Potential effects of environmental contaminants on P450 aromatase activity and DNA damage in swallows from the Rio Grande and Somerville, Texas

USGS Publications Warehouse

Sitzlar, M.A.; Mora, M.A.; Fleming, J.G.W.; Bazer, F.W.; Bickham, J.W.; Matson, C.W.

2009-01-01

Cliff swallows (Petrochelidon pyrrhonota) and cave swallows (P. fulva) were sampled during the breeding season at several locations in the Rio Grande, Texas, to evaluate the potential effects of environmental contaminants on P450 aromatase activity in brain and gonads and DNA damage in blood cells. The tritiated water-release aromatase assay was used to measure aromatase activity and flow cytometry was used to measure DNA damage in nucleated blood cells. There were no significant differences in brain and gonadal aromatase activities or in estimates of DNA damage (HPCV values) among cave swallow colonies from the Lower Rio Grande Valley (LRGV) and Somerville. However, both brain and gonadal aromatase activities were significantly higher (P < 0.05) in male cliff swallows from Laredo than in those from Somerville. Also, DNA damage estimates were significantly higher (P < 0.05) in cliff swallows (males and females combined) from Laredo than in those from Somerville. Contaminants of current high use in the LRGV, such as atrazine, and some of the highly persistent organochlorines, such as toxaphene and DDE, could be potentially associated with modulation of aromatase activity in avian tissues. Previous studies have indicated possible DNA damage in cliff swallows. We did not observe any differences in aromatase activity or DNA damage in cave swallows that could be associated with contaminant exposure. Also, the differences in aromatase activity and DNA damage between male cliff swallows from Laredo and Somerville could not be explained by contaminants measured at each site in previous studies. Our study provides baseline information on brain and gonadal aromatase activity in swallows that could be useful in future studies. ?? 2008 Springer Science+Business Media, LLC.

Mapping potential carbon and timber losses from hurricanes using a decision tree and ecosystem services driver model.

PubMed

Delphin, S; Escobedo, F J; Abd-Elrahman, A; Cropper, W

2013-11-15

Information on the effect of direct drivers such as hurricanes on ecosystem services is relevant to landowners and policy makers due to predicted effects from climate change. We identified forest damage risk zones due to hurricanes and estimated the potential loss of 2 key ecosystem services: aboveground carbon storage and timber volume. Using land cover, plot-level forest inventory data, the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model, and a decision tree-based framework; we determined potential damage to subtropical forests from hurricanes in the Lower Suwannee River (LS) and Pensacola Bay (PB) watersheds in Florida, US. We used biophysical factors identified in previous studies as being influential in forest damage in our decision tree and hurricane wind risk maps. Results show that 31% and 0.5% of the total aboveground carbon storage in the LS and PB, respectively was located in high forest damage risk (HR) zones. Overall 15% and 0.7% of the total timber net volume in the LS and PB, respectively, was in HR zones. This model can also be used for identifying timber salvage areas, developing ecosystem service provision and management scenarios, and assessing the effect of other drivers on ecosystem services and goods. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of oxidative stress in diabetic retinopathy and the beneficial effects of flavonoids.

PubMed

Ola, Mohammad Shamsul; Al-Dosari, Dalia; Alhomida, Abdullah S

2018-05-15

Diabetic retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious changes through dysregulation of cellular physiology that damages both neuronal and vascular cells. Here in this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contributes to retinal pathology in diabetes. As oxidative stress is a central factor in the pathophysiology of DR, antioxidants therapy would be beneficial towards preventing the retinal damage. A number of experimental studies by us and others showed that dietary flavonoids cause reduction in increased oxidative stress and other beneficial effects in diabetic retina. We then discuss the potential beneficial effects of the six major flavonoid families, such as flavonones, flavanols, flavonols, isoflavones, flavones and anthocyanins, which have been studied to improve retinal damage. Flanonoids, being known antioxidants, may ameliorate the retinal degenerative factors including apoptosis, inflammation and neurodegeneration in the diabetic retina. Therefore, intake of potential dietary flavonoids would limit oxidative stress and thereby prevent the retinal damage, and subsequently the development of DR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A damage analysis for brittle materials using stochastic micro-structural information

NASA Astrophysics Data System (ADS)

Lin, Shih-Po; Chen, Jiun-Shyan; Liang, Shixue

2016-03-01

In this work, a micro-crack informed stochastic damage analysis is performed to consider the failures of material with stochastic microstructure. The derivation of the damage evolution law is based on the Helmholtz free energy equivalence between cracked microstructure and homogenized continuum. The damage model is constructed under the stochastic representative volume element (SRVE) framework. The characteristics of SRVE used in the construction of the stochastic damage model have been investigated based on the principle of the minimum potential energy. The mesh dependency issue has been addressed by introducing a scaling law into the damage evolution equation. The proposed methods are then validated through the comparison between numerical simulations and experimental observations of a high strength concrete. It is observed that the standard deviation of porosity in the microstructures has stronger effect on the damage states and the peak stresses than its effect on the Young's and shear moduli in the macro-scale responses.

Structural Damage Prediction and Analysis for Hypervelocity Impacts: Handbook

NASA Technical Reports Server (NTRS)

Elfer, N. C.

1996-01-01

This handbook reviews the analysis of structural damage on spacecraft due to hypervelocity impacts by meteoroid and space debris. These impacts can potentially cause structural damage to a Space Station module wall. This damage ranges from craters, bulges, minor penetrations, and spall to critical damage associated with a large hole, or even rupture. The analysis of damage depends on a variety of assumptions and the area of most concern is at a velocity beyond well controlled laboratory capability. In the analysis of critical damage, one of the key questions is how much momentum can actually be transfered to the pressure vessel wall. When penetration occurs without maximum bulging at high velocity and obliquities (if less momentum is deposited in the rear wall), then large tears and rupture may be avoided. In analysis of rupture effects of cylindrical geometry, biaxial loading, bending of the crack, a central hole strain rate and R-curve effects are discussed.

Role of phenolics from Spondias pinnata bark in amelioration of iron overload induced hepatic damage in Swiss albino mice.

PubMed

Chaudhuri, Dipankar; Ghate, Nikhil Baban; Panja, Sourav; Mandal, Nripendranath

2016-07-26

Crude Spondias pinnata bark extract was previously assessed for its antioxidant, anticancer and iron chelating potentials. The isolated compounds gallic acid (GA) and methyl gallate (MG) were evaluated for their curative potential against iron overload-induced liver fibrosis and hepatocellular damage. In vitro iron chelation property and in vivo ameliorating potential from iron overload induced liver toxicity of GA and MG was assessed by different biochemical assays and histopathological studies. MG and GA demonstrated excellent reducing power activities but iron chelation potential of MG is better than GA. Oral MG treatment in mice displayed excellent efficacy (better than GA) to significantly restore the levels of liver antioxidants, serum markers and cellular reactive oxygen species in a dose-dependent fashion. Apart from these, MG exceptionally prevented lipid peroxidation and protein oxidation whereas GA demonstrated better activity to reduce collagen content, thereby strengthening its position as an efficient drug against hepatic damage/fibrosis, which was further supported by histopathological studies. Alongside, MG efficiently eliminated the cause of liver damage, i.e., excess iron, by chelating free iron and reducing the ferritin-bound iron. The present study confirmed the curative effect of GA and MG against iron overload hepatic damage via their potent antioxidant and iron-chelating potential.

Protective Effect of Edaravone Against Aβ25-35-Induced Mitochondrial Oxidative Damage in SH-SY5Y Cells.

PubMed

Zhang, G-L; Zhang, L; Guo, Y-Y; Ma, Z-L; Wang, H-Y; Li, T; Liu, J; Du, Y; Yao, L; Li, T-T; Du, J-M

2017-05-20

Amyloid-β (Aβ)-induced oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). Recent studies show that Aβ accumulation may lead to mitochondrial oxidative damage. In the present study, we investigated the protective effect of edaravone on mitochondrial damage in SH-SY5Y cells treated with Aβ25-35. SH-SY5Y cells were pre-treated with 20, 40 or 80 μM edaravone before treatment with 25 μM Aβ25-35. After 24h cell culture, cellular apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), ATP levels and mitochondrial morphology were evaluated. SH-SY5Y cells exposed to Aβ25-35 had high levels of apoptosis and ROS; loss of ΔΨm, decreased ATP levels and presence of mitochondrial swelling. However, these effects were significantly inhibited by edaravone pre-treatment. These results indicate that edaravone prevents mitochondria oxidative damage caused by Aβ in SH-SY5Y cells, which suggests that it may have potential clinical application in AD therapy.

Direct and Pollinator-Mediated Effects of Herbivory on Strawberry and the Potential for Improved Resistance

PubMed Central

Muola, Anne; Weber, Daniela; Malm, Lisa E.; Egan, Paul A.; Glinwood, Robert; Parachnowitsch, Amy L.; Stenberg, Johan A.

2017-01-01

The global decline in pollinators has partly been blamed on pesticides, leading some to propose pesticide-free farming as an option to improve pollination. However, herbivores are likely to be more prevalent in pesticide-free environments, requiring knowledge of their effects on pollinators, and alternative crop protection strategies to mitigate any potential pollination reduction. Strawberry leaf beetles (SLB) Galerucella spp. are important strawberry pests in Northern Europe and Russia. Given that SLB attack both leaf and flower tissue, we hypothesized pollinators would discriminate against SLB-damaged strawberry plants (Fragaria vesca, cultivar ‘Rügen’), leading to lower pollination success and yield. In addition we screened the most common commercial cultivar ‘Rügen’ and wild Swedish F. vesca genotypes for SLB resistance to assess the potential for inverse breeding to restore high SLB resistance in cultivated strawberry. Behavioral observations in a controlled experiment revealed that the local pollinator fauna avoided strawberry flowers with SLB-damaged petals. Low pollination, in turn, resulted in smaller more deformed fruits. Furthermore, SLB-damaged flowers produced smaller fruits even when they were hand pollinated, showing herbivore damage also had direct effects on yield, independent of indirect effects on pollination. We found variable resistance in wild woodland strawberry to SLB and more resistant plant genotypes than the cultivar ‘Rügen’ were identified. Efficient integrated pest management strategies should be employed to mitigate both direct and indirect effects of herbivory for cultivated strawberry, including high intrinsic plant resistance. PMID:28572811

Damage pattern as a function of radiation quality and other factors.

PubMed

Burkart, W; Jung, T; Frasch, G

1999-01-01

An understanding of damage pattern in critical cellular structures such as DNA is an important prerequisite for a mechanistic assessment of primary radiation damage, its possible repair, and the propagation of residual changes in somatic and germ cells as potential contributors to disease or ageing. Important quantitative insights have been made recently on the distribution in time and space of critical lesions from direct and indirect action of ionizing radiation on mammalian cells. When compared to damage from chemicals or from spontaneous degradation, e.g. depurination or base deamination in DNA, the potential of even low-LET radiation to create local hot spots of damage from single particle tracks is of utmost importance. This has important repercussions on inferences from critical biological effects at high dose and dose rate exposure situations to health risks at chronic, low-level exposures as experienced in environmental and controlled occupational settings. About 10,000 DNA lesions per human cell nucleus and day from spontaneous degradation and chemical attack cause no apparent effect, but a dose of 4 Gy translating into a similar number of direct and indirect DNA breaks induces acute lethality. Therefore, single lesions cannot explain the high efficiency of ionizing radiation in the induction of mutation, transformation and loss of proliferative capacity. Clustered damage leading to poorly repairable double-strand breaks or even more complex local DNA degradation, correlates better with fixed damage and critical biological endpoints. A comparison with other physical, chemical and biological agents indicates that ionizing radiation is indeed set apart from these by its unique micro- and nano-dosimetric traits. Only a few other agents such as bleomycin have a similar potential to cause complex damage from single events. However, in view of the multi-stage mechanism of carcinogenesis, it is still an open question whether dose-effect linearity for complex primary DNA damage and resulting fixed critical cellular lesions translate into linearity for radiation-induced cancer. To solve this enigma, a quantitative assessment of all genotoxic and harmful non-genotoxic agents affecting the human body would be needed.

Lightning Strike Ablation Damage Influence Factors Analysis of Carbon Fiber/Epoxy Composite Based on Coupled Electrical-Thermal Simulation

NASA Astrophysics Data System (ADS)

Yin, J. J.; Chang, F.; Li, S. L.; Yao, X. L.; Sun, J. R.; Xiao, Y.

2017-10-01

According to the mathematical analysis model constructed on the basis of energy-balance relationship in lightning strike, and accompany with the simplified calculation strategy of composite resin pyrolysis degree dependent electrical conductivity, an effective three dimensional thermal-electrical coupling analysis finite element model of composite laminate suffered from lightning current was established based on ABAQUS, to elucidate the effects of lighting current waveform parameters and thermal/electrical properties of composite laminate on the extent of ablation damage. Simulated predictions agree well with the composite lightning strike directed effect experimental data, illustrating the potential accuracy of the constructed model. The analytical results revealed that extent of composite lightning strike ablation damage can be characterized by action integral validly, there exist remarkable power function relationships between action integral and visual damage area, projected damage area, maximum damage depth and damage volume of ablation damage, and enhancing the electrical conductivity and specific heat of composite, ablation damage will be descended obviously, power function relationships also exist between electrical conductivity, specific heat and ablation damage, however, the impact of thermal conductivity on the extent of ablation damage is not notable. The conclusions obtained provide some guidance for composite anti-lightning strike structure-function integration design.

Aging, Loss-of-Coolant Accident (LOCA), and high potential testing of damaged cables

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vigil, R.A.; Jacobus, M.J.

1994-04-01

Experiments were conducted to assess the effects of high potential testing of cables and to assess the survivability of aged and damaged cables under Loss-of-Coolant Accident (LOCA) conditions. High potential testing at 240 Vdc/mil on undamaged cables suggested that no damage was incurred on the selected virgin cables. During aging and LOCA testing, Okonite ethylene propylene rubber (EPR) cables with a bonded jacket experienced unexpected failures. The failures appear to be primarily related to the level of thermal aging and the presence of a bonded jacket that ages more rapidly than the insulation. For Brand Rex crosslinked polyolefin (XLPO) cables,more » the results suggest that 7 mils of insulation remaining should give the cables a high probability of surviving accident exposure following aging. The voltage necessary to detect when 7 mils of insulation remain on unaged Brand Rex cables is approximately 35 kVdc. This voltage level would almost certainly be unacceptable to a utility for use as a damage assessment tool. However, additional tests indicated that a 35 kvdc voltage application would not damage virgin Brand Rex cables when tested in water. Although two damaged Rockbestos silicone rubber cables also failed during the accident test, no correlation between failures and level of damage was apparent.« less

Computational Implementation of a Thermodynamically Based Work Potential Model For Progressive Microdamage and Transverse Cracking in Fiber-Reinforced Laminates

NASA Technical Reports Server (NTRS)

Pineda, Evan J.; Waas, Anthony M.; Bednarcyk, Brett A.; Collier, Craig S.

2012-01-01

A continuum-level, dual internal state variable, thermodynamically based, work potential model, Schapery Theory, is used capture the effects of two matrix damage mechanisms in a fiber-reinforced laminated composite: microdamage and transverse cracking. Matrix microdamage accrues primarily in the form of shear microcracks between the fibers of the composite. Whereas, larger transverse matrix cracks typically span the thickness of a lamina and run parallel to the fibers. Schapery Theory uses the energy potential required to advance structural changes, associated with the damage mechanisms, to govern damage growth through a set of internal state variables. These state variables are used to quantify the stiffness degradation resulting from damage growth. The transverse and shear stiffness of the lamina are related to the internal state variables through a set of measurable damage functions. Additionally, the damage variables for a given strain state can be calculated from a set of evolution equations. These evolution equations and damage functions are implemented into the finite element method and used to govern the constitutive response of the material points in the model. Additionally, an axial failure criterion is included in the model. The response of a center-notched, buffer strip-stiffened panel subjected to uniaxial tension is investigated and results are compared to experiment.

Landslide risk analysis: a multi-disciplinary methodological approach

NASA Astrophysics Data System (ADS)

Sterlacchini, S.; Frigerio, S.; Giacomelli, P.; Brambilla, M.

2007-11-01

This study describes an analysis carried out within the European community project "ALARM" (Assessment of Landslide Risk and Mitigation in Mountain Areas, 2004) on landslide risk assessment in the municipality of Corvara in Badia, Italy. This mountainous area, located in the central Dolomites (Italian Alps), poses a significant landslide hazard to several man-made and natural objects. Three parameters for determining risk were analysed as an aid to preparedness and mitigation planning: event occurrence probability, elements at risk, and the vulnerability of these elements. Initially, a landslide hazard scenario was defined; this step was followed by the identification of the potential vulnerable elements, by the estimation of the expected physical effects, due to the occurrence of a damaging phenomenon, and by the analysis of social and economic features of the area. Finally, a potential risk scenario was defined, where the relationships between the event, its physical effects, and its economic consequences were investigated. People and public administrators with training and experience in local landsliding and slope processes were involved in each step of the analysis. A "cause-effect" correlation was applied, derived from the "dose-response" equation initially used in the biological sciences and then adapted by economists for the assessment of environmental risks. The relationship was analysed from a physical point of view and the cause (the natural event) was correlated to the physical effects, i.e. the aesthetic, functional, and structural damage. An economic evaluation of direct and indirect damage was carried out considering the assets in the affected area (i.e., tourist flows, goods, transport and the effect on other social and economic activities). This study shows the importance of indirect damage, which is as significant as direct damage. The total amount of direct damage was estimated in 8 913 000 €; on the contrary, indirect damage ranged considerably from 2 840 000 to 9 350 000 €, depending on the selected temporal scenario and the expected closing time of the potentially affected structures. The multi-disciplinary approach discussed in this study may assist local decision makers in determining the nature and magnitude of the expected losses due to a dangerous event, which can be anticipated in a given study area, during a specified time period. Besides, a preventive knowledge of the prospective physical effects and economic consequences may help local decision makers to choose the best prevention and mitigation options and to decide how to allocate resources properly, so that potential benefits are maximised at an acceptable cost.

Blueberry (Vaccinium ashei Reade) extract ameliorates ovarian damage induced by subchronic cadmium exposure in mice: Potential δ-ALA-D involvement.

PubMed

Izaguirry, Aryele Pinto; Soares, Melina Bucco; Vargas, Laura Musacchio; Spiazzi, Cristiano Chiapinotto; Dos Santos Brum, Daniela; Noremberg, Simone; Mendez, Andreas Sebastian Loureiro; Santos, Francielli Weber

2017-01-01

Females are born with a finite number of oocyte-containing follicles and ovary damage results in reduced fertility. Cadmium accumulates in the reproductive system, damaging it, and the cigarette smoke is a potential exposure route. Natural therapies are relevant to health benefits and disease prevention. This study verified the effect of cadmium exposure on the ovaries of mice and the blueberry extract as a potential therapy. Blueberry therapy was effective in restoring reactive species levels and δ-aminolevulinate dehydratase activity, and partially improved the viability of cadmium-disrupted follicles. This therapy was not able to restore the 17 β-hydroxysteroid dehydrogenase activity. Extract HPLC evaluation indicated the presence of quercetin, quercitrin, isoquercetin, and ascorbic acid. Ascorbic acid was the major substance and its concentration was 620.24 µg/mL. Thus, cadmium accumulates in the ovaries of mice after subchronic exposure, inducing cellular damage, and the blueberry extract possesses antioxidant properties that could protect, at least in part, the ovarian tissue from cadmium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 188-196, 2017. © 2015 Wiley Periodicals, Inc.

Experimental and Modelling Investigations of the Coupled Elastoplastic Damage of a Quasi-brittle Rock

NASA Astrophysics Data System (ADS)

Zhang, Jiu-Chang

2018-02-01

Triaxial compression tests are conducted on a quasi-brittle rock, limestone. The analyses show that elastoplastic deformation is coupled with damage. Based on the experimental investigation, a coupled elastoplastic damage model is developed within the framework of irreversible thermodynamics. The coupling effects between the plastic and damage dissipations are described by introducing an isotropic damage variable into the elastic stiffness and yield criterion. The novelty of the model is in the description of the thermodynamic force associated with damage, which is formulated as a state function of both elastic and plastic strain energies. The latter gives a full consideration on the comprehensive effects of plastic strain and stress changing processes in rock material on the development of damage. The damage criterion and potential are constructed to determine the onset and evolution of damage variable. The return mapping algorithms of the coupled model are deduced for three different inelastic corrections. Comparisons between test data and numerical simulations show that the coupled elastoplastic damage model is capable of describing the main mechanical behaviours of the quasi-brittle rock.

Protective effects of skin permeable epidermal and fibroblast growth factor against ultraviolet-induced skin damage and human skin wrinkles.

PubMed

An, Jae Jin; Eum, Won Sik; Kwon, Hyuck Se; Koh, Jae Sook; Lee, Soo Yun; Baek, Ji Hwoon; Cho, Yong-Jun; Kim, Dae Won; Han, Kyu Huyng; Park, Jinseu; Jang, Sang Ho; Choi, Soo Young

2013-12-01

Epidermal and fibroblast growth factor (EGF and FGF1) proteins play an important role in the regeneration and proliferation of skin cells. EGF and FGF1 have considerable potential as possible therapeutic or cosmetic agents for the treatment of skin damage including wrinkles. Using protein transduction domains (PTD), we investigated whether PTD-EGF and FGF1 transduced into skin cells and tissue. Transduced proteins showed protective effects in a UV-induced skin damage model as well as against skin wrinkles. Transduced PTD-EGF and FGF1 proteins were detected by immunofluorescence and immunohistochemistry. The effects of PTD-EGF and FGF1 were examined by WST assay, Western blotting, immunohistochemistry, and skin wrinkle parameters. The PTD-EGF and FGF1 increased cell proliferation and collagen type 1 alpha 1 protein accumulation in skin tissue. Also, PTD-EGF and FGF1 inhibited UV-induced skin damage. Furthermore, topical application of PTD-EGF and FGF1 contained ampoules which were considered to improve the wrinkle parameters of human skin. These results show that PTD-EGF and FGF1 can be a potential therapeutic or cosmetic agent for skin damaged and injury including wrinkles and aging. © 2013 Wiley Periodicals, Inc.

Occupational exposure to antineoplastic agents induces a high level of chromosome damage. Lack of an effect of GST polymorphisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Testa, Antonella; Giachelia, Manuela; Palma, Selena

The aim of our study was to investigate whether occupational exposure to antineoplastic drugs (AND) resulted in genetic damage, possibly indicative of adverse health effects in the long term. We performed a chromosomal aberrations (CA) analysis in peripheral blood lymphocytes (PBL) of a group of 76 trained nurses occupationally exposed to AND. Furthermore, we analysed whether genetic polymorphisms in four metabolic genes of the glutathione S-transferase (GST) family involved in antineoplastic drugs detoxification (GSTM1, GSTT1, GSTP1, GSTA1) had any effect on the yield of chromosomal aberrations in nurses exposed to antineoplastic agents. The exposed group showed a very significant increasemore » of genetic damage (p < 0.0001) potentially indicative of an increased risk of cancer. Unexpectedly, besides the elevated level of chromatid-type aberrations usually related to exposure to chemical agents, we found also severe chromosome damages such as chromosome deletions and dicentric chromosomes, usually related to radiation exposure. No significant association was detected between all GSTs genotypes and chromosome damage. In conclusion, our data show how the occupational exposure to AND is associated to a potential cancer risk, suggesting that current prevention methods do not completely eliminate opportunities for exposure and supporting the need to improve the actual safety practices.« less

Effect of dietary supplementation with Spirulina platensis on Atrazine-induced oxidative stress- mediated hepatic damage and inflammation in the common carp (Cyprinus carpio L.).

PubMed

Toughan, Hosam; Khalil, Samah R; El-Ghoneimy, Ashraf Ahmed; Awad, Ashraf; Seddek, A Sh

2018-03-01

The present study evaluated the potential modulatory effect(s) of dietary supplementation with Spirulina platensis (SP) on Atrazine (ATZ)-induced oxidative stress and inflammation in common carp (Cyprinus carpio L.). Common carp was exposed to ATZ (428μg/L) and SP (1%), either alone or in combination, for 40 days. Subsequently, the treatment groups were evaluated for ATZ-induced oxidative stress-mediated hepatic damage and the potential antioxidant effect(s) of SP supplementation. The results indicated that ATZ exposure led to a significant increase in the oxidative stress as suggested by the increased levels of lipid and DNA oxidative damage markers and the significant decline of antioxidant status biomarkers. Further, a real-time PCR analysis of the liver tissues revealed that the ATZ exposure resulted in the significant modulation of the mRNA expression of cytokines involved in the inflammatory response pathway in the liver, such as Interleukin (IL)-1ß and IL-10. The expression of IL-1ß mRNA was up-regulated while that of IL-10 mRNA was down-regulated. The group subjected to supplementation with SP exhibited a significant decrease in ATZ-induced oxidative stress-mediated hepatotoxic and inflammatory responses; however, these did not attain the levels of the control group. Owing to its ability for protecting against ATZ-induced oxidative stress-mediated hepatic damage in carps, SP could be a potentially effective and promising candidate as a feed additive for carps in aquaculture. Copyright © 2017 Elsevier Inc. All rights reserved.

Dry olive leaf extract counteracts L-thyroxine-induced genotoxicity in human peripheral blood leukocytes in vitro.

PubMed

Topalović, Dijana Žukovec; Živković, Lada; Čabarkapa, Andrea; Djelić, Ninoslav; Bajić, Vladan; Dekanski, Dragana; Spremo-Potparević, Biljana

2015-01-01

The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger.

Dry Olive Leaf Extract Counteracts L-Thyroxine-Induced Genotoxicity in Human Peripheral Blood Leukocytes In Vitro

PubMed Central

Žukovec Topalović, Dijana; Živković, Lada; Čabarkapa, Andrea; Djelić, Ninoslav; Bajić, Vladan; Spremo-Potparević, Biljana

2015-01-01

The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger. PMID:25789081

Construction vibration attenuation with distance and its effect on the quality of early-age concrete.

DOT National Transportation Integrated Search

2011-06-01

Damage to structures due to vibrations from pile driving operations is of great concern to engineers. This : research has stemmed from the need to address potential damage to concrete-filled pipe piles and recently : placed concrete structures that c...

UVA-potentiated damage to calf thymus DNA by Fenton reaction system and protection by para-aminobenzoic acid.

PubMed

Shih, M K; Hu, M L

1996-03-01

Calf thymus DNA was irradiated with low-intensity UVA (main output at 365 nm, 2 mW cm-2 or 36 kJ m-2 for 30 min), and the role of metal ions, hydrogen peroxide and reactive oxygen species (ROS) was examined. DNA damage was measured as thiobarbituric acid-reactive substances (possibly from degradation of deoxyribose) and as changes in ethidium bromide-DNA fluorescence due to unwinding from strand breaks. Under the present experimental conditions, UVA alone or in the presence of H2O2 had no effect on DNA but slightly enhanced the damage by iron/EDTA. Ultraviolet A strongly enhanced DNA damage (ca four- to five-fold) by the Fenton reaction system (50 microM Fe2+/100 microM EDTA + 0.5 mM H2O2). The results suggest that the Fenton reaction system was "photosensitized" to damage DNA by low-intensity UVA radiation. The enhanced damage by UVA was attributed in part to the reduction of Fe3+ to Fe2+. Ultraviolet A had no effect when iron (ferric or ferrous) ions were replaced by Cu2+, Zn2+, Mn2+ or Cd2+. The ROS involved in the UVA-enhanced damage to DNA by the Fenton reagents were OH and, to a lesser extent, superoxide anions. The UVA-potentiated DNA damage by the Fenton reaction system was then used to examine the protective effect of para-aminobenzoate (PABA), a UVB-absorbing sunscreen that protects against photocarcinogenesis in hairless mice. The results show that PABA and mannitol dose-dependently inhibited the damage with concentrations required for 50% inhibition at 0.1 mM and 3 mM, respectively. The protection by PABA was attributed to its radical-scavenging ability because PABA does not absorb light in the UVA region. These findings may be relevant to the biological damage by UVA and suggest that PABA is useful in protection against photocarcinogenesis by wide-range UV radiation.

Herbs with potential nephrotoxic effects according to traditional Persian medicine: Review and assessment of scientific evidence.

PubMed

Kolangi, Fatemeh; Memariani, Zahra; Bozorgi, Mahboubeh; Mozaffarpur, Seyyed Ali; Mirzapour, Mohaddeseh

2018-04-03

The increased use of herbal remedies particularly in patients with kidney diseases indicated the importance of studies which focused on nephrotoxic plants. The present study aimed to review and assess the kidney-damaging herbs mentioned in the Persian medicine [PM] books. The main PM books were searched for nephrotoxic herbs and their relevant reformers traditionally proposed for preventing renal damage. PubMed, Scopus and Google Scholar were investigated for evaluation of the scientific evidence relating to the nephrotoxicity of herbs. A total of 64 plants with kidney damage potential and their reformer medicaments were recorded in 7 sources included in this review. Allium schoenoprasum and Marrubium vulgare were the most repeated and emphasized nephrotoxic plants in PM books, but there was not any relevant scientific evidence. Despite the lack of clinical studies, some evidence was found for 38% of plants that were related to renal damage. The most repeated reformers for reducing the renal side effects mainly consisted of gum tragacanth, gum Arabic, mastic gum, anise, jujube and honey and some evidence was found for their nephroprotective activities. The present study reviewed and assessed the herbs with adverse renal effects in the main PM books. Some evidence was in line with the potential nephrotoxicity of plants and their ‎reformers. Despite the lack of clinical research for evaluation of their renal damage, the herbs may be focused in term of their nephrotoxicity; and there is a need for further studies on the scientific basis of their nephrotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

IL-1β, in contrast to TNFα, is pivotal in blood-induced cartilage damage and is a potential target for therapy.

PubMed

van Vulpen, Lize F D; Schutgens, Roger E G; Coeleveld, Katja; Alsema, Els C; Roosendaal, Goris; Mastbergen, Simon C; Lafeber, Floris P J G

2015-11-05

Joint bleeding after (sports) trauma, after major joint surgery, or as seen in hemophilia in general leads to arthropathy. Joint degeneration is considered to result from the direct effects of blood components on cartilage and indirectly from synovial inflammation. Blood-provided proinflammatory cytokines trigger chondrocytes and induce the production of cartilage-degrading proteases. In the presence of erythrocyte-derived iron, cytokines stimulate radical formation in the vicinity of chondrocytes inducing apoptosis. To unravel the role of interleukin (IL) 1β and tumor necrosis factor (TNF) α in the pathogenesis of this blood-induced cartilage damage, the effect of antagonizing these cytokines was examined in human in vitro cultures. Addition of recombinant human IL-1β monoclonal antibody or IL-1 receptor antagonist resulted in a dose- and time-dependent protection of cartilage from blood-induced damage. In higher concentrations, almost complete normalization of cartilage matrix proteoglycan turnover was achieved. This was accompanied by a reduction in IL-1β and IL-6 production in whole blood cultures, whereas TNFα production remained unaffected. Interestingly, addition of a TNFα monoclonal antibody, although demonstrated to inhibit the direct (transient) effects of TNFα on cartilage, exhibited no effect on blood-induced (prolonged) cartilage damage. It is demonstrated that IL-1β is crucial in the development of blood-induced joint damage, whereas TNFα is not. This hierarchical position of IL-1β in blood-induced joint damage warrants studies on targeting IL-1β to potentially prevent joint degeneration after a joint bleed. © 2015 by The American Society of Hematology.

Repeated exposure of mouse dermal fibroblasts at a sub-cytotoxic dose of UVB leads to premature senescence: a robust model of cellular photoaging.

PubMed

Zeng, Ji-ping; Bi, Bo; Chen, Liang; Yang, Ping; Guo, Yu; Zhou, Yi-qun; Liu, Tian-yi

2014-01-01

Photoaging skin is due to accumulative effect of UV irradiation that mainly imposes its damage on dermal fibroblasts. To mimic the specific cellular responses invoked by long term effect of UVB, it is preferable to develop a photo-damaged model in vitro based on repeated UVB exposure instead of a single exposure. To develop a photo-damaged model of fibroblasts by repeated UVB exposure allowing for investigation of molecular mechanism underlying premature senescence and testing of potential anti-photoaging compounds. Mouse dermal fibroblasts (MDFs) at early passages (passages 1-3) were exposed to a series of 4 sub-cytotoxic dose of UVB. The senescent phenotypes were detected at 24 or 48h after the last irradiation including cell viability, ROS generation, mitochondrial membrane potential, cell cycle, production and degradation of extracellular matrix. Repeated exposure of UVB resulted in remarkable features of senescence. It effectively avoided the disadvantages of single dose such as induction of cell death rather than senescence, inadequate stress resulting in cellular self-rehabilitation. Our work confirms the possibility of detecting cellular machinery that mediates UVB damage to fibroblasts in vitro by repeated exposure, while the potential molecular mechanisms including cell surface receptors, protein kinase signal transduction pathways, and transcription factors remain to be further evaluated. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Spatial variability in oviposition damage by periodical cicadas in a fragmented landscape.

PubMed

Cook, William M; Holt, Robert D; Yao, Jin

2001-03-01

Effects of the periodical cicada (Magicicada spp.) on forest dynamics are poorly documented. A 1998 emergence of M. cassini in eastern Kansas led to colonization of a fragmented experimental landscape undergoing secondary succession. We hypothesized that per-tree rates of oviposition damage by cicadas would reflect: (1) distance from the source of the emergence, (2) patch size, and (3) local tree density. Ovipositing females displayed clear preferences for host species and damage incidence showed predictable spatial patterns. Two species (smooth sumac, Rhus glabra, and eastern red cedar, Juniperus virginiana) were rarely attacked, whereas others (rough-leaved dogwood, Cornus drummondii; slippery elm, Ulmus rubra; box elder, Acer negundo, and honey locust, Gleditsia triacanthos) were strongly attacked. The dominant early successional tree, dogwood, received on average the most attacks. As predicted, attacks per stem declined strongly with distance from the emergence source, and with local stem density (a "dilution" effect). Contrary to expectations, there were more attacks per stem on larger patches. Because ovipositing cicadas cut damaging slits in host tree branches, potentially affecting tree growth rate, competitive ability, and capacity to reproduce, cicada damage could potentially influence spatial variation in secondary succession.

Evaluating the effectiveness of flood damage mitigation measures by the application of Propensity Score Matching

NASA Astrophysics Data System (ADS)

Hudson, P.; Botzen, W. J. W.; Kreibich, H.; Bubeck, P.; Aerts, J. C. J. H.

2014-01-01

The employment of damage mitigation measures by individuals is an important component of integrated flood risk management. In order to promote efficient damage mitigation measures, accurate estimates of their damage mitigation potential are required. That is, for correctly assessing the damage mitigation measures' effectiveness from survey data, one needs to control for sources of bias. A biased estimate can occur if risk characteristics differ between individuals who have, or have not, implemented mitigation measures. This study removed this bias by applying an econometric evaluation technique called Propensity Score Matching to a survey of German households along along two major rivers major rivers that were flooded in 2002, 2005 and 2006. The application of this method detected substantial overestimates of mitigation measures' effectiveness if bias is not controlled for, ranging from nearly € 1700 to € 15 000 per measure. Bias-corrected effectiveness estimates of several mitigation measures show that these measures are still very effective since they prevent between € 6700-14 000 of flood damage. This study concludes with four main recommendations regarding how to better apply Propensity Score Matching in future studies, and makes several policy recommendations.

Evaluating the effectiveness of flood damage mitigation measures by the application of propensity score matching

NASA Astrophysics Data System (ADS)

Hudson, P.; Botzen, W. J. W.; Kreibich, H.; Bubeck, P.; Aerts, J. C. J. H.

2014-07-01

The employment of damage mitigation measures (DMMs) by individuals is an important component of integrated flood risk management. In order to promote efficient damage mitigation measures, accurate estimates of their damage mitigation potential are required. That is, for correctly assessing the damage mitigation measures' effectiveness from survey data, one needs to control for sources of bias. A biased estimate can occur if risk characteristics differ between individuals who have, or have not, implemented mitigation measures. This study removed this bias by applying an econometric evaluation technique called propensity score matching (PSM) to a survey of German households along three major rivers that were flooded in 2002, 2005, and 2006. The application of this method detected substantial overestimates of mitigation measures' effectiveness if bias is not controlled for, ranging from nearly EUR 1700 to 15 000 per measure. Bias-corrected effectiveness estimates of several mitigation measures show that these measures are still very effective since they prevent between EUR 6700 and 14 000 of flood damage per flood event. This study concludes with four main recommendations regarding how to better apply propensity score matching in future studies, and makes several policy recommendations.

Muscle damage and repeated bout effect following blood flow restricted exercise.

PubMed

Sieljacks, Peter; Matzon, Andreas; Wernbom, Mathias; Ringgaard, Steffen; Vissing, Kristian; Overgaard, Kristian

2016-03-01

Blood-flow restricted resistance exercise training (BFRE) is suggested to be effective in rehabilitation training, but more knowledge is required about its potential muscle damaging effects. Therefore, we investigated muscle-damaging effects of BFRE performed to failure and possible protective effects of previous bouts of BFRE or maximal eccentric exercise (ECC). Seventeen healthy young men were allocated into two groups completing two exercise bouts separated by 14 days. One group performed BFRE in both exercise bouts (BB). The other group performed ECC in the first and BFRE in the second bout. BFRE was performed to failure. Indicators of muscle damage were evaluated before and after exercise. The first bout in the BB group led to decrements in maximum isometric torque, and increases in muscle soreness, muscle water retention, and serum muscle protein concentrations after exercise. These changes were comparable in magnitude and time course to what was observed after first bout ECC. An attenuated response was observed in the repeated exercise bout in both groups. We conclude that unaccustomed single-bout BFRE performed to failure induces significant muscle damage. Additionally, both ECC and BFRE can precondition against muscle damage induced by a subsequent bout of BFRE.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Ootegem, Luc; SHERPPA — Ghent University; Verhofstadt, Elsy

Depth–damage-functions, relating the monetary flood damage to the depth of the inundation, are commonly used in the case of fluvial floods (floods caused by a river overflowing). We construct four multivariate damage models for pluvial floods (caused by extreme rainfall) by differentiating on the one hand between ground floor floods and basement floods and on the other hand between damage to residential buildings and damage to housing contents. We do not only take into account the effect of flood-depth on damage, but also incorporate the effects of non-hazard indicators (building characteristics, behavioural indicators and socio-economic variables). By using a Tobit-estimationmore » technique on identified victims of pluvial floods in Flanders (Belgium), we take into account the effect of cases of reported zero damage. Our results show that the flood depth is an important predictor of damage, but with a diverging impact between ground floor floods and basement floods. Also non-hazard indicators are important. For example being aware of the risk just before the water enters the building reduces content damage considerably, underlining the importance of warning systems and policy in this case of pluvial floods. - Highlights: • Prediction of damage of pluvial floods using also non-hazard information • We include ‘no damage cases’ using a Tobit model. • The damage of flood depth is stronger for ground floor than for basement floods. • Non-hazard indicators are especially important for content damage. • Potential gain of policies that increase awareness of flood risks.« less

Fire and explosion hazards to flora and fauna from explosives.

PubMed

Merrifield, R

2000-06-30

Deliberate or accidental initiation of explosives can produce a range of potentially damaging fire and explosion effects. Quantification of the consequences of such effects upon the surroundings, particularly on people and structures, has always been of paramount importance. Information on the effects on flora and fauna, however, is limited, with probably the weakest area lying with fragmentation of buildings and their effects on different small mammals. Information has been used here to gain an appreciation of the likely magnitude of the potential fire and explosion effects on flora and fauna. This is based on a number of broad assumptions and a variety of data sources including World War II bomb damage, experiments performed with animals 30-40 years ago, and more recent field trials on building break-up under explosive loading.

The combined effect of glass buffer strips and stitching on the damage tolerance of composites

NASA Technical Reports Server (NTRS)

Kullerd, Susan M.

1993-01-01

Recent research has demonstrated that through-the-thickness stitching provides major improvements in the damage tolerance of composite laminates loaded in compression. However, the brittle nature of polymer matrix composites makes them susceptible to damage propagation, requiring special material applications and designs to limit damage growth. Glass buffer strips, embedded within laminates, have shown the potential for improving the damage tolerance of unstitched composite laminates loaded in tension. The glass buffer strips, less stiff than the surrounding carbon fibers, arrest crack growth in composites under tensile loads. The present study investigates the damage tolerance characteristics of laminates that contain both stitching and glass buffer strips.

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Juanjuan; Zhang, Yu; Xu, Wentao, E-mail: xuwentaoboy@sina.com

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did notmore » affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by OTA in vitro.« less

Protective Effect of Baccharis trimera Extract on Acute Hepatic Injury in a Model of Inflammation Induced by Acetaminophen

PubMed Central

Pádua, Bruno da Cruz; Rossoni Júnior, Joamyr Victor; de Brito Magalhães, Cíntia Lopes; Chaves, Míriam Martins; Silva, Marcelo Eustáquio; Pedrosa, Maria Lucia; de Souza, Gustavo Henrique Bianco; Brandão, Geraldo Célio; Rodrigues, Ivanildes Vasconcelos; Lima, Wanderson Geraldo; Costa, Daniela Caldeira

2014-01-01

Background. Acetaminophen (APAP) is a commonly used analgesic and antipyretic. When administered in high doses, APAP is a clinical problem in the US and Europe, often resulting in severe liver injury and potentially acute liver failure. Studies have demonstrated that antioxidants and anti-inflammatory agents effectively protect against the acute hepatotoxicity induced by APAP overdose. Methods. The present study attempted to investigate the protective effect of B. trimera against APAP-induced hepatic damage in rats. The liver-function markers ALT and AST, biomarkers of oxidative stress, antioxidant parameters, and histopathological changes were examined. Results. The pretreatment with B. trimera attenuated serum activities of ALT and AST that were enhanced by administration of APAP. Furthermore, pretreatment with the extract decreases the activity of the enzyme SOD and increases the activity of catalase and the concentration of total glutathione. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by APAP. Conclusions. The hepatoprotective action of B. trimera extract may rely on its effect on reducing the oxidative stress caused by APAP-induced hepatic damage in a rat model. General Significance. These results make the extract of B. trimera a potential candidate drug capable of protecting the liver against damage caused by APAP overdose. PMID:25435714

Effects of seminal plasma and flash-freezing on DNA structure of stallion epididymal sperm exposed to different potentiators of DNA damage.

PubMed

Serafini, R; Varner, D D; Blanchard, T L; Teague, S R; LaCaze, K; Love, C C

2018-05-24

The tolerance of sperm DNA structure to seminal plasma and freezing conditions has both clinical and basic biologic relevance. In this study, fresh (FS) or flash-frozen (FZ) stallion epididymal sperm were exposed (SP + ) or unexposed (SP - ) to seminal plasma. Sperm were then evaluated to monitor the degree of change in DNA structure following challenge with chemical (dithiothreitol-DTT), oxidative (iron sulfate; FeSO 4 ) or enzymatic (DNase I) potentiators of DNA damage. For sperm not treated with potentiators (controls), there was no effect of SP treatment (SP - vs. SP + ) or freezing treatment (FS vs. FZ; non-significant) on measures of any DNA assays (i.e., 8-hydroxy, 2'deoxyguanosine [8OHdG], TUNEL, or sperm chromatin structure [SCSA] assays). Group FZ was more susceptible than Group FS to potentiators of DNA damage. Percent 8OHdG-positive sperm was higher in Group FZ/SP - treated with FeSO 4 than all other groups (P < 0.05). Percent TUNEL-positive sperm was similar among FZ/SP - groups treated with DTT, FeSO 4 , or DNase (non-significant) and was higher in these groups than all other treatments (P < 0.05). Percent COMP-α t was higher following treatment with DNase or DTT, as compared to their respective controls, regardless of prior exposure to SP (P < 0.05). Overall, sperm DNA structure was unaffected by seminal plasma or freezing treatment when samples were not exposed to potentiators of sperm DNA damage; however, marked differences were identified in DNA structure when sperm were challenged with chemical, oxidative or enzymatic treatments. These results highlight the importance of challenging DNA structure prior to analysis. The use of potentiators of DNA damage provided a model to evaluate sperm DNA structure following exposure of sperm to various experimental treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

Rapid Multi-Damage Identification for Health Monitoring of Laminated Composites Using Piezoelectric Wafer Sensor Arrays

PubMed Central

Si, Liang; Wang, Qian

2016-01-01

Through the use of the wave reflection from any damage in a structure, a Hilbert spectral analysis-based rapid multi-damage identification (HSA-RMDI) technique with piezoelectric wafer sensor arrays (PWSA) is developed to monitor and identify the presence, location and severity of damage in carbon fiber composite structures. The capability of the rapid multi-damage identification technique to extract and estimate hidden significant information from the collected data and to provide a high-resolution energy-time spectrum can be employed to successfully interpret the Lamb waves interactions with single/multiple damage. Nevertheless, to accomplish the precise positioning and effective quantification of multiple damage in a composite structure, two functional metrics from the RMDI technique are proposed and used in damage identification, which are the energy density metric and the energy time-phase shift metric. In the designed damage experimental tests, invisible damage to the naked eyes, especially delaminations, were detected in the leftward propagating waves as well as in the selected sensor responses, where the time-phase shift spectra could locate the multiple damage whereas the energy density spectra were used to quantify the multiple damage. The increasing damage was shown to follow a linear trend calculated by the RMDI technique. All damage cases considered showed completely the developed RMDI technique potential as an effective online damage inspection and assessment tool. PMID:27153070

Linear-quadratic dose kinetics or dose-dependent repair/misrepair

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braby, L.A.; Nelson, J.M.

1991-09-01

Models for the response of cells exposed to low LET radiation can be grouped into three general types on the basis of assumptions about the nature of the interaction which results in the shoulder of the survival curve. The three forms of interaction are (1) sublethal damage becoming lethal, (2) potentially lethal damage becoming irreparable, and (3) potentially lethal damage saturating'' a repair system. The effects that these three forms of interaction would have on the results of specific types of experiments are investigated. Comparisons with experimental results indicate that only the second type is significant in determining the responsemore » of typical cultured mammalian cells. 5 refs., 2 figs.« less

Critical and subcritical damage monitoring of bonded composite repairs using innovative non-destructive techniques

NASA Astrophysics Data System (ADS)

Grammatikos, S. A.; Kordatos, E. Z.; Aggelis, D. G.; Matikas, T. E.; Paipetis, A. S.

2012-04-01

Infrared Thermography (IrT) has been shown to be capable of detecting and monitoring service induced damage of repair composite structures. Full-field imaging, along with portability are the primary benefits of the thermographic technique. On-line lock-in thermography has been reported to successfully monitor damage propagation or/and stress concentration in composite coupons, as mechanical stresses in structures induce heat concentration phenomena around flaws. During mechanical fatigue, cyclic loading plays the role of the heating source and this allows for critical and subcritical damage identification and monitoring using thermography. The Electrical Potential Change Technique (EPCT) is a new method for damage identification and monitoring during loading. The measurement of electrical potential changes at specific points of Carbon Fiber Reinforced Polymers (CFRPs) under load are reported to enable the monitoring of strain or/and damage accumulation. Along with the aforementioned techniques Finally, Acoustic Emission (AE) method is well known to provide information about the location and type of damage. Damage accumulation due to cyclic loading imposes differentiation of certain parameters of AE like duration and energy. Within the scope of this study, infrared thermography is employed along with AE and EPCT methods in order to assess the integrity of bonded repair patches on composite substrates and to monitor critical and subcritical damage induced by the mechanical loading. The combined methodologies were effective in identifying damage initiation and propagation of bonded composite repairs.

Acute hydrodynamic damage induced by SPLITT fractionation and centrifugation in red blood cells.

PubMed

Urbina, Adriana; Godoy-Silva, Ruben; Hoyos, Mauricio; Camacho, Marcela

2016-05-01

Though blood bank processing traditionally employs centrifugation, new separation techniques may be appealing for large scale processes. Split-flow fractionation (SPLITT) is a family of techniques that separates in absence of labelling and uses very low flow rates and force fields, and is therefore expected to minimize cell damage. However, the hydrodynamic stress and possible consequent damaging effects of SPLITT fractionation have not been yet examined. The aim of this study was to investigate the hydrodynamic damage of SPLITT fractionation to human red blood cells, and to compare these effects with those induced by centrifugation. Peripheral whole blood samples were collected from healthy volunteers. Samples were diluted in a buffered saline solution, and were exposed to SPLITT fractionation (flow rates 1-10 ml/min) or centrifugation (100-1500 g) for 10 min. Cell viability, shape, diameter, mean corpuscular hemoglobin, and membrane potential were measured. Under the operating conditions employed, both SPLITT and centrifugation maintained cell viability above 98%, but resulted in significant sublethal damage, including echinocyte formation, decreased cell diameter, decreased mean corpuscular hemoglobin, and membrane hyperpolarization which was inhibited by EGTA. Wall shear stress and maximum energy dissipation rate showed significant correlation with lethal and sublethal damage. Our data do not support the assumption that SPLITT fractionation induces very low shear stress and is innocuous to cell function. Some changes in SPLITT channel design are suggested to minimize cell damage. Measurement of membrane potential and cell diameter could provide a new, reliable and convenient basis for evaluation of hydrodynamic effects on different cell models, allowing identification of optimal operating conditions on different scales. Copyright © 2016 Elsevier B.V. All rights reserved.

UVA-induced protection of skin through the induction of heme oxygenase-1.

PubMed

Xiang, Yuancai; Liu, Gang; Yang, Li; Zhong, Julia Li

2011-12-01

UVA (320-400 nm) and UVB (290-320 nm) are the major components of solar UV irradiation, which is associated with various pathological conditions. UVB causes direct damage to DNA of epidermal cells and is mainly responsible for erythema, immunosuppression, photoaging, and skin cancer. UVA has oxidizing properties that can cause damage or enhance UVB damaging effects on skin. On the other hand, UVA can also lead to high levels of heme oxygenase-1 (HO-1) expression of cells that can provide an antioxidant effect on skin as well as anti-inflammatory properties in mammals and rodents. Therefore, this review focuses on the potential protection of UVA wavebands for the skin immune response, instead of mechanisms that underlie UVA-induced damage. Also, the role of HO-1 in UVA-mediated protection against UVB-induced immunosuppression in skin will be summarized. Thus, this review facilitates further understanding of potential beneficial mechanisms of UVA irradiation, and using the longer UVA (UVA1, 340-400 nm) in combination with HO-1 for phototherapy and skin protection against sunlight exposure.

6-Gingerol prevents MEHP-induced DNA damage in human umbilical vein endothelia cells.

PubMed

Yang, G; Gao, X; Jiang, L; Sun, X; Liu, X; Chen, M; Yao, X; Sun, Q; Wang, S

2017-11-01

Mono (2-ethylhexyl) phthalate (MEHP) is the principal metabolite of di (2-etylhexyl) phthalate, which is widely used as a plasticizer, especially in medical devices. MEHP has toxic effects on cardiovascular system. The aim of this study was to investigate the possibility that 6-gingerol may inhibit the oxidative DNA damage of MEHP in human umbilical vein endothelial cells (HUVECs) and the potential mechanism. The comet assay was used to monitor DNA strand breaks. We have shown that 6-gingerol significantly reduced the DNA strand breaks caused by MEHP. MEHP increased the levels of reactive oxygen species and malondialdehyde, decreased the level of glutathione and activity of superoxide dismutase, and altered the mitochondrial membrane potential. In addition, DNA damage-associated proteins (p53 and p-Chk2 (T68)) were significantly increased by the treatment of MEHP. Those effects can all be protected by 6-gingerol. The results firmly indicate that 6-gingerol may have a strong protective ability against the DNA damage caused by MEHP in HUVECs, and the mechanism may relate to the antioxidant activity.

Ultrasonic Evaluation of Fatigue Damage

NASA Astrophysics Data System (ADS)

Bayer, P.; Singher, L.; Notea, A.

2004-02-01

Despite the fact that most engineers and designers are aware of fatigue, many severe breakdowns of industrial plant and machinery still occur due to fatigue. In effect, it's been estimated that fatigue causes at least 80% of the failures in modern engineering components. From an operational point of view, the detection of fatigue damage, preferably at a very early stage, is a critically important consideration in order to prevent possible catastrophic equipment failure and associated losses. This paper describes the investigation involving the use of ultrasonic waves as a potential tool for early detection of fatigue damage. The parameters investigated were the ultrasonic wave velocities (longitudinal and transverse waves) and attenuation coefficient before fatigue damage and after progressive stages of fatigue. Although comparatively small uncertainties were observed, the feasibility of utilizing the velocity of ultrasonic waves as a fatigue monitor was barely substantiated within actual research conditions. However, careful measurements of the ultrasonic attenuation parameter had demonstrated its potential to provide an early assessment of damage during fatigue.

Genotoxic effects of camphorquinone and DMT on human oral and intestinal cells.

PubMed

Wessels, Miriam; Rimkus, Julia; Leyhausen, Gabriele; Volk, Joachim; Geurtsen, Werner

2015-10-01

Released components of oral biomaterials can leach into the oral cavity and may subsequently reach the gastrointestinal tract. Camphorquinone (CQ) is the most common used photoinitiator in resinous restorative materials and is often combined with the co-initiator N,N-dimethyl-p-toluidine (DMT). It has been shown that CQ exerts cytotoxic effects, at least partially due to the generation of reactive oxygen species (ROS). Objective of this study was to examine the cytotoxic and genotoxic potential of CQ in human oral keratinocytes (OKF6/TERT2) and immortalized epithelial colorectal adenocarcinoma cells (Caco-2). Furthermore, the effects of visible-light irradiation and the co-initiator DMT were investigated as well as the generation of ROS, the potential protective effect of glutathione (GSH) and a recovery period of CQ-treated Caco-2 cells. The alkaline comet assay was used to determine DNA damage. Additionally, an enzyme modified comet assay was applied, which detects 7,8-dihydro-8-oxoguanine (8-oxoguanine), a reliable marker for oxidative stress. Our data revealed that high concentrations of CQ induced DNA lesions in OKF6/TERT2 cells. This DNA damage is at least partly caused by the generation of 8-oxoguanine. In addition, CQ and DMT increased ROS formation and induced DNA damage in Caco-2 cells. CQ-treatment resulted in generation of 8-oxoguanine. The antioxidant GSH efficiently prevented CQ-associated DNA damage. Furthermore, a recovery following CQ-treatment significantly reduced DNA damage. We conclude that CQ-induced DNA damage is caused by oxidative stress in oral and intestinal cells. These lesions can be prevented and possibly repaired by GSH-treatment and recovery of cells after the photoinitiator is removed from cultures. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Effects of Soil Type on the Damage Potential of Meloidogyne incognita on Soybean.

PubMed

Windham, G L; Barker, K R

1986-07-01

Effects of soil type on the reproduction and damage potential of Meloidogyne incognita on soybean, Glycine max (L.) Merr., were determined at five locations in North Carolina, including one site where plots with six soil types were established. M. incognita reproduced readily on a susceptible soybean cultivar in most soil types, with somewhat limited reproduction in muck soils. The relationship between initial population densities and yield varied among soil types and nematode populations. Yield losses were greatest in sandy and muck soil types, with less nematode damage occurring in the clay soil types. A North Carolina and a Georgia population of M. incognita differed greatly in their ability to reproduce on soybean and suppress growth. The North Carolina population had a moderate effect on yield in 1981 and only a slight effect in 1982. In contrast, a Georgia population severely limited soybean growth and yield at lower initial population densities in 1983, Initial population densities of the nematodes and physical and chemical edaphic factors accounted for much of the variation of soybean yield and nematode reproduction.

Cellular mechanisms of noise-induced hearing loss.

PubMed

Kurabi, Arwa; Keithley, Elizabeth M; Housley, Gary D; Ryan, Allen F; Wong, Ann C-Y

2017-06-01

Exposure to intense sound or noise can result in purely temporary threshold shift (TTS), or leave a residual permanent threshold shift (PTS) along with alterations in growth functions of auditory nerve output. Recent research has revealed a number of mechanisms that contribute to noise-induced hearing loss (NIHL). The principle cause of NIHL is damage to cochlear hair cells and associated synaptopathy. Contributions to TTS include reversible damage to hair cell (HC) stereocilia or synapses, while moderate TTS reflects protective purinergic hearing adaptation. PTS represents permanent damage to or loss of HCs and synapses. While the substrates of HC damage are complex, they include the accumulation of reactive oxygen species and the active stimulation of intracellular stress pathways, leading to programmed and/or necrotic cell death. Permanent damage to cochlear neurons can also contribute to the effects of NIHL, in addition to HC damage. These mechanisms have translational potential for pharmacological intervention and provide multiple opportunities to prevent HC damage or to rescue HCs and spiral ganglion neurons that have suffered injury. This paper reviews advances in our understanding of cellular mechanisms that contribute to NIHL and their potential for therapeutic manipulation. Published by Elsevier B.V.

AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

PubMed Central

Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

2016-01-01

Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

Numerical Implementation of a Multiple-ISV Thermodynamically-Based Work Potential Theory for Modeling Progressive Damage and Failure in Fiber-Reinforced Laminates

NASA Technical Reports Server (NTRS)

Pineda, Evan J.; Waas, Anthony M.

2011-01-01

A thermodynamically-based work potential theory for modeling progressive damage and failure in fiber-reinforced laminates is presented. The current, multiple-internal state variable (ISV) formulation, enhanced Schapery theory (EST), utilizes separate ISVs for modeling the effects of damage and failure. Damage is considered to be the effect of any structural changes in a material that manifest as pre-peak non-linearity in the stress versus strain response. Conversely, failure is taken to be the effect of the evolution of any mechanisms that results in post-peak strain softening. It is assumed that matrix microdamage is the dominant damage mechanism in continuous fiber-reinforced polymer matrix laminates, and its evolution is controlled with a single ISV. Three additional ISVs are introduced to account for failure due to mode I transverse cracking, mode II transverse cracking, and mode I axial failure. Typically, failure evolution (i.e., post-peak strain softening) results in pathologically mesh dependent solutions within a finite element method (FEM) setting. Therefore, consistent character element lengths are introduced into the formulation of the evolution of the three failure ISVs. Using the stationarity of the total work potential with respect to each ISV, a set of thermodynamically consistent evolution equations for the ISVs is derived. The theory is implemented into commercial FEM software. Objectivity of total energy dissipated during the failure process, with regards to refinements in the FEM mesh, is demonstrated. The model is also verified against experimental results from two laminated, T800/3900-2 panels containing a central notch and different fiber-orientation stacking sequences. Global load versus displacement, global load versus local strain gage data, and macroscopic failure paths obtained from the models are compared to the experiments.

A Thermodynamically-Based Mesh Objective Work Potential Theory for Predicting Intralaminar Progressive Damage and Failure in Fiber-Reinforced Laminates

NASA Technical Reports Server (NTRS)

Pineda, Evan J.; Waas, Anthony M.

2012-01-01

A thermodynamically-based work potential theory for modeling progressive damage and failure in fiber-reinforced laminates is presented. The current, multiple-internal state variable (ISV) formulation, enhanced Schapery theory (EST), utilizes separate ISVs for modeling the effects of damage and failure. Damage is considered to be the effect of any structural changes in a material that manifest as pre-peak non-linearity in the stress versus strain response. Conversely, failure is taken to be the effect of the evolution of any mechanisms that results in post-peak strain softening. It is assumed that matrix microdamage is the dominant damage mechanism in continuous fiber-reinforced polymer matrix laminates, and its evolution is controlled with a single ISV. Three additional ISVs are introduced to account for failure due to mode I transverse cracking, mode II transverse cracking, and mode I axial failure. Typically, failure evolution (i.e., post-peak strain softening) results in pathologically mesh dependent solutions within a finite element method (FEM) setting. Therefore, consistent character element lengths are introduced into the formulation of the evolution of the three failure ISVs. Using the stationarity of the total work potential with respect to each ISV, a set of thermodynamically consistent evolution equations for the ISVs is derived. The theory is implemented into commercial FEM software. Objectivity of total energy dissipated during the failure process, with regards to refinements in the FEM mesh, is demonstrated. The model is also verified against experimental results from two laminated, T800/3900-2 panels containing a central notch and different fiber-orientation stacking sequences. Global load versus displacement, global load versus local strain gage data, and macroscopic failure paths obtained from the models are compared to the experiments.

Uncertainty in flood damage estimates and its potential effect on investment decisions

NASA Astrophysics Data System (ADS)

Wagenaar, Dennis; de Bruijn, Karin; Bouwer, Laurens; de Moel, Hans

2015-04-01

This paper addresses the large differences that are found between damage estimates of different flood damage models. It explains how implicit assumptions in flood damage models can lead to large uncertainties in flood damage estimates. This explanation is used to quantify this uncertainty with a Monte Carlo Analysis. This Monte Carlo analysis uses a damage function library with 272 functions from 7 different flood damage models. This results in uncertainties in the order of magnitude of a factor 2 to 5. This uncertainty is typically larger for small water depths and for smaller flood events. The implications of the uncertainty in damage estimates for flood risk management are illustrated by a case study in which the economic optimal investment strategy for a dike segment in the Netherlands is determined. The case study shows that the uncertainty in flood damage estimates can lead to significant over- or under-investments.

Uncertainty in flood damage estimates and its potential effect on investment decisions

NASA Astrophysics Data System (ADS)

Wagenaar, D. J.; de Bruijn, K. M.; Bouwer, L. M.; De Moel, H.

2015-01-01

This paper addresses the large differences that are found between damage estimates of different flood damage models. It explains how implicit assumptions in flood damage models can lead to large uncertainties in flood damage estimates. This explanation is used to quantify this uncertainty with a Monte Carlo Analysis. As input the Monte Carlo analysis uses a damage function library with 272 functions from 7 different flood damage models. This results in uncertainties in the order of magnitude of a factor 2 to 5. The resulting uncertainty is typically larger for small water depths and for smaller flood events. The implications of the uncertainty in damage estimates for flood risk management are illustrated by a case study in which the economic optimal investment strategy for a dike segment in the Netherlands is determined. The case study shows that the uncertainty in flood damage estimates can lead to significant over- or under-investments.

Qualification and Testing of Quantum Cascade Lasers for Harsh Environments

NASA Astrophysics Data System (ADS)

Brauer, C. S.; Myers, T. L.; Cannon, B. D.; Anderson, C. G.; Crowther, B. G.; Hansen, S.

2014-12-01

Quantum cascade lasers (QCLs) offer the potential for the development of novel, laser-based instruments for both terrestrial and space applications. In order to withstand harsh conditions encountered in these environments, lasers must be robust, and rigorous testing is required before new systems can be utilized. A particular concern for space applications is the potential damage to laser performance caused by radiation exposure. While the effects of radiation exposure in diode lasers have been studied extensively, the effect on QCLs, which are fundamentally different from diode lasers, is not well known. We thus present work to quantify the performance of QCLs after exposure to moderate and high levels of radiation from different sources, including protons and gamma rays, to determine the effects of radiation damage.

Simulated Space Environment Effects on a Candidate Solar Sail Material

NASA Technical Reports Server (NTRS)

Kang, Jin Ho; Bryant, Robert G.; Wilkie, W. Keats; Wadsworth, Heather M.; Craven, Paul D.; Nehls, Mary K.; Vaughn, Jason A.

2017-01-01

For long duration missions of solar sails, the sail material needs to survive harsh space environments and the degradation of the sail material controls operational lifetime. Therefore, understanding the effects of the space environment on the sail membrane is essential for mission success. In this study, we investigated the effect of simulated space environment effects of ionizing radiation, thermal aging and simulated potential damage on mechanical, thermal and optical properties of a commercial off the shelf (COTS) polyester solar sail membrane to assess the degradation mechanisms on a feasible solar sail. The solar sail membrane was exposed to high energy electrons (about 70 keV and 10 nA/cm2), and the physical properties were characterized. After about 8.3 Grad dose, the tensile modulus, tensile strength and failure strain of the sail membrane decreased by about 20 95%. The aluminum reflective layer was damaged and partially delaminated but it did not show any significant change in solar absorbance or thermal emittance. The effect on mechanical properties of a pre-cracked sample, simulating potential impact damage of the sail membrane, as well as thermal aging effects on metallized PEN (polyethylene naphthalate) film will be discussed.

Genotoxic effects of environmental endocrine disruptors on the aquatic insect Chironomus riparius evaluated using the comet assay.

PubMed

Martínez-Paz, Pedro; Morales, Mónica; Martínez-Guitarte, José Luis; Morcillo, Gloria

2013-12-12

Genotoxicity is one of the most important toxic endpoints in chemical toxicity testing and environmental risk assessment. The aim of this study was to evaluate the genotoxic potential of various environmental pollutants frequently found in aquatic environments and characterized by their endocrine disrupting activity. Monitoring of DNA damage was undertaken after in vivo exposures of the aquatic larvae of the midge Chironomus riparius, a model organism that represents an abundant and ecologically relevant macroinvertebrate, widely used in freshwater toxicology. DNA-induced damage, resulting in DNA fragmentation, was quantified by the comet assay after short (24 h) and long (96 h) exposures to different concentrations of the selected toxicants: bisphenol A (BPA), nonylphenol (NP), pentachlorophenol (PCP), tributyltin (TBT) and triclosan (TCS). All five compounds were found to have genotoxic activity as demonstrated by significant increases in all the comet parameters (%DNA in tail, tail length, tail moment and Olive tail moment) at all tested concentrations. Persistent exposure did not increase the extent of DNA damage, except for TCS at the highest concentration, but generally there was a reduction in DNA damage thought to be associated with the induction of the detoxification processes and repairing mechanisms. Comparative analysis showed differences in the genotoxic potential between the chemicals, as well as significant time and concentration-dependent variations, which most likely reflect differences in the ability to repair DNA damage under the different treatments. The present report demonstrates the sensitivity of the benthic larvae of C. riparius to these environmental genotoxins suggesting its potential as biomonitor organism in freshwater ecosystems. The results obtained about the DNA-damaging potential of these environmental pollutants reinforce the need for additional studies on the genotoxicity of endocrine active substances that, by linking genotoxic activity to other biological responses, could provide further understanding of adverse effects in aquatic environments. Copyright © 2013 Elsevier B.V. All rights reserved.

Sensitivity of Asteroid Impact Risk to Uncertainty in Asteroid Properties and Entry Parameters

NASA Astrophysics Data System (ADS)

Wheeler, Lorien; Mathias, Donovan; Dotson, Jessie L.; NASA Asteroid Threat Assessment Project

2017-10-01

A central challenge in assessing the threat posed by asteroids striking Earth is the large amount of uncertainty inherent throughout all aspects of the problem. Many asteroid properties are not well characterized and can range widely from strong, dense, monolithic irons to loosely bound, highly porous rubble piles. Even for an object of known properties, the specific entry velocity, angle, and impact location can swing the potential consequence from no damage to causing millions of casualties. Due to the extreme rarity of large asteroid strikes, there are also large uncertainties in how different types of asteroids will interact with the atmosphere during entry, how readily they may break up or ablate, and how much surface damage will be caused by the resulting airbursts or impacts.In this work, we use our Probabilistic Asteroid Impact Risk (PAIR) model to investigate the sensitivity of asteroid impact damage to uncertainties in key asteroid properties, entry parameters, or modeling assumptions. The PAIR model combines physics-based analytic models of asteroid entry and damage in a probabilistic Monte Carlo framework to assess the risk posed by a wide range of potential impacts. The model samples from uncertainty distributions of asteroid properties and entry parameters to generate millions of specific impact cases, and models the atmospheric entry and damage for each case, including blast overpressure, thermal radiation, tsunami inundation, and global effects. To assess the risk sensitivity, we alternately fix and vary the different input parameters and compare the effect on the resulting range of damage produced. The goal of these studies is to help guide future efforts in asteroid characterization and model refinement by determining which properties most significantly affect the potential risk.

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

PubMed

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 potentially harmful or a useful event in radiotherapy. The elevation of damage to tumor cells not directly hit by radiation or the initiation of tumor cell differentiation may increase the therapeutic ratio. If, however, molecular species secreted by irradiated tumor cells in vivo damage neighboring normal cells (epithelial and endothelial cells, fibroblasts, or lymphocytes), the bystander effect would be harmful and could lead to increased side effects in normal tissue. This is especially important in modern radiotherapy, as 3D conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) are aimed at diminishing the radiation dose in normal tissues. Recent in vivo studies on animals indicate that bystander effects may appear in organs and tissues remote from the irradiated field and the extension of tissue damage seems to be tissue-type dependent. However, recent experimental results indicate that non-irradiated cells that are neighbors of irradiated cells may diminish radiation damage in the radiation-focused cells. Less is known about the bystander effect during fractionated irradiation. Thus the clinical implications of the bystander effect and its possible modification for radiotherapeutic usefulness is still under debate.

Effects of Weather Conditions on Oxidative Stress, Oxidative Damage, and Antioxidant Capacity in a Wild-Living Mammal, the European Badger (Meles meles).

PubMed

Bilham, Kirstin; Newman, Chris; Buesching, Christina D; Noonan, Michael J; Boyd, Amy; Smith, Adrian L; Macdonald, David W

Wild-living animals are subject to weather variability that may cause the generation of reactive oxygen species, resulting in oxidative stress and tissue damage, potentially driving demographic responses. Our 3-yr field study investigated the effects of seasonal weather conditions on biomarkers for oxidative stress, oxidative damage, and antioxidant defense in the European badger (Meles meles). We found age class effects: cubs were more susceptible to oxidative stress and oxidative damage than adults, especially very young cubs in the spring, when they also exhibited lower antioxidant biomarkers than adults. Although previous studies have found that intermediate spring and summer rainfall and warmer temperatures favor cub survival, counterintuitively these conditions were associated with more severe oxidative damage. Oxidative damage was high in cubs even when antioxidant biomarkers were high. In contrast, adult responses accorded with previous survival analyses. Wetter spring and summer conditions were associated with higher oxidative damage, but they were also associated with higher antioxidant biomarkers. Autumnal weather did not vary substantially from normative values, and thus effects were muted. Winter carryover effects were partially evident, with drier and milder conditions associated with greater oxidative damage in the following spring but also with higher antioxidant capacity. Plausibly, warmer conditions promoted more badger activity, with associated metabolic costs at a time of year when food supply is limited. Modeling biomarkers against projected climate change scenarios predicted greater future risks of oxidative damage, although not necessarily exceeding antioxidant capacity. This interdisciplinary approach demonstrates that individual adaptive physiological responses are associated with variation in natural environmental conditions.

Open Circuit Resonant Sensors for Composite Damage Detection and Diagnosis

NASA Technical Reports Server (NTRS)

Mielnik, John J., Jr.

2011-01-01

Under the Integrated Vehicle Health Management (IVHM) program work was begun to investigate the feasibility of sensor systems for detecting and diagnosing damage to aircraft composite structures and materials. Specific interest for this study was in damage initiated by environmental storm hazards and the direct effect of lightning strikes on the material structures of a composite aircraft in flight. A series of open circuit resonant sensors was designed, fabricated, characterized, and determined to be a potentially viable means for damage detection and diagnosis of composite materials. The results of this research and development effort are documented in this report.

Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats.

PubMed

Kasote, D M; Badhe, Y S; Zanwar, A A; Hegde, M V; Deshmukh, K K

2012-07-01

to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats. Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl(4) in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl(4) intoxication. Hepatic lipid peroxidation elevated by CCl(4) intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl(4) -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl(4) -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). EPC-BF possesses the significant hepatoprotective activity against CCl(4) induced liver damage, which could be mediated through increase in antioxidant defenses.

