, Yingqun Zhou, Chuanyong GuoDepartment of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai, People's Republic of China *These authors contributed equally to this work Background: Hydrogen sulfide (H2S is known to exert anti-inflammatory properties. Apoptosis and autophagy play important roles in concanavalin A (Con A-induced acute hepatitis. The purpose of this study was to explore both the effect and mechanism of H2S on Con A-induced acute hepatitis. Methods: BALB/c mice were randomized into sham group, Con A-injection group, and 14 µmol/kg of sodium hydrosulfide (NaHS, an H2S donor pretreatment group. Results: Aspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by NaHS pretreatment. NaHS pretreatment significantly reduced the levels of interleukin-6 and tumor necrosis factor-α compared with those of the Con A group. The expression of Bcl-2, Bax, Beclin-1, and LC3-2, which play important roles in the apoptosis and autophagy pathways, were also clearly affected by NaHS. Furthermore, NaHS affected the p-mTOR and p-AKT. Conclusion: H2S attenuates Con A-induced acute hepatitis by inhibiting apoptosis and autophagy, in part, through activation of the PtdIns3K-AKT1 signaling pathway. Keywords: NaHS, apoptosis, PtdIns3K-AKT, autophagy

Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: Implication in manganese-induced pulmonary inflammation

International Nuclear Information System (INIS)

Han, Jeongoh; Lee, Jong-Suk; Choi, Daekyu; Lee, Youna; Hong, Sungchae; Choi, Jungyun; Han, Songyi; Ko, Yujin; Kim, Jung-Ae; Mi Kim, Young; Jung, Yunjin

2009-01-01

Manganese (II), a transition metal, causes pulmonary inflammation upon environmental or occupational inhalation in excess. We investigated a potential molecular mechanism underlying manganese-induced pulmonary inflammation. Manganese (II) delayed HIF-1α protein disappearance, which occurred by inhibiting HIF-prolyl hydroxylase (HPH), the key enzyme for HIF-1α hydroxylation and subsequent von Hippel-Lindau(VHL)-dependent HIF-1α degradation. HPH inhibition by manganese (II) was neutralized significantly by elevated dose of iron. Consistent with this, the induction of cellular HIF-1α protein by manganese (II) was abolished by pretreatment with iron. Manganese (II) induced the HIF-1 target gene involved in pulmonary inflammation, vascular endothelial growth factor (VEGF), in lung carcinoma cell lines. The induction of VEGF was dependent on HIF-1. Manganese-induced VEGF promoted tube formation of HUVEC. Taken together, these data suggest that HIF-1 may be a potential mediator of manganese-induced pulmonary inflammation

Potential future exposure of European land transport infrastructure to rainfall-induced landslides throughout the 21st century

Science.gov (United States)

Schlögl, Matthias; Matulla, Christoph

2018-04-01

In the face of climate change, the assessment of land transport infrastructure exposure towards adverse climate events is of major importance for Europe's economic prosperity and social wellbeing. In this study, a climate index estimating rainfall patterns which trigger landslides in central Europe is analysed until the end of this century and compared to present-day conditions. The analysis of the potential future development of landslide risk is based on an ensemble of dynamically downscaled climate projections which are driven by the SRES A1B socio-economic scenario. Resulting regional-scale climate change projections across central Europe are concatenated with Europe's road and railway network. Results indicate overall increases of landslide occurrence. While flat terrain at low altitudes exhibits an increase of about 1 more potentially landslide-inducing rainfall period per year until the end of this century, higher elevated regions are more affected and show increases of up to 14 additional periods. This general spatial distribution emerges in the near future (2021-2050) but becomes more pronounced in the remote future (2071-2100). Since largest increases are to be found in Alsace, potential impacts of an increasing amount of landslides are discussed using the example of a case study covering the Black Forest mountain range in Baden-Württemberg by further enriching the climate information with additional geodata. The findings derived are suitable to support political decision makers and European authorities in transport, freight and logistics by offering detailed information on which parts of Europe's ground transport network are at particularly high risk concerning landslide activity.

Nutraceutical potential of Aerva lanata (L.) Juss. ex Schult ameliorates secondary complications in streptozotocin-induced diabetic rats.