Biomolecular damage induced by ionizing radiation: the direct and indirect effects of low-energy electrons on DNA.

PubMed

Alizadeh, Elahe; Orlando, Thomas M; Sanche, Léon

2015-04-01

Many experimental and theoretical advances have recently allowed the study of direct and indirect effects of low-energy electrons (LEEs) on DNA damage. In an effort to explain how LEEs damage the human genome, researchers have focused efforts on LEE interactions with bacterial plasmids, DNA bases, sugar analogs, phosphate groups, and longer DNA moieties. Here, we summarize the current understanding of the fundamental mechanisms involved in LEE-induced damage of DNA and complex biomolecule films. Results obtained by several laboratories on films prepared and analyzed by different methods and irradiated with different electron-beam current densities and fluencies are presented. Despite varied conditions (e.g., film thicknesses and morphologies, intrinsic water content, substrate interactions, and extrinsic atmospheric compositions), comparisons show a striking resemblance in the types of damage produced and their yield functions. The potential of controlling this damage using molecular and nanoparticle targets with high LEE yields in targeted radiation-based cancer therapies is also discussed.

Electromagnetic pulse (EMP), Part I: Effects on field medical equipment.

PubMed

Vandre, R H; Klebers, J; Tesche, F M; Blanchard, J P

1993-04-01

The electromagnetic pulse (EMP) from a high-altitude nuclear detonation has the potential to cover an area as large as the continental United States with damaging levels of EMP radiation. In this study, two of seven items of medical equipment were damaged by an EMP simulator. Computer circuit analysis of 17 different items showed that 11 of the 17 items would be damaged by current surges on the power cords, while two would be damaged by current surges on external leads. This research showed that a field commander can expect approximately 65% of his electronic medical equipment to be damaged by a single nuclear detonation as far as 2,200 km away.

Numerical Predictions of Damage and Failure in Carbon Fiber Reinforced Laminates Using a Thermodynamically-Based Work Potential Theory

NASA Technical Reports Server (NTRS)

Pineda, Evan Jorge; Waas, Anthony M.

2013-01-01

A thermodynamically-based work potential theory for modeling progressive damage and failure in fiber-reinforced laminates is presented. The current, multiple-internal state variable (ISV) formulation, referred to as enhanced Schapery theory (EST), utilizes separate ISVs for modeling the effects of damage and failure. Consistent characteristic lengths are introduced into the formulation to govern the evolution of the failure ISVs. Using the stationarity of the total work potential with respect to each ISV, a set of thermodynamically consistent evolution equations for the ISVs are derived. The theory is implemented into a commercial finite element code. The model is verified against experimental results from two laminated, T800/3900-2 panels containing a central notch and different fiber-orientation stacking sequences. Global load versus displacement, global load versus local strain gage data, and macroscopic failure paths obtained from the models are compared against the experimental results.

Effects of bear damage on Douglas-fir lumber recovery

Treesearch

Eini C. Lowell; Dennis Dykstra; George McFadden

2009-01-01

Bear activily resulting in injury to Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco) trees has been documented as early as the mid-1850s in the Pacific Northwest. The study reported in this article was designed to help managers decide whether the common practice of removing the damaged but potentially valuable butt section of the bottom log and...

Predicting spillover risk to non-target plants pre-release: Bikasha collaris a potential biological control agent of Chinese tallowtree (Triadica sebifera)

USDA-ARS?s Scientific Manuscript database

Quarantine host range tests accurately predict direct risk of biological control agents to non-target species. However, a well-known indirect effect of biological control of weeds releases is spillover damage to non-target species. Spillover damage may occur when the population of agents achieves ou...

Simulated Space Environment Effects on a Candidate Solar Sail Material

NASA Technical Reports Server (NTRS)

Kang, Jin Ho; Bryant, Robert G.; Wilkie, W. Keats; Wadsworth, Heather M.; Craven, Paul D.; Nehls, Mary K.; Vaughn, Jason A.

2017-01-01

For long duration missions of solar sail vehicles, the sail material needs to survive the harsh space environment as the degradation of the sail material determines its operational lifetime. Therefore, understanding the effects of the space environment on the sail membrane is essential for mission success. In this study, the effect of simulated space environments of ionizing radiation and thermal aging were investigated. In order to assess some of the potential damage effects on the mechanical, thermal and optical properties of a commercial off the shelf (COTS) polyester solar sail membrane. The solar sail membrane was exposed to high energy electrons [about 70 keV and 10 nA/cm(exp. 2)], and the physical properties were characterized. After about 8.3 Grad dose, the tensile modulus, tensile strength and failure strain of the sail membrane decreased by 20 to 95%. The aluminum reflective layer was damaged and partially delaminated but it did not show any significant change in solar absorbance or thermal emittance. The mechanical properties of a precracked sample, simulating potential impact damage of the sail membrane, as well as thermal aging effects on metallized PEN (polyethylene naphthalate) film, will be discussed.

Stochastic output error vibration-based damage detection and assessment in structures under earthquake excitation

NASA Astrophysics Data System (ADS)

Sakellariou, J. S.; Fassois, S. D.

2006-11-01

A stochastic output error (OE) vibration-based methodology for damage detection and assessment (localization and quantification) in structures under earthquake excitation is introduced. The methodology is intended for assessing the state of a structure following potential damage occurrence by exploiting vibration signal measurements produced by low-level earthquake excitations. It is based upon (a) stochastic OE model identification, (b) statistical hypothesis testing procedures for damage detection, and (c) a geometric method (GM) for damage assessment. The methodology's advantages include the effective use of the non-stationary and limited duration earthquake excitation, the handling of stochastic uncertainties, the tackling of the damage localization and quantification subproblems, the use of "small" size, simple and partial (in both the spatial and frequency bandwidth senses) identified OE-type models, and the use of a minimal number of measured vibration signals. Its feasibility and effectiveness are assessed via Monte Carlo experiments employing a simple simulation model of a 6 storey building. It is demonstrated that damage levels of 5% and 20% reduction in a storey's stiffness characteristics may be properly detected and assessed using noise-corrupted vibration signals.

Dimethyl sulfoxide damages mitochondrial integrity and membrane potential in cultured astrocytes.

PubMed

Yuan, Chan; Gao, Junying; Guo, Jichao; Bai, Lei; Marshall, Charles; Cai, Zhiyou; Wang, Linmei; Xiao, Ming

2014-01-01

Dimethyl sulfoxide (DMSO) is a polar organic solvent that is used to dissolve neuroprotective or neurotoxic agents in neuroscience research. However, DMSO itself also has pharmacological and pathological effects on the nervous system. Astrocytes play a central role in maintaining brain homeostasis, but the effect and mechanism of DMSO on astrocytes has not been studied. The present study showed that exposure of astrocyte cultures to 1% DMSO for 24 h did not significantly affect cell survival, but decreased cell viability and glial glutamate transporter expression, and caused mitochondrial swelling, membrane potential impairment and reactive oxygen species production, and subsequent cytochrome c release and caspase-3 activation. DMSO at concentrations of 5% significantly inhibited cell variability and promoted apoptosis of astrocytes, accompanied with more severe mitochondrial damage. These results suggest that mitochondrial impairment is a primary event in DMSO-induced astrocyte toxicity. The potential cytotoxic effects on astrocytes need to be carefully considered during investigating neuroprotective or neurotoxic effects of hydrophobic agents dissolved by DMSO.

Dimethyl Sulfoxide Damages Mitochondrial Integrity and Membrane Potential in Cultured Astrocytes

PubMed Central

Yuan, Chan; Gao, Junying; Guo, Jichao; Bai, Lei; Marshall, Charles; Cai, Zhiyou; Wang, Linmei; Xiao, Ming

2014-01-01

Dimethyl sulfoxide (DMSO) is a polar organic solvent that is used to dissolve neuroprotective or neurotoxic agents in neuroscience research. However, DMSO itself also has pharmacological and pathological effects on the nervous system. Astrocytes play a central role in maintaining brain homeostasis, but the effect and mechanism of DMSO on astrocytes has not been studied. The present study showed that exposure of astrocyte cultures to 1% DMSO for 24 h did not significantly affect cell survival, but decreased cell viability and glial glutamate transporter expression, and caused mitochondrial swelling, membrane potential impairment and reactive oxygen species production, and subsequent cytochrome c release and caspase-3 activation. DMSO at concentrations of 5% significantly inhibited cell variability and promoted apoptosis of astrocytes, accompanied with more severe mitochondrial damage. These results suggest that mitochondrial impairment is a primary event in DMSO-induced astrocyte toxicity. The potential cytotoxic effects on astrocytes need to be carefully considered during investigating neuroprotective or neurotoxic effects of hydrophobic agents dissolved by DMSO. PMID:25238609

Ethylhexylglycerin Impairs Membrane Integrity and Enhances the Lethal Effect of Phenoxyethanol

PubMed Central

Langsrud, Solveig; Steinhauer, Katrin; Lüthje, Sonja; Weber, Klaus; Goroncy-Bermes, Peter; Holck, Askild L.

2016-01-01

Preservatives are added to cosmetics to protect the consumers from infections and prevent product spoilage. The concentration of preservatives should be kept as low as possible and this can be achieved by adding potentiating agents. The aim of the study was to investigate the mechanisms behind potentiation of the bactericidal effect of a commonly used preservative, 2-phenoxyethanol (PE), by the potentiating agent ethylhexylglycerin (EHG). Sub-lethal concentrations of EHG (0.075%) and PE (0.675%) in combination led to rapid killing of E. coli (> 5 log reduction of cfu after 30 min), leakage of cellular constituents, disruption of the energy metabolism, morphological deformities of cells and condensation of DNA. Used alone, EHG disrupted the membrane integrity even at low concentrations. In conclusion, sub-lethal concentrations of EHG potentiate the effect of PE through damage of the cell membrane integrity. Thus, adding EHG to PE in a 1:9 ratio has a similar effect on membrane damage and bacterial viability as doubling the concentration of PE. This study provides insight about the mechanism of action of a strong potentiating agent, EHG, which is commonly used in cosmetics together with PE. PMID:27783695

Electric arc discharge damage to ion thruster grids

NASA Technical Reports Server (NTRS)

Beebe, D. D.; Nakanishi, S.; Finke, R. C.

1974-01-01

Arcs representative of those occurring between the grids of a mercury ion thruster were simulated. Parameters affecting an arc and the resulting damage were studied. The parameters investigated were arc energy, arc duration, and grid geometry. Arc attenuation techniques were also investigated. Potentially serious damage occurred at all energy levels representative of actual thruster operating conditions. Of the grids tested, the lowest open-area configuration sustained the least damage for given conditions. At a fixed energy level a long duration discharge caused greater damage than a short discharge. Attenuation of arc current using various impedances proved to be effective in reducing arc damage. Faults were also deliberately caused using chips of sputtered materials formed during the operation of an actual thruster. These faults were cleared with no serious grid damage resulting using the principles and methods developed in this study.

Chemotherapeutic-Induced Cardiovascular Dysfunction: Physiological Effects, Early Detection—The Role of Telomerase to Counteract Mitochondrial Defects and Oxidative Stress

PubMed Central

Quryshi, Nabeel; Norwood Toro, Laura E.; Ait-Aissa, Karima; Kong, Amanda; Beyer, Andreas M.

2018-01-01

Although chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (mtDNA) that can lead to oxidative stress-induced cardiovascular apoptosis. Therefore, oncologists and cardiologists maintain a network of communication when dealing with patients during treatment in order to treat and prevent chemotherapy-induced cardiovascular damage; however, there is a need to discover more accurate biomarkers and therapeutics to combat and predict the onset of cardiovascular side effects. Telomerase, originally discovered to promote cellular proliferation, has recently emerged as a potential mechanism to counteract mitochondrial defects and restore healthy mitochondrial vascular phenotypes. This review details mechanisms currently used to assess cardiovascular damage, such as C-reactive protein (CRP) and troponin levels, while also unearthing recently researched biomarkers, including circulating mtDNA, telomere length and telomerase activity. Further, we explore a potential role of telomerase in the mitigation of mitochondrial reactive oxygen species and maintenance of mtDNA integrity. Telomerase activity presents a promising indicator for the early detection and treatment of chemotherapy-derived cardiac damage. PMID:29534446

Trail impacts in Sagarmatha (Mt. Everest) National Park, Nepal: a logistic regression analysis.

PubMed

Nepal, S K

2003-09-01

A trail study was conducted in the Sagarmatha (Mt. Everest) National Park, Nepal, during 1997-1998. Based on that study, this paper examines the spatial variability of trail conditions and analyzes factors that influence trail conditions. Logistic regression (multinomial logit model) is applied to examine the influence of use and environmental factors on trail conditions. The assessment of trail conditions is based on a four-class rating system: (class I, very little damaged; class II, moderately damaged, class III, heavily damaged; and class IV, severely damaged). Wald statistics and a model classification table have been used for data interpretation. Results indicate that altitude, trail gradient, hazard potential, and vegetation type are positively associated with trail condition. Trails are more degraded at higher altitude, on steep gradients, in areas with natural hazard potential, and within shrub/grassland zones. Strong correlations between high levels of trail degradation and higher frequencies of visitors and lodges were found. A detailed analysis of environmental and use factors could provide valuable information to park managers in their decisions about trail design, layout and maintenance, and efficient and effective visitor management strategies. Comparable studies on high alpine environments are needed to predict precisely the effects of topographic and climatic extremes. More refined approaches and experimental methods are necessary to control the effects of environmental factors.

Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells.

PubMed

Kalghatgi, Sameer; Spina, Catherine S; Costello, James C; Liesa, Marc; Morones-Ramirez, J Ruben; Slomovic, Shimyn; Molina, Anthony; Shirihai, Orian S; Collins, James J

2013-07-03

Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics-quinolones, aminoglycosides, and β-lactams-cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic-induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people.

Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells

PubMed Central

Costello, James C.; Liesa, Marc; Morones-Ramirez, J Ruben; Slomovic, Shimyn; Molina, Anthony; Shirihai, Orian S.; Collins, James J.

2013-01-01

Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics—quinolones, aminoglycosides, and β-lactams—cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic–induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-L-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people. PMID:23825301

Modulation of DNA-Induced Damage and Repair Capacity in Humans after Dietary Intervention with Lutein-Enriched Fermented Milk

PubMed Central

Herrero-Barbudo, Carmen; Soldevilla, Beatriz; Pérez-Sacristán, Belén; Blanco-Navarro, Inmaculada; Herrera, Mercedes; Granado-Lorencio, Fernando; Domínguez, Gemma

2013-01-01

Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers. PMID:24040187

Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.

PubMed

Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

2014-08-01

Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.

Damage indication in smart structures using modal effective electromechanical coupling coefficients

NASA Astrophysics Data System (ADS)

Al-Ajmi, M. A.; Benjeddou, A.

2008-06-01

This work explores the use, in structural health monitoring, of the so-called modal effective electromechanical coupling coefficient (EMCC) as a damage indicator for structures with failures such as cracks. For this purpose, a discrete layered finite element (FE) model for smart beams is proposed and applied to short-circuit (SC) and open-circuit (OC) modal analyses of healthy and damaged (cracked) cantilever beams with symmetrically surface-bonded piezoelectric patches. Focus is made here on enhancing the electrical behavior modeling by introducing a quadratic bubble function in the electric potential through-the-thickness approximation. Therefore, the corresponding higher-order potential (HOP) degree of freedom is condensed at the ply level, leading to a passive stiffening effect (SE) similar to the so-called higher-order induced potential (HIP); then the physical equipotential (EP) electrode effect, often neglected in the piezoelectric FE literature, is here implemented after the electrodes' FE assembly. After its validation against available analytical and experimental results, the proposed piezoelectric FE is used for parametric analyses of SC-based and OC-based EMCC change factors (ECFs) and frequency change factors (FCFs) in terms of the crack depth and position ratios. It was found that the EP effect was more influential on the ECF than the SE. However, for the FCFs, the EP effect was influential only when it is defined from the OC frequencies. Finally, the ECFs were found to be higher than the FCFs, in particular for higher modes.

Anthocyanin-rich blackberry extract suppresses the DNA-damaging properties of topoisomerase I and II poisons in colon carcinoma cells.

PubMed

Esselen, Melanie; Boettler, Ute; Teller, Nicole; Bachler, Simone; Hutter, Melanie; Rufer, Corinna E; Skrbek, Susanne; Marko, Doris

2011-07-13

In the present study, we addressed the question whether cyanidin-3-glucoside (C3G) or complex C3G-rich blackberry extracts affect human topoisomerases with special emphasis on the contribution of the potential degradation products phloroglucinol aldehyde (PGA) and protocatechuic acid (PCA). In HT29 colon carcinoma cells a C3G-rich blackberry extract suppressed camptothecin- (CPT-) or doxorubicin- (DOX-) induced stabilization of the covalent DNA-topoisomerase intermediate, thus antagonizing the effects of these classical topoisomerase poisons on DNA integrity. As a single compound, C3G (100 μM) decreased the DNA-damaging effects of CPT as well, but did not significantly affect those induced by DOX. At the highest applied concentration (100 μM), cyanidin protected DNA from CPT- and DOX-induced damage. Earlier reports on DNA-damaging properties of cyanidin were found to result most likely from the formation of hydrogen peroxide as an artifact in the cell culture medium when the incubation was performed in the absence of catalase. The suppression of hydrogen peroxide accumulation, achieved by the addition of catalase, demonstrated that cyanidin does not exhibit DNA-damaging properties in HT29 cells (up to 100 μM). The observed effects on topoisomerase interference and DNA protection against CPT or DOX were clearly limited to the parent compound and were not observed for the potential cyanidin degradation products PGA and PCA.

Evaluation of free radical scavenging capacity and antioxidative damage effect of resveratrol-nanostructured lipid carriers

NASA Astrophysics Data System (ADS)

Jin, Ju; Shi, Fan; Li, Qiu-wen; Li, Pei-shan; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

2016-03-01

Cellular damage induced by free-radicals like reactive oxygen species has been implicated in several diseases. 2, 2-azobis(2-amidino-propane) dihydrochloride(AAPH) generates two potent ROS capable of inducing lipid peroxidation: alkoxy radical(RO-) and peroxy radical(ROO-). These radicals are similar to those that are physiologically active and thus might initiate a cascade of intracellular toxic events leading to oxidation, lipid peroxidation, DNA damage and subsequent cell death. Hence naturally anti-oxidant play a vital role in combating these conditions. In this study, resveratrol loaded nanostructured lipid carriers (Res-NLC) was prepared by hot melting and then high pressure homogenization technique. The effects of Res-NLC on free radical scavenging capacity and antioxidative damage is investigated. The particle size and zeta potential of Res-NLC were 139.3 ± 1.7 nm and -11.21 ± 0.41 mV, respectively. By free radical scavenging assays, the IC50 value of Res-NLC were 19.25, 5.29 μg/mL with DPPH, ABTS assay respectively, and 0.161 mg ferrous sulfate/1 mg Res-NLC with FRAP assay; and by AAPH-induced oxidative injury cell model assay, Res-NLC showed the strong protective effect against the human liver tumor HepG2 cell oxidative stress damage. These results indicated that the antioxidant properties of Res-NLC hold great potential used as an alternative to more toxic synthetic antioxidants as an additive in food, cosmetic and pharmaceutical preparations for the oxidative diseases treatment.

Genotoxic effect of ethacrynic acid and impact of antioxidants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, William M.; Hoffman, Jared D.; Loo, George, E-mail: g_loo@uncg.edu

It is known that ethacrynic acid (EA) decreases the intracellular levels of glutathione. Whether the anticipated oxidative stress affects the structural integrity of DNA is unknown. Therefore, DNA damage was assessed in EA-treated HCT116 cells, and the impact of several antioxidants was also determined. EA caused both concentration-dependent and time-dependent DNA damage that eventually resulted in cell death. Unexpectedly, the DNA damage caused by EA was intensified by either ascorbic acid or trolox. In contrast, EA-induced DNA damage was reduced by N-acetylcysteine and by the iron chelator, deferoxamine. In elucidating the DNA damage, it was determined that EA increased themore » production of reactive oxygen species, which was inhibited by N-acetylcysteine and deferoxamine but not by ascorbic acid and trolox. Also, EA decreased glutathione levels, which were inhibited by N-acetylcysteine. But, ascorbic acid, trolox, and deferoxamine neither inhibited nor enhanced the capacity of EA to decrease glutathione. Interestingly, the glutathione synthesis inhibitor, buthionine sulfoxime, lowered glutathione to a similar degree as EA, but no noticeable DNA damage was found. Nevertheless, buthionine sulfoxime potentiated the glutathione-lowering effect of EA and intensified the DNA damage caused by EA. Additionally, in examining redox-sensitive stress gene expression, it was found that EA increased HO-1, GADD153, and p21mRNA expression, in association with increased nuclear localization of Nrf-2 and p53 proteins. In contrast to ascorbic acid, trolox, and deferoxamine, N-acetylcysteine suppressed the EA-induced upregulation of GADD153, although not of HO-1. Overall, it is concluded that EA has genotoxic properties that can be amplified by certain antioxidants. - Highlights: • Ethacrynic acid (EA) caused cellular DNA damage. • EA-induced DNA damage was potentiated by ascorbic acid or trolox. • EA increased ROS production, not inhibited by ascorbic acid or trolox. • EA decreased glutathione levels, not prevented by ascorbic acid or trolox. • Buthionine sulfoxime intensified the DNA damage caused by EA.« less

In vitro and in vivo photoprotective/photochemopreventive potential of Garcinia brasiliensis epicarp extract.

PubMed

Figueiredo, Sônia Aparecida; Vilela, Fernanda Maria Pinto; da Silva, Claudinei Alves; Cunha, Thiago Mattar; Dos Santos, Marcelo Henrique; Fonseca, Maria José Vieira

2014-02-05

The damaging effects of sunlight to the skin has triggered studies that involve the synthesis and extraction of organic compounds from natural sources that can absorb UV radiation, and studies on polyphenolic compounds with antioxidant and anti-inflammatory properties that can be used as photochemopreventive agents for reducing skin damage. We investigated the in vitro and in vivo photoprotective/photochemopreventive potential of Garcinia brasiliensis epicarp extract (GbEE). We evaluated the cell viability of L929 fibroblasts after UVB exposure using a quartz plate containing the extract solution or the GbEE formulation. The in vivo photoprotective effect of the GbEE formulation was evaluated by measuring the UVB damage-induced decrease in endogenous reduced glutathione (GSH), the increase in myeloperoxidase (MPO) activity and secretion of cytokines IL-1β and TNF-α. The in vitro methodology using fibroblasts showed that the photoprotective properties of the GbEE solutions and 10% GbEE formulation were similar to the commercial sunscreen (SPF-15). In vivo results demonstrated of the GbEE formulation in decreasing UVB induced-damage such as GSH depletion, an increased in MPO activity and secretion of cytokines IL-1β and TNF-α. The results showed that the extract has great potential for use as a sunscreen in topical formulations in addition to UV filters. Copyright © 2014 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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.

Tocotrienols, health and ageing: A systematic review.

PubMed

Georgousopoulou, Ekavi N; Panagiotakos, Demosthenes B; Mellor, Duane D; Naumovski, Nenad

2017-01-01

A systematic review of studies was undertaken to evaluate the potential effect of intake of tocotrienols or circulating levels of tocotrienols on parameters associated with successful ageing, specifically in relation to cognitive function, osteoporosis and DNA damage. Following PRISMA guidelines a systematic review of epidemiological observational studies and clinical trials was undertaken. Inclusion criteria included all English language publications in the databases PubMed and Scopus, through to the end of July 2016. Evidence from prospective and case-control studies suggested that increased blood levels of tocotrienols were associated with favorable cognitive function outcomes. A clinical trial of tocotrienol supplementation for 6 months suggested a beneficial effect of intake on DNA damage rates, but only in elderly people. Regarding osteoporosis, only in vitro studies with cultures of human bone cells were identified, and these demonstrated significant inhibition of osteoclast activity and promotion of osteoblast activity. Research in middle-aged and elderly humans suggests that tocotrienols have a potential beneficial anti-ageing action with respect to cognitive impairment and DNA damage. Clinical trials are required to elucidate these effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Genomic damage induced by 1-MHz ultrasound in vitro.

PubMed

Udroiu, Ion; Marinaccio, Jessica; Bedini, Angelico; Giliberti, Claudia; Palomba, Raffaele; Sgura, Antonella

2018-01-01

Genotoxic effects of therapeutic ultrasound are poorly documented, when compared with the wide use of this physical agent. The aim of this work was to investigate the clastogenic and aneugenic potential of 1 MHz ultrasound, employing intensities (200 and 300 mW/cm 2 ) above the cavitational threshold, but in the range of those normally used in therapeutics. Both normal fibroblasts (AG01522) and tumoral cells (MCF-7) were sonicated. While no effects on viability were noted, significant increases of CREST-negative micronuclei (indicative of clastogenesis) and CREST-positive micronuclei (indicative of aneuploidy) were detected. Clastogenesis was confirmed by increases of γ-H2AX foci, while increases of spindle anomalies confirmed the induction of aneuploidy. Our results confirm previous works that showed ultrasound-induced DNA breakage. Moreover, our experiments show that the known effect of ultrasound-induced damage to microtubules is also able to damage the mitotic spindle and induce aneuploidy. On the overall, this work highlights the importance to further investigate the potential risks related to therapeutics US. Environ. Mol. Mutagen. 59:60-68, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Vernal freeze damage and genetic variation alter tree growth, chemistry, and insect interactions.

PubMed

Rubert-Nason, Kennedy F; Couture, John J; Gryzmala, Elizabeth A; Townsend, Philip A; Lindroth, Richard L

2017-11-01

Anticipated consequences of climate change in temperate regions include early spring warmup punctuated by intermittent hard freezes. Warm weather accelerates leaf flush in perennial woody species, potentially exposing vulnerable young tissues to damaging frosts. We employed a 2 × 6 randomized factorial design to examine how the interplay of vernal (springtime) freeze damage and genetic variation in a hardwood species (Populus tremuloides) influences tree growth, phytochemistry, and interactions with an insect herbivore (Chaitophorus stevensis). Acute effects of freezing included defoliation and mortality. Surviving trees exhibited reduced growth and altered biomass distribution. Reflushed leaves on these trees had lower mass per area, lower lignin concentrations, and higher nitrogen concentrations, altered chemical defence profiles, and supported faster aphid population growth. Many effects varied among plant genotypes and were related with herbivore performance. This study suggests that a single damaging vernal freeze event can alter tree-insect interactions through effects on plant growth and chemistry. Differential responses of various genotypes to freeze damage suggest that more frequent vernal freeze events could also influence natural selection, favouring trees with greater freeze hardiness, and more resistance or tolerance to herbivores following damage. © 2017 John Wiley & Sons Ltd.

Effects of a Mangifera indica L. stem bark extract and mangiferin on radiation-induced DNA damage in human lymphocytes and lymphoblastoid cells.

PubMed

Rodeiro, I; Delgado, R; Garrido, G

2014-02-01

Mangifera indica L. (mango) stem bark aqueous extract (MSBE) that has antioxidant, anti-inflammatory and immunomodulatory properties, can be obtained in Cuba. It is rich in polyphenols, where mangiferin is the main component. In this study, we have tested DNA damage and protection effects of MSBE and mangiferin on primary human lymphocytes and lymphoblastoid cells. Cell suspensions were incubated with the products (50-1000 μg/ml) for experiments on damage induction, and evaluation of any potential protective effects (5-100 μg/ml) for 60 min at 37 °C. Irradiation was performed using a γ-ray source, absorbed dose 5 Gy. At the end of exposure, DNA damage, protection and repair processes were evaluated using the comet assay. MSBE (100-1000 μg/ml) induced DNA damage in a concentration dependent manner in both cell types tested, primary cells being more sensitive. Mangiferin (200 μg/ml) only induced light DNA damage at higher concentrations. DNA repair capacity was not affected after MSBE or mangiferin exposure. On the other hand, MSBE (25 and 50 μg/ml) and mangiferin (5-25 ug/ml) protected against gamma radiation-induced DNA damage. These results show MSBE has protector or harmful effects on DNA in vitro depending on the experimental conditions, which suggest that the extract could be acting as an antioxidant or pro-oxidant product. Mangiferin was involved in protective effects of the extract. © 2013 John Wiley & Sons Ltd.

Effects of climate on emerald ash borer mortality and the potential for ash survival in North America

Treesearch

Ryan D. DeSantis; W. Keith Moser; Dale D. Gormanson; Marshall G. Bartlett; Bradley Vermunt

2013-01-01

Non-native invasive insects such as the emerald ash borer (Agrilus planipennis Fairmaire; EAB) cause billions of dollars; worth of economic damage and unquantifiable but substantial ecological damage in North America each year. There are methods to mitigate, contain, control, or even eradicate some non-native invasive insects, but so far the spread...

Inhibitory effect of essential oils on decay fungi and mold growth on wood

Treesearch

Vina W. Yang; Carol A. Clausen

2007-01-01

Structural damage and potential health risks caused by wood decay and mold fungi in residential structures have been a major concern for homeowners, building contractors and insurance companies alike. The combined damage from decay fungi and mold claims exceeds several billion US dollars annually. Protection against decay and mold growth on wood is a critical economic...

Mitochondrial dependent oxidative stress in cell culture induced by laser radiation at 1265 nm.

PubMed

Saenko, Yury V; Glushchenko, Eugenia S; Zolotovskii, Igor O; Sholokhov, Evgeny; Kurkov, Andrey

2016-04-01

Photodynamic therapy is the main technique applied for surface carcinoma treatment. This technique employs singlet oxygen generated via a laser excited photosensitizer as a main damaging agent. However, prolonged sensitivity to intensive light, relatively low tissue penetration by activating light the cost of photosensitizer (PS) administration can limit photodynamic therapy applications. Early was reported singlet oxygen generation without photosensitizer induced by a laser irradiation at the wavelength of 1250-1270 nm. Here, we study the dynamics of oxidative stress, DNA damage, changes of mitochondrial potential, and mitochondrial mass induced by a laser at 1265 nm have been studied in HCT-116 and CHO-K cells. Laser irradiation of HCT-116 and CHO-K cells has induced a dose-dependent cell death via increasing intracellular reactive oxygen species (ROS) concentration, increase of DNA damage, decrease of mitochondrial potential, and reduced glutathione. It has been shown that, along with singlet oxygen generation, the increase of the intracellular ROS concentration induced by mitochondrial damage contributes to the damaging effect of the laser irradiation at 1265 nm.

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

PubMed

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.

Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats

PubMed Central

Kasote, D. M.; Badhe, Y. S.; Zanwar, A. A.; Hegde, M. V.; Deshmukh, K. K.

2012-01-01

Objective: to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats. Materials and Methods: Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl4 in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. Results: EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl4 intoxication. Hepatic lipid peroxidation elevated by CCl4 intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl4 -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl4 -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). Conclusion: EPC-BF possesses the significant hepatoprotective activity against CCl4 induced liver damage, which could be mediated through increase in antioxidant defenses. PMID:22923966

The protective effect of grape seed procyanidin extract against cadmium-induced renal oxidative damage in mice.

PubMed

Chen, Qing; Zhang, Rong; Li, Wei-min; Niu, Yu-jie; Guo, Hui-cai; Liu, Xue-hui; Hou, Yu-chun; Zhao, Li-juan

2013-11-01

As an important environmental pollutant, cadmium (Cd) can lead to serious renal damage. Grape seed procyanidins extract (GSPE), a biological active component of grape seed, has been shown to possess antioxidative effects. Here, we assessed the protective effect of GSPE on Cd-induced renal damage using animal experiment. After 30 days, the oxidative damage of kidney was evaluated through measurement of superoxide dismutase (SOD), glutathione peroxidation (GSH-Px) and malondialdehyde (MDA). Since, oxidative stress could lead to apoptosis, the renal apoptosis was measured using flow cytometer. Moreover, the expression of apoptosis-related protein Bax and Bcl-2 was analyzed by immunohistochemistry and Western blot. The results showed that Cd led to the decrease of SOD and GSH-Px activities, and the increase of MDA level, induced renal apoptosis. However, the coadministration of GSPE attenuated Cd-induced lipid peroxidation, and antagonized renal apoptosis, probably associated with the expression of Bax and Bcl-2. These data suggested that GSPE has protective effect against renal oxidative damage induced by Cd, which provide a potential natural chemopreventive agent against Cd-poisoning. Copyright © 2013 Elsevier B.V. All rights reserved.

Attenuation of Cisplatin-Induced Neurotoxicity by Cyanidin, a Natural Inhibitor of ROS-Mediated Apoptosis in PC12 Cells.

PubMed

Li, Da-wei; Sun, Jing-yi; Wang, Kun; Zhang, Shuai; Hou, Ya-jun; Yang, Ming-feng; Fu, Xiao-yan; Zhang, Zong-yong; Mao, Lei-lei; Yuan, Hui; Fang, Jie; Fan, Cun-dong; Zhu, Mei-jia; Sun, Bao-liang

2015-10-01

Cisplatin-based chemotherapy in clinic is severely limited by its adverse effect, including neurotoxicity. Oxidative damage contributes to cisplatin-induced neurotoxicity, but the mechanism remains unclearly. Cyanidin, a natural flavonoid compound, exhibits powerful antioxidant activity. Hence, we investigated the protective effects of cyanidin on PC12 cells against cisplatin-induced neurotoxicity and explored the underlying mechanisms. The results showed that cisplatin-induced cytotoxicity was completely reversed by cyanidin through inhibition of PC12 cell apoptosis, as proved by the attenuation of Sub-G1 peak, PARP cleavage, and caspases-3 activation. Mechanistically, cyanidin significantly inhibited reactive oxygen species (ROS)-induced DNA damage in cisplatin-treated PC12 cells. Our findings revealed that cyanidin as an apoptotic inhibitor effectively blocked cisplatin-induced neurotoxicity through inhibition of ROS-mediated DNA damage and apoptosis, predicating its therapeutic potential in prevention of chemotherapy-induced neurotoxicity. Cisplatin caused DNA damage, activated p53, and subsequently induced PC12 cells apoptosis by triggering ROS overproduction. However, cyanidin administration effectively inhibited DNA damage, attenuated p53 phosphorylation, and eventually reversed cisplatin-induced PC12 cell apoptosis through inhibition ROS accumulation.

Amygdala Damage Affects Event-Related Potentials for Fearful Faces at Specific Time Windows

PubMed Central

Rotshtein, Pia; Richardson, Mark P; Winston, Joel S; Kiebel, Stefan J; Vuilleumier, Patrik; Eimer, Martin; Driver, Jon; Dolan, Raymond J

2010-01-01

The amygdala is known to influence processing of threat-related stimuli in distant brain regions, including visual cortex. The time-course of these distant influences is unknown, although this information is important for resolving debates over likely pathways mediating an apparent rapidity in emotional processing. To address this, we recorded event-related potentials (ERPs) to seen fearful face expressions, in preoperative patients with medial temporal lobe epilepsy who had varying degrees of amygdala pathology, plus healthy volunteers. We found that amygdala damage diminished ERPs for fearful versus neutral faces within the P1 time-range, ∼100–150 ms, and for a later component at ∼500–600 ms. Individual severity of amygdala damage determined the magnitude of both these effects, consistent with a causal amygdala role. By contrast, amygdala damage did not affect explicit perception of fearful expressions nor a distinct emotional ERP effect at 150–250 ms. These results demonstrate two distinct time-points at which the amygdala influences fear processing. The data also demonstrate that while not all aspects of expression processing are disrupted by amygdala damage, there is a crucial impact on an early P1 component. These findings are consistent with the existence of multiple processing stages or routes for fearful faces that vary in their dependence on amygdala function. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. PMID:20017134

Chronicles in drug discovery.

PubMed

Davies, Shelley L; Ferrer, Elisa; Moral, Maria Angels

2006-06-01

Chronicles in Drug Discovery features special interest reports on advances in drug discovery. This month we highlight new options to prevent oral mucositis, a treatment-limiting adverse effect of chemotherapy. Studies are currently focusing on mechanism-based therapies to prevent or repair DNA damage to epithelial and submucosal cells and the cascade or events that follow to cause tissue damage or analgesics to ease the associated oral cavity pain. Therapeutic limitations also exist for the use of the highly effective antibiotic gentamicin, as it evokes acute renal failure. Mechanistic investigations have shed some light on potential targets: the kallikreins, peroxynitrite-related pathways, superoxide production and the accumulation of aminoglycosides. New antibiotic strategies for trachoma, the leading cause of preventable blindness, are also explored along with studies to aid the development of vaccine candidates. Finally, we discuss the utility of allosteric-potentiating ligands to modulate nicotinic acetylcholine receptors, mimicking the reward/addictive effects of nicotine, as potential strategies for smoking cessation. (c) 2006 Prous Science. All rights reserved.

Hydrocaffeic and p-coumaric acids, natural phenolic compounds, inhibit UV-B damage in WKD human conjunctival cells in vitro and rabbit eye in vivo.

PubMed

Larrosa, Mar; Lodovici, Maura; Morbidelli, Lucia; Dolara, Piero

2008-10-01

This paper studied the effect on UV-B ocular damage of 10microM hydrocaffeic acid (HCAF) alone and as a mixture (MIX) (5 microM HCAF+5 microM p-coumaric acid). Since ocular UV-B damage is mediated by reactive oxygen species, the aim was to test if HCAF and MIX could reduce oxidation damage in human conjunctival cells (WKD) in vitro and in cornea and sclera of rabbits in vivo. After UVB irradiation (44 J/m(2)) of WKD cells, 8-oxodG levels in DNA were markedly increased and this effect was attenuated by HCAF and MIX. Rabbit eyes were treated by application of HCAF and MIX drops before UV-B exposure (79 J/m(2)). Corneal and scleral DNA oxidation damage, xanthine-oxidase (XO) activity and malondialdehyde levels (MDA) in corneal tissue and prostaglandin E(2) (PGE(2)) in the aqueous humour were reduced by HCAF alone and in combination with p-coumaric acid, showing their potential as a topical treatment against UV-B damage.

Intestinal damage, neurotoxicity and biochemical responses caused by tris (2-chloroethyl) phosphate and tricresyl phosphate on earthworm.

PubMed

Yang, Yang; Xiao, Yao; Chang, Yeqian; Cui, Yibin; Klobučar, Göran; Li, Mei

2018-08-30

Organophosphate esters (OPEs) draw growing concern about characterizing the potential risk on environmental health due to its wide usage and distribution. Two typical types of organophosphate esters (OPEs): tris (2-chloroethyl) phosphate (TCEP) and tricresyl phosphate (TCP) were selected to evaluate toxicity of OPEs to the soil organism like earthworm (Eisenia fetida). Histopathological examination (H&E), oxidative stress, DNA damage and RT-qPCR was used to identify the effects and potential mechanism of their toxicity. Hameatoxylin and eosin (H&E) demonstrated that intestinal cells suffered serious damage, and the observed up-regulation of chitinase and cathepsin L in mRNA levels confirmed it. Both TCEP and TCP significantly increased the DNA damage when the concentrations exceeded 1 mg/kg (p < 0.01), and a dose-response relationship was observed. In addition, TCEP and TCP also changed the acetylcholinesterase (AChE) activity and expression of genes associated with neurotoxic effects in earthworms even under exposure to low OPEs concentration (0.1 mg/kg). Moreover, genes associated with nicotinic acetylcholine receptors (nAChR) and carrier protein further demonstrated that highest concentration of TCEP (10 mg/kg) may have an overloading impact on the cholinergic system of E. fetida. Integrated Biological Response index (IBRv2) showed that TCEP exerted stronger toxicity than TCP under the same concentrations. We deduced that the observed intestinal damage, oxidative stress and neurotoxic effect might be the primary mechanisms of TCEP and TCP toxicity. This study provides insight into the toxicological effects of OPEs on earthworm model, and may be useful for risk assessment of OPEs on soil ecosystems. Copyright © 2018 Elsevier Inc. All rights reserved.

Optimal dose selection of N-methyl-N-nitrosourea for the rat comet assay to evaluate DNA damage in organs with different susceptibility to cytotoxicity.

PubMed

Kitamoto, Sachiko; Matsuyama, Ryoko; Uematsu, Yasuaki; Ogata, Keiko; Ota, Mika; Yamada, Toru; Miyata, Kaori; Funabashi, Hitoshi; Saito, Koichi

2015-07-01

The in vivo rodent alkaline comet assay (comet assay) is a promising technique to evaluate DNA damage in vivo. However, there is no agreement on a method to evaluate DNA damage in organs where cytotoxicity is observed. As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the comet assay, we examined DNA damage in the liver, stomach, and bone marrow of rats given three oral doses of N-methyl-N-nitrosourea (MNU) up to the maximum tolerated dose based on systemic toxicity. MNU significantly increased the % tail DNA in all the organs. Histopathological analysis showed no cytotoxic effect on the liver, indicating clearly that MNU has a genotoxic potential in the liver. In the stomach, however, the cytotoxic effects were very severe at systemically non-toxic doses. Low-dose MNU significantly increased the % tail DNA even at a non-cytotoxic dose, indicating that MNU has a genotoxic potential also in the stomach. Part of the DNA damage at cytotoxic doses was considered to be a secondary effect of severe cell damage. In the bone marrow, both the % tail DNA and incidence of micronucleated polychromatic erythrocytes significantly increased at non-hematotoxic doses, which were different from the non-cytotoxic doses for liver and stomach. These findings indicate that an optimal dose for detecting DNA damage may vary among organs and that careful attention is required to select an optimum dose for the comet assay based on systemic toxicity such as mortality and clinical observations. The present study shows that when serious cytotoxicity is suggested by increased % hedgehogs in the comet assay, histopathological examination should be included for the evaluation of a positive response. Copyright © 2015 Elsevier B.V. All rights reserved.

Next generation testing strategy for assessment of genomic damage: A conceptual framework and considerations.

PubMed

Dearfield, Kerry L; Gollapudi, B Bhaskar; Bemis, Jeffrey C; Benz, R Daniel; Douglas, George R; Elespuru, Rosalie K; Johnson, George E; Kirkland, David J; LeBaron, Matthew J; Li, Albert P; Marchetti, Francesco; Pottenger, Lynn H; Rorije, Emiel; Tanir, Jennifer Y; Thybaud, Veronique; van Benthem, Jan; Yauk, Carole L; Zeiger, Errol; Luijten, Mirjam

2017-06-01

For several decades, regulatory testing schemes for genetic damage have been standardized where the tests being utilized examined mutations and structural and numerical chromosomal damage. This has served the genetic toxicity community well when most of the substances being tested were amenable to such assays. The outcome from this testing is usually a dichotomous (yes/no) evaluation of test results, and in many instances, the information is only used to determine whether a substance has carcinogenic potential or not. Over the same time period, mechanisms and modes of action (MOAs) that elucidate a wider range of genomic damage involved in many adverse health outcomes have been recognized. In addition, a paradigm shift in applied genetic toxicology is moving the field toward a more quantitative dose-response analysis and point-of-departure (PoD) determination with a focus on risks to exposed humans. This is directing emphasis on genomic damage that is likely to induce changes associated with a variety of adverse health outcomes. This paradigm shift is moving the testing emphasis for genetic damage from a hazard identification only evaluation to a more comprehensive risk assessment approach that provides more insightful information for decision makers regarding the potential risk of genetic damage to exposed humans. To enable this broader context for examining genetic damage, a next generation testing strategy needs to take into account a broader, more flexible approach to testing, and ultimately modeling, of genomic damage as it relates to human exposure. This is consistent with the larger risk assessment context being used in regulatory decision making. As presented here, this flexible approach for examining genomic damage focuses on testing for relevant genomic effects that can be, as best as possible, associated with an adverse health effect. The most desired linkage for risk to humans would be changes in loci associated with human diseases, whether in somatic or germ cells. The outline of a flexible approach and associated considerations are presented in a series of nine steps, some of which can occur in parallel, which was developed through a collaborative effort by leading genetic toxicologists from academia, government, and industry through the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Genetic Toxicology Technical Committee (GTTC). The ultimate goal is to provide quantitative data to model the potential risk levels of substances, which induce genomic damage contributing to human adverse health outcomes. Any good risk assessment begins with asking the appropriate risk management questions in a planning and scoping effort. This step sets up the problem to be addressed (e.g., broadly, does genomic damage need to be addressed, and if so, how to proceed). The next two steps assemble what is known about the problem by building a knowledge base about the substance of concern and developing a rational biological argument for why testing for genomic damage is needed or not. By focusing on the risk management problem and potential genomic damage of concern, the next step of assay(s) selection takes place. The work-up of the problem during the earlier steps provides the insight to which assays would most likely produce the most meaningful data. This discussion does not detail the wide range of genomic damage tests available, but points to types of testing systems that can be very useful. Once the assays are performed and analyzed, the relevant data sets are selected for modeling potential risk. From this point on, the data are evaluated and modeled as they are for any other toxicology endpoint. Any observed genomic damage/effects (or genetic event(s)) can be modeled via a dose-response analysis and determination of an estimated PoD. When a quantitative risk analysis is needed for decision making, a parallel exposure assessment effort is performed (exposure assessment is not detailed here as this is not the focus of this discussion; guidelines for this assessment exist elsewhere). Then the PoD for genomic damage is used with the exposure information to develop risk estimations (e.g., using reference dose (RfD), margin of exposure (MOE) approaches) in a risk characterization and presented to risk managers for informing decision making. This approach is applicable now for incorporating genomic damage results into the decision-making process for assessing potential adverse outcomes in chemically exposed humans and is consistent with the ILSI HESI Risk Assessment in the 21st Century (RISK21) roadmap. This applies to any substance to which humans are exposed, including pharmaceuticals, agricultural products, food additives, and other chemicals. It is time for regulatory bodies to incorporate the broader knowledge and insights provided by genomic damage results into the assessments of risk to more fully understand the potential of adverse outcomes in chemically exposed humans, thus improving the assessment of risk due to genomic damage. The historical use of genomic damage data as a yes/no gateway for possible cancer risk has been too narrowly focused in risk assessment. The recent advances in assaying for and understanding genomic damage, including eventually epigenetic alterations, obviously add a greater wealth of information for determining potential risk to humans. Regulatory bodies need to embrace this paradigm shift from hazard identification to quantitative analysis and to incorporate the wider range of genomic damage in their assessments of risk to humans. The quantitative analyses and methodologies discussed here can be readily applied to genomic damage testing results now. Indeed, with the passage of the recent update to the Toxic Substances Control Act (TSCA) in the US, the new generation testing strategy for genomic damage described here provides a regulatory agency (here the US Environmental Protection Agency (EPA), but suitable for others) a golden opportunity to reexamine the way it addresses risk-based genomic damage testing (including hazard identification and exposure). Environ. Mol. Mutagen. 58:264-283, 2017. © 2016 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc. © 2016 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc.

Potential role of punicalagin against oxidative stress induced testicular damage.

PubMed

Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

2016-01-01

Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

Potential role of punicalagin against oxidative stress induced testicular damage

PubMed Central

Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

2016-01-01

Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility. PMID:26763544

Identification of a gene set to evaluate the potential effects of loud sounds from seismic surveys on the ears of fishes: a study with Salmo salar

PubMed Central

Andrews, C D; Payne, J F; Rise, M L

2014-01-01

Functional genomic studies were carried out on the inner ear of Atlantic salmon Salmo salar following exposure to a seismic airgun. Microarray analyses revealed 79 unique transcripts (passing background threshold), with 42 reproducibly up-regulated and 37 reproducibly down-regulated in exposed v. control fish. Regarding the potential effects on cellular energetics and cellular respiration, altered transcripts included those with roles in oxygen transport, the glycolytic pathway, the Krebs cycle and the electron transport chain. Of these, a number of transcripts encoding haemoglobins that are important in oxygen transport were up-regulated and among the most highly expressed. Up-regulation of transcripts encoding nicotinamide riboside kinase 2, which is also important in energy production and linked to nerve cell damage, points to evidence of neuronal damage in the ear following noise exposure. Transcripts related to protein modification or degradation also indicated potential damaging effects of sound on ear tissues. Notable in this regard were transcripts associated with the proteasome–ubiquitin pathway, which is involved in protein degradation, with the transcript encoding ubiquitin family domain-containing protein 1 displaying the highest response to exposure. The differential expression of transcripts observed for some immune responses could potentially be linked to the rupture of cell membranes. Meanwhile, the altered expression of transcripts for cytoskeletal proteins that contribute to the structural integrity of the inner ear could point to repair or regeneration of ear tissues including auditory hair cells. Regarding potential effects on hormones and vitamins, the protein carrier for thyroxine and retinol (vitamin A), namely transthyretin, was altered at the transcript expression level and it has been suggested from studies in mammalian systems that retinoic acid may play a role in the regeneration of damaged hair cells. The microarray experiment identified the transcript encoding growth hormone I as up-regulated by loud sound, supporting previous evidence linking growth hormone to hair cell regeneration in fishes. Quantitative (q) reverse transcription (RT) polymerase chain reaction (qRT-PCR) analyses confirmed dysregulation of some microarray-identified transcripts and in some cases revealed a high level of biological variability in the exposed group. These results support the potential utility of molecular biomarkers to evaluate the effect of seismic surveys on fishes with studies on the ears being placed in a priority category for development of exposure–response relationships. Knowledge of such relationships is necessary for addressing the question of potential size of injury zones. PMID:24814183

Comet assay: a reliable tool for the assessment of DNA damage in different models.

PubMed

Dhawan, Alok; Bajpayee, Mahima; Parmar, Devendra

2009-02-01

New chemicals are being added each year to the existing burden of toxic substances in the environment. This has led to increased pollution of ecosystems as well as deterioration of the air, water, and soil quality. Excessive agricultural and industrial activities adversely affect biodiversity, threatening the survival of species in a particular habitat as well as posing disease risks to humans. Some of the chemicals, e.g., pesticides and heavy metals, may be genotoxic to the sentinel species and/or to non-target species, causing deleterious effects in somatic or germ cells. Test systems which help in hazard prediction and risk assessment are important to assess the genotoxic potential of chemicals before their release into the environment or commercial use as well as DNA damage in flora and fauna affected by contaminated/polluted habitats. The Comet assay has been widely accepted as a simple, sensitive, and rapid tool for assessing DNA damage and repair in individual eukaryotic as well as some prokaryotic cells, and has increasingly found application in diverse fields ranging from genetic toxicology to human epidemiology. This review is an attempt to comprehensively encase the use of Comet assay in different models from bacteria to man, employing diverse cell types to assess the DNA-damaging potential of chemicals and/or environmental conditions. Sentinel species are the first to be affected by adverse changes in their environment. Determination of DNA damage using the Comet assay in these indicator organisms would thus provide information about the genotoxic potential of their habitat at an early stage. This would allow for intervention strategies to be implemented for prevention or reduction of deleterious health effects in the sentinel species as well as in humans.

Evaluation of a threshold-based model of fatigue in gamma titanium aluminide following impact damage

NASA Astrophysics Data System (ADS)

Harding, Trevor Scott

2000-10-01

Recent interest in gamma titanium aluminide (gamma-TiAl) for use in gas turbine engine applications has centered on the low density and good elevated temperature strength retention of gamma-TiAl compared to current materials. However, the relatively low ductility and fracture toughness of gamma-TiAl leads to serious concerns regarding its ability to resist impact damage. Furthermore, the limited fatigue crack growth resistance of gamma-TiAl means that the potential for fatigue failures resulting from impact damage is real if a damage tolerant design approach is used. A threshold-based design approach may be required if fatigue crack growth from potential impact sites is to be avoided. The objective of the present research is to examine the feasibility of a threshold-based approach for the design of a gamma-TiAl low-pressure turbine blade subjected to both assembly-related impact damage and foreign object damage. Specimens of three different gamma-TiAl alloys were damaged in such a way as to simulate anticipated impact damage for a turbine blade. Step-loading fatigue tests were conducted at both room temperature and 600°C. In terms of the assembly-related impact damage, the results indicate that there is reasonably good agreement between the threshold-based predictions of the fatigue strength of damaged specimens and the measured data. However, some discrepancies do exist. In the case of very lightly damaged specimens, prediction of the resulting fatigue strength requires that a very conservative small-crack fatigue threshold be used. Consequently, the allowable design conditions are significantly reduced. For severely damaged specimens, an analytical approach found that the potential effects of residual stresses may be related to the discrepancies observed between the threshold-based model and measured fatigue strength data. In the case of foreign object damage, a good correlation was observed between impacts resulting in large cracks and a long-crack threshold-based approximation of the fatigue strength. However, in the case of smaller impact sites, a lower small-crack threshold appears to be more appropriate. In some cases, a complete perforation of the material, or blowout, would result from the impact. Prediction of the reduction in fatigue strength resulting from this form of damage required the use of a stress concentration factor, rather than a threshold-based prediction.

Comments on potential health effects of MRI-induced DNA lesions: quality is more important to consider than quantity

PubMed Central

Hill, M.A.; O'Neill, P.; McKenna, W.G.

2016-01-01

Magnetic resonance imaging (MRI) is increasingly being used in cardiology to detect heart disease and guide therapy. It is mooted to be a safer alternative to imaging techniques, such as computed tomography (CT) or coronary angiographic imaging. However, there has recently been an increased interest in the potential long-term health risks of MRI, especially in the light of the controversy resulting from a small number of research studies reporting an increase in DNA damage following exposure, with calls to limit its use and avoid unnecessary examination, according to the precautionary principle. Overall the published data are somewhat limited and inconsistent; the ability of MRI to produce DNA lesions has yet to be robustly demonstrated and future experiments should be carefully designed to optimize sensitivity and benchmarked to validate and assess reproducibility. The majority of the current studies have focussed on the initial induction of DNA damage, and this has led to comparisons between the reported induction of γH2AX and implied double-strand break (DSB) yields produced following MRI with induction by imaging techniques using ionizing radiation. However, γH2AX is not only a marker of classical double-ended DSB, but also a marker of stalled replication forks and in certain circumstances stalled DNA transcription. Additionally, ionizing radiation is efficient at producing complex DNA damage, unique to ionizing radiation, with an associated reduction in repairability. Even if the fields associated with MRI are capable of producing DNA damage, the lesions produced will in general be simple, similar to those produced by endogenous processes. It is therefore inappropriate to try and infer cancer risk by simply comparing the yields of γH2AX foci or DNA lesions potentially produced by MRI to those produced by a given exposure of ionizing radiation, which will generally be more biologically effective and have a greater probability of leading to long-term health effects. As a result, it is important to concentrate on more relevant downstream end points (e.g. chromosome aberration production), along with potential mechanisms by which MRI may lead to DNA lesions. This could potentially involve a perturbation in homeostasis of oxidative stress, modifying the background rate of endogenous DNA damage induction. In summary, what the field needs at the moment is more research and less fear mongering. PMID:27550664

Development of a biocidal treatment regime to inhibit biological growths on cultural heritage: BIODAM

NASA Astrophysics Data System (ADS)

Young, M. E.; Alakomi, H.-L.; Fortune, I.; Gorbushina, A. A.; Krumbein, W. E.; Maxwell, I.; McCullagh, C.; Robertson, P.; Saarela, M.; Valero, J.; Vendrell, M.

2008-12-01

Existing chemical treatments to prevent biological damage to monuments often involve considerable amounts of potentially dangerous and even poisonous biocides. The scientific approach described in this paper aims at a drastic reduction in the concentration of biocide applications by a polyphasic approach of biocides combined with cell permeabilisers, polysaccharide and pigment inhibitors and a photodynamic treatment. A variety of potential agents were screened to determine the most effective combination. Promising compounds were tested under laboratory conditions with cultures of rock deteriorating bacteria, algae, cyanobacteria and fungi. A subsequent field trial involved two sandstone types with natural biofilms. These were treated with multiple combinations of chemicals and exposed to three different climatic conditions. Although treatments proved successful in the laboratory, field trials were inconclusive and further testing will be required to determine the most effective treatment regime. While the most effective combination of chemicals and their application methodology is still being optimised, results to date indicate that this is a promising and effective treatment for the control of a wide variety of potentially damaging organisms colonising stone substrates.

Fragmentation increases wind disturbance impacts on forest structure and carbon stocks in a western Amazonian landscape.

PubMed

Schwartz, Naomi B; Uriarte, María; DeFries, Ruth; Bedka, Kristopher M; Fernandes, Katia; Gutiérrez-Vélez, Victor; Pinedo-Vasquez, Miguel A

2017-09-01

Tropical second-growth forests could help mitigate climate change, but the degree to which their carbon potential is achieved will depend on exposure to disturbance. Wind disturbance is common in tropical forests, shaping structure, composition, and function, and influencing successional trajectories. However, little is known about the impacts of extreme winds on second-growth forests in fragmented landscapes, though these ecosystems are often located in mosaics of forest, pasture, cropland, and other land cover types. Indirect evidence suggests that fragmentation increases risk of wind damage in tropical forests, but no studies have found such impacts following severe storms. In this study, we ask whether fragmentation and forest type (old vs. second growth) were associated with variation in wind damage after a severe convective storm in a fragmented production landscape in western Amazonia. We applied linear spectral unmixing to Landsat 8 imagery from before and after the storm, and combined it with field observations of damage to map wind effects on forest structure and biomass. We also used Landsat 8 imagery to map land cover with the goals of identifying old- and second-growth forest and characterizing fragmentation. We used these data to assess variation in wind disturbance across 95,596 ha of forest, distributed over 6,110 patches. We find that fragmentation is significantly associated with wind damage, with damage severity higher at forest edges and in edgier, more isolated patches. Damage was also more severe in old-growth than in second-growth forests, but this effect was weaker than that of fragmentation. These results illustrate the importance of considering landscape context in planning tropical forest restoration and natural regeneration projects. Assessments of long-term carbon sequestration potential need to consider spatial variation in disturbance exposure. Where risk of extreme winds is high, minimizing fragmentation and isolation could increase carbon sequestration potential. © 2017 by the Ecological Society of America.

Binding of Substrate Locks the Electrochemistry of CRY-DASH into DNA Repair.

PubMed

Gindt, Yvonne M; Messyasz, Adriana; Jumbo, Pamela I

2015-05-12

VcCry1, a member of the CRY-DASH family, may serve two diverse roles in vivo, including blue-light signaling and repair of UV-damaged DNA. We have discovered that the electrochemistry of the flavin adenine dinucleotide cofactor of VcCry1 is locked to cycle only between the hydroquinone and neutral semiquinone states when UV-damaged DNA is present. Other potential substrates, including undamaged DNA and ATP, have no discernible effect on the electrochemistry, and the kinetics of the reduction is unaffected by damaged DNA. Binding of the damaged DNA substrate determines the role of the protein and prevents the presumed photochemistry required for blue-light signaling.

The role of membrane cholesterol in determining bile acid cytotoxicity and cytoprotection of ursodeoxycholic acid

PubMed Central

Zhou, Yong; Doyen, Rand; Lichtenberger, Lenard M.

2013-01-01

In cholestatic liver diseases, the ability of hydrophobic bile acids to damage membranes of hepatocytes/ductal cells contributes to their cytotoxicity. However, ursodeoxycholic acid (UDC), a hydrophilic bile acid, is used to treat cholestasis because it protects membranes. It has been well established that bile acids associate with and solubilize free cholesterol (CHOL) contained within the lumen of the gallbladder because of their structural similarities. However, there is a lack of understanding of how membrane CHOL, which is a well-established membrane stabilizing agent, is involved in cytotoxicity of hydrophobic bile acids and the cytoprotective effect of UDC. We utilized phospholipid liposomes to examine the ability of membrane CHOL to influence toxicity of individual bile acids, such as UDC and the highly toxic sodium deoxycholate (SDC), as well as the cytoprotective mechanism of UDC against SDC-induced cytotoxicity by measuring membrane permeation and intramembrane dipole potential. The kinetics of bile acid solubilization of phosphatidylcholine liposomes containing various levels of CHOL was also characterized. It was found that the presence of CHOL in membranes significantly reduced the ability of bile acids to damage synthetic membranes. UDC effectively prevented damaging effects of SDC on synthetic membranes only in the presence of membrane CHOL, while UDC enhances the damaging effects of SDC in the absence of CHOL. This further demonstrates that the cytoprotective effects of UDC depend upon the level of CHOL in the lipid membrane. Thus, changes in cell membrane composition, such as CHOL content, potentially influence the efficacy of UDC as the primary drug used to treat cholestasis. PMID:19150330

40 CFR 264.601 - Environmental performance standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... other vegetation; (8) The potential for health risks caused by human exposure to waste constituents; and... effects on human health or the environment due to migration of waste constituents in surface water, or... human exposure to waste constituents; and (11) The potential for damage to domestic animals, wildlife...

40 CFR 264.601 - Environmental performance standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... other vegetation; (8) The potential for health risks caused by human exposure to waste constituents; and... effects on human health or the environment due to migration of waste constituents in surface water, or... human exposure to waste constituents; and (11) The potential for damage to domestic animals, wildlife...

40 CFR 264.601 - Environmental performance standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... other vegetation; (8) The potential for health risks caused by human exposure to waste constituents; and... effects on human health or the environment due to migration of waste constituents in surface water, or... human exposure to waste constituents; and (11) The potential for damage to domestic animals, wildlife...

The Influence of C-Ions and X-rays on Human Umbilical Vein Endothelial Cells

PubMed Central

Helm, Alexander; Lee, Ryonfa; Durante, Marco; Ritter, Sylvia

2016-01-01

Damage to the endothelium of blood vessels, which may occur during radiotherapy, is discussed as a potential precursor to the development of cardiovascular disease. We thus chose human umbilical vein endothelial cells as a model system to examine the effect of low- and high-linear energy transfer (LET) radiation. Cells were exposed to 250 kV X-rays or carbon ions (C-ions) with the energies of either 9.8 MeV/u (LET = 170 keV/μm) or 91 MeV/u (LET = 28 keV/μm). Subculture of cells was performed regularly up to 46 days (~22 population doublings) post-irradiation. Immediately after exposure, cells were seeded for the colony forming assay. Additionally, at regular intervals, mitochondrial membrane potential (MMP) (JC-1 staining) and cellular senescence (senescence-associated β-galactosidase staining) were assessed. Cytogenetic damage was investigated by the micronucleus assay and the high-resolution multiplex fluorescence in situ hybridization (mFISH) technique. Analysis of radiation-induced damage shortly after exposure showed that C-ions are more effective than X-rays with respect to cell inactivation or the induction of cytogenetic damage (micronucleus assay) as observed in other cell systems. For 9.8 and 91 MeV/u C-ions, relative biological effectiveness values of 2.4 and 1.5 were obtained for cell inactivation. At the subsequent time points, the number of micronucleated cells decreased to the control level. Analysis of chromosomal damage by mFISH technique revealed aberrations frequently involving chromosome 13 irrespective of dose or radiation quality. Disruption of the MMP was seen only a few days after exposure to X-rays or C-ions. Cellular senescence was not altered by radiation at any time point investigated. Altogether, our data indicate that shortly after exposure C-ions were more effective in damaging endothelial cells than X-rays. However, late damage to endothelial cells was not found for the applied conditions and endpoints. PMID:26835420

Neuroprotective effects of tanshinone I from Danshen extract in a mouse model of hypoxia-ischemia

PubMed Central

Lee, Jae-Chul; Park, Joon Ha; Park, Ok Kyu; Kim, In Hye; Yan, Bing Chun; Ahn, Ji Hyeon; Kwon, Seung-Hae; Choi, Jung Hoon

2013-01-01

Hypoxia-ischemia leads to serious neuronal damage in some brain regions and is a strong risk factor for stroke. The aim of this study was to investigate the neuroprotective effect of tanshinone I (TsI) derived from Danshen (Radix Salvia miltiorrhiza root extract) against neuronal damage using a mouse model of cerebral hypoxia-ischemia. Brain infarction and neuronal damage were examined using 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin histochemistry, and Fluoro-Jade B histofluorescence. Pre-treatment with TsI (10 mg/kg) was associated with a significant reduction in infarct volume 1 day after hypoxia-ischemia was induced. In addition, TsI protected against hypoxia-ischemia-induced neuronal death in the ipsilateral region. Our present findings suggest that TsI has strong potential for neuroprotection against hypoxic-ischemic damage. These results may be used in research into new anti-stroke medications. PMID:24179693

Effects of Atmospheric Pressure Plasmas on Isolated and Cellular DNA—A Review

PubMed Central

Arjunan, Krishna Priya; Sharma, Virender K.; Ptasinska, Sylwia

2015-01-01

Atmospheric Pressure Plasma (APP) is being used widely in a variety of biomedical applications. Extensive research in the field of plasma medicine has shown the induction of DNA damage by APP in a dose-dependent manner in both prokaryotic and eukaryotic systems. Recent evidence suggests that APP-induced DNA damage shows potential benefits in many applications, such as sterilization and cancer therapy. However, in several other applications, such as wound healing and dentistry, DNA damage can be detrimental. This review reports on the extensive investigations devoted to APP interactions with DNA, with an emphasis on the critical role of reactive species in plasma-induced damage to DNA. The review consists of three main sections dedicated to fundamental knowledge of the interactions of reactive oxygen species (ROS)/reactive nitrogen species (RNS) with DNA and its components, as well as the effects of APP on isolated and cellular DNA in prokaryotes and eukaryotes. PMID:25642755

Effects of atmospheric pressure plasmas on isolated and cellular DNA-a review.

PubMed

Arjunan, Krishna Priya; Sharma, Virender K; Ptasinska, Sylwia

2015-01-29

Atmospheric Pressure Plasma (APP) is being used widely in a variety of biomedical applications. Extensive research in the field of plasma medicine has shown the induction of DNA damage by APP in a dose-dependent manner in both prokaryotic and eukaryotic systems. Recent evidence suggests that APP-induced DNA damage shows potential benefits in many applications, such as sterilization and cancer therapy. However, in several other applications, such as wound healing and dentistry, DNA damage can be detrimental. This review reports on the extensive investigations devoted to APP interactions with DNA, with an emphasis on the critical role of reactive species in plasma-induced damage to DNA. The review consists of three main sections dedicated to fundamental knowledge of the interactions of reactive oxygen species (ROS)/reactive nitrogen species (RNS) with DNA and its components, as well as the effects of APP on isolated and cellular DNA in prokaryotes and eukaryotes.

Categorizing natural disaster damage assessment using satellite-based geospatial techniques

USGS Publications Warehouse

Myint, S.W.; Yuan, M.; Cerveny, R.S.; Giri, C.

2008-01-01

Remote sensing of a natural disaster's damage offers an exciting backup and/or alternative to traditional means of on-site damage assessment. Although necessary for complete assessment of damage areas, ground-based damage surveys conducted in the aftermath of natural hazard passage can sometimes be potentially complicated due to on-site difficulties (e.g., interaction with various authorities and emergency services) and hazards (e.g., downed power lines, gas lines, etc.), the need for rapid mobilization (particularly for remote locations), and the increasing cost of rapid physical transportation of manpower and equipment. Satellite image analysis, because of its global ubiquity, its ability for repeated independent analysis, and, as we demonstrate here, its ability to verify on-site damage assessment provides an interesting new perspective and investigative aide to researchers. Using one of the strongest tornado events in US history, the 3 May 1999 Oklahoma City Tornado, as a case example, we digitized the tornado damage path and co-registered the damage path using pre- and post-Landsat Thematic Mapper image data to perform a damage assessment. We employed several geospatial approaches, specifically the Getis index, Geary's C, and two lacunarity approaches to categorize damage characteristics according to the original Fujita tornado damage scale (F-scale). Our results indicate strong relationships between spatial indices computed within a local window and tornado F-scale damage categories identified through the ground survey. Consequently, linear regression models, even incorporating just a single band, appear effective in identifying F-scale damage categories using satellite imagery. This study demonstrates that satellite-based geospatial techniques can effectively add spatial perspectives to natural disaster damages, and in particular for this case study, tornado damages.

Categorizing natural disaster damage assessment using satellite-based geospatial techniques

NASA Astrophysics Data System (ADS)

Myint, S. W.; Yuan, M.; Cerveny, R. S.; Giri, C.

2008-07-01

Remote sensing of a natural disaster's damage offers an exciting backup and/or alternative to traditional means of on-site damage assessment. Although necessary for complete assessment of damage areas, ground-based damage surveys conducted in the aftermath of natural hazard passage can sometimes be potentially complicated due to on-site difficulties (e.g., interaction with various authorities and emergency services) and hazards (e.g., downed power lines, gas lines, etc.), the need for rapid mobilization (particularly for remote locations), and the increasing cost of rapid physical transportation of manpower and equipment. Satellite image analysis, because of its global ubiquity, its ability for repeated independent analysis, and, as we demonstrate here, its ability to verify on-site damage assessment provides an interesting new perspective and investigative aide to researchers. Using one of the strongest tornado events in US history, the 3 May 1999 Oklahoma City Tornado, as a case example, we digitized the tornado damage path and co-registered the damage path using pre- and post-Landsat Thematic Mapper image data to perform a damage assessment. We employed several geospatial approaches, specifically the Getis index, Geary's C, and two lacunarity approaches to categorize damage characteristics according to the original Fujita tornado damage scale (F-scale). Our results indicate strong relationships between spatial indices computed within a local window and tornado F-scale damage categories identified through the ground survey. Consequently, linear regression models, even incorporating just a single band, appear effective in identifying F-scale damage categories using satellite imagery. This study demonstrates that satellite-based geospatial techniques can effectively add spatial perspectives to natural disaster damages, and in particular for this case study, tornado damages.

Evaluation of genotoxic effects caused by extracts of chlorinated drinking water using a combination of three different bioassays.

PubMed

Zeng, Qiang; Zhang, Shao-Hui; Liao, Jing; Miao, Dong-Yue; Wang, Xin-Yi; Yang, Pan; Yun, Luo-Jia; Liu, Ai-Lin; Lu, Wen-Qing

2015-10-15

Potential genotoxic effects of chlorinated drinking water now are of a great concern. In this study, raw water, finished water, and tap water from a water plant in Wuhan, China were collected in two different sampling times of the year (January and July). Genotoxic effects of water extracts were evaluated using a combination of three different bioassays: SOS/umu test, HGPRT gene mutation assay, and micronucleus assay, which were separately used to detect DNA damage, gene mutation, and chromosome aberration. The results of three different bioassays showed that all water samples in January and July induced at least one types of genotoxic effects, of which the DNA-damage effects were all detectable. The levels of DNA-damage effects and gene-mutation effects of finished water and tap water in January were higher than those in July. Chlorination could increase the DNA-damage effects of drinking water in January and the gene-mutation effects of drinking water in both January and July, but did not increase the chromosome-aberration effects of drinking water in both January and July. Our results highlighted the importance of using a combination of different bioassays to evaluate the genotoxicity of water samples in different seasons. Copyright © 2015 Elsevier B.V. All rights reserved.

Spatially Informed Plant PRA Models for Security Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wheeler, Timothy A.; Thomas, Willard; Thornsbury, Eric

2006-07-01

Traditional risk models can be adapted to evaluate plant response for situations where plant systems and structures are intentionally damaged, such as from sabotage or terrorism. This paper describes a process by which traditional risk models can be spatially informed to analyze the effects of compound and widespread harsh environments through the use of 'damage footprints'. A 'damage footprint' is a spatial map of regions of the plant (zones) where equipment could be physically destroyed or disabled as a direct consequence of an intentional act. The use of 'damage footprints' requires that the basic events from the traditional probabilistic riskmore » assessment (PRA) be spatially transformed so that the failure of individual components can be linked to the destruction of or damage to specific spatial zones within the plant. Given the nature of intentional acts, extensive modifications must be made to the risk models to account for the special nature of the 'initiating events' associated with deliberate adversary actions. Intentional acts might produce harsh environments that in turn could subject components and structures to one or more insults, such as structural, fire, flood, and/or vibration and shock damage. Furthermore, the potential for widespread damage from some of these insults requires an approach that addresses the impacts of these potentially severe insults even when they occur in locations distant from the actual physical location of a component or structure modeled in the traditional PRA. (authors)« less

Bridging meso- and microscopic anisotropic unilateral damage formulations for microcracked solids

NASA Astrophysics Data System (ADS)

Zhu, Qi-Zhi; Yuan, Shuang-Shuang; Shao, Jian-fu

2017-04-01

A mathematically consistent and unified description of induced anisotropy and unilateral effects constitutes one of the central tasks in the continuum damage theories developed so far. This paper aims at bridging constitutive damage formulations on meso- and micro-scales with an emphasis on a complete mesoscopic determination of material effective properties for microcracked solids. The key is to introduce a new set of invariants in terms of strain tensor and fabric tensor by making use of the Walpole's tensorial base. This invariant set proves to be equivalent to the classical one, while the new one provides great conveniences to high-order orientation-dependent tensor manipulations. When limited to the case of parallel microcracks, potential relations between ten combination coefficients are established by applying continuity conditions. It is found that the dilute approximation with penny-shaped microcracks is a particular case of the present one. By originally introducing effective strain effect, interactions between microcracks are taken into account with comparison to the Mori-Tanaka method as well as the Ponte-Castaneda and Willis scheme. For completeness, discussions are also addressed on macroscopic formulations with high-order damage variables.

Gold nanoparticles induce DNA damage in the blood and liver of rats

NASA Astrophysics Data System (ADS)

Cardoso, Eria; Londero, Eduardo; Ferreira, Gabriela Kozuchovski; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rohr, Paula; da Silva, Luciano; Andrade, Vanessa M.; da Silva Paula, Marcos Marques

2014-11-01

The potential of gold nanoparticles (GNPs) for use in different biological applications has led to a strong interest in the study of their possible deleterious effects in biological systems and how these effects may be mitigated. This study was undertaken to investigate the effects of the acute and chronic administration of GNPs with mean diameters of 10 and 30 nm on deoxyribonucleic acid (DNA) damage in the blood and liver of adult rats. For the acute administration, Wistar adult rats received a single intraperitoneal injection of either GNPs or a saline solution. For the chronic administration, Wistar adult rats received a daily single injection of the same GNPs or saline solution for 28 days. Twenty-four hours after either the single (acute) or final injection (chronic), the rats were euthanised by decapitation, and the blood and liver were isolated for the evaluation of DNA damage. In this study, we demonstrated that the acute and chronic administration of GNPs 10 and 30 nm in size increased the frequency of DNA damage and the damage index in the blood and liver of adult rats. These findings suggest that the DNA damage may be caused by oxidative stress, which occurred regardless of the type of administration and GNP size.

Wind disasters: A comprehensive review of current management strategies

PubMed Central

Marchigiani, Raffaele; Gordy, Stephanie; Cipolla, James; Adams, Raeanna C; Evans, David C; Stehly, Christy; Galwankar, Sagar; Russell, Sarah; Marco, Alan P; Kman, Nicholas; Bhoi, Sanjeev; Stawicki, Stanislaw P A; Papadimos, Thomas J

2013-01-01

Wind disasters are responsible for tremendous physical destruction, injury, loss of life and economic damage. In this review, we discuss disaster preparedness and effective medical response to wind disasters. The epidemiology of disease and injury patterns observed in the early and late phases of wind disasters are reviewed. The authors highlight the importance of advance planning and adequate preparation as well as prompt and well-organized response to potential damage involving healthcare infrastructure and the associated consequences to the medical response system. Ways to minimize both the extent of infrastructure damage and its effects on the healthcare system are discussed, focusing on lessons learned from recent major wind disasters around the globe. Finally, aspects of healthcare delivery in disaster zones are reviewed. PMID:23961458

Biomarkers of aging in Drosophila.

PubMed

Jacobson, Jake; Lambert, Adrian J; Portero-Otín, Manuel; Pamplona, Reinald; Magwere, Tapiwanashe; Miwa, Satomi; Driege, Yasmine; Brand, Martin D; Partridge, Linda

2010-08-01

Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. Dietary restriction thus does not slow accumulation of aging-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of aging-related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of aging-related damage. Using this approach, we assessed several commonly used biomarkers of aging-related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence, fluorescent AGEs are biomarkers of aging-related damage in flies. In contrast, five oxidized and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of aging-related damage. Our approach provides a powerful method for identification of biomarkers of aging.

Biomarkers of ageing in Drosophila

PubMed Central

Jacobson, Jake; Portero-Otín, Manuel; Pamplona, Reinald; Magwere, Tapiwanashe; Miwa, Satomi; Driege, Yasmine; Brand, Martin D.; Partridge, Linda

2015-01-01

Summary Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. DR thus does not slow accumulation of ageing-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of ageing-related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of ageing-related damage. Using this approach, we assessed several commonly used biomarkers of ageing-related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence fluorescent AGEs are biomarkers of ageing-related damage in flies. In contrast, five oxidised and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of ageing-related damage. Our approach provides a powerful method for identification of biomarkers of ageing. PMID:20367621

Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Junqiang; Doi, Hiroshi; Saar, Matthias

2013-12-01

Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome.more » The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy.« less

Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid.

PubMed

Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R; Masliah, Eliezer; Lipton, Stuart A

2015-06-01

Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain barrier to up-regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human-induced pluripotent stem cell-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain. Cyanide, a potential bioterrorist agent, can produce a chronic delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both in vitro and in vivo models through activation of the Nrf2/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid-derived 2)-like 2). © 2015 International Society for Neurochemistry.

The effects of strawberry tree water leaf extract, arbutin and hydroquinone on haematological parameters and levels of primary DNA damage in white blood cells of rats.

PubMed

Jurica, Karlo; Brčić Karačonji, Irena; Kopjar, Nevenka; Shek-Vugrovečki, Ana; Cikač, Tihana; Benković, Vesna

2018-04-06

Strawberry tree (Arbutus unedo L., Ericaceae) leaves represent a potent source of biologically active compounds and have been used for a long to relieve symptoms of various health impairments and diseases. Two major compounds related to their beneficial activities in animals and humans are arbutin and hydroquinone. To establish potential benefit/risk ratio associated with daily oral administration of strawberry tree water leaf extract, arbutin and hydroquinone in doses expected to be non-toxic. We performed a 14-day and a 28-day study on male and female Lewis rats and evaluated main haematological parameters and the effects of treatments on the levels of primary DNA damage in white blood cells (WBC) using the alkaline comet assay. Our findings suggest no significant changes in the haematological parameters following prolonged exposure to strawberry tree water leaf extract, arbutin, and hydroquinone. However, hydroquinone causes increased, and extract as well as arbutin decreased WBC count in male rats compared to control after 14 days of treatment. DNA damage measured in WBC of rats treated with all compounds was below 10% of the DNA in the comet tail, which indicates low genotoxicity. The genotoxic potential of strawberry water leaf extract was within acceptable limits and reflected effects of a complex chemical composition upon DNA. We also observed slight gender- and exposure time- related differences in primary DNA damage in the leucocytes of control and treated rats. Future studies should investigate which doses of strawberry tree water leaf extract would be most promising for the potential use as a substitute for bearberry leaves for treatment of urinary infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Radioprotective potential of histamine on rat small intestine and uterus

PubMed Central

Carabajal, E.; Massari, N.; Croci, M.; Martinel Lamas, D.; Prestifilippo, J.P.; Ciraolo, P.; Bergoc, R.M.; Rivera, E.S.; Medina, V.A.

2012-01-01

The aim of this study was to improve knowledge about histamine radioprotective potential investigating its effect on reducing ionising radiation-induced injury and genotoxic damage on the rat small intestine and uterus. Forty 10-week-old male and 40 female Sprague-Dawley rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a dose of whole-body Cesium-137 irradiation. Three days after irradiation animals were sacrificed and tissues were removed, fixed, and stained with haematoxylin and eosin, and histological characteristics were evaluated. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate chromosomal damage. Histamine treatment reduced radiation-induced mucosal atrophy, oedema and vascular damage produced by ionising radiation, increasing the number of crypts per circumference (239±12 vs 160±10; P<0.01). This effect was associated with a reduction of radiation-induced intestinal crypts apoptosis. Additionally, histamine decreased the frequency of micronuclei formation and also significantly attenuated 8-OHdG immunoreactivity, a marker of DNA oxidative damage. Furthermore, radiation induced flattening of the endometrial surface, depletion of deep glands and reduced mitosis, effects that were completely blocked by histamine treatment. The expression of a proliferation marker in uterine luminal and glandular cells was markedly stimulated in histamine treated and irradiated rats. The obtained evidences indicate that histamine is a potential candidate as a safe radio-protective agent that might increase the therapeutic index of radiotherapy for intra-abdominal and pelvic cancers. However, its efficacy needs to be carefully investigated in prospective clinical trials. PMID:23361244

Recent Advances in Durability and Damage Tolerance Methodology at NASA Langley Research Center

NASA Technical Reports Server (NTRS)

Ransom, J. B.; Glaessgen, E. H.; Raju, I. S.; Harris, C. E.

2007-01-01

Durability and damage tolerance (D&DT) issues are critical to the development of lighter, safer and more efficient aerospace vehicles. Durability is largely an economic life-cycle design consideration whereas damage tolerance directly addresses the structural airworthiness (safety) of the vehicle. Both D&DT methodologies must address the deleterious effects of changes in material properties and the initiation and growth of damage that may occur during the vehicle s service lifetime. The result of unanticipated D&DT response is often manifested in the form of catastrophic and potentially fatal accidents. As such, durability and damage tolerance requirements must be rigorously addressed for commercial transport aircraft and NASA spacecraft systems. This paper presents an overview of the recent and planned future research in durability and damage tolerance analytical and experimental methods for both metallic and composite aerospace structures at NASA Langley Research Center (LaRC).

Preliminary Guidelines for Safe and Effective Use of Hot, High-Pressure Washers for Maintenance Cleaning of Army Vehicles.

DTIC Science & Technology

1982-11-01

26AS TACT (Ctbm onrols st N 19m4i60M, = de IdIM b o1ck numbef) - >While hot, high-pressure washers clean effectively, they can also damage parts on Army...conserve water resources, and reduce the costs of wastewater treatment. The objec- At most Army installations, maintenance cleaning tive of the phase of...Itios Catalog Code 214. Posary not only to control the parameters involved for a more accurate assessment of the potential for damage. 2R. I de ~cia

Effects of ion insertion on cycling performance of miniaturized electrochemical capacitor of carbon nanotubes array.

PubMed

Tsai, Dah-Shyang; Chang, Chuan-hua; Chiang, Wei-Wen; Lee, Kuei-Yi; Huang, Ying-Sheng

2014-10-24

Capacity degradation and ion insertion of a miniaturized electrochemical capacitor are studied using ionic liquid [EMI] [TFSI] as the electrolyte. This capacitor is featured with two comb-like electrodes of vertical carbon nanotubes, ∼70 μm in height and 20 μm in interelectrode gap. We quantify the levels of ion insertion damage with Raman spectroscopy after the electrode experiences 120 consecutive voltammetric cycles to various potential limits. Distinct structural damage emerges due to [EMI] when the negative potential reaches -1.7 V, and those due to [TFSI] arise when the positive potential reaches 1.7 V vs. RHE. Judging from the peak broadenings, [EMI] is more detrimental than [TFSI]. When the voltage window ΔU is set as less than or equal to 2.8 V, both electrode potentials are within the two intercalation limits, little or no decay is observed in 10(4) charge/discharge cycles. When ΔU is 3.4 V, the positive potential exceeds the upper limit, but the negative potential stays within the lower limit, the cell capacitance decreases moderately. When ΔU increases to 3.8 V, both electrodes suffer from damages because of exceeding the intercalation limits. And the cell capacitance decreases substantially, even leading to a premature failure.

Human Lung Cancer Risks from Radon – Part II – Influence from Combined Adaptive Response and Bystander Effects – A Microdose Analysis

PubMed Central

Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

2010-01-01

In the prior Part I, the potential influence of the low level alpha radiation induced bystander effect (BE) on human lung cancer risks was examined. Recent analysis of adaptive response (AR) research results with a Microdose Model has shown that single low LET radiation induced charged particles traversals through the cell nucleus activates AR. We have here conducted an analysis based on what is presently known about adaptive response and the bystander effect (BE) and what new research is needed that can assist in the further evaluation human cancer risks from radon. We find that, at the UNSCEAR (2000) worldwide average human exposures from natural background and man-made radiations, the human lung receives about a 25% adaptive response protection against the radon alpha bystander damage. At the UNSCEAR (2000) minimum range of background exposure levels, the lung receives minimal AR protection but at higher background levels, in the high UNSCEAR (2000) range, the lung receives essentially 100% protection from both the radon alpha damage and also the endogenic, spontaneously occurring, potentially carcinogenic, lung cellular damage. PMID:22461760

Role of climatic factors on damage incidence by Dermolepida albohirtum (Coleoptera: Scarabaeidae), in Burdekin sugarcane fields, Australia.

PubMed

Horsfield, Andrew; Sallam, Mohamed Nader S; Drummond, Frank A; Williams, Don J; Schultz, Rod J

2008-04-01

Inconsistent control of Dermolepida albohirtum (Waterhouse) (Coleoptera: Scarabaeidae) in the period after the removal of organochlorines allowed us to study the impact of climatic variables and insecticide application on subsequent damage in sugarcane (Saccharum spp.). D. albohirtum damage records from the Invicta and Inkerman mill areas of the Burdekin district of North Queensland were compared with climatic averages during spring from 1989 to 2003. D. albohirtum damage demonstrated autocorrelation, indicating that the area of damage will increase from one year to the next if the grub is not effectively controlled. Insecticide use did not significantly impact on the area of damage between 1989 and 2003. Of the climatic variables evaluated, only pan evaporation was significant, and it was inversely related to the subsequent area of grub damage. Therefore, we suggest that weather conditions in spring impact on beetle emergence, feeding, and oviposition. Hot and dry spring weather may reduce beetle activity and ultimately the severity of crop damage, whereas wet and mild spring weather may favor beetle activity and an increase in the area of potential crop damage.

Potential System Vulnerabilities of a Network Enabled Force

DTIC Science & Technology

2004-09-01

of trust in information, loss of context and awareness of others’ needs and reduction of social cohesion . Science - (more specifically systems...and Technology Damaging Social Cohesion NCW champions the concept of dispersed forces as a means to generate effects through approaches other than...Mission Grouping Damaging Social Cohesion This is a slight variation on the vulnerability expressed in 3.9.6 above. If we have agility in mission

Evaluation of the genotoxic and antigenotoxic potential of Baccharis dracunculifolia extract on V79 cells by the comet assay.

PubMed

Munari, Carla Carolina; Alves, Jacqueline Morais; Bastos, Jairo Kenupp; Tavares, Denise Crispim

2010-01-01

Baccharis dracunculifolia (Asteraceae), the main botanical source of green propolis, is a shrub of the Brazilian 'cerrado'. In folk medicine it is used as an anti-inflammatory agent, mainly for the treatment of gastrointestinal diseases. The aim of the present study was to evaluate the genotoxic and antigenotoxic effects of B. dracunculifolia ethyl acetate extract (Bd-EAE) on Chinese hamster lung fibroblasts (V79 cells) by the comet assay. Methyl methanesulfonate (MMS; 200 microM) was used as an inducer of DNA damage. Genotoxicity was evaluated using four different concentrations of Bd-EAE: 12.5, 25.0, 50.0 and 100.0 microg ml(-1). Antigenotoxicity was assessed before, simultaneously, and after treatment with the mutagen. The results showed a significant increase in the frequency of DNA damage in cultures treated with 50.0 and 100.0 microg ml(-1) Bd-EAE. Regarding its antigenotoxic potential, Bd-EAE reduced the frequency of DNA damage induced by MMS. However, this chemopreventive activity depended on the concentrations and treatment regimens used. The antioxidant activity of phenolic components present in Bd-EAE may contribute to reduce the alkylation damage induced by MMS. In conclusion, our findings confirmed the chemopreventive activity of Bd-EAE and showed that this effect occurs under different mechanism.

Monitoring genetic damage to ecosystems from hazardous waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, S.L.

1992-03-01

Applications of ecological toxicity testing to hazardous waste management have increased dramatically over the last few years, resulting in a greater awareness of the need for improved biomonitoring techniques. Our laboratory is developing advanced techniques to assess the genotoxic effects of environmental contamination on ecosystems. We have developed a novel mutagenesis assay using the nematode Caenorhabditis elegans, which is potentially applicable for multimedia studies in soil, sediment, and water. In addition, we are conducting validation studies of a previously developed anaphase aberration test that utilizes sea urchin embryos. Other related efforts include field validation studies of the new tests, evaluationmore » of their potential ecological relevance, and analysis of their sensitivity relative to that of existing toxicity tests that assess only lethal effects, rather than genetic damage.« less

Analysis of Ricefield Land Damage in Denpasar City, Bali, Indonesia

NASA Astrophysics Data System (ADS)

Suyarto, R.; Wiyanti; Dibia, I. N.

2018-02-01

Soil as a natural resource, living area, environmental media, and factors of production including biomass production that supports human life and other living beings must be preserved, on the other hand, uncontrolled biomass production activities can cause soil damage, ultimately can threaten the survival of humans and other living things. Therefore, in order to control soil damage, first must inventories the soil condition data and its damage which then visualised in soil damage potential and soil damage status. The activities of the study are the preparation of a map of the initial soil conditions and the delineation of potentially land degradation distribution. Mapping results are used as work maps for verification on the field to take soil samples and create soil damage status. In general, Denpasar City have soil damage potential at very low, low until medium rate. Soil damage status in Denpasar City generally is low damage of bulk volume, total porosity, soil permeability and electrolyte conductivity which beyond limitation thresholds.

Genotoxic and cytotoxic effects of doxorubicin and silymarin on human hepatocellular carcinoma cells.

PubMed

Yurtcu, E; İşeri, Öd; Sahin, Fi

2014-12-01

The aim of this study was to investigate genotoxic and cytotoxic effects of doxorubicin, silymarin, or in combination on HepG2 cells for 24 and 48 h. Both doxorubicin and silymarin caused dose-dependent inhibition of cell proliferation. After 48 h of treatment, doxorubicin application caused dramatically increased ratio of apoptotic cells. Both 24 and 48 h of silymarin and doxorubicin-silymarin combination caused significant increases in the rate of apoptotic cells. Applications of doxorubicin and silymarin separately for 24 h led to deoxyribonucleic acid (DNA) damages. After 48 h of incubation, doxorubicin-induced genotoxic damage was 2-fold higher than the silymarin-induced damage. After 24 and 48 h, DNA damage in response to combined applications of doxorubicin and silymarin was indifferent from silymarin- and doxorubicin-induced damage respectively. There was not any difference in genotoxicity levels between incubation periods in combined applications of doxorubicin and silymarin. Lipid peroxidation levels increased in all applications. Biopharmacotherapy with chemotherapeutic agents are of interest in the issue of adjuvant therapy. Here, we demonstrate in vitro potential genotoxic and cytotoxic antitumor effect of silymarin on HepG2 cells at achievable plasma level concentrations. © The Author(s) 2014.

Does it make sense to modify tropical cyclones? A decision-analytic assessment.

PubMed

Klima, Kelly; Morgan, M Granger; Grossmann, Iris; Emanuel, Kerry

2011-05-15

Recent dramatic increases in damages caused by tropical cyclones (TCs) and improved understanding of TC physics have led DHS to fund research on intentional hurricane modification. We present a decision analytic assessment of whether it is potentially cost-effective to attempt to lower the wind speed of TCs approaching South Florida by reducing sea surface temperatures with wind-wave pumps. Using historical data on hurricanes approaching South Florida, we develop prior probabilities of how storms might evolve. The effects of modification are estimated using a modern TC model. The FEMA HAZUS-MH MR3 damage model and census data on the value of property at risk are used to estimate expected economic losses. We compare wind damages after storm modification with damages after implementing hardening strategies protecting buildings. We find that if it were feasible and properly implemented, modification could reduce net losses from an intense storm more than hardening structures. However, hardening provides "fail safe" protection for average storms that might not be achieved if the only option were modification. The effect of natural variability is larger than that of either strategy. Damage from storm surge is modest in the scenario studied but might be abated by modification.

Benefits of dietary phytochemical supplementation on eccentric exercise-induced muscle damage: Is including antioxidants enough?

PubMed

Pereira Panza, Vilma Simões; Diefenthaeler, Fernando; da Silva, Edson Luiz

2015-09-01

The purpose of this review was to critically discuss studies that investigated the effects of supplementation with dietary antioxidant phytochemicals on recovery from eccentric exercise-induced muscle damage. The performance of physical activities that involve unaccustomed eccentric muscle actions-such as lowering a weight or downhill walking-can result in muscle damage, oxidative stress, and inflammation. These events may be accompanied by muscle weakness and delayed-onset muscle soreness. According to the current evidences, supplementation with dietary antioxidant phytochemicals appears to have the potential to attenuate symptoms associated with eccentric exercise-induced muscle damage. However, there are inconsistencies regarding the relationship between muscle damage and blood markers of oxidative stress and inflammation. Furthermore, the effectiveness of strategies appear to depend on a number of aspects inherent to phytochemical compounds as well as its food matrix. Methodological issues also may interfere with the proper interpretation of supplementation effects. Thus, the study may contribute to updating professionals involved in sport nutrition as well as highlighting the interest of scientists in new perspectives that can widen dietary strategies applied to training. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of DNA damage in flight personnel by Comet assay.

PubMed

Cavallo, Delia; Tomao, Paola; Marinaccio, Alessandro; Perniconi, Barbara; Setini, Andrea; Palmi, Silvana; Iavicoli, Sergio

2002-04-26

There have been some suggestions that air-crew are at a higher-than-normal risk of developing cancer, since they are exposed to potential genotoxic factors. These include cosmic radiations, airborne pollutants such as the combustion products of jet propulsion, ozone, and electromagnetic fields. We used the Comet assay to investigate DNA damage in flight personnel with the aim of assessing potential health hazards in this occupational category. We studied 40 civil air-crew members who had been flying long-haul routes for at least 5 years, and compared them with a homogeneous control group of 40 healthy male ground staff. The Comet assay, or single-cell gel electrophoresis (SCGE), detects DNA single- and double-strand breaks (DSBs) and alkali-labile lesions in individual cells, and is a powerful and sensitive technique for detecting genetic damage induced by different genotoxic agents. Taking into consideration occupational risk and possible confounding factors, this assay showed a small increase, that did not reach statistical significance, of DNA damage in long-haul crew members compared to controls, indicating a lack of evident genotoxic effects. An association, although again not statistically significant, was found between reduced DNA damage and use of protective drugs (antioxidants).

Scrotal insulation and sperm production in the boar.

PubMed

Parrish, John J; Willenburg, Kilby L; Gibbs, Katelynn M; Yagoda, Kylie B; Krautkramer, Megan M; Loether, Teyanna M; Melo, Fabiana C S A

2017-09-01

Seasonal infertility is a limiting factor in boar fertility, and is increasingly important as climate changes. Spermatogenesis in the boar produces 256 spermatozoa per type A 1 spermatogonium, but the process is inefficient such that only 10-30% of these potential spermatozoa are actually produced. Heat further impacts spermatogenesis by reducing the number of specific germ cells produced while increasing the fraction of abnormal sperm. Early studies used whole-animal exposure to simulate seasonal exposure to heat under production settings, but this approach is associated with many confounding factors that make assessment of the mechanisms of heat-induced damage to spermatogenesis difficult. Scrotal insulation provides a better model to investigate the mechanisms and potential mitigation strategies of heat-induce damage. For example, scrotal insulation helped identify a link between short-term heat stress and damage to meiotic germ cells. This outcome is likely due to changes in the integrity of the blood-testis barrier, which induce apoptosis, autophagy and DNA damage in the germ cells. Further understanding how heat damages spermatogenesis, and whether or not this can be repaired, are crucial to mitigating heat effects on boars in production settings. © 2017 Wiley Periodicals, Inc.

Masking of infrared neural stimulation (INS) in hearing and deaf guinea pigs

NASA Astrophysics Data System (ADS)

Kadakia, Sama; Young, Hunter; Richter, Claus-Peter

2013-03-01

Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also results in thermal damage or the generation of a stress relaxation wave. Stress relaxation waves may result in a direct mechanical stimulation of remaining hair cells in the cochlea, so called optophony. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, acutely deafened, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in acutely deafened animals the masking effect is reduced, and in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.

Aircraft noise effects on cultural resources: Recommendation and rationale for further research

NASA Astrophysics Data System (ADS)

Hanson, Carl E.; King, Kenneth W.; Eagan, Mary Ellen; Horonjeff, Richard D.

1993-05-01

The results are ultimately used to estimate the potential for damage to a wide variety of cultural resources from operations of commercial helicopters. Comparison of measured vibration levels with criteria for damage based on structural velocities will provide a family of restrictions on aircraft operations in the vicinity of sensitive structures. Such restrictions could take the form of minimum separation distances and prohibited maneuvers for helicopters. The results of the study would be presented in a report as a set of recommended procedures for helicopter operations to avoid damage to prehistoric, historic, sensitive, and conventional structures.

Prediction and measurement of radiation damage to CMOS devices on board spacecraft

NASA Technical Reports Server (NTRS)

Cliff, R. A.; Danchenko, V.; Stassinopoulos, E. G.; Sing, M.; Brucker, G. J.; Ohanian, R. S.

1976-01-01

The initial results obtained from the Complementary Metal Oxide Semiconductors Radiation Effects Measurement experiment are presented. Predictions of radiation damage to C-MOS devices are based on standard environment models and computational techniques. A comparison of the shifts in CMOS threshold potentials, that is, those measured in space to those obtained from the on the ground simulation experiment with Co 60, indicated that the measured space damage is greater than predicted by a factor of two for shields thicker than 100 mils (2.54 mm), but agrees well with predictions for the thinner shields.

Medicinal Plants for the Treatment of Local Tissue Damage Induced by Snake Venoms: An Overview from Traditional Use to Pharmacological Evidence

PubMed Central

Félix-Silva, Juliana; Silva-Junior, Arnóbio Antônio; Zucolotto, Silvana Maria

2017-01-01

Snakebites are a serious problem in public health due to their high morbimortality. Most of snake venoms produce intense local tissue damage, which could lead to temporary or permanent disability in victims. The available specific treatment is the antivenom serum therapy, whose effectiveness is reduced against these effects. Thus, the search for complementary alternatives for snakebite treatment is relevant. There are several reports of the popular use of medicinal plants against snakebites worldwide. In recent years, many studies have been published giving pharmacological evidence of benefits of several vegetal species against local effects induced by a broad range of snake venoms, including inhibitory potential against hyaluronidase, phospholipase, proteolytic, hemorrhagic, myotoxic, and edematogenic activities. In this context, this review aimed to provide an updated overview of medicinal plants used popularly as antiophidic agents and discuss the main species with pharmacological studies supporting the uses, with emphasis on plants inhibiting local effects of snake envenomation. The present review provides an updated scenario and insights into future research aiming at validation of medicinal plants as antiophidic agents and strengthens the potentiality of ethnopharmacology as a tool for design of potent inhibitors and/or development of herbal medicines against venom toxins, especially local tissue damage. PMID:28904556

Medicinal Plants for the Treatment of Local Tissue Damage Induced by Snake Venoms: An Overview from Traditional Use to Pharmacological Evidence.

PubMed

Félix-Silva, Juliana; Silva-Junior, Arnóbio Antônio; Zucolotto, Silvana Maria; Fernandes-Pedrosa, Matheus de Freitas

2017-01-01

Snakebites are a serious problem in public health due to their high morbimortality. Most of snake venoms produce intense local tissue damage, which could lead to temporary or permanent disability in victims. The available specific treatment is the antivenom serum therapy, whose effectiveness is reduced against these effects. Thus, the search for complementary alternatives for snakebite treatment is relevant. There are several reports of the popular use of medicinal plants against snakebites worldwide. In recent years, many studies have been published giving pharmacological evidence of benefits of several vegetal species against local effects induced by a broad range of snake venoms, including inhibitory potential against hyaluronidase, phospholipase, proteolytic, hemorrhagic, myotoxic, and edematogenic activities. In this context, this review aimed to provide an updated overview of medicinal plants used popularly as antiophidic agents and discuss the main species with pharmacological studies supporting the uses, with emphasis on plants inhibiting local effects of snake envenomation. The present review provides an updated scenario and insights into future research aiming at validation of medicinal plants as antiophidic agents and strengthens the potentiality of ethnopharmacology as a tool for design of potent inhibitors and/or development of herbal medicines against venom toxins, especially local tissue damage.

Bilirubin and its oxidation products damage brain white matter

PubMed Central

Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

2014-01-01

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases

PubMed Central

Mitra, Joy; Guerrero, Erika N.; Hegde, Pavana M.; Wang, Haibo; Boldogh, Istvan; Rao, Kosagi Sharaf; Mitra, Sankar; Hegde, Muralidhar L.

2014-01-01

The primary cause(s) of neuronal death in most cases of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s) have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS), but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases. PMID:25036887

Sonic hedgehog promotes stem-cell potential of Mueller glia in the mammalian retina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan Jin; Zheng Hua; Xiao Honglei

2007-11-16

Mueller glia have been demonstrated to display stem-cell properties after retinal damage. Here, we report this potential can be regulated by Sonic hedgehog (Shh) signaling. Shh can stimulate proliferation of Mueller glia through its receptor and target gene expressed on them, furthermore, Shh-treated Mueller glia are induced to dedifferentiate by expressing progenitor-specific markers, and then adopt cell fate of rod photoreceptor. Inhibition of signaling by cyclopamine inhibits proliferation and dedifferentiation. Intraocular injection of Shh promotes Mueller glia activation in the photoreceptor-damaged retina, Shh also enhances neurogenic potential by producing more rhodopsin-positive photoreceptors from Mueller glia-derived cells. Together, these results providemore » evidences that Mueller glia act as potential stem cells in mammalian retina, Shh may have therapeutic effects on these cells for promoting the regeneration of retinal neurons.« less

High-temperature annealing of graphite: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Petersen, Andrew; Gillette, Victor

2018-05-01

A modified AIREBO potential was developed to simulate the effects of thermal annealing on the structure and physical properties of damaged graphite. AIREBO parameter modifications were made to reproduce Density Functional Theory interstitial results. These changes to the potential resulted in high-temperature annealing of the model, as measured by stored-energy reduction. These results show some resemblance to experimental high-temperature annealing results, and show promise that annealing effects in graphite are accessible with molecular dynamics and reactive potentials.

DNA damage protective effect of honey-sweetened cashew apple nectar in Drosophila melanogaster

PubMed Central

da Silva, Robson Alves; Dihl, Rafael Rodrigues; Dias, Lucas Pinheiro; Costa, Maiane Papke; de Abreu, Bianca Regina Ribas; Cunha, Kênya Silva; Lehmann, Mauricio

2016-01-01

Abstract Fruits and derivatives, such as juices, are complex mixtures of chemicals, some of which may have mutagenic and/or carcinogenic potential, while others may have antimutagenic and/or anticancer activities. The modulating effects of honey-sweetened cashew apple nectar (HSCAN), on somatic mutation and recombination induced by ethyl methanesulfonate (EMS) and mitomycin C (MMC) were evaluated with the wing spot test in Drosophila melanogaster using co- and post-treatment protocols. Additionally, the antimutagenic activity of two HSCAN components, cashew apple pulp and honey, in MMC-induced DNA damage was also investigated. HSCAN reduced the mutagenic activity of both EMS and MMC in the co-treatment protocol, but had a co-mutagenic effect when post-administered. Similar results were also observed with honey on MMC mutagenic activity. Cashew apple pulp was effective in exerting protective or enhancing effects on the MMC mutagenicity, depending on the administration protocol and concentration used. Overall, these results indicate that HSCAN, cashew apple and honey seem capable of modulating not only the events that precede the induced DNA damages, but also the Drosophila DNA repair processes involved in the correction of EMS and MMC-induced damages. PMID:27560988

FIREMON: Fire effects monitoring and inventory system

Treesearch

Duncan C. Lutes; Robert E. Keane; John F. Caratti; Carl H. Key; Nathan C. Benson; Steve Sutherland; Larry J. Gangi

2006-01-01

Monitoring and inventory to assess the effects of wildland fire is critical for 1) documenting fire effects, 2) assessing ecosystem damage and benefit, 3) evaluating the success or failure of a burn, and 4) appraising the potential for future treatments. However, monitoring fire effects is often difficult because data collection requires abundant funds, resources, and...

The Economic Impact of Air Pollution on Timber Markets: Studies from North America and Europe

Treesearch

Joseph E. de Steiguer; [Editor

1992-01-01

Six papers analyze potential economic effects of forest damage resulting from air pollution.Economic effects in the Southeastern United States, the United States as a whole, Canada, Finland, and Europe as a whole are considered.

Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole

PubMed Central

Buschini, Annamaria; Ferrarini, Lisa; Franzoni, Susanna; Galati, Serena; Lazzaretti, Mirca; Mussi, Francesca; Northfleet de Albuquerque, Cristina; Maria Araújo Domingues Zucchi, Tânia; Poli, Paola

2009-01-01

Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells. PMID:20981287

Genotoxicity revaluation of three commercial nitroheterocyclic drugs: nifurtimox, benznidazole, and metronidazole.

PubMed

Buschini, Annamaria; Ferrarini, Lisa; Franzoni, Susanna; Galati, Serena; Lazzaretti, Mirca; Mussi, Francesca; Northfleet de Albuquerque, Cristina; Maria Araújo Domingues Zucchi, Tânia; Poli, Paola

2009-01-01

Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells.

A scanning probe mounted on a field-effect transistor: Characterization of ion damage in Si.

PubMed

Shin, Kumjae; Lee, Hoontaek; Sung, Min; Lee, Sang Hoon; Shin, Hyunjung; Moon, Wonkyu

2017-10-01

We have examined the capabilities of a Tip-On-Gate of Field-Effect Transistor (ToGoFET) probe for characterization of FIB-induced damage in Si surface. A ToGoFET probe is the SPM probe which the Field Effect Transistor(FET) is embedded at the end of a cantilever and a Pt tip was mounted at the gate of FET. The ToGoFET probe can detect the surface electrical properties by measuring source-drain current directly modulated by the charge on the tip. In this study, a Si specimen whose surface was processed with Ga+ ion beam was prepared. Irradiation and implantation with Ga+ ions induce highly localized modifications to the contact potential. The FET embedded on ToGoFET probe detected the surface electric field profile generated by schottky contact between the Pt tip and the sample surface. Experimentally, it was shown that significant differences of electric field due to the contact potential barrier in differently processed specimens were observed using ToGOFET probe. This result shows the potential that the local contact potential difference can be measured by simple working principle with high sensitivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of the protective effects of ferulic acid and its drug-containing plasma on primary cultured neonatal rat cardiomyocytes with hypoxia/reoxygenation injury

PubMed Central

Ren, Cong; Bao, Yong-rui; Meng, Xian-sheng; Diao, Yun-peng; Kang, Ting-guo

2013-01-01

Backgroud: To simulate the ischemia-reperfusion injury in vivo, hypoxia/reoxygenation injury model was established in vitro and primary cultured neonatal rat cardiomyocytes were underwent hypoxia with hydrosulfite (Na2S2O4) for 1 h followed by 1 h reoxygenation. Materials and Methods: Determination the cell viability by MTT colorimetric assay. We use kit to detect the activity of lactate dehydrogenase (LDH), Na+-K+-ATPase and Ca2+-ATPase. Do research on the effect which ferulic acid and its drug-containing plasma have to self-discipline, conductivity, action potential duration and other electrophysiological phenomena of myocardial cells by direct observation using a microscope and recording method of intracellular action potential. Results: The experimental datum showed that both can reduce the damage hydrosulfite to myocardial cell damage and improve myocardial viability, reduce the amount of LDH leak, increase activity of Na+-K+-ATPase, Ca2+-ATPase, and increase APA (Action potential amplitude), Vmax (Maximum rate of depolarization) and MPD (Maximum potential diastolic). Conclusion: Taken together, therefore, we can get the conclusion that ferulic acid drug-containing plasma has better protective effect injured myocardial cell than ferulic acid. PMID:23930002

Nanoparticles can cause DNA damage across a cellular barrier

NASA Astrophysics Data System (ADS)

Bhabra, Gevdeep; Sood, Aman; Fisher, Brenton; Cartwright, Laura; Saunders, Margaret; Evans, William Howard; Surprenant, Annmarie; Lopez-Castejon, Gloria; Mann, Stephen; Davis, Sean A.; Hails, Lauren A.; Ingham, Eileen; Verkade, Paul; Lane, Jon; Heesom, Kate; Newson, Roger; Case, Charles Patrick

2009-12-01

The increasing use of nanoparticles in medicine has raised concerns over their ability to gain access to privileged sites in the body. Here, we show that cobalt-chromium nanoparticles (29.5 +/- 6.3 nm in diameter) can damage human fibroblast cells across an intact cellular barrier without having to cross the barrier. The damage is mediated by a novel mechanism involving transmission of purine nucleotides (such as ATP) and intercellular signalling within the barrier through connexin gap junctions or hemichannels and pannexin channels. The outcome, which includes DNA damage without significant cell death, is different from that observed in cells subjected to direct exposure to nanoparticles. Our results suggest the importance of indirect effects when evaluating the safety of nanoparticles. The potential damage to tissues located behind cellular barriers needs to be considered when using nanoparticles for targeting diseased states.

Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.

PubMed

Olipitz, Werner; Wiktor-Brown, Dominika; Shuga, Joe; Pang, Bo; McFaline, Jose; Lonkar, Pallavi; Thomas, Aline; Mutamba, James T; Greenberger, Joel S; Samson, Leona D; Dedon, Peter C; Yanch, Jacquelyn C; Engelward, Bevin P

2012-08-01

In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break-induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.

Apigenin attenuates streptozotocin-induced pancreatic β cell damage by its protective effects on cellular antioxidant defense.

PubMed

Wang, Ning; Yi, Wen Jing; Tan, Lu; Zhang, Jia Hui; Xu, Jiamin; Chen, Yi; Qin, Mengting; Yu, Shuang; Guan, Jing; Zhang, Rui

2017-06-01

Pancreatic beta cells are very sensitive to oxidative stress, which is one of the major causes of cell damages in diabetes. Growing interest has focused on the development of effective therapeutics to protect pancreatic cells from oxidative stress and searching for potentially protective antioxidants for treating diabetes. Apigenin, a plant-derived flavonoid, was investigated to determine whether it could protect rat insulinoma cell lines (RINm5F pancreatic beta cells) against streptozotocin (STZ)-induced oxidative damages and the mechanisms implicated. Our results showed that STZ treatment could induce oxidative stress and consequent cytotoxic effects in RINm5F cells. Pretreatment with apigenin effectively decreased the intracellular reactive oxygen species (ROS) production, attenuated cellular DNA damage, diminished lipid peroxidation, relieved protein carbonylation, and restored the cell apoptosis of pancreatic beta cells stressed by STZ. Our further experiments demonstrated that the beneficial effects of apigenin were related to ameliorate the loss of antioxidant enzymes of the STZ-treated cells in the level of gene transcription, protein expression, and enzyme activity. That suggested apigenin was not only a free radical scavenger but also a regulator to antioxidant defenses of pancreatic cells. Taken all together, our findings suggested that apigenin could attenuate the STZ-induced oxidative damages in pancreatic beta cells and might serve as a novel agent for the treatment of diabetes.

Skin cell protection against UVA by Sideroxyl, a new antioxidant complementary to sunscreens.

PubMed

Pygmalion, Marie-Jocelyne; Ruiz, Laetitia; Popovic, Evelyne; Gizard, Julie; Portes, Pascal; Marat, Xavier; Lucet-Levannier, Karine; Muller, Benoit; Galey, Jean-Baptiste

2010-12-01

Oxidative stress resulting from photosensitized ROS production in skin is widely accepted as the main contributor to the deleterious effects of UVA exposure. Among the mechanisms known to be involved in UVA-induced oxidative damage, iron plays a central role. UVA radiation of skin cells induces an immediate release of iron, which can then act as a catalyst for uncontrolled oxidation reactions of cell components. Such site-specific damage can scarcely be counteracted by classical antioxidants. In contrast, iron chelators potentially offer an effective way to protect skin against UVA insults. However, iron chelation is very difficult to achieve without disturbing iron homeostasis or inducing iron depletion. A novel compound was developed to avoid these potentially harmful side effects. Sideroxyl was designed to acquire its strong chelating capability only during oxidative stress according to an original process of intramolecular hydroxylation. Herein, we describe in vitro results demonstrating the protective efficiency of Sideroxyl against deleterious effects of UVA at the molecular, cellular, and tissular levels. First, the Sideroxyl diacid form protects a model protein against UVA-induced photosensitized carbonylation. Second, intracellular ROS are dose-dependently decreased in the presence of Sideroxyl in both human cultured fibroblasts and human keratinocytes. Third, Sideroxyl protects normal human fibroblasts against UVA-induced DNA damage as measured by the comet assay and MMP-1 production. Finally, Sideroxyl provides protection against UVA-induced alterations in human reconstructed skin. These results suggest that Sideroxyl may prevent UVA-induced damage in human skin as a complement to sunscreens, especially in the long-wavelength UVA range. Copyright © 2010 Elsevier Inc. All rights reserved.

Impact of storage induced outgassing organic contamination on laser induced damage of silica optics at 351 nm.

PubMed

Bien-Aimé, K; Belin, C; Gallais, L; Grua, P; Fargin, E; Néauport, J; Tovena-Pecault, I

2009-10-12

The impact of storage conditions on laser induced damage density at 351 nm on bare fused polished silica samples has been studied. Intentionally outgassing of polypropylene pieces on silica samples was done. We evidenced an important increase of laser induced damage density on contaminated samples demonstrating that storage could limit optics lifetime performances. Atomic Force Microscopy (AFM) and Gas Chromatography -Mass Spectrometry (GC-MS) have been used to identify the potential causes of this effect. It shows that a small quantity of organic contamination deposited on silica surface is responsible for this degradation. Various hypotheses are proposed to explain the damage mechanism. The more likely hypothesis is a coupling between surface defects of optics and organic contaminants.

Evaluation of Both Free Radical Scavenging Capacity and Antioxidative Damage Effect of Polydatin.

PubMed

Jin, Ju; Li, Yan; Zhang, Xiuli; Chen, Tongsheng; Wang, Yifei; Wang, Zhiping

Cellular damage such as oxidation and lipid peroxidation, and DNA damage induced by free-radicals like reactive oxygen species, has been implicated in several diseases. Radicals generated by 2,2-azobis (2-amidino-propane) dihydrochloride (AAPH) are similar to physiologically active ones. In this study we found that polydatin, a resveratrol natural precursor derived from many sources, has the capacity of free radical scavenging and antioxidative damage. Using free radical scavenging assays, the IC50 values of polydatin were 19.25 and 5.29 μg/ml with the DPPH and the ABTS assay, respectively, and 0.125 mg ferrous sulfate/1 mg polydatin with the FRAP assay. With the AAPH-induced oxidative injury cell model assay, polydatin showed a strong protective effect against the human liver tumor HepG2 cell oxidative stress damage. These results indicate that the antioxidant properties of polydatin have great potential for use as an alternative to more toxic synthetic antioxidants as an additive in food, cosmetics and pharmaceutical preparations for the treatment of oxidative diseases.

Protective Effects of Processed Ginseng and Its Active Ginsenosides on Cisplatin-Induced Nephrotoxicity: In Vitro and in Vivo Studies.

PubMed

Park, Jun Yeon; Choi, Pilju; Kim, Taejung; Ko, Hyeonseok; Kim, Ho-kyong; Kang, Ki Sung; Ham, Jungyeob

2015-07-01

Although cisplatin can dramatically improve the survival rate in cancer patients, its use is limited by its nephrotoxicity. Previous investigations showed that Panax ginseng contains components that exhibit protective activity against cisplatin-induced nephropathy. The aim of the present study is to investigate the effect of microwave-assisted processing on the protective effect of ginseng and identify ginsenosides that are active against cisplatin-induced kidney damage to evaluate the potential of using ginseng in the management of nephrotoxicity. The LLC-PK1 cell damage by cisplatin was significantly decreased by treatment with microwave-processed ginseng (MG) and ginsenosides Rg3, Rg5, and Rk1. Reduced expression of p53 and c-Jun N-terminal kinase proteins by cisplatin in LLC-PK1 cells was markedly ameliorated after Rg3 and Rg5/Rk1 treatment. Additionally, elevated expression of cleaved caspase-3 was significantly reduced by ginsenosides Rg5, Rk1, and with even greater potency, Rg3. Moreover, MG and its fraction containing active ginsenosides showed protective effects against cisplatin-induced nephropathy in mice. We found that ginsenosides Rg3, Rg5, and Rk1 generated during the heat treatment of ginseng ameliorate renal damage by regulating inflammation and apoptosis. Results of current experiments provide evidence of the renoprotective effects and therapeutic potential of MG and its active ginsenosides, both in vitro and in vivo.

Effects of ionizing radiation on bio-active plant extracts useful for preventing oxidative damages.

PubMed

Mulinacci, Nadia; Valletta, Alessio; Pasqualetti, Valentina; Innocenti, Marzia; Giuliani, Camilla; Bellumori, Maria; De Angelis, Giulia; Carnevale, Alessia; Locato, Vittoria; Di Venanzio, Cristina; De Gara, Laura; Pasqua, Gabriella

2018-04-02

Humans are exposed to ionizing radiations in medical radiodiagnosis and radiotherapy that cause oxidative damages and degenerative diseases. Airplane pilots, and even more astronauts, are exposed to a variety of potentially harmful factors, including cosmic radiations. Among the phytochemicals, phenols are particularly efficient in countering the oxidative stress. In the present study, different extracts obtained from plant food, plant by-products and dietary supplements, have been compared for their antioxidant properties before and after irradiation of 140 cGy, a dose absorbed during a hypothetical stay of three years in the space. All the dry extracts, characterized in terms of vitamin C and phenolic content, remained chemically unaltered and maintained their antioxidant capability after irradiation. Our results suggest the potential use of these extracts as nutraceuticals to protect humans from oxidative damages, even when these extracts must be stored in an environment exposed to cosmic radiations as in a space station.

γ-H2AX as a biomarker for DNA double-strand breaks in ecotoxicology.

PubMed

Gerić, Marko; Gajski, Goran; Garaj-Vrhovac, Vera

2014-07-01

The visualisation of DNA damage response proteins enables the indirect measurement of DNA damage. Soon after the occurrence of a DNA double-strand break (DSB), the formation of γ-H2AX histone variants is to be expected. This review is focused on the potential use of the γ-H2AX foci assay in assessing the genotoxicity of environmental contaminants including cytostatic pharmaceuticals, since standard methods may not be sensitive enough to detect the damaging effect of low environmental concentrations of such drugs. These compounds are constantly released into the environment, potentially representing a threat to water quality, aquatic organisms, and, ultimately, human health. Our review of the literature revealed that this method could be used in the biomonitoring and risk assessment of aquatic systems affected by wastewater from the production, usage, and disposal of cytostatic pharmaceuticals. Copyright © 2014 Elsevier Inc. All rights reserved.

Bioactivation of carboxylic acid compounds by UDP-Glucuronosyltransferases to DNA-damaging intermediates: role of glycoxidation and oxidative stress in genotoxicity.

PubMed

Sallustio, Benedetta C; Degraaf, Yvette C; Weekley, Josephine S; Burcham, Philip C

2006-05-01

Nonenzymatic modification of proteins by acyl glucuronides is well documented; however, little is known about their potential to damage DNA. We have previously reported that clofibric acid undergoes glucuronidation-dependent bioactivation to DNA-damaging species in cultured mouse hepatocytes. The aim of this study was to investigate the mechanisms underlying such DNA damage, and to screen chemically diverse carboxylic acid drugs for their DNA-damaging potential in glucuronidation proficient murine hepatocytes. Cells were incubated with each aglycone for 18 h, followed by assessment of compound cytotoxicity using the MTT assay and evaluation of DNA damage using the Comet assay. Relative cytotoxic potencies were ketoprofen > diclofenac, benoxaprofen, nafenopin > gemfibrozil, probenecid > bezafibrate > clofibric acid. At a noncytotoxic (0.1 mM) concentration, only benoxaprofen, nafenopin, clofibric acid, and probenecid significantly increased Comet moments (P < 0.05 Kruskal-Wallis). Clofibric acid and probenecid exhibited the greatest DNA-damaging potency, producing significant DNA damage at 0.01 mM concentrations. The two drugs produced maximal increases in Comet moment of 4.51 x and 2.57 x control, respectively. The glucuronidation inhibitor borneol (1 mM) abolished the induction of DNA damage by 0.5 mM concentrations of clofibric acid and probenecid. In an in vitro cell-free system, clofibric acid glucuronide was 10 x more potent than glucuronic acid in causing DNA strand-nicking, although both compounds showed similar rates of autoxidation to generate hydroxyl radicals. In cultured hepatocytes, the glycation inhibitor, aminoguanidine, and the iron chelator, desferrioxamine mesylate, inhibited DNA damage by clofibric acid, whereas the free radical scavengers Trolox and butylated hydroxytoluene, and the superoxide dismutase mimetic bis-3,5-diisopropylsalicylate had no effect. In conclusion, clinically relevant concentrations of two structurally unrelated carboxylic acids, probenecid and clofibric acid, induced DNA damage in isolated hepatocytes via glucuronidation- dependent pathways. These findings suggest acyl glucuronides are able to access and damage nuclear DNA via iron-catalyzed glycation/glycoxidative processes.

Is warmer better? Decreased oxidative damage in notothenioid fish after long-term acclimation to multiple stressors.

PubMed

Enzor, Laura A; Place, Sean P

2014-09-15

Antarctic fish of the suborder Notothenioidei have evolved several unique adaptations to deal with subzero temperatures. However, these adaptations may come with physiological trade-offs, such as an increased susceptibility to oxidative damage. As such, the expected environmental perturbations brought on by global climate change have the potential to significantly increase the level of oxidative stress and cellular damage in these endemic fish. Previous single stressor studies of the notothenioids have shown they possess the capacity to acclimate to increased temperatures, but the cellular-level effects remain largely unknown. Additionally, there is little information on the ability of Antarctic fish to respond to ecologically relevant environmental changes where multiple variables change concomitantly. We have examined the potential synergistic effects that increased temperature and Ṗ(CO2) have on the level of protein damage in Trematomus bernacchii, Pagothenia borchgrevinki and Trematomus newnesi, and combined these measurements with changes in total enzymatic activity of catalase (CAT) and superoxide dismutase (SOD) in order to gauge tissue-specific changes in antioxidant capacity. Our findings indicate that total SOD and CAT activity levels displayed only small changes across treatments and tissues. Short-term acclimation to decreased seawater pH and increased temperature resulted in significant increases in oxidative damage. Surprisingly, despite no significant change in antioxidant capacity, cellular damage returned to near-basal levels, and significantly decreased in T. bernacchii, after long-term acclimation. Overall, these data suggest that notothenioid fish currently maintain the antioxidant capacity necessary to offset predicted future ocean conditions, but it remains unclear whether this capacity comes with physiological trade-offs. © 2014. Published by The Company of Biologists Ltd.

Treatment of hypertension and metabolic syndrome: lowering blood pressure is not enough for organ protection, new approach-arterial destiffening.

PubMed

Zimlichman, Reuven

2014-10-01

Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage. Until now, the main approach to reduce CVRF-induced end organ damage was by normalization of CVRFs; this approach was found effective to reduce damage and cardiovascular (CV) events. However, a residual risk always remained even when CVRFs were optimally balanced. An additional risk factor which has an immense effect on the progression of end organ damage is aging. Aging is accompanied by gradual stiffening of the arteries which finally leads to CV events. Until recently, the process of arterial aging was considered as unmodifiable, but this has changed. Arterial stiffening caused by the aging process is similar to the changes seen as a result of CVRF-induced arterial damage. Actually, the presence of CVRFs causes faster arterial stiffening, and the extent of damage is proportional to the severity of the CVRF, the length of its existence, the patient's genetic factors, etc. Conventional treatments of osteoporosis and of hormonal decline at menopause are potential additional approaches to positively affect progression of arterial stiffening. The new approach to further decrease progression of arteriosclerosis, thus preventing events, is the prevention of age-associated arterial structural changes. This approach should further decrease age-associated arterial stiffening. A totally new promising approach is to study the possibility of affecting collagen, elastin, and other components of connective tissue that participate in the process of arterial stiffening. Reduction of pulse pressure by intervention in arterial stiffening process by novel methods as breaking collagen cross-links or preventing their formation is an example of future directions in treatment. This field is of enormous potential that might be revolutionary in inducing further significant reduction of cardiovascular events.

Quantifying the risks of winter damage on overwintering crops under future climates: Will low-temperature damage be more likely in warmer climates?

NASA Astrophysics Data System (ADS)

Vico, G.; Weih, M.

2014-12-01

Autumn-sown crops act as winter cover crop, reducing soil erosion and nutrient leaching, while potentially providing higher yields than spring varieties in many environments. Nevertheless, overwintering crops are exposed for longer periods to the vagaries of weather conditions. Adverse winter conditions, in particular, may negatively affect the final yield, by reducing crop survival or its vigor. The net effect of the projected shifts in climate is unclear. On the one hand, warmer temperatures may reduce the frequency of low temperatures, thereby reducing damage risk. On the other hand, warmer temperatures, by reducing plant acclimation level and the amount and duration of snow cover, may increase the likelihood of damage. Thus, warmer climates may paradoxically result in more extensive low temperature damage and reduced viability for overwintering plants. The net effect of a shift in climate is explored by means of a parsimonious probabilistic model, based on a coupled description of air temperature, snow cover, and crop tolerable temperature. Exploiting an extensive dataset of winter wheat responses to low temperature exposure, the risk of winter damage occurrence is quantified under conditions typical of northern temperate latitudes. The full spectrum of variations expected with climate change is explored, quantifying the joint effects of alterations in temperature averages and their variability as well as shifts in precipitation. The key features affecting winter wheat vulnerability to low temperature damage under future climates are singled out.

Chemical form of selenium differentially influences DNA repair pathways following exposure to lead nitrate.

PubMed

McKelvey, Shauna M; Horgan, Karina A; Murphy, Richard A

2015-01-01

Lead, an environmental toxin is known to induce a broad range of physiological and biochemical dysfunctions in humans through a number of mechanisms including the deactivation of antioxidants thus leading to generation of reactive oxygen species (ROS) and subsequent DNA damage. Selenium on the other hand has been proven to play an important role in the protection of cells from free radical damage and oxidative stress, though its effects are thought to be form and dose dependent. As the liver is the primary organ required for metabolite detoxification, HepG2 cells were chosen to assess the protective effects of various selenium compounds following exposure to the genotoxic agent lead nitrate. Initially DNA damage was quantified using a comet assay, gene expression patterns associated with DNA damage and signalling were also examined using PCR arrays and the biological pathways which were most significantly affected by selenium were identified. Interestingly, the organic type selenium compounds (selenium yeast and selenomethionine) conferred protection against lead induced DNA damage in HepG2 cells; this is evident by reduction in the quantity of DNA present in the comet tail of cells cultured in their presence with lead. This trend also followed through the gene expression changes noted in DNA damage pathways analysed. These results were in contrast with those of inorganic sodium selenite which promoted lead induced DNA damage evident in both the comet assay results and the gene expression analysis. Over all this study provided valuable insights into the effects which various selenium compounds had on the DNA damage and signalling pathway indicating the potential for using organic forms of selenium such as selenium enriched yeast to protect against DNA damaging agents. Copyright © 2014 Elsevier GmbH. All rights reserved.

Consumption of Goats’ Milk Protects Mice From Carbon Tetrachloride-Induced Acute Hepatic Injury and Improves the Associated Gut Microbiota Imbalance

PubMed Central

Zhang, Jiachao; Wang, Zhaoxia; Huo, Dongxue; Shao, Yuyu

2018-01-01

Drugs used to treat liver diseases have serious side effects; it is important to search for safe functional foods with hepatoprotective functions and few side effects. In this study, potential hepatoprotective effects of goats’ milk and cows’ milk on mice with CCl4-induced acute hepatic injury were evaluated. We also elucidated the role of goats’ and cows’ milk on the regulation of CCl4-induced gut microbiota imbalance. In mice with liver damage induced by CCl4, administration of goats’ milk for 7 days prior to injection of CCl4 had beneficial effects on the indicators of liver damage within 1 day: the area of liver necrosis was small; activity of alanine transaminase (ALT) and aspartate transaminase (AST) and expression of the genes CYP2E1 and TNF-α were lower than that of model group of mice. By 7 days after CCl4 injection, there were no significant differences in liver damage indicators (ALT, AST, malondialdehyde, superoxide dismutase, and glutathione) between the goats’ milk group, which continued to receive goats’ milk, and the untreated control group of mice showing that goats’ milk continued to protect against liver damage. Throughout the entire experiment, the community of gut microbes from mice in the goats’ milk treatment was more similar to the untreated control group than to the cows’ milk group and the model group, indicating that intake of goats’ milk prior and post-CCl4 injection effectively prevented and alleviated the intestinal microbial disorder that caused by CCl4 in mice. Our research suggests that goats’ milk could be developed as a potential functional food to prevent/protect against liver injury. PMID:29867999

Damage Analysis of Tensile Deformation of Co-rolled SMATed 304SS

NASA Astrophysics Data System (ADS)

Guo, X.; Leung, A. Y. T.; Chen, A.; Ruan, H.; Lu, J.

2010-05-01

One of recent experimental progresses in strengthening and toughening metals simultaneously is to adopt techniques of surface mechanical attrition treatment (SMAT) and warm co-rolling to 304 stainless steel (SS). To capture deformation behavior and associated damage initiation/evolution process in the co-rolled SMATed 304SS, cohesive finite element method (CFEM) is employed in this paper and simulation results are in agreement with experimental results. Both strengthening effect due to high yield stress of the nanograin layer and toughening effect due to non-localized damage in the nanograin layer are captured. Effect of energy release rate of nanograin layer on failure strain of layered co-rolled SMATed 304SS is investigated. It is found that the more brittle the nanograin layer is, the more potential necking sites in the nanograin layer are, and the more ductile the layered co-rolled SMATed 304SS is.

49 CFR 195.403 - Emergency response training.

Code of Federal Regulations, 2012 CFR

2012-10-01

... to minimize the potential for fire, explosion, toxicity, or environmental damage; and (5) Learn the... changes to the emergency response training program as necessary to ensure that it is effective. (c) Each...

49 CFR 195.403 - Emergency response training.

Code of Federal Regulations, 2011 CFR

2011-10-01

... to minimize the potential for fire, explosion, toxicity, or environmental damage; and (5) Learn the... changes to the emergency response training program as necessary to ensure that it is effective. (c) Each...

49 CFR 195.403 - Emergency response training.

Code of Federal Regulations, 2014 CFR

2014-10-01

... to minimize the potential for fire, explosion, toxicity, or environmental damage; and (5) Learn the... changes to the emergency response training program as necessary to ensure that it is effective. (c) Each...

49 CFR 195.403 - Emergency response training.

Code of Federal Regulations, 2013 CFR

2013-10-01

... to minimize the potential for fire, explosion, toxicity, or environmental damage; and (5) Learn the... changes to the emergency response training program as necessary to ensure that it is effective. (c) Each...

Effects of short-term tocopherol (T) feeding on nitric oxide production and protein nitration following endotoxin (LPS) challenge in beef calves

USDA-ARS?s Scientific Manuscript database

Posttranslational protein tyrosine nitration (pNT) contributes to functional tissue damage during pro-inflammatory stress. With regard to chemical reactivity, a-T has a greater antioxidant potential while '-T has greater ability to inactivate reactive oxynitrogen species potentially involved in pTN ...

Antidiabetics and diuretics show phototoxicity in HaCaT cells

NASA Astrophysics Data System (ADS)

Selvaag, Edgar; Petersen, Anita B.; Gniadecki, Robert; Thorn, Tine; Wulf, Hans Christian

2001-10-01

The antidiabetics tolbutamide, glibenclamide, and glipizide, and the diuretics bendroflumethiazide, butizide, furosemide, hydrochlorothiazide, and trichlormethiazide were investigated for potential phototoxicity in the HaCaT cell line. The cells were incubated with the drugs and then exposed to UVA1 irradiation. The effects of the antioxidants L-ascorbic acid, and (alpha) -tocopherol on oxidative DNA damage were assessed. Bendroflumethiazide, furosemide, hydrochlorothiazide, trichlormethiazide, or tolbutamide induced dose-dependent phototoxicity. Cells incubated with bendroflumethiazide, tolbutamide, and glibenclamide, and irradiated with UVA1 demonstrated an increased oxidative DNA damage. Pre-treatment with L-ascorbic acid, or (alpha) -tocopherol, suppressed the UVA-induced DNA damage in cells incubated with 1 mM of bendroflumethiazide, furosemide, glibenclamide, glipizide, tolbutamide, and trichloromethiazide, further implying the involvement of reactive oxygen species in the phototoxic DNA damage. These results may indicate a link between phototoxic and photocancerogenic potential of the sulfonamide-derived oral antidiabetic and diuretic drugs, as it has previously been recognized for psoralen, chlorpromazine, and fluoroquinolones. Excessive exposure to UV light may be deleterious for patients treated with these drugs.

An investigation of the effects of MitoQ on human peripheral mononuclear cells.

PubMed

Marthandan, Shiva; Murphy, Michael P; Billett, Ellen; Barnett, Yvonne

2011-03-01

MitoQ is a ubiquinone derivative targeted to mitochondria which is known to have both antioxidant and anti-apoptotic properties within mammalian cells. Previous research has suggested that the age-related increase in oxidative DNA damage in T lymphocytes might contribute to their functional decline with age. This paper describes the impact of mitoQ on unchallenged or oxidatively challenged ex vivo human peripheral blood mononuclear cells from healthy 25-30 or 55-60 year old volunteers. When cells were challenged with hydrogen peroxide (H(2)O(2)), following mitoQ treatment (0.1-1.0 μM), the ratio of reduced to oxidized forms of glutathione increased, the levels of oxidative DNA damage decreased and there was an increase in the mitochondrial membrane potential. Low levels of mitoQ (0.1 or 0.25 μM) had no impact on endogenous DNA damage, whilst higher levels (0.5 and 1.0 μM) of mitoQ significantly reduced endogenous levels of DNA damage. The results of this investigation suggest that mitoQ may have anti-immunosenescent potential.

Acoustic Emission Beamforming for Detection and Localization of Damage

NASA Astrophysics Data System (ADS)

Rivey, Joshua Callen

The aerospace industry is a constantly evolving field with corporate manufacturers continually utilizing innovative processes and materials. These materials include advanced metallics and composite systems. The exploration and implementation of new materials and structures has prompted the development of numerous structural health monitoring and nondestructive evaluation techniques for quality assurance purposes and pre- and in-service damage detection. Exploitation of acoustic emission sensors coupled with a beamforming technique provides the potential for creating an effective non-contact and non-invasive monitoring capability for assessing structural integrity. This investigation used an acoustic emission detection device that employs helical arrays of MEMS-based microphones around a high-definition optical camera to provide real-time non-contact monitoring of inspection specimens during testing. The study assessed the feasibility of the sound camera for use in structural health monitoring of composite specimens during tensile testing for detecting onset of damage in addition to nondestructive evaluation of aluminum inspection plates for visualizing stress wave propagation in structures. During composite material monitoring, the sound camera was able to accurately identify the onset and location of damage resulting from large amplitude acoustic feedback mechanisms such as fiber breakage. Damage resulting from smaller acoustic feedback events such as matrix failure was detected but not localized to the degree of accuracy of larger feedback events. Findings suggest that beamforming technology can provide effective non-contact and non-invasive inspection of composite materials, characterizing the onset and the location of damage in an efficient manner. With regards to the nondestructive evaluation of metallic plates, this remote sensing system allows us to record wave propagation events in situ via a single-shot measurement. This is a significant improvement over the conventional wave propagation tracking technique based on laser doppler vibrometry that requires synchronization of data acquired from numerous excitations and measurements. The proposed technique can be used to characterize and localize damage by detecting the scattering, attenuation, and reflections of stress waves resulting from damage and defects. These studies lend credence to the potential development of new SHM/NDE techniques based on acoustic emission beamforming for characterizing a wide spectrum of damage modes in next-generation materials and structures without the need for mounted contact sensors.

Comparative kinetics of damage to the plasma and mitochondrial membranes by intra-cellularly synthesized and externally-provided photosensitizers using multi-color FACS.

PubMed

Haupt, Sara; Malik, Zvi; Ehrenberg, Benjamin

2014-01-01

Photodynamic therapy (PDT) of cancer involves inflicting lethal damage to the cells of malignant tumors, primarily by singlet oxygen that is generated following light-absorption in a photosensitizer molecule. Dysfunction of cells is manifested in many ways, including peroxidation of cellular components, membrane rupture, depolarization of electric potentials, termination of mitochondrial activity, onset of apoptosis and necrosis and eventually cell lysis. These events do not necessarily occur in linear fashion and different types of damage to cell components occur, most probably, in parallel. In this report we measured the relative rates of damage to two cellular membranes: the plasma membrane and the mitochondrial membrane. We employed photosensitizers of diverse hydrophobicities and used different incubation procedures, which lead to their different intra-cellular localizations. We monitored the damage that was inflicted on these membranes, by employing optical probes of membrane integrity, in a multi-color FACS experiment. The potentiometric indicator JC-1 monitored the electric cross-membrane potential of the mitochondria and the fluorometric indicator Draq7 monitored the rupture of the plasma membrane. We show that the electric depolarization of the mitochondrial membrane and the damage to the enveloping plasma membrane proceed with different kinetics that reflect the molecular character and intracellular location of the sensitizer: PpIX that is synthesized in the cells from ALA causes rapid mitochondrial damage and very slow damage to the plasma membrane, while externally added PpIX has an opposite effect. The hydrophilic sensitizer HypS4 can be taken up by the cells by different incubation conditions, and these affect its intracellular location, and as a consequence either the plasma membrane or the mitochondria is damaged first. A similar correlation was found for additional extracellularly-provided photosensitizers HP and PpIX.

Environmental and medical geochemistry in urban disaster response and preparedness

USGS Publications Warehouse

Plumlee, Geoffrey S.; Morman, Suzette A.; Cook, A.

2012-01-01

History abounds with accounts of cities that were destroyed or significantly damaged by natural or anthropogenic disasters, such as volcanic eruptions, earthquakes, wildland–urban wildfires, hurricanes, tsunamis, floods, urban firestorms, terrorist attacks, and armed conflicts. Burgeoning megacities place ever more people in the way of harm from future disasters. In addition to the physical damage, casualties, and injuries they cause, sudden urban disasters can also release into the environment large volumes of potentially hazardous materials. Environmental and medical geochemistry investigations help us to (1) understand the sources and environmental behavior of disaster materials, (2) assess potential threats the materials pose to the urban environment and health of urban populations, (3) develop strategies for their cleanup/disposal, and (4) anticipate and mitigate potential environmental and health effects from future urban disasters.

Myoprotective Potential of Creatine Is Greater than Whey Protein after Chemically-Induced Damage in Rat Skeletal Muscle

PubMed Central

Cooke, Matthew B.; Stathis, Christos G.; Hayes, Alan

2018-01-01

The myoprotective effects of creatine monohydrate (CR) and whey protein (WP) are equivocal, with the use of proxy measures of muscle damage making interpretation of their effectiveness limited. The purpose of the study was to determine the effects of CR and WP supplementation on muscle damage and recovery following controlled, chemically-induced muscle damage. Degeneration of the extensor digitorum longus (EDL) muscle was induced by bupivacaine in rats supplemented with either CR, WP, or standard rat chow (CON). At day 7 and 14 post-myotoxic injury, injured EDL muscles were surgically removed and tested for isometric contractile properties, followed by the contralateral, non-injured EDL muscle. At the completion of testing, muscles were snap-frozen in liquid nitrogen and stored for later analysis. Data were analyzed using analysis of variance. Creatine-supplemented muscles displayed a greater proportion of non-damaged (intact) fibers (p = 0.002) and larger cross-sectional areas of regenerating and non-damaged fibers (p = 0.024) compared to CON muscles at day 7 post-injury. At day 14 post-injury, CR-supplemented muscles generated higher absolute forces concomitant with greater contractile protein levels compared to CON (p = 0.001, p = 0.008) and WP-supplemented muscles (p = 0.003, p = 0.006). Creatine supplementation appears to offer an element of myoprotection which was not observed following whey protein supplementation. PMID:29710855

Mobile phone radiation-induced free radical damage in the liver is inhibited by the antioxidants N-acetyl cysteine and epigallocatechin-gallate.

PubMed

Ozgur, Elcin; Güler, Göknur; Seyhan, Nesrin

2010-11-01

To investigate oxidative damage and antioxidant enzyme status in the liver of guinea pigs exposed to mobile phone-like radiofrequency radiation (RFR) and the potential protective effects of N-acetyl cysteine (NAC) and epigallocatechin-gallate (EGCG) on the oxidative damage. Nine groups of guinea pigs were used to study the effects of exposure to an 1800-MHz Global System for Mobile Communications (GSM)-modulated signal (average whole body Specific Absorption Rate (SAR) of 0.38 W/kg, 10 or 20 min per day for seven days) and treatment with antioxidants. Significant increases in malondialdehyde (MDA) and total nitric oxide (NO(x)) levels and decreases in activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and glutathione peroxidase (GSH-Px) were observed in the liver of guinea pigs after RFR exposure. Only NAC treatment induces increase in hepatic GSH-Px activities, whereas EGCG treatment alone attenuated MDA level. Extent of oxidative damage was found to be proportional to the duration of exposure (P < 0.05). Mobile phone-like radiation induces oxidative damage and changes the activities of antioxidant enzymes in the liver. The adverse effect of RFR may be related to the duration of mobile phone use. NAC and EGCG protect the liver tissue against the RFR-induced oxidative damage and enhance antioxidant enzyme activities.

Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj

Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophinmore » (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA damage.« less

Progranulin, a Major Secreted Protein of Mouse Adipose-Derived Stem Cells, Inhibits Light-Induced Retinal Degeneration

PubMed Central

Tsuruma, Kazuhiro; Yamauchi, Mika; Sugitani, Sou; Otsuka, Tomohiro; Ohno, Yuta; Nagahara, Yuki; Ikegame, Yuka; Shimazawa, Masamitsu; Yoshimura, Shinichi; Iwama, Toru

2014-01-01

Adipose tissue stromal vascular fraction contains mesenchymal stem cells, which show protective effects when administered to damaged tissues, mainly through secreted trophic factors. We examined the protective effects of adipose-derived stem cells (ASCs) and ASC-conditioned medium (ASC-CM) against retinal damage and identified the neuroprotective factors in ASC-CM. ASCs and mature adipocytes were isolated from mouse subcutaneous tissue. ASCs were injected intravitreally in a mouse model of light-induced retinal damage, and ASC injection recovered retinal function as measured by electroretinogram and inhibited outer nuclear layer, thinning, without engraftment of ASCs. ASC-CM and mature adipocyte-conditioned medium were collected after 72 hours of culture. In vitro, H2O2- and light-induced cell death was reduced in a photoreceptor cell line with ASC-CM but not with mature adipocyte-conditioned medium. In vivo, light-induced photoreceptor damage was evaluated by measurement of outer nuclear layer thickness at 5 days after light exposure and by electroretinogram recording. ASC-CM significantly inhibited photoreceptor degeneration and retinal dysfunction after light exposure. Progranulin was identified as a major secreted protein of ASCs that showed protective effects against retinal damage in vitro and in vivo. Furthermore, progranulin phosphorylated extracellular signal-regulated kinase, cAMP response element binding protein, and hepatocyte growth factor receptor, and protein kinase C signaling pathways were involved in the protective effects of progranulin. These findings suggest that ASC-CM and progranulin have neuroprotective effects in the light-induced retinal-damage model. Progranulin may be a potential target for the treatment of the degenerative diseases of the retina. PMID:24233842

Progranulin, a major secreted protein of mouse adipose-derived stem cells, inhibits light-induced retinal degeneration.

PubMed

Tsuruma, Kazuhiro; Yamauchi, Mika; Sugitani, Sou; Otsuka, Tomohiro; Ohno, Yuta; Nagahara, Yuki; Ikegame, Yuka; Shimazawa, Masamitsu; Yoshimura, Shinichi; Iwama, Toru; Hara, Hideaki

2014-01-01

Adipose tissue stromal vascular fraction contains mesenchymal stem cells, which show protective effects when administered to damaged tissues, mainly through secreted trophic factors. We examined the protective effects of adipose-derived stem cells (ASCs) and ASC-conditioned medium (ASC-CM) against retinal damage and identified the neuroprotective factors in ASC-CM. ASCs and mature adipocytes were isolated from mouse subcutaneous tissue. ASCs were injected intravitreally in a mouse model of light-induced retinal damage, and ASC injection recovered retinal function as measured by electroretinogram and inhibited outer nuclear layer, thinning, without engraftment of ASCs. ASC-CM and mature adipocyte-conditioned medium were collected after 72 hours of culture. In vitro, H2O2- and light-induced cell death was reduced in a photoreceptor cell line with ASC-CM but not with mature adipocyte-conditioned medium. In vivo, light-induced photoreceptor damage was evaluated by measurement of outer nuclear layer thickness at 5 days after light exposure and by electroretinogram recording. ASC-CM significantly inhibited photoreceptor degeneration and retinal dysfunction after light exposure. Progranulin was identified as a major secreted protein of ASCs that showed protective effects against retinal damage in vitro and in vivo. Furthermore, progranulin phosphorylated extracellular signal-regulated kinase, cAMP response element binding protein, and hepatocyte growth factor receptor, and protein kinase C signaling pathways were involved in the protective effects of progranulin. These findings suggest that ASC-CM and progranulin have neuroprotective effects in the light-induced retinal-damage model. Progranulin may be a potential target for the treatment of the degenerative diseases of the retina.

DNA damage in B and T lymphocytes of farmers during one pesticide spraying season.

PubMed

Lebailly, Pierre; Mirey, Gladys; Herin, Fabrice; Lecluse, Yannick; Salles, Bernard; Boutet-Robinet, Elisa

2015-10-01

The effect of one pesticide spraying season on DNA damage was measured on B and T lymphocytes among open-field farmers and controls. At least two peripheral blood samples were collected from each individual: one in a period without any pesticide application, several weeks after the last use (January, at period P0), and another in the intensive pesticide spraying period (May or June, at period P4). DNA damage was studied by alkaline comet assay on isolated B or T lymphocytes. Longitudinal comparison of DNA damage observed at both P0 and P4 periods revealed a statistically significant genotoxic effect of the pesticide spraying season in both B (P = 0.02) and T lymphocytes (P = 0.02) in exposed farmers. In contrast, non-farmers did not show any significant modifications. DNA damage levels in B and T lymphocytes were significantly higher in farmers than in non-farmers during the P4 period (P = 0.003 and P = 0.001 for B and T lymphocytes, respectively) but not during the P0 period. The seasonal effect observed among farmers was not correlated with either total farm area, farm area devoted to crops or recent solar exposure. On average, farmers used pesticides for 21 days between P0 and P4. Between the two time points studied, there was a tendency for a potential effect of the number of days of fungicide treatments (r (2) = 0.43; P = 0.11) on T lymphocyte DNA damage. A genotoxic effect was found in lymphocytes of farmers exposed to pesticides, suggesting in particular the possible implication of fungicides.

Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats

PubMed Central

King, Tristan J.; Shandala, Tetyana; Lee, Alice M.; Foster, Bruce K.; Chen, Ke-Ming; Howe, Peter R.; Xian, Cory J.

2015-01-01

Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage. PMID:26258775

Thermomechanical Fatigue Durability of T650-35/PMR-15 Sheet Molding Compound

NASA Technical Reports Server (NTRS)

Castelli, Michael G.; Sutter, James K.; Benson, Dianne

1998-01-01

Although polyimide based composites have been used for many years in a wide variety of elevated temperature applications, very little work has been done to examine the durability and damage behavior under more prototypical thermomechanical fatigue (TMF) loadings. Synergistic effects resulting from simultaneous temperature and load cycling can potentially lead to enhanced, if not unique, damage modes and contribute to a number of nonlinear deformation responses. The goal of this research was to examine the effects of a TMF loading spectrum, representative of a gas turbine engine compressor application, on a polyimide sheet molding compound (SMC). High performance SMCs present alternatives to prepreg forms with great potential for low cost component production through less labor intensive, more easily automated manufacturing. To examine the issues involved with TMF, a detailed experimental investigation was conducted to characterize the durability of a T650-35/PMR-15 SMC subjected to TMF mission cycle loadings. Fatigue damage progression was tracked through macroscopic deformation and elastic stiffness. Additional properties, such as the glass transition temperature (T(sub g) and dynamic mechanical properties were examined. The fiber distribution orientation was also characterized through a detailed quantitative image analysis. Damage tolerance was quantified on the basis of residual static tensile properties after a prescribed number of TMF missions. Detailed microstructural examinations were conducted using optical and scanning electron microscopy to characterize the local damage. The imposed baseline TMF missions had only a modest impact on inducing fatigue damage with no statistically significant degradation occurring in the measured macroscopic properties. Microstructural damage was, however, observed subsequent to 100 h of TMF cycling which consisted primarily of fiber debonding and transverse cracking local to predominantly transverse fiber bundles. The TMF loadings did introduce creep related effects (strain accumulation) which led to rupture in some of the more aggressive stress scenarios examined. In some cases this creep behavior occurred at temperatures in excess of 150 C below commonly cited values for T(sub g). Thermomechanical exploratory creep tests revealed that the SMC was subject to time dependent deformation at stress/temperature thresholds of 150 MPa/230 C and 170 MPa/180 C.

Individual- and scattered-tree influences on ultraviolet irradiance

Treesearch

Gordon M. Heisler; Richard H. Gao, Wei Grant

2003-01-01

Many of the potential effects of ultraviolet radiation (UVR--damage to materials, altered herbivory of insects and activity of microbes, modified growth of vegetation, and adverse or beneficial effects on human health?are modified by the presence of trees that influence UVR exposure to various degrees. Though tree effects on total solar irradiance have been...

Ion Plume Damage in Formation Flight Regimes

NASA Astrophysics Data System (ADS)

Young, Jarred Alexander

This effort examines the potential for damage from plume impingement from an electric propulsion system within spacecraft missions that utilize a formation flight architecture. Specifically, the potential erosion of a structural material (Aluminum) and anti-reflective coatings for solar cell coverglass are explored. Sputter yields for the materials of Aluminum, Magnesium Fluoride, and Indium Tin Oxide are experimentally validated using an electrostatic ion source at energies varying from 500-1500 eV. Erosion depths are analyzed using white-light optical profilometry to measure potential depths up to 1 microm. This erosion data was then utilized to create (or augment) Bohdansky and Yamamura theoretical curve fits for multiple incidence angles to look at theoretical sputter effects within formation flight regimes at multiple formation distances from 50-1000 m. The damage from these electric propulsion plumes is explored throughout multiple orbital conditions from LEO, Sun-Synchronous, and GEO. Factors affecting erosion are: plume density, local geomagnetic field environment and incidence angles of target surfaces. Results from this simulated study show significant erosion with GEO with minor erosion in some LEO and all Sun-Synchronous cases.

Ozonized sunflower oil reduces oxidative damage induced by indomethacin in rat gastric mucosa.

PubMed

Zamora, Z; González, R; Guanche, D; Merino, N; Menéndez, S; Hernández, F; Alonso, Y; Schulz, S

2008-01-01

This study was carried out in order to investigate the potential cytoprotective effects of ozonized sunflower oil (OSO) in the damage of rat gastric mucosa induced by indomethacin and also to elucidate the role of reactive oxygen species (ROS), lipid peroxidation and some constituents of antioxidant defense such as superoxide dismutase (SOD) and catalase (CAT) in these effects. The gastric damage was induced by indomethacin (20 mg/kg) as solution in 0.5% sodium bicarbonate and given intragastrically. Three hours later OSO (4, 12 and 24 mg/kg) and cimetidine 25 mg/kg were administered also by oral route. Four hours thereafter the rats were killed and the stomachs were removed for biochemical analysis and histological study. The gastric ulcer index was reduced by OSO and cimetidine. OSO also reduced TBARS concentration, but it increased SOD activity in gastric mucosa homogenates. In contrast, CAT activity was not significantly modified the treatment. Histological study confirmed the cytoprotective effects of OSO in rat gastric mucosa damaged by indomethacin. It was concluded that cytoprotective effects of OSO in rat gastric mucosa are mediated at least partially by upregulation of the antioxidant system and mainly SOD.

Cavitation damage prediction for spallation target vessels by assessment of acoustic vibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Futakawa, Masatoshi; Kogawa, Hiroyuki; Hasegawa, Shoichi

2008-01-01

Liquid-mercury target systems for MW-class spallation neutron sources are being developed around the world. Proton beams are used to induce the spallation reaction. At the moment the proton beam hits the target, pressure waves are generated in the mercury because of the abrupt heat deposition. The pressure waves interact with the target vessel leading to negative pressure that may cause cavitation along the vessel wall. In order to estimate the cavitation erosion, i.e. the pitting damage formed by the collapse of cavitation bubbles, off-beam tests were performed by using an electric magnetic impact testing machine (MIMTM), which can impose equivalentmore » pressure pulses in mercury. The damage potential was defined based on the relationship between the pitting damage and the time-integrated acoustic vibration induced by impact due to the bubble collapses. Additionally, the damage potential was measured in on-beam tests carried out by using the proton beam at WNR (Weapons Neutron Research) facility in Los Alamos Neutron Science Center (LANSCE). In this paper, the concept of the damage potential, the relationship between the pitting damage formation and the damage potential both in off-beam and on-beam tests is shown.« less

ShakeCast: Automating and improving the use of shakemap for post-earthquake deeision-making and response

USGS Publications Warehouse

Wald, D.; Lin, K.-W.; Porter, K.; Turner, Loren

2008-01-01

When a potentially damaging earthquake occurs, utility and other lifeline managers, emergency responders, and other critical users have an urgent need for information about the impact on their particular facilities so they can make appropriate decisions and take quick actions to ensure safety and restore system functionality. ShakeMap, a tool used to portray the extent of potentially damaging shaking following an earthquake, on its own can be useful for emergency response, loss estimation, and public information. However, to take full advantage of the potential of ShakeMap, we introduce ShakeCast. ShakeCast facilitates the complicated assessment of potential damage to a user's widely distributed facilities by comparing the complex shaking distribution with the potentially highly variable damageability of their inventory to provide a simple, hierarchical list and maps of structures or facilities most likely impacted. ShakeCast is a freely available, post-earthquake situational awareness application that automatically retrieves earthquake shaking data from ShakeMap, compares intensity measures against users' facilities, sends notifications of potential damage to responsible parties, and generates facility damage maps and other Web-based products for both public and private emergency managers and responders. ?? 2008, Earthquake Engineering Research Institute.

A study of DNA protective effect of orange juice supplementation.

PubMed

Szeto, Yim Tong; To, Tai Lun; Pak, Sok Cheon; Kalle, Wouter

2013-05-01

The potential acute genoprotective effect of orange juice supplementation was investigated. Six healthy subjects (aged 33 to 60 years; 3 women and 3 men) were asked to drink 400 mL of commercial orange juice, which contained 100 mg vitamin C and 40.8 g sugar. Venous blood (2 mL) was taken before and 2 h after ingestion (test trial). A week later, the subjects were asked to repeat the trial by drinking 400 mL water with 100 mg vitamin C and 40.8 g glucose (control trial). Lymphocytes isolated from blood samples underwent comet assay on the day of collection. Pre- and postingestion DNA damage scores were measured in both the test and control trials. Results showed that there was a significant decrease in DNA damage induced by hydrogen peroxide after 2 h of supplementation with orange juice, and no change in baseline DNA damage. There was no significant decrease in the DNA damage in lymphocytes in the control trial.

In vitro antioxidant properties, DNA damage protective activity, and xanthine oxidase inhibitory effect of cajaninstilbene acid, a stilbene compound derived from pigeon pea [Cajanus cajan (L.) Millsp.] leaves.

PubMed

Wu, Nan; Kong, Yu; Fu, Yujie; Zu, Yuangang; Yang, Zhiwei; Yang, Mei; Peng, Xiao; Efferth, Thomas

2011-01-12

The antioxidant properties, DNA damage protective activities, and xanthine oxidase (XOD) inhibitory effect of cajaninstilbene acid (CSA) derived from pigeon pea leaves were studied in the present work. Compared with resveratrol, CSA showed stronger antioxidant properties, DNA damage protective activity, and XOD inhibition activity. The IC(50) values of CSA for superoxide radical scavenging, hydroxyl radical scavenging, nitric oxide scavenging, reducing power, lipid peroxidation, and XOD inhibition were 19.03, 6.36, 39.65, 20.41, 20.58, and 3.62 μM, respectively. CSA possessed good protective activity from oxidative DNA damage. Furthermore, molecular docking indicated that CSA was more potent than resveratrol or allopurinol to interact with the active site of XOD (calculated free binding energy: -229.71 kcal mol(-1)). On the basis of the results, we conclude that CSA represents a valuable natural antioxidant source and may potentially be applicable in health food industry.

Future property damage from flooding: sensitivities to economy and climate change

DOE PAGES

Liu, Jing; Hertel, Thomas; Diffenbaugh, Noah; ...

2015-08-09

Using a unique dataset for Indiana counties during the period 1995-2012, we estimate the effects of flood hazard, asset exposure, and social vulnerability on property damage. This relationship then is combined with the expected level of future flood risks to project property damage from flooding in 2030 under various scenarios. We compare these scenario projections to identify which risk management strategy offers the greatest potential to mitigate flooding loss. Results show that by 2030, county level flooding hazard measured by extreme flow volume and frequency will increase by an average of 16.2% and 7.4%, respectively. The total increase in propertymore » damages projected under different model specifications range from 13.3% to 20.8%. Across models future damages consistently exhibit the highest sensitivity to future increases in asset exposure, reinforcing the importance of non-structural measures in managing floodplain development.« less

Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats.

PubMed

El-Akabawy, Gehan; El-Kholy, Wael

2014-05-01

Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain. Copyright © 2014 Elsevier GmbH. All rights reserved.

Cardanol: toxicogenetic assessment and its effects when combined with cyclophosphamide

PubMed Central

Schneider, Beatriz Ursinos Catelan; Meza, Alisson; Beatriz, Adilson; Pesarini, João Renato; de Carvalho, Pamela Castilho; Mauro, Mariana de Oliveira; Karaziack, Caroline Bilhar; Cunha-Laura, Andréa Luiza; Monreal, Antônio Carlos Duenhas; Matuo, Renata; de Lima, Dênis Pires; Oliveira, Rodrigo Juliano

2016-01-01

Abstract Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide. PMID:27303909

Leucocytes DNA damage in mice exposed to JS-118 by the comet assay.

PubMed

Zhang, Tao; Hu, Jiye; Zhang, Yuchao; Zhao, Qianfei; Ning, Jun

2011-09-01

JS-118 is an extensively used insecticide in China. The present study investigated the genotoxic effect of JS-118 on whole blood at 24, 48, 72 and 96 h by using alkaline comet assay. Male Kunming mice were given 6.25, 12.5, 25, 50 and 100 mg/kg BW of JS-118 intraperitoneally. A statistically significant increase in all comet parameters indicating DNA damage was observed at 24 h post-treatment (p < 0.05). A clear concentration-dependent increase of DNA damage was revealed as evident by the OTM (arbitrary units), tail length (µm) and tail DNA (%). From 48 h post-treatment, a gradual decrease in mean comet parameters was noted. By 96 h of post-treatment, the mean comet tail length reached control levels indicating repair of damaged DNA. This study on mice showed different DNA damage depending on the concentration of JS-118 and the period of treatment. The present study provided further information of the potential risk of the genetic damage caused by JS-118.

Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

DTIC Science & Technology

2010-01-01

mice: protective effect of alpha - lipoic acid . Behav Brain Res 2007b; 177(1): 7-14. [8] Manda K, Ueno M, Anzai K. Melatonin mitigates oxidative...Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha - lipoic acid . Behav Brain Res 2008b...1977; 171(1): 39-50. [6] Manda K, Ueno M, Moritake T, Anzai K. - Lipoic acid attenuates x-irradiation-induced oxidative stress in mice. Cell Biol

Protection against acetaminophen-induced acute liver failure by omentum adipose tissue derived stem cells through the mediation of Nrf2 and cytochrome P450 expression.

PubMed

Huang, Yu-Jen; Chen, Poda; Lee, Chih-Yuan; Yang, Sin-Yu; Lin, Ming-Tsan; Lee, Hsuan-Shu; Wu, Yao-Ming

2016-01-19

Acetaminophen (APAP) overdose causes acute liver failure (ALF) in animals and humans via the rapid depletion of intracellular glutathione (GSH) and the generation of excess reactive oxygen species (ROS) that damage hepatocytes. Stem cell therapy is a potential treatment strategy for ALF. We isolated mesenchymal stem cells (MSCs) from mice omentum adipose tissue-derived stem cells (ASCs) and transplanted them into a mouse model of APAP-induced ALF to explore their therapeutic potential. In addition, we performed in vitro co-culture studies with omentum-derived ASCs and primary isolated hepatocytes to demonstrate the hepatoprotective effect of omentum-derived ASCs on hepatocytes that were subjected to APAP-induced damage. ASC transplantation significantly improved the survival rate of mice with ALF and attenuated the severity of APAP-induced liver damage by suppressing cytochrome P450 activity to reduce the accumulation of toxic nitrotyrosine and the upregulation of NF-E2-related factor 2 (Nrf2) expression, resulting in an increase in the subsequent antioxidant activity. These effects protected the hepatocytes from APAP-induced damage through the suppression of downstream MAPK signal activation and inflammatory cytokine production. our results demonstrate that omentum-derived ASCs are an alternative source of ASCs that regulate the antioxidant response and may represent a beneficial therapeutic strategy for ALF.

Low-concentration BPAF- and BPF-induced cell biological effects are mediated by ROS in MCF-7 breast cancer cells.

PubMed

Lei, Bingli; Sun, Su; Xu, Jie; Feng, Chenglian; Yu, Yingxin; Xu, Gang; Wu, Minghong; Peng, Wei

2018-02-01

Reactive oxygen species (ROS) induced by bisphenol A (BPA) have been implicated in cellular oxidative damage and carcinogenesis. It is not known whether the potential alternatives of BPA, bisphenol AF (BPAF), and bisphenol F (BPF) can also induce ROS involved in mediating biological responses. This study evaluated the toxicity of BPAF and BPF on cell proliferation, DNA damage, intracellular calcium homeostasis, and ROS generation in MCF-7 human breast cancer cells. The results showed that BPAF at 0.001-1 μM and BPF at 0.01-1 μM significantly increased cell viability and at 25 and 50 μM, both compounds decreased cell viability. At 0.01-10 μM, both BPAF and BPF increased DNA damage and significantly elevated ROS and intracellular Ca 2+ levels in MCF-7 cells. These biological effects were attenuated by the ROS scavenger N-acetylcysteine (NAC), indicating that ROS played a key role in the observed biological effects of BPAF and BPF on MCF-7 cells. These findings can deepen our understanding on the toxicity of BPAF and BPF, and provide basis data to further evaluate the potential health harm and establish environmental standard of BPAF and BPF.

Integration of genotoxicity and population genetic analyses in kangaroo rats (Dipodomys merriami) exposed to radionuclide contamination at the Nevada Test Site, USA

USGS Publications Warehouse

Theodorakis, Christopher W.; Bickham, John W.; Lamb, Trip; Medica, Philip A.; Lyne, T. Barrett

2001-01-01

We examined effects of radionuclide exposure at two atomic blast sites on kangaroo rats (Dipodomys merriami) at the Nevada Test Site, Nevada, USA, using genotoxicity and population genetic analyses. We assessed chromosome damage by micronucleus and flow cytometric assays and genetic variation by randomly amplified polymorphic DNA (RAPD) and mitochondrial DNA (mtDNA) analyses. The RAPD analysis showed no population structure, but mtDNA exhibited differentiation among and within populations. Genotoxicity effects were not observed when all individuals were analyzed. However, individuals with mtDNA haplotypes unique to the contaminated sites had greater chromosomal damage than contaminated-site individuals with haplotypes shared with reference sites. When interpopulation comparisons used individuals with unique haplotypes, one contaminated site had greater levels of chromosome damage than one or both of the reference sites. We hypothesize that shared-haplotype individuals are potential migrants and that unique-haplotype individuals are potential long-term residents. A parsimony approach was used to estimate the minimum number of migration events necessary to explain the haplotype distributions on a phylogenetic tree. The observed predominance of migration events into the contaminated sites supported our migration hypothesis. We conclude the atomic blast sites are ecological sinks and that immigration masks the genotoxic effects of radiation on the resident populations.

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice

PubMed Central

Salgueiro, Andréia Caroline Fernandes; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Puntel, Robson Luiz; Puntel, Gustavo Orione

2016-01-01

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential. PMID:26839634

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice.

PubMed

Salgueiro, Andréia Caroline Fernandes; Folmer, Vanderlei; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Franco, Jeferson Luis; Puntel, Robson Luiz; Puntel, Gustavo Orione

2016-01-01

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

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

PubMed

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

2016-10-01

The main components of sunlight reaching the eye lens are UVA and visible light exerting their photo-damaging effects indirectly by the aid of endogenous photosensitizer molecules such as riboflavin (RF). In this study, lens proteins solutions were incubated with RF and exposed to the sunlight. Then, gel mobility shift analysis and different spectroscopic assessments were applied to examine the structural damaging effects of solar radiation on these proteins. Exposure of lens proteins to direct sunlight, in the presence of RF, leads to marked structural crosslinking, oligomerization and proteolytic instability. These structural damages were also accompanied with reduction in the emission fluorescence of Trp and Tyr and appearance of a new absorption peak between 300 and 400nm which can be related to formation of new chromophores. Also, photo-oxidation of lens crystallins increases their oligomeric size distribution as examined by dynamic light scattering analysis. The above mentioned structural insults, as potential sources of sunlight-induced senile cataract and blindness, were significantly attenuated in the presence of ascorbic acid and glutathione which are two important components of lens antioxidant defense system. Therefore, the powerful antioxidant defense mechanism of eye lens is an important barrier against molecular photo-damaging effects of solar radiations during the life span. Copyright © 2016 Elsevier B.V. All rights reserved.

High-fidelity Modeling of Local Effects of Damage for Derated Offshore Wind Turbines

NASA Astrophysics Data System (ADS)

Richards, Phillip W.; Griffith, D. Todd; Hodges, Dewey H.

2014-06-01

Offshore wind power production is an attractive clean energy option, but the difficulty of access can lead to expensive and rare opportunities for maintenance. As part of the Structural Health and Prognostics Management (SHPM) project at Sandia National Laboratories, smart loads management (controls) are investigated for their potential to increase the fatigue life of offshore wind turbine rotor blades. Derating refers to altering the rotor angular speed and blade pitch to limit power production and loads on the rotor blades. High- fidelity analysis techniques like 3D finite element modeling (FEM) should be used alongside beam models of wind turbine blades to characterize these control strategies in terms of their effect to mitigate fatigue damage and extend life of turbine blades. This study will consider a commonly encountered damage type for wind turbine blades, the trailing edge disbond, and show how FEM can be used to quantify the effect of operations and control strategies designed to extend the fatigue life of damaged blades. The Virtual Crack Closure Technique (VCCT) will be used to post-process the displacement and stress results to provide estimates of damage severity/criticality and provide a means to estimate the fatigue life under a given operations and control strategy.

Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications for clinical use.

PubMed

Baxter-Holland, Mia; Dass, Crispin R

2018-03-01

The use of doxorubicin, an antineoplastic medication used for the treatment of cancers via mechanisms that prevent replication of cells or lead to their death, can result in damage to healthy cells as well as malignant. Among the affected cells are mesenchymal stem cells (MSCs), which are involved in the maintenance and repair of tissues in the body. This review explores the mechanisms of biological effects and damage attributed to doxorubicin on MSCs. The PubMed database was used as a source of literature for this review. Doxorubicin has the potential to lead to significant and irreversible damage to the human bone marrow environment, including MSCs. The primary known mechanism of these changes is through free radical damage and activation of apoptotic pathways. The presence of MSCs in culture or in vivo appears to either suppress or promote tumour growth. Interactions between doxorubicin and MSCs have the potential to increase chemotherapy resistance. Doxorubicin-induced damage to MSCs is of concern clinically. However, MSCs also have been associated with resistance of tumour cells to drugs including doxorubicin. Further studies, particularly in vivo, are needed to provide consistent results of how the doxorubicin-induced changes to MSCs affect treatment and patient health. © 2018 Royal Pharmaceutical Society.

The combination of naproxen and citral reduces nociception and gastric damage in rats.

PubMed

Ortiz, Mario I; Ramírez-Montiel, Martha L; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Cariño-Cortés, Raquel

2010-10-01

It has been shown that the association of non-steroidal anti-inflammatory drugs with plant extracts can increase their antinociceptive activity, allowing the use of lower doses and, thus, limiting side effects. Therefore, the aim of this study was to examine the effects of the interaction between naproxen and citral on nociception and gastric injury in rats. Naproxen, citral, or combinations of naproxen and citral produced an antinociceptive effect. The administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or the naproxen-citral combination. The ED(50) value was estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED(50) for the antinociceptive effect (423.8 mg/kg) was not significantly different from the observed experimental value (359.0 mg/kg); hence, the interaction between naproxen and citral mediating the antinociceptive effect is additive. These data suggest that the naproxen-citral combination interacts at the systemic level, produces minor gastric damage, and potentially has therapeutic advantages for the clinical treatment of inflammatory pain.

Genotoxic effect of 6-gingerol on human hepatoma G2 cells.

PubMed

Yang, Guang; Zhong, Laifu; Jiang, Liping; Geng, Chengyan; Cao, Jun; Sun, Xiance; Ma, Yufang

2010-04-15

6-gingerol, a major component of ginger, has antioxidant, anti-apoptotic, and anti-inflammatory activities. However, some dietary phytochemicals possess pro-oxidant effects as well, and the risk of adverse effects is increased by raising the use of doses. The aim of this study was to assess the genotoxic effects of 6-gingerol and to clarify the mechanisms, using human hepatoma G2 (HepG2) cells. Exposure of the cells to 6-gingerol caused significant increase of DNA migration in comet assay, increase of micronuclei frequencies at high concentrations at 20-80 and 20-40 microM, respectively. These results indicate that 6-gingerol caused DNA strand breaks and chromosome damage. To further elucidate the underlying mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH). In addition, the level of oxidative DNA damage was evaluated by immunocytochemical analysis on 8-hydroxydeoxyguanosine (8-OHdG). Results showed that lysosomal membrane stability was reduced after treatment by 6-gingerol (20-80 microM) for 40 min, mitochondrial membrane potential decreased after treatment for 50 min, GSH and ROS levels were significantly increased after treatment for 60 min. These suggest 6-gingerol induces genotoxicity probably by oxidative stress; lysosomal and mitochondrial damage were observed in 6-gingerol-induced toxicity. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Thermal-based treatment options for localized prostate cancer.

PubMed

Koch, Michael O; Gardner, Thomas A

2005-09-01

It seems clear that thermal-based therapies of prostate cancer have the potential to completely eradicate the prostate gland. Technical modifications continue to improve our ability to use these modalities more effectively, which can be seen in the ever decreasing morbidity from damage to adjacent structures. These treatments offer potential major advantages over surgery and radiation-based treatment modalities.

Protective effect of alprazolam against sleep deprivation-induced behavior alterations and oxidative damage in mice.

PubMed

Singh, Anant; Kumar, Anil

2008-04-01

Sleep deprivation is considered as a risk factor for various diseases. Sleep deprivation leads to behavioral, hormonal, neurochemical and biochemical alterations in the animals. The present study was designed to explore the possible involvement of GABAergic mechanism in protective effect of alprazolam against 72h sleep deprivation-induced behavior alterations and oxidative damage in mice. In the present study, sleep deprivation caused anxiety-like behavior, weight loss, impaired ambulatory movements and oxidative damage as indicated by increase in lipid peroxidation, nitrite level and depletion of reduced glutathione and catalase activity in sleep-deprived mice brain. Treatment with alprazolam (0.25 and 0.5 mg/kg, ip) significantly improved behavioral alterations. Biochemically, alprazolam treatment significantly restored depleted reduced glutathione, catalase activity, reversed raised lipid peroxidation and nitrite level. Combination of flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) with lower dose of alprazolam (0.25mg/kg) significantly antagonized protective effect of alprazolam. However, combination of muscimol (0.05 mg/kg) with alprazolam (0.25 mg/kg, ip) potentiated protective effect of alprazolam. On the basis of these results, it might be suggested that alprazolam might produce protective effect by involving GABAergic system against sleep deprivation-induced behavior alterations and related oxidative damage.

Lamb wave propagation in Z-pin reinforced co-cured composite pi-joints

NASA Astrophysics Data System (ADS)

Swenson, Eric D.; Soni, Som R.; Kapoor, Hitesh

2010-04-01

This paper presents an initial study on Lamb wave propagation characteristics in z-pin reinforced, co-cured composite pi-joints for the purposes of structural health monitoring (SHM). Pi-joint test articles were designed and created to replicate a co-cured, all composite skin-spar joint found within a typical aircraft wing structure. Because pi-joints exhibit various complex damage modes, formal studies are required if SHM systems are to be developed to monitor these types of joints for potential damage. Experiments were conducted on a undamaged (healthy) and damaged test articles where Lamb waves were excited using one lead zirconate titanate (PZT) transducer. A three-dimensional (3D) scanning laser Doppler vibrometer (LDV) was used to collect high-density scans of both the in-plane and out-of-plane velocity measurements. In the damaged test article, where delamination, matrix cracking, and fiber breakage can clearly be seen, changes in both the fundamental antisymmetric A0 and symmetric S0 Lamb wave modes are apparent. In both test articles, the effects of narrow geometry, discontinuity due to the attachment of the web, and thickness has detectable effects on Lamb wave propagation. From the comparisons between Lamb waves propagating through the undamaged and damaged test articles, it is clear that damage can be detected using Lamb waves in z-pin reinforced, co-cured composite pi-joints for this case of extensive damage.

Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats.

PubMed

Indran, M; Mahmood, A A; Kuppusamy, U R

2008-09-01

The effects of Carica papaya leaf (CPL) aqueous extract on alcohol induced acute gastric damage and the immediate blood oxidative stress level were studied in rats. The results showed that gastric ulcer index was significantly reduced in rats pretreated with CPL extract as compared with alcohol treated controls. The in vitro studies using 2,2-Diphenyl-1-Picryl-Hydrazyl (DPPH) assay showed strong antioxidant nature of CPL extract. Biochemical analysis indicated that the acute alcohol induced damage is reflected in the alterations of blood oxidative indices and CPL extract offered some protection with reduction in plasma lipid peroxidation level and increased erythrocyte glutathione peroxidase activity. Carica papaya leaf may potentially serve as a good therapeutic agent for protection against gastric ulcer and oxidative stress.

Protective effect of KI in mtDNA in porcine thyroid: comparison with KIO₃ and nDNA.

PubMed

Karbownik-Lewinska, Malgorzata; Stepniak, Jan; Milczarek, Magdalena; Lewinski, Andrzej

2015-03-01

Iodine, bivalent iron (Fe²⁺), and hydrogen peroxide (H₂O₂), all significantly affecting the red-ox balance, are required for thyroid hormone synthesis. Intracellular iodine excess (≥10⁻³ M) transiently blocks thyroid hormonogenesis (an adaptive mechanism called Wolff-Chaikoff effect). The aim of the study was to evaluate the effects of iodine, used as potassium iodide (KI) or potassium iodate (KIO₃), in concentrations corresponding to those typical for Wolff-Chaikoff effect, on the level of oxidative damage to nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) isolated from porcine thyroid under basal conditions and in the presence of Fenton reaction (Fe²⁺+H₂O₂ → Fe³⁺+(·)OH + OH⁻) substrates. Thyroid nDNA and mtDNA were incubated in the presence of either KI or KIO₃ (2.5-50 mM), without/with FeSO₄ (30 µM) + H₂O₂ (0.5 mM). Index of DNA damage, i.e., 8-oxo-7,8-dihydro-2'-deoxyguanosine, was measured by HPLC. Neither KI nor KIO₃ increased the basal level of 8-oxodG in both nDNA and mtDNA. KI-in all used concentrations-completely prevented the damaging effect of Fenton reaction substrates in mtDNA, and it partially prevented this damage in nDNA. KIO₃ partially prevented Fe²⁺+H₂O₂-induced oxidative damage in both DNA only in its highest used concentrations (≥25 mM). Without additional prooxidative abuse, both iodine compounds, i.e., KI and KIO₃, seem to be safe in terms of their potential oxidative damage to DNA in the thyroid. The superiority of KI over KIO₃ relies on its stronger protective effects against oxidative damage to mtDNA, which constitutes an argument for its preferential utility in iodine prophylaxis.

Agmatine effects on mitochondrial membrane potential and NF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells.

PubMed

Condello, Salvatore; Currò, Monica; Ferlazzo, Nadia; Caccamo, Daniela; Satriano, Joseph; Ientile, Riccardo

2011-01-01

Agmatine, an endogenous arginine metabolite, has been proposed as a novel neuromodulator that plays protective roles in the CNS in several models of cellular damage. However, the mechanisms involved in these protective effects in neurodegenerative diseases are poorly understood. The present study was undertaken to investigate the effects of agmatine on cell injury induced by rotenone, commonly used in establishing in vivo and in vitro models of Parkinson's disease, in human-derived dopaminergic neuroblastoma cell line (SH-SY5Y). We report that agmatine dose-dependently suppressed rotenone-induced cellular injury through a reduction of oxidative stress. Similar effects were obtained by spermine, suggesting a scavenging effect for these compounds. However, unlike spermine, agmatine also prevented rotenone-induced nuclear factor-κB nuclear translocation and mitochondrial membrane potential dissipation. Furthermore, rotenone-induced increase in apoptotic markers, such as caspase 3 activity, Bax expression and cytochrome c release, was significantly attenuated with agmatine treatment. These findings demonstrate mitochondrial preservation with agmatine in a rotenone model of apoptotic cell death, and that the neuroprotective action of agmatine appears because of suppressing apoptotic signalling mechanisms. Thus, agmatine may have therapeutic potential in the treatment of Parkinson's disease by protecting dopaminergic neurons.

Caffeinol at the receptor level; Anti-ischemic effect of NMDA receptor blockade is potentiated by caffeine

PubMed Central

Zhao, Xiurong; Strong, Roger; Piriyawat, Paisith; Palusinski, Robert; Grotta, James C.; Aronowski, Jaroslaw

2010-01-01

Background and Purpose Although caffeinol (combination of low dose of caffeine and ethanol) was shown to robustly reduce stroke damage in experimental models and is now in clinical evaluation for treatment of ischemic stroke, little is known about the potential mechanism of its action. Methods We have used an in vivo excitotoxicity model based on intracortical infusion of NMDA and model of reversible focal ischemia to demonstrate NMDA receptor inhibition as one potential mechanism of Caffeinol anti-ischemic activity. Results Caffeinol reduced the size of excitotoxic lesion and substitution of ethanol in Caffeinol with CNS-1102 and MK-801, but not with MgSO4, produced treatment with strong synergistic effect that was at least as robust in reducing ischemic damage as Caffeinol. This NMDA receptor antagonist and caffeine combination showed long window of opportunity, activity in spontaneously hypertensive rats, and unlike Caffeinol was fully effective in animals chronically pre-treated with ethanol. Conclusions Our study suggests that anti-excitotoxic properties may underlie some of the anti-ischemic effect of Caffeinol. This study provides strong evidence that the anti-ischemic effect of NMDA receptor blockers in general can be dramatically augmented by caffeine, thus opening a possibility for new utilization of NMDA-based pharmacology in the treatment of stroke. PMID:20044532

Proof of Concept for an Ultrasensitive Technique to Detect and Localize Sources of Elastic Nonlinearity Using Phononic Crystals.

PubMed

Miniaci, M; Gliozzi, A S; Morvan, B; Krushynska, A; Bosia, F; Scalerandi, M; Pugno, N M

2017-05-26

The appearance of nonlinear effects in elastic wave propagation is one of the most reliable and sensitive indicators of the onset of material damage. However, these effects are usually very small and can be detected only using cumbersome digital signal processing techniques. Here, we propose and experimentally validate an alternative approach, using the filtering and focusing properties of phononic crystals to naturally select and reflect the higher harmonics generated by nonlinear effects, enabling the realization of time-reversal procedures for nonlinear elastic source detection. The proposed device demonstrates its potential as an efficient, compact, portable, passive apparatus for nonlinear elastic wave sensing and damage detection.

Effect of stainless steel manual metal arc welding fume on free radical production, DNA damage, and apoptosis induction.

PubMed

Antonini, James M; Leonard, Stephen S; Roberts, Jenny R; Solano-Lopez, Claudia; Young, Shih-Houng; Shi, Xianglin; Taylor, Michael D

2005-11-01

Questions exist concerning the potential carcinogenic effects after welding fume exposure. Welding processes that use stainless steel (SS) materials can produce fumes that may contain metals (e.g., Cr, Ni) known to be carcinogenic to humans. The objective was to determine the effect of in vitro and in vivo welding fume treatment on free radical generation, DNA damage, cytotoxicity and apoptosis induction, all factors possibly involved with the pathogenesis of lung cancer. SS welding fume was collected during manual metal arc welding (MMA). Elemental analysis indicated that the MMA-SS sample was highly soluble in water, and a majority (87%) of the soluble metal was Cr. Using electron spin resonance (ESR), the SS welding fume had the ability to produce the biologically reactive hydroxyl radical (*OH), likely as a result of the reduction of Cr(VI) to Cr(V). In vitro treatment with the MMA-SS sample caused a concentration-dependent increase in DNA damage and lung macrophage death. In addition, a time-dependent increase in the number of apoptotic cells in lung tissue was observed after in vivo treatment with the welding fume. In summary, a soluble MMA-SS welding fume was found to generate reactive oxygen species and cause DNA damage, lung macrophage cytotoxicity and in vivo lung cell apoptosis. These responses have been shown to be involved in various toxicological and carcinogenic processes. The effects observed appear to be related to the soluble component of the MMA-SS sample that is predominately Cr. A more comprehensive in vivo animal study is ongoing in the laboratory that is continuing these experiments to try to elucidate the potential mechanisms that may be involved with welding fume-induced lung disease.

Feral livestock threatens landscapes dominated by columnar cacti

NASA Astrophysics Data System (ADS)

Malo, J. E.; Acebes, P.; Giannoni, S. M.; Traba, J.

2011-05-01

The introduction and naturalization of alien species represents a serious threat to many natural protected areas. One such case of worldwide concern is the impact of feral livestock on arid ecosystems. Damage suffered by Echinopsis (= Trichocereus) terscheckii dominating the landscape of rocky slopes was surveyed in seven locations within the Ischigualasto-Talampaya World Heritage Site (Argentina) by measuring the frequency, position on the plant and extent of damage. At the same time we employed transects to estimate the abundance of autochtonous and feral large herbivores ( Lama guanicoe, Bos taurus, Equus asinus) from their dung. Our results show relatively high damage levels (40-77% of individuals damaged, more than 5 dm 3 removed by plant in some sites), particularly within 0.50-1.75 m above the ground, showing herbivores to be the main responsible for them. We also found significant differences between sites in variables measuring damage level and in the intensity of use by the two feral livestock species but not by guanacos. The frequency of damaged cacti below 1.75 m (but not above) was significantly positively correlated among locations with the frequencies of cattle and donkey dung, and the damage suffered by individual cacti was also correlated with donkey and cattle dung in their surroundings after correcting for spatial effects. However, all correlations were non-significant in the case of guanacos. We conclude that the continued presence of feral livestock, particularly donkeys, leads to damages to columnar cacti with potential effects on their populations and the physiognomy of this protected landscape.

Open Circuit Resonant (SansEC) Sensor for Composite Damage Detection and Diagnosis in Aircraft Lightning Environments

NASA Technical Reports Server (NTRS)

Wang, Chuantong; Dudley, Kenneth L.; Szatkowski, George N.

2012-01-01

Composite materials are increasingly used in modern aircraft for reducing weight, improving fuel efficiency, and enhancing the overall design, performance, and manufacturability of airborne vehicles. Materials such as fiberglass reinforced composites (FRC) and carbon-fiber-reinforced polymers (CFRP) are being used to great advantage in airframes, wings, engine nacelles, turbine blades, fairings, fuselage and empennage structures, control surfaces and coverings. However, the potential damage from the direct and indirect effects of lightning strikes is of increased concern to aircraft designers and operators. When a lightning strike occurs, the points of attachment and detachment on the aircraft surface must be found by visual inspection, and then assessed for damage by maintenance personnel to ensure continued safe flight operations. In this paper, a new method and system for aircraft in-situ damage detection and diagnosis are presented. The method and system are based on open circuit (SansEC) sensor technology developed at NASA Langley Research Center. SansEC (Sans Electric Connection) sensor technology is a new technical framework for designing, powering, and interrogating sensors to detect damage in composite materials. Damage in composite material is generally associated with a localized change in material permittivity and/or conductivity. These changes are sensed using SansEC. Unique electrical signatures are used for damage detection and diagnosis. NASA LaRC has both experimentally and theoretically demonstrated that SansEC sensors can be effectively used for in-situ composite damage detection.

Effect of complex polyphenols and tannins from red wine on DNA oxidative damage of rat colon mucosa in vivo.

PubMed

Giovannelli, L; Testa, G; De Filippo, C; Cheynier, V; Clifford, M N; Dolara, P

2000-10-01

Dietary polyphenols have been reported to have a variety of biological actions, including anti-carcinogenic, antioxidant and anti-inflammatory activities. In the present study we have evaluated the effect of an oral treatment with complex polyphenols and tannins from red wine and tea on DNA oxidative damage in the rat colon mucosa. Isolated colonocytes were prepared from the colon mucosa of rats treated for ten days with either wine complex polyphenols (57.2 mg/kg/d) or thearubigin (40 mg/kg/d) by oral gavage. Colonocyte oxidative DNA damage was analysed at the single cell level using a modification of the comet assay technique. The results show that wine complex polyphenols and tannins induce a significant decrease (-62% for pyrimidine and -57% for purine oxidation) in basal DNA oxidative damage in colon mucosal cells without affecting the basal level of single-strand breaks. On the other hand, tea polyphenols, namely a crude extract of thearubigin, did not affect either strand breaks or pyrimidine oxidation in colon mucosal cells. Our experiments are the first demonstration that dietary polyphenols can modulate in vivo oxidative damage in the gastrointestinal tract of rodents. These data support the hypothesis that dietary polyphenols might have both a protective and a therapeutic potential in oxidative damage-related pathologies.

Spatial Information in Support of 3D Flood Damage Assessment of Buildings at Micro Level: A Review

NASA Astrophysics Data System (ADS)

Amirebrahimi, S.; Rajabifard, A.; Sabri, S.; Mendis, P.

2016-10-01

Floods, as the most common and costliest natural disaster around the globe, have adverse impacts on buildings which are considered as major contributors to the overall economic damage. With emphasis on risk management methods for reducing the risks to structures and people, estimating damage from potential flood events becomes an important task for identifying and implementing the optimal flood risk-reduction solutions. While traditional Flood Damage Assessment (FDA) methods focus on simple representation of buildings for large-scale damage assessment purposes, recent emphasis on buildings' flood resilience resulted in development of a sophisticated method that allows for a detailed and effective damage evaluation at the scale of building and its components. In pursuit of finding the suitable spatial information model to satisfy the needs of implementing such frameworks, this article explores the technical developments for an effective representation of buildings, floods and other required information within the built environment. The search begins with the Geospatial domain and investigates the state-of-the-art and relevant developments from data point of view in this area. It is further extended to other relevant disciplines in the Architecture, Engineering and Construction domain (AEC/FM) and finally, even some overlapping areas between these domains are considered and explored.

Tiny Stowaways: Analyzing the Economic Benefits of a U.S. Environmental Protection Agency Permit Regulating Ballast Water Discharges

NASA Astrophysics Data System (ADS)

Lovell, Sabrina J.; Drake, Lisa A.

2009-03-01

The U.S. Environmental Protection Agency has proposed permitting ballast water discharges—a benefit of which would be to reduce the economic damages associated with the introduction and spread of aquatic invasive species. Research on ship-borne aquatic invasive species has been conducted in earnest for decades, but determining the economic damages they cause remains troublesome. Furthermore, with the exception of harmful algal blooms, the economic consequences of microscopic invaders have not been studied, despite their potentially great negative effects. In this paper, we show how to estimate the economic benefits of preventing the introduction and spread of harmful bacteria, microalgae, and viruses delivered in U.S. waters. Our calculations of net social welfare show the damages from a localized incident, cholera-causing bacteria found in shellfish in the Gulf of Mexico, to be approximately 706,000 (2006). On a larger scale, harmful algal species have the potential to be transported in ships’ ballast tanks, and their effects in the United States have been to reduce commercial fisheries landings and impair water quality. We examine the economic repercussions of one bloom-forming species. Finally, we consider the possible translocation within the Great Lakes of a virus that has the potential to harm commercial and recreational fisheries. These calculations illustrate an approach to quantifying the benefits of preventing invasive aquatic microorganisms from controls on ballast water discharges.

Tiny stowaways: analyzing the economic benefits of a U.S. Environmental Protection Agency permit regulating ballast water discharges.

PubMed

Lovell, Sabrina J; Drake, Lisa A

2009-03-01

The U.S. Environmental Protection Agency has proposed permitting ballast water discharges--a benefit of which would be to reduce the economic damages associated with the introduction and spread of aquatic invasive species. Research on ship-borne aquatic invasive species has been conducted in earnest for decades, but determining the economic damages they cause remains troublesome. Furthermore, with the exception of harmful algal blooms, the economic consequences of microscopic invaders have not been studied, despite their potentially great negative effects. In this paper, we show how to estimate the economic benefits of preventing the introduction and spread of harmful bacteria, microalgae, and viruses delivered in U.S. waters. Our calculations of net social welfare show the damages from a localized incident, cholera-causing bacteria found in shellfish in the Gulf of Mexico, to be approximately $706,000 (2006$). On a larger scale, harmful algal species have the potential to be transported in ships' ballast tanks, and their effects in the United States have been to reduce commercial fisheries landings and impair water quality. We examine the economic repercussions of one bloom-forming species. Finally, we consider the possible translocation within the Great Lakes of a virus that has the potential to harm commercial and recreational fisheries. These calculations illustrate an approach to quantifying the benefits of preventing invasive aquatic microorganisms from controls on ballast water discharges.

Assessment of the protective potential of Premna tomentosa (L. Verbenaceae) extract on lipid profile and lipid-metabolizing enzymes in acetaminophen-intoxicated rats.

PubMed

Devi, Kasi Pandima; Sreepriya, Meenakshi; Balakrishna, Kedike; Veluchamy, Gopalasamy; Devaki, Thiruvegadam

2004-06-01

The liver is often damaged by environmental toxins, poor eating habits, alcohol and over-the-counter drug use that damage and weaken the liver, leading to important public health problems such as hepatitis, cirrhosis, and alcoholic liver diseases. It is cardinal to treat liver disorders, because it affects the biochemistry of the cell directly. Damage to the liver can be prevented by including a balanced diet that includes nutrients and herbs that support a healthy liver. Premna tomentosa (PT) is one such herbal drug used widely in India for the treatment of liver disorders, and we have already reported the hepatoprotective potential and antioxidant property of methanolic extract of PT leaves. Because injury to the liver can promote a variety of reactions with consequent effect on lipids, the present study was designed to elucidate the hypolipidemic effect of PT extract in acetaminophen (AA)-induced hepatotoxicity in rats. Animals were pretreated with PT extract (750 mg/kg, orally) for 15 days and then induced with hepatotoxicity by AA (640 mg/kg, intraperitoneally). PT extract pretreatment significantly inhibited induced alterations in the levels of cholesterol, triglycerides, free fatty acids, phospholipids, serum lipoproteins, and lipid-metabolizing enzymes. The results indicate that PT extract improves lipid metabolism and has the potential for use in hepatic disorders. Copyright Mary Ann Liebert, Inc.

Nasal mucosa and blood cell transcriptome profiles do not reflect respiratory symptoms associated with moisture-damage.

PubMed

Ndika, Joseph; Suojalehto, Hille; Täubel, Martin; Lehto, Maili; Karvala, Kirsi; Pallasaho, Paula; Sund, Jukka; Auvinen, Petri; Järvi, Kati; Pekkanen, Juha; Kinaret, Pia; Greco, Dario; Hyvärinen, Anne; Alenius, Harri

2018-05-04

Upper and lower respiratory symptoms and asthma are adverse health effects associated with moisture-damaged buildings. Quantitative measures to detect adverse health effects related to exposure to dampness and mold are needed. Here, we investigate differences in gene expression between occupants of moisture-damaged and reference buildings. Moisture-damaged (N=11) and control (N=5) buildings were evaluated for dampness and mold by trained inspectors. The transcriptomics cohort consisted of nasal brushings and peripheral blood mononuclear cells (PBMCs) from 86 teachers, with/without self-perceived respiratory symptoms. Subject categories comprised reference (R) and damaged (D) buildings with (S) or without (NS) symptoms; i.e. R-S, R-NS, DS and D-NS. Component analyses and k-means clustering of transcriptome profiles did not distinguish building status (R/D) or presence of respiratory symptoms (S/NS). Only one nasal mucosa gene (YBX3P1) exhibited a significant change in expression between D-S and D-NS. Nine other nasal mucosa genes were differentially expressed between R-S and D-S teachers. No differentially expressed genes were identified in PBMCs. We conclude that the observed mRNA differences provide very weak biological evidence for adverse health effects associated with subject occupancy of the specified moisture-damaged buildings. This emphasizes the need to evaluate all potential factors (including those not related to toxicity) influencing perceived/self-reported ill-health in moisture-damaged buildings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis.

PubMed

Lowes, Damon A; Thottakam, Bensita M V; Webster, Nigel R; Murphy, Michael P; Galley, Helen F

2008-12-01

Sepsis is characterised by a systemic dysregulated inflammatory response and oxidative stress, often leading to organ failure and death. Development of organ dysfunction associated with sepsis is now accepted to be due at least in part to oxidative damage to mitochondria. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and which has been shown to decrease mitochondrial damage in animal models of oxidative stress. We hypothesised that if oxidative damage to mitochondria does play a significant role in sepsis-induced organ failure, then MitoQ should modulate inflammatory responses, reduce mitochondrial oxidative damage, and thereby ameliorate organ damage. To assess this, we investigated the effects of MitoQ in vitro in an endothelial cell model of sepsis and in vivo in a rat model of sepsis. In vitro MitoQ decreased oxidative stress and protected mitochondria from damage as indicated by a lower rate of reactive oxygen species formation (P=0.01) and by maintenance of the mitochondrial membrane potential (P<0.005). MitoQ also suppressed proinflammatory cytokine release from the cells (P<0.05) while the production of the anti-inflammatory cytokine interleukin-10 was increased by MitoQ (P<0.001). In a lipopolysaccharide-peptidoglycan rat model of the organ dysfunction that occurs during sepsis, MitoQ treatment resulted in lower levels of biochemical markers of acute liver and renal dysfunction (P<0.05), and mitochondrial membrane potential was augmented (P<0.01) in most organs. These findings suggest that the use of mitochondria-targeted antioxidants such as MitoQ may be beneficial in sepsis.

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina

PubMed Central

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro

2018-01-01

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. Highlights: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms. PMID:29748512

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina.

PubMed

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro; Ohira, Akihiro

2018-05-10

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O -glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut ( Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.

The Effect of a Grape Seed Extract on Radiation-Induced DNA Damage in Human Lymphocytes

NASA Astrophysics Data System (ADS)

Dicu, Tiberius; Postescu, Ion D.; Foriş, Vasile; Brie, Ioana; Fischer-Fodor, Eva; Cernea, Valentin; Moldovan, Mircea; Cosma, Constantin

2009-05-01

Plant-derived antioxidants due to their phenolic compounds content are reported as potential candidates for reducing the levels of oxidative stress in living organisms. Grape seed extracts are very potent antioxidants and exhibit numerous interesting pharmacologic activities. Hydroethanolic (50/50, v/v) standardized extract was obtained from red grape seed (Vitis vinifera, variety Burgund Mare—BM). The total polyphenols content was evaluated by Folin-Ciocalteu procedure and expressed as μEq Gallic Acid/ml. The aim of this study was to evaluate the potential antioxidant effects of different concentrations of BM extract against 60Co γ-rays induced DNA damage in human lymphocytes. Samples of human lymphocytes were incubated with BM extract (12.5, 25.0 and 37.5 μEq GA/ml, respectively) administered at 30 minutes before in vitro irradiation with γ-rays (2 Gy). The DNA damage and repair in lymphocytes were evaluated using alkaline comet assay. Using the lesion score, the radiation-induced DNA damage was found to be significantly different (p<0.05) from control, both in the absence and presence of BM extract (except the lymphocytes treated with 37.5 μEq GA/ml BM extract). DNA repair analyzed by incubating the irradiated cells at 37° C and 5% CO2 atmosphere for 2 h, indicated a significant difference (p<0.05) in the lymphocytes group treated with 25.0 μEq GA/ml BM extract, immediately and two hours after irradiation. These results suggest radioprotective effects after treatment with BM extract in human lymphocytes.

Hepatic ischemia-reperfusion injury: roles of Ca2+ and other intracellular mediators of impaired bile flow and hepatocyte damage.

PubMed

Nieuwenhuijs, Vincent B; De Bruijn, Menno T; Padbury, Robert T A; Barritt, Gregory J

2006-06-01

Liver resection and liver transplantation have been successful in the treatment of liver tumors and end-stage liver disease. This success has led to an expansion in the pool of patients potentially treatable by liver surgery and, in the case of transplantation, to a shortage of liver donors. At present, there are significant numbers of potential candidates for liver resection and liver donation who have fatty livers, are aged, or have livers damaged by chemotherapy. All of these are at high risk for ischemic reperfusion (IR) injury. The aims of this review are to assess current knowledge of the clinical effectiveness of ischemic preconditioning and intermittent ischemia in reducing IR damage in liver surgery; to evaluate the use of bile flow as a sensitive indicator of IR liver damage; and to analyze the molecular mechanisms, especially intracellular Ca2+, involved in IR injury and ischemic preconditioning. It is concluded that bile flow is a sensitive indicator of IR injury. Together with reactive oxygen species (ROS) and other extracellular and intracellular signaling molecules, intracellular Ca2+ in hepatocytes plays a key role in the normal regulation of bile flow and in IR-induced injury and cell death. Ischemic preconditioning is an effective strategy to reduce IR injury but there is considerable scope for improvement, especially in patients with fatty and aged livers. The development of effective new strategies to reduce IR injury will depend on improved understanding of the molecular mechanisms involved, especially by gaining a better perspective of the relative importance of the various intrahepatocyte signaling pathways involved.

Evaluation of effectiveness of Er,Cr:YSGG laser for root canal disinfection: theoretical simulation of temperature elevations in root dentin.

PubMed

Zhu, L; Tolba, M; Arola, D; Salloum, M; Meza, F

2009-07-01

Erbium, chromium: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) lasers are currently being investigated for disinfecting the root canal system. Prior to using laser therapy, it is important to understand the temperature distribution and to assess thermal damage to the surrounding tissue. In this study, a theoretical simulation using the Pennes bioheat equation is conducted to evaluate how heat spreads from the canal surface using an Er,Cr:YSGG laser. Results of the investigation show that some of the proposed treatment protocols for killing bacteria in the deep dentin are ineffective, even for long heating durations. Based on the simulation, an alternative treatment protocol is identified that has improved effectiveness and is less likely to introduce collateral damage to the surrounding tissue. The alternative protocol uses 350 mW laser power with repeating laser tip movement to achieve bacterial disinfection in the deep dentin (800 microm lateral from the canal surface), while avoiding thermal damage to the surrounding tissue (T<47 degrees C). The alternative treatment protocol has the potential to not only achieve bacterial disinfection of deep dentin but also shorten the treatment time, thereby minimizing potential patient discomfort during laser procedures.

New Therapeutic Concept of NAD Redox Balance for Cisplatin Nephrotoxicity

PubMed Central

Oh, Gi-Su; Kim, Hyung-Jin; Shen, AiHua; Lee, Su-Bin; Yang, Sei-Hoon; Shim, Hyeok; Cho, Eun-Young; Kwon, Kang-Beom; Kwak, Tae Hwan; So, Hong-Seob

2016-01-01

Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects such as ototoxicity, nephrotoxicity, and peripheral neuropathy. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses are closely associated with cisplatin-induced nephrotoxicity; however, the precise mechanism remains unclear. The cofactor nicotinamide adenine dinucleotide (NAD+) has emerged as a key regulator of cellular energy metabolism and homeostasis. Recent studies have demonstrated associations between disturbance in intracellular NAD+ levels and clinical progression of various diseases through the production of reactive oxygen species and inflammation. Furthermore, we demonstrated that reduction of the intracellular NAD+/NADH ratio is critically involved in cisplatin-induced kidney damage through inflammation and oxidative stress and that increase of the cellular NAD+/NADH ratio suppresses cisplatin-induced kidney damage by modulation of potential damage mediators such as oxidative stress and inflammatory responses. In this review, we describe the role of NAD+ metabolism in cisplatin-induced nephrotoxicity and discuss a potential strategy for the prevention or treatment of cisplatin-induced adverse effects with a particular focus on NAD+-dependent cellular pathways. PMID:26881219

Hole hopping through tyrosine/tryptophan chains protects proteins from oxidative damage

PubMed Central

Gray, Harry B.; Winkler, Jay R.

2015-01-01

Living organisms have adapted to atmospheric dioxygen by exploiting its oxidizing power while protecting themselves against toxic side effects. Reactive oxygen and nitrogen species formed during oxidative stress, as well as high-potential reactive intermediates formed during enzymatic catalysis, could rapidly and irreversibly damage polypeptides were protective mechanisms not available. Chains of redox-active tyrosine and tryptophan residues can transport potentially damaging oxidizing equivalents (holes) away from fragile active sites and toward protein surfaces where they can be scavenged by cellular reductants. Precise positioning of these chains is required to provide effective protection without inhibiting normal function. A search of the structural database reveals that about one third of all proteins contain Tyr/Trp chains composed of three or more residues. Although these chains are distributed among all enzyme classes, they appear with greatest frequency in the oxidoreductases and hydrolases. Consistent with a redox-protective role, approximately half of the dioxygen-using oxidoreductases have Tyr/Trp chain lengths ≥3 residues. Among the hydrolases, long Tyr/Trp chains appear almost exclusively in the glycoside hydrolases. These chains likely are important for substrate binding and positioning, but a secondary redox role also is a possibility. PMID:26195784

Assessing changes in extreme convective precipitation from a damage perspective

NASA Astrophysics Data System (ADS)

Schroeer, K.; Tye, M. R.

2016-12-01

Projected increases in high-intensity short-duration convective precipitation are expected even in regions that are likely to become more arid. Such high intensity precipitation events can trigger hazardous flash floods, debris flows and landslides that put people and local assets at risk. However, the assessment of local scale precipitation extremes is hampered by its high spatial and temporal variability. In addition to which, not only are extreme events rare, but such small scale events are likely to be underreported where they don't coincide with the observation network. Rather than focus solely on the convective precipitation, understanding the characteristics of these extremes which drive damage may be more effective to assess future risks. Two sources of data are used in this study. First, sub-daily precipitation observations over the Southern Alps enable an examination of seasonal and regional patterns in high-intensity convective precipitation and their relationship with weather types. Secondly, reports of private loss and damage on a household scale are used to identify which events are most damaging, or what conditions potentially enhance the vulnerability to these extremes.This study explores the potential added value from including recorded loss and damage data to understand the risks from summertime convective precipitation events. By relating precipitation generating weather types to the severity of damage we hope to develop a mechanism to assess future risks. A further benefit would be to identify from damage reports the likely occurrence of precipitation extremes where no direct observations are available and use this information to validate remotely sensed observations.

Effects of core body temperature on changes in spinal somatosensory-evoked potential in acute spinal cord compression injury: an experimental study in the rat.

PubMed

Jou, I M

2000-08-01

Acute spinal cord injury was induced by a clip compression model in rats to approximate spinal cord injury encountered in spinal surgery. Spinal somatosensory-evoked potential neuromonitoring was used to study the electrophysiologic change. To compare and correlate changes in evoked potential after acute compression at different core temperatures with postoperative neurologic function and histologic change, to evaluate current intraoperative neuromonitoring warning criteria for neural damage, and to confirm the protective effect of hypothermia in acute spinal cord compression injury by electrophysiologic, histologic, and clinical observation. With the increase in aggressive correction of spinal deformities, and the invasiveness of surgical instruments, the incidence of neurologic complication appears to have increased despite the availability of sensitive intraoperative neuromonitoring techniques designed to alert surgeons to impending neural damage. Many reasons have been given for the frequent failures of neuromonitoring, but the influence of temperature-a very important and frequently encountered factor-on evoked potential has not been well documented. Specifically, decrease in amplitude and elongation of latency seem not to have been sufficiently taken into account when intraoperative neuromonitoring levels were interpreted and when acceptable intraoperative warning criteria were determined. Experimental acute spinal cord injury was induced in rats by clip compression for two different intervals and at three different core temperatures. Spinal somatosensory-evoked potential, elicited by stimulating the median nerve and recorded from the cervical interspinous C2-C3, was monitored immediately before and after compression, and at 15-minute intervals for 1 hour. Spinal somatosensory-evoked potential change is almost parallel to temperature-based amplitude reduction and latency elongation. Significant neurologic damage induced by acute compression of the cervical spinal cord produced a degree of effect on the amplitude of spinal somatosensory-evoked potential in normothermic conditions that differed from the effect in moderately hypothermic conditions. Using the same electromonitoring criteria,moderately hypothermic groups showed a significantly higher false-negative rate statistically (35%) than normothermic groups (10%). Systemic cooling may protect against the detrimental effects of aggressive spinal surgical procedures. There is still not enough published information available to establish statistically and ethically acceptable intraoperative neuromonitoring warning and intervention criteria conclusively. Therefore, an urgent need exists for further investigation. Although a reduction of more than 50% in evoked potential still seems acceptable as an indicator of impending neural function loss, maintenance of more than 50% of baseline evoked potential is no guarantee of normal postoperative neural function, especially at lower than normal temperatures.

DNA damaging potential of Ganoderma lucidum extracts.

PubMed

Gurovic, María Soledad Vela; Viceconte, Fátima R; Pereyra, Marcelo T; Bidegain, Maximiliano A; Cubitto, María Amelia

2018-05-10

Ganoderma lucidum (Lingzhi or Reishi) is a medicinal mushroom historically used in Asian countries to treat a wide variety of diseases and prolong life. In the last years, G. lucidum has been internationally recognized as an effective adjuvant in cancer treatment. Among active components, the most recent research indicates that polysaccharides modulate the immune response favoring the recovery from toxicity of chemo and radiotherapy while triterpenes are cytotoxic to tumoral cells mainly by altering gene expression. Beyond this body of evidence on the efficacy of G. lucidum in cancer treatment, it is not yet understood whether these extracts exert the same mechanisms of action than current antitumoral drugs. In this study, we tested the DNA damaging potential of G. lucidum extracts by the β-galactosidase biochemical prophage induction assay (BIA) using doxorubicin, a DNA intercalating agent, as a positive control. This assay was traditionally used to screen microbial metabolites towards antitumoral agents. Here, we used this bacterial assay for the first time to assess DNA damage of herbal drugs. After a bioguided assay, only a purified fraction of G. lucidum containing a mixture of C16 and C18:1 fatty acids exerted weak activity which could not be attributed to direct interaction with DNA. At the same concentrations, the induction observed for doxorubicin was clearly contrasting. The micro BIA assay could be successfully used to demonstrate differences in cellular effects between G. lucidum extracts and doxorubicin. These results showed that G. lucidum extracts display weak DNA damaging potential. Since DNA injury promotes aging and cancer, our results substantiate the traditional use of this mushroom to prolong life. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of medical malpractice liability on rate of referrals received by specialist physicians.

PubMed

Xu, Xiao; Spurr, Stephen J; Nan, Bin; Fendrick, A Mark

2013-10-01

Using nationally representative data from the United States, this paper analyzed the effect of a state’s medical malpractice environment on referral visits received by specialist physicians. The analytic sample included 12,839 ambulatory visits to specialist care doctors in office-based settings in the United States during 2003–2007. Whether the patient was referred for the visit was examined for its association with the state’s malpractice environment, assessed by the frequency and severity of paid medical malpractice claims, medical malpractice insurance premiums and an indicator for whether the state had a cap on non-economic damages. After accounting for potential confounders such as economic or professional incentives within practices, the analysis showed that statutory caps on non-economic damages of $250,000 were significantly associated with lower likelihood of a specialist receiving referrals, suggesting a potential impact of a state’s medical malpractice environment on physicians’ referral behavior.

Review article: anthranoid laxatives and their potential carcinogenic effects.

PubMed

van Gorkom, B A; de Vries, E G; Karrenbeld, A; Kleibeuker, J H

1999-04-01

Anthranoid laxatives are widely used laxatives of natural origin. Because of their chemical structure they are carried unabsorbed to the large bowel, where metabolism to the active aglycones takes place. These aglycones exert their laxative effect by damaging epithelial cells, which leads directly and indirectly to changes in absorption, secretion and motility. Damaged epithelial cells can be found as apoptotic bodies in the pigmented colonic mucosa, characteristic for pseudomelanosis coli. Pseudomelanosis coli is a condition caused by chronic (ab)use of anthranoid laxatives and has recently been associated with an increased risk of colorectal carcinoma. In vitro and animal studies have shown a potential role of anthranoid laxatives in both the initiation and promotion of tumorigenesis. Studies in humans have also suggested tumour promoting activities for these laxatives. Although the short-term use of these substances is generally safe, long-term use cannot be recommended.

The Effect of Medical Malpractice Liability on Rate of Referrals Received by Specialist Physicians

PubMed Central

Xu, Xiao; Spurr, Stephen J.; Nan, Bin; Fendrick, A. Mark

2013-01-01

Using nationally representative data from the U.S., this paper analyzed the effect of a state’s medical malpractice environment on referral visits received by specialist physicians. The analytic sample included 12,839 ambulatory visits to specialist care doctors in office-based settings in the U.S. during 2003–2007. Whether the patient was referred for the visit was examined for its association with the state’s malpractice environment, assessed by the frequency and severity of paid medical malpractice claims, medical malpractice insurance premiums, and an indicator for whether the state had a cap on noneconomic damages. After accounting for potential confounders such as economic or professional incentives within practices, the analysis showed that statutory caps on noneconomic damages of $250,000 were significantly associated with lower likelihood of a specialist receiving referrals, suggesting a potential impact of a state’s medical malpractice environment on physicians’ referral behavior. PMID:23527533

An in vitro investigation of the temperature rises produced in dentine by Nd:YAG laser light with and without water cooling.

PubMed

Gow, A M; McDonald, A V; Pearson, G J; Setchell, D J

1999-01-01

Infrared lasers are reported to have thermal side effects which may damage pulp tissue. This study investigated the thermal effects of the pulsed Nd:YAG laser. Prepared, extracted teeth were measured prior to irradiation. Temperature was recorded using a thermocouple/data logging system. Laser irradiation was carried out with or without water spray for an exposure time of ten seconds. Results indicated that dry irradiation produced unacceptable temperature rises with dentine thicknesses used. Wet irradiation produced a significantly lower temperature rise. It was concluded that the Nd:YAG laser produced thermal effects which could potentially cause pulpal trauma. A water coolant was effective in reducing these thermal effects, but the temperature rise achieved whilst using water coolant may still cause pulpal damage.

Risk-rating Saratoga Spittlebug Damage by Abundance of Alternate-host Plants

Treesearch

Louis F. Wilson

1971-01-01

The potential damage of the Saratoga spittlebug to red pine can be predicted by comparing the percentage of ground occupied by sweet-fern with the percentage of ground cover occupied by other nymphal host plants. A risk-rating graph is used to estimate potential damage.

Emerging metrology for high-throughput nanomaterial genotoxicology.

PubMed

Nelson, Bryant C; Wright, Christa W; Ibuki, Yuko; Moreno-Villanueva, Maria; Karlsson, Hanna L; Hendriks, Giel; Sims, Christopher M; Singh, Neenu; Doak, Shareen H

2017-01-01

The rapid development of the engineered nanomaterial (ENM) manufacturing industry has accelerated the incorporation of ENMs into a wide variety of consumer products across the globe. Unintentionally or not, some of these ENMs may be introduced into the environment or come into contact with humans or other organisms resulting in unexpected biological effects. It is thus prudent to have rapid and robust analytical metrology in place that can be used to critically assess and/or predict the cytotoxicity, as well as the potential genotoxicity of these ENMs. Many of the traditional genotoxicity test methods [e.g. unscheduled DNA synthesis assay, bacterial reverse mutation (Ames) test, etc.,] for determining the DNA damaging potential of chemical and biological compounds are not suitable for the evaluation of ENMs, due to a variety of methodological issues ranging from potential assay interferences to problems centered on low sample throughput. Recently, a number of sensitive, high-throughput genotoxicity assays/platforms (CometChip assay, flow cytometry/micronucleus assay, flow cytometry/γ-H2AX assay, automated 'Fluorimetric Detection of Alkaline DNA Unwinding' (FADU) assay, ToxTracker reporter assay) have been developed, based on substantial modifications and enhancements of traditional genotoxicity assays. These new assays have been used for the rapid measurement of DNA damage (strand breaks), chromosomal damage (micronuclei) and for detecting upregulated DNA damage signalling pathways resulting from ENM exposures. In this critical review, we describe and discuss the fundamental measurement principles and measurement endpoints of these new assays, as well as the modes of operation, analytical metrics and potential interferences, as applicable to ENM exposures. An unbiased discussion of the major technical advantages and limitations of each assay for evaluating and predicting the genotoxic potential of ENMs is also provided. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society 2016.