Science.gov (United States)

Riya, M P; Antu, K A; Pal, S; Srivastava, A K; Sharma, S; Raghu, K G

2014-09-01

Nutraceuticals provide health benefits beyond their basic nutrition by modulating a number of biochemical pathways. They are derived from natural products and have gained recognition worldwide as an adjuvant or therapy in the treatment of metabolic disorders such as diabetes. Although the regulation of blood glucose with drugs and insulin greatly reduces the incidence of secondary complications, the need for long-term treatment raises issues of tolerance and affordability. Therefore, the aim of the present study is to explore the nutraceutical potential of Aerva lanata, a herb widely used for its culinary and therapeutic potential in streptozotocin (STZ)-induced diabetic rats. Treatment with 70% ethanolic extract (ALE) at 500 mg per kg b.w per day for 21 days significantly improved the fasting blood glucose (120.33 ± 1.99 mg dL(-1)), insulin level (9.81 ± 0.38 mU L(-1)), HbA1c (7.3 ± 0.36%) and glycogen content in the liver (35.33 ± 1.38 mg g(-1) protein) and muscle (7.67 ± 0.11 mg g(-1) protein) compared to diabetic controls. The extract also showed a significant decrease in blood glucose by 47.29% towards the end of 2 h in oral glucose tolerance test on Day 21. Its therapeutic potential could be partly attributable to the presence of flavonoids, tannins and terpenes (alpha amyrin, betulin and beta sitosterol) along with micronutrients such as potassium, magnesium, calcium and zinc. Hence, we suggest the suitability of Aerva lanata as a nutraceutical for diabetic patients.

Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases.

Science.gov (United States)

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

2009-11-01

Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-alpha) and also induced allogeneic naive CD4(+) T cells to proliferate and to produce type 1 cytokines such as interferon-gamma and tumor necrosis factor-alpha. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and

Effect of Postactivation Potentiation Induced by Elastic Resistance on Kinematics and Performance in a Roundhouse Kick of Trained Martial Arts Practitioners.

Science.gov (United States)

Aandahl, Håkon S; Von Heimburg, Erna; Van den Tillaar, Roland

2018-04-01

Aandahl, HS, Von Heimburg, E, and Van den Tillaar, R. Effect of postactivation potentiation induced by elastic resistance on kinematics and performance in a roundhouse kick of trained martial arts practitioners. J Strength Cond Res 32(4): 990-996, 2018-The aim of this study was to examine whether kicking with elastic resistance during warm-up could initiate postactivation potentiation (PAP), and thereby positively influence kinematics and performance on subsequent explosive roundhouse kicking. Five women and 11 men (n = 16) with a background in kickboxing (n = 10) or taekwondo (n = 6) performed 2 warm-up strategies with 3 subsequent test kicks 5-8 minutes after a PAP-inducing exercise. Kicking performance, defined as roundhouse kicking velocity with the foot, was measured using 3D motion capture (500 Hz) with a 15 marker lower-body 3D model. In addition, electromyography of the prime movers-vastus lateralis, vastus medialis, and rectus femoris muscles-was measured to confirm the presence of PAP. Kicking velocity of the foot increased by 3.3% after performing a warming-up strategy including kicking with elastic resistance (p = 0.009, η = 0.32). Increases were also recorded in muscle activity in vastus medialis (35.2%, p = 0.05, η = 0.18) and rectus femoris (43.9%, p = 0.04, η = 0.20). These findings indicate that performing a warm-up strategy including kicking with elastic resistance can have a positive effect on kicking performance in a roundhouse kick.

Tumorigenic Potential of Extracellular Matrix Metalloproteinase Inducer

Science.gov (United States)

Zucker, Stanley; Hymowitz, Michelle; Rollo, Ellen E.; Mann, Richard; Conner, Cathleen E.; Cao, Jian; Foda, Hussein D.; Tompkins, David C.; Toole, Bryan P.

2001-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs. PMID:11395366

FBSAD Reef Fish-HABITAT Quadrat Surveys at Hawaii Island (Big Island, Main Hawaiian Islands), 2006 and 2007; Kaneohe Bay (Oahu, Main Hawaiian Islands), 2007 only; and Midway Atoll (Northwestern Hawaiian Islands), 2006 and 2007 (NODC Accession 0056602)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Habitat quadrats were surveyed at 1 to 5 m depths using transects conducted at a total seven (7) sites: (1-2) at 2 longshore sites on the leeward coast (South Kohala...

FBSAD PREDATOR Reef Fish Belt Transect Survey at Hawaii Island (Big Island), Main Hawaiian Islands, 2006 and 2007; Oahu (Kaneohe Bay), Main Hawaiian Islands, 2007 only; and Midway Atoll, Northwestern Hawaiian Islands (NWHI), 2006 and 2007 (NODC Accession 0056602)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt transects were conducted at 1 to ~5 m depths at a total seven (7) sites: at (1-2) 2 longshore sites on the leeward coast (South Kohala district) of...

Monthly mean wind stress along the coast of the north Indian Ocean

Digital Repository Service at National Institute of Oceanography (India)

Shetye, S.R.; Shenoi, S.S.C.; Antony, M.K.; Krishnakumar, V.

Monthly-mean wind stress and its longshore and offshore components have been computed using the bulk aerodynamic method for each of a string of 36 two-degree-latitude by two-degree-longitude squares along the coast of the north Indian Ocean...

Seasonal cycle of surface circulation in the coastal North Indian Ocean

Digital Repository Service at National Institute of Oceanography (India)

Shetye, S.R.; Shenoi, S.S.C.

with similar patterns of longshore current and wind stress; (ii) circulation off the west coast of India is consistent with the dynamics of a wind-driven eastern boundary current only during the southwest monsoon. During the northeast monsoon it is possible...

RIP current zones along beaches in Goa, west coast of India

Digital Repository Service at National Institute of Oceanography (India)

Chandramohan, P.; SanilKumar, V.; Jena, B.K.

Goa has a 125-km-long coastline of which two-thirds consists of beautiful sandy beaches. There are mainly 17 beaches having significant importance of tourism. Sporadically, surf drownings have been reported at a few stretches of the beach. Longshore...

Fisheries Biology and Stock Assessment Division (FBSAD) Recruit and Predator Reef Fish Belt Transect and Habitat Surveys at Big Island (Hawaii Island) in May-June 2009 (NODC Accession 0073870)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt transects were conducted at 1 to ~ 5 m depths at a total two (2) sites: at 2 longshore sites on the leeward coast (South Kohala district) of the Big...

FBSAB PREDATOR Reef Fish Belt Transect Surveys at Hawaii Island (Big Island), Main Hawaiian Islands, 2009 (NODC Accession 0073870)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt transects were conducted at 1 to ~5 m depths at a total two (2) sites: at 2 longshore sites on the leeward coast (South Kohala district) of the Big...

FBSAD PREDATOR Reef Fish Belt Transect Survey at Hawaii Island (Big Island), Main Hawaiian Islands, 2008; and Midway Atoll, Northwestern Hawaiian Islands (NWHI), 2008 (NODC Accession 0067519)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt transects were conducted at 1 to ~5 m depths at a total four (4) sites: at (1-2) 2 longshore sites on the leeward coast (South Kohala district) of...

FBSAD RECRUIT Reef Fish Belt Transect Survey at Hawaii Island (Big Island), Main Hawaiian Islands, 2008; and Midway Atoll, Northwestern Hawaiian Islands (NWHI), 2008 (NODC Accession 0067519)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt transects were conducted at 1 to ~ 5 m depths at a total four (4) sites: at (1-2) 2 longshore sites on the leeward coast (South Kohala district) of...

FBSAD RECRUIT Reef Fish Belt Transect Survey at Hawaii Island (Big Island), Main Hawaiian Islands, 2006 and 2007; Oahu (Kaneohe Bay), Main Hawaiian Islands, 2007 only; and Midway Atoll, Northwestern Hawaiian Islands (NWHI), 2006 and 2007 (NODC Accession 0056602)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt transects were conducted at 1 to ~ 5 m depths at a total seven (7) sites: at (1-2) 2 longshore sites on the leeward coast (South Kohala district) of...

FBSAD Reef Fish-HABITAT Quadrat Surveys at Hawaii Island (Big Island, Main Hawaiian Islands), 2008; and Midway Atoll (Northwestern Hawaiian Islands), 2008 (NODC Accession 0067519)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Habitat quadrats were surveyed at 1 to ~5 m depths using transects conducted at a total four (4) sites: (1-2) at 2 longshore sites on the leeward coast (South Kohala...