Anti-oxidative cellular protection effect of fasting-induced autophagy as a mechanism for hormesis.

PubMed

Moore, Michael N; Shaw, Jennifer P; Ferrar Adams, Dawn R; Viarengo, Aldo

2015-06-01

The aim of this investigation was to test the hypothesis that fasting-induced augmented lysosomal autophagic turnover of cellular proteins and organelles will reduce potentially harmful lipofuscin (age-pigment) formation in cells by more effectively removing oxidatively damaged proteins. An animal model (marine snail--common periwinkle, Littorina littorea) was used to experimentally test this hypothesis. Snails were deprived of algal food for 7 days to induce an augmented autophagic response in their hepatopancreatic digestive cells (hepatocyte analogues). This treatment resulted in a 25% reduction in the cellular content of lipofuscin in the digestive cells of the fasting animals in comparison with snails fed ad libitum on green alga (Ulva lactuca). Similar findings have previously been observed in the digestive cells of marine mussels subjected to copper-induced oxidative stress. Additional measurements showed that fasting significantly increased cellular health based on lysosomal membrane stability, and reduced lipid peroxidation and lysosomal/cellular triglyceride. These findings support the hypothesis that fasting-induced augmented autophagic turnover of cellular proteins has an anti-oxidative cytoprotective effect by more effectively removing damaged proteins, resulting in a reduction in the formation of potentially harmful proteinaceous aggregates such as lipofuscin. The inference from this study is that autophagy is important in mediating hormesis. An increase was demonstrated in physiological complexity with fasting, using graph theory in a directed cell physiology network (digraph) model to integrate the various biomarkers. This was commensurate with increased health status, and supportive of the hormesis hypothesis. The potential role of enhanced autophagic lysosomal removal of damaged proteins in the evolutionary acquisition of stress tolerance in intertidal molluscs is discussed and parallels are drawn with the growing evidence for the involvement of autophagy in hormesis and anti-ageing processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessing the Social and Environmental Costs of Institutional ...

EPA Pesticide Factsheets

Background/Question/Methods: Release of N to air, land and water has a host of effects on human health, ecosystems and the economy, many of which scientists and economists are just beginning to develop methods to quantify. In order to understand the broader connections to sustainability, more effort is needed to connect N release to the environment with the impacts on social and economic systems. We estimate the damage costs associated with the institutional nitrogen (N) footprint and explore how this information could be used to create more sustainable institutions. Potential damages associated with the release of NOx and N2O to air and release of N to water were estimated using a cost per unit N approach. Results/Conclusions: Annual potential damage costs to human health, agriculture and natural ecosystems associated with the N footprint of institutions were $10.5 million USD (2014) at the University of Virginia (UVA) and $3.0 million USD at the University of New Hampshire (UNH). Costs associated with the release of nitrogen oxides (NOx) to human health, in particular the use of coal-derived energy, were the largest component of damage at UVA. At UNH the energy N footprint is much lower because of a co-generation source, and thus the majority of damages were associated with food production. Annual damages associated with release of N from food production were very similar at the two universities ($1.37 vs. $1.66 million at UVA and UNH respectively). T

Benchmarking Discount Rate in Natural Resource Damage Assessment with Risk Aversion.

PubMed

Wu, Desheng; Chen, Shuzhen

2017-08-01

Benchmarking a credible discount rate is of crucial importance in natural resource damage assessment (NRDA) and restoration evaluation. This article integrates a holistic framework of NRDA with prevailing low discount rate theory, and proposes a discount rate benchmarking decision support system based on service-specific risk aversion. The proposed approach has the flexibility of choosing appropriate discount rates for gauging long-term services, as opposed to decisions based simply on duration. It improves injury identification in NRDA since potential damages and side-effects to ecosystem services are revealed within the service-specific framework. A real embankment case study demonstrates valid implementation of the method. © 2017 Society for Risk Analysis.

Ultrasound Imaging of DNA-Damage Effects in Live Cultured Cells and in Brain Tissue.

PubMed

Tadayyon, Hadi; Gangeh, Mehrdad J; Vlad, Roxana; Kolios, Michael C; Czarnota, Gregory J

2017-01-01

High-frequency ultrasound (>20 MHz) spectroscopy can be used to detect noninvasively DNA damage in cell samples in vitro, and in live tissue both ex vivo and in vivo. This chapter focuses on the former two aspects. Experimental evidence suggests that morphological changes that occur in cells undergoing apoptosis result in changes in frequency-dependent ultrasound backscatter. With advances in research, ultrasound spectroscopy is advancing the boundaries of fast, label-free, noninvasive DNA damage detection technology with potential use in personalized medicine and early therapy response monitoring. Depending on the desired resolution, parametric ultrasound images can be computed and displayed within minutes to hours after ultrasound examination for cell death.

Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures

PubMed Central

Qi, Weidong; Ding, Dalian; Salvi*, Richard J.

2008-01-01

The amphipathic molecule dimethyl sulphoxide (DMSO) is a solvent often used to dissolve compounds applied to the inner ear; however, little is known about its potential cytotoxic side effects. To address this question, we applied 0.1 to 6% DMSO for 24 h to cochlear organotypic cultures from postnatal day 3 rats and examined its cytotoxic effects. DMSO concentrations of 0.1% and 0.25% caused little or no damage. However, concentrations between 0.5 and 6% resulted in stereocilia damage, hair cell swelling and a dose-dependent loss of hair cells. Hair cell damage began in the basal turn of the cochlea and spread towards the apex with increasing concentration. Surprisingly, DMSO-induced damage was greater for inner hair cells than outer hair cell whereas nearby supporting cells were largely unaffected. Most hair cell death was associated with nuclear shrinkage and fragmentation, morphological features consistent with apoptosis. DMSO treatment induced TUNEL positive staining in many hair cells and activated both initiator caspase-9 and caspase-8 and executioner caspase-3; this suggests that apoptosis is initiated by both intrinsic mitochondrial and extrinsic membrane cell death signaling pathways. PMID:18207679

Anti-oxidative protection against iron overload-induced liver damage in mice by Cajanus cajan (L.) Millsp. leaf extract.

PubMed

Sarkar, Rhitajit; Hazra, Bibhabasu; Mandal, Nripendranath

2013-02-01

In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload.

Phase 2 trial of daily, oral epigallocatechin gallate in patients with light-chain amyloidosis.

PubMed

Meshitsuka, Sohsuke; Shingaki, Sumito; Hotta, Masatoshi; Goto, Miku; Kobayashi, Makoto; Ukawa, Yuuichi; Sagesaka, Yuko M; Wada, Yasuyo; Nojima, Masanori; Suzuki, Kenshi

2017-03-01

Previous studies have suggested that an increase in mitochondrial reactive oxygen species may cause organ damage in patients with light-chain (AL) amyloidosis; however, this damage can be decreased by antioxidant-agent treatment. Epigallocatechin gallate (EGCG), the major natural catechin in green tea, has potent antioxidant activity. Because EGCG has recently been reported to have a favorable toxicity profile for treating amyloidosis, we sought to examine the clinical efficacy and toxicity of EGCG in patients with AL amyloidosis. Fifty-seven patients were randomly assigned to the EGCG and observation groups and observed for six months. There were no increases in grade 3-5 adverse events and EGCG therapy was well tolerated. Although a decrease in the urinary albumin level was found in the EGCG group in patients with obvious albuminuria after treatment initiation, its antioxidant activity may not be sufficient to clarify the potential effect of EGCG in patients with AL amyloidosis. Because some of the biological markers responsible for organ damage were well correlated to the level of antioxidant potential in patients' plasma, the status of oxidative stress in the blood may indicate the extent of organ damage in clinical situations.

Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis.

PubMed

Ji, Chao; Yang, Bo; Huang, Shu-Ying; Huang, Jin-Wen; Cheng, Bo

2017-12-02

The role of UVB in skin photo damages has been widely reported. Overexposure to UVB will induce severe DNA damages in epidermal cells and cause most cytotoxic symptoms. In the present study, we tested the potential activity of salubrinal, a selective inhibitor of Eukaryotic Initiation Factor 2 (eIF2) -alpha phosphatase, against UV-induced skin cell damages. We first exposed human fibroblasts to UVB radiation and evaluated the cytosolic Ca 2+ level as well as the induction of ER stress. We found that UVB radiation induced the depletion of ER Ca 2+ and increased the expression of ER stress marker including phosphorylated PERK, CHOP, and phosphorylated IRE1α. We then determined the effects of salubrinal in skin cell death induced by UVB radiation. We observed that cells pre-treated with salubrinal had a higher survival rate compared to cells treated with UVB alone. Pre-treatment with salubrinal successfully re-established the ER function and Ca 2+ homeostasis. Our results suggest that salubrinal can be a potential therapeutic agents used in preventing photoaging and photo damages. Copyright © 2017 Elsevier Inc. All rights reserved.

The potential impact of ozone on materials in the U.K.

NASA Astrophysics Data System (ADS)

Lee, David S.; Holland, Michael R.; Falla, Norman

Recent reports have highlighted the potential damage caused to a range of media, including materials, by ozone (O 3). The limited data available indicate significant damage to rubber products and surface coatings but either insignificant or unquantifiable damage to textiles and other polymeric materials at the range of atmospheric concentrations encountered in the U.K. Materials in the indoor environment have been excluded from economic analyses. Legislation was put in place in 1993 in the U.K. in order to reduce NO x (NO x = NO + NO 2) and VOC (volatile organic compounds) emissions from motor vehicles which is likely to result in reduced peak O 3 episodes but increased average levels of O 3 in urban areas which may result in increased damage to materials. A detailed assessment of the costs of O 3 damage to materials is not currently possible because of insufficient information on relevant dose-response functions and the stock at risk. Alternative methods were thus adopted to determine the potential scale of the problem. Scaling of U.S. estimates made in the late 1960s provides a range for the U.K. of £170 million-£345 million yr -1 in current terms. This includes damage to surface coatings and elastomers, and the cost of antiozonant protection applied to rubber goods. Independent estimates were made of the costs of protecting rubber goods in the U.K. These were based on the size of the antiozonant market, and provide cost ranges of £25 million-£63 million yr -1 to manufacturers and £25 million-£189 million yr -1 to consumers. The only rubber goods for which a damage estimate (not including protection costs) could be made were tyres, using data from the U.S.A. and information on annual tyre sales in the U.K. A range of £0-£4 million yr -1 was estimated. The cost of damage to other rubber goods could not be quantified because of a lack of data on both the stock at risk and exposure-response functions. The effect of O 3 on the costs of repainting were estimated under scenarios of increased urban concentrations of O 3 using damage functions derived from the literature. The cost was estimated to be in the range of £0-£60 million yr -1 for a change from 15 to 20 ppb O 3, and £0 to £182 million yr -1 for a change from 15 to 30 ppb O 3. The wide ranges derived for effects on surface coatings are a reflection of the uncertainty associated with the dose-response functions used.

Insect damage influences heat and water stress resistance gene expression in field grown popcorn: Implications in developing varieties adapted to climate change

USDA-ARS?s Scientific Manuscript database

Warming climatic conditions can pose potential problems for crop production, but detailed effects at the molecular level on potentially affected crop plants are lacking. Popcorn is a valuable snack food worldwide, and is difficult to improve by breeding due to multigenic influences on popping. It ha...

Annosus Root Disease Hazard Rating, Detection, and Management Strategies in the Southeastern United States

Treesearch

S. A. Alexander

1989-01-01

Annosus root disease (ARD), is the major root disease of pines in the southeastern United States where severely affected trees exhibit growth loss. Assessing the potential damage of ARD is essential for making effective disease control and management decisions. A soil hazard rating system developed to identify potential for tree mortality is described. The Annosus...

Interplay of space radiation and microgravity in DNA damage and DNA damage response.

PubMed

Moreno-Villanueva, María; Wong, Michael; Lu, Tao; Zhang, Ye; Wu, Honglu

2017-01-01

In space, multiple unique environmental factors, particularly microgravity and space radiation, pose constant threat to the DNA integrity of living organisms. Specifically, space radiation can cause damage to DNA directly, through the interaction of charged particles with the DNA molecules themselves, or indirectly through the production of free radicals. Although organisms have evolved strategies on Earth to confront such damage, space environmental conditions, especially microgravity, can impact DNA repair resulting in accumulation of severe DNA lesions. Ultimately these lesions, namely double strand breaks, chromosome aberrations, micronucleus formation, or mutations, can increase the risk for adverse health effects, such as cancer. How spaceflight factors affect DNA damage and the DNA damage response has been investigated since the early days of the human space program. Over the years, these experiments have been conducted either in space or using ground-based analogs. This review summarizes the evidence for DNA damage induction by space radiation and/or microgravity as well as spaceflight-related impacts on the DNA damage response. The review also discusses the conflicting results from studies aimed at addressing the question of potential synergies between microgravity and radiation with regard to DNA damage and cellular repair processes. We conclude that further experiments need to be performed in the true space environment in order to address this critical question.

Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair.

PubMed

Mohamad, Osama; Sishc, Brock J; Saha, Janapriya; Pompos, Arnold; Rahimi, Asal; Story, Michael D; Davis, Anthony J; Kim, D W Nathan

2017-06-09

Compared to conventional photon-based external beam radiation (PhXRT), carbon ion radiotherapy (CIRT) has superior dose distribution, higher linear energy transfer (LET), and a higher relative biological effectiveness (RBE). This enhanced RBE is driven by a unique DNA damage signature characterized by clustered lesions that overwhelm the DNA repair capacity of malignant cells. These physical and radiobiological characteristics imbue heavy ions with potent tumoricidal capacity, while having the potential for simultaneously maximally sparing normal tissues. Thus, CIRT could potentially be used to treat some of the most difficult to treat tumors, including those that are hypoxic, radio-resistant, or deep-seated. Clinical data, mostly from Japan and Germany, are promising, with favorable oncologic outcomes and acceptable toxicity. In this manuscript, we review the physical and biological rationales for CIRT, with an emphasis on DNA damage and repair, as well as providing a comprehensive overview of the translational and clinical data using CIRT.

The effect of red light irradiation on spermatozoa DNA

NASA Astrophysics Data System (ADS)

Chow, Kay W.; Preece, Daryl; Gomez-Godinez, Veronica; Berns, Michael W.

2016-09-01

A key goal in the conservation of endangered species is to increase successful reproduction. In cases where traditional methods of in vitro fertilization are unsuccessful, new methods of assisted reproduction are needed. One option is selective fertilization via optically trapped sperm. A more passive option is red light irradiation. Red light irradiation has been shown to increase sperm motility, thus increasing fertilizing potential. However, there is some concern that exposure to laser irradiation induces the production of oxidative species in cells, which can be damaging to DNA. In order to test the safety of irradiating sperm, sperm samples were exposed to 633 nm laser light and their DNA were tested for oxidative damage. Using fluorescence microscopy, antibody staining, and ELISA to detect oxidative DNA damage, it was concluded that red light irradiation does not pose a safety risk to sperm DNA. The use of red light on sperm has potential in both animal conservation and human reproduction techniques. This method can also be used in conjunction with optical trapping for viable sperm selection.

Journal of the Chinese Institute of Engineers. Special Issue: Commemoration of Chi-Chi Earthquake (II)

NASA Astrophysics Data System (ADS)

2002-09-01

Contents include the following: Deep Electromagnetic Images of Seismogenic Zone of the Chi-Chi (Taiwan) Earthquake; New Techniques for Stress-Forecasting Earthquakes; Aspects of Characteristics of Near-Fault Ground Motions of the 1999 Chi-Chi (Taiwan) Earthquake; Liquefaction Damage and Related Remediation in Wufeng after the Chi-Chi Earthquake; Fines Content Effects on Liquefaction Potential Evaluation for Sites Liquefied during Chi-Chi Earthquake 1999; Damage Investigation and Liquefaction Potential Analysis of Gravelly Soil; Dynamic Characteristics of Soils in Yuan-Lin Liquefaction Area; A Preliminary Study of Earthquake Building Damage and Life Loss Due to the Chi-Chi Earthquake; Statistical Analyses of Relation between Mortality and Building Type in the 1999 Chi-Chi Earthquake; Development of an After Earthquake Disaster Shelter Evaluation Model; Posttraumatic Stress Reactions in Children and Adolescents One Year after the 1999 Taiwan Chi-Chi Earthquake; Changes or Not is the Question: the Meaning of Posttraumatic Stress Reactions One Year after the Taiwan Chi-Chi Earthquake.

Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair

PubMed Central

Mohamad, Osama; Sishc, Brock J.; Saha, Janapriya; Pompos, Arnold; Rahimi, Asal; Story, Michael D.; Davis, Anthony J.; Kim, D.W. Nathan

2017-01-01

Compared to conventional photon-based external beam radiation (PhXRT), carbon ion radiotherapy (CIRT) has superior dose distribution, higher linear energy transfer (LET), and a higher relative biological effectiveness (RBE). This enhanced RBE is driven by a unique DNA damage signature characterized by clustered lesions that overwhelm the DNA repair capacity of malignant cells. These physical and radiobiological characteristics imbue heavy ions with potent tumoricidal capacity, while having the potential for simultaneously maximally sparing normal tissues. Thus, CIRT could potentially be used to treat some of the most difficult to treat tumors, including those that are hypoxic, radio-resistant, or deep-seated. Clinical data, mostly from Japan and Germany, are promising, with favorable oncologic outcomes and acceptable toxicity. In this manuscript, we review the physical and biological rationales for CIRT, with an emphasis on DNA damage and repair, as well as providing a comprehensive overview of the translational and clinical data using CIRT. PMID:28598362

Economic impacts of a California tsunami

USGS Publications Warehouse

Rose, Adam; Wing, Ian Sue; Wei, Dan; Wein, Anne

2016-01-01

The economic consequences of a tsunami scenario for Southern California are estimated using computable general equilibrium analysis. The economy is modeled as a set of interconnected supply chains interacting through markets but with explicit constraints stemming from property damage and business downtime. Economic impacts are measured by the reduction of Gross Domestic Product for Southern California, Rest of California, and U.S. economies. For California, total economic impacts represent the general equilibrium (essentially quantity and price multiplier) effects of lost production in industries upstream and downstream in the supply-chain of sectors that are directly impacted by port cargo disruptions at Port of Los Angeles and Port of Long Beach (POLA/POLB), property damage along the coast, and evacuation of potentially inundated areas. These impacts are estimated to be $2.2 billion from port disruptions, $0.9 billion from property damages, and $2.8 billion from evacuations. Various economic-resilience tactics can potentially reduce the direct and total impacts by 80–85%.

Inhibitors of soluble epoxide hydrolase minimize ischemia-reperfusion-induced cardiac damage in normal, hypertensive, and diabetic rats.

PubMed

Islam, Oliul; Patil, Prashanth; Goswami, Sumanta K; Razdan, Rema; Inamdar, Mohammed N; Rizwan, Mohammed; Mathew, Jubin; Inceoglu, Bora; Stephen Lee, Kin S; Hwang, Sung H; Hammock, Bruce D

2017-06-01

We designed a study to evaluate the cardioprotective effect of two soluble epoxide hydrolase (sEH) inhibitors, 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl)urea (TPPU) and trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB), in ischemia-reperfusion (IR) model. Cardioprotective effects of the sEH inhibitors were evaluated against IR-induced myocardial damage in hearts from normal, hypertensive, and diabetic rats using Langendorff's apparatus. In addition, the effect of sEH inhibitors on endothelial function was evaluated in vitro and ex vivo using isolated rat thoracic aorta. Ischemia-reperfusion (IR) increased the myocardial damage in hearts from normal rats. IR-induced myocardial damage was augmented in hearts isolated from hypertensive and diabetic rats. Myocardial damage as evident from increase in the activities of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in heart perfusate was associated with significant decrease in the heart rate and developed tension, and increase in the resting tension in isolated heart. Both sEH inhibitors protected the heart in normal, hypertensive, and diabetic rats subjected to IR injury. The sEH inhibitor t-TUCB relaxed phenylephrine precontracted aorta from normal rats. Relaxant effect of acetylcholine (ACh) was reduced in aortas from diabetic and hypertensive rats compared to normal rats. Pretreatment of sEH inhibitors to diabetic and hypertensive rats increased relaxant effect of ACh on aortas isolated from these rats. Prophylactic treatment with sEH inhibitors decreased myocardial damage due to IR, hypertension and diabetes, and decreased endothelial dysfunction created by diabetes and hypertension. Therefore, inhibitors of sEH are useful probes to study cardiovascular pathology, and inhibition of the sEH is a potential approach in the management of IR-induced cardiac damage and endothelial dysfunction-related cardiovascular disorders. © 2017 John Wiley & Sons Ltd.

Therapeutic effects of date palm (Phoenix dactylifera L.) pollen extract on cadmium-induced testicular toxicity.

PubMed

El-Neweshy, M S; El-Maddawy, Z K; El-Sayed, Y S

2013-12-01

Cadmium (Cd) is a well-known testicular toxicant. This study was designed to explore the long-term effects of a single low dose of Cd on spermatogenesis, and testicular dysfunction and oxidative stress, and the therapeutic potential of date palm pollen extract (DPP) in averting such reproductive damage. Adult male Wistar rats received a single intraperitoneal injection of CdCl2 (0 or 1 mg kg(-1) ). Twenty-four hours later, they started receiving DPP (0 or 40 mg kg(-1) ) orally, once daily for 56 consecutive days. Cd exposure caused significant reproductive damage via reduced weight of the reproductive organs, which includes spermatological damage (decreased sperm count and motility and increased rates of sperm abnormalities), increased oxidative stress (increased malondialdehyde and decreased reduced glutathione levels), histological alterations (necrosis, inefficient to completely arrest spermatogenesis and a reduced Johnsen's score) and decreased serum testosterone level. DPP restored spermatogenesis and attenuated the toxic effects of Cd on the reproductive system to the levels observed in the control animals. These findings support the hypothesis that the testis is particularly sensitive to Cd, which can cause testicular damage and infertility. Treatment with DPP can ameliorate the deleterious effects of Cd, probably by activating testicular endocrine and antioxidant systems. © 2012 Blackwell Verlag GmbH.

DNA and BSA damage inhibitory activities, and anti-acetylcholinesterase, anti-porcine α-amylase and antioxidant properties of Dolichos lablab beans.

PubMed

Habib, Hosam M; Theuri, Serah W; Kheadr, Ehab; Mohamed, Fedah E

2017-02-22

The underutilized Kenyan variety of Dolichos lablab bean seeds serve as a good source of natural antioxidants, which can probably be effective in reducing the risk of occurrence of several diseases. This study was undertaken for the first time to address the limited knowledge regarding the antioxidant activities of lablab beans. Moreover, their DNA damage inhibitory activity, bovine serum albumin (BSA) damage inhibitory activity, and the inhibition of acetylcholinesterase and porcine α-amylase were also investigated. The antioxidant capacity of Dolichos lablab bean seeds extracted with methanol, water or methanol/water combination was evaluated by the ferric-reducing antioxidant power (FRAP) assay, free radical-scavenging activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) radical-scavenging assay, and 2,20-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Results reported in the present study indicate that water, methanol and water/methanol extracts of lablab bean flour exhibited good antioxidant activity by effectively scavenging various free radicals, such as DPPH, NO, and ABTS radicals. The extracts also exhibited protective effects against DNA and BSA damage and inhibitory effects on porcine α-amylase. Findings of this study suggest that extracts from the lablab bean flour would have potential application in food supplements, and pharmaceutical and cosmetic industries.

DNA-dependent protein kinase modulates the anti-cancer properties of silver nanoparticles in human cancer cells.

PubMed

Lim, Hui Kheng; Gurung, Resham Lal; Hande, M Prakash

2017-12-01

Silver nanoparticles (Ag-np) were reported to be toxic to eukaryotic cells. These potentially detrimental effects of Ag-np can be advantageous in experimental therapeutics. They are currently being employed to enhance the therapeutic efficacy of cancer drugs. In this study, we demonstrate that Ag-np treatment trigger the activation of DNA-PKcs and JNK pathway at selected doses, presumably as a physiologic response to DNA damage and repair in normal and malignant cells. Ag-np altered the telomere dynamics by disrupting the shelterin complex located at the telomeres and telomere lengths. The genotoxic effect of Ag-np was not restricted to telomeres but the entire genome as Ag-np induced γ-H2AX foci formation, an indicator of global DNA damage. Inhibition of DNA-PKcs activity sensitised the cancer cells towards the cytotoxicity of Ag-np and substantiated the damaging effect of Ag-np at telomeres in human cancer cells. Abrogation of JNK mediated DNA repair and extensive damage of telomeres led to greater cell death following Ag-np treatment in DNA-PKcs inhibited cancer cells. Collectively, this study suggests that improved anti-proliferative and cytotoxic effects of Ag-np treatment in cancer cells can be achieved by the inhibition of DNA-PKcs. Copyright © 2017 Elsevier B.V. All rights reserved.

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment.

PubMed

Lewis, Sheena E M; John Aitken, R; Conner, Sarah J; Iuliis, Geoffry De; Evenson, Donald P; Henkel, Ralph; Giwercman, Aleksander; Gharagozloo, Parviz

2013-10-01

Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract, the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency. Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. With all of these fertility check points, it shows more promise than conventional semen parameters from a diagnostic perspective. Despite this, few infertility clinics use it routinely. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the strengths and weaknesses and clinical applicability of current sperm DNA fragmentation tests. Next, the biological significance of DNA damage in the male germ line is considered. Finally, as sperm DNA damage is often the result of increased oxidative stress in the male reproductive tract, the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. As those working in this field of clinical research, we conclude that DNA damage in human spermatozoa is an important attribute of semen quality which should be carefully assessed in the clinical work up of infertile couples and that properly controlled trials addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Morphine protects SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine-induced cell damage: involvement of anti-oxidant, calcium blocking, and anti-apoptotic properties.

PubMed

Elyasi, Leila; Eftekhar-Vaghefi, Seyed Hassan; Esmaeili-Mahani, Saeed

2014-06-01

Parkinson's disease is a neurodegenerative disorder characterized by progressive and selective death of dopaminergic neurons. Understanding the neuroprotective effects of chemical reagents has attracted increasing attention. The μ opioid agonist morphine exerts both toxic and protective effects. However, until recently, the neuroprotective role of morphine against 6-hydroxydopamine (6-OHDA)-induced cell death has not been studied. Here, we investigated the effects of morphine on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson's disease. Cell damage was induced by 150 μM 6-OHDA, and the cells' viability was examined by MTT assay. Intracellular calcium, reactive oxygen species (ROS), and mitochondrial membrane potential were determined by the fluorescence spectrophotometry method. Fragmented DNA and biochemical markers of apoptosis were also determined by gel electrophoresis and immunoblotting, respectively. The data showed that 6-OHDA caused a loss of cell viability and mitochondrial membrane potential. In addition, intracellular ROS and calcium levels, activated caspase-3, Bax:Bcl-2 ratio, cytochrome c release, as well as DNA fragmentation were significantly increased in 6-OHDA-treated cells. Incubation of SH-SY5Y cells with morphine (100 μM) elicited a protective effect and reduced biochemical markers of cell damage and death. These results suggest that morphine has neuroprotective effects against 6-OHDA-induced neurotoxicity, and such effects are accompanied by its anti-oxidant, calcium blocking, and anti-apoptotic properties.

The effects PCSO-524®, a patented marine oil lipid and omega-3 PUFA blend derived from the New Zealand green lipped mussel (Perna canaliculus), on indirect markers of muscle damage and inflammation after muscle damaging exercise in untrained men: a randomized, placebo controlled trial.

PubMed

Mickleborough, Timothy D; Sinex, Jacob A; Platt, David; Chapman, Robert F; Hirt, Molly

2015-01-01

The purpose of the present study was to evaluate the effects of PCSO-524®, a marine oil lipid and n-3 LC PUFA blend, derived from New Zealand green- lipped mussel (Perna canaliculus), on markers of muscle damage and inflammation following muscle damaging exercise in untrained men. Thirty two untrained male subjects were randomly assigned to consume 1200 mg/d of PCSO- 524® (a green-lipped mussel oil blend) or placebo for 26 d prior to muscle damaging exercise (downhill running), and continued for 96 h following the muscle damaging exercise bout. Blood markers of muscle damage (skeletal muscle slow troponin I, sTnI; myoglobin, Mb; creatine kinase, CK), and inflammation (tumor necrosis factor, TNF-α), and functional measures of muscle damage (delayed onset muscle soreness, DOMS; pressure pain threshold, PPT; knee extensor joint range of motion, ROM; isometric torque, MVC) were assessed pre- supplementation (baseline), and multiple time points post-supplementation (before and after muscle damaging exercise). At baseline and 24 h following muscle damaging exercise peripheral fatigue was assessed via changes in potentiated quadriceps twitch force (∆Qtw,pot) from pre- to post-exhaustive cycling ergometer test in response to supra-maximal femoral nerve stimulation. Compared to placebo, supplementation with the green-lipped mussel oil blend significantly attenuated (p < 0.05) sTnI and TNF-α at 2, 24, 48, 72 and 96 h., Mb at 24, 48, 72, 96 h., and CK-MM at all-time points following muscle damaging exercise, significantly reduced (p < 0.05) DOMS at 72 and 96 h post-muscle damaging exercise, and resulted in significantly less strength loss (MVC) and provided a protective effect against joint ROM loss at 96 h post- muscle damaging exercise. At 24 h after muscle damaging exercise perceived pain was significantly greater (p < 0.05) compared to baseline in the placebo group only. Following muscle damaging exercise ∆Qtw,pot was significantly less (p < 0.05) on the green-lipped mussel oil blend compared to placebo. Supplementation with a marine oil lipid and n-3 LC PUFA blend (PCSO-524®), derived from the New Zealand green lipped mussel, may represent a useful therapeutic agent for attenuating muscle damage and inflammation following muscle damaging exercise.

Irradiation response of commercial, high-Tc superconducting tapes: Electromagnetic transport properties

DOE PAGES

Gapud, A. A.; Greenwood, N. T.; Alexander, J. A.; ...

2015-07-01

Effects of low dose irradiation on the electrical transport current properties of commercially available high-temperature superconducting, coated-conductor tapes were investigated, in view of potential applications in the irradiative environment of fusion reactors. Three different tapes, each with unique as-grown flux-pinning structures, were irradiated with Au and Ni ions at energies that provide a range of damage effects, with accumulated damage levels near that expected for conductors in a fusion reactor environment. Measurements using transport current determined the pre- and post-irradiation resistivity, critical current density, and pinning force density, yielding critical temperatures, irreversibility lines, and inferred vortex creep rates. Results showmore » that at the irradiation damage levels tested, any detriment to as-grown pre-irradiation properties is modest; indeed in one case already-superior pinning forces are enhanced, leading to higher critical currents.« less

Innate Immunity and Inflammation Post-Stroke: An α7-Nicotinic Agonist Perspective

PubMed Central

Neumann, Silke; Shields, Nicholas J.; Balle, Thomas; Chebib, Mary; Clarkson, Andrew N.

2015-01-01

Stroke is one of the leading causes of death and long-term disability, with limited treatment options available. Inflammation contributes to damage tissue in the central nervous system across a broad range of neuropathologies, including Alzheimer’s disease, pain, Schizophrenia, and stroke. While the immune system plays an important role in contributing to brain damage produced by ischemia, the damaged brain, in turn, can exert a powerful immune-suppressive effect that promotes infections and threatens the survival of stroke patients. Recently the cholinergic anti-inflammatory pathway, in particular its modulation using α7-nicotinic acetylcholine receptor (α7-nAChR) ligands, has shown potential as a strategy to dampen the inflammatory response and facilitate functional recovery in stroke patients. Here we discuss the current literature on stroke-induced inflammation and the effects of α7-nAChR modulators on innate immune cells. PMID:26690125

Innate Immunity and Inflammation Post-Stroke: An α7-Nicotinic Agonist Perspective.

PubMed

Neumann, Silke; Shields, Nicholas J; Balle, Thomas; Chebib, Mary; Clarkson, Andrew N

2015-12-04

Stroke is one of the leading causes of death and long-term disability, with limited treatment options available. Inflammation contributes to damage tissue in the central nervous system across a broad range of neuropathologies, including Alzheimer's disease, pain, Schizophrenia, and stroke. While the immune system plays an important role in contributing to brain damage produced by ischemia, the damaged brain, in turn, can exert a powerful immune-suppressive effect that promotes infections and threatens the survival of stroke patients. Recently the cholinergic anti-inflammatory pathway, in particular its modulation using α7-nicotinic acetylcholine receptor (α7-nAChR) ligands, has shown potential as a strategy to dampen the inflammatory response and facilitate functional recovery in stroke patients. Here we discuss the current literature on stroke-induced inflammation and the effects of α7-nAChR modulators on innate immune cells.

In vitro and in vivo models of colorectal cancer: antigenotoxic activity of berries.

PubMed

Brown, Emma M; Latimer, Cheryl; Allsopp, Philip; Ternan, Nigel G; McMullan, Geoffery; McDougall, Gordon J; Stewart, Derek; Crozier, Alan; Rowland, Ian; Gill, Chris I R

2014-05-07

The etiology of colorectal cancer (CRC), a common cause of cancer-related mortality globally, has strong associations with diet. There is considerable epidemiological evidence that fruits and vegetables are associated with reduced risk of CRC. This paper reviews the extensive evidence, both from in vitro studies and animal models, that components of berry fruits can modulate biomarkers of DNA damage and that these effects may be potentially chemoprotective, given the likely role that oxidative damage plays in mutation rate and cancer risk. Human intervention trials with berries are generally consistent in indicating a capacity to significantly decrease oxidative damage to DNA, but represent limited evidence for anticarcinogenicity, relying as they do on surrogate risk markers. To understand the effects of berry consumption on colorectal cancer risk, future studies will need to be well controlled, with defined berry extracts, using suitable and clinically relevant end points and considering the importance of the gut microbiota.

A study and comparison of the effects of low speed change vehicle collisions on the human body.

PubMed

Hoyes, Philip; Henderson, Brian

2013-03-01

In motor vehicle collisions there is a well-established relationship between the level of damage sustained by the vehicle, its change in speed during the collision period, the movement of occupants and the potential for their injury. Greater damage, with respect to structure, means a greater potential for injury. In terms of rear-end impacts, speed change thresholds for injury have been suggested in previous literature. This research uses human test subjects and three full-scale vehicle, rear-end collisions to investigate the correlation between speed change and occupant movement and uses it to test the suggestion of a second threshold where the accelerations are similar to an everyday activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of Peanut-Tobacco Rotations on Population Dynamics of Meloidogyne arenaria in Mixed Race Populations.

PubMed

Hirunsalee, A; Barker, K R; Beute, M K

1995-06-01

A 3-year microplot study was initiated to characterize the population dynamics, reproduction potential, and survivorship of single or mixed populations of Meloidogyne arenaria race 1 (Ma1) and race 2 (Ma2), as affected by crop rotations of peanut 'Florigiant' and M. incognita races 1 and 3-resistant 'McNair 373' and susceptible 'Coker 371-Gold' tobacco. Infection, reproduction, and root damage by Ma2 on peanut and by Ma1 on resistant tobacco were limited in the first year. Infection, reproduction, and root-damage potentials on susceptible tobacco were similar for Ma1 and Ma2. In the mixed (1:1) population, Ma1 was dominant on peanut and Ma2 was dominant on both tobacco cultivars. Crop rotation affected the population dynamics of different nematode races. For years 2 and 3, the low numbers of Ma1 and Ma2 from a previous-year poor host increased rapidly on suitable hosts. Ma1 had greater reproduction factors ([RF] = population density at harvest/population density at preplandng) than did Ma2 and Ma1 + Ma2 in second-year peanut plots following first-year resistant tobacco, and in third-year peanut plots following second-year tobacco. In mixed infestations, Ma1 predominated over Ma2 in previous-year peanut plots, whereas Ma2 predominated over Ma1 in previous-year tobacco plots. Moderate damage on resistant tobacco was induced by Ma1 in the second year. In the third year, moderate damage on peanut was associated with 'Ma2' from previous-year peanut plots. The resistant tobacco supported sufficient reproduction of Ma1 over 2 years to effect moderate damage and yield suppression to peanut in year 3.

Effects of Peanut-Tobacco Rotations on Population Dynamics of Meloidogyne arenaria in Mixed Race Populations

PubMed Central

Hirunsalee, Anan; Barker, K. R.; Beute, M. K.

1995-01-01

A 3-year microplot study was initiated to characterize the population dynamics, reproduction potential, and survivorship of single or mixed populations of Meloidogyne arenaria race 1 (Ma1) and race 2 (Ma2), as affected by crop rotations of peanut 'Florigiant' and M. incognita races 1 and 3-resistant 'McNair 373' and susceptible 'Coker 371-Gold' tobacco. Infection, reproduction, and root damage by Ma2 on peanut and by Ma1 on resistant tobacco were limited in the first year. Infection, reproduction, and root-damage potentials on susceptible tobacco were similar for Ma1 and Ma2. In the mixed (1:1) population, Ma1 was dominant on peanut and Ma2 was dominant on both tobacco cultivars. Crop rotation affected the population dynamics of different nematode races. For years 2 and 3, the low numbers of Ma1 and Ma2 from a previous-year poor host increased rapidly on suitable hosts. Ma1 had greater reproduction factors ([RF] = population density at harvest/population density at preplandng) than did Ma2 and Ma1 + Ma2 in second-year peanut plots following first-year resistant tobacco, and in third-year peanut plots following second-year tobacco. In mixed infestations, Ma1 predominated over Ma2 in previous-year peanut plots, whereas Ma2 predominated over Ma1 in previous-year tobacco plots. Moderate damage on resistant tobacco was induced by Ma1 in the second year. In the third year, moderate damage on peanut was associated with 'Ma2' from previous-year peanut plots. The resistant tobacco supported sufficient reproduction of Ma1 over 2 years to effect moderate damage and yield suppression to peanut in year 3. PMID:19277278

Polyphenol-enriched Vaccinium uliginosum L. fractions reduce retinal damage induced by blue light in A2E-laden ARPE19 cell cultures and mice.

PubMed

Lee, Bom-Lee; Kang, Jung-Hwan; Kim, Hye-Mi; Jeong, Se-Hee; Jang, Dae-Sik; Jang, Young-Pyo; Choung, Se-Young

2016-12-01

Polyphenols exert beneficial effects on vision. We hypothesized that polyphenol components of Vaccinium uliginosum L. (V.U.) extract protect retinal pigment epithelial (RPE) cells against blue light-induced damage. Our aim was to test extracts containing polyphenol components to ascertain effects to reduce damage against blue light in RPEs. We measured the activity in fractions eluted from water, ethanol, and HP20 resin (FH), and found that the FH fraction had the highest beneficial activity. We isolated the individual active compounds from the FH fraction using chromatographic techniques, and found that FH contained flavonoids, anthocyanins, phenyl propanoids, and iridoids. Cell cultures of A2E-laden ARPE-19 exposed to blue light after treatment with V.U. extract fractions and their individual constituents indicated improvement. V uliginosum L extract fractions and constituent compounds significantly reduced A2E photo-oxidation-induced RPE cell death and inhibited intracellular A2E accumulation. Furthermore, Balb/c male mice were exposed to blue light at 10000 lux for 1 h/d for 2 weeks to induce retinal damage. One week after the final blue light exposure, retinal damage evaluated revealed that the outer nuclear layer thickness and nuclei count were improved. Histologic examination of murine photoreceptor cells demonstrated that FH, rich in polyphenols, inhibited the loss of outer nuclear layer thickness and nuclei. Our findings suggest that V.U. extract and eluted fractions are a potential source of bioactive compounds that potentially serve a therapeutic approach for age-related macular degeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Compensatory responses in plant-herbivore interactions: Impacts of insects on leaf water relations

NASA Astrophysics Data System (ADS)

Peschiutta, María L.; Bucci, Sandra J.; Scholz, Fabián G.; Goldstein, Guillermo

2016-05-01

Herbivore damage to leaves has been typically evaluated in terms of fractions of area removed; however morpho-physiological changes in the remaining tissues can occur in response to removal. We assessed the effects of partial removal of the leaf mesophyll by Caliroa cerasi (Hymenoptera) on leaf hydraulic conductance (Kleaf), vascular architecture, water relations and leaf size of three Prunus avium cultivars. The insect feeds on the leaf mesophyll leaving the vein network intact (skeletonization). Within each cultivar there were trees without infestations and trees chronically infested, at least over the last three years. Leaf size of intact leaves tended to be similar during leaf expansion before herbivore attack occurs across infested and non-infested trees. However, after herbivore attack and when the leaves were fully expanded, damaged leaves were smaller than leaves from non-infested trees. Damaged area varied between 21 and 31% depending on cultivar. The non-disruption of the vascular system together with either vein density or capacitance increased in damaged leaves resulted in similar Kleaf and stomatal conductance in infested and non-infested trees. Non-stomatal water loss from repeated leaf damage led to lower leaf water potentials in two of the infested cultivars. Lower leaf osmotic potentials and vulnerability to loss of Kleaf were observed in infested plants. Our results show that skeletonization resulted in compensatory changes in terms of water relations and hydraulics traits and in cultivar-specific physiological changes in phylogenetic related P. avium. Our findings indicate that detrimental effects of herbivory on the photosynthetic surface are counterbalanced by changes providing higher drought resistance, which has adaptive significance in ecosystems where water availability is low and furthermore where global climate changes would decrease soil water availability in the future even further.

Protein phosphatase 2A inhibition enhances radiation sensitivity and reduces tumor growth in chordoma.

PubMed

Hao, Shuyu; Song, Hua; Zhang, Wei; Seldomridge, Ashlee; Jung, Jinkyu; Giles, Amber J; Hutchinson, Marsha-Kay; Cao, Xiaoyu; Colwell, Nicole; Lita, Adrian; Larion, Mioara; Maric, Dragan; Abu-Asab, Mones; Quezado, Martha; Kramp, Tamalee; Camphausen, Kevin; Zhuang, Zhengping; Gilbert, Mark R; Park, Deric M

2018-05-18

Standard therapy for chordoma consists of surgical resection followed by high-dose irradiation. Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase involved in signal transduction, cell cycle progression, cell differentiation, and DNA repair. LB100 is a small-molecule inhibitor of PP2A designed to sensitize cancer cells to DNA damage from irradiation and chemotherapy. A recently completed phase I trial of LB100 in solid tumors demonstrated its safety. Here, we show the therapeutic potential of LB100 in chordoma. Three patient-derived chordoma cell lines were used: U-CH1, JHC7, and UM-Chor1. Cell proliferation was determined with LB100 alone and in combination with irradiation. Cell cycle progression was assessed by flow cytometry. Quantitative γ-H2AX immunofluorescence and immunoblot evaluated the effect of LB100 on radiation-induced DNA damage. Ultrastructural evidence for nuclear damage was investigated using Raman imaging and transmission electron microscopy. A xenograft model was established to determine potential clinical utility of adding LB100 to irradiation. PP2A inhibition in concert with irradiation demonstrated in vitro growth inhibition. The combination of LB100 and radiation also induced accumulation at the G2/M phase of the cell cycle, the stage most sensitive to radiation-induced damage. LB100 enhanced radiation-induced DNA double-strand breaks. Animals implanted with chordoma cells and treated with the combination of LB100 and radiation demonstrated tumor growth delay. Combining LB100 and radiation enhanced DNA damage-induced cell death and delayed tumor growth in an animal model of chordoma. PP2A inhibition by LB100 treatment may improve the effectiveness of radiation therapy for chordoma.

Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

PubMed Central

Kwon, Jee Young; Koedrith, Preeyaporn; Seo, Young Rok

2014-01-01

Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. PMID:25565845

Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity Short Running Title: Genotoxicity of ZnO NPs

PubMed Central

Scherzad, Agmal; Meyer, Till; Kleinsasser, Norbert

2017-01-01

Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival. PMID:29240707

Influence of heavy ions on cell survival, cytogenetic damage and mitochondrial function of human endothelial cells

NASA Astrophysics Data System (ADS)

Ritter, Sylvia; Helm, Alexander; Lee, Ryonfa; Pollet, Dieter; Durante, Marco

There is increasing evidence that there is an elevated risk of cardiovascular disease among atomic bomb survivors and radiotherapy patients, typically developing with a long latency. However, essentially no information is available on the potential cardiovascular risks associated with space radiation, in particular heavy ions. To address this issue, we have chosen human umbilical vein endothelial cells (HUVEC) as a model system. Cells at an early passage number were irradiated with 0.1 to 4 Gy of either 9.8 MeV/u C-ions (LET=170 keV/µm), 91 MeV/u C-ions (LET=29 keV/µm) or 250 kV X-rays. Cells were regularly subcultured up to 40 days (20 population doublings) post-irradiation. Immediately after exposure cell inactivation was deter-mined by the colony forming assay. Furthermore, at selected time-points cytogenetic damage (formation of micronuclei in binucleated cells) and the mitochondrial membrane potential ΨM (flow cytometric analysis following JC-1 staining) were assessed. Measurement of the directly induced radiation damage showed that 9.8 MeV/u and 91 MeV/u C-ions were more effective than X-rays (i.e. about 3 and 2 times, respectively) with respect to cell inactivation or the in-duction of cytogenetic damage. At the subsequent days in the irradiated cultures the number of cells with micronuclei declined to the control level (3-5Altogether our data indicate that under the applied radiation conditions the integrity of mitochondria which play a significant role in the regulation of cardiovascular cell function is not impaired. With respect to directly induced genetic damage C-ions are more effective than X-rays as observed in other cell systems. If the effectiveness of charged particles for the occurrence of late chromosomal damage in endothelial cells is higher than that of sparsely ionizing radiation needs further clarification. The data obtained up to now indicate that sophisticated cytogenetic techniques have to be applied in order to draw any firm conclusions.

The impact of lymphocyte isolation on induced DNA damage in human blood samples measured by the comet assay.

PubMed

Bausinger, Julia; Speit, Günter

2016-09-01

The comet assay is frequently used in human biomonitoring for the detection of exposure to genotoxic agents. Peripheral blood samples are most frequently used and tested either as whole blood or after isolation of lymphocytes (i.e. peripheral blood mononuclear cells, PBMC). To investigate a potential impact of lymphocyte isolation on induced DNA damage in human blood samples, we exposed blood ex vivo to mutagens with different modes of genotoxic action. The comet assay was performed either directly with whole blood at the end of the exposure period or with lymphocytes isolated directly after exposure. In addition to the recommended standard protocol for lymphocyte isolation, a shortened protocol was established to optimise the isolation procedure. The results indicate that the effects of induced DNA strand breaks and alkali-labile sites induced by ionising radiation and alkylants, respectively, are significantly reduced in isolated lymphocytes. In contrast, oxidative DNA base damage (induced by potassium bromate) and stable bulky adducts (induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide; BPDE) seem to be less affected. Our findings suggest that in vivo-induced DNA damage might also be reduced in isolated lymphocytes in comparison with the whole blood depending of the types of DNA damage induced. Because only small genotoxic effects can generally be expected in human biomonitoring studies with the comet assay after occupational and environmental exposure to genotoxic agents, any loss might be relevant and should be avoided. The possibility of such effects and their potential impact on variability of comet assay results in human biomonitoring should be considered when performing or evaluating such kind of studies. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.

PubMed

Tan, Xiao-Hua; Zheng, Xiao-Meng; Yu, Li-Xia; He, Jian; Zhu, Hong-Mei; Ge, Xiu-Ping; Ren, Xiao-Li; Ye, Fa-Qing; Bellusci, Saverio; Xiao, Jian; Li, Xiao-Kun; Zhang, Jin-San

2017-11-01

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and K ATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the K ATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Greenhouse Studies of Thiamethoxam Effects on Pea Leaf Weevil, Sitona lineatus

PubMed Central

Cárcamo, Héctor; Herle, Carolyn; Hervet, Vincent

2012-01-01

The pea leaf weevil, Sitona lineatus L. (Coleoptera: Curculionidae), has recently emerged as an important pest of field peas in the Canadian prairies. Systemic seed-coated insecticides may provide a tool for the integrated pest management of this pest. Therefore, several controlled assays were performed in order to determine effects of a recently registered neonicotinoid, (thiamethoxam) on S. lineatus damage to foliage, weevil mortality, fertility, egg viability, larval mortality, and root nodule damage. Foliage damage was reduced by thiamethoxam relative to untreated controls during the seedling stage (2nd–5th nodes), but weevil adult mortality was only 15–30%. Fertility was reduced substantially through an extra seven-day delay in the preoviposition period and reduced egg-laying rate during the first 20 days of the study (92% lower than controls). Overall egg viability was lower in females fed foliage grown from thiamethoxamtreated seeds. Larval survivorship and nodule damage were also lower, but only when eggs were added to treated plants at the 2nd node stage. When eggs were added late, at the 5th node stage, thiamethoxam had no effect on larval survivorship or nodule damage. The results of this study led to the conclusion that seed treatments such as thiamethoxam have potential to be used as tools that will aid in the integrated pest management of S. lineatus, especially in combination with other methods such as biocontrol and trap crops. PMID:23461362

Mequindox induced cellular DNA damage via generation of reactive oxygen species.

PubMed

Liu, Jing; Ouyang, Man; Jiang, Jun; Mu, Peiqiang; Wu, Jun; Yang, Qi; Zhang, Caihui; Xu, Weiying; Wang, Lijuan; Huen, Michael S Y; Deng, Yiqun

2012-01-24

Mequindox, a quinoxaline-N-dioxide derivative that possesses antibacterial properties, has been widely used as a feed additive in the stockbreeding industry in China. While recent pharmacological studies have uncovered potential hazardous effects of mequindox, exactly how mequindox induces pathological changes and the cellular responses associated with its consumption remain largely unexplored. In this study, we investigated the cellular responses associated with mequindox treatment. We report here that mequindox inhibits cell proliferation by arresting cells at the G2/M phase of the cell cycle. Interestingly, this mequindox-associated deleterious effect on cell proliferation was observed in human, pig as well as chicken cells, suggesting that mequindox acts on evolutionarily conserved target(s). To further understand the mequindox-host interaction and the mechanism underlying mequindox-induced cell cycle arrest, we measured the cellular content of DNA damage, which is known to perturb cell proliferation and compromise cell survival. Accordingly, using γ-H2AX as a surrogate marker for DNA damage, we found that mequindox treatment induced cellular DNA damage, which paralleled the chemical-induced elevation of reactive oxygen species (ROS) levels. Importantly, expression of the antioxidant enzyme catalase partially alleviated these mequindox-associated effects. Taken together, our results suggest that mequindox cytotoxicity is attributable, in part, to its role as a potent inducer of DNA damage via ROS. © 2011 Elsevier B.V. All rights reserved.

Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

PubMed

Park, Susanna S

2016-04-01

Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

Cumulative co-seismic fault damage and feedbacks on earthquake rupture

NASA Astrophysics Data System (ADS)

Mitchell, T. M.; Aben, F. M.; Ostermeijer, G.; Rockwell, T. K.; Doan, M. L.

2017-12-01

The importance of the damage zone in the faulting and earthquake process is widely recognized, but our understanding of how damage zones are created, what their properties are, and how they feed back into the seismic cycle, is remarkably poorly known. Firstly, damaged rocks have reduced elastic moduli, cohesion and yield strength, which can cause attenuation and potentially non-linear wave propagation effects during ruptures. Secondly, damaged fault rocks are generally more permeable than intact rocks, and hence play a key role in the migration of fluids in and around fault zones over the seismic cycle. Finally, the dynamic generation of damage as the earthquake propagates can itself influence the dynamics of rupture propagation, by increasing the amount of energy dissipation, decreasing the rupture velocity, modifying the size of the earthquake, changing the efficiency of weakening mechanisms such as thermal pressurisation of pore fluids, and even generating seismic waves itself . All of these effects imply that a feedback exists between the damage imparted immediately after rupture propagation, at the early stages of fault slip, and the effects of that damage on subsequent ruptures dynamics. In recent years, much debate has been sparked by the identification of so-called `pulverized rocks' described on various crustal-scale faults, a type of intensely damaged fault rock which has undergone minimal shear strain, and the occurrence of which has been linked to damage induced by transient high strain-rate stress perturbations during earthquake rupture. Damage induced by such transient stresses, whether compressional or tensional, likely constitute heterogeneous modulations of the remote stresses that will impart significant changes on the strength, elastic and fluid flow properties of a fault zone immediately after rupture propagation, at the early stage of fault slip. In this contribution, we will demonstrate laboratory and field examples of two dynamic mechanisms that have been proposed for the generation of pulverized rocks; (i) compressive loading by high-frequency stress pulses due to the radiation of seismic waves and (ii) explosive dilation in tension in rocks containing pressurized pore fluids.

UVA-UVB photoprotective activity of topical formulations containing Morinda citrifolia extract.

PubMed

Serafini, Mairim Russo; Detoni, Cassia Britto; Menezes, Paula dos Passos; Pereira Filho, Rose Nely; Fortes, Vanessa Silveira; Vieira, Maria José Fonseca; Guterres, Sílvia Stanisçuaski; Cavalcanti de Albuquerque Junior, Ricardo Luiz; Araújo, Adriano Antunes de Souza

2014-01-01

Exposure to solar radiation, particularly its ultraviolet (UV) component, has a variety of harmful effects on human health. Some of these effects include sunburn cell formations, basal and squamous cell cancers, melanoma, cataracts, photoaging of the skin, and immune suppression. The beneficial photoprotective effects of topical formulations with the extract, Morinda citrifolia, have not been investigated. This present study aims to investigate the potential benefits of M. citrifolia topical application on the dorsal skin of mice, exposed to UVA-UVB light. Using 7 days of treatment, [before (baseline values) and 20 h after UV exposure], the thickness, skin barrier damage (TEWL), erythema, and histological alterations were evaluated. The results showed that the formulations containing the extract protected the skin against UV-induced damage.

Ex-vivo multiphoton analysis of rabbit corneal wound healing following photorefractive keratectomy

NASA Astrophysics Data System (ADS)

Wang, Tsung-Jen; Lo, Wen; Dong, Chen-Yuan; Hu, Fung-Rong

2008-02-01

The aim of this study is to assess the application of multiphoton autofluorescence and second harmonic generation (SHG) microscopy for investigating corneal wound healing after high myopic (-10.0D) photorefractive keratectomy (PRK) procedures on the rabbit eyes. The effect of PRK on the morphology and distribution of keratocytes were investigated using multiphoton excited autofluorescence imaging, while the effect of PRK on the arrangement of collagen fibers was monitored by second-harmonic generation imaging. Without histological processing, multiphoton microscopy is able to characterize corneal damage and wound healing from PRK. Our results show that this technique has potential application in the clinical evaluation of corneal damage due to refractive surgery, and may be used to study the unwanted side effects of these procedures.

Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erkekoglu, Pinar; Hacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara; Rachidi, Walid

2010-10-01

Di(2-ethylhexyl)-phthalate (DEHP) is the most abundantly used phthalate derivative, inevitable environmental exposure of which is suspected to contribute to the increasing incidence of testicular dysgenesis syndrome in humans. Oxidative stress and mitochondrial dysfunction in germ cells are suggested to contribute to phthalate-induced disruption of spermatogenesis in rodents, and Leydig cells are one of the main targets of phthalates' testicular toxicity. Selenium is known to be involved in the modulation of intracellular redox equilibrium, and plays a critical role in testis, sperm, and reproduction. This study was aimed to investigate the oxidative stress potential of DEHP and its consequences in testicularmore » cells, and examine the possible protective effects of selenium using the MA-10 mouse Leydig tumor cell line as a model. In the presence and absence of selenium compounds [30 nM sodium selenite (SS), and 10 {mu}M selenomethionine (SM)], the effects of exposure to DEHP and its main metabolite mono(2-ethylhexyl)-phthalate (MEHP) on the cell viability, enzymatic and non-enzymatic antioxidant status, ROS production, p53 expression, and DNA damage by alkaline Comet assay were investigated. The overall results of this study demonstrated the cytotoxicity and genotoxicity potential of DEHP, where MEHP was found to be more potent than the parent compound. SS and SM produced almost the same level of protection against antioxidant status modifying effects, ROS and p53 inducing potentials, and DNA damaging effects of the two phthalate derivatives. It was thus shown that DEHP produced oxidative stress in MA-10 cells, and selenium supplementation appeared to be an effective redox regulator in the experimental conditions used in this study, emphasizing the critical importance of the appropriate selenium status.« less

NADH fluorescence imaging and the histological impact of cortical spreading depolarization during the acute phase of subarachnoid hemorrhage in rats.

PubMed

Shimizu, Tomohisa; Hishikawa, Tomohito; Nishihiro, Shingo; Shinji, Yukei; Takasugi, Yuji; Haruma, Jun; Hiramatsu, Masafumi; Kawase, Hirokazu; Sato, Sachiko; Mizoue, Ryoichi; Takeda, Yoshimasa; Sugiu, Kenji; Morimatsu, Hiroshi; Date, Isao

2018-01-01

OBJECTIVE Although cortical spreading depolarization (CSD) has been observed during the early phase of subarachnoid hemorrhage (SAH) in clinical settings, the pathogenicity of CSD is unclear. The aim of this study is to elucidate the effects of loss of membrane potential on neuronal damage during the acute phase of SAH. METHODS Twenty-four rats were subjected to SAH by the perforation method. The propagation of depolarization in the brain cortex was examined by using electrodes to monitor 2 direct-current (DC) potentials and obtaining NADH (reduced nicotinamide adenine dinucleotide) fluorescence images while exposing the parietal-temporal cortex to ultraviolet light. Cerebral blood flow (CBF) was monitored in the vicinity of the lateral electrode. Twenty-four hours after onset of SAH, histological damage was evaluated at the DC potential recording sites. RESULTS Changes in DC potentials (n = 48 in total) were sorted into 3 types according to the appearance of ischemic depolarization in the entire hemisphere following induction of SAH. In Type 1 changes (n = 21), ischemic depolarization was not observed during a 1-hour observation period. In Type 2 changes (n = 13), the DC potential demonstrated ischemic depolarization on initiation of SAH and recovered 80% from the maximal DC deflection during a 1-hour observation period (33.3 ± 15.8 minutes). In Type 3 changes (n = 14), the DC potential displayed ischemic depolarization and did not recover during a 1-hour observation period. Histological evaluations at DC potential recording sites showed intact tissue at all sites in the Type 1 group, whereas in the Type 2 and Type 3 groups neuronal damage of varying severity was observed depending on the duration of ischemic depolarization. The duration of depolarization that causes injury to 50% of neurons (P 50 ) was estimated to be 22.4 minutes (95% confidence intervals 17.0-30.3 minutes). CSD was observed in 3 rats at 6 sites in the Type 1 group 5.1 ± 2.2 minutes after initiation of SAH. On NADH fluorescence images CSD was initially observed in the anterior cortex; it propagated through the entire hemisphere in the direction of the occipital cortex at a rate of 3 mm/minute, with repolarization in 2.3 ± 1.2 minutes. DC potential recording sites that had undergone CSD were found to have intact tissue 24 hours later. Compared with depolarization that caused 50% neuronal damage, the duration of CSD was too short to cause histological damage. CONCLUSIONS CSD was successfully visualized using NADH fluorescence. It propagated from the anterior to the posterior cortex along with an increase in CBF. The duration of depolarization in CSD (2.3 ± 1.2 minutes) was far shorter than that causing 50% neuronal damage (22.4 minutes) and was not associated with histological damage in the current experimental setting.

Messages from the Other Side: Parasites Receive Damage Cues from their Host Plants.

PubMed

Tjiurutue, Muvari Connie; Stevenson, Philip C; Adler, Lynn S

2016-08-01

As sessile organisms, plants rely on their environment for cues indicating imminent herbivory. These cues can originate from tissues on the same plant or from different individuals. Since parasitic plants form vascular connections with their host, parasites have the potential to receive cues from hosts that allow them to adjust defenses against future herbivory. However, the role of plant communication between hosts and parasites for herbivore defense remains poorly investigated. Here, we examined the effects of damage to lupine hosts (Lupinus texensis) on responses of the attached hemiparasite (Castilleja indivisa), and indirectly, on a specialist herbivore of the parasite, buckeyes (Junonia coenia). Lupines produce alkaloids that act as defenses against herbivores that can be taken up by the parasite. We found that damage to lupine host plants by beet armyworm (Spodoptera exigua) significantly increased jasmonic acid (JA) levels in both the lupine host and parasite, suggesting uptake of phytohormones or priming of parasite defenses by using host cues. However, lupine host damage did not induce changes in alkaloid levels in the hosts or parasites. Interestingly, the parasite had substantially higher concentrations of JA and alkaloids compared to lupine host plants. Buckeye herbivores consumed more parasite tissue when attached to damaged compared to undamaged hosts. We hypothesize that increased JA due to lupine host damage induced higher iridoid glycosides in the parasite, which are feeding stimulants for this specialist herbivore. Our results demonstrate that damage to hosts may affect both parasites and associated herbivores, indicating cascading effects of host damage on multiple trophic levels.

Copper toxicity, oxidative stress, and antioxidant nutrients.

PubMed

Gaetke, Lisa M; Chow, Ching Kuang

2003-07-15

Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Although normally bound to proteins, Cu may be released and become free to catalyze the formation of highly reactive hydroxyl radicals. Data obtained from in vitro and cell culture studies are largely supportive of Cu's capacity to initiate oxidative damage and interfere with important cellular events. Oxidative damage has been linked to chronic Cu-overload and/or exposure to excess Cu caused by accidents, occupational hazards, and environmental contamination. Additionally, Cu-induced oxidative damage has been implicated in disorders associated with abnormal Cu metabolism and neurodegenerative changes. Interestingly, a deficiency in dietary Cu also increases cellular susceptibility to oxidative damage. A number of nutrients have been shown to interact with Cu and alter its cellular effects. Vitamin E is generally protective against Cu-induced oxidative damage. While most in vitro or cell culture studies show that ascorbic acid aggravates Cu-induced oxidative damage, results obtained from available animal studies suggest that the compound is protective. High intakes of ascorbic acid and zinc may provide protection against Cu toxicity by preventing excess Cu uptake. Zinc also removes Cu from its binding site, where it may cause free radical formation. Beta-carotene, alpha-lipoic acid and polyphenols have also been shown to attenuate Cu-induced oxidative damage. Further studies are needed to better understand the cellular effects of this essential, but potentially toxic, trace mineral and its functional interaction with other nutrients.

Distinct effects of acute and chronic sleep loss on DNA damage in rats.

PubMed

Andersen, M L; Ribeiro, D A; Bergamaschi, C T; Alvarenga, T A; Silva, A; Zager, A; Campos, R R; Tufik, S

2009-04-30

The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. The results showed DNA damage in blood cells of rats submitted to PSD for 96 h. Brain tissue showed extensive genotoxic damage in PSD rats (both 24 and 96 h), though the effect was more pronounced in the 96 h group. Rats allowed to recover from the PSD-96 h and SR-21 days treatments showed DNA damage as compared to negative controls. Liver and heart did not display any genotoxicity activity. Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.

SAFRR Tsunami Scenario: Economic Impacts and Resilience

NASA Astrophysics Data System (ADS)

Wein, A. M.; Rose, A.; Sue Wing, I.; Wei, D.

2013-12-01

Business interruption (BI) losses for the SAFRR tsunami scenario are derived from the forecasted physical damages of about 100 million at the Ports of Los Angeles (LA) and Long Beach (LB), and 700 million in marina damages, and 2 billion in inundated property damages along the California coast. Economic impacts are measured by the reduction in California's gross domestic product (GDP). The analysis involves several steps. First, estimates are made of immediate business interruption losses due to physical damage to facilities or to disruption of production. Second, total economic impacts (consisting of both direct and indirect effects) are measured by a general equilibrium (quantity and price multiplier effects) of lost production in other sectors through ripple effects upstream and downstream along the supply chain. Third, many types of resilience are applied to demonstrate their potential reductions of the impacts. At the Ports of LA and LB, a two-day port shutdown, cargo losses, and additional terminal downtimes would expose 1.2 billion of trade (import and export) value associated with over 4 billion of BI losses. The sectors potentially most affected by trade disruptions are leather, metal, and motor vehicle manufacturing. Excess capacity, inventories, export conversion, and conservation could reduce the direct trade impacts by 85%. Production recapture alone (including clearing the backlog of waiting ships) could reduce BI losses by 85%. The Port of LA commercial fishing would be subject to damages to the fleet, perished fish that cannot be landed, and lost fishing days. Although BI losses are relatively small, the southern Californian fishing sector could incur a 4% drop in output. The impacts would depend on the speed at which boats are repaired and whether lost fishing days can be made up. Ship-building and repair could also be negatively affected, but these impacts would be offset somewhat by reconstruction. Effects on commercial fishing in other locations were not closely examined to assess the impacts. Extensive damages to marinas along the California coast could result in 30 million BI losses in terms of GDP. Interestingly, the service sectors including and relating to marinas (recreation, food services, and retail) indicate possible gains (of .02-1%) from price increases greater than the losses from quantity decreases. Sectors associated with development (residential construction, water and sewage, and health care) could suffer the most with losses of .03% or less. However, these sectors will likely also be bolstered by reconstruction. Economic hardships would be localized and the resilience of the marina sector would depend on alternative moorings and excess capacity elsewhere. Inundated coastal property damages could generate 1.7 billion of BI losses. Application of sector recapture factors (e.g., using overtime) alone could reduce these losses by 80%. For the overall set of loss categories, BI losses amount to 6 billion, and resilience strategies indicate the potential to reduce these economic impacts by 80-90%.

Recent Advances in Tissue Engineering Strategies for the Treatment of Joint Damage.

PubMed

Stephenson, Makeda K; Farris, Ashley L; Grayson, Warren L

2017-08-01

While the clinical potential of tissue engineering for treating joint damage has yet to be realized, research and commercialization efforts in the field are geared towards overcoming major obstacles to clinical translation, as well as towards achieving engineered grafts that recapitulate the unique structures, function, and physiology of the joint. In this review, we describe recent advances in technologies aimed at obtaining biomaterials, stem cells, and bioreactors that will enable the development of effective tissue-engineered treatments for repairing joint damage. 3D printing of scaffolds is aimed at improving the mechanical structure and microenvironment necessary for bone regeneration within a damaged joint. Advances in our understanding of stem cell biology and cell manufacturing processes are informing translational strategies for the therapeutic use of allogeneic and autologous cells. Finally, bioreactors used in combination with cells and biomaterials are promising strategies for generating large tissue grafts for repairing damaged tissues in pre-clinical models. Together, these advances along with ongoing research directions are making tissue engineering increasingly viable for the treatment of joint damage.

Low dose radiation adaptive protection to control neurodegenerative diseases.

PubMed

Doss, Mohan

2014-05-01

Concerns have been expressed recently regarding the observed increased DNA damage from activities such as thinking and exercise. Such concerns have arisen from an incomplete accounting of the full effects of the increased oxidative damage. When the effects of the induced adaptive protective responses such as increased antioxidants and DNA repair enzymes are taken into consideration, there would be less endogenous DNA damage during the subsequent period of enhanced defenses, resulting in improved health from the thinking and exercise activities. Low dose radiation (LDR), which causes oxidative stress and increased DNA damage, upregulates adaptive protection systems that may decrease diseases in an analogous manner. Though there are ongoing debates regarding LDR's carcinogenicity, with two recent advisory committee reports coming to opposite conclusions, data published since the time of the reports have overwhelmingly ruled out its carcinogenicity, paving the way for consideration of its potential use for disease reduction. LDR adaptive protection is a promising approach to control neurodegenerative diseases, for which there are no methods of prevention or cure. Preparation of a compelling ethics case would pave the way for LDR clinical studies and progress in dealing with neurodegenerative diseases.

Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures.

PubMed

Baumeister, Philipp; Reiter, Maximilian; Kleinsasser, Norbert; Matthias, Christoph; Harréus, Ulrich

2009-06-01

Although epidemiological studies indicate cancer preventive effects of diets rich in fruit and vegetables, large clinical intervention studies conducted to evaluate dietary supplementation with micronutrients, mostly vitamins, showed disappointing results in large parts. In contrast, there is encouraging epidemiologic data indicating great chemopreventive potential of a large group of phytochemicals, namely polyphenols. This study shows the DNA protective effect epigallocatechin-3-gallate, a tea catechin, and one of the best-studied substances within this group, on carcinogen-induced DNA fragmentation in upper aerodigestive tract cells. Cell cultures from fresh oropharyngeal mucosa biopsies were preincubated with epigallocatechin-3-gallate in different concentrations before DNA damage was introduced with the metabolically activated carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide or cigarette smoke condensate. Effects on resulting DNA fragmentation were measured using the alkaline single-cell microgel electrophoresis (comet assay). Epigallocatechin-3-gallate significantly reduced benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage by up to 51% (P<0.001). Fragmentation induced by cigarette smoke condensate could be lowered by 47% (P<0.001). Data suggest a cancer preventive potential of epigallocatechin-3-gallate as demonstrated on a subcellular level. An additional mechanism of tea catechin action is revealed by using a primary mucosa culture model.

Jatropha curcas leaf and bark fractions protect against ultraviolet radiation-B induced DNA damage in human peripheral blood lymphocytes.

PubMed

Sundari, J; Selvaraj, R; Rajendra Prasad, N; Elumalai, R

2013-11-01

The present study is conducted to investigate the antioxidant potential of Jatropha curcas root bark extract (RB4 fraction) and leaf extract (L1 fraction), and to study their effects on UVB-radiation-induced DNA damage in cultured human blood lymphocytes. In this study, J. curcas showed strong antioxidant property in different free radical scavenging systems. Both the fractions effectively scavenged hydroxyl (OH), superoxide anion (O₂(·-)), 1,1-diphenyl-2-picrylhydrazyl (DPPH·) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS(·+)) in a concentration-dependent manner. The IC₅₀ (Inhibitory Concentration 50) values of J. curcas fractions were compared to standard ascorbic acid used in this study. The antioxidant potential of a compound was directly proportional to the photoprotective effect. In this study, human peripheral blood lymphocytes (HPBL) were exposed to UVB-radiation and there was an increase in comet attributes (% tail DNA, tail length, tail movement and Olive tail moment). Jatropha curcas RB4 fraction and L1 fraction treatment before UVB-irradiation significantly decreased the % tail DNA, tail length, tail moment and Olive tail moment in irradiated HPBL. These results suggested that J. curcas exhibited strong antioxidant property and RB4 and L1 fractions protected UVB-radiation-induced DNA damage in HPBL. Copyright © 2013 Elsevier B.V. All rights reserved.

Redox proteomic evaluation of oxidative modification and recovery in a 3D reconstituted human skin tissue model exposed to UVB.

PubMed

Dyer, J M; Haines, S R; Thomas, A; Wang, W; Walls, R J; Clerens, S; Harland, D P

2017-04-01

Exposure to UV in humans resulting in sunburn triggers a complex series of events that are a mix of immediate and delayed damage mediation and healing. While studies on the effects of UV exposure on DNA damage and repair have been reported, changes in the oxidative modification of skin proteins are poorly understood at the molecular level, despite the important role played by structural proteins in skin tissue, and the effect of the integrity of these proteins on skin appearance and health. Proteomic molecular mapping of oxidation was here applied to try to enhance understanding of skin damage and recovery from oxidative damage and UVB exposure. A redox proteomic-based approach was applied to evaluating skin protein modification when exposed to varying doses of UVB after initial oxidative stress, via tracking changes in protein oxidation during the healing process in vitro using a full-thickness reconstituted human skin tissue model. Bioassays and structural evaluation confirmed that our cultured skin tissues underwent a normal physiological response to UVB exposure. A set of potential skin marker peptides was generated, for use in tracking skin protein oxidative modification. Exposure to UVB after thermal oxidative stress was found to result in higher levels of skin protein oxidation than a non-irradiated control for up to seven days after exposure. Recovery of the skin proteins from oxidative stress, as assessed by the overall protein oxidation levels, was found to be impaired by UVB exposure. Oxidative modification was largely observed in skin structural proteins. Exposure of skin proteins to UVB exacerbates oxidative damage to structural skin proteins, with higher exposure levels leading to increasingly impaired recovery from this damage. This has potential implications for the functional performance of the proteins and inter-related skin health and cosmetic appearance. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

A study to evaluate the effect of nootropic drug-piracetam on DNA damage in leukocytes and macrophages.