76 FR 5402 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Gear...

Science.gov (United States)

2011-01-31

... for OMB Review; Comment Request; Gear Certification ACTION: Notice. SUMMARY: The Department of Labor...) sponsored information collection request (ICR) titled, ``Gear Certification,'' to the Office of Management... cranes, derricks, and accessory gear used in the longshoring, marine terminal, and shipyard industries...

Fisheries Biology and Stock Assessment Division (FBSAD) Recruit and Predator Reef Fish Belt Transect and Habitat Quadrat Surveys at Hawaii Island and Midway Atoll, 2006-2007; and Oahu, 2007 only (NODC Accession 0056602)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Shore-based belt and habitat quadrats were surveyed using transects at 1 to ~5 m depths at a total seven (7) sites: at (1-2) 2 longshore sites on the leeward coast...

29 CFR 1918.106 - Payment for protective equipment.

Science.gov (United States)

2010-07-01

... pay for non-specialty safety-toe protective footwear (including steel-toe shoes or steel-toe boots... Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Personal Protective Equipment...

Automated Data Collection for Determining Statistical Distributions of Module Power Undergoing Potential-Induced Degradation: Preprint

Energy Technology Data Exchange (ETDEWEB)

Hacke, P.; Spataru, S.

2014-08-01

We propose a method for increasing the frequency of data collection and reducing the time and cost of accelerated lifetime testing of photovoltaic modules undergoing potential-induced degradation (PID). This consists of in-situ measurements of dark current-voltage curves of the modules at elevated stress temperature, their use to determine the maximum power at 25 degrees C standard test conditions (STC), and distribution statistics for determining degradation rates as a function of stress level. The semi-continuous data obtained by this method clearly show degradation curves of the maximum power, including an incubation phase, rates and extent of degradation, precise time to failure, and partial recovery. Stress tests were performed on crystalline silicon modules at 85% relative humidity and 60 degrees C, 72 degrees C, and 85 degrees C. Activation energy for the mean time to failure (1% relative) of 0.85 eV was determined and a mean time to failure of 8,000 h at 25 degrees C and 85% relative humidity is predicted. No clear trend in maximum degradation as a function of stress temperature was observed.

Anticancer potential of Conium maculatum extract against cancer cells in vitro: Drug-DNA interaction and its ability to induce apoptosis through ROS generation.

Science.gov (United States)

Mondal, Jesmin; Panigrahi, Ashis Kumar; Khuda-Bukhsh, Anisur Rahman

2014-08-01

Conium maculatum extract is used as a traditional medicine for cervix carcinoma including homeopathy. However, no systematic work has so far been carried out to test its anti-cancer potential against cervix cancer cells in vitro. Thus, in this study, we investigated whether ethanolic extract of conium is capable of inducing cytotoxicity in different normal and cancer cell lines including an elaborate study in HeLa cells. Conium's effects on cell cycle, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential (MMP) and apoptosis, if any, were analyzed through flow cytometry. Whether Conium could damage DNA and induce morphological changes were also determined microscopically. Expression of different proteins related to cell death and survival was critically studied by western blotting and ELISA methods. If Conium could interact directly with DNA was also determined by circular dichroism (CD) spectroscopy. Conium treatment reduced cell viability and colony formation at 48 h and inhibited cell proliferation, arresting cell cycle at sub-G stage. Conium treatment lead to increased generation of reactive oxygen species (ROS) at 24 h, increase in MMP depolarization, morphological changes and DNA damage in HeLa cells along with externalization of phosphatidyl serine at 48 hours. While cytochrome c release and caspase-3 activation led HeLa cells toward apoptosis, down-regulation of Akt and NFkB inhibited cellular proliferation, indicating the signaling pathway to be mediated via the mitochondria-mediated caspase-3-dependent pathway. CD-spectroscopy revealed that Conium interacted with DNA molecule. Overall results validate anti-cancer potential of Conium and provide support for its use in traditional systems of medicine.

Healing Potential of Picrorhiza kurroa (Scrofulariaceae rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration.

Directory of Open Access Journals (Sweden)

Bandyopadhyay Sandip K

2008-01-01

Full Text Available Abstract Background The present study was undertaken to evaluate the potential of the rhizomes of the Indian medicinal plant, Picrorhiza kurroa in healing indomethacin-induced acute stomach ulceration in mice and examine its capacity to modulate oxidative stress and the levels of prostaglandin (PGE2 and EGF during the process. Methods Male swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o., single dose were treated up to 7 days with different doses of the methanol extract of P. kurroa rhizomes (designated as PK. The healing capacity of the most effective dose of PK (20 mg/kg, p. o. × 3 d was compared with that of omeprazole (Omez (3 mg/kg, p. o. × 3 d. The effects of the drug-treatment for one and three days on the biochemical parameters were assessed by comparing the results with that of untreated mice of the 1st and 3rd day of ulceration. The stomach tissues of the mice were used for the biochemical analysis. Results The macroscopic indices revealed maximum ulceration on the 3rd day after indomethacin administration, which was effectively healed by PK. Under the optimized treatment regime, PK and Omez reduced the ulcer indices by 45.1% (P P Compared to the ulcerated untreated mice, those treated with PK for 3 days showed decreased the levels of thiobarbituric acid reactive substances (TBARS (32.7%, P P P 2 (21.4%, P P P P P P P Conclusion PK (20 mg/kg, p. o. × 3 days could effectively heal indomethacin-induced stomach ulceration in mice by reducing oxidative stress, and promoting mucin secretion, prostaglandin synthesis and augmenting expressions of cyclooxygenase enzymes and growth factors.

29 CFR 1910.16 - Longshoring and marine terminals.

Science.gov (United States)

2010-07-01

...) Commercial diving operations. Subpart T; (iii) Electrical. Subpart S when shore-based electrical... sulfide, § 1910.1000 (See § 1918.94 (f)). (x) Powered industrial truck operator training, Subpart N... facilities contiguous to electrical power generating plants. (2) Part 1910 does not apply to marine terminals...

D-Serine rescues the deficits of hippocampal long-term potentiation and learning and memory induced by sodium fluoroacetate.

Science.gov (United States)

Han, Huili; Peng, Yan; Dong, Zhifang

2015-06-01

It is well known that bidirectional glia-neuron interactions play important roles in the neurophysiological and neuropathological processes. It is reported that impairing glial functions with sodium fluoroacetate (FAC) impaired hippocampal long-term depression (LTD) and spatial memory retrieval. However, it remains unknown whether FAC impairs hippocampal long-term potentiation (LTP) and learning and/or memory, and if so, whether pharmacological treatment with exogenous d-serine can recuse the impairment. Here, we reported that systemic administration of FAC (3mg/kg, i.p.) before training resulted in dramatic impairments of spatial learning and memory in water maze and fear memory in contextual fear conditioning. Furthermore, the behavioral deficits were accompanied by impaired LTP induction in the hippocampal CA1 area of brain slices. More importantly, exogenous d-serine treatment succeeded in recusing the deficits of hippocampal LTP and learning and memory induced by FAC. Together, these results suggest that astrocytic d-serine may be essential for hippocampal synaptic plasticity and memory, and that alteration of its levels may be relevant to the induction and potentially treatment of psychiatric and neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Solar ultraviolet radiation-induced DNA damage in aquatic organisms: potential environmental impact

International Nuclear Information System (INIS)

Haeder, Donat-P.; Sinha, Rajeshwar P.

2005-01-01

Continuing depletion of stratospheric ozone and subsequent increases in deleterious ultraviolet (UV) radiation at the Earth's surface have fueled the interest in its ecological consequences for aquatic ecosystems. The DNA is certainly one of the key targets for UV-induced damage in a variety of aquatic organisms. UV radiation induces two of the most abundant mutagenic and cytotoxic DNA lesions, cyclobutane pyrimidine dimers (CPDs) and pyrimidine pyrimidone photoproducts (6-4PPs) and their Dewar valence isomers. However, aquatic organisms have developed a number of repair and tolerance mechanisms to counteract the damaging effects of UV on DNA. Photoreactivation with the help of the enzyme photolyase is one of the most important and frequently occurring repair mechanisms in a variety of organisms. Excision repair, which can be distinguished into base excision repair (BER) and nucleotide excision repair (NER), also play an important role in DNA repair in several organisms with the help of a number of glycosylases and polymerases, respectively. In addition, mechanisms such as mutagenic repair or dimer bypass, recombinational repair, cell-cycle checkpoints, apoptosis and certain alternative repair pathways are also operative in various organisms. This review deals with the UV-induced DNA damage and repair in a number of aquatic organisms as well as methods of detecting DNA damage