PubMed

Singh, Sarika; Goswami, Poonam; Swarnkar, Supriya; Singh, Sheelendra Pratap; Wahajuddin; Nath, Chandishwar; Sharma, Sharad

2011-11-27

Piracetam is a nootropic drug that protects neurons in neuropathological and age-related diseases and the activation and modulation of peripheral blood cells in patients with neuropathological conditions is well known. Therefore, in the present study, in vivo, ex vivo, and in vitro tests were conducted to investigate the effect of piracetam on leukocytes and macrophages. Lipopolysaccharide (LPS) causes oxidative DNA damage; thus, in the present study, LPS was used as a tool to induce DNA damage. In vivo experiments were conducted on Sprague Dawley rats, and piracetam (600mg/kg, oral) was provided for five consecutive days. On the fifth day, a single injection of LPS (10mg/kg, i.p.) was administered. Three hours after LPS injection, blood leukocytes and peritoneal macrophages were collected and processed, and a variety of different assays were conducted. Ex vivo treatments were performed on isolated rat blood leukocytes, and in vitro experiments were conducted on rat macrophage cell line J774A.1. Cell viability and the level of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and DNA damage were estimated in untreated (control) and piracetam-, LPS- and LPS+piracetam-treated leukocytes and macrophages. In vivo experiments revealed that rats pretreated with piracetam were significantly protected against LPS-induced increases in ROS levels and DNA damage. Ex vivo isolated leukocytes and J774A.1 cells treated with LPS exhibited augmented ROS levels and DNA damage, which were attenuated with piracetam treatment. Thus, the present study revealed the salutary effect of piracetam against LPS-induced oxidative stress and DNA damage in leukocytes and macrophages. Copyright © 2011 Elsevier B.V. All rights reserved.

Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.

PubMed

Tran, Thai Q; Ishak Gabra, Mari B; Lowman, Xazmin H; Yang, Ying; Reid, Michael A; Pan, Min; O'Connor, Timothy R; Kong, Mei

2017-11-01

Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.

Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes

PubMed Central

Tran, Thai Q.; Ishak Gabra, Mari B.; Lowman, Xazmin H.; Yang, Ying; Reid, Michael A.; Pan, Min; O’Connor, Timothy R.

2017-01-01

Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer. PMID:29107960

Impact damage resistance of composite fuselage structure, part 1

NASA Technical Reports Server (NTRS)

Dost, E. F.; Avery, W. B.; Ilcewicz, L. B.; Grande, D. H.; Coxon, B. R.

1992-01-01

The impact damage resistance of laminated composite transport aircraft fuselage structures was studied experimentally. A statistically based designed experiment was used to examine numerous material, laminate, structural, and extrinsic (e.g., impactor type) variables. The relative importance and quantitative measure of the effect of each variable and variable interactions on responses including impactor dynamic response, visibility, and internal damage state were determined. The study utilized 32 three-stiffener panels, each with a unique combination of material type, material forms, and structural geometry. Two manufacturing techniques, tow placement and tape lamination, were used to build panels representative of potential fuselage crown, keel, and lower side-panel designs. Various combinations of impactor variables representing various foreign-object-impact threats to the aircraft were examined. Impacts performed at different structural locations within each panel (e.g., skin midbay, stiffener attaching flange, etc.) were considered separate parallel experiments. The relationship between input variables, measured damage states, and structural response to this damage are presented including recommendations for materials and impact test methods for fuselage structure.

Comparative efficacy of storage bags, storability and damage potential of bruchid beetle.

PubMed

Harish, G; Nataraja, M V; Ajay, B C; Holajjer, Prasanna; Savaliya, S D; Gedia, M V

2014-12-01

Groundnut during storage is attacked by number of stored grain pests and management of these insect pests particularly bruchid beetle, Caryedon serratus (Oliver) is of prime importance as they directly damage the pod and kernels. In this regard different storage bags that could be used and duration up to which we can store groundnut has been studied. Super grain bag recorded minimum number of eggs laid and less damage and minimum weight loss in pods and kernels in comparison to other storage bags. Analysis of variance for multiple regression models were found to be significant in all bags for variables viz, number of eggs laid, damage in pods and kernels, weight loss in pods and kernels throughout the season. Multiple comparison results showed that there was a high probability of eggs laid and pod damage in lino bag, fertilizer bag and gunny bag, whereas super grain bag was found to be more effective in managing the C. serratus owing to very low air circulation.

Cytogenetic damage analysis in mice chronically exposed to low-dose internal tritium beta-particle radiation.

PubMed

Roch-Lefèvre, Sandrine; Grégoire, Eric; Martin-Bodiot, Cécile; Flegal, Matthew; Fréneau, Amélie; Blimkie, Melinda; Bannister, Laura; Wyatt, Heather; Barquinero, Joan-Francesc; Roy, Laurence; Benadjaoud, Mohamed; Priest, Nick; Jourdain, Jean-René; Klokov, Dmitry

2018-06-08

The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal β-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 - 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo , the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be higher than currently assumed.

The simultaneous detection of mitochondrial DNA damage from sun-exposed skin of three whale species and its association with UV-induced microscopic lesions and apoptosis.

PubMed

Bowman, Amy; Martinez-Levasseur, Laura M; Acevedo-Whitehouse, Karina; Gendron, Diane; Birch-Machin, Mark A

2013-07-01

Due to life history and physiological constraints, cetaceans (whales) are unable to avoid prolonged exposure to external environmental insults, such as solar ultraviolet radiation (UV). The majority of studies on the effects of UV on skin are restricted to humans and laboratory animals, but it is important to develop tools to understand the effects of UV damage on large mammals such as whales, as these animals are long-lived and widely distributed, and can reflect the effects of UV across a large geographical range. We and others have used mitochondrial DNA (mtDNA) as a reliable marker of UV-induced damage particularly in human skin. UV-induced mtDNA strand breaks or lesions accumulate throughout the lifespan of an individual, thus constituting an excellent biomarker for cumulative exposure. Based on our previous studies in human skin, we have developed for the first time in the literature a quantitative real-time PCR methodology to detect and quantify mtDNA lesions in skin from sun-blistered whales. Furthermore the methodology allows for simultaneous detection of mtDNA damage in different species. Therefore using 44 epidermal mtDNA samples collected from 15 blue whales, 10 fin whales, and 19 sperm whales from the Gulf of California, Mexico, we quantified damage across 4.3 kilobases, a large region of the ~16,400 base pair whale mitochondrial genome. The results show a range of mtDNA damage in the skin of the three different whale species. This previously unreported observation was correlated with apoptotic damage and microscopic lesions, both of which are markers of UV-induced damage. As is the case in human studies, this suggests the potential use of mtDNA as a biomarker for measuring the effect of cumulative UV exposure in whales and may provide a platform to help understand the effects of changing global environmental conditions. Copyright © 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.

NITROGEN DIOXIDE, PULMONARY FUNCTION, AND RESPIRATORY DISEASE

EPA Science Inventory

Concern as to the toxicity of the oxides of nitrogen has been frequently expressed in clinical and toxicological literature. Oxides of nitrogen are highly reactive compounds and suggest toxic effects on biological systems. The earliest evidence for potential damage to man occurre...

Possible Involvement of Nitric Oxide Modulatory Mechanisms in the Neuroprotective Effect of Centella asiatica Against Sleep Deprivation Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation.

PubMed

Chanana, Priyanka; Kumar, Anil

2016-04-01

Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72-h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF-alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti-anxiety like effect and attenuated oxidative damage and TNF α level as compared to sleep-deprived 72-h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD-induced anxiety-like behaviour, oxidative damage and neuroinflammation in mice. Copyright © 2016 John Wiley & Sons, Ltd.

The fruit extract of Berberis crataegina DC: exerts potent antioxidant activity and protects DNA integrity.

PubMed

Charehsaz, Mohammad; Sipahi, Hande; Celep, Engin; Üstündağ, Aylin; Cemiloğlu Ülker, Özge; Duydu, Yalçın; Aydın, Ahmet; Yesilada, Erdem

2015-04-17

Dried fruits of Berberis crataegina (Berberidaceae) have been frequently consumed as food garniture in Turkish cuisine, while its fruit paste has been used to increase stamina and in particular to prevent from cardiovascular dysfunctions in Northeastern Black Sea region of Turkey. This study investigated this folkloric information in order to explain the claimed healing effects as well as to evaluate possible risks. Total phenolic, flavonoid and proanthocyanidin contents and antioxidant capacity of the methanolic fruit extract were evaluated through several in vitro assays. The cytotoxic and genotoxic effects of B. crataegina fruit extract were also assessed in both cervical cancer cell line (HeLa) and human peripheral blood lymphocytes. The extract showed protective effects against ferric-induced oxidative stress and had a relatively good antioxidant activity. It also ameliorated the H2O2 mediated DNA damage in lymphocytes, suggesting the protective effect against oxidative DNA damage. The methanolic extract of B. crataegina fruits may be a potential antioxidant nutrient and also may exert a protective role against lipid peroxidation as well as oxidative DNA damage.

Damage to Candida albicans Hyphae and Pseudohyphae by the Myeloperoxidase System and Oxidative Products of Neutrophil Metabolism In Vitro

PubMed Central

Diamond, Richard D.; Clark, Robert A.; Haudenschild, Christian C.

1980-01-01

In previous studies, we noted that Candida hyphae and pseudohyphae could be damaged and probably killed by neutrophils, primarily by oxygen-dependent nonphagocytic mechanisms. In extending these studies, amount of damage to hyphae again was measured by inhibition of [14C]cytosine uptake. Neutrophils from only one of four patients with chronic granulomatous disease damaged hyphae at all, and neutrophils from this single patient damaged hyphae far less efficiently than simultaneously tested neutrophils from normal control subjects. Neutrophils from neither of two subjects with hereditary myeloperoxidase deficiency damaged the hyphae. This confirmed the importance of oxidative mechanisms in general and myeloperoxidase-mediated systems in particular in damaging Candida hyphae. Several potentially fungicidal oxidative intermediates are produced by metabolic pathways of normal neutrophils, but their relative toxicity for Candida hyphae was previously unknown. To help determine this, cell-free in vitro systems were used to generate these potentially microbicidal products. Myeloperoxidase with hydrogen peroxide, iodide, and chloride resulted in 91.2% damage to hyphal inocula in 11 experiments. There was less damage when either chloride or iodide was omitted, and no damage when myeloperoxidase was omitted or inactivated by heating. Azide, cyanide, and catalase (but not heated catalase) inhibited the damage. Systems for generation of hydrogen peroxide could replace reagent hydrogen peroxide in the myeloperoxidase system. These included glucose oxidase, in the presence of glucose, and xanthine oxidase, in the presence of either hypoxanthine or acetaldehyde. In the presence of myeloperoxidase and a halide, the toxicity of the xanthine oxidase system was not inhibited by superoxide dismutase and, under some conditions, was marginally increased by this enzyme. This suggested that superoxide radical did not damage hyphae directly but served primarily as an intermediate in the production of hydrogen peroxide. The possible damage to hyphae by singlet oxygen was examined using photoactivation of rose bengal. This dye damaged hyphae in the presence of light and oxygen. The effect was almost completely inhibited by putative quenchers of singlet oxygen: histidine, tryptophan, and 1,4-diazobicyclo[2.2.2]octane. These agents also inhibited damage to hyphae by myeloperoxidase, halide, and either hydrogen peroxide or a peroxide source (xanthine oxidase plus acetaldehyde). Myeloperoxidase-mediated damage to hyphae was also inhibited by dimethyl sulfoxide, an antioxidant and scavenger of the hydroxyl radical. These data support the involvement of oxidative mechanisms and the myeloperoxidase-H2O2-halide system, in particular in damaging hyphae in vitro and perhaps in vivo as well. Images PMID:6253527

Renal and Glycemic Effects of High-Dose Chromium Picolinate in db/db Mice: Assessment of DNA Damage

PubMed Central

Mozaffari, Mahmood S.; Baban, Babak; Abdelsayed, Rafik; Liu, Jun Yao; Wimborne, Hereward; Rodriguez, Nancy; Abebe, Worku

2011-01-01

This study examined renal and glycemic effects of chromium picolinate (Cr(pic)3) supplementation in the context of its purported potential for DNA damage. In preventional protocol, male obese diabetic db/db mice were fed diets either lacking or containing 5, 10 or 100 mg/kg chromium as Cr(pic)3 from 6 to 24 weeks of age; male lean nondiabetic db/m mice served as controls. Untreated db/db mice displayed increased plasma glucose and insulin, hemoglobin A1c, renal tissue advanced glycation end (AGE) products, albuminuria, glomerular mesangial expansion, urinary 8-hydroxydeoxyguanosine (8-OHdG, an index of oxidative DNA damage) and renal tissue immunostaining for γH2AX (a marker of double-strand DNA breaks) compared to db/m controls. Creatinine clearance was lower while blood pressure was similar between untreated db/db mice and their db/m controls. High Cr(pic)3 intake (i.e., 100 mg/kg diet) mildly improved glycemic status and albuminuria without affecting blood pressure or creatinine clearance. Treatment with Cr(pic)3 did not increase DNA damage despite marked renal accumulation of chromium. In interventional protocol, effects of diets containing 0, 100 and 250 mg/kg supplemental chromium, from 12 to 24 weeks of age, were examined in db/db mice. The results generally revealed similar effects to those of the 100 mg/kg diet of the preventional protocol. In conclusion, the severely hyperglycemic db/db mouse displays renal structural and functional abnormalities in association with DNA damage. High-dose Cr(pic)3 treatment mildly improves glycemic control and it causes moderate reduction in albuminuria, without affecting histopathological appearance of the kidney and increasing the risk for DNA damage. PMID:21959055

Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage.

PubMed

Mozaffari, Mahmood S; Baban, Babak; Abdelsayed, Rafik; Liu, Jun Yao; Wimborne, Hereward; Rodriguez, Nancy; Abebe, Worku

2012-08-01

This study examined renal and glycemic effects of chromium picolinate [Cr(pic)3] supplementation in the context of its purported potential for DNA damage. In preventional protocol, male obese diabetic db/db mice were fed diets either lacking or containing 5, 10 or 100 mg/kg chromium as Cr(pic)3 from 6 to 24 weeks of age; male lean nondiabetic db/m mice served as controls. Untreated db/db mice displayed increased plasma glucose and insulin, hemoglobin A1c, renal tissue advanced glycation end products, albuminuria, glomerular mesangial expansion, urinary 8-hydroxydeoxyguanosine (an index of oxidative DNA damage) and renal tissue immunostaining for γH2AX (a marker of double-strand DNA breaks) compared to db/m controls. Creatinine clearance was lower in untreated db/db mice than their db/m controls, while blood pressure was similar. High Cr(pic)3 intake (i.e., 100-mg/kg diet) mildly improved glycemic status and albuminuria without affecting blood pressure or creatinine clearance. Treatment with Cr(pic)3 did not increase DNA damage despite marked renal accumulation of chromium. In interventional protocol, effects of diets containing 0, 100 and 250 mg/kg supplemental chromium, from 12 to 24 weeks of age, were examined in db/db mice. The results generally revealed similar effects to those of the 100-mg/kg diet of the preventional protocol. In conclusion, the severely hyperglycemic db/db mouse displays renal structural and functional abnormalities in association with DNA damage. High-dose Cr(pic)3 treatment mildly improves glycemic control, and it causes moderate reduction in albuminuria, without affecting the histopathological appearance of the kidney and increasing the risk for DNA damage. Copyright © 2012 Elsevier Inc. All rights reserved.

Generation and development of damage in double forged tungsten in different combined regimes of irradiation with extreme heat loads

NASA Astrophysics Data System (ADS)

Paju, Jana; Väli, Berit; Laas, Tõnu; Shirokova, Veroonika; Laas, Katrin; Paduch, Marian; Gribkov, Vladimir A.; Demina, Elena V.; Prusakova, Marina D.; Pimenov, Valeri N.; Makhlaj, Vadym A.; Antonov, Maksim

2017-11-01

Armour materials in fusion devices, especially in the region of divertor, are exposed to a continuous heat and particle load. In addition, several off-normal events can reach the material during a work session. Calculations show that the effects of plasma and heat during such events can lead to cracking, erosion and detachment of the armour material. On the other hand, mutual and combined influences of different kinds of heat and particle loads can lead to the amplification of defects or vice versa, to the mitigation of damages. Therefore, the purpose of the study is to investigate the plasma induced damages on samples of double forged tungsten, which is considered a potential candidate for armour material of future tokamak's divertor. The combined effect of different kinds of plasma induced damages was investigated and analysed in this research. The study was conducted by irradiating the samples in various irradiation regimes twice, to observe the accumulation of the damages. Afterwards the analysis of micro-topography, scanning electron microscopy images and electrical conductivity measurements was used. Results indicate that double-forging improved the tungsten's durability to irradiation. Nevertheless, powerful pulses lead to significant damage of the sample, which will lead to further deterioration in the bulk. Although the average micro-roughness on the sample's surface does not change, the overall height/depth ratios can change.

Bioanalytical and chemical assessment of the disinfection by-product formation potential: role of organic matter.

PubMed

Farré, Maria José; Day, Sophie; Neale, Peta A; Stalter, Daniel; Tang, Janet Y M; Escher, Beate I

2013-09-15

Disinfection by-products (DBP) formed from natural organic matter and disinfectants like chlorine and chloramine may cause adverse health effects. Here, we evaluate how the quantity and quality of natural organic matter and other precursors influence the formation of DBPs during chlorination and chloramination using a comprehensive approach including chemical analysis of regulated and emerging DBPs, total organic halogen quantification, organic matter characterisation and bioanalytical tools. In vitro bioassays allow us to assess the hazard potential of DBPs early in the chain of cellular events, when the DBPs react with their molecular target(s) and activate stress response and defence mechanisms. Given the reactive properties of known DBPs, a suite of bioassays targeting reactive modes of toxic action including genotoxicity and sensitive early warning endpoints such as protein damage and oxidative stress were evaluated in addition to cytotoxicity. Coagulated surface water was collected from three different drinking water treatment plants, along with reverse osmosis permeate from a desalination plant, and DBP formation potential was assessed after chlorination and chloramination. While effects were low or below the limit of detection before disinfection, the observed effects and DBP levels increased after disinfection and were generally higher after chlorination than after chloramination, indicating that chlorination forms higher concentrations of DBPs or more potent DBPs in the studied waters. Bacterial cytotoxicity, assessed using the bioluminescence inhibition assay, and induction of the oxidative stress response were the most sensitive endpoints, followed by genotoxicity. Source waters with higher dissolved organic carbon levels induced increased DBP formation and caused greater effects in the endpoints related to DNA damage repair, glutathione conjugation/protein damage and the Nrf2 oxidative stress response pathway after disinfection. Fractionation studies indicated that all molecular weight fractions of organic carbon contributed to the DBP formation potential, with the humic rich fractions forming the greatest amount of DBPs, while the low molecular weight fractions formed more brominated DBPs due to the high bromide to organic carbon ratio. The presence of higher bromide concentrations also led to a higher fraction of brominated DBPs as well as proportionally higher effects. This study demonstrates how a suite of analytical and bioanalytical tools can be used to effectively characterise the precursors and formation potential of DBPs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Induction of cross-tolerance between protective effect of morphine and nicotine in 6-hydroxydopamine-induce neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells.

PubMed

Elyasi, Leila; Eftekhar-Vaghefi, Seyed Hassan; Asadi-Shekaaria, Majid; Esmaeili-Mahani, Saeed

2018-06-27

Parkinson's disease is a progressive neurodegenerative disease characterized by progressive and selective death of dopaminergic neurons. It has been reported that nicotine and morphine have protective roles during neuronal damage in Parkinson's disease. In addition, the induction of cross-tolerance between their biological effects has been shown in numerous reports. Here, we investigated the effects of nicotine and morphine on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson's disease. Cell damage was induced by 150 μM 6-OHDA and the cells viability was examined by MTT assay. Intracellular reactive oxygen species, calcium level and mitochondrial membrane potential were determined by fluorescence spectrophotometer method. Biochemical markers of apoptosis were also evaluated by immunoblotting. The data showed that morphine and nicotine prevent 6-OHDA- induced cell damage and apoptosis. However, the protective effects of nicotine were not observed in chronic morphine-pretreated cells. Morphine had no protective effects in chronic nicotine-incubated cells. A cross-tolerance between protective effects of morphine and nicotine was occurred in 6-OHDA-induced SH-SY5Y cell toxicity.

Effect of curing agents on the oxidative and nitrosative damage to meat proteins during processing of fermented sausages.

PubMed

Villaverde, A; Morcuende, D; Estévez, M

2014-07-01

The effect of increasing concentrations of curing agents, ascorbate (0, 250, and 500 ppm), and nitrite (0, 75, and 150 ppm), on the oxidative and nitrosative damage to proteins during processing of fermented sausages was studied. The potential influence of these reactions on color and texture of the fermented sausages was also addressed. Nitrite had a pro-oxidant effect on tryptophan depletion and promoted the formation of protein carbonyls and Schiff bases. The nitration degree in the fermented sausages was also dependent on nitrite concentration. On the other hand, ascorbate acted as an efficient inhibitor of the oxidative and nitrosative damage to meat proteins. As expected, nitrite clearly favored the formation of the cured red color and ascorbate acted as an enhancer of color formation. Nitrite content was positively correlated with hardness. The chemistry behind the action of nitrite and ascorbate on muscle proteins during meat fermentation is thoroughly discussed. The results suggest that ascorbate (500 ppm) may be required to compensate the pro-oxidant impact of nitrite on meat proteins. This study provides insight on the action of curing agents on meat proteins during processing of fermented sausages. This chemistry background provides understanding of the potential influence of the oxidative and nitrosative damage to proteins on the quality of processed muscle foods. The study provides novel information on the impact of the combination of nitrite and ascorbate on the chemical deterioration of proteins and the influence on particular quality traits of fermented sausages. These data may be of interest for the design of cured muscle foods of enhanced quality. © 2014 Institute of Food Technologists®

Phototoxic effects of an operating microscope on the ocular surface and tear film.

PubMed

Hwang, Hyung Bin; Kim, Hyun Seung

2014-01-01

We evaluated light exposure-induced dry eye syndrome by investigating the phototoxic effects of an operating microscope on the ocular surface and tear film in rabbits. Sixty eyes of 30 rabbits were divided into 3 groups based on the intensity of light exposure received from an operating microscope: Control group, no exposure to light; group A, 40,000-lx intensity for 30 minutes; and group B, 100,000-lx intensity for 30 minutes. To evaluate the potential damage to the ocular surface and tear film, Schirmer tests, rose bengal staining, and conjunctival impression cytology were performed before the light exposure and at 1, 3, and 5 days afterward. In addition, the expression of interleukin 1-beta was analyzed in tear samples. The expression of mucin 5AC was evaluated using immunofluorescence staining, and periodic acid-Schiff staining was conducted on conjunctival tissues. Corneal and conjunctival tissues were observed by means of electron microscopy. Potential damage to the ocular surface and tear film was found in the light-exposed groups as evidenced by decreased aqueous tear production, devitalized corneal and conjunctival epithelial cells, squamous metaplasia of conjunctival epithelial cells, decreased conjunctival goblet cell density, decreased expression of mucin 5AC, ultrastructural cellular damage to corneal and conjunctival tissues, and increased interleukin 1-beta expression in tears. This damage was more noticeable in group B than in group A (P < 0.05). Light exposure from an operating microscope had phototoxic effects on the ocular surface and tear film in this in vivo experiment. These changes seemed to intensify as the intensity of the light increased. Therefore, excessive light exposure during ophthalmic procedures could be a pathogenic factor in dry eye syndrome after a surgery is performed.

Citral and eugenol modulate DNA damage and pro-inflammatory mediator genes in murine peritoneal macrophages.

PubMed

Porto, Marilia de Paula; da Silva, Glenda Nicioli; Luperini, Bruno Cesar Ottoboni; Bachiega, Tatiana Fernanda; de Castro Marcondes, João Paulo; Sforcin, José Maurício; Salvadori, Daisy Maria Fávero

2014-11-01

Citral and eugenol have been broadly studied because of their anti-inflammatory, antioxidant and antiparasitic potentials. In this study, the effects of citral (25, 50 and 100 µg/mL) and eugenol (0.31, 0.62, 1.24 and 2.48 µg/mL) on the expression (RT-PCR) of the pro-inflammatory mediator genes NF-κB1, COX-2 and TNF-α were evaluated in mouse peritoneal macrophages with or without activation by a bacterial lipopolysaccharide (LPS). Additionally, the genotoxic potentials of two compounds and their capacities to modulate the DNA damage induced by doxorubicin (DXR) were investigated using the comet assay. The data revealed that neither citral nor eugenol changed COX-2, NF-κB1 or TNF-α expression in resting macrophages. However, in LPS-activated cells, citral induced the hypoexpression of COX-2 (100 µg/mL) and TNF-α (50 and 100 µg/mL). Hypoexpression of TNF-α was also detected after cellular exposure to eugenol at the highest concentration (2.48 µg/mL). Both compounds exhibited genotoxic potential (citral at 50 and 100 µg/mL and eugenol at all concentrations) but also showed chemopreventive effects, in various treatment protocols. Both citral and eugenol might modulate inflammatory processes and DXR-induced DNA damage, but the use of these compounds must be viewed with caution because they are also able to induce primary DNA lesions.

Late biological effects of heavy charged particles: Cataracts, vascular injury and life shortening in mice

NASA Astrophysics Data System (ADS)

Ainsworth, E. J.; Jose, J. G.; Barker, M. E.; Alpen, E. L.

1980-07-01

Risks associated with extended habitation in a space environment, particularly hazards to space workers that might result from exposure to high energy heavy ion particles (HZE), were studied. Biological effects of HZE were investigated in mice to assess their potential adverse health hazards. The potential effects of HZE particles on the crystalline lens of the eye and the carcinogenic effects and blood vessel (vascular) damage from radiation were evaluated by a risk assessment. Animal experiments to evaluate dose response relationships for tumor induction/promotion and for vascular injury were introduced. Cataract productions and preliminary results on cacinogenic and vascular effects are presented for perspective.

Late biological effects of heavy charged particles: Cataracts, vascular injury and life shortening in mice

NASA Technical Reports Server (NTRS)

Ainsworth, E. J.; Jose, J. G.; Barker, M. E.; Alpen, E. L.

1980-01-01

Risks associated with extended habitation in a space environment, particularly hazards to space workers that might result from exposure to high energy heavy ion particles (HZE), were studied. Biological effects of HZE were investigated in mice to assess their potential adverse health hazards. The potential effects of HZE particles on the crystalline lens of the eye and the carcinogenic effects and blood vessel (vascular) damage from radiation were evaluated by a risk assessment. Animal experiments to evaluate dose response relationships for tumor induction/promotion and for vascular injury were introduced. Cataract productions and preliminary results on cacinogenic and vascular effects are presented for perspective.

Groundwater potential for water supply during droughts in Korea

NASA Astrophysics Data System (ADS)

Hyun, Y.; Cha, E.; Moon, H. J.

2016-12-01

Droughts have been receiving much attention in Korea because severe droughts occurred in recent years, causing significant social, economic and environmental damages in some regions. Residents in agricultural area, most of all, were most damaged by droughts with lack of available water supplies to meet crop water demands. In order to mitigate drought damages, we present a strategy to keep from agricultural droughts by using groundwater to meet water supply as a potential water resource in agricultural areas. In this study, we analyze drought severity and the groundwater potential to mitigate social and environmental damages caused by droughts in Korea. We evaluate drought severity by analyzing spatial and temporal meteorological and hydrological data such as rainfall, water supply and demand. For drought severity, we use effective drought index along with the standardized precipitation index (SPI) and standardized runoff index(SRI). Water deficit during the drought period is also quantified to consider social and environmental impact of droughts. Then we assess the feasibility of using groundwater as a potential source for groundwater impact mitigation. Results show that the agricultural areas are more vulnerable to droughts and use of groundwater as an emergency water resource is feasible in some regions. For a case study, we select Jeong-Sun area located in Kangwon providence having well-developed Karst aquifers and surrounded by mountains. For Jeong-Sun area, we quantify groundwater potential use, design the method of water supply by using groundwater, and assess its economic benefit. Results show that water supply system with groundwater abstraction can be a good strategy when droughts are severe for an emergency water supply in Jeong-Sun area, and groundwater can also be used not only for a dry season water supply resource, but for everyday water supply system. This case study results can further be applicable to some regions with no sufficient water infrastructure and high groundwater use potential. For concrete conclusions, rigorous study on performance evaluation of water supply using groundwater is further needed.

ShakeCast: Automating and Improving the Use of ShakeMap for Post-Earthquake Decision- Making and Response

NASA Astrophysics Data System (ADS)

Lin, K.; Wald, D. J.

2007-12-01

ShakeCast is a freely available, post-earthquake situational awareness application that automatically retrieves earthquake shaking data from ShakeMap, compares intensity measures against users" facilities, sends notifications of potential damage to responsible parties, and generates facility damage maps and other Web-based products for emergency managers and responders. ShakeMap, a tool used to portray the extent of potentially damaging shaking following an earthquake, provides overall information regarding the affected areas. When a potentially damaging earthquake occurs, utility and other lifeline managers, emergency responders, and other critical users have an urgent need for information about the impact on their particular facilities so they can make appropriate decisions and take quick actions to ensure safety and restore system functionality. To this end, ShakeCast estimates the potential damage to a user's widely distributed facilities by comparing the complex shaking distribution with the potentially highly variable damageability of their inventory to provide a simple, hierarchical list and maps showing structures or facilities most likely impacted. All ShakeMap and ShakeCast files and products are non-propriety to simplify interfacing with existing users" response tools and to encourage user-made enhancement to the software. ShakeCast uses standard RSS and HTTP requests to communicate with the USGS Web servers that host ShakeMaps, which are widely-distributed and heavily mirrored. The RSS approach allows ShakeCast users to initiate and receive selected ShakeMap products and information on software updates. To assess facility damage estimates, ShakeCast users can combine measured or estimated ground motion parameters with damage relationships that can be pre-computed, use one of these ground motion parameters as input, and produce a multi-state discrete output of damage likelihood. Presently three common approaches are being used to provide users with an indication of damage: HAZUS-based, intensity-based, and customized damage functions. Intensity-based thresholds are for locations with poorly established damage relationships; custom damage levels are for advanced ShakeCast users such as Caltrans which produces its own set of damage functions that correspond to the specific details of each California bridge or overpass in its jurisdiction. For users whose portfolio of structures is comprised of common, standard designs, ShakeCast offers a simplified structural damage-state estimation capability adapted from the HAZUS-MH earthquake module (NIBS and FEMA, 2003). Currently the simplified fragility settings consist of 128 combinations of HAZUS model building types, construction materials, building heights, and building-code eras.

Protective Effect of Hydroxychloroquine on Renal Damage in Patients with Lupus Nephritis: Data from LUMINA, a Multiethnic U.S. Cohort

PubMed Central

Pons-Estel, Guillermo J.; Alarcón, Graciela S.; McGwin, Gerald; Danila, Maria I.; Zhang, Jie; Bastian, Holly M.; Reveille, John D.; Vilá, Luis M.

2010-01-01

Objective To assess if hydroxychloroquine can delay renal damage development in lupus nephritis patients. Methods Lupus nephritis patients (n=256) from LUMINA (n=635), a multiethnic cohort of African Americans, Hispanics and Caucasians, age ≥16 years, disease duration ≤5 years at baseline (T0) were studied. Renal damage was defined per the SLICC Damage Index (≥1 of the following lasting at least six months: estimated/measured glomerular filtration rate <50%, 24-hour proteinuria ≥3.5 g and/or end-stage renal disease, regardless of dialysis or transplantation). Patients with renal damage before T0 were excluded (n=53). The association between hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potentially confounders. Kaplan-Meier survival curves based on hydroxychloroquine intake or World Health Organization (WHO) Class glomerulonephritis were also derived. Results Sixty-three (31.0%) of 203 patients developed renal damage over a mean (standard deviation) disease duration of 5.2 (3.5) years. The most frequent renal damage domain item was proteinuria. Hydroxychloroquine-takers (79.3%) exhibited a lower frequency of WHO Class IV glomerulonephritis, lower disease activity and received lower glucocorticoid doses than non-takers. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (HR=0.12; 95% CI 0.02-0.97; p=0.0464) and reduced (HR=0.29; 95%CI 0.13-0.68; p=0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in hydroxychloroquine non-takers and in WHO Class IV glomerulonephritis (p<0.0001). Conclusions After adjusting for possible confounding factors the protective effect of hydroxychloroquine in retarding renal damage occurrence in SLE is still evident. PMID:19479701

Dynamics of animal movement in an ecological context: dragonfly wing damage reduces flight performance and predation success.

PubMed

Combes, S A; Crall, J D; Mukherjee, S

2010-06-23

Much of our understanding of the control and dynamics of animal movement derives from controlled laboratory experiments. While many aspects of animal movement can be probed only in these settings, a more complete understanding of animal locomotion may be gained by linking experiments on relatively simple motions in the laboratory to studies of more complex behaviours in natural settings. To demonstrate the utility of this approach, we examined the effects of wing damage on dragonfly flight performance in both a laboratory drop-escape response and the more natural context of aerial predation. The laboratory experiment shows that hindwing area loss reduces vertical acceleration and average flight velocity, and the predation experiment demonstrates that this type of wing damage results in a significant decline in capture success. Taken together, these results suggest that wing damage may take a serious toll on wild dragonflies, potentially reducing both reproductive success and survival.

NASALIFE - Component Fatigue and Creep Life Prediction Program

NASA Technical Reports Server (NTRS)

Gyekenyesi, John Z.; Murthy, Pappu L. N.; Mital, Subodh K.

2014-01-01

NASALIFE is a life prediction program for propulsion system components made of ceramic matrix composites (CMC) under cyclic thermo-mechanical loading and creep rupture conditions. Although the primary focus was for CMC components, the underlying methodologies are equally applicable to other material systems as well. The program references empirical data for low cycle fatigue (LCF), creep rupture, and static material properties as part of the life prediction process. Multiaxial stresses are accommodated by Von Mises based methods and a Walker model is used to address mean stress effects. Varying loads are reduced by the Rainflow counting method or a peak counting type method. Lastly, damage due to cyclic loading and creep is combined with Minor's Rule to determine damage due to cyclic loading, damage due to creep, and the total damage per mission and the number of potential missions the component can provide before failure.

Oxidative damage and cell-programmed death induced in Zea mays L. by allelochemical stress.

PubMed

Ciniglia, Claudia; Mastrobuoni, Francesco; Scortichini, Marco; Petriccione, Milena

2015-05-01

The allelochemical stress on Zea mays was analyzed by using walnut husk washing waters (WHWW), a by-product of Juglans regia post-harvest process, which possesses strong allelopathic potential and phytotoxic effects. Oxidative damage and cell-programmed death were induced by WHWW in roots of maize seedlings. Treatment induced ROS burst, with excess of H2O2 content. Enzymatic activities of catalase were strongly increased during the first hours of exposure. The excess in malonildialdehyde following exposure to WHWW confirmed that oxidative stress severely damaged maize roots. Membrane alteration caused a decrease in NADPH oxidase activity along with DNA damage as confirmed by DNA laddering. The DNA instability was also assessed through sequence-related amplified polymorphism assay, thus suggesting the danger of walnut processing by-product and focusing the attention on the necessity of an efficient treatment of WHWW.

Comparison of silvicultural and natural disturbance effects on terrestrial salamanders in northern hardwood forests

Treesearch

Daniel J. Hocking; Kimberly J. Babbitt; Mariko Yamasaki

2013-01-01

In forested ecosystems timber harvesting has the potential to emulate natural disturbances, thereby maintaining the natural communities adapted to particular disturbances. We compared the effects of even-aged (clearcut and patch cut) and uneven-aged (group cut, single-tree selection) timber management techniques with natural ice-storm damage and unmanipulated reference...

Fetal Alcohol Effects in Children: Cognitive, Educational, and Behavioral Considerations.

ERIC Educational Resources Information Center

Horowitz, Sheldon

The effects of alcohol on the developing fetus are examined. Noted is the existence of both structural problems (such as microcephaly and cardiac anomalies) and behavioral problems (such as mental retardation and speech and language deficits). The potential damage of alcohol at a very early stage of fetal development is discussed. It is thought…

Environmental exposure to human carcinogens in teenagers and the association with DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franken, Carmen, E-mail: carmen.franken@vito.be

Background: We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods: Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid asmore » a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Results: Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel and t,t-muconic acid were inversely associated with the alkaline comet assay. Conclusion: This cross-sectional study found associations between current environmental exposure to (potential) human carcinogens in 14–15-year-old Flemish adolescents and short-term (oxidative) damage to DNA. Prospective follow-up will be required to investigate whether long-term effects may occur due to complex environmental exposures. - Highlights: • Exposure to (potential) carcinogens is associated with (oxidative) damage to DNA. • Most associations of exposures are with urinary 8-OHdG. • 1-Hydroxypyrene and chromium are associated with the comet assay and 8-OHdG. • PFOA is associated with higher levels of DNA damage in the alkaline comet assay.« less

Potentials of Optical Damage Assessment Techniques in Automotive Crash-Concepts composed of FRP-Steel Hybrid Material Systems

NASA Astrophysics Data System (ADS)

Dlugosch, M.; Spiegelhalter, B.; Soot, T.; Lukaszewicz, D.; Fritsch, J.; Hiermaier, S.

2017-05-01

With car manufacturers simultaneously facing increasing passive safety and efficiency requirements, FRP-metal hybrid material systems are one way to design lightweight and crashworthy vehicle structures. Generic automotive hybrid structural concepts have been tested under crash loading conditions. In order to assess the state of overall damage and structural integrity, and primarily to validate simulation data, several NDT techniques have been assessed regarding their potential to detect common damage mechanisms in such hybrid systems. Significant potentials were found particularly in combining 3D-topography laser scanning and X-Ray imaging results. Ultrasonic testing proved to be limited by the signal coupling quality on damaged or curved surfaces.

Application of Advanced Nondestructive Evaluation Techniques for Cylindrical Composite Test Samples

NASA Technical Reports Server (NTRS)

Martin, Richard E.; Roth, Donald J.; Salem, Jonathan A.

2013-01-01

Two nondestructive methods were applied to composite cylinder samples pressurized to failure in order to determine manufacturing quality and monitor damage progression under load. A unique computed tomography (CT) image processing methodology developed at NASA Glenn Research was used to assess the condition of the as-received samples while acoustic emission (AE) monitoring was used to identify both the extent and location of damage within the samples up to failure. Results show the effectiveness of both of these methods in identifying potentially critical fabrication issues and their resulting impact on performance.

Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells.

PubMed

Moore, Darcie L; Jessberger, Sebastian

2017-01-01

Accumulating evidence suggests that mammalian cells asymmetrically segregate cellular components ranging from genomic DNA to organelles and damaged proteins during cell division. Asymmetric inheritance upon mammalian cell division may be specifically important to ensure cellular fitness and propagate cellular potency to individual progeny, for example in the context of somatic stem cell division. We review here recent advances in the field and discuss potential effects and underlying mechanisms that mediate asymmetric segregation of cellular components during mammalian cell division. Copyright © 2016 Elsevier Ltd. All rights reserved.

Track structure model for damage to mammalian cell cultures during solar proton events

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.; Townsend, L. W.; Shinn, J. L.; Katz, R.

1992-01-01

Solar proton events (SPEs) occur infrequently and unpredictably, thus representing a potential hazard to interplanetary space missions. Biological damage from SPEs will be produced principally through secondary electron production in tissue, including important contributions due to delta rays from nuclear reaction products. We review methods for estimating the biological effectiveness of SPEs using a high energy proton model and the parametric cellular track model. Results of the model are presented for several of the historically largest flares using typical levels and body shielding.

Mineralogical control on thermal damage and the presence of a thermal Kaiser effect during temperature-cycling experiments

NASA Astrophysics Data System (ADS)

Browning, J.; Daoud, A.; Meredith, P. G.; Mitchell, T. M.

2017-12-01

Volcanic and geothermal systems are in part controlled by the mechanical and thermal stresses acting on them and so it is important to understand the response of volcanic rocks to thermo-mechanical loading. One such response is the well-known `Kaiser stress-memory' effect observed under cyclic mechanical loading. By contrast, the presence of an analogous `Kaiser temperature-memory effect' during cyclic thermal loading has received little attention. We have therefore explored the possibility of a Kaiser temperature-memory effect using three igneous rocks of different composition, grain size and origin; Slaufrudalur Granophyre (SGP), Nea Kameni Andesite (NKA) and Seljadalur Basalt (SB). We present results from a series of thermal stressing experiments in which acoustic emissions (AE) were recorded contemporaneously with changing temperature. Samples of each rock were subjected to both a single heating and cooling cycle to a maximum temperature of 900 °C and multiple heating/cooling cycles to peak temperatures of 350°C, 500°C, 700°C and 900 °C (all at a constant rate of 1°C/min on heating and a natural cooling rate of <1°C/min). Porosity, permeability and P-wave velocity measurements were made on each sample both before and after thermal treatment. We use the onset of AEs as a proxy for the onset of thermal cracking. This clearly demonstrates the presence of a Kaiser temperature-memory effect in SGP, but not in either NKA and SB. We further find that the vast majority of thermal crack damage is generated upon cooling in the finer grained materials (NKA and SB), but that substantial thermal crack damage is generated during heating in the coarser grained SGP. The total amount of crack damage generated due to heating or cooling is dependent on the mineral composition and, most importantly, the grain size and arrangement, as well as the maximum temperature to which the rock is exposed. Knowledge of thermal stress history and the presence of a Kaiser temperature-memory effect is potentially important in understanding magma chamber dynamics, where the cyclic nature of mechanical and thermal inflation and deflation can lead to sequential accumulation of damage, potentially leading to critical rupture.

Regulatory effects of curcumin on lipid accumulation in monocytes/macrophages

USDA-ARS?s Scientific Manuscript database

Recent evidence suggests potential benefits from phytochemicals and micronutrients in protecting against oxidative and lipid-mediated damage, but the molecular mechanisms of these actions are still unclear. Here we investigated whether the dietary polyphenol curcumin can modulate the accumulation of...

Oxidative Stress, Inflammation, and DNA Damage Responses Elicited by Silver, Titanium Dioxide, and Cerium Oxide Nanomaterials

EPA Science Inventory

Previous literature on the biological effects of engineered nanomaterials has focused largely on oxidative stress and inflammation endpoints without further investigating potential pathways. Here we examine time-sensitive biological response pathways affected by engineered nanoma...

Severe tissue damage in Atlantic cod larvae under increasing ocean acidification

NASA Astrophysics Data System (ADS)

Frommel, Andrea Y.; Maneja, Rommel; Lowe, David; Malzahn, Arne M.; Geffen, Audrey J.; Folkvord, Arild; Piatkowski, Uwe; Reusch, Thorsten B. H.; Clemmesen, Catriona

2012-01-01

Ocean acidification, caused by increasing atmospheric concentrations of CO2 (refs , , ), is one of the most critical anthropogenicthreats to marine life. Changes in seawater carbonate chemistry have the potential to disturb calcification, acid-base regulation, blood circulation and respiration, as well as the nervous system of marine organisms, leading to long-term effects such as reduced growth rates and reproduction. In teleost fishes, early life-history stages are particularly vulnerable as they lack specialized internal pH regulatory mechanisms. So far, impacts of relevant CO2 concentrations on larval fish have been found in behaviour and otolith size, mainly in tropical, non-commercial species. Here we show detrimental effects of ocean acidification on the development of a mass-spawning fish species of high commercial importance. We reared Atlantic cod larvae at three levels of CO2, (1) present day, (2) end of next century and (3) an extreme, coastal upwelling scenario, in a long-term ( months) mesocosm experiment. Exposure to CO2 resulted in severe to lethal tissue damage in many internal organs, with the degree of damage increasing with CO2 concentration. As larval survival is the bottleneck to recruitment, ocean acidification has the potential to act as an additional source of natural mortality, affecting populations of already exploited fish stocks.

Development of evaluation metod of flood risk in Tokyo metropolitan area

NASA Astrophysics Data System (ADS)

Hirano, J.; Dairaku, K.

2012-12-01

Flood is one of the most significant natural hazards in Japan. In particular, the Tokyo metropolitan area has been affected by several large flood disasters. Investigating potential flood risk in Tokyo metropolitan area is important for development of climate change adaptation strategy. We aim to develop a method for evaluating flood risk in Tokyo Metropolitan area by considering effect of historical land use and land cover change, socio-economic change, and climatic change. Ministry of land, infrastructure, transport and tourism in Japan published "Statistics of flood", which contains data for flood causes, number of damaged houses, area of wetted surface, and total amount of damage for each flood at small municipal level. Based on these flood data, we constructed a flood database system for Tokyo metropolitan area for the period from 1961 to 2008 by using ArcGIS software.Based on these flood data , we created flood risk curve, representing the relation ship between damage and exceedbability of flood for the period 1976-2008. Based on the flood risk cruve, we aim to evaluate potential flood risk in the Tokyo metropolitan area and clarify the cause of regional difference in flood risk at Tokyo metropolitan area by considering effect of socio-economic change and climate change

Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo.

PubMed

Brönnimann, Daniel; Bouchet, Audrey; Schneider, Christoph; Potez, Marine; Serduc, Raphaël; Bräuer-Krisch, Elke; Graber, Werner; von Gunten, Stephan; Laissue, Jean Albert; Djonov, Valentin

2016-09-19

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25-100 μm wide) and minibeams (200-800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a(+) thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool.

Squalene Inhibits ATM-Dependent Signaling in γIR-Induced DNA Damage Response through Induction of Wip1 Phosphatase.

PubMed

Tatewaki, Naoto; Konishi, Tetsuya; Nakajima, Yuki; Nishida, Miyako; Saito, Masafumi; Eitsuka, Takahiro; Sakamaki, Toshiyuki; Ikekawa, Nobuo; Nishida, Hiroshi

2016-01-01

Ataxia telangiectasia mutated (ATM) kinase plays a crucial role as a master controller in the cellular DNA damage response. Inhibition of ATM leads to inhibition of the checkpoint signaling pathway. Hence, addition of checkpoint inhibitors to anticancer therapies may be an effective targeting strategy. A recent study reported that Wip1, a protein phosphatase, de-phosphorylates serine 1981 of ATM during the DNA damage response. Squalene has been proposed to complement anticancer therapies such as chemotherapy and radiotherapy; however, there is little mechanistic information supporting this idea. Here, we report the inhibitory effect of squalene on ATM-dependent DNA damage signals. Squalene itself did not affect cell viability and the cell cycle of A549 cells, but it enhanced the cytotoxicity of gamma-irradiation (γIR). The in vitro kinase activity of ATM was not altered by squalene. However, squalene increased Wip1 expression in cells and suppressed ATM activation in γIR-treated cells. Consistent with the potential inhibition of ATM by squalene, IR-induced phosphorylation of ATM effectors such as p53 (Ser15) and Chk1 (Ser317) was inhibited by cell treatment with squalene. Thus, squalene inhibits the ATM-dependent signaling pathway following DNA damage through intracellular induction of Wip1 expression.

The evaluation of distributed damage in concrete based on sinusoidal modeling of the ultrasonic response.

PubMed

Sepehrinezhad, Alireza; Toufigh, Vahab

2018-05-25

Ultrasonic wave attenuation is an effective descriptor of distributed damage in inhomogeneous materials. Methods developed to measure wave attenuation have the potential to provide an in-site evaluation of existing concrete structures insofar as they are accurate and time-efficient. In this study, material classification and distributed damage evaluation were investigated based on the sinusoidal modeling of the response from the through-transmission ultrasonic tests on polymer concrete specimens. The response signal was modeled as single or the sum of damping sinusoids. Due to the inhomogeneous nature of concrete materials, model parameters may vary from one specimen to another. Therefore, these parameters are not known in advance and should be estimated while the response signal is being received. The modeling procedure used in this study involves a data-adaptive algorithm to estimate the parameters online. Data-adaptive algorithms are used due to a lack of knowledge of the model parameters. The damping factor was estimated as a descriptor of the distributed damage. The results were compared in two different cases as follows: (1) constant excitation frequency with varying concrete mixtures and (2) constant mixture with varying excitation frequencies. The specimens were also loaded up to their ultimate compressive strength to investigate the effect of distributed damage in the response signal. The results of the estimation indicated that the damping was highly sensitive to the change in material inhomogeneity, even in comparable mixtures. In addition to the proposed method, three methods were employed to compare the results based on their accuracy in the classification of materials and the evaluation of the distributed damage. It is shown that the estimated damping factor is not only sensitive to damage in the final stages of loading, but it is also applicable in evaluating micro damages in the earlier stages providing a reliable descriptor of damage. In addition, the modified amplitude ratio method is introduced as an improvement of the classical method. The proposed methods were validated to be effective descriptors of distributed damage. The presented models were also in good agreement with the experimental data. Copyright © 2018 Elsevier B.V. All rights reserved.

In field damage of high and low cyanogenic cassava due to a generalist insect herbivore Cyrtomenus bergi (Hemiptera: Cydnidae).

PubMed

Riis, Lisbeth; Bellotti, Anthony Charles; Castaño, Oscar

2003-12-01

The hypothesis that cyanogenic potential in cassava roots deters polyphagous insects in the field is relevant to current efforts to reduce or eliminate the cyanogenic potential in cassava. To test this hypothesis, experiments were conducted in the field under natural selection pressure of the polyphagous root feeder Cyrtomenus bergi Froeschner (Hemiptera: Cydnidae). A number of cassava varieties (33) as well as 13 cassava siblings and their parental clone, each representing a determined level of cyanogenic potential (CNP), were scored for damage caused by C. bergi and related to CNP and nonglycosidic cyanogens, measured as hydrogen cyanide. Additionally, 161 low-CNP varieties (< 50 ppm hydrogen cyanide, fresh weight) from the cassava germplasm core collection at Centro Internacional de Agricultura Tropical (CIAT) were screened for resistance/tolerance to C. bergi. Low root damage scores were registered at all levels of CNP. Nevertheless, CNP and yield (or root size) partly explained the damage in cassava siblings (r2 = 0.82) and different cassava varieties (r2 = 0.42), but only when mean values of damage scores were used. This relation was only significant in one of two crop cycles. A logistic model describes the underlying negative relation between CNP and damage. An exponential model describes the underlying negative relation between root size and damage. Damage, caused by C. bergi feeding, released nonglycosidic cyanogens, and an exponential model fits the underlying positive relation. Fifteen low-CNP clones were selected for potential resistance/tolerance against C. bergi.

Gadolinium-based nanoparticles to improve the hadrontherapy performances.

PubMed

Porcel, Erika; Tillement, Olivier; Lux, François; Mowat, Pierre; Usami, Noriko; Kobayashi, Katsumi; Furusawa, Yoshiya; Le Sech, Claude; Li, Sha; Lacombe, Sandrine

2014-11-01

Nanomedicine is proposed as a novel strategy to improve the performance of radiotherapy. High-Z nanoparticles are known to enhance the effects of ionizing radiation. Recently, multimodal nanoparticles such as gadolinium-based nanoagents were proposed to amplify the effects of x-rays and g-rays and to improve MRI diagnosis. For tumors sited in sensitive tissues, childhood cases and radioresistant cancers, hadrontherapy is considered superior to x-rays and g-rays. Hadrontherapy, based on fast ion radiation, has the advantage of avoiding damage to the tissues behind the tumor; however, the damage caused in front of the tumor is its major limitation. Here, we demonstrate that multimodal gadolinium-based nanoparticles amplify cell death with fast ions used as radiation. Molecular scale experiments give insights into the mechanisms underlying the amplification of radiation effects. This proof-of-concept opens up novel perspectives for multimodal nanomedicine in hadrontherapy, ultimately reducing negative radiation effects in healthy tissues in front of the tumor. Gadolinium-chelating polysiloxane nanoparticles were previously reported to amplify the anti-tumor effects of x-rays and g-rays and to serve as MRI contrast agents. Fast ion radiation-based hadrontherapy avoids damage to the tissues behind the tumor, with a major limitation of tissue damage in front of the tumor. This study demonstrates a potential role for the above nanoagents in optimizing hadrontherapy with preventive effects in healthy tissue and amplified cell death in the tumor. Copyright © 2014 Elsevier Inc. All rights reserved.

risk factor Inn (INNrisk) - transdisciplinary analysis of the 2005 flood in the province of Tyrol, Austria

NASA Astrophysics Data System (ADS)

Kleewein, Klaus; Pfurtscheller, Clemens; Borsdorf, Axel

2010-05-01

The transdisciplinary project INNrisk, in collaboration with public risk and disaster management, investigates the severe floods of 22nd and 23rd of August, 2005, and their effects within the federal province of Tyrol. The inundation and accompanying processes (e.g. debris flows, log jams, underwashing of infrastructure) caused by the river Inn and its tributaries created a dangerous situation for Tyrol. The overall economic loss of direct assets is said to amount to ca. 500 million Euros. Climate change has basically been causing a statistical increase of damaging floods within the Alpine Space in recent decades while increasing vulnerability at the same time. The expansion of settlements is one factor in the threat to large numbers of people and growing economic losses. However, the disasters of the last decade provide an opportunity for analysing the flood process in terms of natural-science and geographical aspects as well as in terms of economic and statistical ones. This should lead to a better understanding of triggers and effects in those areas where humans are active and form the basis for mitigation and adaptation strategies. The results of such analyses represent valuable information for public risk and disaster management, particularly in presenting the effects on public and private households. The INNrisk project primarily aims to assess the framework conditions in systemic-legal terms and to analyse human actions during the floods in relation to various plans and the damage potentials resulting from them. The assessed losses depend to a great extent on the actions taken during the emergency and on flood operations by the public emergency management and local fire departments, which are in charge of floods and related processes in the case of Austria. Assessment will be carried out by analysing a database of series of human actions for the duration of the emergeny and increased risk. The project also strives to arrive at a macro- and mesoeconomic assessment of the damages by category (infrastructure, buildings, vehicles, etc.) and sector, as well as gauging potential positive effects on the regional economy. It can be assumed that the main beneficiaries of natural hazard processes in Alpine regions are the building and construction industry, transportation businesses and their suppliers. For this part of the project, a georeferenced database will be designed to get an idea of spatial distribution, loss patterns and local specifics compared with natural scientific parameters of the 2005 flood. An overall analysis serves to identify potential improvements within public disaster management and to sketch damage limitation strategies. The project results are of great value, not just for damage prevention measures against future Inn floods, which are likely to occur more frequently and in greater intensity as a result of global warming, but also for other rivers in the Alps. The results of this research may form the basis for developing effective adaptation strategies to climate change and the resulting potential threats to river valleys.

Genotoxic potential of copper oxide nanoparticles in the bivalve mollusk Mytilus trossulus

NASA Astrophysics Data System (ADS)

Chelomin, Victor P.; Slobodskova, Valentina V.; Zakhartsev, Maksim; Kukla, Sergey

2017-04-01

Copper oxide nanoparticles (CuO-NPs) are among the most widely used metal oxide nanoparticles, which increases the chance of their being released into the marine environment. As the applications of these particles have increased in recent years, their potential impact on the health of marine biota has also increased. However, the toxicological effects of these NPs in the marine environment are poorly known. In the present study, the DNA damaging potential of CuO-NPs in the marine eastern mussel Mytilus trossulus was evaluated and compared to that of dissolved copper exposures. Genotoxicity was assessed by the single cell gel electrophoresis (comet) assay in mussel gill and digestive gland cells. The results showed that copper in both forms (CuO-NPs and dissolved copper) was accumulated to different extents in mussel tissues. The mussel exposed to the dissolved copper attained higher concentrations of copper in the gills than in the digestive gland. In contrast to these results, it was found that CuO-NPs could induce much higher copper accumulation in the digestive gland than in the gills. A clear and statistically significant increase in DNA damage was found in both tissues of the Cu-exposed group compared to the control mussels. Our results indicated that the CuO-NP exposure produced remarkable effects and increased DNA damage significantly in mussel gill cells only. It should be noted that the digestive gland cells were prone to accumulation following CuO-NPs when compared to the gill cells, while the gill cells were more sensitive to the genotoxic effects of CuO-NPs. These results also suggested the need for a complete risk assessment of engineered particles before its arrival in the consumer market.

DNA Protection against Oxidative Damage Using the Hydroalcoholic Extract of Garcinia mangostana and Alpha-Mangostin.

PubMed

Carvalho-Silva, Ronaldo; Pereira, Alanna Cibelle Fernandes; Dos Santos Alves, Rúbens Prince; Guecheva, Temenouga N; Henriques, João A P; Brendel, Martin; Pungartnik, Cristina; Rios-Santos, Fabrício

2016-01-01

Garcinia mangostana, popularly known as "mangosteen fruit," originates from Southeast Asia and came to Brazil about 80 years ago where it mainly grows in the states of Pará and Bahia. Although mangosteen or its extracts have been used for ages in Asian folk medicine, data on its potential genotoxicity is missing. We, therefore, evaluated genotoxicity/mutagenicity of hydroethanolic mangosteen extract [HEGM, 10 to 640 μg/mL] in established test assays (Comet assay, micronucleus test, and Salmonella/microsome test). In the Comet assay, HEGM-exposed human leukocytes showed no DNA damage. No significant HEGM-induced mutation in TA98 and TA100 strains of Salmonella typhimurium (with or without metabolic activation) was observed and HEGM-exposed human lymphocytes had no increase of micronuclei. However, HEGM suggested exposure concentration-dependent antigenotoxic potential in leukocytes and antioxidant potential in the yeast Saccharomyces cerevisiae. HEGM preloading effectively protected against H2O2-induced DNA damage in leukocytes (Comet assay). Preloading of yeast with HEGM for up to 4 h significantly protected the cells from lethality of chronic H2O2-exposure, as expressed in better survival. Absence of genotoxicity and demonstration of an antigenotoxic and antioxidant potential suggest that HEGM or some substances contained in it may hold promise for pharmaceutical or nutraceutical application.

DNA Protection against Oxidative Damage Using the Hydroalcoholic Extract of Garcinia mangostana and Alpha-Mangostin

PubMed Central

Carvalho-Silva, Ronaldo; Pereira, Alanna Cibelle Fernandes; dos Santos Alves, Rúbens Prince; Guecheva, Temenouga N.; Henriques, João A. P.; Brendel, Martin; Rios-Santos, Fabrício

2016-01-01

Garcinia mangostana, popularly known as “mangosteen fruit,” originates from Southeast Asia and came to Brazil about 80 years ago where it mainly grows in the states of Pará and Bahia. Although mangosteen or its extracts have been used for ages in Asian folk medicine, data on its potential genotoxicity is missing. We, therefore, evaluated genotoxicity/mutagenicity of hydroethanolic mangosteen extract [HEGM, 10 to 640 μg/mL] in established test assays (Comet assay, micronucleus test, and Salmonella/microsome test). In the Comet assay, HEGM-exposed human leukocytes showed no DNA damage. No significant HEGM-induced mutation in TA98 and TA100 strains of Salmonella typhimurium (with or without metabolic activation) was observed and HEGM-exposed human lymphocytes had no increase of micronuclei. However, HEGM suggested exposure concentration-dependent antigenotoxic potential in leukocytes and antioxidant potential in the yeast Saccharomyces cerevisiae. HEGM preloading effectively protected against H2O2-induced DNA damage in leukocytes (Comet assay). Preloading of yeast with HEGM for up to 4 h significantly protected the cells from lethality of chronic H2O2-exposure, as expressed in better survival. Absence of genotoxicity and demonstration of an antigenotoxic and antioxidant potential suggest that HEGM or some substances contained in it may hold promise for pharmaceutical or nutraceutical application. PMID:27042187

Single and Combined Effects of Deoxynivalenol Mycotoxin and a Microbial Feed Additive on Lymphocyte DNA Damage and Oxidative Stress in Broiler Chickens

PubMed Central

Awad, Wageha A.; Ghareeb, Khaled; Dadak, Agnes; Hess, Michael; Böhm, Josef

2014-01-01

The immune and intestinal epithelial cells are particularly sensitive to the toxic effects of deoxynivalenol (DON). The aim of this experiment was to study the effects of DON and/or a microbial feed additive on the DNA damage of blood lymphocytes and on the level of thiobarbituric acid reactive substance (TBARS) as an indicator of lipid peroxidation and oxidative stress in broilers. A total of forty 1-d-old broiler chicks were randomly assigned to 1 of 4 dietary treatments (10 birds per group) for 5 wk. The dietary treatments were 1) basal diet; 2) basal diet contaminated with 10 mg DON/kg feed; 3) basal diet contaminated with 10 mg DON/kg feed and supplemented with 2.5 kg/ton of feed of Mycofix Select; 4) basal diet supplemented with Mycofix Select (2.5 kg/ton of feed). At the end of the feeding trial, blood were collected for measuring the level of lymphocyte DNA damage of blood and the TBARS level was measured in plasma, heart, kidney, duodenum and jejunum. The dietary exposure of DON caused a significant increase (P = 0.001) of DNA damage in blood lymphocytes (31.99±0.89%) as indicated in the tail of comet assay. Interestingly addition of Mycofix Select to DON contaminated diet decreased (P = 0.001) the DNA damage (19.82±1.75%) induced by DON. In order to clarify the involvement of lipid peroxidation in the DNA damage of DON, TBARS levels was measured. A significant increase (P = 0.001) in the level of TBARS (23±2 nmol/mg) was observed in the jejunal tissue suggesting that the lipid peroxidation might be involved in the DNA damage. The results indicate that DON is cytotoxic and genotoxic to the chicken intestinal and immune cells and the feed additive have potential ability to prevent DNA damage induced by DON. PMID:24498242

Effects of optimism on recovery and mental health after a tornado outbreak.

PubMed

Carbone, Eric G; Echols, Erin Thomas

2017-05-01

Dispositional optimism, a stable expectation that good things will happen, has been shown to improve health outcomes in a wide range of contexts, but very little research has explored the impact of optimism on post-disaster health and well-being. Data for this study come from the Centers for Disease Control and Prevention's Public health systems and mental health community recovery (PHSMHCR) Survey. Participants included 3216 individuals living in counties affected by the April 2011 tornado outbreak in Mississippi and Alabama. This study assesses the effect of dispositional optimism on post-disaster recovery and mental health. Dispositional optimism was found to have a positive effect on personal recovery and mental health after the disaster. Furthermore, it moderated the relationship between level of home damage and personal recovery as well as the relationship between home damage and post-traumatic stress disorder (PTSD), with stronger effects for those with increased levels of home damage. The utility of screening for optimism is discussed, along with the potential for interventions to increase optimism as a means of mitigating adverse mental health effects and improving the recovery of individuals affected by disasters and other traumatic events.

Effects of optimism on recovery and mental health after a tornado outbreak

PubMed Central

Carbone, Eric G.; Echols, Erin Thomas

2017-01-01

Objective Dispositional optimism, a stable expectation that good things will happen, has been shown to improve health outcomes in a wide range of contexts, but very little research has explored the impact of optimism on post-disaster health and well-being. Design Data for this study come from the Centers for Disease Control and Prevention’s Public health systems and mental health community recovery (PHSMHCR) Survey. Participants included 3216 individuals living in counties affected by the April 2011 tornado outbreak in Mississippi and Alabama. Main outcome measures This study assesses the effect of dispositional optimism on post-disaster recovery and mental health. Results Dispositional optimism was found to have a positive effect on personal recovery and mental health after the disaster. Furthermore, it moderated the relationship between level of home damage and personal recovery as well as the relationship between home damage and post-traumatic stress disorder (PTSD), with stronger effects for those with increased levels of home damage. Conclusions The utility of screening for optimism is discussed, along with the potential for interventions to increase optimism as a means of mitigating adverse mental health effects and improving the recovery of individuals affected by disasters and other traumatic events. PMID:28156138

Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcinogenesis.

PubMed

Sirerol, J Antoni; Feddi, Fatima; Mena, Salvador; Rodriguez, María L; Sirera, Paula; Aupí, Miguel; Pérez, Salvador; Asensi, Miguel; Ortega, Angel; Estrela, José M

2015-08-01

The aim of our study was to investigate in the SKH-1 hairless mouse model the effect of pterostilbene (Pter), a natural dimethoxy analog of resveratrol (Resv), against procarcinogenic ultraviolet B radiation (UVB)-induced skin damage. Pter prevented acute UVB (360 mJ/cm(2))-induced increase in skin fold, thickness, and redness, as well as photoaging-associated skin wrinkling and hyperplasia. Pter, but not Resv, effectively prevented chronic UVB (180 mJ/cm(2), three doses/week for 6 months)-induced skin carcinogenesis (90% of Pter-treated mice did not develop skin carcinomas, whereas a large number of tumors were observed in all controls). This anticarcinogenic effect was associated with (a) maintenance of skin antioxidant defenses (i.e., glutathione (GSH) levels, catalase, superoxide, and GSH peroxidase activities) close to control values (untreated mice) and (b) an inhibition of UVB-induced oxidative damage (using as biomarkers 8-hydroxy-2'-deoxyguanosine, protein carbonyls, and isoprostanes). The molecular mechanism underlying the photoprotective effect elicited by Pter was further evaluated using HaCaT immortalized human keratinocytes and was shown to involve potential modulation of the Nrf2-dependent antioxidant response. Copyright © 2015 Elsevier Inc. All rights reserved.

Chemotherapeutic potential of quercetin on human bladder cancer cells.

PubMed

Oršolić, Nada; Karač, Ivo; Sirovina, Damir; Kukolj, Marina; Kunštić, Martina; Gajski, Goran; Garaj-Vrhovac, Vera; Štajcar, Damir

2016-07-28

In an effort to improve local bladder cancer control, we investigated the cytotoxic and genotoxic effects of quercetin on human bladder cancer T24 cells. The cytotoxic effect of quercetin against T24 cells was examined by MTT test, clonogenic assay as well as DNA damaging effect by comet assay. In addition, the cytotoxic effect of quercetin on the primary culture of papillary urothelial carcinoma (PUC), histopathological stage T1 of low- or high-grade tumours, was investigated. Our analysis demonstrated a high correlation between reduced number of colony and cell viability and an increase in DNA damage of T24 cells incubated with quercetin at doses of 1 and 50 µM during short term incubation (2 h). At all exposure times (24, 48 and 72 h), the efficacy of quercetin, administered at a 10× higher dose compared to T24 cells, was statistically significant (P < 0.05) for the primary culture of PUC. In conclusion, our study suggests that quercetin could inhibit cell proliferation and colony formation of human bladder cancer cells by inducing DNA damage and that quercetin may be an effective chemopreventive and chemotherapeutic agent for papillary urothelial bladder cancer after transurethral resection.

Estimation of potential impacts and natural resource damages of oil.

PubMed

McCay, Deborah French; Rowe, Jill Jennings; Whittier, Nicole; Sankaranarayanan, Sankar; Etkin, Dagmar Schmidt

2004-02-27

Methods were developed to estimate the potential impacts and natural resource damages resulting from oil spills using probabilistic modeling techniques. The oil fates model uses wind data, current data, and transport and weathering algorithms to calculate mass balance of fuel components in various environmental compartments (water surface, shoreline, water column, atmosphere, sediments, etc.), oil pathway over time (trajectory), surface distribution, shoreline oiling, and concentrations of the fuel components in water and sediments. Exposure of aquatic habitats and organisms to whole oil and toxic components is estimated in the biological model, followed by estimation of resulting acute mortality and ecological losses. Natural resource damages are based on estimated costs to restore equivalent resources and/or ecological services, using Habitat Equivalency Analysis (HEA) and Resource Equivalency Analysis (REA) methods. Oil spill modeling was performed for two spill sites in central San Francisco Bay, three spill sizes (20th, 50th, and 95th percentile volumes from tankers and larger freight vessels, based on an analysis of likely spill volumes given a spill has occurred) and four oil types (gasoline, diesel, heavy fuel oil, and crude oil). The scenarios were run in stochastic mode to determine the frequency distribution, mean and standard deviation of fates, impacts, and damages. This work is significant as it demonstrates a statistically quantifiable method for estimating potential impacts and financial consequences that may be used in ecological risk assessment and cost-benefit analyses. The statistically-defined spill volumes and consequences provide an objective measure of the magnitude, range and variability of impacts to wildlife, aquatic organisms and shorelines for potential spills of four oil/fuel types, each having distinct environmental fates and effects.

Size-dependent cytotoxicity of yttrium oxide nanoparticles on primary osteoblasts in vitro

NASA Astrophysics Data System (ADS)

Zhou, Guoqiang; Li, Yunfei; Ma, Yanyan; Liu, Zhu; Cao, Lili; Wang, Da; Liu, Sudan; Xu, Wenshi; Wang, Wenying

2016-05-01

Yttrium oxide nanoparticles are an excellent host material for the rare earth metals and have high luminescence efficiency providing a potential application in photodynamic therapy and biological imaging. In this study, the effects of yttrium oxide nanoparticles with four different sizes were investigated using primary osteoblasts in vitro. The results demonstrated that the cytotoxicity generated by yttrium oxide nanoparticles depended on the particle size, and smaller particles possessed higher toxicological effects. For the purpose to elucidate the relationship between reactive oxygen species generation and cell damage, cytomembrane integrity, intracellular reactive oxygen species level, mitochondrial membrane potential, cell apoptosis rate, and activity of caspase-3 in cells were then measured. Increased reactive oxygen species level was also observed in a size-dependent way. Thus, our data demonstrated that exposure to yttrium oxide nanoparticles resulted in a size-dependent cytotoxicity in cultured primary osteoblasts, and reactive oxygen species generation should be one possible damage pathway for the toxicological effects produced by yttrium oxide particles. The results may provide useful information for more rational applications of yttrium oxide nanoparticles in the future.

Water availability limits tolerance of apical damage in the Chilean tarweed Madia sativa

NASA Astrophysics Data System (ADS)

Gonzáles, Wilfredo L.; Suárez, Lorena H.; Molina-Montenegro, Marco A.; Gianoli, Ernesto

2008-07-01

Plant tolerance is the ability to reduce the negative impact of herbivory on plant fitness. Numerous studies have shown that plant tolerance is affected by nutrient availability, but the effect of soil moisture has received less attention. We evaluated tolerance of apical damage (clipping that mimicked insect damage) under two watering regimes (control watering and drought) in the tarweed Madia sativa (Asteraceae). We recorded number of heads with seeds and total number of heads as traits related to fitness. Net photosynthetic rate, water use efficiency, number of branches, shoot biomass, and the root:shoot biomass ratio were measured as traits potentially related to tolerance via compensatory responses to damage. In the drought treatment, damaged plants showed ≈43% reduction in reproductive fitness components in comparison with undamaged plants. In contrast, there was no significant difference in reproductive fitness between undamaged and damaged plants in the control watering treatment. Shoot biomass was not affected by apical damage. The number of branches increased after damage in both water treatments but this increase was limited by drought stress. Net photosynthetic rate increased in damaged plants only in the control watering treatment. Water use efficiency increased with drought stress and, in plants regularly watered, also increased after damage. Root:shoot ratio was higher in the low water treatment and damaged plants tended to reduce root:shoot ratio only in this water treatment. It is concluded that water availability limits tolerance to apical damage in M. sativa, and that putative compensatory mechanisms are differentially affected by water availability.