Low concentration of exogenous carbon monoxide protects mammalian cells against proliferation induced by radiation-induced bystander effect

International Nuclear Information System (INIS)

Tong, Liping; Yu, K.N.; Bao, Lingzhi; Wu, Wenqing; Wang, Hongzhi; Han, Wei

2014-01-01

Highlights: • We show the possibility of modulate proliferation induced by radiation-induced bystander effect with low concentration carbon monoxide. • Carbon monoxide inhibited proliferation via modulating the transforming growth factor β1 (TGF-β1)/nitric oxide (NO) signaling pathway. • Exogenous carbon monoxide has potential application in clinical radiotherapy. - Abstract: Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after α-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor β1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy

Low concentration of exogenous carbon monoxide protects mammalian cells against proliferation induced by radiation-induced bystander effect

Energy Technology Data Exchange (ETDEWEB)

Tong, Liping [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Bao, Lingzhi; Wu, Wenqing; Wang, Hongzhi [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Han, Wei, E-mail: hanw@hfcas.cn [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China)

2014-01-15

Highlights: • We show the possibility of modulate proliferation induced by radiation-induced bystander effect with low concentration carbon monoxide. • Carbon monoxide inhibited proliferation via modulating the transforming growth factor β1 (TGF-β1)/nitric oxide (NO) signaling pathway. • Exogenous carbon monoxide has potential application in clinical radiotherapy. - Abstract: Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after α-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor β1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy.

The Geomorphic System and the Effects of Human Interference at Gold Coast Beach in Tainan, Taiwan

Science.gov (United States)

Lin, Tsung-Yi

2017-04-01

The Gold Coast beach in Tainan, Taiwan, located between Anping harbor and Ur-Jen river mouth, is the subject of this study, which characterizes the beach's geomorphic system through the analysis of information such as sediment grain size, mineral composition, and periodic measurements of morphological changes of the beach. Based upon such characterizations, further analysis is conducted on the effects that human activities of the last 15 years have upon the geomorphic changes within the Gold Coast beach. The study shows that the median grain size of the Gold Coast beach's sediment is medium sand. The mineral composition includes mainly slate fragments and quartz grains, with small amounts of feldspar, sandstone and shell fragments. Based on a comprehensive study of the longshore distribution of beach sediment size and mineral composition of southwestern coast of Taiwan, as well as, the long-term, monitored data of waves, tides, and currents in this region, we conclude that the main process responsible for the sand accumulation at Gold Coast beach is the prevailing longshore sand transport from south to north. The southern breakwater of Anping harbor plays a role in intercepting the longshore transport sand and helps form the beach. Since the Ur-Jen river flows through a mudstone region, the suspended sediment plume during the flood season does not provide much sediment source to the sandy beach. A monthly beach profile survey project conducted between the years 1999 to 2000 revealed that the beach elevation and width had experienced an obvious seasonal change. The beach widened during the winter, but narrowed in the summer due to typhoon wave erosion. When the subaerial beach was eroded, a submerged longshore bar that was oriented almost parallel to the shoreline had formed at a distance about 400-600 meter away. With this observation, we can conclude that beach morphology is also influenced by various seasonal wave actions that affect onshore and offshore sand

Potential of Gene Editing and Induced Pluripotent Stem Cells (iPSCs) in Treatment of Retinal Diseases.

Science.gov (United States)

Chuang, Katherine; Fields, Mark A; Del Priore, Lucian V

2017-12-01

The advent of gene editing has introduced the ability to make changes to the genome of cells, thus allowing for correction of genetic mutations in patients with monogenic diseases. Retinal diseases are particularly suitable for the application of this new technology because many retinal diseases, such as Stargardt disease, retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA), are monogenic. Moreover, gene delivery techniques such as the use of adeno-associated virus (AAV) vectors have been optimized for intraocular use, and phase III trials are well underway to treat LCA, a severe form of inherited retinal degeneration, with gene therapy. This review focuses on the use of gene editing techniques and another relatively recent advent, induced pluripotent stem cells (iPSCs), and their potential for the study and treatment of retinal disease. Investment in these technologies, including overcoming challenges such as off-target mutations and low transplanted cell integration, may allow for future treatment of many debilitating inherited retinal diseases.