Effect of Pelargonium reniforme roots on alcohol-induced liver damage and oxidative stress.

PubMed

Adewusi, Emmanuel Adekanmi; Afolayan, Anthony Jide

2010-09-01

Ethnobotanical surveys conducted on Pelargonium reniforme Curtis (Geraniaceae) have shown that the aqueous root extracts are used to treat alcohol-induced liver damage. We evaluated the antioxidant properties of the extract and its effects on alcohol-induced hepatotoxicity using Wistar rats. Alcohol-induced hepatotoxicity studies were carried out by observing the effect of the aqueous root extract on some liver marker enzymes, bilirubin, and total protein after liver damage. The levels of some phenolic compounds were determined by standard methods. Also, the reducing power of the plant extract and its ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH*) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS*+) radicals were determined to evaluate its antioxidant activity. The results obtained show that the plant extract possessed significant antioxidant activity. It had a significant level of phenolic compounds, scavenged DPPH* and ABTS*+ radicals effectively, and demonstrated good reducing power. This may indicate that the plant contained compounds which can remove toxic metabolites following alcohol abuse. Serum analysis of animals treated with only ethanol showed a significant increase in the levels of liver marker enzymes and total and unconjugated bilirubin, while a significant decrease was observed in the levels of conjugated bilirubin and total proteins. Administration of the plant extract restored the levels of these markers to normal levels, and this indicates the ability of the plant extract to restore normal functioning of a damaged liver. The study shows that P. reniforme is a potential source of antioxidants and compounds which are useful in treating alcoholic liver damage.

Cooperative biological effects between ionizing radiation and other physical and chemical agents.

PubMed

Manti, Lorenzo; D'Arco, Annalisa

2010-01-01

Exposure to ionizing radiation (IR), at environmentally and therapeutically relevant doses or as a result of diagnostics or accidents, causes cyto- and genotoxic damage. However, exposure to IR alone is a rare event as it occurs in spatial and temporal combination with several physico-chemical agents. Some of these are of known noxiousness, as is the case with chemical compounds at high dose, hence additive/synergistic effects can be expected or have been demonstrated. Conversely, the cellular toxicity of other agents, such as non-ionizing electromagnetic fields (EMFs), is only presumed and their short- and long-term cooperation on IR-induced damage remains undetermined. In this review, we shall examine evidence in support of the interplay between spatially and/or temporally related environmentally relevant stressors. In vitro or animal-based studies as well as epidemiological surveys have generally examined the combined action of no more than a couple of known or potentially DNA-damaging agents. Moreover, most existing research mainly focused on short-term effects of combined exposures. Hence, it is important that quantitative research addresses the issue of the possible cooperation between chronic exposure to environmental trace contaminants and exposure to EMFs, examining not only the modulation of damage acutely induced by IR but also long-term genome stability. 2010 Elsevier B.V. All rights reserved.

Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress.

PubMed

Wong, Sing Wan; Yao, Yifei; Hong, Ye; Ma, Zhiyao; Kok, Stanton H L; Sun, Shan; Cho, Michael; Lee, Kenneth K H; Mak, Arthur F T

2017-04-01

High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H 2 O 2 ). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H 2 O 2 . These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

UVA-UVB Photoprotective Activity of Topical Formulations Containing Morinda citrifolia Extract

PubMed Central

Serafini, Mairim Russo; Detoni, Cassia Britto; Menezes, Paula dos Passos; Pereira Filho, Rose Nely; Fortes, Vanessa Silveira; Vieira, Maria José Fonseca; Guterres, Sílvia Stanisçuaski; de Albuquerque Junior, Ricardo Luiz Cavalcanti; Araújo, Adriano Antunes de Souza

2014-01-01

Exposure to solar radiation, particularly its ultraviolet (UV) component, has a variety of harmful effects on human health. Some of these effects include sunburn cell formations, basal and squamous cell cancers, melanoma, cataracts, photoaging of the skin, and immune suppression. The beneficial photoprotective effects of topical formulations with the extract, Morinda citrifolia, have not been investigated. This present study aims to investigate the potential benefits of M. citrifolia topical application on the dorsal skin of mice, exposed to UVA-UVB light. Using 7 days of treatment, [before (baseline values) and 20 h after UV exposure], the thickness, skin barrier damage (TEWL), erythema, and histological alterations were evaluated. The results showed that the formulations containing the extract protected the skin against UV-induced damage. PMID:25133171

Reduction of hydrogen peroxide-induced erythrocyte damage by Carica papaya leaf extract

PubMed Central

Okoko, Tebekeme; Ere, Diepreye

2012-01-01

Objective To investigate the in vitro antioxidant potential of Carica papaya (C. papaya) leaf extract and its effect on hydrogen peroxide-induced erythrocyte damage assessed by haemolysis and lipid peroxidation. Methods Hydroxyl radical scavenging activities, hydrogen ion scavenging activity, metal chelating activity, and the ferrous ion reducing ability were assessed as antioxidant indices. In the other experiment, human erythrocytes were treated with hydrogen peroxide to induce erythrocyte damage. The extract (at various concentrations) was subsequently incubated with the erythrocytes and later analysed for haemolysis and lipid peroxidation as indices for erythrocyte damage. Results Preliminary investigation of the extract showed that the leaf possessed significant antioxidant and free radical scavenging abilities using in vitro models in a concentration dependent manner (P<0.05). The extract also reduced hydrogen peroxide induced erythrocyte haemolysis and lipid peroxidation significantly when compared with ascorbic acid (P<0.05). The IC50 values were 7.33 mg/mL and 1.58 mg/mL for inhibition of haemolysis and lipid peroxidation, respectively. In all cases, ascorbic acid (the reference antioxidant) possessed higher activity than the extract. Conclusions The findings show that C. papaya leaves possess significant bioactive potential which is attributed to the phytochemicals which act in synergy. Thus, the leaves can be exploited for pharmaceutical and nutritional purposes. PMID:23569948

Reduction of hydrogen peroxide-induced erythrocyte damage by Carica papaya leaf extract.

PubMed

Okoko, Tebekeme; Ere, Diepreye

2012-06-01

To investigate the in vitro antioxidant potential of Carica papaya (C. papaya) leaf extract and its effect on hydrogen peroxide-induced erythrocyte damage assessed by haemolysis and lipid peroxidation. Hydroxyl radical scavenging activities, hydrogen ion scavenging activity, metal chelating activity, and the ferrous ion reducing ability were assessed as antioxidant indices. In the other experiment, human erythrocytes were treated with hydrogen peroxide to induce erythrocyte damage. The extract (at various concentrations) was subsequently incubated with the erythrocytes and later analysed for haemolysis and lipid peroxidation as indices for erythrocyte damage. Preliminary investigation of the extract showed that the leaf possessed significant antioxidant and free radical scavenging abilities using in vitro models in a concentration dependent manner (P<0.05). The extract also reduced hydrogen peroxide induced erythrocyte haemolysis and lipid peroxidation significantly when compared with ascorbic acid (P<0.05). The IC50 values were 7.33 mg/mL and 1.58 mg/mL for inhibition of haemolysis and lipid peroxidation, respectively. In all cases, ascorbic acid (the reference antioxidant) possessed higher activity than the extract. The findings show that C. papaya leaves possess significant bioactive potential which is attributed to the phytochemicals which act in synergy. Thus, the leaves can be exploited for pharmaceutical and nutritional purposes.

Base excision repair: NMR backbone assignments of Escherichia coli formamidopyrimidine-DNA glycosylase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchko, Garry W.; Wallace, Susan S.; Kennedy, Michael A.

2002-03-01

Oxidative damage is emerging as one of the most important mechanisms responsible for mutagenesis, carcinogenesis, aging, and various diseases (Farr and Kogma, 1991). One of the potential targets for oxidation is cellular DNA. While exposure to exogenous agents, such as ionizing radiation and chemicals, contributes to damaging DNA, the most important oxidative agents are endogenous, such as the reactive free radicals produced during normal oxidative metabolism (Adelman et., 1988). To mitigate the potentially deleterious effects of oxidative DNA damage virtually all aerobic organisms have developed complex repair mechanisms (Petit and Sancar, 1999). One repair mechanism, base excision repair (BER), appearsmore » to be responsible for replacing most oxidative DNA damage (David and Williams, 1998). Formamidopyrimidine-DNA glycosylase (Fpg), a 269-residue metalloprotein with a molecular weight of 30.2 kDa, is a key BER enzyme in prokaryotes (Boiteaux et al., 1987). Substrates recognized and released by Fpg include 7,8-dihydro-8-oxoguanine (8-oxoG), 2,6 diamino-4-hydroxy-5-formamido pyrimidine (Fapy-G), the adenine equivalents 8-oxoA and Fapy-A, 5-hydroxycytosine, 5-hydroxyuracil, B ureidoisobutiric acid, and a-R-hydroxy-B-ureidoisobutiric acid (Freidberg et al., 1995). In vitro Fpg bind double-stranded DNA and performs three catalytic activities: (i) DNA glycosylase, (ii) AP lyase, and (iii) deoxyribophosphodiesterase.« less

Bubbly cavitating flow generation and investigation of its erosional nature for biomedical applications.

PubMed

Koşar, Ali; Şeşen, Muhsincan; Oral, Ozlem; Itah, Zeynep; Gozuacik, Devrim

2011-05-01

This paper presents a study that investigates the destructive energy output resulting from hydrodynamic bubbly cavitation in microchannels and its potential use in biomedical applications. The research performed in this study includes results from bubbly cavitation experiments and findings showing the destructive effects of bubbly cavitating flow on selected solid specimens and live cells. The bubbles generated by hydrodynamic cavitation are highly destructive at the surfaces of the target medium on which they are carefully focused. The resulting destructive energy output could be effectively used for biomedical treatments, such as destroying kidney stones (renal calculi) or killing cancer cells. Motivated by this potential, the cavitation damage to cancerous cells and material removal from chalk pieces (which possess similar material properties as some kidney stones) was investigated. Our results showed that cavitation could induce damage both on chalk pieces and leukemia/lymphoma cells. We discovered that hydrodynamic cavitation exposure had early and delayed effects on cancer cell survival. Hence, the potential of hydrodynamic bubbly cavitation generated at the microscale for biomedical treatments was revealed using the microchannel configuration as a microorifice (with an inner diameter of 147 μm and a length of 1.52 cm), which acts as the source of bubbly cavitating flows. © 2011 IEEE

STRUCTURAL INTEGRITY MONITORING FOR IMPROVED DRINKING WATER INFRASTRUCTURE SUSTAINABILITY

EPA Science Inventory

Structural integrity monitoring (SIM) is the systematic detection, location, and quantification of pipe wall damage or associated indicators. Each of the adverse situations below has the potential to be reduced by more effective and economical SIM of water mains:
1) the dr...

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects

PubMed Central

Darwazeh, Rami; Yan, Yi

2013-01-01

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study. PMID:25206579

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects.

PubMed

Darwazeh, Rami; Yan, Yi

2013-10-05

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

Nano-antioxidants: An emerging strategy for intervention against neurodegenerative conditions.

PubMed

Sandhir, Rajat; Yadav, Aarti; Sunkaria, Aditya; Singhal, Nitin

2015-10-01

Oxidative stress has for long been linked to the neuronal cell death in many neurodegenerative conditions. Conventional antioxidant therapies have been less effective in preventing neuronal damage caused by oxidative stress due to their inability to cross the blood brain barrier. Nanoparticle antioxidants constitute a new wave of antioxidant therapies for prevention and treatment of diseases involving oxidative stress. It is believed that nanoparticle antioxidants have strong and persistent interactions with biomolecules and would be more effective against free radical induced damage. Nanoantioxidants include inorganic nanoparticles possessing intrinsic antioxidant properties, nanoparticles functionalized with antioxidants or antioxidant enzymes to function as an antioxidant delivery system. Nanoparticles containing antioxidants have shown promise as high-performance therapeutic nanomedicine in attenuating oxidative stress with potential applications in treating and preventing neurodegenerative conditions. However, to realize the full potential of nanoantioxidants, negative aspects associated with the use of nanoparticles need to be overcome to validate their long term applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Potential Protective Effects of 2-aminoethyl Diphenylborinate against Inner Ear Acoustic Trauma: Experimental Study Using Transmission and Scanning Electron Microscopy.

PubMed

Kaymakçı, Mustafa; Acar, Mustafa; Burukoglu, Dilek; Kutlu, Hatice Mehtap; Shojaolsadati, Paria; Cingi, Cemal; Bayar Muluk, Nuray

2015-04-01

In this prospective experimental study, we investigated the preventive effects of 2-aminoethyl diphenylborinate (2-APB) in rats exposed to acoustic trauma (AT). Light microscopic, transmission electron microscopic (TEM), and scanning electron microscopic (SEM) examinations were performed. Eighteen healthy Wistar albino rats were divided into the following three groups: groups 1 (control), 2 (AT), and 3 (AT+APB). The rats in groups 2 and 3 were exposed to AT; in group 3 rats, 2-APB at 2 mg/kg was also administered, initially transperitoneally, after 10 min. During the light microscopic, TEM, and SEM examinations, the structures of the cochlear hair cells, stereocilia, and Deiter's cells were normal in the control group. In the AT group, the organ of Corti and proximate structures were damaged according to the light microscopic examination. During the TEM examination, intense cellular damage and stereocilia loss were detected, while during the SEM examination, extensive damage and stereocilia loss were observed. Decreased damage with preserved cochlear structure was detected during the light microscopic examination in the AT+APB group than in the AT group. During the TEM and SEM examinations, although stereocilia loss occurred in the AT+APB group, near-normal cell, cilia, and tectorial membrane structures were also observed in the AT+APB group compared with the AT group. 2-APB may have protective effects against AT damage of the cochlea. The main mechanism underlying this effect is the inhibition of the vasoconstriction of the cochlear spiral modiolar artery, thereby improving cochlear blood flow. We conclude that 2-APB may also be effective if used immediately following AT.

Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?

PubMed

Sanchis-Gomar, F; Pareja-Galeano, H; Perez-Quilis, C; Santos-Lozano, A; Fiuza-Luces, C; Garatachea, N; Lippi, G; Lucia, A

2015-01-01

Intensive muscular activity can trigger oxidative stress, and free radicals may hence be generated by working skeletal muscle. The role of the enzyme xanthine oxidase as a generating source of free radicals is well documented and therefore is involved in the skeletal muscle damage as well as in the potential transient cardiovascular damage induced by high-intensity physical exercise. Allopurinol is a purine hypoxanthine-based structural analog and a well-known inhibitor of xanthine oxidase. The administration of the xanthine oxidase inhibitor allopurinol may hence be regarded as promising, safe, and an economic strategy to decrease transient skeletal muscle damage (as well as heart damage, when occurring) in top-level athletes when administered before a competition or a particularly high-intensity training session. Although continuous administration of allopurinol in high-level athletes is not recommended due to its possible role in hampering training-induced adaptations, the drug might be useful in non-athletes. Exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals participating in a type of intense exercise to which they are not accustomed. This condition can cause exercise-related myoglobinuria, thus increasing the risk of acute renal failure and is also associated with sickle cell trait. In this manuscript, we have reviewed the recent evidence about the effects of allopurinol on exercise-induced muscle damage. More research is needed to determine whether allopurinol may be useful for preventing not only exertional rhabdomyolysis and acute renal damage but also skeletal muscle wasting in critical illness as well as in immobilized, bedridden, sarcopenic or cachectic patients.

Moderate acute intake of de-alcoholized red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo -- results of a comparative in vivo intervention study in younger men.

PubMed

Greenrod, W; Stockley, C S; Burcham, P; Abbey, M; Fenech, M

2005-12-11

Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, de-alcoholized red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of de-alcoholized red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R=-0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin.

Probiotic Bacillus coagulans GBI-30, 6086 reduces exercise-induced muscle damage and increases recovery

PubMed Central

Jäger, Ralf; Shields, Kevin A.; Lowery, Ryan P.; De Souza, Eduardo O.; Partl, Jeremy M.; Hollmer, Chase; Purpura, Martin

2016-01-01

Objective. Probiotics have been reported to support healthy digestive and immune function, aid in protein absorption, and decrease inflammation. Further, a trend to increase vertical jump power has been observed following co-administration of protein and probiotics in resistance-trained subjects. However, to date the potential beneficial effect of probiotics on recovery from high intensity resistance exercise have yet to be explored. Therefore, this study examined the effect of co-administration of protein and probiotics on muscle damage, recovery and performance following a damaging exercise bout. Design. Twenty nine (n = 29) recreationally-trained males (mean ± SD; 21.5 ± 2.8 years; 89.7 ± 28.2 kg; 177.4 ± 8.0 cm) were assigned to consume either 20 g of casein (PRO) or 20 g of casein plus probiotic (1 billion CFU Bacillus coagulans GBI-30, 6086, PROBC) in a crossover, diet-controlled design. After two weeks of supplementation, perceptional measures, athletic performance, and muscle damage were analyzed following a damaging exercise bout. Results. The damaging exercise bout significantly increased muscle soreness, and reduced perceived recovery; however, PROBC significantly increased recovery at 24 and 72 h, and decreased soreness at 72 h post exercise in comparison to PRO. Perceptual measures were confirmed by increases in CK (PRO: +266.8%, p = 0.0002; PROBC: +137.7%, p = 0.01), with PROBC showing a trend towards reduced muscle damage (p = 0.08). The muscle-damaging exercise resulted in significantly increased muscle swelling and Blood Urea Nitrogen levels in both conditions with no difference between groups. The strenuous exercise significantly reduced athletic performance in PRO (Wingate Peak Power; PRO: (−39.8 watts, −5.3%, p = 0.03)), whereas PROBC maintained performance (+10.1 watts, +1.7%). Conclusions. The results provide evidence that probiotic supplementation in combination with protein tended to reduce indices of muscle damage, improves recovery, and maintains physical performance subsequent to damaging exercise. PMID:27547577

[Dose rate-dependent cellular and molecular effects of ionizing radiation].

PubMed

Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

2008-09-11

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

Antitumor Effects of Palladium-α-Lipoic Acid Complex Formulation as an Adjunct in Radiotherapy.

PubMed

Veena, Ravindran Kalathil; Ajith, Thekkuttuparambil Ananthanarayanan; Janardhanan, Kainoor Krishnankutty; Antonawich, Francis

2016-01-01

Several investigations have been initiated to enhance the antitumor effect of radiation and ameliorate its adverse effects such as reducing blood cell counts and causing DNA damage in normal cells. Compounds that enhance the antitumor activity of radiation without reducing blood cell counts or damaging DNA in normal cells can be of immense use as an adjunct in radiotherapy. We evaluated the antitumor effect of a specific set of minerals, vitamins, and amino acids (Poly-MVA) (2 mL/kg, per os), with and without radiation, against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines that were transplanted in a solid-tumor model. Whole-body γ-radiation exposure (2 Gy) was performed using 60Co. Poly-MVA enhanced the antitumor effect of radiation when administered beforehand. Furthermore, Poly-MVA administered once daily for 2 wk, immediately after 4 Gy irradiation, protected DNA damage in peripheral blood. It also rendered protection against the radiation-induced reduction of platelet count. The unique electronic and redox properties of palladium-α-lipoic acid complex in Poly-MVA appear to be responsible for the exhibited effect. The results conclude that the antitumor-enhancing and normal cell-protective effect of Poly-MVA warrants additional studies for its potential clinical application.

Modeling Space Radiation with Radiomimetic Agent Bleomycin

NASA Technical Reports Server (NTRS)

Lu, Tao

2017-01-01

Space radiation consists of proton and helium from solar particle events (SPE) and high energy heavy ions from galactic cosmic ray (GCR). This mixture of radiation with particles at different energy levels has different effects on biological systems. Currently, majority studies of radiation effects on human were based on single-source radiation due to the limitation of available method to model effects of space radiation on living organisms. While NASA Space Radiation Laboratory is working on advanced switches to make it possible to have a mixed field radiation with particles of different energies, the radiation source will be limited. Development of an easily available experimental model for studying effects of mixed field radiation could greatly speed up our progress in our understanding the molecular mechanisms of damage and responses from exposure to space radiation, and facilitate the discovery of protection and countermeasures against space radiation, which is critical for the mission to Mars. Bleomycin, a radiomimetic agent, has been widely used to study radiation induced DNA damage and cellular responses. Previously, bleomycin was often compared to low low Linear Energy Transfer (LET) gamma radiation without defined characteristics. Our recent work demonstrated that bleomycin could induce complex clustered DNA damage in human fibroblasts that is similar to DNA damage induced by high LET radiation. These type of DNA damage is difficult to repair and can be visualized by gamma-H2Ax staining weeks after the initial insult. The survival ratio between early and late plating of human fibroblasts after bleomycin treatment is between low LET and high LET radiation. Our results suggest that bleomycin induces DNA damage and other cellular stresses resembling those resulted from mixed field radiation with both low and high LET particles. We hypothesize that bleomycin could be used to mimic space radiation in biological systems. Potential advantages and limitations of using bleomycin to treat biological specimen as an easily available model to study effects of space radiation on biological systems and to develop countermeasures for space radiation associated risks will be discussed.

In vivo evaluation of the genetic toxicity of Rubus niveus Thunb. (Rosaceae) extract and initial screening of its potential chemoprevention against doxorubicin-induced DNA damage.

PubMed

Tolentino, Flora; Araújo, Priscila Alves de; Marques, Eduardo de Souza; Petreanu, Marcel; Andrade, Sérgio Faloni de; Niero, Rivaldo; Perazzo, Fábio F; Rosa, Paulo César Pires; Maistro, Edson Luis

2015-04-22

Rubus niveus Thunb. plant belongs to Rosaceae family and have been used traditionally to treat wounds, burns, inflammation, dysentery, diarrhea and for curing excessive bleeding during menstrual cycle. The present study was undertaken to investigate the in vivo genotoxicity of Rubus niveus aerial parts extract and its possible chemoprotection on doxorubicin (DXR)-induced DNA damage. In parallel, the main phytochemicals constituents in the extract were determined. The animals were exposed to the extract for 24 and 48 h, and the doses selected were 500, 1000 and 2000 mg/kg b.w. administered by gavage alone or prior to DXR (30 mg/kg b.w.) administered by intraperitoneal injection. The endpoints analyzed were DNA damage in bone marrow and peripheral blood cells assessed by the alkaline alkaline (pH>13) comet assay and bone marrow micronucleus test. The results of chemical analysis of the extract showed the presence of tormentic acid, stigmasterol, quercitinglucoronide (miquelianin) and niga-ichigoside F1 as main compounds. Both cytogenetic endpoints analyzed showed that there were no statistically significant differences (p>0.05) between the negative control and the treated groups with the two higher doses of Rubus niveus extract alone, demonstrating absence of genotoxic and mutagenic effects. Aneugenic/clastogenic effect was observed only at 2000 mg/kg dose. On the other hand, in the both assays and all tested doses were observed a significant reduction of DNA damage and chromosomal aberrations in all groups co-treated with DXR and extract compared to those which received only DXR. These results indicate that Rubus niveus aerial parts extract did not revealed any genotoxic effect, but presented some aneugenic/clastogenic effect at higher dose; and suggest that it could be a potential adjuvant against development of second malignant neoplasms caused by the cancer chemotherapic DXR. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.

PubMed

Bisht, Rohit; Joshi, Bhuwan Chandra; Kalia, Ajudhiya Nath; Prakash, Atish

2017-09-01

Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-β) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich fraction of UD contain flavonoids and phenolic compounds, which have a promising approach in therapeutics of PD.

Evaluation of truncation error and adaptive grid generation for the transonic full potential flow calculations

NASA Technical Reports Server (NTRS)

Nakamura, S.

1983-01-01

The effects of truncation error on the numerical solution of transonic flows using the full potential equation are studied. The effects of adapting grid point distributions to various solution aspects including shock waves is also discussed. A conclusion is that a rapid change of grid spacing is damaging to the accuracy of the flow solution. Therefore, in a solution adaptive grid application an optimal grid is obtained as a tradeoff between the amount of grid refinement and the rate of grid stretching.

PAXIP1 potentiates the combination of WEE1 inhibitor AZD1775 and platinum agents in lung cancer

PubMed Central

Jhuraney, Ankita; Woods, Nicholas T.; Wright, Gabriela; Rix, Lily; Kinose, Fumi; Kroeger, Jodi L.; Remily-Wood, Elizabeth; Cress, W. Douglas; Koomen, John M.; Brantley, Stephen G.; Gray, Jhanelle E.; Haura, Eric B.; Rix, Uwe; Monteiro, Alvaro N.

2016-01-01

The DNA damage response (DDR) involves a complex network of signaling events mediated by modular protein domains such as the BRCT (BRCA1 C-terminal) domain. Thus, proteins that interact with BRCT domains and are a part of the DDR constitute potential targets for sensitization to DNA damaging chemotherapy agents. We performed a pharmacological screen to evaluate seventeen kinases, identified in a BRCT-mediated interaction network as targets to enhance platinum-based chemotherapy in lung cancer. Inhibition of mitotic kinase WEE1 was found to have the most effective response in combination with platinum compounds in lung cancer cell lines. In the BRCT-mediated interaction network, WEE1 was found in complex with PAXIP1, a protein containing six BRCT domains involved in transcription and in the cellular response to DNA damage. We show that PAXIP1 BRCT domains regulate WEE1-mediated phosphorylation of CDK1. Further, ectopic expression of PAXIP1 promotes enhanced caspase 3-mediated apoptosis in cells treated with WEE1 inhibitor AZD1775 (formerly, MK-1775) and cisplatin compared with cells treated with AZD1775 alone. Cell lines and patient-derived xenograft models expressing both PAXIP1 and WEE1 exhibited synergistic effects of AZD1775 and cisplatin. In summary, PAXIP1 is involved in sensitizing lung cancer cells to the WEE1 inhibitor AZD1775 in combination with platinum-based treatment. We propose that WEE1 and PAXIP1 levels may be used as mechanism-based biomarkers of response when WEE1 inhibitor AZD1775 is combined with DNA damaging agents. PMID:27196765

Evaluation of the genotoxic potential of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites, glycidol and beta-chlorolactic acid, using the single cell gel/comet assay.

PubMed

El Ramy, R; Ould Elhkim, M; Lezmi, S; Poul, J M

2007-01-01

3-monochloropropane-1,2-diol (3-MCPD) is a member of a group of chemicals known as chloropropanols. It is found in many foods and food ingredients as a result of food processing. 3-MCPD is regarded as a rat carcinogen known to induce Leydig-cell and mammary gland tumours in males and kidney tumours in both genders. The aim of our study was to clarify the possible involvement of genotoxic mechanisms in 3-MCPD induced carcinogenicity at the target organ level. For that purpose, we evaluated DNA damages in selected target (kidneys and testes) and non-target (blood leukocytes, liver and bone marrow) male rat organs by the in vivo alkaline single cell gel electrophoresis (comet) assay, 3 and 24 h after 3-MCPD oral administration to Sprague-Dawley and Fisher 344 adult rats. 3-MCPD may be metabolised to a genotoxic intermediate, glycidol, whereas the predominant urinary metabolite in rats following 3-MCPD administration is beta-chlorolactic acid. Therefore, we also studied the DNA damaging effects of 3-MCPD and its metabolites, glycidol and beta-chlorolactic acid, in the in vitro comet assay on CHO cells. Our results show the absence of genotoxic potential of 3-MCPD in vivo in the target as well as in the non-target organs. Glycidol, the epoxide metabolite, induced DNA damages in CHO cells. beta-Chlorolactic acid, the main metabolite of 3-MCPD in rats, was shown to be devoid of DNA-damaging effects in vitro in mammalian cells.

Post-head-emergence frost in wheat and barley: defining the problem, assessing the damage, and identifying resistance.

PubMed

Frederiks, T M; Christopher, J T; Sutherland, M W; Borrell, A K

2015-06-01

Radiant frost is a significant production constraint to wheat (Triticum aestivum) and barley (Hordeum vulgare), particularly in regions where spring-habit cereals are grown through winter, maturing in spring. However, damage to winter-habit cereals in reproductive stages is also reported. Crops are particularly susceptible to frost once awns or spikes emerge from the protection of the flag leaf sheath. Post-head-emergence frost (PHEF) is a problem distinct from other cold-mediated production constraints. To date, useful increased PHEF resistance in cereals has not been identified. Given the renewed interest in reproductive frost damage in cereals, it is timely to review the problem. Here we update the extent and impacts of PHEF and document current management options to combat this challenge. We clarify terminology useful for discussing PHEF in relation to chilling and other freezing stresses. We discuss problems characterizing radiant frost, the environmental conditions leading to PHEF damage, and the effects of frost at different growth stages. PHEF resistant cultivars would be highly desirable, to both reduce the incidence of direct frost damage and to allow the timing of crop maturity to be managed to maximize yield potential. A framework of potential adaptation mechanisms is outlined. Clarification of these critical issues will sharpen research focus, improving opportunities to identify genetic sources for improved PHEF resistance. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Characterization of the damage of Spodoptera eridania (Cramer) and Spodoptera cosmioides (Walker) (Lepidoptera: Noctuidae) to structures of cotton plants].

PubMed

Santos, Karen B Dos; Meneguim, Ana M; Santos, Walter J Dos; Neves, Pedro M O J; Santos, Rachel B Dos

2010-01-01

The cotton plant, Gossypium hirsutum, hosts various pests that damage different structures. Among these pests, Spodoptera cosmioides (Walker) and Spodoptera eridania (Cramer) (Lepidoptera: Noctuidae) are considered important. The objectives of this study were to characterize and to quantify the potential damage of S. eridania and S. cosmioides feeding on different structures of cotton plants. For this purpose, newly-hatched larvae were reared on the following plant parts: leaf and flower bud; leaf and boll; flower bud or boll; and leaf, flower bud and boll. The survival of S. cosmioides and S. eridania was greater than 80% and 70% for larvae fed on cotton plant parts offered separately or together, respectively. One larva of S. eridania damaged 1.7 flower buds, but did not damage bolls, while one larva of S. cosmioides damaged 5.2 flower buds and 3.0 cotton bolls. Spodoptera eridania and S. cosmioides can be considered species with potential to cause economic damage to cotton plants because they can occur throughout cotton developmental stages causing defoliation and losses of reproductive structures. Therefore, the results validate field observations that these two species of Spodoptera are potential pests for cotton.

Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides.

PubMed

Zitnay, Jared L; Li, Yang; Qin, Zhao; San, Boi Hoa; Depalle, Baptiste; Reese, Shawn P; Buehler, Markus J; Yu, S Michael; Weiss, Jeffrey A

2017-03-22

Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury.

Effects of forest road amelioration techniques on soil bulk density, surface runoff, sediment transport, soil moisture and seedling growth

Treesearch

Randy K. Kolka; Mathew F. Smidt

2004-01-01

Although numerous methods have been used to retire roads, new technologies have evolved that can potentially ameliorate soil damage, lessen ,the generation of nonpoint source pollution and increase tree productivity on forest roads. In this study we investigated the effects of three forest road amelioration techniques, subsoiling, recontouring and traditional...

Spruce aphid, Elatobium abietinum (Walker): Life history and damage to Engelmann spruce in the Pinaleno Mountains, Arizona

Treesearch

Ann M. Lynch

2009-01-01

Spruce aphid is an exotic insect recently introduced to the Pinaleno Mountains. It feeds on dormant Engelmann spruce, and possible effects include tree-growth suppression, tree mortality, and reduction in seed and cone production. Potential longer-term effects include changes in forest structure and species composition - primarily through reduction in Engelmann spruce...

The Role of Gap Junction Communication and Oxidative Stress in the Propagation of Toxic Effects among High-Dose α-Particle-Irradiated Human Cells

PubMed Central

Autsavapromporn, Narongchai; de Toledo, Sonia M.; Little, John B.; Jay-Gerin, Jean-Paul; Harris, Andrew L.; Azzam, Edouard I.

2011-01-01

We investigated the roles of gap junction communication and oxidative stress in modulating potentially lethal damage repair in human fibroblast cultures exposed to doses of α particles or γ rays that targeted all cells in the cultures. As expected, α particles were more effective than γ rays at inducing cell killing; further, holding γ-irradiated cells in the confluent state for several hours after irradiation promoted increased survival and decreased chromosomal damage. However, maintaining α-particle-irradiated cells in the confluent state for various times prior to subculture resulted in increased rather than decreased lethality and was associated with persistent DNA damage and increased protein oxidation and lipid peroxidation. Inhibiting gap junction communication with 18-α-glycyrrhetinic acid or by knockdown of connexin43, a constitutive protein of junctional channels in these cells, protected against the toxic effects in α-particle-irradiated cell cultures during confluent holding. Upregulation of antioxidant defense by ectopic overexpression of glutathione peroxidase protected against cell killing by α particles when cells were analyzed shortly after exposure. However, it did not attenuate the decrease in survival during confluent holding. Together, these findings indicate that the damaging effect of α particles results in oxidative stress, and the toxic effects in the hours after irradiation are amplified by intercellular communication, but the communicated molecule(s) is unlikely to be a substrate of glutathione peroxidase. PMID:21388278

Introducing ShakeMap to potential users in Puerto Rico using scenarios of damaging historical and probable earthquakes

NASA Astrophysics Data System (ADS)

Huerfano, V. A.; Cua, G.; von Hillebrandt, C.; Saffar, A.

2007-12-01

The island of Puerto Rico has a long history of damaging earthquakes. Major earthquakes from off-shore sources have affected Puerto Rico in 1520, 1615, 1670, 1751, 1787, 1867, and 1918 (Mueller et al, 2003; PRSN Catalogue). Recent trenching has also yielded evidence of possible M7.0 events inland (Prentice, 2000). The high seismic hazard, large population, high tsunami potential and relatively poor construction practice can result in a potentially devastating combination. Efficient emergency response in event of a large earthquake will be crucial to minimizing the loss of life and disruption of lifeline systems in Puerto Rico. The ShakeMap system (Wald et al, 2004) developed by the USGS to rapidly display and disseminate information about the geographical distribution of ground shaking (and hence potential damage) following a large earthquake has proven to be a vital tool for post earthquake emergency response efforts, and is being adopted/emulated in various seismically active regions worldwide. Implementing a robust ShakeMap system is among the top priorities of the Puerto Rico Seismic Network. However, the ultimate effectiveness of ShakeMap in post- earthquake response depends not only on its rapid availability, but also on the effective use of the information it provides. We developed ShakeMap scenarios of a suite of damaging historical and probable earthquakes that severely impact San Juan, Ponce, and Mayagüez, the 3 largest cities in Puerto Rico. Earthquake source parameters were obtained from McCann and Mercado (1998); and Huérfano (2004). For historical earthquakes that generated tsunamis, tsunami inundation maps were generated using the TIME method (Shuto, 1991). The ShakeMap ground shaking maps were presented to local and regional governmental and emergency response agencies at the 2007 Annual conference of the Puerto Rico Emergency Management and Disaster Administration in San Juan, PR, and at numerous other emergency management talks and training sessions. Economic losses are estimated using the ShakeMap scenario ground motions (Saffar, 2007). The calibration tasks necessary in generating these scenarios (developing Vs30 maps, attenuation relationships) complement the on-going efforts of the Puerto Rico Seismic Network to generate ShakeMaps in real-time.

Potential hepatoprotective effects of new Cuban natural products in rat hepatocytes culture.

PubMed

Rodeiro, I; Donato, M T; Martínez, I; Hernández, I; Garrido, G; González-Lavaut, J A; Menéndez, R; Laguna, A; Castell, J V; Gómez-Lechón, M J

2008-08-01

The protective effects of five Cuban natural products (Mangifera indica L. (MSBE), Erythroxylum minutifolium, Erythroxylum confusum, Thalassia testudinum and Dictyota pinnatifida extracts and mangiferin) on the oxidative damage induced by model toxicants in rat hepatocyte cultures were studied. Cells were pre-incubated with the natural products (5-200 microg/mL) for 24 h. Then hepatotoxins (tert-butyl hydroperoxide, ethanol, carbon tetrachloride and lipopolysaccharide) were individually added and post-incubated for another 24 h. After treatments, cell viability was determined using the MTT assay. Mangiferin and MSBE exhibited the highest cytoprotective potential (EC50 between 50 and 125 microg/mL), followed by T. testudinum and Erythroxylum extracts, whereas no significant protective effects was produced by Dictyota extract treatment. Antioxidant properties of the natural products against lipid peroxidation and GSH depletion induced by tert-butyl hydroperoxide were then investigated. The results show that at 36 h pre-treatment of cells with mangiferin or MSBE, concentrations of T. testudinum and Erythroxylum extracts ranging from 25 to 100 microg/mL significantly inhibited lipid peroxidation induced by tert-butyl hydroperoxide (100 and 250 microM) and increased the GSH levels reduced by the toxicant. D. pinnatifida inhibited lipid peroxidation, but did not preserve GSH levels. In conclusion, MSBE, E. minutifolium, E. confusum and T. testudinum extracts and mangiferin showed hepatoprotective activity against induced damage in all the experimental series, where mangiferin and the extracts of MSBE and T. testudinum were the best candidates to inhibit "in vitro" damage to rat hepatocytes. This hepatoprotective effect found could be associated with the antioxidant properties observed for the products.

Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arriba, G. de; Seccion de Nefrologia del Hospital Universitario de Guadalajara; Departamento de Medicina de la Universidad de Alcala de Henares

Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry andmore » confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondria.« less

School attendance and daily respiratory symptoms in children: influence of moisture damage.

PubMed

Casas, L; Espinosa, A; Pekkanen, J; Asikainen, A; Borràs-Santos, A; Jacobs, J; Krop, E J M; Täubel, M; Hyvärinen, A; Heederik, D; Zock, J-P

2017-03-01

We investigated the effect of weekends and school holidays on the daily frequency and severity of respiratory and other symptoms among children attending schools with (index) or without (reference) moisture damage in Spain, the Netherlands, and Finland. Throughout 1 year, parents of 419 children with a respiratory condition attending index (n=15) or reference (n=10) primary schools completed three symptom diaries. We assessed associations between lower respiratory tract, upper respiratory tract or allergy, and other symptom scores and school day, weekend, or summer holiday using mixed regression models stratified by country and moisture damage. We evaluated interactions between moisture damage and type of day. We combined country-specific estimates (incidence rate ratios [IRRs] and 95% confidence interval [CI]) in meta-analyses. Symptom scores were lower during weekends and holiday. Lower respiratory tract symptoms were statistically significantly less common during holiday with strongest effect in index schools (IRR=0.7; CI=0.6-0.8). Reporting of other symptoms was more reduced during holiday in index (IRR=0.6; CI=0.4-0.9) than in reference (IRR=0.95; CI=0.8-1.2) schools (interaction P<.01). In conclusion, symptoms were less frequent and/or severe during summer holiday and weekends. This pattern was stronger among children attending moisture-damaged schools, suggesting potential improvement in moisture damage-related symptoms during school breaks. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nano-sized fractions.

PubMed

Proquin, Héloïse; Rodríguez-Ibarra, Carolina; Moonen, Carolyn G J; Urrutia Ortega, Ismael M; Briedé, Jacob J; de Kok, Theo M; van Loveren, Henk; Chirino, Yolanda I

2017-01-01

Since 1969, the European Union approves food-grade titanium dioxide (TiO 2 ), also known as E171 colouring food additive. E171 is a mixture of micro-sized particles (MPs) and nano-sized particles (NPs). Previous studies have indicated adverse effects of oral exposure to E171, i.e. facilitation of colon tumour growth. This could potentially be partially mediated by the capacity to induce reactive oxygen species (ROS). The aim of the present study is to determine whether E171 exposure induces ROS formation and DNA damage in an in vitro model using human Caco-2 and HCT116 cells and to investigate the contribution of the separate MPs and NPs TiO 2 fractions to these effects. After suspension of the particles in Hanks' balanced salt solution buffer and cell culture medium with either bovine serum albumin (BSA) or foetal bovine serum, characterization of the particles was performed by dynamic light scattering, ROS formation was determined by electron spin/paramagnetic resonance spectroscopy and DNA damage was determined by the comet and micronucleus assays. The results showed that E171, MPs and NPs are stable in cell culture medium with 0.05% BSA. The capacity for ROS generation in a cell-free environment was highest for E171, followed by NPs and MPs. Only MPs were capable to induce ROS formation in exposed Caco-2 cells. E171, MPs and NPs all induced single-strand DNA breaks. Chromosome damage was shown to be induced by E171, as tested with the micronucleus assay in HCT116 cells. In conclusion, E171 has the capability to induce ROS formation in a cell-free environment and E171, MPs and NPs have genotoxic potential. The capacity of E171 to induce ROS formation and DNA damage raises concerns about potential adverse effects associated with E171 (TiO 2 ) in food. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Assessment of DNA damage in a group of professional dancers during a 10-month dancing season.

PubMed

Esteves, Filipa; Teixeira, Eduardo; Amorim, Tânia; Costa, Carla; Pereira, Cristiana; Fraga, Sónia; De Andrade, Vanessa Moraes; Teixeira, João Paulo; Costa, Solange

2017-01-01

Despite the numerous health benefits of physical activity, some studies reported that increased intensity and duration may induce oxidative stress in several cellular components including DNA. The aim of this study was to assess the level of basal DNA damage as well as oxidative DNA damage in a group of professional dancers before and after a 10-month dancing season. A group of individuals from general population was also assessed as a control. The alkaline version of the comet assay was the method selected to measure both basal DNA damage and oxidative stress, since this method quantifies both endpoints. In order to measure oxidative stress, the comet assay was coupled with a lesion-specific endonuclease (formamidopyrimidine glycosylase) to detect oxidized purines. The levels of oxidative DNA damage in dancers were significantly increased after the dancing season. Pre-season levels of oxidative DNA damage were lower in dancers than those obtained from the general population, suggesting an adaptation of antioxidant system in dancers. Results of the present biomonitoring study indicate the need for more effective measures to protect ballet dancers from potentially occupational health risks related to regular intensive physical exercise.

Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury.

PubMed

Adlam, Victoria J; Harrison, Joanne C; Porteous, Carolyn M; James, Andrew M; Smith, Robin A J; Murphy, Michael P; Sammut, Ivan A

2005-07-01

Mitochondrial oxidative damage contributes to a wide range of pathologies, including cardiovascular disorders and neurodegenerative diseases. Therefore, protecting mitochondria from oxidative damage should be an effective therapeutic strategy. However, conventional antioxidants have limited efficacy due to the difficulty of delivering them to mitochondria in situ. To overcome this problem, we developed mitochondria-targeted antioxidants, typified by MitoQ, which comprises a lipophilic triphenylphosphonium (TPP) cation covalently attached to a ubiquinol antioxidant. Driven by the large mitochondrial membrane potential, the TPP cation concentrates MitoQ several hundred-fold within mitochondria, selectively preventing mitochondrial oxidative damage. To test whether MitoQ was active in vivo, we chose a clinically relevant form of mitochondrial oxidative damage: cardiac ischemia-reperfusion injury. Feeding MitoQ to rats significantly decreased heart dysfunction, cell death, and mitochondrial damage after ischemia-reperfusion. This protection was due to the antioxidant activity of MitoQ within mitochondria, as an untargeted antioxidant was ineffective and accumulation of the TPP cation alone gave no protection. Therefore, targeting antioxidants to mitochondria in vivo is a promising new therapeutic strategy in the wide range of human diseases such as Parkinson's disease, diabetes, and Friedreich's ataxia where mitochondrial oxidative damage underlies the pathology.

Evaluation of cytotoxic, membrane, and DNA damaging effects of Thymus revolutus Célak essential oil on different cancer cells.

PubMed

Özkan, Aysun; Erdoğan, Ayşe

2017-04-18

In this study, we evaluated Thymus revolutus Célak essential oil and its two main constituents, γ-terpinene and p-cymene, as potential oxidative agents against lung cancer and epidermoid carcinoma cells. Cell viability assessment was made by CellTiter-Blue1397904493 cell viability and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after treatment with 5-600 μg/mL concentrations of essential oil, γ-terpinene, and p-cymene. Malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels in parental H1299, epirubicin-resistant (drug-resistant) H1299, A549, and A431 cells were also assayed after essential oil, γ-terpinene, and p-cymene had been administered for 24 h. Glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GRx), and glucose 6-phosphate dehydrogenase (G6PD) activities were determined. Parental H1299 cells were found to be more sensitive to the cytotoxic effects of all compounds. While A431 cells had the highest membrane damage, which was caused by essential oil (IC 50 and IC 70 ), A549 cells had the highest DNA damage at IC 50 and IC 70 p-cymene concentrations. G6PD, GST, GRx, and GPx enzyme activities of cells, which increased against these compounds, depended on concentrations, incubation times, and antioxidant capacities of the cells. This study suggests that different cancer cells showed different cellular responses against potential antitumor and prooxidative effects of the essential oil and its two main constituents.

Round window administration of gentamicin: a new method for the study of ototoxicity of cochlear hair cells.

PubMed

Husmann, K R; Morgan, A S; Girod, D A; Durham, D

1998-11-01

Damage to inner ear sensory hair cells after systemic administration of ototoxic drugs has been documented in humans and animals. Birds have the ability to regenerate new hair cells to replace those damaged by drugs or noise. Unfortunately, the systemic administration of gentamicin damages both ears in a variable fashion with potentially confounding systemic drug effects. We developed a method of direct application of gentamicin to one cochlea of hatchling chickens, allowing the other ear to serve as a within-animal control. We tested variables including the vehicle for application, location of application, dosage, and duration of gentamicin exposure. After 5 or 28 days survival, the percent length damage to the cochlea and regeneration of hair cells was evaluated using scanning electron microscopy. Controls consisted of the opposite unexposed cochlea and additional animals which received saline instead of gentamicin. Excellent damage was achieved using gentamicin-soaked Gelfoam pledgets applied to the round window membrane. The percent length damage could be varied from 15 to 100% by changing the dosage of gentamicin, with exposures as short as 30 min. No damage was observed in control animals. Regeneration of hair cells was observed in both the base and apex by 28 days survival.

Do native parasitic plants cause more damage to exotic invasive hosts than native non-invasive hosts? An implication for biocontrol.

PubMed

Li, Junmin; Jin, Zexin; Song, Wenjing

2012-01-01

Field studies have shown that native, parasitic plants grow vigorously on invasive plants and can cause more damage to invasive plants than native plants. However, no empirical test has been conducted and the mechanism is still unknown. We conducted a completely randomized greenhouse experiment using 3 congeneric pairs of exotic, invasive and native, non-invasive herbaceous plant species to quantify the damage caused by parasitic plants to hosts and its correlation with the hosts' growth rate and resource use efficiency. The biomass of the parasitic plants on exotic, invasive hosts was significantly higher than on congeneric native, non-invasive hosts. Parasites caused more damage to exotic, invasive hosts than to congeneric, native, non-invasive hosts. The damage caused by parasites to hosts was significantly positively correlated with the biomass of parasitic plants. The damage of parasites to hosts was significantly positively correlated with the relative growth rate and the resource use efficiency of its host plants. It may be the mechanism by which parasitic plants grow more vigorously on invasive hosts and cause more damage to exotic, invasive hosts than to native, non-invasive hosts. These results suggest a potential biological control effect of native, parasitic plants on invasive species by reducing the dominance of invasive species in the invaded community.

Dampness and Moisture Problems in Norwegian Homes

PubMed Central

Becher, Rune; Høie, Anja Hortemo; Bakke, Jan Vilhelm; Holøs, Sverre Bjørn; Øvrevik, Johan

2017-01-01

The occurrence of dampness and mold in the indoor environment is associated with respiratory-related disease outcomes. Thus, it is pertinent to know the magnitude of such indoor environment problems to be able to estimate the potential health impact in the population. In the present study, the moisture damage in 10,112 Norwegian dwellings was recorded based on building inspection reports. The levels of moisture damage were graded based on a condition class (CC), where CC0 is immaculate and CC1 acceptable (actions not required), while CC2 and CC3 indicate increased levels of damage that requires action. Of the 10,112 dwellings investigated, 3125 had verified moisture or mold damage. This amounts to 31% of the surveyed dwellings. Of these, 27% had CC2 as the worst grade, whereas 4% had CC3 as the worst grade level. The room types and building structures most prone to moisture damage were (in rank order) crawl spaces, basements, un-insulated attics, cooling rooms, and bathrooms. The high proportion of homes with moisture damage indicate a possible risk for respiratory diseases in a relatively large number of individuals, even if only the more extensive moisture damages and those located in rooms where occupants spend the majority of their time would have a significant influence on adverse health effects. PMID:29039816

Long-term population patterns of rodents and associated damage in German forestry.

PubMed

Imholt, Christian; Reil, Daniela; Plašil, Pavel; Rödiger, Kerstin; Jacob, Jens

2017-02-01

Several rodent species can damage forest trees, especially at young tree age in afforestation. Population outbreaks of field voles (Microtus agrestis L.) and bank voles (Myodes glareolus Schreber) in particular can cause losses. Analyses of long-term time series indicate good synchrony of population abundance in rodent species associated with damage in forestry. This synchrony could be related to the effect of beech (Fagus spec.) mast in the previous year on population growth rates of both species. In shorter time series from Eastern Germany, damage in forestry was mostly associated with autumn abundances of rodents. Environmental factors such as beech mast and snow cover did not explain additional variation in rodent damage to trees. Beech mast is a good indicator of long-term rodent abundance in Northern German afforestation areas. However, rodent damage to forestry in Central Germany did not seem to depend on environmental parameters other than rodent abundance at large scale. As a result, there is still uncertainty about the link between environmental predictors and rodent damage to forestry, and further experimental work is required to identify suitable environmental drivers and their interplay with other potential factors such as the local predator community. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Analysis of potential urban unstable areas and landslide-induced damages on Volterra historical site through a remote sensing approach

NASA Astrophysics Data System (ADS)

Del Soldato, Matteo; Bianchini, Silvia; Nolesini, Teresa; Frodella, William; Casagli, Nicola

2017-04-01

Multisystem remote sensing techniques were exploited to provide a comprehensive overview of Volterra (Italy) site stability with regards to its landscape, urban fabric and cultural heritage. Interferometric Synthetic Aperture Radar (InSAR) techniques allow precise measurements of Earth surface displacement, as well as the detection of building deformations on large urban areas. In the field of cultural heritage conservation Infrared thermography (IRT) provides surface temperature mapping and therefore detects various potential criticalities, such as moisture, seepage areas, cracks and structural anomalies. Between winter 2014 and spring 2015 the historical center and south-western sectors of Volterra (Tuscany region, central Italy) were affected by instability phenomena. The spatial distribution, typology and effect on the urban fabrics of the landslide phenomena were investigated by analyzing the geological and geomorphological settings, traditional geotechnical monitoring and advanced remote sensing data such as Persistent Scatterers Interferometry (PSI). The ground deformation rates and the maximum settlement values derived from SAR acquisitions of historical ENVISAT and recent COSMO-SkyMed sensors, in 2003-2009 and 2010-2015 respectively, were compared with background geological data, constructive features, in situ evidences and detailed field inspections in order to classify landslide-damaged buildings. In this way, the detected movements and their potential correspondences with recognized damages were investigated in order to perform an assessment of the built-up areas deformations and damages on Volterra. The IRT technique was applied in order to survey the surface temperature of the historical Volterra wall-enclosure, and allowed highlighting thermal anomalies on this cultural heritage element of the site. The obtained results permitted to better correlate the landslide effects of the recognized deformations in the urban fabric, in order to provide useful information for future risk mitigation strategies to be planned by the local authorities and the involved technicians and conservators.

Surficial geologic map of the Germantown quadrangle, Shelby County, Tennessee

USGS Publications Warehouse

Arsdale, Roy Van

2004-01-01

The depiction of geology on this map is designed to aid in urban planning and analysis of potential damage in the event of strong earthquake motion. The geologic map by itself does not analyze potential earthquake damage, but is designed to be used by seismologists who perform such analyses. The nature of geologic materials to a degree determines the severity of damage to infrastructure sustained during a strong earthquake.

A new survey tool to assess pluvial damage to residential buildings

NASA Astrophysics Data System (ADS)

Rözer, Viktor; Spekkers, Matthieu; ten Veldhuis, Marie-Claire; Kreibich, Heidi

2017-04-01

Pluvial floods have caused severe damage to urban dwellings in Europe and elsewhere in recent years. These type of flood events are caused by storm events with exceptionally high rainfall rates, which lead to inundation of streets and buildings and are commonly associated with a failure of the urban drainage system. Therefore, pluvial floods often happen with little warning and in areas that are not obviously prone to flooding. With a predicted increase in extreme weather events as well as an ongoing urbanization, pluvial flood damage is expected to increase in the future. So far little research was done on the adverse consequences of pluvial floods, as empirical damage data of pluvial flooding is scarce. Therefore, a newly developed survey tool to assess pluvial flood damage as well as the results of a comparison between two international pluvial flood case studies are presented. The questionnaire used in the two study areas was developed with the aim to create a harmonized transnational pluvial flood damage survey that can potentially be extended to other European countries. New indicator variables have been developed to account for different national and regional standards in building structure, early warning, socio-economic data and recovery. The surveys comprise interviews with 510 households in the Münster area (Germany) and 349 households in Amsterdam (the Netherlands), which were affected by the heavy rainfall events on July 28 2014. The respondents were asked more than 80 questions about the damage to their building structure and contents, as well as on topics such as early warning, emergency and precautionary measures, building properties and hazard characteristics. A comparison of the two surveys revealed strong similarities concerning damage reducing effects and the popularity of precautionary measures, besides significant differences between the mean water levels inside the house as well as the median of the building structure and content damage. A comparison between the relative damage contributions for different entry points of water into the house indicates an effect of regional distinctions in building topology on the total damage. The results of this comparison give important insights for the development and transferability of pluvial flood damage models.

Retinal damage profiles and neuronal effects of laser treatment: comparison of a conventional photocoagulator and a novel 3-nanosecond pulse laser.

PubMed

Wood, John P M; Shibeeb, O'Sam; Plunkett, Malcolm; Casson, Robert J; Chidlow, Glyn

2013-03-28

To determine detailed effects to retinal cells and, in particular, neurons following laser photocoagulation using a conventional 532 nm Nd:YAG continuous wave (CW) laser. Furthermore, to determine whether a novel 3 ns pulse laser (retinal regeneration therapy; 2RT) could specifically ablate retinal pigment epithelium (RPE) cells without causing collateral damage to other retinal cells. Adult Dark Agouti (DA) rats were separated into four groups: control, CW laser (12.7 J/cm(2)/pulse, 100 ms pulse duration), or 3 ns pulse 2RT laser at one of two energy settings ("High," 2RT-H, 163 mJ/cm(2)/pulse; "Low," 2RT-L, 109 mJ/cm(2)/pulse). Animals were treated and killed after 6 hours to 7 days, and retina/RPE was analyzed by histologic assessment, Western blot, polymerase chain reaction, and immunohistochemistry. Both lasers caused focal loss of RPE cells with no destruction of Bruch's membrane; RPE cells were present at lesion sites again within 7 days of treatments. CW and 2RT-H treatments caused extensive and moderate damage, respectively, to the outer retina. There were no obvious effects to horizontal, amacrine, or ganglion cells, as defined by immunolabeling, but an activation of PKCα within bipolar cells was noted. There was little discernible damage to any cells other than the RPE with the 2RT-L treatment. Conventional laser photocoagulation caused death of RPE cells with associated widespread damage to the outer retina but little influence on the inner retina. The novel 3 ns 2RT laser, however, was able to selectively kill RPE cells without causing collateral damage to photoreceptors. Potential benefits of this laser for clinical treatment of diabetic macular edema are discussed.

Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacNaughton, W.K.; Wallace, J.L.; Cirino, G.

1989-01-01

The role that nitric oxide, an endothelium-derived relaxing factor, may play in the regulation of gastric mucosal defense was investigated by assessing the potential protective actions of this factor against the damage caused by ethanol in an ex vivo chamber preparation of the rat stomach. Topical application of glyceryl trinitrate and sodium nitroprusside, which have been shown to release nitric oxide, markedly reduced the area of 70% ethanol-induced hemorrhagic damage. Topical application of a 0.01% solution of authentic nitric oxide also significantly reduced the severity of mucosal damage. Pretreatment with indomethacin precluded the involvement of endogenous prostaglandins in the protectivemore » effects of these agents. The protective effects of NO were transient, since a delay of 5 minutes between NO administration and ethanal administration resulted in a complete loss of the protective activity. The protection against ethanol afforded by 10 ug/ml nitroprusside could be completely reversed by intravenous infusion of either 1% methylene blue or 1 mM hemoglobin, both of which inhibit vasodilation induced by nitric oxide. Intravenous infusion of 1% methylene blue significantly increased the susceptibility of the mucosa to damage induced by topical 20% ethanol.« less

Solar ultraviolet radiation induces biological alterations in human skin in vitro: relevance of a well-balanced UVA/UVB protection.

PubMed

Bernerd, Francoise; Marionnet, Claire; Duval, Christine

2012-06-01

Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV) exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA) were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid

PubMed Central

Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R.; Masliah, Eliezer; Lipton, Stuart A.

2015-01-01

Cyanide is a life threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species (ROS). This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain-barrier to upregulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human induced pluripotent stem cell (hiPSC)-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino (NSA) mouse model of cyanide poisoning that simulates damage observed in the human brain. PMID:25692407

The effects of global climate change on Southeast Asia: A survey of likely impacts and problems of adaptation

NASA Technical Reports Server (NTRS)

Njoto, Sukrisno; Howe, Charles W.

1991-01-01

Study results indicate the likelihood of significant net damages from climate change, in particular damages from sea-level rise and higher temperatures that seem unlikely to be offset by favorable shifts in precipitation and carbon dioxide. Also indicated was the importance of better climate models, in particular models that can calculate climate change on a regional scale appropriate to policy-making. In spite of this potential for damage, there seems to be a low level of awareness and concern, probably caused by the higher priority given to economic growth and reinforced by the great uncertainty in the forecasts. The common property nature of global environment systems also leads to a feeling of helplessness on the part of country governments.

DNA damage induces down-regulation of Prp19 via impairing Prp19 stability in hepatocellular carcinoma cells.

PubMed

Yin, Jie; Zhang, Yi-An; Liu, Tao-Tao; Zhu, Ji-Min; Shen, Xi-Zhong

2014-01-01

Pre-mRNA processing factor 19 (Prp19) activates pre-mRNA spliceosome and also mediates DNA damage response. Prp19 overexpression in cells with functional p53 leads to decreased apoptosis and increases cell survival after DNA damage. Here we showed that in hepatocellular carcinoma (HCC) cells with inactive p53 or functional p53, Prp19 was down-regulated due to the impaired stability under chemotherapeutic drug treatment. Silencing Prp19 expression enhanced apoptosis of HCC cells with or without chemotherapeutic drug treatment. Furthermore high level of Prp19 may inhibit chemotherapeutic drugs induced apoptosis in hepatocellular carcinoma cells through modulating myeloid leukemia cell differentiation 1 expression. These results indicated that targeting Prp19 may potentiate pro-apoptotic effect of chemotherapeutic agents on HCC.

Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

PubMed

Lorimore, S A; Wright, E G

2003-01-01

To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The induction of bystander effects and instabilities may reflect interrelated aspects of a non-specific inflammatory-type response to radiation-induced stress and injury and be involved in a variety of the pathological consequences of radiation exposures.

A combined analytical formulation and genetic algorithm to analyze the nonlinear damage responses of continuous fiber toughened composites

NASA Astrophysics Data System (ADS)

Jeon, Haemin; Yu, Jaesang; Lee, Hunsu; Kim, G. M.; Kim, Jae Woo; Jung, Yong Chae; Yang, Cheol-Min; Yang, B. J.

2017-09-01

Continuous fiber-reinforced composites are important materials that have the highest commercialized potential in the upcoming future among existing advanced materials. Despite their wide use and value, their theoretical mechanisms have not been fully established due to the complexity of the compositions and their unrevealed failure mechanisms. This study proposes an effective three-dimensional damage modeling of a fibrous composite by combining analytical micromechanics and evolutionary computation. The interface characteristics, debonding damage, and micro-cracks are considered to be the most influential factors on the toughness and failure behaviors of composites, and a constitutive equation considering these factors was explicitly derived in accordance with the micromechanics-based ensemble volume averaged method. The optimal set of various model parameters in the analytical model were found using modified evolutionary computation that considers human-induced error. The effectiveness of the proposed formulation was validated by comparing a series of numerical simulations with experimental data from available studies.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes.

PubMed

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes

PubMed Central

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications. PMID:28078052

A biological evaluation of DNA damage detected by comet assay in healthy populations residing in areas that differ in lung cancer incidence.

PubMed

Heepchantree, Worapa; Paratasilpin, Thipmani; Kangwanpong, Daoroong

2006-06-01

The comet assay was performed to evaluate the effect of environmental exposure between human populations residing in two areas that differ in lung cancer incidence, Saraphi (n = 91) and Chom Thong (n = 94). Three parameters, the tail length, tail intensity, and tail moment, were used to detect DNA damage in peripheral blood and stimulated lymphocytes with and without the DNA repair inhibitor, aphidicolin. Internal standards, cryopreserved isolated lymphocytes, and isolated lymphocytes irradiated with 2 Gy gamma rays, were used to correct the interexperimental variability. Results revealed a significant difference between two populations only when the tail length was used to measure DNA damage. The evaluation of various potential confounding factors, such as gender, pesticide exposure, smoking, alcohol drinking, and fermented tea leaf or betel nut chewing, indicated no significant influence in DNA damage. In conclusion, significant difference in DNA damage, detected only by tail length between the two populations residing in the areas with different incidence of lung cancer, may reflect a nonhazardous level of exposure to toxic substances.

Damage Detection for Historical Architectures Based on Tls Intensity Data

NASA Astrophysics Data System (ADS)

Li, Q.; Cheng, X.

2018-04-01

TLS (Terrestrial Laser Scanner) has long been preferred in the cultural heritage field for 3D documentation of historical sites thanks to its ability to acquire the geometric information without any physical contact. Besides the geometric information, most TLS systems also record the intensity information, which is considered as an important measurement of the spectral property of the scanned surface. Recent studies have shown the potential of using intensity for damage detection. However, the original intensity is affected by scanning geometry such as range and incidence angle and other factors, thus making the results less accurate. Therefore, in this paper, we present a method to detect certain damage areas using the corrected intensity data. Firstly, two data-driven models have been developed to correct the range and incidence angle effect. Then the corrected intensity is used to generate 2D intensity images for classification. After the damage areas being detected, they are re-projected to the 3D point cloud for better visual representation and further investigation. The experiment results indicate the feasibility and validity of the corrected intensity for damage detection.

Damage detection of structures with detrended fluctuation and detrended cross-correlation analyses

NASA Astrophysics Data System (ADS)

Lin, Tzu-Kang; Fajri, Haikal

2017-03-01

Recently, fractal analysis has shown its potential for damage detection and assessment in fields such as biomedical and mechanical engineering. For its practicability in interpreting irregular, complex, and disordered phenomena, a structural health monitoring (SHM) system based on detrended fluctuation analysis (DFA) and detrended cross-correlation analysis (DCCA) is proposed. First, damage conditions can be swiftly detected by evaluating ambient vibration signals measured from a structure through DFA. Damage locations can then be determined by analyzing the cross correlation of signals of different floors by applying DCCA. A damage index is also proposed based on multi-scale DCCA curves to improve the damage location accuracy. To verify the performance of the proposed SHM system, a four-story numerical model was used to simulate various damage conditions with different noise levels. Furthermore, an experimental verification was conducted on a seven-story benchmark structure to assess the potential damage. The results revealed that the DFA method could detect the damage conditions satisfactorily, and damage locations can be identified through the DCCA method with an accuracy of 75%. Moreover, damage locations can be correctly assessed by the damage index method with an improved accuracy of 87.5%. The proposed SHM system has promising application in practical implementations.

Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion.

PubMed

Khaldy, Hoda; Escames, Germaine; León, Josefa; Bikjdaouene, Leila; Acuña-Castroviejo, Darío

2003-01-01

Previous studies showed a synergistic effect of melatonin and deprenyl against dopamine (DA) autoxidation in vitro. Since oxidative stress is implicated in Parkinson's disease (PD), we explored the effects of melatonin plus deprenyl administration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in C57/Bl6 mice. Melatonin, but not deprenyl prevents the inhibition of mitochondrial complex I and the oxidative damage in nigrostriatal neurons induced by MPTP. With the dose used deprenyl recovers 50% DA levels and tyrosine hydroxylase activity depressed by the neurotoxin, normalizing locomotor activity of mice. Melatonin, which was unable to counteract MPTP-induced DA depletion and inhibition of tyrosine hydroxylase activity, potentiates the effect of deprenyl on catecholamine turnover and mice ambulatory activity. These results suggest a dissociation of complex I inhibition from DA depletion in this model of Parkinson's disease. The data also support that a combination of melatonin, which improves mitochondrial electron transport chain and reduces oxidative damage, and deprenyl, which promotes the specific function of the rescued neurons, i.e. DA turnover, may be a promising strategy for the treatment of PD.

Artemisinin Protects Retinal Neuronal Cells against Oxidative Stress and Restores Rat Retinal Physiological Function from Light Exposed Damage.

PubMed

Yan, Fengxia; Wang, Haitao; Gao, Yang; Xu, Jiangping; Zheng, Wenhua

2017-08-16

Oxidative stress plays a key role in the pathogenesis of age-related macular degeneration (AMD), a leading cause of severe visual loss and blindness in the aging population which lacks any effective treatments currently. In this study, artemisinin, a well-known antimalarial drug was found to suppress hydrogen peroxide (H 2 O 2 )-induced cell death in retinal neuronal RGC-5 cells. Artemisinin, in the therapeutically relevant dosage, concentration-dependently attenuated the accumulation of intracellular reactive oxygen species (ROS), increased mitochondrial membrane potential and decreased cell apoptosis in RGC-5 cells induced by H 2 O 2 . Western blot analysis showed that artemisinin upregulated the phosphorylation of p38 and extracellular signal-regulated kinases1/2 (ERK1/2) and reversed the inhibitory effect of H 2 O 2 on the phosphorylation of these two kinases. Moreover, protective effect of artemisinin was blocked by the p38 kinase inhibitor PD169316 or ERK1/2 kinase pathway inhibitor PD98059, respectively. In contrast, c-Jun N-terminal kinase inhibitor and rapamycin had no effect in the protective effect of artemisinin. Taken together, these results demonstrated that artemisinin promoted the survival of RGC-5 cells from H 2 O 2 toxicity via the activation of the p38 and ERK1/2 pathways. Interestingly, intravitreous injection of artimisinin, concentration-dependently reversed light exposed-damage (a dry AMD animal model) of rat retinal physiological function detected by flash electroretinogram. These results indicate that artemisinin can protect retinal neuronal functions from H 2 O 2 -induced damage in vitro and in vivo and suggest the potential application of artemisinin as a new drug in the treatment of retinal disorders like AMD.

An effective approach for road asset management through the FDTD simulation of the GPR signal

NASA Astrophysics Data System (ADS)

Benedetto, Andrea; Pajewski, Lara; Adabi, Saba; Kusayanagi, Wolfgang; Tosti, Fabio

2015-04-01

Ground-penetrating radar is a non-destructive tool widely used in many fields of application including pavement engineering surveys. Over the last decade, the need for further breakthroughs capable to assist end-users and practitioners as decision-support systems in more effective road asset management is increasing. In more details and despite the high potential and the consolidated results obtained over years by this non-destructive tool, pavement distress manuals are still based on visual inspections, so that only the effects and not the causes of faults are generally taken into account. In this framework, the use of simulation can represent an effective solution for supporting engineers and decision-makers in understanding the deep responses of both revealed and unrevealed damages. In this study, the potential of using finite-difference time-domain simulation of the ground-penetrating radar signal is analyzed by simulating several types of flexible pavement at different center frequencies of investigation typically used for road surveys. For these purposes, the numerical simulator GprMax2D, implementing the finite-difference time-domain method, was used, proving to be a highly effective tool for detecting road faults. In more details, comparisons with simplified undisturbed modelled pavement sections were carried out showing promising agreements with theoretical expectations, and good chances for detecting the shape of damages are demonstrated. Therefore, electromagnetic modelling has proved to represent a valuable support system in diagnosing the causes of damages, even for early or unrevealed faults. Further perspectives of this research will be focused on the modelling of more complex scenarios capable to represent more accurately the real boundary conditions of road cross-sections. Acknowledgements - This work has benefited from networking activities carried out within the EU funded COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar".

Three-dimensional analysis of a faulted CO 2 reservoir using an Eshelby-Mori-Tanaka approach to rock elastic properties and fault permeability

DOE PAGES

Nguyen, Ba Nghiep; Hou, Zhangshuan; Last, George V.; ...

2016-09-29

This work develops a three-dimensional multiscale model to analyze a complex CO 2 faulted reservoir that includes some key geological features of the San Andreas and nearby faults southwest of the Kimberlina site. The model uses the STOMP-CO 2 code for flow modeling that is coupled to the ABAQUS® finite element package for geomechanical analysis. A 3D ABAQUS® finite element model is developed that contains a large number of 3D solid elements with two nearly parallel faults whose damage zones and cores are discretized using the same continuum elements. Five zones with different mineral compositions are considered: shale, sandstone, faultmore » damaged sandstone, fault damaged shale, and fault core. Rocks’ elastic properties that govern their poroelastic behavior are modeled by an Eshelby-Mori-Tanka approach (EMTA). EMTA can account for up to 15 mineral phases. The permeability of fault damage zones affected by crack density and orientations is also predicted by an EMTA formulation. A STOMP-CO 2 grid that exactly maps the ABAQUS® finite element model is built for coupled hydro-mechanical analyses. Simulations of the reservoir assuming three different crack pattern situations (including crack volume fraction and orientation) for the fault damage zones are performed to predict the potential leakage of CO 2 due to cracks that enhance the permeability of the fault damage zones. Here, the results illustrate the important effect of the crack orientation on fault permeability that can lead to substantial leakage along the fault attained by the expansion of the CO 2 plume. Potential hydraulic fracture and the tendency for the faults to slip are also examined and discussed in terms of stress distributions and geomechanical properties.« less

Three-dimensional analysis of a faulted CO 2 reservoir using an Eshelby-Mori-Tanaka approach to rock elastic properties and fault permeability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Ba Nghiep; Hou, Zhangshuan; Last, George V.

This work develops a three-dimensional multiscale model to analyze a complex CO 2 faulted reservoir that includes some key geological features of the San Andreas and nearby faults southwest of the Kimberlina site. The model uses the STOMP-CO 2 code for flow modeling that is coupled to the ABAQUS® finite element package for geomechanical analysis. A 3D ABAQUS® finite element model is developed that contains a large number of 3D solid elements with two nearly parallel faults whose damage zones and cores are discretized using the same continuum elements. Five zones with different mineral compositions are considered: shale, sandstone, faultmore » damaged sandstone, fault damaged shale, and fault core. Rocks’ elastic properties that govern their poroelastic behavior are modeled by an Eshelby-Mori-Tanka approach (EMTA). EMTA can account for up to 15 mineral phases. The permeability of fault damage zones affected by crack density and orientations is also predicted by an EMTA formulation. A STOMP-CO 2 grid that exactly maps the ABAQUS® finite element model is built for coupled hydro-mechanical analyses. Simulations of the reservoir assuming three different crack pattern situations (including crack volume fraction and orientation) for the fault damage zones are performed to predict the potential leakage of CO 2 due to cracks that enhance the permeability of the fault damage zones. Here, the results illustrate the important effect of the crack orientation on fault permeability that can lead to substantial leakage along the fault attained by the expansion of the CO 2 plume. Potential hydraulic fracture and the tendency for the faults to slip are also examined and discussed in terms of stress distributions and geomechanical properties.« less

11th International Conference of Radiation Research

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1999-07-18

Topics discussed in the conference included the following: Radiation Physics, Radiation Chemistry and modelling--Radiation physics and dosimetry; Electron transfer in biological media; Radiation chemistry; Biophysical and biochemical modelling; Mechanisms of DNA damage; Assays of DNA damage; Energy deposition in micro volumes; Photo-effects; Special techniques and technologies; Oxidative damage. Molecular and cellular effects-- Photobiology; Cell cycle effects; DNA damage: Strand breaks; DNA damage: Bases; DNA damage Non-targeted; DNA damage: other; Chromosome aberrations: clonal; Chromosomal aberrations: non-clonal; Interactions: Heat/Radiation/Drugs; Biochemical effects; Protein expression; Gene induction; Co-operative effects; ``Bystander'' effects; Oxidative stress effects; Recovery from radiation damage. DNA damage and repair -- DNAmore » repair genes; DNA repair deficient diseases; DNA repair enzymology; Epigenetic effects on repair; and Ataxia and ATM.« less

Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34+ stem cell potential in rat experimental hyperuricemia.

PubMed

Kocic, Gordana; Sokolovic, Dusan; Jevtovic, Tatjana; Cvetkovic, Tatjana; Veljkovic, Andrej; Kocic, Hristina; Stojanovic, Svetlana; Jovanovic, Aneta; Jovanovic, Jelena; Zivkovic, Petar

2014-11-01

Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34(+), CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34(+) stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34(+). Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Systemic estimation of the effect of photodynamic therapy of cancer

NASA Astrophysics Data System (ADS)

Kogan, Eugenia A.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Loschenov, Victor B.; Volkova, Anna I.; Posypanova, Anna M.

1997-12-01

The effects of photodynamic therapy (PDT) of cancer needs objective estimation and its unification in experimental as well as in clinical studies. They must include not only macroscopical changes but also the complex of following morphological criteria: (1) the level of direct tumor damage (direct necrosis and apoptosis); (2) the level of indirect tumor damage (ischemic necrosis); (3) the signs of vascular alterations; (4) the local and systemic antiblastome resistance; (5) the proliferative activity and malignant potential of survival tumor tissue. We have performed different regimes PDT using phthalocyanine derivatives. The complex of morphological methods (Ki-67, p53, c-myc, bcl-2) was used. Obtained results showed the connection of the tilted morphological criteria with tumor regression.

The effect of hyperthermia on the radiation response of crypt cells in mouse jejunum

NASA Technical Reports Server (NTRS)

Wilson, J. D.

1978-01-01

The effect of hyperthermia and/or gamma-radiation on the survival of intestinal crypt cells was studied in BDF sub 1 mice using a microcolony assay. Hyperthermia treatments, which in themselves caused no detectable cell lethality, inhibited the capacity of crypt cells to repair sublethal radiation damage. In addition, heat applied either before or after single radiation exposures potentiated lethal damage to crypt cells; the degree of enhancement was dependent on the time interval between treatments. At the levels of heating employed, DNA synthesis in the intestinal epithelium was significantly reduced immediately following exposure, but returned rapidly to normal levels. No further disturbances in cellular kinetics were observed for up to 10 days after heating.

Towards a Fuzzy Bayesian Network Based Approach for Safety Risk Analysis of Tunnel-Induced Pipeline Damage.

PubMed

Zhang, Limao; Wu, Xianguo; Qin, Yawei; Skibniewski, Miroslaw J; Liu, Wenli

2016-02-01

Tunneling excavation is bound to produce significant disturbances to surrounding environments, and the tunnel-induced damage to adjacent underground buried pipelines is of considerable importance for geotechnical practice. A fuzzy Bayesian networks (FBNs) based approach for safety risk analysis is developed in this article with detailed step-by-step procedures, consisting of risk mechanism analysis, the FBN model establishment, fuzzification, FBN-based inference, defuzzification, and decision making. In accordance with the failure mechanism analysis, a tunnel-induced pipeline damage model is proposed to reveal the cause-effect relationships between the pipeline damage and its influential variables. In terms of the fuzzification process, an expert confidence indicator is proposed to reveal the reliability of the data when determining the fuzzy probability of occurrence of basic events, with both the judgment ability level and the subjectivity reliability level taken into account. By means of the fuzzy Bayesian inference, the approach proposed in this article is capable of calculating the probability distribution of potential safety risks and identifying the most likely potential causes of accidents under both prior knowledge and given evidence circumstances. A case concerning the safety analysis of underground buried pipelines adjacent to the construction of the Wuhan Yangtze River Tunnel is presented. The results demonstrate the feasibility of the proposed FBN approach and its application potential. The proposed approach can be used as a decision tool to provide support for safety assurance and management in tunnel construction, and thus increase the likelihood of a successful project in a complex project environment. © 2015 Society for Risk Analysis.

Risk preferences in strategic wildfire decision making: a choice experiment with U.S. wildfire managers.

PubMed

Wibbenmeyer, Matthew J; Hand, Michael S; Calkin, David E; Venn, Tyron J; Thompson, Matthew P

2013-06-01

Federal policy has embraced risa management as an appropriate paradigm for wildfire management. Economic theory suggests that over repeated wildfire events, potential economic costs and risas of ecological damage are optimally balanced when management decisions are free from biases, risa aversion, and risa seeking. Of primary concern in this article is how managers respond to wildfire risa, including the potential effect of wildfires (on ecological values, structures, and safety) and the likelihood of different fire outcomes. We use responses to a choice experiment questionnaire of U.S. federal wildfire managers to measure attitudes toward several components of wildfire risa and to test whether observed risa attitudes are consistent with the efficient allocation of wildfire suppression resources. Our results indicate that fire managers' decisions are consistent with nonexpected utility theories of decisions under risa. Managers may overallocate firefighting resources when the likelihood or potential magnitude of damage from fires is low, and sensitivity to changes in the probability of fire outcomes depends on whether probabilities are close to one or zero and the magnitude of the potential harm. © 2012 Society for Risk Analysis.

Tenofovir-induced kidney injury.

PubMed

Gitman, Michael D; Hirschwerk, David; Baskin, Cindy H; Singhal, Pravin C

2007-03-01

Tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor with activity against both HIV and the hepatitis B virus. It has had minimal nephrotoxic effects in early clinical trials, but as clinical use has widened, case reports describing tenofovir-induced renal tubular damage, Fanconi's syndrome and diabetes insipidus have been described. The authors review the pharmacokinetics, mechanism of action and clinical uses of tenofovir disoproxil fumarate. The large clinical trials, as well as the case reports of tenofovir-induced kidney injury, are also reviewed. The potential mechanism of renal damage is discussed and recommendations for evaluation and treatment of tenofovir-induced kidney injury are given.

Structural health monitoring and damage evaluation for steel confined reinforced concrete column using the acoustic emission technique

NASA Astrophysics Data System (ADS)

Du, Fangzhu; Li, Dongsheng

2018-03-01

As a new kind of composite structures, the using of steel confined reinforced concrete column attract increasing attention in civil engineer. During the damage process, this new structure offers highly complex and invisible failure mechanism due to the combination effects of steel tubes, concrete, and steel rebar. Acoustic emission (AE) technique has been extensively studied in nondestructive testing (NDT) and is currently applied in civil engineering for structural health monitoring (SHM) and damage evaluation. In the present study, damage property and failure evolution of steel confined and unconfined reinforced concrete (RC) columns are investigated under quasi-static loading through (AE) signal. Significantly improved loading capacity and excellent energy dissipation characteristic demonstrated the practicality of that proposed structure. AE monitoring results indicated that the progressive deformation of the test specimens occur in three stages representing different damage conditions. Sentry function compares the logarithm ratio between the stored strain energy (Es) and the released acoustic energy (Ea); explicitly disclose the damage growth and failure mechanism of the test specimens. Other extended AE features including index of damage (ID), and relax ratio are calculated to quantitatively evaluate the damage severity and critical point. Complicated temporal evolution of different AE features confirms the potential importance of integrated analysis of two or more parameters. The proposed multi-indicators analysis is capable of revealing the damage growth and failure mechanism for steel confined RC columns, and providing critical warning information for structure failure.

Novel Application of Stem Cell-Derived Neurons to Evaluate the Time-and Dose-Dependent Progression of Excitotoxic Injury

DTIC Science & Technology

2013-05-14

enzymes . At sufficiently high doses of glutamate, this process culminates in excitogenic cell death [1]. Treatments to mitigate neuronal damage during...To evaluate the potential for therapeutic screening, we assessed the effect of several small molecule antagonists on excitotoxicity in a moderate...C. Current clamp recordings showing repeated overshooting action potentials are evoked by injection of a 75 pA current. D. Voltage-clamp recordings

The irritation potential and reservoir effect of mild soaps.

PubMed

Lodén, Marie; Buraczewska, Izabela; Edlund, Fredrik

2003-08-01

Identification and reduction of external noxious factors is one key point in the strategy for the treatment and reduction of contact dermatitis. A wide variety of soaps on the market are claimed to be suitable for the use on sensitive skin due to their mildness. The aim of the present study was to illustrate possible differences in the irritation potential of 8 products and to investigate whether surfactant residues may form an irritant reservoir on the skin. The study was double-blind, randomized using healthy human volunteers. The inherent capacity of the products to induce irritation was determined using conventional patch test technique, whereas detection of potential surfactant residues on the skin was done using a methodology developed in the 1960s for detection of the corticosteroid reservoir in the stratum corneum. The method comprised the release of active substance from the stratum corneum reservoir by occlusion of the skin with an aluminium chamber, followed by evaluation of the biological response. In the present study, the soap-treated area was rinsed with water and then occluded. Instrumental measurements of the transepidermal water loss and superficial skin blood flow served as indicators of the injurious effects of the products. The results showed large differences in irritation potential between the products, and some of them demonstrated considerable damaging effect. Moreover, the study proved the presence of barrier-impairing residues on the skin after rinsing with water. Subclinical skin damage can make the skin vulnerable to further irritation and delay recovery of chronic irritant contact dermatitis.

Probabilistic evaluation of damage potential in earthquake-induced liquefaction in a 3-D soil deposit

NASA Astrophysics Data System (ADS)

Halder, A.; Miller, F. J.

1982-03-01

A probabilistic model to evaluate the risk of liquefaction at a site and to limit or eliminate damage during earthquake induced liquefaction is proposed. The model is extended to consider three dimensional nonhomogeneous soil properties. The parameters relevant to the liquefaction phenomenon are identified, including: (1) soil parameters; (2) parameters required to consider laboratory test and sampling effects; and (3) loading parameters. The fundamentals of risk based design concepts pertient to liquefaction are reviewed. A detailed statistical evaluation of the soil parameters in the proposed liquefaction model is provided and the uncertainty associated with the estimation of in situ relative density is evaluated for both direct and indirect methods. It is found that the liquefaction potential the uncertainties in the load parameters could be higher than those in the resistance parameters.

Earthquake hazards to domestic water distribution systems in Salt Lake County, Utah

USGS Publications Warehouse

Highland, Lynn M.

1985-01-01

A magnitude-7. 5 earthquake occurring along the central portion of the Wasatch Fault, Utah, may cause significant damage to Salt Lake County's domestic water system. This system is composed of water treatment plants, aqueducts, distribution mains, and other facilities that are vulnerable to ground shaking, liquefaction, fault movement, and slope failures. Recent investigations into surface faulting, landslide potential, and earthquake intensity provide basic data for evaluating the potential earthquake hazards to water-distribution systems in the event of a large earthquake. Water supply system components may be vulnerable to one or more earthquake-related effects, depending on site geology and topography. Case studies of water-system damage by recent large earthquakes in Utah and in other regions of the United States offer valuable insights in evaluating water system vulnerability to earthquakes.

Eradication of Invading Insect Populations: From Concepts to Applications

Treesearch

Andrew M. Liebhold; Ludek Berec; Eckehard G. Brockerhoff; Rebecca S. Epanchin-Niell; Alan Hastings; Daniel A. Herms; John M. Kean; Deborah G. McCullough; David M. Suckling; Patrick C. Tobin; Takehiko Yamanaka

2016-01-01

Eradication is the deliberate elimination of a species from an area. Given that international quarantine measures can never be 100% effective, surveillance for newly arrived populations of nonnative species coupled with their eradication represents an important strategy for excluding potentially damaging insect species. Historically, eradication efforts have not always...

Fire Hazards of Windowless Buildings.

ERIC Educational Resources Information Center

Juillerat, Ernest E.

1964-01-01

In response to the fast growing prominence of windowless buildings due to potential or possible aesthetic, psychological, and economic advantages, this article was written to discuss--(1) effects of windowless construction on the life safety of building occupants, (2) the possible extents of fire damage to the building and its contents, and (3)…

Who Is Afraid of Math? Two Sources of Genetic Variance for Mathematical Anxiety

ERIC Educational Resources Information Center

Wang, Zhe; Hart, Sara Ann; Kovas, Yulia; Lukowski, Sarah; Soden, Brooke; Thompson, Lee A.; Plomin, Robert; McLoughlin, Grainne; Bartlett, Christopher W.; Lyons, Ian M.; Petrill, Stephen A.

2014-01-01

Background: Emerging work suggests that academic achievement may be influenced by the management of affect as well as through efficient information processing of task demands. In particular, mathematical anxiety has attracted recent attention because of its damaging psychological effects and potential associations with mathematical problem solving…

Persistence of chromosome aberrations in mice acutely exposed to 56Fe+26 ions.

PubMed

Tucker, James D; Marples, Brian; Ramsey, Marilyn J; Lutze-Mann, Louise H

2004-06-01

Space exploration has the potential to yield exciting and significant discoveries, but it also brings with it many risks for flight crews. Among the less well studied of these are health effects from space radiation, which includes the highly charged, energetic particles of elements with high atomic numbers that constitute the galactic cosmic rays. In this study, we demonstrated that 1 Gy iron ions acutely administered to mice in vivo resulted in highly complex chromosome damage. We found that all types of aberrations, including dicentrics as well as translocations, insertions and acentric fragments, disappear rapidly with time after exposure, probably as a result of the death of heavily damaged cells, i.e. cells with multiple and/or complex aberrations. In addition, numerous cells have apparently simple exchanges as their only aberrations, and these cells appear to survive longer than heavily damaged cells. Eight weeks after exposure, the frequency of cells showing cytogenetic damage was reduced to less than 20% of the levels evident at 1 week, with little further decline apparent over an additional 8 weeks. These results indicate that exposure to 1 Gy iron ions produces heavily damaged cells, a small fraction of which appear to be capable of surviving for relatively long periods. The health effects of exposure to high-LET radiation in humans on prolonged space flights should remain a matter of concern.

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration.

PubMed

Romero, Juan Ignacio; Holubiec, Mariana Inés; Tornatore, Tamara Logica; Rivière, Stéphanie; Hanschmann, Eva-Maria; Kölliker-Frers, Rodolfo Alberto; Tau, Julia; Blanco, Eduardo; Galeano, Pablo; Rodríguez de Fonseca, Fernando; Lillig, Christopher Horst; Capani, Francisco

2017-01-01

The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury.

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration

PubMed Central

Holubiec, Mariana Inés; Tornatore, Tamara Logica; Rivière, Stéphanie; Kölliker-Frers, Rodolfo Alberto; Tau, Julia; Blanco, Eduardo; Galeano, Pablo; Lillig, Christopher Horst

2017-01-01

The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury. PMID:28706574

Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo

PubMed Central

Brönnimann, Daniel; Bouchet, Audrey; Schneider, Christoph; Potez, Marine; Serduc, Raphaël; Bräuer-Krisch, Elke; Graber, Werner; von Gunten, Stephan; Laissue, Jean Albert; Djonov, Valentin

2016-01-01

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25–100 μm wide) and minibeams (200–800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a+ thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool. PMID:27640676

A comparative study on radioprotective effect of N-acetylcysteine against 12C6+ ion versus X-rays

NASA Astrophysics Data System (ADS)

Liu, Yang; Zhang, Hong; Zhang, Luwei

Purpose: The aim of this study was to evaluate the different protective efficacy of N-acetylcysteine (NAC, 200 mg/kg dose) against 12C6+ ion (4 Gy) and X-rays (4 Gy) - induced damage in vivo model. Method: Kung-Ming female mice were divided into six groups, each composed of twelve animals: control group, two irradiation groups, and two NAC-treated groups, as well as NAC alone-treated group. An acute study was carried out to determine alterations in the oxidative stress (malondialdehyde level) using with colorimetric method and cell apoptosis measuring by flow cytometry as well as DNA-single strand break analyzing by comet assay at 2h after irradiation in mouse liver. Results: Compared with respective irradiation group, NAC can significantly ameliorate injury induced by two types of ionizing irradiation, which marked by the decrease of malondialdehyde level, and the reduction of apoptosis cells percentage and DNA damage. But the greater efficacy of NAC was prominently observed to inhibit the damage induced by X-rays, suggesting that NAC-mediated protective effect is more advisable to X-rays than 12C6+ ion irradiation. Moreover, NAC treatment alone did not result in any damage as compared to the control group. Conclusion: NAC may merit development as a potential radioprotective agent. Furthermore, NAC might exert its best effort to respond X rays-caused damage.

Observations of Building Performance under Combined Wind and Surge Loading from Hurricane Harvey

NASA Astrophysics Data System (ADS)

Lombardo, F.; Roueche, D. B.; Krupar, R. J.; Smith, D. J.; Soto, M. G.

2017-12-01

Hurricane Harvey struck the Texas coastline on August 25, 2017, as a Category 4 hurricane - the first major hurricane to reach the US in twelve years. Wind gusts over 130 mph and storm surge as high as 12.5 ft caused widespread damage to buildings and critical infrastructure in coastal communities including Rockport, Fulton, Port Aransas and Aransas Pass. This study presents the methodology and preliminary observations of a coordinated response effort to document residential building performance under wind and storm surge loading. Over a twelve day survey period the study team assessed the performance of more than 1,000 individual, geo-located residential buildings. Assessments were logged via a smartphone application to facilitate rapid collection and collation of geotagged photographs, building attributes and structural details, and structural damage observations. Detailed assessments were also made of hazard intensity, specifically storm surge heights and both wind speed and direction indicators. Preliminary observations and findings will be presented, showing strong gradients in damage between inland and coastal regions of the affected areas that may be due in part to enhanced individual loading effects of wind and storm surge and potentially joint-hazard loading effects. Contributing factors to the many cases of disproportionate damage observed in close proximity will also be discussed. Ongoing efforts to relate building damage to near-surface hazard measurements (e.g., radar, anemometry) in close proximity will also be described.

Radiation Damage in XFEL: Case study from the oxygen-evolving complex of Photosystem II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amin, Muhamed; Badawi, Ashraf; Obayya, S. S.

Structural changes induced by radiation damage in X-ray crystallography hinder the ability to understand the structure/function relationship in chemical reactions. Serial femtosecond crystallography overcomes this problem by exposing the sample to very short and intense laser pulse leading to measurement before destruction. Here we use molecular modeling to map the radiation damage during the 10–50 fs to the intensity, the energy and the time duration of the laser pulse on the oxygen-evolving complex (OEC) of photosystem II. In the model, the nuclei move classically in a fully quantum potential created by electron density under the effect of strong laser pulsemore » in the Ehrenfest dynamics regime. The results show that the Mn-Mn and Mn-Ca distances are less affected by radiation damage due to the their heavy masses, while one μ-oxo bridge (O5) moves significantly. The radiation damage may induce conformational changes of the water ligands but only bond elongation for the amino acids ligands. These effects are relatively intensity independent from 10 16 to 10 17 W/cm 2, but changes increase dramatically if the beam intensity is increased to 10 18 W/cm 2. Finally, in addition, the self amplified spontaneous emission (SASE) nature of the laser beam does not affect the dynamics of the ions.« less

Radiation Damage in XFEL: Case study from the oxygen-evolving complex of Photosystem II

DOE PAGES

Amin, Muhamed; Badawi, Ashraf; Obayya, S. S.

2016-11-09

Structural changes induced by radiation damage in X-ray crystallography hinder the ability to understand the structure/function relationship in chemical reactions. Serial femtosecond crystallography overcomes this problem by exposing the sample to very short and intense laser pulse leading to measurement before destruction. Here we use molecular modeling to map the radiation damage during the 10–50 fs to the intensity, the energy and the time duration of the laser pulse on the oxygen-evolving complex (OEC) of photosystem II. In the model, the nuclei move classically in a fully quantum potential created by electron density under the effect of strong laser pulsemore » in the Ehrenfest dynamics regime. The results show that the Mn-Mn and Mn-Ca distances are less affected by radiation damage due to the their heavy masses, while one μ-oxo bridge (O5) moves significantly. The radiation damage may induce conformational changes of the water ligands but only bond elongation for the amino acids ligands. These effects are relatively intensity independent from 10 16 to 10 17 W/cm 2, but changes increase dramatically if the beam intensity is increased to 10 18 W/cm 2. Finally, in addition, the self amplified spontaneous emission (SASE) nature of the laser beam does not affect the dynamics of the ions.« less

Evaluation of Dicyphus hersperus (Heteroptera: Miridae) for biological control of Frankliniella occidentalis (Thysanoptera: Thripidae) on greenhouse tomato.

PubMed

Shipp, J L; Wang, K

2006-04-01

The effectiveness of inoculative releases of the mirid predator Dicyphus hesperus Knight for control of Frankliniella occidentalis (Pergande) on greenhouse tomatoes was evaluated in terms of suppression of the population densities of F. occidentalis and associated fruit damage in the presence of the predator over two seasonal trials. An inoculative release of one D. hesperus per plant (approximately 0.1:10 predator:prey ratio) at a high F. occidentalis population density (140 thrips per plant) suppressed the thrips population density to a significantly lower level, compared with the nonrelease greenhouse, but not below a thrips level that caused economic fruit damage. As the predator:prey ratio increased to approximately 0.5:10 D. hesperus:F. occidentalis, the mean percentage of the thrips-damaged fruit in the D. hesperus release greenhouse decreased to 1.6%. However, the amount of fruit feeding by D. hesperus was highly correlated to the availability of prey (or predator:prey ratio) under greenhouse conditions. D. hesperus-induced fruit damage occurred when the predator:prey ratio was >1:10 D. hesperus:F. occidentalis. Considering the potential risk of fruit damage by D. hesperus and the need for effective control of F. occidentalis, a 0.5-1:10 D. hesperus:F. occidentalis ratio is recommended when the thrips population density is in the range of 60-150 thrips per plant.

Effects of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites on DNA damage and repair under in vitro conditions.

PubMed

Ozcagli, Eren; Alpertunga, Buket; Fenga, Concettina; Berktas, Mehmet; Tsitsimpikou, Christina; Wilks, Martin F; Tsatsakis, Αristidis M

2016-03-01

3-monochloropropane-1,2-diol (3-MCPD) is a food contaminant that occurs during industrial production processes and can be found mainly in fat and salt containing products. 3-MCPD has exhibited mutagenic activity in vitro but not in vivo, however, a genotoxic mechanism for the occurrence of kidney tumors has not so far been excluded. The main pathway of mammalian 3-MCPD metabolism is via the formation of β--chlorolactatic acid and formation of glycidol has been demonstrated in bacterial metabolism. The aim of this study was to investigate genotoxic and oxidative DNA damaging effects of 3-MCPD and its metabolites, and to provide a better understanding of their roles in DNA repair processes. DNA damage was assessed by alkaline comet assay in target rat kidney epithelial cell lines (NRK-52E) and human embryonic kidney cells (HEK-293). Purine and pyrimidine base damage, H2O2 sensitivity and DNA repair capacity were assessed via modified comet assay. The results revealed in vitro evidence for increased genotoxicity and H2O2 sensitivity. No association was found between oxidative DNA damage and DNA repair capacity with the exception of glycidol treatment at 20 μg/mL. These findings provide further insights into the mechanisms underlying the in vitro genotoxic potential of 3-MCPD and metabolites. Copyright © 2016 Elsevier Ltd. All rights reserved.

MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung cancer cells: more bad news than good?

PubMed

Abbas, Hussein H K; Alhamoudi, Kheloud M H; Evans, Mark D; Jones, George D D; Foster, Steven S

2018-04-16

Targeted therapies are based on exploiting cancer-cell-specific genetic features or phenotypic traits to selectively kill cancer cells while leaving normal cells unaffected. Oxidative stress is a cancer hallmark phenotype. Given that free nucleotide pools are particularly vulnerable to oxidation, the nucleotide pool sanitising enzyme, MTH1, is potentially conditionally essential in cancer cells. However, findings from previous MTH1 studies have been contradictory, meaning the relevance of MTH1 in cancer is still to be determined. Here we ascertained the role of MTH1 specifically in lung cancer cell maintenance, and the potential of MTH1 inhibition as a targeted therapy strategy to improve lung cancer treatments. Using siRNA-mediated knockdown or small-molecule inhibition, we tested the genotoxic and cytotoxic effects of MTH1 deficiency on H23 (p53-mutated), H522 (p53-mutated) and A549 (wildtype p53) non-small cell lung cancer cell lines relative to normal MRC-5 lung fibroblasts. We also assessed if MTH1 inhibition augments current therapies. MTH1 knockdown increased levels of oxidatively damaged DNA and DNA damage signaling alterations in all lung cancer cell lines but not normal fibroblasts, despite no detectable differences in reactive oxygen species levels between any cell lines. Furthermore, MTH1 knockdown reduced H23 cell proliferation. However, unexpectedly, it did not induce apoptosis in any cell line or enhance the effects of gemcitabine, cisplatin or radiation in combination treatments. Contrastingly, TH287 and TH588 MTH1 inhibitors induced apoptosis in H23 and H522 cells, but only increased oxidative DNA damage levels in H23, indicating that they kill cells independently of DNA oxidation and seemingly via MTH1-distinct mechanisms. MTH1 has a NSCLC-specific p53-independent role for suppressing DNA oxidation and genomic instability, though surprisingly the basis of this may not be reactive-oxygen-species-associated oxidative stress. Despite this, overall our cell viability data indicates that targeting MTH1 will likely not be an across-the-board effective NSCLC therapeutic strategy; rather it induces non-cytotoxic DNA damage that could promote cancer heterogeneity and evolution.

Damage detection of rotating wind turbine blades using local flexibility method and long-gauge fiber Bragg grating sensors

NASA Astrophysics Data System (ADS)

Hsu, Ting-Yu; Shiao, Shen-Yuan; Liao, Wen-I.

2018-01-01

Wind turbines are a cost-effective alternative energy source; however, their blades are susceptible to damage. Therefore, damage detection of wind turbine blades is of great importance for condition monitoring of wind turbines. Many vibration-based structural damage detection techniques have been proposed in the last two decades. The local flexibility method, which can determine local stiffness variations of beam-like structures by using measured modal parameters, is one of the most promising vibration-based approaches. The local flexibility method does not require a finite element model of the structure. A few structural modal parameters identified from the ambient vibration signals both before and after damage are required for this method. In this study, we propose a damage detection approach for rotating wind turbine blades using the local flexibility method based on the dynamic macro-strain signals measured by long-gauge fiber Bragg grating (FBG)-based sensors. A small wind turbine structure was constructed and excited using a shaking table to generate vibration signals. The structure was designed to have natural frequencies as close as possible to those of a typical 1.5 MW wind turbine in real scale. The optical fiber signal of the rotating blades was transmitted to the data acquisition system through a rotary joint fixed inside the hollow shaft of the wind turbine. Reversible damage was simulated by aluminum plates attached to some sections of the wind turbine blades. The damaged locations of the rotating blades were successfully detected using the proposed approach, with the extent of damage somewhat over-estimated. Nevertheless, although the specimen of wind turbine blades cannot represent a real one, the results still manifest that FBG-based macro-strain measurement has potential to be employed to obtain the modal parameters of the rotating wind turbines and then locations of wind turbine segments with a change of rigidity can be estimated effectively by utilizing these identified parameters.

Damage methodology approach on a composite panel based on a combination of Fringe Projection and 2D Digital Image Correlation

NASA Astrophysics Data System (ADS)

Felipe-Sesé, Luis; Díaz, Francisco A.

2018-02-01

The recent improvement in accessibility to high speed digital cameras has enabled three dimensional (3D) vibration measurements employing full-field optical techniques. Moreover, there is a need to develop a cost-effective and non-destructive testing method to quantify the severity of damages arising from impacts and thus, enhance the service life. This effect is more interesting in composite structures since possible internal damage has low external manifestation. Those possible damages have been previously studied experimentally by using vibration testing. Namely, those analyses were focused on variations in the modal frequencies or, more recently, mode shapes variations employing punctual accelerometers or vibrometers. In this paper it is presented an alternative method to investigate the severity of damage on a composite structure and how the damage affects to its integrity through the analysis of the full field modal behaviour. In this case, instead of punctual measurements, displacement maps are analysed by employing a combination of FP + 2D-DIC during vibration experiments in an industrial component. In addition, to analyse possible mode shape changes, differences between damaged and undamaged specimens are studied by employing a recent methodology based on Adaptive Image Decomposition (AGMD) procedure. It will be demonstrated that AGMD Image decomposition procedure, which decompose the displacement field into shape descriptors, is capable to detect and quantify the differences between mode shapes. As an application example, the proposed approach has been evaluated on two large industrial components (car bonnets) made of short-fibre reinforced composite. Specifically, the evolution of normalized AGMD shape descriptors has been evaluated for three different components with different damage levels. Results demonstrate the potential of the presented approach making it possible to measure the severity of a structural damage by evaluating the mode shape based in the analysis of its shape descriptors.

Asymmetrical Damage Partitioning in Bacteria: A Model for the Evolution of Stochasticity, Determinism, and Genetic Assimilation

PubMed Central

Chao, Lin; Rang, Camilla Ulla; Proenca, Audrey Menegaz; Chao, Jasper Ubirajara

2016-01-01

Non-genetic phenotypic variation is common in biological organisms. The variation is potentially beneficial if the environment is changing. If the benefit is large, selection can favor the evolution of genetic assimilation, the process by which the expression of a trait is transferred from environmental to genetic control. Genetic assimilation is an important evolutionary transition, but it is poorly understood because the fitness costs and benefits of variation are often unknown. Here we show that the partitioning of damage by a mother bacterium to its two daughters can evolve through genetic assimilation. Bacterial phenotypes are also highly variable. Because gene-regulating elements can have low copy numbers, the variation is attributed to stochastic sampling. Extant Escherichia coli partition asymmetrically and deterministically more damage to the old daughter, the one receiving the mother’s old pole. By modeling in silico damage partitioning in a population, we show that deterministic asymmetry is advantageous because it increases fitness variance and hence the efficiency of natural selection. However, we find that symmetrical but stochastic partitioning can be similarly beneficial. To examine why bacteria evolved deterministic asymmetry, we modeled the effect of damage anchored to the mother’s old pole. While anchored damage strengthens selection for asymmetry by creating additional fitness variance, it has the opposite effect on symmetry. The difference results because anchored damage reinforces the polarization of partitioning in asymmetric bacteria. In symmetric bacteria, it dilutes the polarization. Thus, stochasticity alone may have protected early bacteria from damage, but deterministic asymmetry has evolved to be equally important in extant bacteria. We estimate that 47% of damage partitioning is deterministic in E. coli. We suggest that the evolution of deterministic asymmetry from stochasticity offers an example of Waddington’s genetic assimilation. Our model is able to quantify the evolution of the assimilation because it characterizes the fitness consequences of variation. PMID:26761487

Effects of branched-chain amino acids supplementation on both plasma amino acids concentration and muscle energetics changes resulting from muscle damage: A randomized placebo controlled trial.

PubMed

Fouré, Alexandre; Nosaka, Kazunori; Gastaldi, Marguerite; Mattei, Jean-Pierre; Boudinet, Hélène; Guye, Maxime; Vilmen, Christophe; Le Fur, Yann; Bendahan, David; Gondin, Julien

2016-02-01

Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Asymmetrical Damage Partitioning in Bacteria: A Model for the Evolution of Stochasticity, Determinism, and Genetic Assimilation.

PubMed

Chao, Lin; Rang, Camilla Ulla; Proenca, Audrey Menegaz; Chao, Jasper Ubirajara

2016-01-01

Non-genetic phenotypic variation is common in biological organisms. The variation is potentially beneficial if the environment is changing. If the benefit is large, selection can favor the evolution of genetic assimilation, the process by which the expression of a trait is transferred from environmental to genetic control. Genetic assimilation is an important evolutionary transition, but it is poorly understood because the fitness costs and benefits of variation are often unknown. Here we show that the partitioning of damage by a mother bacterium to its two daughters can evolve through genetic assimilation. Bacterial phenotypes are also highly variable. Because gene-regulating elements can have low copy numbers, the variation is attributed to stochastic sampling. Extant Escherichia coli partition asymmetrically and deterministically more damage to the old daughter, the one receiving the mother's old pole. By modeling in silico damage partitioning in a population, we show that deterministic asymmetry is advantageous because it increases fitness variance and hence the efficiency of natural selection. However, we find that symmetrical but stochastic partitioning can be similarly beneficial. To examine why bacteria evolved deterministic asymmetry, we modeled the effect of damage anchored to the mother's old pole. While anchored damage strengthens selection for asymmetry by creating additional fitness variance, it has the opposite effect on symmetry. The difference results because anchored damage reinforces the polarization of partitioning in asymmetric bacteria. In symmetric bacteria, it dilutes the polarization. Thus, stochasticity alone may have protected early bacteria from damage, but deterministic asymmetry has evolved to be equally important in extant bacteria. We estimate that 47% of damage partitioning is deterministic in E. coli. We suggest that the evolution of deterministic asymmetry from stochasticity offers an example of Waddington's genetic assimilation. Our model is able to quantify the evolution of the assimilation because it characterizes the fitness consequences of variation.

Assessment of flood risk in Tokyo metropolitan area

NASA Astrophysics Data System (ADS)

Hirano, J.; Dairaku, K.

2013-12-01

Flood is one of the most significant natural hazards in Japan. The Tokyo metropolitan area has been affected by several large flood disasters. Therefore, investigating potential flood risk in Tokyo metropolitan area is important for development of adaptation strategy for future climate change. We aim to develop a method for evaluating flood risk in Tokyo Metropolitan area by considering effect of historical land use and land cover change, socio-economic change, and climatic change. Ministry of land, infrastructure, transport and tourism in Japan published 'Statistics of flood', which contains data for flood causes, number of damaged houses, area of wetted surface, and total amount of damage for each flood at small municipal level. By using these flood data, we estimated damage by inundation inside a levee for each prefecture based on a statistical method. On the basis of estimated damage, we developed flood risk curves in the Tokyo metropolitan area, representing relationship between damage and exceedance probability of flood for the period 1976-2008 for each prefecture. Based on the flood risk curve, we attempted evaluate potential flood risk in the Tokyo metropolitan area and clarify the cause for regional difference of flood risk. By analyzing flood risk curves, we found out regional differences of flood risk. We identified high flood risk in Tokyo and Saitama prefecture. On the other hand, flood risk was relatively low in Ibaraki and Chiba prefecture. We found that these regional differences of flood risk can be attributed to spatial distribution of entire property value and ratio of damaged housing units in each prefecture.We also attempted to evaluate influence of climate change on potential flood risk by considering variation of precipitation amount and precipitation intensity in the Tokyo metropolitan area. Results shows that we can evaluate potential impact of precipitation change on flood risk with high accuracy by using our methodology. Acknowledgments This study is conducted as part of the research subject "Vulnerability and Adaptation to Climate Change in Water Hazard Assessed Using Regional Climate Scenarios in the Tokyo Region' (National Research Institute for Earth Science and Disaster Prevention; PI: Koji Dairaku) of Research Program on Climate Change Adaptation (RECCA) and was supported by the SOUSEI Program, funded by Ministry of Education, Culture, Sports, Science and Technology, Government of Japan

X-ray lasers: Strategic problems and potential as an in-orbit exoatmospheric ballistic missile defense system

NASA Astrophysics Data System (ADS)

Perusich, Karl Anthony

1986-12-01

The problems and potential of a single proposed ballistic missile defense system, the X-ray laser-armed satellite, are examined in this research. Specifically, the X-ray laser satellite system is examined to determine its impact on the issues of cost-effectiveness and crisis stability. To examime the cost-effectiveness and the crisis stability of the X-ray laser satellites, a simulation of a nuclear exchange was constructed. The X-ray laser satellites were assumed to be vulnerable to attack from energy satellites with limited satellite-to-satellite lethal ranges. Symmetric weapons and force postures were used. Five principal weapon classes were used in the model: ICMBs, SLBMs, X-ray laser satellites, bombers, and endo-atmospheric silo defenses. Also, the orbital dynamics of the ballistic missiles and satellites were simulated. The cost-effectiveness of the X-ray laser satellites was determined for two different operational capabilities, damage-limitation and assured destruction. The following conclusions were reached. The effects of deployment of a new weapon system on the Triad as a whole should be examined. The X-ray laser was found to have little effectiveness as a damage-limiting weapon for a defender. For an assured destruction capability, X-ray laser satellites could be part of a minimum-cost force mix with that capability.

Protection of Momordica charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway.

PubMed

Duan, Zhen-Zhen; Zhou, Xiao-Ling; Li, Yi-Hang; Zhang, Feng; Li, Feng-Ying; Su-Hua, Qi

2015-01-01

It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.

The predominant protective effect of tianeptine over other antidepressants in models of neuronal apoptosis: the effect blocked by inhibitors of MAPK/ERK1/2 and PI3-K/Akt pathways.

PubMed

Jantas, D; Krawczyk, S; Lason, W

2014-02-01

Tianeptine (Tian) possesses neuroprotective potential, however, little is known about the effect of this drug in models of neuronal apoptosis. In the present study, we aimed (1) to compare the neuroprotective capacities of some antidepressants (ADs) in the models of staurosporine (St)- and doxorubicin (Dox)-evoked cell death, activating the intracellular and the extracellular apoptotic pathway, respectively; (2) to identify the Tian-modulated steps underlying its neuroprotective action; (3) to test the effect of various ADs against Dox-evoked cell damage in glia cells. Primary neuronal and glia cell cultures and retinoic acid-differentiated human neuroblastoma SH-SY5Y (RA-SH-SY5Y) cells were co-treated with imipramine, fluoxetine, citalopram, reboxetine, mirtazapine or Tian and St or Dox. The data showed the predominant neuroprotective effect of Tian over other tested ADs against St- and Dox-induced cell damage in primary neurons and in RA-SH-SY5Y cells. This effect was shown to be caspase-3-independent but connected with attenuation of DNA fragmentation. Moreover, neuroprotection elicited by Tian was blocked by pharmacological inhibitors of MAPK/ERK1/2 and PI3-K/Akt signaling pathways as well by inhibitor of necroptosis, necrostatin-1. Interestingly, the protective effects of all tested ADs were demonstrated in primary glia cells against the Dox-evoked cell damage. The obtained data suggests the glial cells as a common target for protective action of various ADs whereas in relation to neuronal cells only Tian possesses such properties, at least against St- and Dox-induced cell damage. Moreover, this neuroprotective effect of Tian is caspase-3-independent and engages the regulation of survival pathways (MAPK/ERK1/2 and PI3-K/Akt).

Identifying Patterns in Extreme Precipitation Risk and the Related Impacts

NASA Astrophysics Data System (ADS)

Schroeer, K.; Tye, M. R.

2017-12-01

Extreme precipitation can harm human life and assets through flooding, hail, landslides, or debris flows. Flood risk assessments typically concentrate on river or mountain torrent channels, using water depth, flow velocity, and/or sediment deposition to quantify the risk. In addition, extreme events with high recurrence intervals are often the main focus. However, damages from short-term and localized convective showers often occur away from watercourses. Also, damages from more frequent small scale extremes, although usually less disastrous, can accumulate to considerable financial burdens. Extreme convective precipitation is expected to intensify in a warmer climate, and vulnerability patterns might change in tandem with changes in the character of precipitation and flood types. This has consequences for adaptation planners who want to establish effective protection measures and reduce the cost from natural hazards. Here we merge hydrological and exposure data to identify patterns of risk under varying synoptic conditions. Exposure is calculated from a database of 76k damage claims reported to the national disaster fund in 480 municipalities in south eastern Austria from 1990-2015. Hydrological data comprise sub-daily precipitation (59 gauges) and streamflow (62 gauges) observations. We use synoptic circulation types to identify typical precipitation patterns. They indicate the character of precipitation even if a gauge is not in close proximity, facilitating potential future research with regional climate model data. Results show that more claims are reported under synoptic conditions favouring convective precipitation (on average 1.5-3 times more than on other days). For agrarian municipalities, convective precipitation damages are among the costliest after long low-intensity precipitation events. In contrast, Alpine communities are particularly vulnerable to convective high-intensity rainfall. In addition to possible observational error, uncertainty is present in damage reporting errors, claims from private insurers and adaptation effects after damaging events. As for the latter, preliminary results indicate that investments regularly occur after big events, which may skew subsequent damage claims. Their effectiveness, though, needs to be analyzed in future research.

Protection of ionizing radiation-induced cytogenetic damage by hydroalcoholic extract of Cynodon dactylon in Chinese hamster lung fibroblast cells and human peripheral blood lymphocytes.

PubMed

Rao, Bola Sadashiva Satish; Upadhya, Dinesh; Adiga, Satish Kumar

2008-01-01

The radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (family: Poaceae) against radiation-induced cytogenetic damage was analyzed using Chinese hamster lung fibroblast (V79) cells and human peripheral blood lymphocytes (HPBLs) growing in vitro. Induction of micronuclei was used as an index of cytogenetic damage, evaluated in cytokinesis blocked binucleate cells. The hydroalcoholic Cynodon dactylon extract (CDE) rendered protection against the radiation-induced DNA damage, as evidenced by the significant (p<0.001) reduction in micronucleated binucleate cells (MNBNC%) after various doses of CDE treatment in V79 cells and HPBLs. The optimum dose of CDE (40 and 50 microg/ml in HPBLs and V79 cells, respectively) with the greatest reduction in micronuclei was further used in combination with various doses of gamma radiation (0.5, 1, 2, 3, and 4 Gy) exposed 1 h after CDE treatment. A linear dose-dependent MNBNC% increase in radiation alone group was observed, while 40/50 microg/ml CDE significantly resulted in the reduction of MNBNC%, compared to the respective radiation alone groups. CDE resulted in a dose-dependent increase in free radical scavenging ability against various free radicals, viz., 2, 2-diphenyl-2-picryl-hydrazyl (DPPH); 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS); superoxide anion (O2*-); hydroxyl radical (OH*) and nitric oxide radical (NO*) generated in vitro. Also, an excellent (70%) inhibition of lipid peroxidation in vitro was observed at a dose of 300 microg/ml CDE, attaining the saturation point at higher doses. The present findings demonstrated the radioprotective effect of CDE, also rendering protection against radiation-induced genomic instability and DNA damage. The observed radioprotective effect may be partly attributed to the free radical scavenging and antilipid peroxidative potential of CDE.

Usability of aerial video footage for 3-D scene reconstruction and structural damage assessment

NASA Astrophysics Data System (ADS)

Cusicanqui, Johnny; Kerle, Norman; Nex, Francesco

2018-06-01

Remote sensing has evolved into the most efficient approach to assess post-disaster structural damage, in extensively affected areas through the use of spaceborne data. For smaller, and in particular, complex urban disaster scenes, multi-perspective aerial imagery obtained with unmanned aerial vehicles and derived dense color 3-D models are increasingly being used. These type of data allow the direct and automated recognition of damage-related features, supporting an effective post-disaster structural damage assessment. However, the rapid collection and sharing of multi-perspective aerial imagery is still limited due to tight or lacking regulations and legal frameworks. A potential alternative is aerial video footage, which is typically acquired and shared by civil protection institutions or news media and which tends to be the first type of airborne data available. Nevertheless, inherent artifacts and the lack of suitable processing means have long limited its potential use in structural damage assessment and other post-disaster activities. In this research the usability of modern aerial video data was evaluated based on a comparative quality and application analysis of video data and multi-perspective imagery (photos), and their derivative 3-D point clouds created using current photogrammetric techniques. Additionally, the effects of external factors, such as topography and the presence of smoke and moving objects, were determined by analyzing two different earthquake-affected sites: Tainan (Taiwan) and Pescara del Tronto (Italy). Results demonstrated similar usabilities for video and photos. This is shown by the short 2 cm of difference between the accuracies of video- and photo-based 3-D point clouds. Despite the low video resolution, the usability of these data was compensated for by a small ground sampling distance. Instead of video characteristics, low quality and application resulted from non-data-related factors, such as changes in the scene, lack of texture, or moving objects. We conclude that not only are current video data more rapidly available than photos, but they also have a comparable ability to assist in image-based structural damage assessment and other post-disaster activities.

Vitamin U has a protective effect on valproic acid-induced renal damage due to its anti-oxidant, anti-inflammatory, and anti-fibrotic properties.

PubMed

Gezginci-Oktayoglu, Selda; Turkyilmaz, Ismet Burcu; Ercin, Merve; Yanardag, Refiye; Bolkent, Sehnaz

2016-01-01

The aim of present study was to investigate the effect of vitamin U (vit U, S-methylmethionine) on oxidative stress, inflammation, and fibrosis within the context of valproic acid (VPA)-induced renal damage. In this study, female Sprague Dawley rats were randomly divided into four groups: Group I consisted of intact animals, group II was given vit U (50 mg/kg/day, by gavage), group III was given VPA (500 mg/kg/day, intraperitonally), and group IV was given VPA + vit U. The animals were treated by vit U 1 h prior to treatment with VPA every day for 15 days. The following results were obtained in vit U + VPA-treated rats: (i) the protective effect of vit U on renal damage was shown by a significant decrease in histopathological changes and an increase in Na(+)/K(+)-ATPase activity; (ii) anti-oxidant property of vit U was demonstrated by a decrease in malondialdehyde levels and xanthine oxidase activity and an increase in glutathione levels, catalase and superoxide dismutase activities; (iii) anti-inflammatory property of vit U was demonstrated by a decrease in tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1 levels, and adenosine deaminase activity; (iv) anti-fibrotic effect of vit U was shown by a decrease in transforming growth factor-β, collagen-1 levels, and arginase activity. Collectively, these data show that VPA is a promoter of inflammation, oxidative stress, and fibrosis which resulted in renal damage. Vit U can be proposed as a potential candidate for preventing renal damage which arose during the therapeutic usage of VPA.

Effects Of Moisture On Zinc Orthotitanate Paint

NASA Technical Reports Server (NTRS)

Mon, Gordon R.; Gonzalez, Charles C.; Ross, JR., Ronald g.; Wen, Liang C.; O'Donnell, Timothy

1991-01-01

Report presents results of tests of electrical conductivity and resistance to corrosion of zinc orthotitanate (ZOT) paint. Measured effects of temperature, humidity, and vacuum on ceramic paint. Used as temperature-control coating designed to have low and stable ratio of absorptance to emittance for heat radiation. Helps to prevent buildup of static electric charge and helps to protect electronic circuitry from potentially damaging static discharges.

Avalanche related damage potential - changes of persons and mobile values since the mid-twentieth century, case study Galtür

NASA Astrophysics Data System (ADS)

Keiler, M.; Zischg, A.; Fuchs, S.; Hama, M.; Stötter, J.

2005-01-01

When determining risk related to natural hazard processes, many studies neglect the investigations of the damage potential or are limited to the assessment of immobile values like buildings. However, persons as well as mobile values form an essential part of the damage potential. Knowledge of the maximum number of exposed persons in an endangered area is of great importance for elaborating evacuation plans and immediate measures in case of catastrophes. In addition, motor vehicles can also be highly damaged, as was shown by the analysis of avalanche events. With the removal of mobile values in time as a preventive measure this kind of damage can be minimised. This study presents a method for recording the maximum number of exposed persons and monetarily assessing motor vehicles in the municipality of Galtür (Tyrol, Austria). Moreover, general developments of the damage potential due to significant socio-economic changes since the mid-twentieth century are pointed out in the study area. The present situation of the maximum number of persons and mobile values in the official avalanche hazard zones of the municipality is described in detail. Information on the number of persons is derived of census data, tourism and employment statistics. During the winter months, a significant increase overlaid by strong short-term fluctuation in the number of persons can be noted. These changes result from a higher demand of tourism related manpower as well as from varying occupancy rates. The number of motor vehicles in endangered areas is closely associated to the number of exposed persons. The potential number of motor vehicles is investigated by means of mapping, statistics on the stock of motor vehicles and the density distribution. Diurnal and seasonal fluctuations of the investigated damage potential are pointed out. The recording of the number of persons and mobile values in endangered areas is vital for any disaster management.

DNA damage in outdoor workers occupationally exposed to environmental air pollutants

PubMed Central

Tovalin, H; Valverde, M; Morandi, M T; Blanco, S; Whitehead, L; Rojas, E

2006-01-01

Background Health concerns about the exposure to genotoxic and carcinogenic agents in the air are particularly significant for outdoor workers in less developed countries. Aims To investigate the association between personal exposure to a group of air pollutants and severity of DNA damage in outdoor workers from two Mexican cities. Methods DNA damage (Comet assay) and personal exposure to volatile organic compounds, PM2.5, and ozone were investigated in 55 outdoor and indoor workers from México City and Puebla. Results In México City, outdoor workers had greater DNA damage, reflected by a longer tail length, than indoor workers (median 46.8 v 30.1 μm), and a greater percentage of highly damaged cells (cells with tail length ⩾41 μm); in Puebla, outdoor and indoor workers had similar DNA damage. There were more alkali labile sites in outdoor than indoor workers. The DNA damage magnitude was positively correlated with PM2.5 and ozone exposure. Outdoor and indoor workers with ⩾60% of highly damaged cells (highly damaged workers) had significantly higher exposures to PM2.5, ozone, and some volatile organic compounds. The main factors associated with the highly damaged workers were ozone, PM2.5, and 1‐ethyl‐2‐methyl benzene exposure. Conclusions With this approach, the effects of some air pollutants could be correlated with biological endpoints from the Comet assay. It is suggested that the use of personal exposure assessment and biological endpoints evaluation could be an important tool to generate a more precise assessment of the associated potential health risks. PMID:16556741

Multi-effect of the water-soluble Moringa oleifera lectin against Serratia marcescens and Bacillus sp.: antibacterial, antibiofilm and anti-adhesive properties.

PubMed

Moura, M C; Trentin, D S; Napoleão, T H; Primon-Barros, M; Xavier, A S; Carneiro, N P; Paiva, P M G; Macedo, A J; Coelho, L C B B

2017-10-01

To evaluate the antibiofilm potential of water-soluble Moringa oleifera seed lectin (WSMoL) on Serratia marcescens and Bacillus sp. WSMoL inhibited biofilm formation by S. marcescens at concentrations lower than 2·6 μg ml -1 and impaired bacterial growth at higher concentrations, avoiding biofilm formation. For Bacillus sp., the lectin inhibited bacterial growth at all concentrations. The antibiofilm action of WSMoL is associated with damage to bacterial cells. WSMoL did not disrupt preformed S. marcescens biofilms but was able to damage cells inside them. On the other hand, the lectin reduced the number of cells in Bacillus sp. biofilm treated with it. WSMoL was able to control biofilm formation when immobilized on glass surface (116 μg cm -2 ), damaging S. marcescens cells and avoiding adherence of Bacillus sp. cells on glass. The Bacillus sp. isolate is member of Bacillus subtilis species complex and closely related to species of the conspecific 'amyloliquefaciens' group. WSMoL prevented biofilm development by S. marcescens and Bacillus sp. and the antibiofilm effect is also observed when the lectin is immobilized on glass. Taking together, our results provide support to the potential use of WSMoL for controlling biofilm formation by bacteria. © 2017 The Society for Applied Microbiology.

A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells.

PubMed

Hegde, Mahesh; Vartak, Supriya V; Kavitha, Chandagirikoppal V; Ananda, Hanumappa; Prasanna, Doddakunche S; Gopalakrishnan, Vidya; Choudhary, Bibha; Rangappa, Kanchugarakoppal S; Raghavan, Sathees C

2017-05-31

Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5g) for its ability to inhibit cell proliferation in different cancer models. Interestingly, 5g interfered with cell proliferation in both, cell lines and tumor cells leading to significant G2/M arrest. 5g treatment resulted in elevated levels of ROS and subsequently, DNA double-strand breaks (DSBs) explaining observed G2/M arrest. Consistently, we observed deregulation of many cell cycle associated proteins such as CDK1, BCL2 and their phosphorylated form, CyclinB1, CDC25c etc. Besides, 5g treatment led to decreased levels of mitochondrial membrane potential and activation of apoptosis. Interestingly, 5g administration inhibited tumor growth in mice without significant side effects. Thus, our study identifies 5g as a potent biochemical inhibitor to induce G2/M phase arrest of the cell cycle, and demonstrates its anticancer properties both ex vivo and in vivo.

Solar Irradiance Changes And Photobiological Effects At Earth's Surface Following Astrophysical Ionizing Radiation Events

NASA Astrophysics Data System (ADS)

Thomas, Brian; Neale, Patrick

2016-01-01

Astrophysical ionizing radiation events have been recognized as a potential threat to life on Earth for decades. Although there is some direct biological damage on the surface from redistributed radiation several studies have indicated that the greatest long term threat is from ozone depletion and subsequent heightened solar ultraviolet (UV) radiation. It is known that organisms exposed to this irradiation experience harmful effects such as sunburn and even direct damage to DNA, proteins, or other cellular structures. Simulations of the atmospheric effects of a variety of events (such as supernovae, gamma-ray bursts, and solar proton events) have been previously published, along with estimates of biological damage at Earth's surface. In the present work, we employed a radiative transfer model to expand and improve calculations of surface-level irradiance and biological impacts following an ionizing radiation event. We considered changes in surface-level UVB, UVA, and photosynthetically active radiation (visible light). Using biological weighting functions we have considered a wide range of effects, including: erythema and skin cancer in humans; inhibition of photosynthesis in the diatom Phaeodactylum sp. and dinoflagellate Prorocentrum micans inhibition of carbon fixation in Antarctic phytoplankton; inhibition of growth of oat (Avena sativa L. cv. Otana) seedlings; and cataracts. We found that past work overestimated UVB irradiance, but that relative estimates for increase in exposure to DNA damaging radiation are still similar to our improved calculations. We also found that the intensity of biologically damaging radiation varies widely with organism and specific impact considered; these results have implications for biosphere-level damage following astrophysical ionizing radiation events. When considering changes in surface-level visible light irradiance, we found that, contrary to previous assumptions, a decrease in irradiance is only present for a short time in very limited geographical areas; instead we found a net increase for most of the modeled time-space region. This result has implications for proposed climate changes associated with ionizing radiation events.

Dynamics of animal movement in an ecological context: dragonfly wing damage reduces flight performance and predation success

PubMed Central

Combes, S. A.; Crall, J. D.; Mukherjee, S.

2010-01-01

Much of our understanding of the control and dynamics of animal movement derives from controlled laboratory experiments. While many aspects of animal movement can be probed only in these settings, a more complete understanding of animal locomotion may be gained by linking experiments on relatively simple motions in the laboratory to studies of more complex behaviours in natural settings. To demonstrate the utility of this approach, we examined the effects of wing damage on dragonfly flight performance in both a laboratory drop–escape response and the more natural context of aerial predation. The laboratory experiment shows that hindwing area loss reduces vertical acceleration and average flight velocity, and the predation experiment demonstrates that this type of wing damage results in a significant decline in capture success. Taken together, these results suggest that wing damage may take a serious toll on wild dragonflies, potentially reducing both reproductive success and survival. PMID:20236968

Silibinin enhances the repair of ultraviolet B-induced DNA damage by activating p53-dependent nucleotide excision repair mechanism in human dermal fibroblasts

PubMed Central

Guillermo-Lagae, Ruth; Deep, Gagan; Ting, Harold; Agarwal, Chapla; Agarwal, Rajesh

2015-01-01

Ultraviolet radiation B (UVB) is the main cause of DNA damage in epidermal cells; and if not repaired, this DNA damage leads to skin cancer. In earlier studies, we have reported that natural flavonolignan silibinin exerts strong chemopreventive efficacy against UVB-induced skin damage and carcinogenesis; however mechanistic studies are still being actively pursued. Here, we investigated the role of nucleotide excision repair (NER) pathway in silibinin's efficacy to repair UVB-induced DNA damage. Normal human dermal fibroblasts (NHDFs) were exposed to UVB (1 mJ/cm2) with pre- or post- silibinin (100 μM) treatment, and cyclobutane pyrimidine dimers (CPDs) formation/repair was measured. Results showed that post-UVB silibinin treatment accelerates DNA repair via activating the NER pathway including the expression of XPA (xeroderma pigmentosum complementation group A), XPB, XPC, and XPG. In UVB exposed fibroblasts, silibinin treatment also increased p53 and GADD45α expression; the key regulators of the NER pathway and DNA repair. Consistently, post-UVB silibinin treatment increased the mRNA transcripts of XPA and GADD45α. Importantly, silibinin showed no effect on UVB-induced DNA damage repair in XPA- and XPB-deficient human dermal fibroblasts suggesting their key role in silibinin-mediated DNA damage repair. Moreover, in the presence of pifithrin-α, an inhibitor of p53, the DNA repair efficacy of silibinin was compromised associated with a reduction in XPA and GADD45α transcripts. Together, these findings suggest that silibinin's efficacy against UVB-induced photodamage is primarily by inhibiting NER and p53; and these findings further support silibinin's usage as a potential inexpensive, effective, and non-toxic agent for skin cancer chemoprevention. PMID:26447614

Silibinin enhances the repair of ultraviolet B-induced DNA damage by activating p53-dependent nucleotide excision repair mechanism in human dermal fibroblasts.

PubMed

Guillermo-Lagae, Ruth; Deep, Gagan; Ting, Harold; Agarwal, Chapla; Agarwal, Rajesh

2015-11-24

Ultraviolet radiation B (UVB) is the main cause of DNA damage in epidermal cells; and if not repaired, this DNA damage leads to skin cancer. In earlier studies, we have reported that natural flavonolignan silibinin exerts strong chemopreventive efficacy against UVB-induced skin damage and carcinogenesis; however mechanistic studies are still being actively pursued. Here, we investigated the role of nucleotide excision repair (NER) pathway in silibinin's efficacy to repair UVB-induced DNA damage. Normal human dermal fibroblasts (NHDFs) were exposed to UVB (1 mJ/cm2) with pre- or post- silibinin (100 μM) treatment, and cyclobutane pyrimidine dimers (CPDs) formation/repair was measured. Results showed that post-UVB silibinin treatment accelerates DNA repair via activating the NER pathway including the expression of XPA (xeroderma pigmentosum complementation group A), XPB, XPC, and XPG. In UVB exposed fibroblasts, silibinin treatment also increased p53 and GADD45α expression; the key regulators of the NER pathway and DNA repair. Consistently, post-UVB silibinin treatment increased the mRNA transcripts of XPA and GADD45α. Importantly, silibinin showed no effect on UVB-induced DNA damage repair in XPA- and XPB-deficient human dermal fibroblasts suggesting their key role in silibinin-mediated DNA damage repair. Moreover, in the presence of pifithrin-α, an inhibitor of p53, the DNA repair efficacy of silibinin was compromised associated with a reduction in XPA and GADD45α transcripts. Together, these findings suggest that silibinin's efficacy against UVB-induced photodamage is primarily by inhibiting NER and p53; and these findings further support silibinin's usage as a potential inexpensive, effective, and non-toxic agent for skin cancer chemoprevention.

Paraheliotropic leaf movement in Siratro as a protective mechanism against drought-induced damage to primary photosynthetic reactions: damage by excessive light and heat.

PubMed

Ludlow, M M; Björkman, O

1984-11-01

Damage to primary photosynthetic reactions by drought, excess light and heat in leaves of Macroptilium atropurpureum Dc. cv. Siratro was assessed by measurements of chlorophyll fluorescence emission kinetics at 77 K (-196°C). Paraheliotropic leaf movement protected waterstressed Siratro leaves from damage by excess light (photoinhibition), by heat, and by the interactive effects of excess light and high leaf temperatures. When the leaves were restrained to a horizontal position, photoinhibition occurred and the degree of photoinhibitory damage increased with the time of exposure to high levels of solar radiation. Severe inhibition was followed by leaf death, but leaves gradually recovered from moderate damage. This drought-induced photoinhibitory damage seemed more closely related to low leaf water potential than to low leaf conductance. Exposure to leaf temperatures above 42°C caused damage to the photosynthetic system even in the dark and leaves died at 48°C. Between 42 and 48°C the degree of heat damage increased with the time of exposure, but recovery from moderate heat damage occurred over several days. The threshold temperature for direct heat damage increased with the growth temperature regime, but was unaffected by water-stress history or by current leaf water status. No direct heat damage occurred below 42°C, but in water-stressed plants photoinhibition increased with increasing leaf temperature in the range 31-42°C and with increasing photon flux density up to full sunglight values. Thus, water stress evidently predisposes the photosynthetic system to photoinhibition and high leaf temperature exacerbates this photoinhibitory damage. It seems probable that, under the climatic conditions where Siratro occurs in nature, but in the absence of paraheliotropic leaf movement, photoinhibitory damage would occur more frequently during drought than would direct heat damage.

Effects of seaweed-restructured pork diets enriched or not with cholesterol on rat cholesterolaemia and liver damage.

PubMed

Schultz Moreira, Adriana R; García-Fernández, Rosa A; Bocanegra, Aranzazu; Méndez, M Teresa; Bastida, Sara; Benedí, Juana; Sánchez-Reus, M Isabel; Sánchez-Muniz, Francisco J

2013-06-01

Seaweed enriched-restructured pork (RP) is a potential functional food. However, indications of adverse effects associated with herbal medications, which include among others liver failure, toxic hepatitis, and death have been reported. Cholesterol feeding produces hepatomegalia and fat liver infiltration. The effect of seaweed-RP diet, cholesterol-enriched or not, on plasma cholesterol, liver damage markers, structure, and cytochrome CYP4A-1 were evaluated after 5 wk. Eight rat groups were fed a mix of 85% AIN-93M rodent-diet plus 15% RP. The Cholesterol-control (CC), Cholesterol-Wakame (CW), Cholesterol-Nori (CN) and Cholesterol-Sea Spaghetti (CS) groups respectively consumed similar diets to control (C), Wakame (W), Nori (N), and Sea Spaghetti (S) but as part of hypercholesterolaemic diets. CN and CS significantly blocked the hypercholesterolaemic effect observed in CC group. After 5-wk, N and S diets increased the CYP4A-1 expression. However, seaweed-RPs were unable to reduce the histological liver alterations observed in CC group. Larger and more abundant hepatocellular alterations were found in CS and CN rats suggesting that the hypocholesterolaemic effects of these seaweed-RPs seem to be a two-edged sword as they increased liver damage. Future studies are needed to understand the involved mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Caffeic acid and quercetin protect erythrocytes against the oxidative stress and the genotoxic effects of lambda-cyhalothrin in vitro.

PubMed

Abdallah, Fatma Ben; Fetoui, H; Fakhfakh, F; Keskes, L

2012-01-01

Lambda-cyhalothrin (LTC) is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activities used to control wide range of insect pests in a variety of applications. The aim of this study was to examine (i) the potency of LTC to induce oxidative stress response in rat erythrocytes in vitro and (ii) the role of caffeic acid (20 μM) and/or quercetin (10 μM) in preventing the cytotoxic effects. Erythrocytes were divided into four portions. The erythrocytes of the first portion were incubated for 4 h at 37°C with different concentrations (0, 50 and 100 μM) of LTC. The others portions were pretreated with caffeic acid and/or quercetin for 30 min prior to LTC incubation. Lipid peroxidation, protein oxidation, antioxidant enzyme activities and DNA damage were examined. LTC at different concentrations causes increased levels of lipid peroxidation, protein oxidation, DNA damage and decreased antioxidant enzyme activities. Combined caffeic acid and quercetin pretreatments significantly reduced the levels of lipid peroxidation markers, that is thiobarbituric acid reactive substance (TBARS), protein carbonyls (PCO) and decreased DNA damage in LTC portion. Further, combined caffeic acid and quercetin pretreatment maintain antioxidant enzyme activities and glutathione content near to normal values. These results suggest that LTC exerts its toxic effect by increasing lipid peroxidation, altering the antioxidant enzyme activities and DNA damage. Caffeic acid and quercetin pretreatments prevent the toxic effects of LTC, suggesting their role as a potential antioxidant.

Protective effect of alpha glucosyl hesperidin (G-hesperidin) on chronic vanadium induced testicular toxicity and sperm nuclear DNA damage in male Sprague Dawley rats.

PubMed

Vijaya Bharathi, B; Jaya Prakash, G; Krishna, K M; Ravi Krishna, C H; Sivanarayana, T; Madan, K; Rama Raju, G A; Annapurna, A

2015-06-01

The study was conducted to evaluate the vanadium-induced testicular toxicity and its effect on sperm parameters, sperm nuclear DNA damage and histological alterations in Sprague Dawley rats and to assess the protective effect of G-hesperidin against this damage. Treatment of rats with vanadium at a dose of 1 mg kg bw(-1) for 90 days resulted in significant reduction in serum testosterone levels, sperm count and motility. Further, a parallel increase in abnormal sperm morphology and adverse histopathological changes in testis was also associated with vanadium administration when compared to normal control. Moreover, sperm chromatin dispersion assay revealed that vanadium induces sperm nuclear DNA fragmentation. A marked increase in testicular malondialdehyde levels and decreased activity of antioxidant enzymes such as superoxide dismutase and catalase indicates vanadium-induced oxidative stress. Co-administration of G-hesperidin at a dose of 25 and 50 mg kg bw(-1) significantly attenuated the sperm parameters and histological changes by restoring the antioxidant levels in rat testis. These results suggested that vanadium exposure caused reduced bioavailability of androgens to the tissue and increased free radical formation, thereby causing structural and functional changes in spermatozoa. G-hesperidin exhibited antioxidant effect by protecting the rat testis against vanadium-induced oxidative damage, further ensures antioxidant potential of bioflavonoids. © 2014 Blackwell Verlag GmbH.

Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

PubMed Central

Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

2016-01-01

Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes. PMID:26907305

Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes.

PubMed

Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

2016-02-19

Following one of the world's largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

Understanding cancer development processes after HZE-particle exposure: roles of ROS, DNA damage repair and inflammation.

PubMed

Sridharan, D M; Asaithamby, A; Bailey, S M; Costes, S V; Doetsch, P W; Dynan, W S; Kronenberg, A; Rithidech, K N; Saha, J; Snijders, A M; Werner, E; Wiese, C; Cucinotta, F A; Pluth, J M

2015-01-01

During space travel astronauts are exposed to a variety of radiations, including galactic cosmic rays composed of high-energy protons and high-energy charged (HZE) nuclei, and solar particle events containing low- to medium-energy protons. Risks from these exposures include carcinogenesis, central nervous system damage and degenerative tissue effects. Currently, career radiation limits are based on estimates of fatal cancer risks calculated using a model that incorporates human epidemiological data from exposed populations, estimates of relative biological effectiveness and dose-response data from relevant mammalian experimental models. A major goal of space radiation risk assessment is to link mechanistic data from biological studies at NASA Space Radiation Laboratory and other particle accelerators with risk models. Early phenotypes of HZE exposure, such as the induction of reactive oxygen species, DNA damage signaling and inflammation, are sensitive to HZE damage complexity. This review summarizes our current understanding of critical areas within the DNA damage and oxidative stress arena and provides insight into their mechanistic interdependence and their usefulness in accurately modeling cancer and other risks in astronauts exposed to space radiation. Our ultimate goals are to examine potential links and crosstalk between early response modules activated by charged particle exposure, to identify critical areas that require further research and to use these data to reduced uncertainties in modeling cancer risk for astronauts. A clearer understanding of the links between early mechanistic aspects of high-LET response and later surrogate cancer end points could reveal key nodes that can be therapeutically targeted to mitigate the health effects from charged particle exposures.

Is There a Causal Association between Genotoxicity and the Imposex Effect?

PubMed Central

Hagger, Josephine A.; Depledge, Michael H.; Oehlmann, Jörg; Jobling, Susan; Galloway, Tamara S.

2006-01-01

There is a growing body of evidence that indicates common environmental pollutants are capable of disrupting reproductive and developmental processes by interfering with the actions of endogenous hormones. Many reports of endocrine disruption describe changes in the normal development of organs and tissues that are consistent with genetic damage, and recent studies confirm that many chemicals classified to have hormone-modulating effects also possess carcinogenic and mutagenic potential. To date, however, there have been no conclusive examples linking genetic damage with perturbation of endocrine function and adverse effects in vivo. Here, we provide the first evidence of DNA damage associated with the development of imposex (the masculinization of female gastropods considered to be the result of alterations to endocrine-mediated pathways) in the dog-whelk Nucella lapillus. Animals (n = 257) that displayed various stages of tributyltin (TBT)-induced imposex were collected from sites in southwest England, and their imposex status was determined by physical examination. Linear regression analysis revealed a very strong relationship (correlation coefficient of 0.935, p < 0.0001) between the degree of imposex and the extent of DNA damage (micronucleus formation) in hemocytes. Moreover, histological examination of a larger number of dog-whelks collected from sites throughout Europe confirmed the presence of hyperplastic growths, primarily on the vas deferens and penis in both TBT-exposed male snails and in females that exhibited imposex. A strong association was found between TBT body burden and the prevalence of abnormal growths, thereby providing compelling evidence to support the hypothesis that environmental chemicals that affect reproductive processes do so partly through DNA damage pathways. PMID:16818242

Tm:fiber laser ablation with real-time temperature monitoring for minimizing collateral thermal damage: ex vivo dosimetry for ovine brain.

PubMed

Tunc, Burcu; Gulsoy, Murat

2013-01-01

The thermal damage of the surrounding tissue can be an unwanted result of continuous-wave laser irradiations. In order to propose an effective alternative to conventional surgical techniques, photothermal damage must be taken under control by a detailed dose study. Real-time temperature monitoring can be also an effective way to get rid of these negative effects. The aim of the present study is to investigate the potential of a new laser-thermoprobe, which consists of a continuous-wave 1,940-nm Tm:fiber laser and a thermocouple measurement system for brain surgery in an ex vivo study. A laser-thermoprobe was designed for using the near-by tissue temperature as a real-time reference for the applicator. Fresh lamb brain tissues were used for experiments. 320 laser shots were performed on both cortical and subcortical tissue. The relationship between laser parameters, temperature changes, and ablation (removal of tissue) efficiency was determined. The correlation between rate of temperature change and ablation efficiency was calculated. Laser-thermoprobe leads us to understand the basic laser-tissue interaction mechanism in a very cheap and easy way, without making a change in the experimental design. It was also shown that the ablation and coagulation (thermally irreversible damage) diameters could be predicted, and carbonization can be avoided by temperature monitoring. Copyright © 2013 Wiley Periodicals, Inc.