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma

Science.gov (United States)

2013-01-01

Introduction The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. Methods The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). Results IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Conclusions Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS. PMID:24499523

Sildenafil protects against bile duct ligation induced hepatic fibrosis in rats: Potential role for silent information regulator 1 (SIRT1).

Science.gov (United States)

Abd El Motteleb, Dalia M; Ibrahim, Islam A A E-H; Elshazly, Shimaa M

2017-11-15

Hepatic fibrosis is a potential health problem that may end with life-threatening cirrhosis and primary liver cancer. Recent studies point out to the protective effects of silent information regulator1 (SIRT1), against different models of organs fibrosis. This work aimed to investigate the possible protective effect of sildenafil (SIRT1 activator) against hepatic fibrosis induced by bile duct ligation (BDL). Firstly, three different doses of sildenafil (5, 10, 20mg/kg/day) were investigated; to detect the most protective one against BDL induced liver dysfunction and hepatic fibrosis. The most protective dose is then used; to study its effect on BDL induced SIRT1 downregulation, imbalance of oxidant/antioxidant status, increased inflammatory cytokines and fibrosis. Sildenafil (20mg/kg/day) was the most protective one, it caused upregulation of SIRT1, reduction of hepatic malondialdehyde (MDA) content, increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenease (HO)-1, reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Hepatic content of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NFκB) expression & content displayed significant reductions with sildenafil treatment, Furthermore, sildenafil caused marked reductions of transforming growth factor (TGF)-β content, expression of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), α-smooth muscle actin (α-SMA), fibronectin, collagen I (α1) and hydroxyproline content. However, sildenafil protective effects were significantly reduced by co-administration of EX527 (SIRT1 inhibitor). Our work showed, for the first time that, sildenafil has promising protective effects against BDL induced liver dysfunction and hepatic fibrosis. These effects may be, in part, mediated by up regulation of SIRT1. Copyright © 2017. Published by Elsevier Inc.

Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice

Directory of Open Access Journals (Sweden)

Carlton Susan M

2010-03-01

Full Text Available Abstract Background Cisplatin is primarily used for treatment of ovarian and testicular cancer. Oxaliplatin is the only effective treatment for metastatic colorectal cancer. Both are known to cause dose related, cumulative toxic effects on the peripheral nervous system and thirty to forty percent of cancer patients receiving these agents experience painful peripheral neuropathy. The mechanisms underlying painful platinum-induced neuropathy remain poorly understood. Previous studies have demonstrated important roles for TRPV1, TRPM8, and TRPA1 in inflammation and nerve injury induced pain. Results In this study, using real-time, reverse transcriptase, polymerase chain reaction (RT-PCR, we analyzed the expression of TRPV1, TRPM8, and TRPA1 induced by cisplatin or oxaliplatin in vitro and in vivo. For in vitro studies, cultured E15 rat dorsal root ganglion (DRG neurons were treated for up to 48 hours with cisplatin or oxaliplatin. For in vivo studies, trigeminal ganglia (TG were isolated from mice treated with platinum drugs for three weeks. We show that cisplatin and oxaliplatin-treated DRG neurons had significantly increased in TRPV1, TRPA1, and TRPM8 mRNA expression. TG neurons from cisplatin treated mice had significant increases in TRPV1 and TRPA1 mRNA expression while oxaliplatin strongly induced only TRPA1. Furthermore, compared to the cisplatin-treated wild-type mice, cisplatin-treated TRPV1-null mice developed mechanical allodynia but did not exhibit enhancement of noxious heat- evoked pain responses. Immunohistochemistry studies showed that cisplatin-treated mice had no change in the proportion of the TRPV1 immunopositive TG neurons. Conclusion These results indicate that TRPV1 and TRPA1 could contribute to the development of thermal hyperalgesia and mechanical allodynia following cisplatin-induced painful neuropathy but that TRPV1 has a crucial role in cisplatin-induced thermal hyperalgesia in vivo.

Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway

Directory of Open Access Journals (Sweden)

Douglas Blackiston

2011-01-01

Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest’s environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl. Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT. These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior.