Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guérin vaccination against tuberculosis.

PubMed

Abubakar, I; Pimpin, L; Ariti, C; Beynon, R; Mangtani, P; Sterne, J A C; Fine, P E M; Smith, P G; Lipman, M; Elliman, D; Watson, J M; Drumright, L N; Whiting, P F; Vynnycky, E; Rodrigues, L C

2013-09-01

Recent evidence suggests that the duration of protection by bacillus Calmette-Guérin (BCG) may exceed previous estimates with potential implications for estimating clinical and cost-efficacy. To estimate the protection and duration of protection provided by BCG vaccination against tuberculosis, explore how this protection changes with time since vaccination, and examine the reasons behind the variation in protection and the rate of waning of protection. Electronic databases including MEDLINE, Excerpta Medica Database (EMBASE), Cochrane Databases, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE), Web of Knowledge, Biosciences Information Service (BIOSIS), Latin American and Caribbean Health Sciences Literature (LILACs), MEDCARIB Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from inception to May 2009. Index to Theses, System for Information on Grey Literature in Europe (SIGLE), Centre for Agricultural Bioscience International (CABI) Abstracts, Scopus, Article First, Academic Complete, Africa-Wide Information, Google Scholar, Global Health, British National Bibliography for Report Literature, and clinical trial registration websites were searched from inception to October 2009. Electronic databases searches, screening of identified studies, data extraction and analysis were undertaken. Meta-analysis was used to present numerical and graphical summaries of clinical efficacy and efficacy by time since vaccination. Evidence of heterogeneity was assessed using the tau-squared statistic. Meta-regression allowed the investigation of observed heterogeneity. Factors investigated included BCG strain, latitude, stringency of pre-BCG vaccination tuberculin testing, age at vaccination, site of disease, study design and vulnerability to biases. Rate of waning of protection was estimated using the ratio of the measure of efficacy after 10 years compared with the efficacy in the first 10 years of a study. Study selection. A total of 21,030 references were identified, providing data on 132 studies after abstract and full-text review. Efficacy. Protection against pulmonary tuberculosis in adults is variable, ranging from substantial protection in the UK MRC trial {rate ratio 0.22 [95% confidence interval (CI) 0.16 to 0.31]}, to absence of clinically important benefit, as in the large Chingleput trial [rate ratio 1.05 (95% CI 0.88 to 1.25)] and greater in latitudes further away from the equator. BCG vaccination efficacy was usually high, and varied little by form of disease (with higher protection against meningeal and miliary tuberculosis) or study design when BCG vaccination was given only to infants or to children after strict screening for tuberculin sensitivity. High levels of protection against death were observed from both trials and observational studies. The observed protective effect of BCG vaccination did not differ by the strain of BCG vaccine used in trials. Reviewed studies showed that BCG vaccination protects against pulmonary and extrapulmonary tuberculosis for up to 10 years. Most studies either did not follow up participants for long enough or had very few cases after 15 years. This should not be taken to indicate an absence of effect: five studies (one trial and four observational studies) provided evidence of measurable protection at least 15 years after vaccination. Efficacy declined with time. The rate of decline was variable, with faster decline in latitudes further from the equator and in situations where BCG vaccination was given to tuberculin-sensitive participants after stringent tuberculin testing. The main limitation of this review relates to quality of included trials, most of which were conducted before current standards for reporting were formulated. In addition, data were lacking in some areas and the review had to rely on evidence from observational studies. BCG vaccination protection against tuberculosis varies between populations, to an extent that cannot be attributed to chance alone. Failure to exclude those already sensitised to mycobacteria and study latitude closer to the equator were associated with lower efficacy. These factors explained most of the observed variation. There is good evidence that BCG vaccination protection declines with time and that protection can last for up to 10 years. Data on protection beyond 15 years are limited; however, a small number of trials and observational studies suggest that BCG vaccination may protect for longer. Further studies are required to investigate the duration of protection by BCG vaccination. The National Institute for Health Research Health Technology Assessment programme.

Associations of contextual risk and protective factors with fathers’ parenting practices in the post-deployment environment

PubMed Central

Davis, Laurel; Hanson, Sheila K.; Zamir, Osnat; Gewirtz, Abigail H.; DeGarmo, David S.

2015-01-01

Deployment separation and reunifications are salient contexts that directly impact effective family functioning and parenting for military fathers. Yet, we know very little about determinants of post-deployed father involvement and effective parenting. The present study examined hypothesized risk and protective factors of observed parenting for 282 post-deployed fathers who served in the Army National Guard/Reserves. Pre-intervention data were employed from fathers participating in the After Deployment, Adaptive Parenting Tools (ADAPT) randomized control trial. Parenting practices were obtained from direct observation of father-child interaction and included measures of problem solving, harsh discipline, positive involvement, encouragement, and monitoring. Risk factors included combat exposure, negative life events, months deployed, and PTSD symptoms. Protective factors included education, income, dyadic adjustment, and social support. Results of a structural equation model predicting an effective parenting construct indicated that months deployed, income, and father age were most related to observed parenting, explaining 16% of the variance. We are aware of no other study utilizing direct parent-child observations of father’s parenting skills following overseas deployment. Implications for practice and preventive intervention are discussed. PMID:26213794

GENO PROTECTIVE AND ANTI-APOPTOTIC EFFECT OF GREEN TEA AGAINST PERINATAL LIPOPOLYSACCHARIDE-EXPOSURE INDUCED LIVER TOXICITY IN RAT NEWBORNS

PubMed Central

Allam, Ahmed A.; Gabr, Sami A.; Ajarem, Jamaan; Alghadir, Ahmad H.; Sekar, Revathi; Chow, Billy KC

2017-01-01

Background: This study aims to examine the protective effect of green tea on the disturbances in oxidative stress and apoptosis related factors, mostly produced due to perinatal lipopolysaccharide (LPS) exposure, that subsequently induces liver cell damage. Materials and Methods: Anti-free radical, Antioxidant, scavenging, geno-protective, and antiapoptotic activity of aqueous green tea extract (AGTE) were assessed against LPS-induced hepatic dysfunction in newborn-rats. AGTE at doses of 100 & 200 mg/kg was orally administered daily to rat dams, during gestation and lactation. Results: AGTE was observed to exhibit protective effects by significantly attenuating LPS-induced alterations in serum AST, ALT, bilirubin, and albumin levels. Significant increase in the total antioxidant capacity (TAC), DNA contents, and reduction in nitric oxide (NO) levels were observed in AGTE treated rats comparing LPS-toxicated ones. Additionally, AGTE treatment significantly down-regulated apoptotic markers and this effect was directly correlated to the degree of hepatic fibrosis. The possible mechanisms of the potential therapeutic-liver protective effect of AGTE could be due to free radical scavenging potential and antiapoptotic properties caused by the presence of antioxidant polyphenolic components in AGTE. Conclusion: We thereby propose, based on our findings, that the anti-free radical and anti-apoptotic inducing properties of AGTE active constituents attribute to its functional efficacy as anti-fibrotic agent. PMID:28573233

Chemical Risk Assessment: Selected Federal Agencies’ Procedures, Assumptions, and Policies

DTIC Science & Technology

2001-08-01

adverse effects of exposures to hazardous substances or situations. It is a complex but valuable set of tools for federal regulatory agencies, helping...Act DES diethylstilbestrol DOT Department of Transportation ED effective dose EPA Environmental Protection Agency EPCRA Emergency Planning and...ISO International Organization for Standardization LED lowest effective dose LOAEL lowest observed adverse effect level LOEL lowest observed effect

Updated postlicensure surveillance of the meningococcal C conjugate vaccine in England and Wales: effectiveness, validation of serological correlates of protection, and modeling predictions of the duration of herd immunity.

PubMed

Campbell, Helen; Andrews, Nick; Borrow, Ray; Trotter, Caroline; Miller, Elizabeth

2010-05-01

Meningococcal serogroup C conjugate (MCC) vaccines were licensed in the United Kingdom more than 10 years ago based on correlates of protection that had previously been established for serogroup C-containing polysaccharide vaccines by using the serum bactericidal antibody (SBA) assay. These correlates of protection were subsequently validated against postlicensure estimates of observed vaccine effectiveness up to 7 to 9 months after the administration of the MCC vaccine. Vaccine effectiveness was, however, shown to fall significantly more than 1 year after the administration of a 3-dose course in infancy. Despite this finding, the marked impact on serogroup C disease has been sustained, with the lowest recorded incidence (0.02 case per 100,000 population) in the 2008-2009 epidemiological year, mainly due to the indirect herd immunity effect of the vaccine in reducing carriage. Updated estimates of vaccine effectiveness through 30 June 2009 confirmed high short-term protection after vaccination in infancy, at 97% (95% confidence interval [CI], 91% to 99%), falling to 68% (95% CI, -63% to 90%) more than a year after vaccination. The observed vaccine effectiveness more than 12 months postvaccination was consistent with measured declining SBA levels, but confidence intervals were imprecise; vaccine effectiveness estimates were consistent with SBA titers of 1:4 or 1:8 as correlates of long-term protection after a primary course in infants. Modeling suggested that protection against carriage persists for at least 3 years and predicted the stabilization of serogroup C disease at low levels (fewer than 50 cases per year) up to 2015-2016.

Updated Postlicensure Surveillance of the Meningococcal C Conjugate Vaccine in England and Wales: Effectiveness, Validation of Serological Correlates of Protection, and Modeling Predictions of the Duration of Herd Immunity ▿

PubMed Central

Campbell, Helen; Andrews, Nick; Borrow, Ray; Trotter, Caroline; Miller, Elizabeth

2010-01-01

Meningococcal serogroup C conjugate (MCC) vaccines were licensed in the United Kingdom more than 10 years ago based on correlates of protection that had previously been established for serogroup C-containing polysaccharide vaccines by using the serum bactericidal antibody (SBA) assay. These correlates of protection were subsequently validated against postlicensure estimates of observed vaccine effectiveness up to 7 to 9 months after the administration of the MCC vaccine. Vaccine effectiveness was, however, shown to fall significantly more than 1 year after the administration of a 3-dose course in infancy. Despite this finding, the marked impact on serogroup C disease has been sustained, with the lowest recorded incidence (0.02 case per 100,000 population) in the 2008-2009 epidemiological year, mainly due to the indirect herd immunity effect of the vaccine in reducing carriage. Updated estimates of vaccine effectiveness through 30 June 2009 confirmed high short-term protection after vaccination in infancy, at 97% (95% confidence interval [CI], 91% to 99%), falling to 68% (95% CI, −63% to 90%) more than a year after vaccination. The observed vaccine effectiveness more than 12 months postvaccination was consistent with measured declining SBA levels, but confidence intervals were imprecise; vaccine effectiveness estimates were consistent with SBA titers of 1:4 or 1:8 as correlates of long-term protection after a primary course in infants. Modeling suggested that protection against carriage persists for at least 3 years and predicted the stabilization of serogroup C disease at low levels (fewer than 50 cases per year) up to 2015-2016. PMID:20219881

The protective effect of intratympanic dexamethasone on streptomycin ototoxicity in rats.

PubMed

Gül, Aylin; Şengül, Engin; Yılmaz, Beyhan; Özkurt, Fazıl Emre; Akdağ, Mehmet; Keleş, Ayşenur; Topçu, İsmail

2017-06-01

The purpose of this experimental study was to investigate the protective role of intratympanically administered dexamethasone on the inner ears of rats that were exposed to streptomycin ototoxicity. Twenty-four adult Wistar albino rats were separated into 4 groups: Group 1 (only streptomycin), Group 2 (only intratympanic dexamethasone), Group 3 (streptomycin and intratympanic dexamethasone), and Group 4 (streptomycin and intratympanic saline). All rats were evaluated with distortion product otoacoustic emissions (DPOAE) tests before the start of treatment and on the day it ended. On the 45th day, after the final DPOAE tests, animals of all groups were sacrificed under general anesthesia. The differences between the amplitudes of DPOAE results were determined, and hearing results were statistically analyzed. Also, the cochleas of each rat were histopathologically evaluated under a light microscope with hematoxylin and eosin staining. In the intratympanic dexamethasone group it was observed that cochlear hair cells were mostly protected. No significant difference was seen between the DPOAE results before and after treatment (p >0.05). On the other hand, loss was observed in the hearing functions and hair cells of the rats that received streptomycin and streptomycin plus intratympanic saline (p <0.05). In the streptomycin plus intratympanic dexamethasone group, the cochlear hair cells were partially protected. A significant difference was observed when the DPOAE results (DP-grams) of the streptomycin plus intratypmanic dexamethasone group were compared to those of the streptomycin plus intratympanic saline group (p <0.05). After the experimental study, ototoxic effects of the administration of streptomycin and intratympanic dexamethasone were observed on the rats' cochlear hair cells. We conclude that intratympanic dexamethasone has protective effects against this cochlear damage in rats.

Protection by Isoprene against Singlet Oxygen in Leaves

PubMed Central

Affek, Hagit P.; Yakir, Dan

2002-01-01

Isoprene (2-methyl-1,3-butadiene) protection against effects of singlet oxygen was investigated in Myrtus communis and Rhamnus alaternus. In M. communis, singlet oxygen produced in the leaves by Rose Bengal (RB) led to a 65% decrease in net assimilation rates within 3 h, whereas isoprene emission rates showed either a 30% decrease at ambient CO2 concentrations or a 70% increase under high CO2. In both cases, these changes led to an increase in calculated internal isoprene concentrations. The isoprene protection effect was directly demonstrated by fumigation of young (non-emitting) leaves, treated with RB or bromoxynil (simulating photoinhibition). There was 42% and 29% reduction in the damage to net assimilation compared with non-fumigated leaves for RB or bromoxynil, respectively. In R. alaternus, similar effects of RB on net assimilation were observed, and additional fluorescence measurements showed a significantly smaller decrease in Fv/Fm in isoprene-fumigated young leaves treated with RB (from 0.78 to 0.52), compared with non-fumigated leaves (from 0.77 to 0.27). The internal isoprene concentrations used in this study and possible rate of 1O2 production in leaves indicate that the protective effects observed should be beneficial also under natural conditions. PMID:12011357

[Protective effect and mechanism of compound Ginkgo biloba granules on oxidative stress injury of HUVEC].

PubMed

Li, Qi; Chen, Xi; Kan, Xiao-Xi; Li, Yu-Jie; Yang, Qing; Wang, Ya-Jie; Chen, Ying; Weng, Xiao-Gang; Cai, Wei-Yan; Huang, He-Fei; Zhu, Xiao-Xin

2016-02-01

To reveal the protective and anti-apoptosis effect of compound Ginkgo biloba granules on oxidative stress injury of human umbilical vein endothelial cells (HUVEC). Negative control group, H2O2 model group and 4 drug pretreatment groups (80, 160, 320, 640 mg• L⁻¹) were established. The cell proliferation, morphological changes in each group after oxidative stress injury was detected by MTT assay and through microscope observation respectively. The content of LDH, MDA, SOD and NO and SOD activity in supernatant were detected to judge the protection effect of the drugs on endothelial cells. The protective effect on HUVEC apoptosis was analyzed by Caspase-3 activity test and Annexin V-FITC/PI staining. Western blot was used to observe the expression of apoptosis-related proteins Bcl-2 and Bax. Results showed that 1 200 μmol• L⁻¹ H2O2 can induce oxidative stress injury in endothelial cells and reduce the cell survival rate; cell proliferation inhibition degree is positively correlated with the effect time of H2O2. Besides, 80, 160, 320 640 mg•L⁻¹ compound Ginkgo biloba granules can protect HUVEC from oxidative stress injury, recover the normal proliferation level of cells, improve their state, prohibit cell apoptosis, and can up-regulate and down-regulate the expression level of Bcl-2 and Bax respectively. In conclusion, compound G. biloba granules can protect HUVEC from the oxidative stress injury induced by H2O2, its mechanism may be correlated with inhibition of the mitochondrial apoptotic pathway in HUVEC. Copyright© by the Chinese Pharmaceutical Association.

Concentration-Dependent Protection by Ethanol Extract of Propolis against γ-Ray-Induced Chromosome Damage in Human Blood Lymphocytes.

PubMed

Montoro, A; Barquinero, J F; Almonacid, M; Montoro, A; Sebastià, N; Verdú, G; Sahuquillo, V; Serrano, J; Saiz, M; Villaescusa, J I; Soriano, J M

2011-01-01

Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect, in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP), including 20, 40, 120, 250, 500, 750, 1000, and 2000 μg mL(-1) and then exposed to 2 Gy γ-rays. A significant and concentration-dependent decrease is observed in the frequency of chromosome aberrations in samples treated with EEP. The protection against the formation of dicentrics was concentration-dependent, with a maximum protection at 120 μg mL(-1) of EEP. The observed frequency of dicentrics is described as negative exponential function, indicating that the maximum protectible fraction of dicentrics is approximately 44%. Free radical scavenging and antioxidant activities are the mechanisms that these substances use to protect cells from ionizing radiation.

Concentration-Dependent Protection by Ethanol Extract of Propolis against γ-Ray-Induced Chromosome Damage in Human Blood Lymphocytes

PubMed Central

Montoro, A.; Barquinero, J. F.; Almonacid, M.; Montoro, A.; Sebastià, N.; Verdú, G.; Sahuquillo, V.; Serrano, J.; Saiz, M.; Villaescusa, J. I.; Soriano, J. M.

2011-01-01

Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect, in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP), including 20, 40, 120, 250, 500, 750, 1000, and 2000 μg mL−1 and then exposed to 2 Gy γ-rays. A significant and concentration-dependent decrease is observed in the frequency of chromosome aberrations in samples treated with EEP. The protection against the formation of dicentrics was concentration-dependent, with a maximum protection at 120 μg mL−1 of EEP. The observed frequency of dicentrics is described as negative exponential function, indicating that the maximum protectible fraction of dicentrics is approximately 44%. Free radical scavenging and antioxidant activities are the mechanisms that these substances use to protect cells from ionizing radiation. PMID:20981159

HPV Vaccine Effective at Multiple Anatomic Sites

Cancer.gov

A new study from NCI researchers finds that the HPV vaccine protects young women from infection with high-risk HPV types at the three primary anatomic sites where persistent HPV infections can cause cancer. The multi-site protection also was observed at l

Feasibility of a community intervention for the prevention of suicide and alcohol abuse with Yup'ik Alaska Native youth: the Elluam Tungiinun and Yupiucimta Asvairtuumallerkaa studies.

PubMed

Mohatt, Gerald V; Fok, Carlotta Ching Ting; Henry, David; Allen, James

2014-09-01

The Elluam Tungiinun and Yupiucimta Asvairtuumallerkaa studies evaluated the feasibility of a community intervention to prevent suicide and alcohol abuse among rural Yup'ik Alaska Native youth in two remote communities. The intervention originated in an Indigenous model of protection, and its development used a community based participatory research process. Feasibility assessment aimed to assess the extent to which (1) the intervention could be implemented in rural Alaska Native communities, and (2) the intervention was capable of producing measurable effects. Scales maximally sensitive to change were derived from earlier measurement work, and the study contrasted implementation process and outcomes across the two communities. In one community, medium dose response effects (d = .30-.50), with dose defined as number of intervention activities attended, were observed in the growth of intermediate protective factors and ultimate variables. In the other community, medium dose effects were observed for one intermediate protective factor variable, and small dose effects were observed in ultimate variables. Differences across communities in resources supporting intervention explain these contrasting outcomes. Results suggest implementation in these rural Alaska settings is feasible when sufficient resources are available to sustain high levels of local commitment. In such cases, measureable effects are sufficient to warrant a prevention trial.

The effects of compliance cost and specific consequence information on the use of safety equipment.

PubMed

Hathaway, J A; Dingus, T A

1992-12-01

The effects of compliance cost and warning content on the use of protective eyewear by racquetball players were evaluated. Four-hundred-twenty subjects were observed for use of eye protection in a field setting. Results indicate that proximal placement of eyewear and the inclusion of specific consequence warning information increased safety equipment use. Implications of this research for augmenting warning effectiveness and safety are discussed.

Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom

PubMed Central

Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Aguiyi, John C.

2012-01-01

Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value. PMID:21785646

Stable Nighttime Light Decreased in Protected Area of California: Findings from DMSP-OLS Observations and the Importance for Protected Area Policy Making

NASA Astrophysics Data System (ADS)

Jia, S.; Gillespie, T. W.

2016-12-01

Stable nighttime light, an indicator of persisting human activity and light pollution is a well-recognized disturbance to the wilderness of protected areas (PAs). Mostly supported by in situ observations, very limited studies of light pollution for PAs focused at a regional level and on a continuous time span to support policy making effectively. DMSP-OLS stable nighttime series provide continuous observation of nightlight and have been widely applied in studies focusing on human activities. In this study, we employed inter-calibrated DMSP-OLS nightlight series from 1992 to 2012 to evaluate the change of intensity and extension of stable nighttime light inside California PAs. We observed a decrease of stable nighttime light and a shrinkage in spatial extent in PAs located in all ecoregions from 1992 to 2012, especially before 2004. Such decrease and shrinkage occurred mostly in southern California and the Bay Area where mega metropolitan clusters locate. The successful application of protecting strategies in PAs and the improved technologies of lighting may contribute to the relieving of light pollution in PAs. However, the stable nighttime light slightly increased since 2004, when there was limited room for stricter protective regulations and the pressure from population growth persisted. Population density explained most spatial distribution of nightlight in years with census tract level demographic data available, except PAs with the highest wilderness such as Sierra Nevada Mts. We anticipate to improve the models with the newest remote sensing nighttime product from NASA Suomi-NPP and annually updated demographic data from American Community Survey at census tract level in the future to provide a cost-effective evaluation on protecting strategies. Such evaluation will support land managers of PAs and local policy-makers for modification and proposal of policies.

Metabolomics reveals the sex-specific effects of the SORT1 low-density lipoprotein cholesterol locus in healthy young adults.

PubMed

Klein, Matthias S; Connors, Kimberly E; Shearer, Jane; Vogel, Hans J; Hittel, Dustin S

2014-11-07

Metabolite profiles of individuals possessing either the cardiovascular risk or protective variants of the low-density lipoprotein cholesterol (LDL-C) associated 1p13.3 locus of the SORT1 gene (rs646776) were analyzed. Serum metabolites and lipids were assessed using LC-MS-based metabolomics in a healthy young population (n = 138: 95 males, 43 females). Although no significant differences were observed in the combined cohort, divergent sex effects were identified. Females carrying the protective allele showed increased phosphatidylcholines, very long chain fatty acids (>C20), and unsaturated fatty acids. Unsaturated fatty acids are considered to be protective against cardiovascular disease. In contrast, males carrying the protective allele exhibited decreased long-chain fatty acids (≤C20) and sphingomyelins, which is similarly considered to decrease cardiovascular disease risk. No significant changes in clinically assessed lipids such as LDL-C, high-density lipoprotein (HDL-C), total cholesterol, or triglycerides were observed in females, whereas only LDL-C was significantly changed in males. This indicates that, apart from reducing LDL-C, other mechanisms may contribute to the protective effect of the SORT1 locus. Thus, the analysis of metabolic biomarkers might reveal early disease development that may be overlooked by relying on standard clinical parameters.

Multiple protective effect of peptides released from Olea europaea and Prunus persica seeds against oxidative damage and cancer cell proliferation.

PubMed

Hernández-Corroto, Ester; Marina, María Luisa; García, María Concepción

2018-04-01

The long exposition to reactive species results in oxidative stress which has been related with the development of cancer and other serious diseases. Olea europaea and Prunus persica seeds present a high protein content and preliminary results demonstrated their high potency to obtain bioactive peptides. The protective effect against oxidative damage exerted by peptides released from Olea europaea and Prunus persica seeds has been evaluated in this work. Seed hydrolysates showed protection against oxidation through four different mechanisms: inhibition of the formation of hydroxyl radicals, scavenging of free radicals, reduction of oxidizing compounds, and inhibition of lipid peroxidation. Moreover, seed hydrolysates also reduced the oxidative stress induced by an oxidizing agent on human cancer cells. Despite protection evaluated by individual mechanisms seemed to be significantly affected by the seed genotype, overall protection of seed hydrolysates was not so different. Seeds hydrolysates were not cytotoxic on normal cells but they demonstrated antiproliferative effect on human cancer cells (HeLa, PC-3, and HT-29). Peptides in all seed hydrolysates were sequenced by RP-HPLC-ESI-Q-TOF. Eighteen common peptides were observed among olive seed hydrolysates while a wider variability was observed among Prunus seed hydrolysates. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical Risk Assessment: Traditional vs Public Health Perspectives

PubMed Central

Axelrad, Daniel A.; Bahadori, Tina; Bussard, David; Cascio, Wayne E.; Deener, Kacee; Dix, David; Thomas, Russell S.; Kavlock, Robert J.; Burke, Thomas A.

2017-01-01

Preventing adverse health effects of environmental chemical exposure is fundamental to protecting individual and public health. When done efficiently and properly, chemical risk assessment enables risk management actions that minimize the incidence and effects of environmentally induced diseases related to chemical exposure. However, traditional chemical risk assessment is faced with multiple challenges with respect to predicting and preventing disease in human populations, and epidemiological studies increasingly report observations of adverse health effects at exposure levels predicted from animal studies to be safe for humans. This discordance reinforces concerns about the adequacy of contemporary risk assessment practices for protecting public health. It is becoming clear that to protect public health more effectively, future risk assessments will need to use the full range of available data, draw on innovative methods to integrate diverse data streams, and consider health endpoints that also reflect the range of subtle effects and morbidities observed in human populations. Considering these factors, there is a need to reframe chemical risk assessment to be more clearly aligned with the public health goal of minimizing environmental exposures associated with disease. PMID:28520487

Hypertension and vascular dementia in the elderly: the potential role of anti-hypertensive agents.

PubMed

Coca, Antonio

2013-09-01

Vascular dementia (VaD) - a severe form of vascular cognitive impairment - and cognitive decline are associated with hypertension and therefore it seems logical to consider that reducing BP with anti-hypertensive therapy may protect against the development/onset of cognitive function impairment or dementia. This narrative, non-systematic review discusses the available evidence on the potential correlation between the use of anti-hypertensive agents and the risk of VaD and cognitive decline. MEDLINE was searched for inclusion of relevant studies. No limitations in time were considered. A consensus on the potential effects of anti-hypertensive treatment in the reduction of VaD and associated cognitive decline has not been reached. A protective effect of anti-hypertensive agents has been observed in a number of studies although it is still unclear whether different classes of anti-hypertensive agents have a different effect on the development of VaD. The protective effect of anti-hypertensive agents appears to depend on the specific drug used - positive effects have been observed with calcium channel blockers (CCBs), such as lercanidipine and nitrendipine, the combination perindopril-indapamide and telmisartan.

Ebselen reduces the toxicity of mechlorethamine in A-431 cells via inhibition of apoptosis.

PubMed

Lulla, Anju; Pino, Maria A; Piętka-Ottlik, Magdalena; Młochowski, Jacek; Sparavalo, Oleksiy; Billack, Blase

2013-06-01

A series of test compounds were evaluated for an ability to reduce the toxicity of the nitrogen mustard mechlorethamine (HN2) in vitro. The test compounds included resveratrol, pterostilbene, vitamin C, ebselen, ebselen diselenide, and ebselen-sulfur. Among them, ebselen demonstrated the highest degree of protection against HN2 toxicity. To this end, pretreatment of the cells with ebselen offered protection against the toxicant whereas no protection was observed when cells were first incubated with HN2 and then treated with ebselen. Significant increases in caspase 3 and caspase 9 activities were observed in response to HN2, and ebselen was found to reduce these effects. Taken together, the data presented here indicate that ebselen is an effective countermeasure to nitrogen mustard in vitro, which is worthy of future investigation in vivo. © 2013 Wiley Periodicals, Inc.

Protective and ameliorative effect of sea buckthorn leaf extract supplementation on lead induced hemato-biochemical alterations in Wistar rats.

PubMed

Zargar, Rizwana; Raghuwanshi, Pratiksha; Rastogi, Ankur; Koul, Aditi Lal; Khajuria, Pallavi; Ganai, Aafreen Wahid; Kour, Sumeet

2016-09-01

To evaluate the protective and ameliorative effect of aqueous sea buckthorn leaf extract (SLE) on hemato-biochemical profile in lead intoxicated Wistar rats. An experiment was conducted for 60 days. 36 adult male Wistar rats with a mean body weight of 177.8±12.6 g were divided into five groups and were subjected to various daily oral treatment regimens. Group I served as a negative control receiving only feed and water, Group II (positive control for lead) received lead acetate at 250 ppm in drinking water, and Group III (positive control for SLE) received SLE at 100 mg/kg b.wt. Animals in Group IV received a combination of lead acetate at 250 ppm in drinking water for the first 45 days and SLE at 100 mg/kg b.wt. throughout the experimental period of 60-day, and in Group V for the last 15 days of the trial after the administration of lead acetate until the first 45 days of the trial to study the protective and ameliorating effects of SLE, respectively. Blood samples were collected from retro-orbital fossa of each rat on 0 th , 45 th , and 60 th day of the experiment for hemato-biochemical analysis including hemoglobin (Hb), packed cell volume (PCV), serum total protein, albumin, globulin, albumin:globulin ratio, cholesterol, urea, and creatinine. Significantly (p<0.01) lower levels of serum total proteins and albumin, and a significantly (p<0.01) higher serum cholesterol, urea and creatinine levels were observed in Group II (lead intoxicated group) in comparison to Group I (negative control). Administration of SLE at 100 mg/kg body wt. to lead intoxicated Wistar rats resulted in normalization of almost all the biochemical parameters studied in both the treatment Groups, i.e., IV and V (protective and ameliorative). However, the effects were more pronounced in the protective group. No effects of SLE supplementation were observed on Hb levels. PCV levels improved in protective groups, but no effect was observed in ameliorative group in comparison to lead intoxicated groups. SLE administration at 100 mg/kg b.wt. to lead intoxicated Wistar rats may be used to protect/ameliorate lead induced biochemical alterations in Wistar rats.

Protective effects of vaccines against Bordetella parapertussis in a mouse intranasal challenge model.

PubMed

Komatsu, Eiji; Yamaguchi, Fuminori; Eguchi, Masahiro; Watanabe, Mineo

2010-06-17

Bordetella parapertussis causes typical whooping cough, as does Bordetella pertussis. However, current commercial vaccines are ineffective against B. parapertussis. In an effort to develop vaccines that are effective in protecting against both B. pertussis and B. parapertussis, we examined the protective effects of vaccines prepared from whole-cells and from recombinant proteins derived from B. parapertussis in a mouse intranasal challenge model. We confirmed current pertussis vaccines did not induce protective immunity against B. parapertussis in the mouse model. A whole-cell vaccine prepared from B. parapertussis induced protective immunity against B. parapertussis but not against B. pertussis, suggesting a combination of a current pertussis vaccine with a whole-cell parapertussis vaccine might prevent whooping cough caused by both species of Bordetella. We also found that filamentous hemagglutinin was a protective antigen of B. parapertussis. Our observations should lead to the development of new pertussis vaccines that can control the two prevalent forms of whooping cough.

Evaluation of the matrix effect on gas chromatography--mass spectrometry with carrier gas containing ethylene glycol as an analyte protectant.

PubMed

Fujiyoshi, Tomoharu; Ikami, Takahito; Sato, Takashi; Kikukawa, Koji; Kobayashi, Masato; Ito, Hiroshi; Yamamoto, Atsushi

2016-02-19

The consequences of matrix effects in GC are a major issue of concern in pesticide residue analysis. The aim of this study was to evaluate the applicability of an analyte protectant generator in pesticide residue analysis using a GC-MS system. The technique is based on continuous introduction of ethylene glycol into the carrier gas. Ethylene glycol as an analyte protectant effectively compensated the matrix effects in agricultural product extracts. All peak intensities were increased by this technique without affecting the GC-MS performance. Calibration curves for ethylene glycol in the GC-MS system with various degrees of pollution were compared and similar response enhancements were observed. This result suggests a convenient multi-residue GC-MS method using an analyte protectant generator instead of the conventional compensation method for matrix-induced response enhancement adding the mixture of analyte protectants into both neat and sample solutions. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical Risk Assessment: Traditional vs Public Health ...

EPA Pesticide Factsheets

Preventing adverse health impacts from exposures to environmental chemicals is fundamental to protecting individual and public health. When done efficiently and properly, chemical risk assessment enables risk management actions that minimize the incidence and impacts of environmentally-induced diseases related to chemical exposure. However, traditional chemical risk assessment is faced with multiple challenges with respect to predicting and preventing disease in human populations, and epidemiological studies increasingly report observations of adverse health effects at exposure levels predicted from animal studies to be safe for humans. This discordance reinforces concerns about the adequacy of contemporary risk assessment practices (Birnbaum, Burke, & Jones, 2016) for protecting public health. It is becoming clear that to protect public health more effectively, future risk assessments will need to use the full range of available data, draw on innovative methods to integrate diverse data streams, and consider health endpoints that also reflect the range of subtle effects and morbidities observed in human populations. Given these factors, there is a need to reframe chemical risk assessment to be more clearly aligned with the public health goal of minimizing environmental exposures associated with disease. Preventing adverse health impacts from exposures to environmental chemicals is fundamental to protecting individual and public health. Chemical risk assessments

Dissecting the indirect effects caused by vaccines into the basic elements.

PubMed

Scarbrough Lefebvre, Carla D; Terlinden, Augustin; Standaert, Baudouin

2015-01-01

Vaccination directly protects vaccinated individuals, but it also has the potential for indirectly protecting the unvaccinated in a population (herd protection). Unintended negative consequences such as the re-manifestation of infection, mainly expressed as age shifts, result from vaccination programs as well. We discuss the necessary conditions for achieving optimal herd protection (i.e., high quality vaccine-induced immunity, substantial effect on the force of infection, and appropriate vaccine coverage and distribution), as well as the conditions under which age shifts are likely to occur. We show examples to illustrate these effects. Substantial ambiguity in observing and quantifying these indirect vaccine effects makes accurate evaluation troublesome even though the nature of these outcomes may be critical for accurate assessment of the economic value when decision makers are evaluating a novel vaccine for introduction into a particular region or population group. More investigation is needed to identify and develop successful assessment methodologies for precisely analyzing these outcomes.

The Effects of Perceived Normative Pressure and Observability of Behavior on Intention to Perform Sun Protection and Nutrition Behaviors on Behalf of Young Children among Parents

PubMed Central

Lewis, Nehama

2012-01-01

This paper describes research on two normative concepts thought to impact health behaviors: injunctive and descriptive norms. The study tests whether the extent to which the same health behavior is enacted in an observable or non-observable setting will lead to variation in normative influence on parent intention. In on-line experiments conducted in winter 2009, 467 participants were randomized to a behavioral scenario in which the health behavior was described as occurring in an observable or non-observable setting. For sun protection behaviors, observability primed the influence of descriptive norms on intention. For nutrition behaviors, observability primed the influence of injunctive norms on intention. Across both conditions, observability of the behavioral scenario increased the strength of the association between norms and intention. PMID:24610959

Governance regime and location influence avoided deforestation success of protected areas in the Brazilian Amazon.

PubMed

Nolte, Christoph; Agrawal, Arun; Silvius, Kirsten M; Soares-Filho, Britaldo S

2013-03-26

Protected areas in tropical countries are managed under different governance regimes, the relative effectiveness of which in avoiding deforestation has been the subject of recent debates. Participants in these debates answer appeals for more strict protection with the argument that sustainable use areas and indigenous lands can balance deforestation pressures by leveraging local support to create and enforce protective regulations. Which protection strategy is more effective can also depend on (i) the level of deforestation pressures to which an area is exposed and (ii) the intensity of government enforcement. We examine this relationship empirically, using data from 292 protected areas in the Brazilian Amazon. We show that, for any given level of deforestation pressure, strictly protected areas consistently avoided more deforestation than sustainable use areas. Indigenous lands were particularly effective at avoiding deforestation in locations with high deforestation pressure. Findings were stable across two time periods featuring major shifts in the intensity of government enforcement. We also observed shifting trends in the location of protected areas, documenting that between 2000 and 2005 strictly protected areas were more likely to be established in high-pressure locations than in sustainable use areas and indigenous lands. Our findings confirm that all protection regimes helped reduce deforestation in the Brazilian Amazon.

Governance regime and location influence avoided deforestation success of protected areas in the Brazilian Amazon

PubMed Central

Nolte, Christoph; Agrawal, Arun; Silvius, Kirsten M.; Soares-Filho, Britaldo S.

2013-01-01

Protected areas in tropical countries are managed under different governance regimes, the relative effectiveness of which in avoiding deforestation has been the subject of recent debates. Participants in these debates answer appeals for more strict protection with the argument that sustainable use areas and indigenous lands can balance deforestation pressures by leveraging local support to create and enforce protective regulations. Which protection strategy is more effective can also depend on (i) the level of deforestation pressures to which an area is exposed and (ii) the intensity of government enforcement. We examine this relationship empirically, using data from 292 protected areas in the Brazilian Amazon. We show that, for any given level of deforestation pressure, strictly protected areas consistently avoided more deforestation than sustainable use areas. Indigenous lands were particularly effective at avoiding deforestation in locations with high deforestation pressure. Findings were stable across two time periods featuring major shifts in the intensity of government enforcement. We also observed shifting trends in the location of protected areas, documenting that between 2000 and 2005 strictly protected areas were more likely to be established in high-pressure locations than in sustainable use areas and indigenous lands. Our findings confirm that all protection regimes helped reduce deforestation in the Brazilian Amazon. PMID:23479648

Ulcers in restrained rats: Study of protective substances

NASA Technical Reports Server (NTRS)

Buche, L.; Gallaire, D.

1980-01-01

The genesis of ulcers in restrained rats is discussed through an investigation of the relationship between the protective effects of nervous system effectual substances examined vis-a-vis ulcers in restrained rats and their elective or secondary pharmacologic effects. The substances used were capable of either peripheral parasympatholytic, sympatholytic, ganglioplegic, spasmolytic effects or central, hypnotic, tranquilizing, neuroleptic, analgesic effects. The regular and considerable protection observed with parasympatholytics (atropine sulfate, benzylonium bromide, dihexyverine, J.L. 1344) and a ganglioplegic (pentamethonium) is a function of their anticholinergic properties. It is of less importance with dibenamine, a sympatholytic action on the adrenergic receptors. Among the central depressive substances tested (hypnotics, tranquilizers, neuroleptics, analgesic), phenobarbital at a nonhypnotic dose, and dextromoramide at a nonanalgesic dose, show antiulcerous effects, which are found with chlorpromazine only at cataleptogenic doses.

Effect of Therapeutic Plasma Exchange on Immunoglobulins in Myasthenia Gravis

PubMed Central

Guptill, Jeffrey T.; Juel, Vern C.; Massey, Janice M.; Anderson, Amanda C.; Chopra, Manisha; Yi, John S.; Esfandiari, Ehsanollah; Buchanan, Tim; Smith, Bryan; Atherfold, Paul; Jones, Emma; Howard, James F.

2017-01-01

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune diseases populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR+ MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age=72.9 years; baseline MG-Composite=21; median TPE treatments=6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (approximately 60–70% reduction). Three weeks post-TPE mean AChR autoantibody, total IgG, IgG1 and IgG2 titers were below the reference range and had not recovered to within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an “overshoot” of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further supports the concept of rapid immunoglobulin depletion for the treatment of patients with MG. PMID:27684107

Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis.

PubMed

Guptill, Jeffrey T; Juel, Vern C; Massey, Janice M; Anderson, Amanda C; Chopra, Manisha; Yi, John S; Esfandiari, Ehsanollah; Buchanan, Tim; Smith, Bryan; Atherfold, Paul; Jones, Emma; Howard, James F

2016-11-01

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age = 72.9 years; baseline MG-Composite = 21; median TPE treatments = 6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (∼60-70% reduction). Three weeks post-TPE, mean AChR autoantibody, total IgG, IgG1, and IgG2 titers were below the reference range and had not recovered within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an "overshoot" of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further support the concept of rapid immunoglobulin depletion for the treatment of patients with MG.

Observed and Self-Reported Pesticide Protective Behaviors of Latino Migrant and Seasonal Farmworkers

PubMed Central

Walton, AnnMarie Lee; LePrevost, Catherine; Wong, Bob; Linnan, Laura; Sanchez-Birkhead, Ana; Mooney, Kathi

2016-01-01

Agricultural pesticide exposure has potential adverse health effects for farmworkers that may be reduced by pesticide protective behaviors (PPBs). The Environmental Protection Agency’s (EPA) Worker Protection Standard (WPS) requires PPBs be taught to farmworkers prior to field work. Studies to date have not utilized observational methods to evaluate the degree to which PPBs are practiced by Latino migrant and seasonal farmworkers in the United States. The purpose of this study was to describe, compare, and contrast observed and self-reported PPBs used by Latino farmworkers; both PPBs that the WPS requires be taught and other PPBs were included. Observed and self-reported data were collected from 71 Latino farmworkers during the 2014 tobacco growing season in North Carolina. Participants were consistent in reporting and using long pants and closed shoes in the field most of the time. In addition, gloves, hats/bandanas, and water-resistant outerwear were frequently observed, although they are not required to be taught by the WPS. Farmworkers reported more long-sleeve (p = .028) and glove use (p = .000) than what was observed. It was uncommon to observe washing behavior before eating or drinking, even when washing supplies were available. Washing behaviors were significantly overreported for hand (p = .000; (p = .000) and face (p = .000; (p = .058) washing before eating and drinking in the field. This study documents that protective clothing behaviors that the WPS requires be taught, plus a few others are commonly practiced by Latino migrant and seasonal farmworkers, but washing behaviors in the field are not. Targeted strategies to improve washing behaviors in the field are needed. PMID:26918841

Absence of protection from West Nile virus disease and adverse effects in red legged partridges after non-structural NS1 protein administration.

PubMed

Rebollo, Belén; Llorente, Francisco; Pérez-Ramírez, Elisa; Sarraseca, Javier; Gallardo, Carmina; Risalde, María Ángeles; Höfle, Ursula; Figuerola, Jordi; Soriguer, Ramón C; Venteo, Ángel; Jiménez-Clavero, Miguel Ángel

2018-02-01

The red-legged partridge (Alectoris rufa) is a competent host for West Nile virus (WNV) replication and highly susceptible to WNV disease. With the aim to assess in this species whether the inoculation of non-structural protein NS1 from WNV elicits a protective immune response against WNV infection, groups of partridges were inoculated with recombinant NS1 (NS1 group) or an unrelated recombinant protein (mock group), and challenged with infectious WNV. A third group received no inoculation prior to challenge (challenge group). The NS1 group failed to elicit detectable antibodies to NS1 while in the mock group a specific antibody response was observed. Moreover, no protection against WNV disease was observed in the NS1 group, but rather, it showed significantly higher viral RNA load and delayed neutralizing antibody response, and suffered a more severe clinical disease, which resulted in higher mortality. This adverse effect has not been observed before and warrants further investigations. Copyright © 2018 Elsevier Ltd. All rights reserved.

The protective effect of calcium against genotoxicity of lead acetate administration on bone marrow and spermatocyte cells of mice in vivo.

PubMed

Aboul-Ela, Ezzat I

2002-04-26

The protective effect of calcium given orally by gavage with two doses (40 and 80mg/kg body weight) was evaluated against clastogenecity induced by lead acetate with two concentrations (200 and 400mg/kg diet) on bone marrow and spermatocyte cells of mice in vivo. The parameter screened was percentage of chromosomal aberrations with and without gaps and sperm abnormalities. Statistical analyses indicated the protection efficacy of calcium with the high dose rather than the other in both types of mouse cells. The observation from the laboratory tests, dealing that lead acetate can be considered as an environmental genotoxic material. We recommended that it must be administered of calcium (as calcium chloride) as a protective agent to reduce the genotoxic effect of lead in the somatic and germ cells.

Status epilepticus induction has prolonged effects on the efficacy of antiepileptic drugs in the 6-Hz seizure model.

PubMed

Leclercq, Karine; Kaminski, Rafal M

2015-08-01

Several factors may influence the efficacy of antiepileptic drugs (AEDs) in patients with epilepsy, and treatment resistance could be related to genetics, neuronal network alterations, and modification of drug transporters or targets. Consequently, preclinical models used for the identification of potential new, more efficacious AEDs should reflect at least a few of these factors. Previous studies indicate that induction of status epilepticus (SE) may alter drug efficacy and that this effect could be long-lasting. In this context, we wanted to assess the protective effects of mechanistically diverse AEDs in mice subjected to pilocarpine-induced SE in another seizure model. We first determined seizure thresholds in mice subjected to pilocarpine-induced SE in the 6-Hz model, 2 weeks and 8 weeks following SE. We then evaluated the protective effects of mechanistically diverse AEDs in post-SE and control animals. No major differences in 6-Hz seizure susceptibility were observed between control groups, while the seizure threshold of pilocarpine mice at 8 weeks after SE was higher than at 2 weeks and higher than in control groups. Treatment with AEDs revealed major differences in drug response depending on their mechanism of action. Diazepam produced a dose-dependent protection against 6-Hz seizures in control and pilocarpine mice, both at 2 weeks and 8 weeks after SE, but with a more pronounced increase in potency in post-SE animals at 2 weeks. Levetiracetam induced a potent and dose-dependent protection in pilocarpine mice, 2 weeks after SE, while its protective effects were observed only at much higher doses in control mice. Its potency decreased in post-SE mice at 8 weeks and was very limited (30% protection at the highest tested dose) in the control group. Carbamazepine induced a dose-dependent protection at 2 weeks in control mice but only limited effect (50% at the highest tested dose) in pilocarpine mice. Its efficacy deeply decreased in post-SE mice at 8 weeks after SE. Perampanel and phenytoin showed almost comparable protective effects in all groups of mice. These experiments confirm that prior SE may have an impact on both potency and efficacy of AEDs and indicate that this effect may be dependent on the underlying epileptogenic processes. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

PubMed Central

Park, Jong-Hyeon; Lee, Kwang-Nyeong; Kim, Se-Kyung; You, Su-Hwa; Kim, Taeseong; Tark, Dongseob; Lee, Hyang-Sim; Seo, Min-Goo; Kim, Byounghan

2015-01-01

ABSTRACT Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-αγ) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-αγ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Ad-porcine IFN-αγ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. IMPORTANCE The use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against FMDV, although the virus has associated mechanisms of resistance to type I interferons and siRNAs. We have developed recombinant adenoviruses for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-αγ) as well as 3 small interfering RNAs (Ad-3siRNA) to enhance the inhibitory effects of these antiviral agents observed in previous studies. Here, we show enhanced antiviral effects against FMDV by combination treatment with Ad-porcine IFN-αγ and Ad-3siRNA to overcome the mechanisms of resistance of FMDV in swine. PMID:26041279

Acetaminophen hepatotoxicity and sterile inflammation: The mechanism of protection of Chlorogenic acid.

PubMed

Jaeschke, Hartmut

2016-01-05

Acetaminophen hepatotoxicity is characterized by extensive necrotic cell death and a sterile inflammatory response. A recent report suggested that a therapeutic intervention with chlorogenic acid, a dietary polyphenolic compound, protects against acetaminophen-induced liver injury by inhibiting the inflammatory injury. The purpose of this letter is to discuss a number of reasons why the protective mechanism of chlorogenic acid against acetaminophen hepatotoxicity does not involve an anti-inflammatory effect and provides an alternative explanation for the observed protection. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Early Potent Protection against Heterologous SIVsmE660 Challenge Following Live Attenuated SIV Vaccination in Mauritian Cynomolgus Macaques

PubMed Central

Berry, Neil; Ham, Claire; Mee, Edward T.; Rose, Nicola J.; Mattiuzzo, Giada; Jenkins, Adrian; Page, Mark; Elsley, William; Robinson, Mark; Smith, Deborah; Ferguson, Deborah; Towers, Greg; Almond, Neil; Stebbings, Richard

2011-01-01

Background Live attenuated simian immunodeficiency virus (SIV) vaccines represent the most effective means of vaccinating macaques against pathogenic SIV challenge. However, thus far, protection has been demonstrated to be more effective against homologous than heterologous strains. Immune correlates of vaccine-induced protection have also been difficult to identify, particularly those measurable in the peripheral circulation. Methodology/Principal Findings Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM) against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8. MCM provided a characterised host genetic background with limited Major Histocompatibility Complex (MHC) and TRIM5α allelic diversity. Early protection, observed as soon as 3 weeks post-vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthrough cases where simultaneous identification of vaccine and challenge viruses by virus-specific PCR was indicative of active co-infection. Persistence of the vaccine virus in a range of lymphoid tissues was typified by a consistent level of SIV RNA positive cells in protected vaccinates. However, no association between MHC class I /II haplotype or TRIM5α polymorphism and study outcome was identified. Conclusion/Significance This SIV vaccine study, conducted in MHC-characterised MCM, demonstrated potent protection against the pathogenic, heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level of protection against this viral stock by intravenous challenge has not been hitherto observed. The mechanism(s) of protection by vaccination with live attenuated SIV must account for the heterologous and early protection data described in this study, including those which relate to the innate immune system. PMID:21853072

The Protective Effect of Whole Honey and Phenolic Extract on Oxidative DNA Damage in Mice Lymphocytes Using Comet Assay.

PubMed

Cheng, Ni; Wang, Yuan; Cao, Wei

2017-12-01

In this study, the antioxidant activity and the protective effect against hydrogen peroxide-induced DNA damage were assessed for five honeys of different botanical origin. Seven phenolic acids were detected in the honey samples. Ferulic acid was the most abundant phenolic acid detected in longan honey, jujube honey and buckwheat honey. Ellagic acid, p-hydroxybenzoic acid and protocatechuic acid were the main phenolic acids detected in vitex honey. Of all honey samples tested, the highest total phenolic content and antioxidant activity were found in buckwheat honey, whereas the lowest total phenolic content and antioxidant activity were found in locust honey. Treatment with hydrogen peroxide induced a 62% increase in tail DNA in mice lymphocytes, and all studied honeys significantly inhibited this effect (P < 0.05). The buckwheat honey with higher antioxidant capability also exhibited super protective effect than others. Phenolic extracts of honey displayed greater protective effects than whole honey in comet assay. The hydrogen peroxide-generated increase in 8-hydroxy-2-deoxyguanosine (8-OHdG) was effectively inhibited by the honeys studied (P < 0.05). Moreover, a dose-effect relationship between honey concentration and its protective effect was clearly observed in this study. It can be deduced that phenolic acids of honey can penetrate into lymphocytes and protect DNA from oxidative damage by scavenging hydrogen peroxide and/or chelating ferrous ions.

40 CFR 26.405 - Observational research involving greater than minimal risk but presenting the prospect of direct...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Observational research involving... Section 26.405 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Observational Research: Additional Protections for Children Involved as Subjects in Observational...

Mucosal Vaccination for Prevention of HIV Infection and AIDS.

PubMed

Aldovini, Anna

2016-01-01

Most of HIV infections occur via the genital tract or the rectum and HIV replicates at high levels in lymphoid organs and intestinal mucosa, likely requiring a more diversified immunity than pathogens restricted to a single mucosal site, such as the gastrointestinal tract for Vibrio cholera, or the respiratory airways for the influenza virus. Numerous AIDS vaccine candidates are under development and a general observation obtained from preclinical trials in non-human primates that failed to provide sterilizing immunity is that some infection protection or delayed onset of disease is observed in the presence of anti-SIV immunity. Recent clinical trials support difficulties to reproduce in humans the results observed in simian models, but at least one of them indicated that some protection of infection can be achieved. However, given the limited efficacy observed in the RV144 trial and concerns voiced in its statistical interpretation, preclinical trials should explore more effective immunogens, whether new or as combinations of existing ones, and mucosal routes of vaccinations in addition to the systemic routes, with the goal to maximize vaccination-mediated protection. The rationale for generating both strong mucosal and systemic immunity comes from animal experiments, recent clinical trials, and other successful vaccines currently in use. Mucosal responses against SIV have been induced with a variety of SIV antigens and via different mucosal routes with a spectrum of effects on protection. This review covers the rational and the experimental data that support the validity to explore mucosal immunization for HIV infection and AIDS prevention.

Effects of spray drift of glyphosate on nontarget terrestrial plants-A critical review.

PubMed

Cederlund, Harald

2017-11-01

Glyphosate is a widely used broad-spectrum postemergent herbicide used for weed control in both agricultural and nonagricultural settings. Spray drift of glyphosate can pose a risk to nontarget terrestrial plants and plant communities outside the intended area of application, but the lack of a well-established predicted-no-effect drift rate makes properly assessing such risk difficult. For this reason, a literature review and meta-analysis was carried out with the aim to determine the level of drift that is likely to cause harm to plants and to explore what spray-reducing targets would be sufficiently protective. No-observed-adverse effect rates, lowest-observed-adverse effect rates, and effect rates giving 10, 25, and 50% effects were extracted from a total of 39 different publications. The data were combined per species, and species sensitivity distributions were constructed and fitted with a log-logistic model to assess protectiveness. No systematic differences were detected between the responses of monocotyledons or dicotyledons, but wild plants were found to be generally less sensitive to glyphosate drift than domesticated plants. The results indicate that restricting spray drift to a level below 5 g a.e./ha would protect approximately 95% of all higher plant species against minor adverse effects of glyphosate drift and that rates below 1 to 2 g a.e./ha would be almost completely protective. No studies were encountered that evaluated effects of spray drift against nonvascular plants, and therefore, the conclusions are only valid for vascular plants. Environ Toxicol Chem 2017;36:2879-2886. © 2017 SETAC. © 2017 SETAC.

Epidemiologic Studies of Isoflavones & Mammographic Density

PubMed Central

Maskarinec, Gertraud; Verheus, Martijn; Tice, Jeffrey A.

2010-01-01

Isoflavones, phytoestrogens in soy beans with estrogen-like properties, have been examined for their cancer protective effects. Mammographic density is a strong predictor of breast cancer. This review summarizes studies that have examined the association between isoflavones and breast density. Observational investigations in Hawaii and Singapore suggest slightly lower breast density among women of Asian descent with regular soy intake, but two larger studies from Japan and Singapore did not observe a protective effect. The findings from seven randomized trials with primarily Caucasian women indicate that soy or isoflavones do not modify mammographic density. Soy foods and isoflavone supplements within a nutritional range do not appear to modify breast cancer risk as assessed by mammographic density. PMID:22253990

Enhancement of observability and protection of smart power system

NASA Astrophysics Data System (ADS)

Siddique, Abdul Hasib

It is important for a modern power grid to be smarter in order to provide reliable and sustainable supply of electricity. Traditional way of receiving data from the wired system is a very old and outdated technology. For a quicker and better response from the electric system, it is important to look at wireless systems as a feasible option. In order to enhance the observability and protection it is important to integrate wireless technology with the modern power system. In this thesis, wireless network based architecture for wide area monitoring and an alternate method for performing current measurement for protection of generators and motors, has been adopted. There are basically two part of this project. First part deals with the wide area monitoring of the power system and the second part focuses more on application of wireless technology from the protection point of view. A number of wireless method have been adopted in both the part, these includes Zigbee, analog transmission (Both AM and FM) and digital transmission. The main aim of our project was to propose a cost effective wide area monitoring and protection method which will enhance the observability and stability of power grid. A new concept of wireless integration in the power protection system has been implemented in this thesis work.

Effects of Mutations on Replicative Fitness and Major Histocompatibility Complex Class I Binding Affinity Are Among the Determinants Underlying Cytotoxic-T-Lymphocyte Escape of HIV-1 Gag Epitopes.

PubMed

Du, Yushen; Zhang, Tian-Hao; Dai, Lei; Zheng, Xiaojuan; Gorin, Aleksandr M; Oishi, John; Wu, Ting-Ting; Yoshizawa, Janice M; Li, Xinmin; Yang, Otto O; Martinez-Maza, Otoniel; Detels, Roger; Sun, Ren

2017-11-28

Certain "protective" major histocompatibility complex class I (MHC-I) alleles, such as B*57 and B*27, are associated with long-term control of HIV-1 in vivo mediated by the CD8 + cytotoxic-T-lymphocyte (CTL) response. However, the mechanism of such superior protection is not fully understood. Here we combined high-throughput fitness profiling of mutations in HIV-1 Gag, in silico prediction of MHC-peptide binding affinity, and analysis of intraperson virus evolution to systematically compare differences with respect to CTL escape mutations between epitopes targeted by protective MHC-I alleles and those targeted by nonprotective MHC-I alleles. We observed that the effects of mutations on both viral replication and MHC-I binding affinity are among the determinants of CTL escape. Mutations in Gag epitopes presented by protective MHC-I alleles are associated with significantly higher fitness cost and lower reductions in binding affinity with respect to MHC-I. A linear regression model accounting for the effect of mutations on both viral replicative capacity and MHC-I binding can explain the protective efficacy of MHC-I alleles. Finally, we found a consistent pattern in the evolution of Gag epitopes in long-term nonprogressors versus progressors. Overall, our results suggest that certain protective MHC-I alleles allow superior control of HIV-1 by targeting epitopes where mutations typically incur high fitness costs and small reductions in MHC-I binding affinity. IMPORTANCE Understanding the mechanism of viral control achieved in long-term nonprogressors with protective HLA alleles provides insights for developing functional cure of HIV infection. Through the characterization of CTL escape mutations in infected persons, previous researchers hypothesized that protective alleles target epitopes where escape mutations significantly reduce viral replicative capacity. However, these studies were usually limited to a few mutations observed in vivo Here we utilized our recently developed high-throughput fitness profiling method to quantitatively measure the fitness of mutations across the entirety of HIV-1 Gag. The data enabled us to integrate the results with in silico prediction of MHC-peptide binding affinity and analysis of intraperson virus evolution to systematically determine the differences in CTL escape mutations between epitopes targeted by protective HLA alleles and those targeted by nonprotective HLA alleles. We observed that the effects of Gag epitope mutations on HIV replicative fitness and MHC-I binding affinity are among the major determinants of CTL escape. Copyright © 2017 Du et al.

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.

Selectivity in the Addition Reactions of Organometallic Reagents to Aziridine-2-carboxaldehydes: The Effects of Protecting Groups and Substitution Patterns

PubMed Central

Kulshrestha, Aman; Schomaker, Jennifer M.; Holmes, Daniel; Staples, Richard J.; Jackson, James E.; Borhan, Babak

2014-01-01

Good to excellent stereo-selectivity has been found in the addition reactions of Grignard and organo-zinc reagents to N-protected aziridine-2-carboxaldehydes. Specifically, high syn selectivity was obtained with benzyl-protected cis, tert-butyloxycar-bonyl-protected trans, and tosyl-pro-tected 2,3-disubstituted aziridine-2-car-boxaldehydes. Furthermore, rate and selectivity effects of ring substituents, temperature, solvent, and Lewis acid and base modifiers were studied. The diastereomeric preference of addition is dominated by the substrate aziri-dines’ substitution pattern and especially the electronic character and conformational preferences of the nitrogen protecting groups. To help rationalize the observed stereochemical outcomes, conformational and electronic structural analyses of a series of model systems representing the various substitution patterns have been explored by density functional calculations at the B3LYP/6–31G* level of theory with the SM8 solvation model to account for solvent effects. PMID:21928447

Melatonin in concentrated ethanol and ethanol alone attenuate methamphetamine-induced dopamine depletions in C57BL/6J mice.

PubMed

Yu, L; Cherng, C-F G; Chen, C

2002-12-01

The present study aimed to investigate the protective effects of melatonin, ethanol and temperature changes on methamphetamine-induced neurotoxicity in both sexes of mice. Mice exhibited a similar degree of striatal dopamine depletion when methamphetamine was administered during the light and dark cycles. Moreover, 10 mg/kg, but not 5 mg/kg, of methamphetamine, significantly increased body temperature even though dopamine depletions were observed following both doses. Melatonin (80 mg/kg) dissolved in 30% (v/v) ethanol and 30% ethanol alone exerted a moderate to full protection against methamphetamine-induced dopamine depletions in both sexes of mice, whereas the same dose of melatonin in 3% ethanol exerted no protective effect. Furthermore, ethanol attenuated methamphetamine-induced dopamine depletions in a dose-dependent manner with the exception of high efficacy of ethanol at low doses. Finally, the protective effects of ethanol were not blocked by bicuculline. Together, we conclude that ethanol may protect mice against methamphetamine-induced dopamine depletion probably via non-GABAA receptor activation.

Thermal treatment of bentonite reduces aflatoxin b1 adsorption and affects stem cell death.

PubMed

Nones, Janaína; Nones, Jader; Riella, Humberto Gracher; Poli, Anicleto; Trentin, Andrea Gonçalves; Kuhnen, Nivaldo Cabral

2015-10-01

Bentonites are clays that highly adsorb aflatoxin B1 (AFB1) and, therefore, protect human and animal cells from damage. We have recently demonstrated that bentonite protects the neural crest (NC) stem cells from the toxicity of AFB1. Its protective effects are due to the physico-chemical properties and chemical composition altered by heat treatment. The aim of this study is to prepare and characterize the natural and thermal treatments (125 to 1000 °C) of bentonite from Criciúma, Santa Catarina, Brazil and to investigate their effects in the AFB1 adsorption and in NC cell viability after challenging with AFB1. The displacement of water and mineralogical phases transformations were observed after the thermal treatments. Kaolinite disappeared at 500 °C and muscovite and montmorillonite at 1000 °C. Slight changes in morphology, chemical composition, and density of bentonite were observed. The adsorptive capacity of the bentonite particles progressively reduced with the increase in temperature. The observed alterations in the structure of bentonite suggest that the heat treatments influence its interlayer distance and also its adsorptive capacity. Therefore, bentonite, even after the thermal treatment (125 to 1000 °C), is able to increase the viability of NC stem cells previously treated with AFB1. Our results demonstrate the effectiveness of bentonite in preventing the toxic effects of AFB1. Copyright © 2015 Elsevier B.V. All rights reserved.

Antioxidant capacity of pure compounds and complex mixtures evaluated by the ORAC-pyrogallol red assay in the presence of Triton X-100 micelles.

PubMed

Romero, Max; Rojano, Benjamin; Mella-Raipán, Jaime; Pessoa-Mahana, Carlos David; Lissi, Eduardo; López-Alarcón, Camilo

2010-09-01

The protective effect of different antioxidants and complex mixtures on the consumption of pyrogallol red (PGR) induced by peroxyl radicals was studied in the absence and presence of Triton X-100 micelles. The presence of micelles decreased significantly the protection of PGR afforded by lipophilic antioxidants (β-carotene, octyl gallate), while no effect of micelles was observed for hydrophilic antioxidants such as Trolox, caffeic acid, gallic acid, and ascorbic acid. In the presence of complex mixtures a clear effect of Triton X-100 micelles was also observed in the protection afforded by wines, tea infusions, and seed extracts of Eugenia jambolana and Myrciaria cauliflora. On the other hand, no effect of micelles was observed for orange juice and pulp fruit extracts. The ORAC (Oxygen Radical Absorbance Capacity) index was evaluated in the absence (ORAC-PGR) and presence of Triton X-100 micelles (ORAC-PGR(MIC)). Triton X-100 micelles affect ORAC-PGR values of antioxidants in a lipophilicity-dependent way. From the obtained results, we conclude that ORAC-PGR and ORAC-PGR(MIC) assays could be considered as an alternative to estimate the antioxidant ability (ORAC-PGR) and to infer the association to Triton X-100 micelles (ORAC-PGR/ORAC-PGR(MIC)) of pure antioxidants and their complex mixtures.

The Protective Effect of Brown-, Gray-, and Blue-Tinted Lenses against Blue LED Light-Induced Cell Death in A2E-Laden Human Retinal Pigment Epithelial Cells.

PubMed

Park, Sang-Il; Jang, Young Pyo

2017-01-01

A2E-laden ARPE-19 cells were exposed to a blue light to induce cytotoxicity, in order to investigate the protective effects of various tinted ophthalmic lenses against photo-induced cytotoxicity in human retinal pigment epithelial (RPE) cells laden with A2E, known to be among the etiologies of age-related macular degeneration (AMD). Different-colored tinted lenses with varying levels of tint and different filtering characteristics, such as polarized, blue-cut, and photochromatic lenses, were placed over the cells, and the protective efficacies thereof were evaluated by lactate dehydrogenase assay. When tinted lenses were placed over ARPE-19 cells, there were different reductions in cytotoxicity according to the colors and tint levels. The level of protection afforded by brown-tinted lenses was 6.9, 36.1, and 49% with a tint level of 15, 50, and 80%, respectively. For gray-tinted lenses, the protective effect was 16.3, 35, and 43.4% for the corresponding degree of tint, respectively. In the case of blue-tinted lenses, a protective effect of 20% was observed with 80% tinted lenses, but 15 and 50% tinted lenses provided no significant protection. In addition, photochromic lenses showed a protective effect but blue-cut lenses and polarized lenses provided no significant protection. Tinted lenses significantly reduced cytotoxicity in RPE cells irradiated with blue light. The protection was more efficient in lenses with a brown or gray tint than in blue-tinted lenses. Tinted glasses may provide significant protection against potential blue-light-induced photochemical and photo-oxidative damage in RPE cells. © 2016 S. Karger AG, Basel.

Development of concepts for the protection of space launchers against lightning

NASA Astrophysics Data System (ADS)

Taillet, Joseph

1988-12-01

Following a review of the characteristics of lightning and the effects of lightning on space launchers, various strategies for protection against lightning are discussed. Special attention is given to the damage inflicted on the Apollo 12 and Atlas/Centaur vehicles by lightning. It is demonstrated that the protection of space launchers is best performed by the real-time observation of atmospheric discharges at high altitude by such systems as the interferometric lightning alert system, SAFIR.

Endotoxin and cancer chemo-prevention.

PubMed

Mastrangelo, Giuseppe; Fadda, Emanuela; Cegolon, Luca

2013-10-01

Reduced rates of lung cancer have been observed in several occupational groups exposed to high levels of organic dusts contaminated by endotoxin. The underlying anti-neoplastic mechanism of endotoxin may be an increased secretion of endogenous anti-neoplastic mediators and activation of the toll-like receptors (TLR). A detoxified endotoxin derivative, Monophosphoryl Lipid A (MPL(®)) is marketed in Europe since 1999 as part of the adjuvant systems in allergy vaccines for treatment of allergic rhino-conjunctivitis and allergic asthma. Over 200,000 patients have used them to date (nearly 70% in Germany). Since detailed exposure (MPL(®) dose and timing of administration) and individual data are potentially available, an observational follow-up study could be conducted in Germany to investigate the protective effect of MPL(®) against cancer, comparing cancer incidence in two groups of patients with allergic rhinitis: those treated with allergoids plus MPL(®) and those treated with a vaccine including the same allergoids but not MPL(®). The protective effect of MPL(®) could be quantified in ever and never smokers. If this proposed observational study provides evidence of protective effects, MPL(®) could be immediately used as a chemo-preventive agent since it is already in use as adjuvant in human vaccines against cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of Ionizing Radiation on Arylesterase and Cholinesterase.

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

Augustinsson, Klas-Bertil; Jonsson, Gunnel; Sparrman, Berndt

1961-01-01

The effects of Co 60 gamma radiation on arylesterase and cholinesterase of human blood plasma were compared using solid preparations of purified enzymes containing various amounts of water. In the case of cholinesterase a water content of 12% exerted maximum protection against irradiation. Such a protection by water was not observed with arylesterase. Finally, in aqueous solutions cholinesterase was more resistant to irradiation by gamma rays than was arylesterase when irradiation was performed in an atmosphere of nitrogen.

Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques.

PubMed

Sui, Yongjun; Zhu, Qing; Gagnon, Susan; Dzutsev, Amiran; Terabe, Masaki; Vaccari, Monica; Venzon, David; Klinman, Dennis; Strober, Warren; Kelsall, Brian; Franchini, Genoveffa; Belyakov, Igor M; Berzofsky, Jay A

2010-05-25

Adjuvant effects on innate as well as adaptive immunity may be critical for inducing protection against mucosal HIV and simian immunodeficiency virus (SIV) exposure. We therefore studied effects of Toll-like receptor agonists and IL-15 as mucosal adjuvants on both innate and adaptive immunity in a peptide/poxvirus HIV/SIV mucosal vaccine in macaques, and made three critical observations regarding both innate and adaptive correlates of protection: (i) adjuvant-alone without vaccine antigen impacted the intrarectal SIVmac251 challenge outcome, correlating with surprisingly long-lived APOBEC3G (A3G)-mediated innate immunity; in addition, even among animals receiving vaccine with adjuvants, viral load correlated inversely with A3G levels; (ii) a surprising threshold-like effect existed for vaccine-induced adaptive immunity control of viral load, and only antigen-specific polyfunctional CD8(+) T cells correlated with protection, not tetramer(+) T cells, demonstrating the importance of T-cell quality; (iii) synergy was observed between Toll-like receptor agonists and IL-15 for driving adaptive responses through the up-regulation of IL-15Ralpha, which can present IL-15 in trans, as well as for driving the innate A3G response. Thus, strategic use of molecular adjuvants can provide better mucosal protection through induction of both innate and adaptive immunity.

Leaky vaccines protect highly exposed recipients at a lower rate: implications for vaccine efficacy estimation and sieve analysis.

PubMed

Edlefsen, Paul T

2014-01-01

"Leaky" vaccines are those for which vaccine-induced protection reduces infection rates on a per-exposure basis, as opposed to "all-or-none" vaccines, which reduce infection rates to zero for some fraction of subjects, independent of the number of exposures. Leaky vaccines therefore protect subjects with fewer exposures at a higher effective rate than subjects with more exposures. This simple observation has serious implications for analysis methodologies that rely on the assumption that the vaccine effect is homogeneous across subjects. We argue and show through examples that this heterogeneous vaccine effect leads to a violation of the proportional hazards assumption, to incomparability of infected cases across treatment groups, and to nonindependence of the distributions of the competing failure processes in a competing risks setting. We discuss implications for vaccine efficacy estimation, correlates of protection analysis, and mark-specific efficacy analysis (also known as sieve analysis).

Protective effect of dietary fenugreek (Trigonella foenum-graecum) seeds and garlic (Allium sativum) on induced oxidation of low-density lipoprotein in rats.

PubMed

Mukthamba, Puttaswamy; Srinivasan, Krishnapura

2016-01-01

Dietary fenugreek seeds (Trigonella foenum-graecum) and garlic (Allium sativum) have been previously observed to have cardioprotective influence in experimentally induced myocardial infarction in rats. Since low-density lipoprotein (LDL) oxidation is a key factor in the arteriosclerotic process, we evaluated their potential in minimizing the LDL oxidation in rats. Fenugreek seeds, garlic, and their combination were included along with a high-cholesterol diet for 8 weeks. Iron-induced oxidation of LDL in vivo was considerably lowered by dietary fenugreek and garlic. The extent of copper-induced oxidation of isolated LDL in vitro was also significantly lesser in fenugreek-fed or fenugreek+garlic-fed rats. Anodic electrophoretic mobility of the oxidized LDL on agarose gel in case of spice-fed animals was decreased and hence consistent with the observed protective influence on LDL oxidation. Dietary fenugreek, garlic, and their combination significantly lowered lipid peroxide levels in plasma, liver, and heart in iron (II)-administered rats. The results suggest that these two dietary spices have protective effect on LDL oxidation under normal situation as well as in hypercholesterolemic situation. The protective effect of the combination of dietary fenugreek and garlic on LDL oxidation both in vivo and in vitro was greater than that of the individual spices. The protective effect of dietary fenugreek and garlic on LDL oxidation both in vivo and in vitro as evidenced in the present study is suggestive of their cardioprotective potential since LDL oxidation is a key factor in the arteriosclerotic process.

Corrosion product layers on magnesium alloys AZ31 and AZ61: Surface chemistry and protective ability

NASA Astrophysics Data System (ADS)

Feliu, S.; Llorente, I.

2015-08-01

This paper studies the chemical composition of the corrosion product layers formed on magnesium alloys AZ31 and AZ61 following immersion in 0.6 M NaCl, with a view to better understanding their protective action. Relative differences in the chemical nature of the layers were quantified by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), energy dispersive analysis of X-ray (EDX) and low-angle X-ray diffraction (XRD). Corrosion behavior was investigated by Electrochemical Impedance Spectroscopy (EIS) and hydrogen evolution measurement. An inhibitive effect from the corrosion product layers was observed from EIS, principally in the case of AZ31, as confirmed by hydrogen evolution tests. A link was found between carbonate enrichment observed by XPS in the surface of the corrosion product layer, concomitant with the increase in the protective properties observed by EIS.

SunSmart: evaluation of a pilot school-based sun protection intervention in Hispanic early adolescents

PubMed Central

Miller, K. A.; Langholz, B. M.; Ly, T.; Harris, S. C.; Richardson, J. L.; Peng, D. H.; Cockburn, M. G.

2015-01-01

The incidence of melanoma is rising among Hispanic populations in the United States. The purpose of this study is to evaluate the impact of a pilot sun safety educational intervention conducted from 2006 to 2012 on Hispanic early adolescents in a high ultraviolet environment. Nineteen schools with high Hispanic enrollment were recruited from urban neighborhoods in Los Angeles. The analytic sample was restricted to students identifying as Hispanic or Latino (n = 777). A mixed effects linear model was used to test mean changes from pre- to posttest on students’ sun protection knowledge, attitudes and behaviors. Significant improvements were observed across several cognitive outcomes related to sun protection, including knowledge of and attitudes toward sun protection and self-efficacy to wear sunscreen. However, changes in sun protective behaviors were not achieved. Although some improvements were observed, future studies should identify the factors that motivate sun protection in this population and develop tailored prevention strategies, as improving the sun safe behaviors of Hispanic youths may aid in reducing the risk of melanoma in adulthood in this population. PMID:25801103

Oxidative Stress Response Induced by Butachlor in Zebrafish Embryo/Larvae: The Protective Effect of Vitamin C.

PubMed

Xiang, Qingqing; Xu, Bofan; Ding, Yilun; Liu, Xiaoyi; Zhou, Ying; Ahmad, Farooq

2018-02-01

The widespread contamination and persistence of the herbicide butachlor in the environment resulted in the exposure of non-target organisms. The present study investigated the toxicity effect of butachlor (1-15 µmol/L) and the protective effect of vitamin C (VC) against butachlor-induced toxicity in zebrafish. It was found that butachlor significantly increased the mortality and malformation rates in a dose-dependent manner, which caused elevation in reactive oxygen species (ROS) and malondialdehyde (MDA) after 72 h exposure. Compared with butachlor treatment group, the protective effect of VC against butachlor-induced toxicity were observed after adding 40, 80 mg/L VC respectively. VC significantly decreased the mortality, malformation rates, ROS, MDA, and normalized antioxidant enzymes activities of zebrafish after 72 h exposure. The result shows VC has mitigative effect on butachlor-induced toxicity and it can be used as an effective antioxidant in aquaculture.

[Study on the liver-protective and choleretic effect of zhizi baipi soup and its disassembled prescription].

PubMed

Xiao, Xu; Zhu, Ji-Xiao; Luo, Guang-Ming; Li, Lei; Zhu, Yu-Ye; Zeng, Jin-Xiang; Wang, Xiao-Yun; Wu, Bo

2013-07-01

To investigate the effect of Zhizi Baipi soup and its disassembled prescription on protecting liver and improving choleresis and explore the regularity of Zhizi Baipi soup composition. The model of mouse liver injury induced by carbon tetraehlofide (CCl4) was used to observe the effects of Zhizi Baipi soup and its disassembled prescription by oral adminstration, the bile volume was determinied by common bile duct drainage. Zhizi Baipi soup and each treatment group with gardenia could significantly inhibit the increased serum ATL and AST activities, reduce liver MDA level, and significantly promote the bile flow and bilirubin in bile in normal rats. Zhizi Baipi soup has effects on protecting liver and increasing bile secretion, its monarch drug, gardenia plays an important role in the decoction, the effect of eliminating dampness and heat are mainly ascribed to the synergic effect of gardenia and phellodendron.

Associations between dietary intake of choline and betaine and lung cancer risk.

PubMed

Ying, Jun; Rahbar, Mohammad H; Hallman, D Michael; Hernandez, Ladia M; Spitz, Margret R; Forman, Michele R; Gorlova, Olga Y

2013-01-01

Evidence from human and animal research indicates that choline metabolic pathways may be activated during a variety of diseases, including cancer. We report results of a case-control study of 2821 lung cancer cases and 2923 controls that assessed associations of choline and betaine dietary intakes with lung cancer. Using multivariable logistic regression analyses, we report a significant association between higher betaine intake and lower lung cancer risk that varied by smoking status. Specifically, no significant association was observed between betaine intake and lung cancer among never-smokers. However, higher betaine intake was significantly associated with reduced lung cancer risk among smokers, and the protective effect was more evident among current than former smokers: for former and current smokers, the ORs (95% CI) of lung cancer for individuals with highest as compared to lowest quartiles of intake were 0.70(0.55-0.88) and 0.51(0.39-0.66) respectively. Significant linear trend of higher betaine intake and lower lung cancer risk was observed among both former (p(trend) = 0.002) and current (p(trend)<0.0001) smokers. A similar protective effect was also observed with choline intake both in overall analysis as well as among current smokers, with p-values for chi-square tests being 0.001 and 0.004 respectively, but the effect was less evident, as no linear trend was observed. Our results suggest that choline and betaine intake, especially higher betaine intake, may be protective against lung cancer through mitigating the adverse effect of smoking.

Associations between Dietary Intake of Choline and Betaine and Lung Cancer Risk

PubMed Central

Ying, Jun; Rahbar, Mohammad H.; Hallman, D. Michael; Hernandez, Ladia M.; Spitz, Margret R.; Forman, Michele R.; Gorlova, Olga Y.

2013-01-01

Evidence from human and animal research indicates that choline metabolic pathways may be activated during a variety of diseases, including cancer. We report results of a case-control study of 2821 lung cancer cases and 2923 controls that assessed associations of choline and betaine dietary intakes with lung cancer. Using multivariable logistic regression analyses, we report a significant association between higher betaine intake and lower lung cancer risk that varied by smoking status. Specifically, no significant association was observed between betaine intake and lung cancer among never-smokers. However, higher betaine intake was significantly associated with reduced lung cancer risk among smokers, and the protective effect was more evident among current than former smokers: for former and current smokers, the ORs (95% CI) of lung cancer for individuals with highest as compared to lowest quartiles of intake were 0.70(0.55–0.88) and 0.51(0.39–0.66) respectively. Significant linear trend of higher betaine intake and lower lung cancer risk was observed among both former (ptrend = 0.002) and current (ptrend<0.0001) smokers. A similar protective effect was also observed with choline intake both in overall analysis as well as among current smokers, with p-values for chi-square tests being 0.001 and 0.004 respectively, but the effect was less evident, as no linear trend was observed. Our results suggest that choline and betaine intake, especially higher betaine intake, may be protective against lung cancer through mitigating the adverse effect of smoking. PMID:23383301

Taurine-induced attenuation of MPP+ neurotoxicity in vitro: a possible role for the GABA(A) subclass of GABA receptors.

PubMed

O'Byrne, M B; Tipton, K F

2000-05-01

Taurine is a sulphur-containing beta-amino acid found in high (millimolar) concentrations in excitable tissues such as brain and heart. Its suggested roles include osmoregulator, thermoregulator, neuromodulator, and potential neurotransmitter. This amino acid has also been shown to be released in large concentrations during ischaemia and excitotoxin-induced neuronal damage. Here we report a protective effect of taurine against MPP(+)-induced neurotoxicity in coronal slices from rat brain. Significant protective effects were observed at taurine concentrations of 20 and 1 mM, suggesting a potential role for taurine in cases of neuronal insult. Studies with the synthetic taurine analogues taurine phosphonate, guanidinoethane sulphonate, and trimethyltaurine suggested the observed effect to be mediated via an extracellular mechanism. The use of GABA receptor ligands muscimol and bicuculline indicated the effect to be mediated through activation of GABA(A) receptors.

Confounding of the association between statins and Parkinson disease: systematic review and meta-analysis.

PubMed

Bykov, Katsiaryna; Yoshida, Kazuki; Weisskopf, Marc G; Gagne, Joshua J

2017-03-01

Both statins and higher serum cholesterol have been reported to reduce to risk of Parkinson Disease (PD). Given the importance of adjusting for cholesterol levels when evaluating the effect of statins, we assessed whether the protective effect of statins would remain when adjustment for cholesterol is performed. We conducted a systematic review of epidemiologic studies that reported quantitative estimates of the association between statins and incident PD and were published through February 2016. Random-effects meta-analysis was used to assess the effect of statins on PD separately among the studies that adjusted for either cholesterol or hyperlipidemia and studies that did not. Ten eligible studies that evaluated the use of statins and incident PD were identified. Among the six studies that did not adjust for cholesterol, a protective effect of statins was observed (relative risk 0.75; 95% confidence intervals (CI) 0.60 to 0.92). Excluding studies with possible bias because of reverse causation or stratifying on study design did not affect the results. No protective effect was observed among the four studies that adjusted for either cholesterol of hyperlipidemia (relative risk 0.91; 95%CI 0.68 to 1.22). The effect estimate for studies that adjusted for cholesterol was 1.04 (95%CI 0.68 to 1.59) when a study with immortal time bias was excluded. The apparent protective effect of statins on risk of PD is at least partially explained by confounding by statin indication. Immortal time bias and healthy user effects also could have contributed to biased results. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Protective effects of different marigold (Calendula officinalis L.) and rosemary cream preparations against sodium-lauryl-sulfate-induced irritant contact dermatitis.

PubMed

Fuchs, S M; Schliemann-Willers, S; Fischer, T W; Elsner, P

2005-01-01

In the present study, we evaluated the protective action of cream preparations containing seven different types of marigold and rosemary extracts in vivo in healthy volunteers with experimentally induced irritant contact dermatitis (ICD). Marigold and rosemary extracts in base cream DAC (Deutscher Arzneimittel-Codex = German Pharmaceutical Codex) were tested in a 4-day repetitive irritation test using sodium lauryl sulfate. The effect was evaluated visually and quantified by noninvasive bioengineering methods, namely chromametry and tewametry. When the test products were applied parallel to the induction period of ICD, a statistically significant protective effect of all cream preparations was observed by all methods. This effect, although not statistically significant, was superior to control by undyed marigold und faradiol ester-enriched extracts in chromametry and by dyed and undyed rosemary extracts in tewametry. The sequential treatment (postirritation) once a day for 5 days was without any effect. Thus, a protective effect of some marigold and rosemary extracts against ICD could be shown in the elicitation phase. Copyright (c) 2005 S. Karger AG, Basel.

Assessment of antioxidative, chelating, and DNA-protective effects of selected essential oil components (eugenol, carvacrol, thymol, borneol, eucalyptol) of plants and intact Rosmarinus officinalis oil.

PubMed

Horvathova, Eva; Navarova, Jana; Galova, Eliska; Sevcovicova, Andrea; Chodakova, Lenka; Snahnicanova, Zuzana; Melusova, Martina; Kozics, Katarina; Slamenova, Darina

2014-07-16

Selected components of plant essential oils and intact Rosmarinus officinalis oil (RO) were investigated for their antioxidant, iron-chelating, and DNA-protective effects. Antioxidant activities were assessed using four different techniques. DNA-protective effects on human hepatoma HepG2 cells and plasmid DNA were evaluated with the help of the comet assay and the DNA topology test, respectively. It was observed that whereas eugenol, carvacrol, and thymol showed high antioxidative effectiveness in all assays used, RO manifested only antiradical effect and borneol and eucalyptol did not express antioxidant activity at all. DNA-protective ability against hydrogen peroxide (H2O2)-induced DNA lesions was manifested by two antioxidants (carvacrol and thymol) and two compounds that do not show antioxidant effects (RO and borneol). Borneol was able to preserve not only DNA of HepG2 cells but also plasmid DNA against Fe(2+)-induced damage. This paper evaluates the results in the light of experiences of other scientists.

Synthesis, characterization, and corrosion protection properties of poly( N-(methacryloyloxymethyl) benzotriazole- co-methyl methacrylate) on mild steel

NASA Astrophysics Data System (ADS)

Srikanth, A. P.; Lavanya, A.; Nanjundan, S.; Rajendran, N.

2006-12-01

The copolymers from different feed ratios of N-(methacryloyloxymethyl) benzotriazole (MMBT) and methyl methacrylate (MMA) has been synthesised using free radical solution polymerization technique and characterized using FT-IR and 13C NMR spectroscopy. The thermal stability of the polymers was studied using theremogravimetrtic analysis (TGA). The corrosion behaviors of mild steel specimens dip coated with different composition of copolymers have been evaluated by potentiodynamic polarization and electrochemical impedance spectroscopic (EIS) method. These electrochemical properties were observed in 0.1 M HCl medium. The polarization and impedance measurements showed different corrosion protection efficiency with change in composition of the copolymers. It was found that the corrosion protection properties are owing to the barrier effect of the polymer layer covered on the mild steel surfaces. However, it was observed that the copolymer obtained from 1:1 mole ratio of MMBT and MMA exhibited better protection efficiency than other combinations.

Dissecting the indirect effects caused by vaccines into the basic elements

PubMed Central

Scarbrough Lefebvre, Carla D; Terlinden, Augustin; Standaert, Baudouin

2015-01-01

Vaccination directly protects vaccinated individuals, but it also has the potential for indirectly protecting the unvaccinated in a population (herd protection). Unintended negative consequences such as the re-manifestation of infection, mainly expressed as age shifts, result from vaccination programs as well. We discuss the necessary conditions for achieving optimal herd protection (i.e., high quality vaccine-induced immunity, substantial effect on the force of infection, and appropriate vaccine coverage and distribution), as well as the conditions under which age shifts are likely to occur. We show examples to illustrate these effects. Substantial ambiguity in observing and quantifying these indirect vaccine effects makes accurate evaluation troublesome even though the nature of these outcomes may be critical for accurate assessment of the economic value when decision makers are evaluating a novel vaccine for introduction into a particular region or population group. More investigation is needed to identify and develop successful assessment methodologies for precisely analyzing these outcomes. PMID:26186100

Plant-derived phenolic compounds prevent the DNA single-strand breakage and cytotoxicity induced by tert-butylhydroperoxide via an iron-chelating mechanism.

PubMed Central

Sestili, Piero; Diamantini, Giuseppe; Bedini, Annalida; Cerioni, Liana; Tommasini, Ilaria; Tarzia, Giorgio; Cantoni, Orazio

2002-01-01

The protective effects of selected members from a series of caffeic acid esters and flavonoids were tested in various toxicity paradigms using U937 cells, previously shown to be sensitive to either iron chelators or bona fide radical scavengers or to both classes of compounds. It was found that all the protective polyphenols were active at very low concentrations and that their effects were observed only under those conditions in which iron chelators also afforded protection. Consistently, active polyphenolic compounds, unlike the inactive ones, effectively chelated iron in an in vitro system. It follows that, at least under the experimental conditions utilized in the present study, the most prominent activity of these polyphenolic compounds resides in their ability to chelate iron. Further studies revealed that the protective effects afforded by the caffeic acid esters and flavonoids were largely mediated by the catechol moiety and that the relative biological potency of these compounds was a direct function of their lipophilicity. PMID:11988084

Biochemical and immunological mechanisms by which sickle cell trait protects against malaria.

PubMed

Gong, Lauren; Parikh, Sunil; Rosenthal, Philip J; Greenhouse, Bryan

2013-09-11

Sickle cell trait (HbAS) is the best-characterized genetic polymorphism known to protect against falciparum malaria. Although the protective effect of HbAS against malaria is well known, the mechanism(s) of protection remain unclear. A number of biochemical and immune-mediated mechanisms have been proposed, and it is likely that multiple complex mechanisms are responsible for the observed protection. Increased evidence for an immune component of protection as well as novel mechanisms, such as enhanced tolerance to disease mediated by HO-1 and reduced parasitic growth due to translocation of host micro-RNA into the parasite, have recently been described. A better understanding of relevant mechanisms will provide valuable insight into the host-parasite relationship, including the role of the host immune system in protection against malaria.

Biochemical and immunological mechanisms by which sickle cell trait protects against malaria

PubMed Central

2013-01-01

Sickle cell trait (HbAS) is the best-characterized genetic polymorphism known to protect against falciparum malaria. Although the protective effect of HbAS against malaria is well known, the mechanism(s) of protection remain unclear. A number of biochemical and immune-mediated mechanisms have been proposed, and it is likely that multiple complex mechanisms are responsible for the observed protection. Increased evidence for an immune component of protection as well as novel mechanisms, such as enhanced tolerance to disease mediated by HO-1 and reduced parasitic growth due to translocation of host micro-RNA into the parasite, have recently been described. A better understanding of relevant mechanisms will provide valuable insight into the host-parasite relationship, including the role of the host immune system in protection against malaria. PMID:24025776

Ecotoxicological effect characterisation of widely used organic UV filters.

PubMed

Kaiser, D; Sieratowicz, A; Zielke, H; Oetken, M; Hollert, H; Oehlmann, J

2012-04-01

Chemical UV filters are used in sun protection and personal care products in order to protect consumers from skin cancer induced by ultraviolet (UV) radiation. The present study aims to evaluate the effects of three common UV filters butyl-methoxydibenzoylmethane (B-MDM) ethylhexyl-methoxycinnamate (EHMC) and octocrylene (OCR) on aquatic organism, focussing particularly on infaunal and epibentic invertebrates (Chironomus riparius, Lumbriculus variegatus, Melanoides tuberculata and Potamopyrgus antipodarum). Due to their life habits, these organism are especially affected by lipophilic substances. Additionally, two direct sediment contact assays utilising zebra fish (Danio rerio) embryos and bacteria (Arthrobacter globiformis) were conducted. EHMC caused a toxic effect on reproduction in both snails with lowest observed effect concentrations (LOEC) of 0.4 mg/kg (Potamopyrgus antipodarum) and 10 mg/kg (Melanoides tuberculata). At high concentrations sublethal effects could be observed for D. rerio after exposure to EHMC (NOEC 100 mg/kg). B-MDM and OCR showed no effects on any of the tested organism. Copyright © 2011 Elsevier Ltd. All rights reserved.

Predicting sun protection behaviors using protection motivation variables.

PubMed

Ch'ng, Joanne W M; Glendon, A Ian

2014-04-01

Protection motivation theory components were used to predict sun protection behaviors (SPBs) using four outcome measures: typical reported behaviors, previous reported behaviors, current sunscreen use as determined by interview, and current observed behaviors (clothing worn) to control for common method bias. Sampled from two SE Queensland public beaches during summer, 199 participants aged 18-29 years completed a questionnaire measuring perceived severity, perceived vulnerability, response efficacy, response costs, and protection motivation (PM). Personal perceived risk (similar to threat appraisal) and response likelihood (similar to coping appraisal) were derived from their respective PM components. Protection motivation predicted all four SPB criterion variables. Personal perceived risk and response likelihood predicted protection motivation. Protection motivation completely mediated the effect of response likelihood on all four criterion variables. Alternative models are considered. Strengths and limitations of the study are outlined and suggestions made for future research.

Effect of flow velocity on erosion-corrosion behaviour of QSn6 alloy

NASA Astrophysics Data System (ADS)

Huang, Weijiu; Zhou, Yongtao; Wang, Zhenguo; Li, Zhijun; Zheng, Ziqing

2018-05-01

The erosion-corrosion behaviour of QSn6 alloy used as propellers in marine environment was evaluated by erosion-corrosion experiments with/without cathodic protection, electrochemical tests and scanning electron microscope (SEM) observations. The analysis was focused on the effect of flow velocity. The dynamic polarization curves showed that the corrosion rate of the QSn6 alloy increased as the flow velocity increased, due to the protective surface film removal at higher velocities. The lowest corrosion current densities of 1.26 × 10‑4 A cm‑2 was obtained at the flow velocity of 7 m s‑1. Because of the higher particle kinetic energies at higher flow velocity, the mass loss rate of the QSn6 alloy increased as the flow velocity increased. The mass loss rate with cathodic protection was lower than that without cathodic protection under the same conditions. Also, the lowest mass loss rate of 0.7 g m‑2 · h‑1 was acquired at the flow velocity of 7 m s‑1 with cathodic protection. However, the increase rate of corrosion rate and mass loss were decreased with increasing the flow velocity. Through observation the SEM morphologies of the worn surfaces, the main wear mechanism was ploughing with/without cathodic protection. The removal rates of the QSn6 alloy increased as the flow velocity increased in both pure erosion and erosion-corrosion, whereas the erosion and corrosion intensified each other. At the flow velocity of 7 m s‑1, the synergy rate (ΔW) exceeded by 5 times the erosion rate (Wwear). Through establishment and observation the erosion-corrosion mechanism map, the erosion-corrosion was the dominant regime in the study due to the contribution of erosion on the mass loss rate exceeded the corrosion contribution. The QSn6 alloy with cathodic protection is feasible as propellers, there are higher security at lower flow velocity, such as the flow velocity of 7 m s‑1 in the paper.

Protective effects of platinum nanoparticles against UV-light-induced epidermal inflammation.

PubMed

Yoshihisa, Yoko; Honda, Ayumi; Zhao, Qing-Li; Makino, Teruhiko; Abe, Riichiro; Matsui, Kotaro; Shimizu, Hiroshi; Miyamoto, Yusei; Kondo, Takashi; Shimizu, Tadamichi

2010-11-01

Intracellular reactive oxygen species (ROS) and apoptosis play important roles in the ultraviolet (UV)-induced inflammatory responses in the skin. Metal nanoparticles have been developed to increase the catalytic activity of metals, which is because of the large surface area of smaller particles. Platinum nanoparticles (nano-Pt) protected by poly acrylic acid were manufactured by reduction with ethanol. A marked increase in ROS production was observed in UV-treated HaCaT keratinocytes cell lines, while a decrease in ROS production was observed in nano-Pt-treated cells. Pretreatment of the cells with nano-Pt also caused a significant inhibition of UVB- and UVC-induced apoptosis. Furthermore, we found that mice treated with nano-Pt gel prior to UV irradiation showed significant inhibition of UVB-induced inflammation and UVA-induced photoallergy compared to UV-irradiated control mice. These results suggest that nano-Pt effectively protects against UV-induced inflammation by decreasing ROS production and inhibiting apoptosis in keratinocytes. © 2010 John Wiley & Sons A/S.

The role of the ICRP in radiation protection--a view from industry.

PubMed

Henrichs, K

2003-01-01

It is the objective of this paper to discuss some aspects concerning the role and importance of the ICRP. Here, this is done with a background of practical radiation protection in industry. The author organises and controls radiation protection for a worldwide operating company, for which efficiently realised radiation safety is as relevant for its workplaces as for its products and services. According to the author's subjective observation, the ICRP has a decreasing importance in operational radiation protection. However, there are growing demands on the ICRP as it is the only basis for internationally compatible regulations and standards. It is the merit of the ICRP that an international comparison of legal protection systems and concepts should give a much more homogeneous picture than that for any other safety and protection issue. The most valuable asset of the ICRP is its credibility as a scientific authority solely committed to the effective protection of people. But its success also brings with it an obligation: there is an increasing need for more effective communication to non-experts. This and other expectations for the future are briefly discussed.

[Study of the radioprotective effects of TMG on teratogenic malformations in irradiated mice].

PubMed

Gu, Y; Hasegawa, T; Kim, H; Suzuki, I; Mori, T; Yamamoto, Y

2000-12-01

ICR mice fetuses in the organogenesis stage were used to clarify experimentally the mechanism of the protective effect of vitamin E derivant (TMG: 2-(alpha-D-Glucopyranosyl) methyl-2, -5, -7, -8-Teramethylchorman-6-working woman) on the effects of radiation. The authors paid careful attention to radiation, and the radioprotective effects of TMG on the induction of malformations was examined. Radiation is an important consideration because of its widespread use in the areas of medicine, nuclear energy, and industry. Malformations induced by radiation at the organogenesis stage, skeletal malformations, and the effects at the cellular level of embryos were examined in this research. Further, the mechanism of the protection effect of TMG against radiation-induced malformations was analyzed and observed experimentally. Thus, this study was done to provide fundamental data on the radioprotective agent TMG. It was clear that TMG exerted radioprotective effects against embryonic death and the rate of teratogenesis when administered before exposure. Such effects were also exerted against skeletal malformations and fetal body weight. In summary, radioprotective effects were observed at the whole-body level as well as at the cellular level.

Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists

PubMed Central

Sadek, Bassem; Saad, Ali; Schwed, Johannes Stephan; Weizel, Lilia; Walter, Miriam; Stark, Holger

2016-01-01

Phenytoin (PHT), valproic acid, and modern antiepileptic drugs (AEDs), eg, remacemide, loreclezole, and safinamide, are only effective within a maximum of 70%–80% of epileptic patients, and in many cases the clinical use of AEDs is restricted by their side effects. Therefore, a continuous need remains to discover innovative chemical entities for the development of active and safer AEDs. Ligands targeting central histamine H3 receptors (H3Rs) for epilepsy might be a promising therapeutic approach. To determine the potential of H3Rs ligands as new AEDs, we recently reported that no anticonvulsant effects were observed for the (S)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propanamide (1). In continuation of our research, we asked whether anticonvulsant differences in activities will be observed for its R-enantiomer, namely, (R)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propaneamide (2) and analogs thereof, in maximum electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced convulsion models in rats having PHT and valproic acid (VPA) as reference AEDs. Unlike the S-enantiomer (1), the results show that animals pretreated intraperitoneally (ip) with the R-enantiomer 2 (10 mg/kg) were moderately protected in MES and STR induced models, whereas proconvulsant effect was observed for the same ligand in PTZ-induced convulsion models. However, animals pretreated with intraperitoneal doses of 5, 10, or 15 mg/kg of structurally bulkier (R)-enantiomer (3), in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol, and its (S)-enantiomer (4) significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the (R)-enantiomer (3) in MES model were significantly greater than those of the standard H3R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and reversed when rats were pretreated with the selective H3R agonist R-(α)-methyl-histamine. Comparisons of the observed antagonistic in vitro affinities among the ligands 1–6 revealed profound stereoselectivity at human H3Rs with varying preferences for this receptor subtype. Moreover, the in vivo anticonvulsant effects observed in this study for ligands 1–6 showed stereoselectivity in different convulsion models in male adult rats. PMID:27853355

Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists.

PubMed

Sadek, Bassem; Saad, Ali; Schwed, Johannes Stephan; Weizel, Lilia; Walter, Miriam; Stark, Holger

2016-01-01

Phenytoin (PHT), valproic acid, and modern antiepileptic drugs (AEDs), eg, remacemide, loreclezole, and safinamide, are only effective within a maximum of 70%-80% of epileptic patients, and in many cases the clinical use of AEDs is restricted by their side effects. Therefore, a continuous need remains to discover innovative chemical entities for the development of active and safer AEDs. Ligands targeting central histamine H 3 receptors (H 3 Rs) for epilepsy might be a promising therapeutic approach. To determine the potential of H 3 Rs ligands as new AEDs, we recently reported that no anticonvulsant effects were observed for the ( S )-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propanamide ( 1 ). In continuation of our research, we asked whether anticonvulsant differences in activities will be observed for its R -enantiomer, namely, ( R )-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propaneamide ( 2 ) and analogs thereof, in maximum electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced convulsion models in rats having PHT and valproic acid (VPA) as reference AEDs. Unlike the S -enantiomer ( 1 ), the results show that animals pretreated intraperitoneally (ip) with the R -enantiomer 2 (10 mg/kg) were moderately protected in MES and STR induced models, whereas proconvulsant effect was observed for the same ligand in PTZ-induced convulsion models. However, animals pretreated with intraperitoneal doses of 5, 10, or 15 mg/kg of structurally bulkier ( R )-enantiomer ( 3 ), in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol, and its ( S )-enantiomer ( 4 ) significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the ( R )-enantiomer ( 3 ) in MES model were significantly greater than those of the standard H 3 R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and reversed when rats were pretreated with the selective H 3 R agonist R -(α)-methyl-histamine. Comparisons of the observed antagonistic in vitro affinities among the ligands 1 - 6 revealed profound stereoselectivity at human H 3 Rs with varying preferences for this receptor subtype. Moreover, the in vivo anticonvulsant effects observed in this study for ligands 1 - 6 showed stereoselectivity in different convulsion models in male adult rats.

Modification of radiobiological effects of 171 MeV protons by elements of physical protection

NASA Astrophysics Data System (ADS)

Bulinina, Taisia; Shurshakov, Vyacheslav; Ivanov, Alexander; Molokanov, Alexander

2016-07-01

Space radiation includes protons of various energies. Physical protection is effective in the case of low energy protons (50-100 MeV) and becomes insufficient for radiation with a high part of high-energy protons. In the experiment performed on outbred mice, the purpose of the study was to evaluate the radiobiological effect of 171 MeV protons and protons modified by elements of physical protection of the spacecraft, on a complex of indicators of the functional condition of the system hematopoiesis and the central nervous system in 24 hours after irradiation at 20 cGy dose. The spacecraft radiation protection elements used in the experiment were a construction of wet hygiene wipes called a «protective curtain», and a glass plate imitating an ISS window. Mass thickness of the " protective curtain" in terms of water equivalent was ̴ 6,2 g/cm2. Physical shielding along the path of 171 MeV protons increases their linear energy transfer leading to the absorbed dose elevation and strengthening of the radiobiological effect. In the experiment, the two types of shielding together raised the absorbed dose from 20 to 23.2 cGy. Chemically different materials (glass and water in the wipes) were found to exert unequal modifying effects on physical and biological parameters of the proton-irradiated mice. There was a distinct dose-dependent reduction of bone marrow cellularity within the dose range from 20 cGy to 23.2 cGy in 24 hours after exposure. No modifying effect of the radiation protection elements on spontaneous motor activity was discovered when compared with entrance protons. The group of animals protected by the glass plate exhibited normal orientative-trying reactions and weakened grip with the forelimbs. The effects observed in the experiment indicate the necessity to carry out comprehensive radiobiological researches (physical, biological and mathematical) in assessing the effects of physical protection, that are actual for ensuring radiation safety of crews in interplanetary flights.

40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in observational... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Additional protections for pregnant...

40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in observational... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Additional protections for pregnant...

40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in observational... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Additional protections for pregnant...

40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in observational... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Additional protections for pregnant...

40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in observational... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Additional protections for pregnant...

Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine.

PubMed

Lee, Young J; Lee, Jeong Y; Jang, Yo H; Seo, Sang-Uk; Chang, Jun; Seong, Baik L

2018-01-01

The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3 -/- TLR7 -/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

Efficacy of Glutathione in Ameliorating Sulfur Mustard Analog-Induced Toxicity in Cultured Skin Epidermal Cells and in SKH-1 Mouse Skin In Vivo

PubMed Central

Tewari-Singh, Neera; Agarwal, Chapla; Huang, Jie; Day, Brian J.; White, Carl W.

2011-01-01

Exposure to chemical warfare agent sulfur mustard (HD) is reported to cause GSH depletion, which plays an important role in HD-linked oxidative stress and skin injury. Using the HD analog 2-chloroethyl ethyl sulfide (CEES), we evaluated the role of GSH and its efficacy in ameliorating CEES-caused skin injury. Using mouse JB6 and human HaCaT epidermal keratinocytes, we observed both protective and therapeutic effects of exogenous GSH (1 or 10 mM) in attenuating a CEES-caused decrease in cell viability and DNA synthesis, as well as S and G2M phase arrest in cell cycle progression. However, the protective effect of GSH was stronger than its ability to reverse CEES-induced cytotoxic effect. The observed effect of GSH could be associated with an increase in intracellular GSH levels after its treatment before or after CEES exposure, which strongly depleted cellular GSH levels. N-Acetyl cysteine, a GSH precursor, also showed both protective and therapeutic effects against CEES-caused cytotoxicity. Buthionine sulfoximine, which reduces cellular GSH levels, caused an increased CEES cytotoxicity in both JB6 and HaCaT cells. In further studies translating GSH effects in cell culture, pretreatment of mice with 300 mg/kg GSH via oral gavage 1 h before topical application of CEES resulted in significant protection against CEES-caused increase in skin bifold and epidermal thickness, apoptotic cell death, and myeloperoxidase activity, which could be associated with increased skin GSH levels. Together, these results highlight GSH efficacy in ameliorating CEES-caused skin injury and further support the need for effective antioxidant countermeasures against skin injury by HD exposure. PMID:20974699

Efficacy of glutathione in ameliorating sulfur mustard analog-induced toxicity in cultured skin epidermal cells and in SKH-1 mouse skin in vivo.

PubMed

Tewari-Singh, Neera; Agarwal, Chapla; Huang, Jie; Day, Brian J; White, Carl W; Agarwal, Rajesh

2011-02-01

Exposure to chemical warfare agent sulfur mustard (HD) is reported to cause GSH depletion, which plays an important role in HD-linked oxidative stress and skin injury. Using the HD analog 2-chloroethyl ethyl sulfide (CEES), we evaluated the role of GSH and its efficacy in ameliorating CEES-caused skin injury. Using mouse JB6 and human HaCaT epidermal keratinocytes, we observed both protective and therapeutic effects of exogenous GSH (1 or 10 mM) in attenuating a CEES-caused decrease in cell viability and DNA synthesis, as well as S and G(2)M phase arrest in cell cycle progression. However, the protective effect of GSH was stronger than its ability to reverse CEES-induced cytotoxic effect. The observed effect of GSH could be associated with an increase in intracellular GSH levels after its treatment before or after CEES exposure, which strongly depleted cellular GSH levels. N-Acetyl cysteine, a GSH precursor, also showed both protective and therapeutic effects against CEES-caused cytotoxicity. Buthionine sulfoximine, which reduces cellular GSH levels, caused an increased CEES cytotoxicity in both JB6 and HaCaT cells. In further studies translating GSH effects in cell culture, pretreatment of mice with 300 mg/kg GSH via oral gavage 1 h before topical application of CEES resulted in significant protection against CEES-caused increase in skin bifold and epidermal thickness, apoptotic cell death, and myeloperoxidase activity, which could be associated with increased skin GSH levels. Together, these results highlight GSH efficacy in ameliorating CEES-caused skin injury and further support the need for effective antioxidant countermeasures against skin injury by HD exposure.

The protective effect of LRRK2 p.R1398H on risk of Parkinson’s disease is independent of MAPT and SNCA variants

PubMed Central

Heckman, Michael G.; Elbaz, Alexis; Soto-Ortolaza, Alexandra I.; Serie, Daniel J.; Aasly, Jan O.; Annesi, Grazia; Auburger, Georg; Bacon, Justin A.; Boczarska-Jedynak, Magdalena; Bozi, Maria; Brighina, Laura; Chartier-Harlin, Marie-Christine; Dardiotis, Efthimios; Destée, Alain; Ferrarese, Carlo; Ferraris, Alessandro; Fiske, Brian; Gispert, Suzana; Hadjigeorgiou, Georgios M.; Hattori, Nobutaka; Ioannidis, John P. A.; Jasinska-Myga, Barbara; Jeon, Beom S.; Kim, Yun Joong; Klein, Christine; Kruger, Rejko; Kyratzi, Elli; Lin, Chin-Hsien; Lohmann, Katja; Loriot, Marie-Anne; Lynch, Timothy; Mellick, George D.; Mutez, Eugénie; Opala, Grzegorz; Park, Sung Sup; Petrucci, Simona; Quattrone, Aldo; Sharma, Manu; Silburn, Peter A.; Sohn, Young Ho; Stefanis, Leonidas; Tadic, Vera; Tomiyama, Hiroyuki; Uitti, Ryan J.; Valente, Enza Maria; Vassilatis, Demetrios K.; Vilariño-Güell, Carles; White, Linda R.; Wirdefeldt, Karin; Wszolek, Zbigniew K.; Wu, Ruey-Meei; Xiromerisiou, Georgia; Maraganore, Demetrius M.; Farrer, Matthew J.; Ross, Owen A.

2013-01-01

The best validated susceptibility variants for Parkinson’s disease (PD) are located in the alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes. Recently, a protective p.N551K-R1398H-K1423K haplotype in the leucine-rich repeat kinase 2 (LRRK2) gene was identified, with p.R1398H appearing to be the most likely functional variant. To date, the consistency of the protective effect of LRRK2 p.R1398H across MAPT and SNCA variant genotypes has not been assessed. To address this, we examined four SNCA variants (rs181489, rs356219, rs11931074, rs2583988), the MAPT H1-haplotype defining variant rs1052553, and LRRK2 p.R1398H (rs7133914) in Caucasian (N=10,322) and Asian (N=2,289) series. There was no evidence of an interaction of LRRK2 p.R1398H with MAPT or SNCA variants (all P≥0.10); the protective effect of p.R1398H was observed at similar magnitude across MAPT and SNCA genotypes, and the risk effects of MAPT and SNCA variants were observed consistently for LRRK2 p.R1398H genotypes. Our results indicate that the association of LRRK2 p.R1398H with PD is independent of SNCA and MAPT variants, and vice versa, in Caucasian and Asian populations. PMID:23962496

Assessment of the effects of heat and NBC (nuclear, biological, and chemical) protective clothing on performance of critical military tasks. Final report

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

Fine, B.J.; Kobrick, J.L.

Chemical protective clothing seriously degrades the performance of soldiers doing physical work in the heat. However, little is known about the combined effects of heat and protective clothing on mental performance. This study examined the effects of heat on the sustained cognitive performance of sedentary soldiers clad in NBC protective clothing. Twenty male soldiers trained for two weeks on tasks resembling those performed by fire direction center, forward observer and communications personnel. Then, they performed the tasks for seven-hour periods on four successive days in hot (91 F, 61% RH) and normal (70 F, 35% RH or 55 F, 35%more » RH) conditions, with and without protective clothing (MOPP IV). Conclusions: The data indicate quite conclusively that after four to five hours of exposure to a moderately hot environment, the cognitive performance of a group of highly trained soldiers, clad in the MOPP IV configuration of NBC protective clothing, began to deteriorate markedly. Two individuals became heat casualties and had to be evacuated from the chamber for medical reasons. A significant number of personnel had the integrity of their protective clothing compromised by sweat after as little as three hours of exposure to heat and virtually no physical activity.« less

Assessment of the Effectiveness of Combat Eyewear Protection Against Blast Overpressure.

PubMed

Sundaramurthy, A; Skotak, M; Alay, E; Unnikrishnan, G; Mao, H; Duan, X; Williams, S T; Harding, T H; Chandra, N; Reifman, J

2018-07-01

It is unclear whether combat eyewear used by U. S. Service members is protective against blast overpressures (BOPs) caused by explosive devices. Here, we investigated the mechanisms by which BOP bypasses eyewear and increases eye surface pressure. We performed experiments and developed three-dimensional (3D) finite element (FE) models of a head form (HF) equipped with an advanced combat helmet (ACH) and with no eyewear, spectacles, or goggles in a shock tube at three BOPs and five head orientations relative to the blast wave. Overall, we observed good agreement between experimental and computational results, with average discrepancies in impulse and peak-pressure values of less than 15% over 90 comparisons. In the absence of eyewear and depending on the head orientation, we identified three mechanisms that contributed to pressure loading on the eyes. Eyewear was most effective at 0 deg orientation, with pressure attenuation ranging from 50 (spectacles) to 80% (goggles) of the peak pressures observed in the no-eyewear configuration. Spectacles and goggles were considerably less effective when we rotated the HF in the counter-clockwise direction around the superior-inferior axis of the head. Surprisingly, at certain orientations, spectacles yielded higher maximum pressures (80%) and goggles yielded larger impulses (150%) than those observed without eyewear. The findings from this study will aid in the design of eyewear that provides better protection against BOP.

Vaccine-induced protection against anthrax in cheetah (Acinonyx jubatus) and black rhinoceros (Diceros bicornis).

PubMed

Turnbull, P C B; Tindall, B W; Coetzee, J D; Conradie, C M; Bull, R L; Lindeque, P M; Huebschle, O J B

2004-09-03

Institution of a policy of vaccination in endangered species with a vaccine not previously administered to it cannot be undertaken lightly. This applies even more in the case of cheetah (Acinonyx jubatus) with their unusually monomorphic gene pool and the potential restrictions this places on their immune responses. However, the recently observed mortalities from anthrax in these animals in the Etosha National Park, Namibia, made it imperative to evaluate vaccination. Black rhinoceros (Diceros bicornis), another endangered species in the park, have been vaccinated for over three decades but the effectiveness of this has never been evaluated. Passive protection tests in A/J mice using sera from 12 cheetahs together with enzyme immunoassay indicated that cheetah are able to mount seemingly normal primary and secondary humoral immune responses to the Sterne 34F2 live spore livestock vaccine. Overall protection rates in mice injected with the sera rose and fell in concert with rises and declines in antibody titres, although fine analysis showed that the correlation between titre and protection was complex. Once a high level of protection (96% of mice 1 month after a second booster in the cheetahs) had been achieved, the duration of substantial protection appeared good (60% of the mice 5 months after the second booster). Protection conferred on mice by sera from three of four vaccinated rhino was almost complete, but, obscurely, none of the mice receiving serum from the fourth rhino were protected. Sera from three park lions with naturally acquired high antibody titres, included as controls, also conferred high levels of protection. For the purposes of wildlife management, the conclusions were that vaccination of cheetah with the standard animal anthrax vaccine causes no observable ill effect in the animals and does appear to confer protective immunity. At least one well-separated booster does appear to be desirable. Vaccination of rhino also appears to be justified from the limited data obtained.

Effects of alcohol on platelet functions.

PubMed

Renaud, S C; Ruf, J C

1996-03-15

Recent epidemiologic studies have consistently shown that moderate intake of alcoholic beverages protect against morbidity and mortality from coronary heart disease and ischemic stroke. By contrast, alcohol drinking may also predispose to cerebral hemorrhage. These observations suggest an effect of alcohol similar to that of aspirin. Several studies in humans and animals have shown that the immediate effect of alcohol, either added in vitro to platelets or 10 to 20 min after ingestion, is to decrease platelet aggregation in response to most agonists (thrombin, ADP, epinephrine, collagen). Several hours later, as, in free-living populations deprived of drinking since the previous day it is mostly secondary aggregation to ADP and epinephrine and aggregation to collagen that are still inhibited in alcohol drinkers. By contrast, in binge drinkers or in alcoholics after alcohol withdrawal, response to aggregation, especially that induced by thrombin, is markedly increased. This rebound phenomenon, easily reproduced in rats, may explain ischemic strokes or sudden death known to occur after episodes of drunkenness. The platelet rebound effect of alcohol drinking was not observed with moderate red wine consumption in man. The protection afforded by wine has been recently duplicated in rats by grape tannins added to alcohol. This protection was associated with a decrease in the level of conjugated dienes, the first step in lipid peroxidation. In other words, wine drinking does not seem to be associated with the increased peroxidation usually observed with spirit drinking. Although further studies are required, the platelet rebound effect of alcohol drinking could be associated with an excess of lipid peroxides known to increase platelet reactivity, especially to thrombin.

[Prevention of hand dermatoses in small catering enterprises].

PubMed

Kurpiewska, Joanna; Liwkowicz, Jolanta; Padlewska, Kamila

2013-01-01

Work in catering and food processing is mostly performed by hands. Mechanical, thermal and chemical agents, as well as damp working conditions and frequent hand washing aggravate skin irritation. The aim of the study was to test the efficacy of hydrophobic skin protection measure at these workplaces. We recommended the prevention of contact skin disorders by using hydrophobic skin protection measure. The study was conducted in a group of 20 food service sector workers, They were interviewed about skin problems and skin protection measures. Tolb assess the effect of the protective preparation on the skin dermatological test procedures, corneometry and sebumetry, were applied, as well as the level of transepidermal water loss (TEWL) was measured. The same survey was performed in the control group composed of 10 workers who used and 10 who did not use barrier preparation. The respondents declared dryness, roughness, peeling, burning, redness, erythema of the skin. All who had applied barrier cream observed a significant improvement of the skin hydration increased by about 30%, and lubrication of the skin - by 11 times on average. Also the level of TEWL decreased by about 25%. The improvement of skin conditions and reduction of skin disorders were observed confirming the effectiveness of the protection of the skin from exposure to harmful factors. Knowledge about prevention of skin diseases should be promoted among employees of catering enterprises.

Biological effects of tritium on fish cells in the concentration range of international drinking water standards.

PubMed

Stuart, Marilyne; Festarini, Amy; Schleicher, Krista; Tan, Elizabeth; Kim, Sang Bog; Wen, Kendall; Gawlik, Jilian; Ulsh, Brant

2016-10-01

To evaluate whether the current Canadian tritium drinking water limit is protective of aquatic biota, an in vitro study was designed to assess the biological effects of low concentrations of tritium, similar to what would typically be found near a Canadian nuclear power station, and higher concentrations spanning the range of international tritium drinking water standards. Channel catfish peripheral blood B-lymphoblast and fathead minnow testis cells were exposed to 10-100,000 Bq l(-1) of tritium, after which eight molecular and cellular endpoints were assessed. Increased numbers of DNA strand breaks were observed and ATP levels were increased. There were no increases in γH2AX-mediated DNA repair. No differences in cell growth were noted. Exposure to the lowest concentrations of tritium were associated with a modest increase in the viability of fathead minnow testicular cells. Using the micronucleus assay, an adaptive response was observed in catfish B-lymphoblasts. Using molecular endpoints, biological responses to tritium in the range of Canadian and international drinking water standards were observed. At the cellular level, no detrimental effects were noted on growth or cycling, and protective effects were observed as an increase in cell viability and an induced resistance to a large challenge dose.

The corrosion protection of AA2024-T3 aluminium alloy by leaching of lithium-containing salts from organic coatings.

PubMed

Visser, Peter; Liu, Yanwen; Zhou, Xiaorong; Hashimoto, Teruo; Thompson, George E; Lyon, Stuart B; van der Ven, Leendert G J; Mol, Arjan J M C; Terryn, Herman A

2015-01-01

Lithium carbonate and lithium oxalate were incorporated as leachable corrosion inhibitors in model organic coatings for the protection of AA2024-T3. The coated samples were artificially damaged with a scribe. It was found that the lithium-salts are able to leach from the organic coating and form a protective layer in the scribe on AA2024-T3 under neutral salt spray conditions. The present paper shows the first observation and analysis of these corrosion protective layers, generated from lithium-salt loaded organic coatings. The scribed areas were examined by scanning and transmission electron microscopy before and after neutral salt spray exposure (ASTM-B117). The protective layers typically consist of three different layered regions, including a relatively dense layer near the alloy substrate, a porous middle layer and a flake-shaped outer layer, with lithium uniformly distributed throughout all three layers. Scanning electron microscopy and white light interferometry surface roughness measurements demonstrate that the formation of the layer occurs rapidly and, therefore provides an effective inhibition mechanism. Based on the observation of this work, a mechanism is proposed for the formation of these protective layers.

SunSmart: evaluation of a pilot school-based sun protection intervention in Hispanic early adolescents.

PubMed

Miller, K A; Langholz, B M; Ly, T; Harris, S C; Richardson, J L; Peng, D H; Cockburn, M G

2015-06-01

The incidence of melanoma is rising among Hispanic populations in the United States. The purpose of this study is to evaluate the impact of a pilot sun safety educational intervention conducted from 2006 to 2012 on Hispanic early adolescents in a high ultraviolet environment. Nineteen schools with high Hispanic enrollment were recruited from urban neighborhoods in Los Angeles. The analytic sample was restricted to students identifying as Hispanic or Latino (n = 777). A mixed effects linear model was used to test mean changes from pre- to posttest on students' sun protection knowledge, attitudes and behaviors. Significant improvements were observed across several cognitive outcomes related to sun protection, including knowledge of and attitudes toward sun protection and self-efficacy to wear sunscreen. However, changes in sun protective behaviors were not achieved. Although some improvements were observed, future studies should identify the factors that motivate sun protection in this population and develop tailored prevention strategies, as improving the sun safe behaviors of Hispanic youths may aid in reducing the risk of melanoma in adulthood in this population. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Selection of the Optimal Herbal Compositions of Red Clover and Pomegranate According to Their Protective Effect against Climacteric Symptoms in Ovariectomized Mice.

PubMed

Kang, Su Jin; Choi, Beom Rak; Kim, Seung Hee; Yi, Hae Yeon; Park, Hye Rim; Song, Chang Hyun; Ku, Sae Kwang; Lee, Young Joon

2016-07-23

This study aimed to ascertain the optimal range of red clover dry extracts (RC) and dried pomegranate concentrate powder (PCP) to induce anti-climacteric effects. Thus, the dose ranges showing protective effect of mixed formulae consisting of RC and PCP were examined in ovariectomized mice. At 28 days after bilateral ovariectomy (OVX), mixed herbal compositions (RC:PCP = 1:1, 1:2, 1:4, 1:8, 2:1, 4:1, and 8:1) were administered orally, at 120 mg/kg once daily for 84 days. We evaluated that RC and PCP mixture attenuate OVX-caused obesity, hyperlipidemia, hepatic steatosis, and osteoporosis. Compared to OVX-induced control mice, body weight and abdominal fat weight in OVX-induced mice were significantly decreased, concomitantly with increase of uterus weight by RC:PCP mixture. Additionally, significant increases in serum estradiol levels were observed in all RC:PCP-treated mice. RC:PCP mixture also showed protective effect against OVX-induced hyperlipidemia, hepatic steatosis. Total body and femur mean bone mineral density (BMD), osteocalcin, bALP contents were effectively increased by RC:PCP mixture. Taken together, RC:PCP mixture (2:1, 1:1, and 4:1) has remarkable protective effects against the changes induced by OVX. In particular, RC:PCP mixture (2:1) shows the strongest effect and may be considered as a potential protective agent against climacteric symptoms.

Selection of the Optimal Herbal Compositions of Red Clover and Pomegranate According to Their Protective Effect against Climacteric Symptoms in Ovariectomized Mice

PubMed Central

Kang, Su Jin; Choi, Beom Rak; Kim, Seung Hee; Yi, Hae Yeon; Park, Hye Rim; Song, Chang Hyun; Ku, Sae Kwang; Lee, Young Joon

2016-01-01

This study aimed to ascertain the optimal range of red clover dry extracts (RC) and dried pomegranate concentrate powder (PCP) to induce anti-climacteric effects. Thus, the dose ranges showing protective effect of mixed formulae consisting of RC and PCP were examined in ovariectomized mice. At 28 days after bilateral ovariectomy (OVX), mixed herbal compositions (RC:PCP = 1:1, 1:2, 1:4, 1:8, 2:1, 4:1, and 8:1) were administered orally, at 120 mg/kg once daily for 84 days. We evaluated that RC and PCP mixture attenuate OVX-caused obesity, hyperlipidemia, hepatic steatosis, and osteoporosis. Compared to OVX-induced control mice, body weight and abdominal fat weight in OVX-induced mice were significantly decreased, concomitantly with increase of uterus weight by RC:PCP mixture. Additionally, significant increases in serum estradiol levels were observed in all RC:PCP-treated mice. RC:PCP mixture also showed protective effect against OVX-induced hyperlipidemia, hepatic steatosis. Total body and femur mean bone mineral density (BMD), osteocalcin, bALP contents were effectively increased by RC:PCP mixture. Taken together, RC:PCP mixture (2:1, 1:1, and 4:1) has remarkable protective effects against the changes induced by OVX. In particular, RC:PCP mixture (2:1) shows the strongest effect and may be considered as a potential protective agent against climacteric symptoms. PMID:27455321

Carotid artery stenting with double cerebral embolic protection in asymptomatic patients - a diffusion-weighted MRI controlled study.

PubMed

Vuruskan, Ertan; Saracoglu, Erhan; Ergun, Ugur; Poyraz, Fatih; Duzen, İrfan Veysel

2017-01-01

The aim of this study was to compare the simultaneous double-protection method (proximal balloon plus distal filter) with distal-filter protection or proximal-balloon protection alone in asymptomatic patients during carotid artery stenting. 119 consecutive patients were investigated for carotid artery stentings in the extracranial internal carotid artery with the use of distal filters (n = 41, 34.4 %), proximal balloon (MoMa) protection (n = 40, 33.6 %) or double protection (n = 38, 31.9 %). Magnetic resonance imaging (MRI) was performed on all patients before the procedure, and control diffusion-weighted MRI (DW-MRI) was obtained within 24-48 h after the procedure. Procedural data, complications, success rate, major adverse cardiovascular events, and MRI findings were collected. New cerebral high-intensity (HI) lesions were observed in 47 (39.4 %) patients. HI lesions were observed in 22 (53.6 %), 15 (37.5 %), and 10 (26.3 %) of the patients with distal filters, proximal protection, and double protection, respectively (p = 0.004). The average number of HI lesions on DW-MRI was 1.80 in the distal-filter group, 0.90 in the proximal-balloon group, and 0.55 in the double-protection group (p < 0.001). Procedure and fluoroscopy times were slightly longer in the double-protection group compared to the distal- or proximal-protection groups (p = 0.001). The double (proximal plus distal) cerebral embolic protection technique is safe and effective for minimizing the risk of cerebral embolization, even in patients with asymptomatic carotid artery stenosis, despite slightly longer procedure and fluoroscopy times.
.

Controlled hydrostatic pressure stress downregulates the expression of ribosomal genes in preimplantation embryos: a possible protection mechanism?

PubMed

Bock, I; Raveh-Amit, H; Losonczi, E; Carstea, A C; Feher, A; Mashayekhi, K; Matyas, S; Dinnyes, A; Pribenszky, C

2016-04-01

The efficiency of various assisted reproductive techniques can be improved by preconditioning the gametes and embryos with sublethal hydrostatic pressure treatment. However, the underlying molecular mechanism responsible for this protective effect remains unknown and requires further investigation. Here, we studied the effect of optimised hydrostatic pressure treatment on the global gene expression of mouse oocytes after embryonic genome activation. Based on a gene expression microarray analysis, a significant effect of treatment was observed in 4-cell embryos derived from treated oocytes, revealing a transcriptional footprint of hydrostatic pressure-affected genes. Functional analysis identified numerous genes involved in protein synthesis that were downregulated in 4-cell embryos in response to hydrostatic pressure treatment, suggesting that regulation of translation has a major role in optimised hydrostatic pressure-induced stress tolerance. We present a comprehensive microarray analysis and further delineate a potential mechanism responsible for the protective effect of hydrostatic pressure treatment.

The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis

PubMed Central

Arndt, Mary Ann; Battaglia, Valentina; Parisi, Eva; Lortie, Mark J.; Isome, Masato; Baskerville, Christopher; Pizzo, Donald P.; Ientile, Riccardo; Colombatto, Sebastiano; Toninello, Antonio; Satriano, Joseph

2009-01-01

Agmatine, an endogenous metabolite of arginine, selectively suppresses growth in cells with high proliferative kinetics, such as transformed cells, through depletion of intracellular polyamine levels. In the present study, we depleted intracellular polyamine content with agmatine to determine if attrition by cell death contributes to the growth-suppressive effects. We did not observe an increase in necrosis, DNA fragmentation, or chromatin condensation in Ha-Ras-transformed NIH-3T3 cells administered agmatine. In response to Ca2+-induced oxidative stress in kidney mitochondrial preparations, agmatine demonstrated attributes of a free radical scavenger by protecting against the oxidation of sulfhydryl groups and decreasing hydrogen peroxide content. The functional outcome was a protective effect against Ca2+-induced mitochondrial swelling and mitochondrial membrane potential collapse. We also observed decreased expression of proapoptotic Bcl-2 family members and of execution caspase-3, implying antiapoptotic potential. Indeed, we found that apoptosis induced by camptothecin or 5-fluorourocil was attenuated in cells administered agmatine. Agmatine may offer an alternative to the ornithine decarboxylase inhibitor difluoromethyl ornithine for depletion of intracellular polyamine content while avoiding the complications of increasing polyamine import and reducing the intracellular free radical scavenger capacity of polyamines. Depletion of intracellular polyamine content with agmatine suppressed cell growth, yet its antioxidant capacity afforded protection from mitochondrial insult and resistance to cellular apoptosis. These results could explain the beneficial outcomes observed with agmatine in models of injury and disease. PMID:19321739

Do We Really Need to Wear Proper Eye Protection When Using Holmium:YAG Laser During Endourologic Procedures? Results from an Ex Vivo Animal Model on Pig Eyes.

PubMed

Villa, Luca; Cloutier, Jonathan; Compérat, Eva; Kronemberg, Peter; Charlotte, Frederic; Berthe, Laurent; Rouchausse, Yann; Salonia, Andrea; Montorsi, Francesco; Traxer, Olivier

2016-03-01

We sought to evaluate the effect of holmium:yttrium-aluminum-garnet (Ho:YAG) laser exposure on ex vivo pig eyes and to test the protective action of different glasses in preventing eye lesions in case of accident. We pointed the tip of a Ho:YAG laser fiber from different distances (0, 3, 5, 8, 10, and 20 cm, respectively) toward the center of the pupil of the pig eye. The Ho:YAG laser was activated for 1 or 5 seconds at three different settings (0.5 J-20 Hz, 1 J-10 Hz, and 2 J-10 Hz, respectively). The experiment was repeated using laser safety glasses and eyeglasses. A total of 78 pig eyes were used. The effects of the Ho:YAG laser on pig eyes were assessed by histopathology. Comparable laser emission experiments were performed on thermal paper at different distances using different pulse energies. Ho:YAG laser-induced corneal lesions were observed in unprotected eyes, ranging from superficial burning lesions to full-thickness necrotic areas, and were directly related to pulse energy and time of exposure and inversely related to the distance from the eye. When the laser was placed 5 cm or more, no corneal damage was observed regardless of the laser setting and the time of exposure. Similar distance/energy level relationships were observed on thermal paper. No damage was observed to the lens or the retina in any of the Ho-YAG laser-treated eyes or in any of the eyes protected by laser safety and eyeglasses. Ho:YAG lasers can cause damage when set to high energy, but only to the cornea, from close distances (0-5 cm) and in the absence of eye protection. Eyeglasses are equally effective in preventing laser damage as laser safety glasses.

Protective Effects of Parent-College Student Communication During the First Semester of College

PubMed Central

Small, Meg L.; Morgan, Nicole; Abar, Caitlin; Maggs, Jennifer L.

2011-01-01

Objective Recent studies suggest that parents maintain influence as their adolescents transition into college. Advances in communication technology make frequent communication between parents and college students easy and affordable. This study examines the protective effect of parent-college student communication on student drinking behaviors, estimated peak blood alcohol concentration (eBAC), and serious negative consequences of drinking. Participants Participants were 746 first-year, first-time, full-time students at a large university in the U.S. Methods Participants completed a baseline and 14 daily web-based surveys. Results The amount of time spent communicating with parents on weekend days predicted the number of drinks consumed, heavy drinking, and peak eBAC consistent with a protective within-person effect. No association between communication and serious negative consequences was observed. Conclusions Encouraging parents to communicate with their college students, particularly on weekend days, could be a relatively simple, easily implemented protective process to reduce dangerous drinking behaviors. PMID:21660810

Childhood infectious diseases and risk of leukaemia in an adult population.

PubMed

Parodi, Stefano; Crosignani, Paolo; Miligi, Lucia; Nanni, Oriana; Ramazzotti, Valerio; Rodella, Stefania; Costantini, Adele Seniori; Tumino, Rosario; Vindigni, Carla; Vineis, Paolo; Stagnaro, Emanuele

2013-10-15

Our study is aimed at investigating the association between common childhood infectious diseases (measles, chickenpox, rubella, mumps and pertussis) and the risk of developing leukaemia in an adult population. A reanalysis of a large population-based case-control study was carried out. Original data included 1,771 controls and 649 leukaemia cases from 11 Italian areas. To contain recall bias, the analysis was restricted to subjects directly interviewed and with a good quality interview (1,165 controls and 312 cases). Odds ratios (ORs) and their related 95% confidence intervals (95% CIs) were estimated by unconditional polychotomous logistic regression model adjusting for age, gender and occupational and lifestyle exposures. A protective effect of at least one infection (OR = 0.66, 95% CI: 0.45-0.97), measles (OR = 0.57, 95% CI: 0.39-0.82) and pertussis (OR = 0.66, 95% CI: 0.45-0.98) was observed for chronic lymphoid leukaemia (CLL). The number of infections was strongly inversely associated with the risk of CLL (p = 0.002, test for trend). With regard to the other types of leukaemia, only a protective effect of pertussis was observed for AML (OR = 0.52, 95% CI: 0.32-0.87). Our results pointed out a protective role of childhood infectious diseases on the risk of CLL in adults. Although a specific antioncogenic effect of some infectious disease, especially measles, cannot be ruled out, the observed decrease of risk with increasing number of infections suggests that a more general "hygiene hypothesis" could be the most likely explanation of the detected association. The protective role of pertussis remains to be elucidated. Copyright © 2013 UICC.

Structural drivers and social protection: mechanisms of HIV risk and HIV prevention for South African adolescents.

PubMed

Cluver, Lucie Dale; Orkin, Frederick Mark; Meinck, Franziska; Boyes, Mark Edward; Sherr, Lorraine

2016-01-01

Social protection is high on the HIV-prevention agenda for youth in sub-Saharan Africa. However, questions remain: How do unconditional cash transfers work? What is the effect of augmenting cash provision with social care? And can "cash plus care" social protection reduce risks for adolescents most vulnerable to infection? This study tackles these questions by first identifying mediated pathways to adolescent HIV risks and then examining potential main and moderating effects of social protection in South Africa. This study was a prospective observational study of 3515 10-to-17-year-olds (56.7% female; 96.8% one-year retention). Within randomly selected census areas in four rural and urban districts in two South African provinces, all homes with a resident adolescent were sampled between 2009/2010 and 2011/2012. Measures included 1) potential structural drivers of HIV infection such as poverty and community violence; 2) HIV risk behaviours; 3) hypothesized psychosocial mediating factors; and 4) types of social protection involving cash and care. Using gender-disaggregated analyses, longitudinal mediation models were tested for potential main and moderating effects of social protection. Structural drivers were associated with increased onset of adolescent HIV risk behaviour (p<0.001, B=0.06, SE=0.01), fully mediated by increased psychosocial problems. Both cash and care aspects of social protection were associated with reductions in HIV risk behaviour and psychosocial deprivations. In addition, cash social protection moderated risk pathways: for adolescent girls and boys experiencing more acute structural deprivation, social protection had the greatest associations with HIV risk prevention (e.g. moderation effects for girls: B=-0.08, p<0.002 between structural deprivation and psychosocial problems, and B=-0.07, p<0.001 between psychosocial problems and HIV risk behaviour). Adolescents with the greatest structural deprivation are at higher risk of HIV, but social protection has the greatest prevention effects for the most vulnerable. Social protection comprising unconditional cash plus care was associated with reduced risk pathways through moderation and main effects, respectively. Our findings suggest the importance of social protection within a combination package of HIV-prevention approaches.

Structural drivers and social protection: mechanisms of HIV risk and HIV prevention for South African adolescents

PubMed Central

Cluver, Lucie Dale; Orkin, Frederick Mark; Meinck, Franziska; Boyes, Mark Edward; Sherr, Lorraine

2016-01-01

Introduction Social protection is high on the HIV-prevention agenda for youth in sub-Saharan Africa. However, questions remain: How do unconditional cash transfers work? What is the effect of augmenting cash provision with social care? And can “cash plus care” social protection reduce risks for adolescents most vulnerable to infection? This study tackles these questions by first identifying mediated pathways to adolescent HIV risks and then examining potential main and moderating effects of social protection in South Africa. Methods This study was a prospective observational study of 3515 10-to-17-year-olds (56.7% female; 96.8% one-year retention). Within randomly selected census areas in four rural and urban districts in two South African provinces, all homes with a resident adolescent were sampled between 2009/2010 and 2011/2012. Measures included 1) potential structural drivers of HIV infection such as poverty and community violence; 2) HIV risk behaviours; 3) hypothesized psychosocial mediating factors; and 4) types of social protection involving cash and care. Using gender-disaggregated analyses, longitudinal mediation models were tested for potential main and moderating effects of social protection. Results Structural drivers were associated with increased onset of adolescent HIV risk behaviour (p<0.001, B=0.06, SE=0.01), fully mediated by increased psychosocial problems. Both cash and care aspects of social protection were associated with reductions in HIV risk behaviour and psychosocial deprivations. In addition, cash social protection moderated risk pathways: for adolescent girls and boys experiencing more acute structural deprivation, social protection had the greatest associations with HIV risk prevention (e.g. moderation effects for girls: B=−0.08, p<0.002 between structural deprivation and psychosocial problems, and B=−0.07, p<0.001 between psychosocial problems and HIV risk behaviour). Conclusions Adolescents with the greatest structural deprivation are at higher risk of HIV, but social protection has the greatest prevention effects for the most vulnerable. Social protection comprising unconditional cash plus care was associated with reduced risk pathways through moderation and main effects, respectively. Our findings suggest the importance of social protection within a combination package of HIV-prevention approaches. PMID:27086838

Session 21.3 - Radio and Optical Site Protection

NASA Astrophysics Data System (ADS)

Sefako, Ramotholo

2016-10-01

Advancement in radio technology means that radio astronomy has to share the radio spectrum with many other non-astronomical activities, majority of which increase radio frequency interference (RFI), and therefore detrimentally affecting the radio observations at the observatory sites. Major radio facilities such as the SKA, in both South Africa and Australia, and the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in China will be very sensitive, and therefore require protection against RFI. In the case of optical astronomy, the growing urbanisation and industrialisation led to optical astronomy becoming impossible near major cities due to light and dust pollution. Major optical and IR observatories are forced to be far away in remote areas, where light pollution is not yet extreme. The same is true for radio observatories, which have to be sited away from highly RFI affected areas near populated regions and major cities. In this review, based on the Focus Meeting 21 (FM21) oral presentations at the IAU General Assembly on 11 August 2015, we give an overview of the mechanisms that have evolved to provide statutory protection for radio astronomy observing, successes (e.g at 21 cm HI line), defeats and challenges at other parts of the spectrum. We discuss the available legislative initiatives to protect the radio astronomy sites for large projects like SKA (in Australia and South Africa), and FAST against the RFI. For optical protection, we look at light pollution with examples of its effect at Xinglong observing station of the National Astronomical Observatories of China (NAOC), Ali Observatory in Tibet, and Asiago Observatory in Italy, as well as the effect of conversion from low pressure sodium lighting to LEDs in the County of Hawaii.

The big picture: does colonoscopy work?

PubMed

Hewett, David G; Rex, Douglas K

2015-04-01

Colonoscopy for average-risk colorectal cancer screening has transformed the practice of gastrointestinal medicine in the United States. However, although the dominant screening strategy, its use is not supported by randomized controlled trials. Observational data do support a protective effect of colonoscopy and polypectomy on colorectal cancer incidence and mortality, but the level of protection in the proximal colon is variable and operator-dependent. Colonoscopy by high-level detectors remains highly effective, and ongoing quality improvement initiatives should consider regulatory factors that motivate changes in physician behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Gene–Environment Correlation: Difficulties and a Natural Experiment–Based Strategy

PubMed Central

Li, Jiang; Liu, Hexuan; Guo, Guang

2013-01-01

Objectives. We explored how gene–environment correlations can result in endogenous models, how natural experiments can protect against this threat, and if unbiased estimates from natural experiments are generalizable to other contexts. Methods. We compared a natural experiment, the College Roommate Study, which measured genes and behaviors of college students and their randomly assigned roommates in a southern public university, with observational data from the National Longitudinal Study of Adolescent Health in 2008. We predicted exposure to exercising peers using genetic markers and estimated environmental effects on alcohol consumption. A mixed-linear model estimated an alcohol consumption variance that was attributable to genetic markers and across peer environments. Results. Peer exercise environment was associated with respondent genotype in observational data, but not in the natural experiment. The effects of peer drinking and presence of a general gene–environment interaction were similar between data sets. Conclusions. Natural experiments, like random roommate assignment, could protect against potential bias introduced by gene–environment correlations. When combined with representative observational data, unbiased and generalizable causal effects could be estimated. PMID:23927502

Permethrin treated clothing to protect outdoor workers: evaluation of different methods for mosquito exposure against populations with differing resistance status.

PubMed

Richards, Stephanie L; Agada, Nwanne; Balanay, Jo Anne G; White, Avian V

2018-02-01

Minimizing arthropod exposure (e.g. mosquito and tick bites) is vital to protect health of outdoor workers. Personal protective measures can help protect against exposure. Here, the quantity of permethrin was evaluated for different fabric types after washing. Cone and petri dish exposure assays were used to investigate the knockdown/mortality of permethrin-susceptible and permethrin-resistant populations of mosquitoes. Permethrin-treated clothing was effective against the tested mosquito population that was susceptible to permethrin but not a permethrin-resistant population. Permethrin quantity was significantly highest in the 100% cotton fabric and for the 0 wash group. Permethrin quantity in fabrics decreased with washing. No significant differences (p > 0.05) were observed in knockdown/mortality rates for either exposure method. The protective effect of permethrin-treated clothing against mosquitoes is impacted by many factors, e.g. wash frequency, fabric type, and the susceptibility/resistance status of local mosquito populations.

Effect of pH on subunit association and heat protection of soybean alpha-galactosidase

NASA Technical Reports Server (NTRS)

Porter, J. E.; Sarikaya, A.; Herrmann, K. M.; Ladisch, M. R.; Mitchell, C. A. (Principal Investigator)

1992-01-01

Soybeans contain the enzyme alpha-galactosidase, which hydrolyzes alpha-1, 6 linkages in stachyose and raffinose to give sucrose and galactose. We have found that galactose, a competitive product inhibitor of alpha-galactosidase, strongly promotes the heat stability of the tetrameric form of the enzyme at pH 4.0 and at temperatures of up to 70 degrees C for 60 min. Stachyose and raffinose also protect alpha-galactosidase from denaturation at pH 4.0 although to a lesser extent. Glucose and mannose have little effect. At pH 7.0 the enzyme is a monomer, and galactose has no effect on the heat stability of the enzyme. In the absence of heat protection of the enzyme by added sugars, a series deactivation mechanism was found to describe the deactivation data. In comparison, a unimolecular, non-first order deactivation model applies at pH 4.0, where heat protection effects were observed. At a temperature above 60 degrees C, simple deactivation is a suitable model. The results suggest that alpha-galactosidase conformation and heat stability are directly related.

The effect of fathers or father figures on child behavioral problems in families referred to child protective services.

PubMed

Marshall, D B; English, D J; Stewart, A J

2001-11-01

This study examines some possible effects of the presence and quality of parent-child interaction of fathers and father figures on the behavior of young children in a sample of families reported to child protective services. Whereas the presence or absence of a father or father figure seemed to make little difference in child behavioral problems at age 4, lower levels of aggression and depression were observed for children by age 6 if an adult male in some form of father-like relationship was present in the child's life. When controlling for mother's ethnicity, child's gender, the number of referrals to child protective services, and the presence of domestic violence, the direct effect of a father/father figure was no longer significant but remained in the multivariate models as a significant interaction term.

Evaluation of Effect CAT -262C/T, SOD + 35A/C, GPx1 Pro197Leu Polymorphisms in Patients with IBD in the Polish Population.

PubMed

Mrowicki, Jerzy; Mrowicka, Małgorzata; Majsterek, Ireneusz; Mik, Michał; Dziki, Adam; Dziki, Łukasz

2016-12-01

Inflammatory bowel disease (IBD) are a heterogeneous group of disorders in the course dominated by chronic, recurrent gastrointestinal inflammation. It is believed that the activation of IBD occurs in patients with a genetic predisposition to their development. Chronic inflammation develops as a result of an excessive reaction of the immune system principally under the influence of environmental risk factors. Among them, it has been shown that the mechanism of oxidative stress is associated with the pathophysiology of inflammatory bowel disease, responsible for the commencement and progress of these diseases. The aim of the study was the relationship between single nucleotide polymorphisms (SNPs) of individual antioxidant enzymes, and the prevalence of inflammatory bowel disease that may be associated with increased levels of oxidative stress. A total of 111 IBD patients, including 65 patients with ulcerative colitis (UC) and 46 with Crohn's disease (CD) and 125 healthy controls recruited from the Polish population, were genotyped for CAT -262C / T (rs1001179), SOD + 35A / C (rs2234694), GPx Pro 197 Leu polymorphisms. Genotyping of CAT, SOD, GPx gene polymorphism was performed by a RFLP-PCR. The performed analysis of genetic polymorphisms of antioxidant enzymes showed that polymorphic variant of the CAT -262 C / T may have protective effects in patients with ulcerative colitis in the range of genotype C / T; OR = 0.49 (0.25-0.99), p = 0.044. Trend protective, but statistically unrelated, it was also observed for genotype T / T and T allele of the same polymorphism and genotypes and alleles + 35A / C SOD1 in UC as well as polymorphic variants CAT -262 C / T, Pro197Leu of GPx1, + 35A / C SOD1 in CD. The results were compared with a control group of potentially healthy individuals without such diseases. It has been shown that the polymorphism of antioxidant enzymes CAT gene -262 C / T may have protective effects in patients who are carriers of a genotype C / T at the UC. The potential protective effect without statistical relationships were also observed for other genotypes and alleles studied polymorphic variants of antioxidant enzymes in CD and CAT- 262C / T and + 35 A / C SOD1 in UC. Conducted our audit should be extended to more group of patients in order to assess whether or not to confirm the observed during analysis, the protective effect of CAT-262 C / T in ulcerative colitis and other trends observed for other polymorphic variants tested genes.

Training of interventional cardiologists in radiation protection--the IAEA's initiatives.

PubMed

Rehani, Madan M

2007-01-08

The International Atomic Energy Agency (IAEA) has initiated a major international initiative to train interventional cardiologists in radiation protection as a part of its International Action Plan on the radiological protection of patients. A simple programme of two days' training has been developed, covering possible and observed radiation effects among patients and staff, international standards, dose management techniques, examples of good and bad practice and examples indicating prevention of possible injuries as a result of good practice of radiation protection. The training material is freely available on CD from the IAEA. The IAEA has conducted two events in 2004 and 2005 and number of events are planned in 2006. The survey conducted among the cardiologists participating in these programmes indicates that over 80% of them were attending such a structured programme on radiation protection for the first time. As the magnitude of X-ray usage in cardiology grows to match that in interventional radiology, the standards of training on radiation effects, radiation physics and radiation protection in interventional cardiology should also match those in interventional radiology.

Thienopyrimidine-type compounds protect Arabidopsis plants against the hemibiotrophic fungal pathogen Colletotrichum higginsianum and bacterial pathogen Pseudomonas syringae pv. maculicola.

PubMed

Narusaka, Mari; Narusaka, Yoshihiro

2017-03-04

Plant activators activate systemic acquired resistance-like defense responses or induced systemic resistance, and thus protect plants from pathogens. We screened a chemical library composed of structurally diverse small molecules. We isolated six plant immune-inducing thienopyrimidine-type compounds and their analogous compounds. It was observed that the core structure of thienopyrimidine plays a role in induced resistance in plants. Furthermore, we highlight the protective effect of thienopyrimidine-type compounds against both hemibiotrophic fungal pathogen, Colletotrichum higginsianum, and bacterial pathogen, Pseudomonas syringae pv. maculicola, in Arabidopsis thaliana. We suggest that thienopyrimidine-type compounds could be potential lead compounds as novel plant activators, and can be useful and effective agrochemicals against various plant diseases.

Photo-damage protective effect of two facial products, containing a unique complex of Dead Sea minerals and Himalayan actives.

PubMed

Wineman, Eitan; Portugal-Cohen, Meital; Soroka, Yoram; Cohen, Dror; Schlippe, Gerrit; Voss, Werner; Brenner, Sarah; Milner, Yoram; Hai, Noam; Ma'or, Zeevi

2012-09-01

Skin appearance is badly affected when exposed to solar UV rays, which encourage physiological and structural cutaneous alterations that eventually lead to skin photo-damage. To test the capability of two facial preparations, extreme day cream (EXD) and extreme night treatment (EXN), containing a unique complex of Dead Sea water and three Himalayan extracts, to antagonize biological effects induced by photo-damage. Pieces of organ cultures of human skin were used as a model to assess the biological effects of UVB irradiation and the protective effect of topical application of two Extreme preparations. Skin pieces were analyzed for mitochondrial activity by MTT assay, for apoptosis by caspase 3 assay, and for cytokine secretion by solid phase ELISA. Human subjects were tested to evaluate the effect of Extreme preparations on skin wrinkle depth using PRIMOS and skin hydration by a corneometer. UVB irradiation induced cell apoptosis in the epidermis of skin organ cultures and increased their pro-inflammatory cytokine, tumor necrosis α (TNFα) secretion. Topical applications of both preparations significantly attenuated all these effects. Furthermore, in human subjects, a reduction in wrinkle depth and an elevation in the intense skin moisture were observed. The observations clearly show that EXD and EXN preparations have protective anti-apoptotic and anti-inflammatory properties that can attenuate biological effects of skin photo-damage. Topical application of the preparations improves skin appearance by reducing its wrinkles depth and increasing its moisturizing impact. © 2012 Wiley Periodicals, Inc.

Protective effects of phenolics rich extract of ginger against Aflatoxin B1-induced oxidative stress and hepatotoxicity.

PubMed

A V, Vipin; K, Raksha Rao; Kurrey, Nawneet Kumar; K A, Anu Appaiah; G, Venkateswaran

2017-07-01

Aflatoxin B 1 (AFB 1 ) is one of the predominant mycotoxin contaminant in food and feed, causing oxidative stress and hepatotoxicity. Ginger phenolics have been reported for its antioxidant potential and hepatoprotective activity. The present study investigated the protective effects of phenolics rich ginger extract (GE) against AFB 1 induced oxidative stress and hepatotoxicity, in vitro and in vivo. The phenolic acid profiles of GE showed 6-gingerol and 6-shogaol as predominant components. Pretreatment of HepG2 cells with GE significantly inhibited the production of intracellular reactive oxygen species (ROS), DNA strand break, and cytotoxicity induced by AFB 1 . A comparable effect was observed in in vivo. Male Wistar rats were orally treated with GE (100 and 250mg/kg) daily, with the administration of AFB 1 (200μg/kg) every alternative day for 28days. Treatment with GE significantly reduced AFB 1 induced toxicity on the serum markers of liver damage. In addition, GE also showed significant hepatoprotective effect by reducing the lipid peroxidation and by enhancing the antioxidant enzymes activities. These results combined with liver histopathological observations indicated that GE has potential protective effect against AFB 1 induced hepatotoxicity. Additionally, administration of GE up-regulated Nrf2/HO-1 pathway, which further proved the efficiency of GE to inhibit AFB 1 induced hepatotoxicity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Protecting children from violence and maltreatment: a qualitative comparative analysis assessing the implementation of U.N. CRC Article 19.

PubMed

Svevo-Cianci, Kimberly A; Hart, Stuart N; Rubinson, Claude

2010-01-01

(1) To identify which United Nations Convention on the Rights of the Child (CRC) recommended child protection (CP) measures, such as policy, reporting systems, and services for child abuse and neglect (CAN) victims, individually or in combination, were most important in establishing a basic level of child protection in 42 countries; and (2) to assess whether these measures were necessary or sufficient to achieve basic child protection in developing and industrialized countries. Child protection and/or rights expert respondents from 42 countries completed a questionnaire on CRC Article 19 (CRC19) required CP measures implementation and rated their country's effectiveness in implementation, the current level of effectiveness of child protection, and the relevance of improvements in child protection since the CRC was adopted in 1989. Information from the Committee on the Rights of the Child Concluding Observations, as well as UNICEF and WHO indicators on child health and protection issues were used to check and supplement responses. Qualitative comparative analysis (QCA) was used to identify child protection measure implementation effectiveness. Results indicate that child protection judged as comparatively more successful among study countries is a result of having the following measures in place from two types of social programs: a CP infrastructure (legislation plus services) and at least one information-based intervention support program. Fourteen (33%) countries were determined to have established at least a basic CP system toward protection of children from violence and maltreatment. These countries reported having the three required elements described above. The study reinforces the need for governments to take a systems approach to child protection, including policy/legislation, information-based programs and social services, as well as professional training and public awareness raising. The top-ranked countries included: Australia, Bahrain, Belgium, Brazil, Canada, Estonia, Germany, Italy, Jordan, Lebanon, Malaysia, Republic of Korea, the Russian Federation, and the United Kingdom. Governments need to establish CP systems with multiple, well-integrated, effective CP measures as elaborated above, working with trained professionals and also raising public awareness to ensure successful protection for all children in every country. Partial measures are not effective. Further, in addition to establishing, implementing, and evaluating the effectiveness of professional interventions, the actual outcomes for children, not studied or reported on here, need to be the priority focus for child protection going forward. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

40 CFR 26.302 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Definitions. 26.302 Section 26.302 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Observational Research: Additional Protections for Pregnant Women and Fetuses Involved as Subjects in Observational...

40 CFR 26.302 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Definitions. 26.302 Section 26.302 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Observational Research: Additional Protections for Pregnant Women and Fetuses Involved as Subjects in Observational...

40 CFR 26.302 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Definitions. 26.302 Section 26.302 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Observational Research: Additional Protections for Pregnant Women and Fetuses Involved as Subjects in Observational...

40 CFR 26.302 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Definitions. 26.302 Section 26.302 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Observational Research: Additional Protections for Pregnant Women and Fetuses Involved as Subjects in Observational...

40 CFR 26.302 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Definitions. 26.302 Section 26.302 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Observational Research: Additional Protections for Pregnant Women and Fetuses Involved as Subjects in Observational...

Herd effect from influenza vaccination in non-healthcare settings: a systematic review of randomised controlled trials and observational studies

PubMed Central

Mertz, Dominik; Fadel, Shaza A.; Lam, Po-Po; Tran, Dat; Srigley, Jocelyn A; Asner, Sandra A; Science, Michelle; Kuster, Stefan P; Nemeth, Johannes; Johnstone, Jennie; Ortiz, Justin R; Loeb, Mark

2016-01-01

Influenza vaccination programmes are assumed to have a herd effect and protect contacts of vaccinated persons from influenza virus infection. We searched MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Global Health and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to March 2014 for studies assessing the protective effect of influenza vaccination vs no vaccination on influenza virus infections in contacts. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. Of 43,082 screened articles, nine randomised controlled trials (RCTs) and four observational studies were eligible. Among the RCTs, no statistically significant herd effect on the occurrence of influenza in contacts could be found (OR: 0.62; 95% CI: 0.34–1.12). The one RCT conducted in a community setting, however, showed a significant effect (OR: 0.39; 95% CI: 0.26–0.57), as did the observational studies (OR: 0.57; 95% CI: 0.43–0.77). We found only a few studies that quantified the herd effect of vaccination, all studies except one were conducted in children, and the overall evidence was graded as low. The evidence is too limited to conclude in what setting(s) a herd effect may or may not be achieved. PMID:27784531

DC vaccination with anti-CD25 treatment leads to long-term immunity against experimental glioma

PubMed Central

Maes, Wim; Rosas, Georgina Galicia; Verbinnen, Bert; Boon, Louis; De Vleeschouwer, Steven; Ceuppens, Jan L.; Van Gool, Stefaan W.

2009-01-01

We studied the feasibility, efficacy, and mechanisms of dendritic cell (DC) immunotherapy against murine malignant glioma in the experimental GL261 intracranial (IC) tumor model. When administered prophylactically, mature DCs (DCm) ex vivo loaded with GL261 RNA (DCm-GL261-RNA) protected half of the vaccinated mice against IC glioma, whereas treatment with mock-loaded DCm or DCm loaded with irrelevant antigens did not result in tumor protection. In DCm-GL261-RNA–vaccinated mice, a tumor-specific cellular immune response was observed ex vivo in the spleen and tumor-draining lymph node cells. Specificity was also shown in vivo on the level of tumor challenge. Depletion of CD8+ T-cells by anti-CD8 treatment at the time of tumor challenge demonstrated their essential role in vaccine- mediated antitumor immunity. Depletion of CD25+ regulatory T-cells (Tregs) by anti-CD25 (aCD25) treatment strongly enhanced the efficacy of DC vaccination and was itself also protective, independently of DC vaccination. However, DC vaccination was essential to protect the animals from IC tumor rechallenge. No long-term protection was observed in animals that initially received aCD25 treatment only. In mice that received DC and/or aCD25 treatment, we retrieved tumor-specific brain-infiltrating cytotoxic T-lymphocytes. These data clearly demonstrate the effectiveness of DC vaccination for the induction of long-lasting immunological protection against IC glioma. They also show the beneficial effect of Treg depletion in this kind of glioma immunotherapy, even combined with DC vaccination. PMID:19336528

Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus.

PubMed

Habibi, Maximillian S; Jozwik, Agnieszka; Makris, Spyridon; Dunning, Jake; Paras, Allan; DeVincenzo, John P; de Haan, Cornelis A M; Wrammert, Jens; Openshaw, Peter J M; Chiu, Christopher

2015-05-01

Despite relative antigenic stability, respiratory syncytial virus (RSV) reinfects throughout life. After more than 40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. To characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development. We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B-cell frequencies and antibody longevity. Despite moderately high levels of preexisting serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from polymerase chain reaction-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects but correlated with plasmablasts that peaked around Day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, in which virus-specific IgA memory B cells were readily recovered. This observed specific defect in IgA memory may partly explain the ability of RSV to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone.

Direct and protective effects of single or combined addition of vincristine and ε-viniferin on human HepG2 cellular oxidative stress markers in vitro.

PubMed

Tarhan, Seda; Özdemir, Filiz; İncesu, Zerrin; Demirkan, Emine Sütken

2016-08-01

The objective of this study is to examine the direct effects of low doses and high doses of ε-viniferin, a substance known to be an antioxidant, and vincristine sulphate, a chemotherapeutic agent, alone and in combination [ε-viniferin + vincristine] on HepG2 cell strain, as well as evaluate oxidative stress after incubation periods of 3, 6, and 24 h. Direct effect was determined right after the incubation period; however, for protective effect, antioxidant protection response was determined after the treatment for 1 h with 500 μM H2O2, which is an oxidative stressor. For this purpose, superoxide dismutase was determined for enzyme activity, and lipid hydroperoxide (LPO) and reduced glutathione concentrations were studied as indicators of oxidative stress. Results show that low [3.63 µM vincristine + 3.75 µM ε-viniferin] and high [11.25 µM vincristine + 15.8 µM ε-viniferin] doses of combination groups showed similar direct antioxidant effect on LPO levels as protective when compared to the H2O2 control group (p < 0.05). Superoxide dismutase enzyme showed a direct antioxidant effect in low and high dose combination groups. In addition, when the incubation period was increased to 24 h, a protective effect was observed in both dose groups (p < 0.05). Reduced glutathione activities showed a direct effect in the low dose combination group, and a protective effect in both the low and high doses in the 24 h. These results show that combined usage of drugs in HepG2 cell strain possesses a protective effect against exogenically produced oxidative stress conditions.

The protective role of the Bowman-Birk protease inhibitor in soybean lunasin digestion: the effect of released peptides on colon cancer growth.

PubMed

Cruz-Huerta, Elvia; Fernández-Tomé, Samuel; Arques, M Carmen; Amigo, Lourdes; Recio, Isidra; Clemente, Alfonso; Hernández-Ledesma, Blanca

2015-08-01

Lunasin is a naturally-occurring peptide demonstrating chemopreventive, antioxidant and anti-inflammatory properties. To exhibit these activities, orally ingested lunasin needs to survive proteolytic attack of digestive enzymes to reach target tissues in active form/s. Preliminary studies suggested the protective role of protease inhibitors, such as the Bowman-Birk inhibitor and Kunitz-trypsin inhibitor, against lunasin's digestion by both pepsin and pancreatin. This work describes in depth the behaviour of lunasin under conditions simulating the transit through the gastrointestinal tract in the absence or presence of soybean Bowman-Birk isoinhibitor 1 (IBB1) in both active and inactive states. By liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the remaining lunasin at the end of gastric and gastro-duodenal phases was quantified. Protection against the action of pepsin was independent of the amount of IBB1 present in the analyzed samples, whereas an IBB1 dose-dependent protective effect against trypsin and chymotrypsin was observed. Peptides released from lunasin and inactive IBB1 were identified by MS/MS. The remaining lunasin and IBB1 as well as their derived peptides could be responsible for the anti-proliferative activity against colon cancer cells observed for the digests obtained at the end of simulated gastrointestinal digestion.

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

PubMed

Li, Hao; Wang, Xing-Xing; Wang, Bin; Fu, Lei; Liu, Guan; Lu, Yu; Cao, Min; Huang, Hairong; Javid, Babak

2017-05-09

The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.

DNA damage by various radiations

NASA Astrophysics Data System (ADS)

Hasegawa, K.; Yoshioka, H.; Yoshioka, H.

1997-01-01

In an attempt to shed light on the influence of tritiated water on DNA we have investigated the post-irradiation damage with a simple plasmid DNA, pBR322 and pUC18. The survival of covalently closed circular (CCC) DNA form was directly followed by agarose gel electrophoresis. The survival percentage of DNA in tritiated water was almost the same as with the irradiation with X-rays at the same absorbed dose. For irradiation with γ-rays, on the other hand, the decay rate was larger than those observed with both tritiated water and X-rays. The percentages of breakage for DNA in tritiated water, X-rays and γ-rays were found to be 34, 38 and 33% at 100 Gy of absorbed dose. The effect of dose rate was not observed for irradiation with tritiated water, X-rays and γ-rays. In order to study protection of DNA against radiation, we investigated the protecting effect of tea catechin which is the main component of (-)-epigallocatechin gallate (EGCg). The protection mechanism for DNA against radiation-induced scission has been studied using ESR spin-trapping method.

Selol, an organic selenium donor, prevents lipopolysaccharide-induced oxidative stress and inflammatory reaction in the rat brain.

PubMed

Dominiak, Agnieszka; Wilkaniec, Anna; Jęśko, Henryk; Czapski, Grzegorz A; Lenkiewicz, Anna M; Kurek, Eliza; Wroczyński, Piotr; Adamczyk, Agata

2017-09-01

Neuroinflammation and oxidative stress are key intertwined pathological factors in many neurological, particularly neurodegenerative diseases, such as Alzheimer's and Parkinson's disorders as well as autism. The present study was conducted to evaluate the protective effects of Selol, an organic selenium donor, against lipopolysaccharide (LPS)-mediated inflammation in rat brain. The results demonstrated that the peripheral administration of LPS in a dose of 100 μg/kg b.w. evoked typical pathological reaction known as systemic inflammatory response. Moreover, we observed elevated blood levels of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress, as well as increased concentration of tumor necrosis factor-α (TNF-α) in LPS-treated animals. Selol significantly prevented these LPS-evoked changes. Subsequently, Selol protected against LPS-induced up-regulation of proinflammatory cytokines (Tnfa, Ifng, Il6) in rat brain cortex. The molecular mechanisms through which Selol prevented the neuroinflammation were associated with the inhibition of oxidized glutathione (GSSG) accumulation and with an increase of glutathione-associated enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR) as well as thioredoxin reductase (TrxR) activity and expression. Finally, we observed that Selol administration effectively protected against LPS-induced changes in the expression of brain-derived neurotrophic factor (Bdnf). In conclusion, our studies indicated that Selol effectively protects against LPS-induced neuroinflammation by inhibiting pro-inflammatory cytokine release, by boosting antioxidant systems, and by augmenting BDNF level. Therefore, Selol could be a multi-potent and effective drug useful in the treatment and prevention of brain disorders associated with neuroinflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation*

PubMed Central

Benilova, Iryna; Gallardo, Rodrigo; Ungureanu, Andreea-Alexandra; Castillo Cano, Virginia; Snellinx, An; Ramakers, Meine; Bartic, Carmen; Rousseau, Frederic; Schymkowitz, Joost; De Strooper, Bart

2014-01-01

Missense mutations in alanine 673 of the amyloid precursor protein (APP), which corresponds to the second alanine of the amyloid β (Aβ) sequence, have dramatic impact on the risk for Alzheimer disease; A2V is causative, and A2T is protective. Assuming a crucial role of amyloid-Aβ in neurodegeneration, we hypothesized that both A2V and A2T mutations cause distinct changes in Aβ properties that may at least partially explain these completely different phenotypes. Using human APP-overexpressing primary neurons, we observed significantly decreased Aβ production in the A2T mutant along with an enhanced Aβ generation in the A2V mutant confirming earlier data from non-neuronal cell lines. More importantly, thioflavin T fluorescence assays revealed that the mutations, while having little effect on Aβ42 peptide aggregation, dramatically change the properties of the Aβ40 pool with A2V accelerating and A2T delaying aggregation of the Aβ peptides. In line with the kinetic data, Aβ A2T demonstrated an increase in the solubility at equilibrium, an effect that was also observed in all mixtures of the A2T mutant with the wild type Aβ40. We propose that in addition to the reduced β-secretase cleavage of APP, the impaired propensity to aggregate may be part of the protective effect conferred by A2T substitution. The interpretation of the protective effect of this mutation is thus much more complicated than proposed previously. PMID:25253695

Oligomeric proanthocyanidins inhibit apoptosis of chondrocytes induced by interleukin-1β.

PubMed

Yin, Meng-Hong; Wang, Yi-Teng; Li, Qing; Lv, Guo-Feng

2017-10-01

Oligomeric proanthocyanidin (OPC) is a water-soluble plant polyphenolic compound known for its cytoprotective effects in various tissue types. However, its effect on chondrocytes has not been well characterized. The present study aimed to investigate the effect of OPC on interleukin‑1β (IL‑1β)‑induced apoptosis in chondrocytes, and to determine the mechanisms underlying the protective effects of OPC. Knee articular chondrocytes obtained from 6‑week‑old SPF Kunming mice were cultured and serially passaged. First‑generation chondrocytes were selected for subsequent experiments following toluidine blue staining. Subsequent to IL‑1β and OPC administration, an MTT assay was performed to examine the viability rate of chondrocytes, and the optimal drug concentration was determined. The fluorescence dye 2',7'-dichlorofluorescein diacetate was used to determine the intracellular content of reactive oxygen species (ROS). Mitochondrial membrane potential (MMP) was measured using a 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide (JC‑1) assay. The apoptosis rate of chondrocytes was assessed using an Annexin V‑FITC/PI assay and ultrastructural changes were observed under an electron microscope. The results demonstrated that OPC increased the survival rate of chondrocytes against IL‑1β‑induced apoptosis. The most significant protective effect of OPC was observed at the concentration of 0.050 mg/ml. OPC reversed the increased ROS content and MMP levels, and inhibited IL‑1β‑induced apoptosis in chondrocytes. In addition, OPC was revealed to protect the ultrastructural integrity of chondrocytes. Taken together, the results of the present study suggest that OPC protects chondrocytes against IL‑1β‑induced damage by decreasing ROS content and MMP levels.

Protective effects of a zinc-hydroxyapatite toothpaste on enamel erosion: SEM study

PubMed Central

Colombo, Marco; Beltrami, Riccardo; Rattalino, Davide; Mirando, Maria; Chiesa, Marco; Poggio, Claudio

2016-01-01

Summary Aim The aim of the present in vitro study was to evaluate the protective effects of a zinc-hydroxyapatite toothpaste against an erosive challenge produced by a soft drink (Coca-Cola) using Scanning Electron Microscopy (SEM). Methods Forty specimens were assigned to 4 groups of 10 specimens each (group 1: no erosive challenge, no toothpaste treatment, group 2: erosive challenge, no toothpaste treatment, group 3: erosive challenge, fluoride toothpaste treatment, group 4: erosive challenge, zinc-hydroxyapatite toothpaste treatment). The surface of each specimen was imaged by SEM. A visual rating system was used to evaluate the condition of the enamel surface; results were analyzed by nonparametric statistical methods. Results Statistically significant differences were found between the samples untreated and those immersed in Coca-Cola (group 1, 2); the highest grade of damage was found in group 2, while the lowest grade was recorded in the samples of group 4. Comparing the groups, the two analyzed toothpaste tended to protect in different extend. Conclusions In this study treatment of erosively challenged enamel with Zn-Hap toothpaste showed a clear protective effect. This was greater than the effect observed for a normal fluoride toothpaste and confirmed the potential benefit the Zn-HAP technology can provide in protecting enamel from erosive acid challenges. PMID:28149449

Protective effects of a zinc-hydroxyapatite toothpaste on enamel erosion: SEM study.

PubMed

Colombo, Marco; Beltrami, Riccardo; Rattalino, Davide; Mirando, Maria; Chiesa, Marco; Poggio, Claudio

2016-01-01

The aim of the present in vitro study was to evaluate the protective effects of a zinc-hydroxyapatite toothpaste against an erosive challenge produced by a soft drink (Coca-Cola) using Scanning Electron Microscopy (SEM). Forty specimens were assigned to 4 groups of 10 specimens each (group 1: no erosive challenge, no toothpaste treatment, group 2: erosive challenge, no toothpaste treatment, group 3: erosive challenge, fluoride toothpaste treatment, group 4: erosive challenge, zinc-hydroxyapatite toothpaste treatment). The surface of each specimen was imaged by SEM. A visual rating system was used to evaluate the condition of the enamel surface; results were analyzed by nonparametric statistical methods. Statistically significant differences were found between the samples untreated and those immersed in Coca-Cola (group 1, 2); the highest grade of damage was found in group 2, while the lowest grade was recorded in the samples of group 4. Comparing the groups, the two analyzed toothpaste tended to protect in different extend. In this study treatment of erosively challenged enamel with Zn-Hap toothpaste showed a clear protective effect. This was greater than the effect observed for a normal fluoride toothpaste and confirmed the potential benefit the Zn-HAP technology can provide in protecting enamel from erosive acid challenges.

Investigation of Effectiveness of Air-Heating a Hollow Steel Propeller for Protection Against Icing. 1: Unpartitioned Blades

NASA Technical Reports Server (NTRS)

Mulholland, Donald R.; Perkins, Porter J.

1948-01-01

An investigation to determine the effectiveness of icing protection afforded by air-heating hollow steel unpartitioned propeller blades has been conducted In the NACA Cleveland icing research tunnel. The propeller used was a production model modified with blade shank and tip openings to permit internal passage of heated air. Blade-surface and heated-air temperatures were obtained and photographic observations of Ice formations were made with variations In icing intensity and heating rate to the blades. For the conditions of Icing to which the propeller was subjected, it was found that adequate ice protection was afforded with a heating rate of 40 1 000 Btu per hour per blade. With less than 40,000 Btu per hour per blade, ice protection failed because of significant ice accretions on the leading edge. The chordwise distribution of heat was unsatisfactory with most of the available heat dissipated well back of the leading edge on both the thrust and camber face's instead of at the leading edge where it was most needed. A low utilization of available heat for icing protection is indicated by a beat-exchanger effectiveness of approximately 47 percent.

Virus-Like Particle Vaccine Protects against 2009 H1N1 Pandemic Influenza Virus in Mice

PubMed Central

Quan, Fu-Shi; Vunnava, Aswani; Compans, Richard W.; Kang, Sang-Moo

2010-01-01

Background The 2009 influenza pandemic and shortages in vaccine supplies worldwide underscore the need for new approaches to develop more effective vaccines. Methodology/Principal Findings We generated influenza virus-like particles (VLPs) containing proteins derived from the A/California/04/2009 virus, and tested their efficacy as a vaccine in mice. A single intramuscular vaccination with VLPs provided complete protection against lethal challenge with the A/California/04/2009 virus and partial protection against A/PR/8/1934 virus, an antigenically distant human isolate. VLP vaccination induced predominant IgG2a antibody responses, high hemagglutination inhibition (HAI) titers, and recall IgG and IgA antibody responses. HAI titers after VLP vaccination were equivalent to those observed after live virus infection. VLP immune sera also showed HAI responses against diverse geographic pandemic isolates. Notably, a low dose of VLPs could provide protection against lethal infection. Conclusion/Significance This study demonstrates that VLP vaccination provides highly effective protection against the 2009 pandemic influenza virus. The results indicate that VLPs can be developed into an effective vaccine, which can be rapidly produced and avoid the need to isolate high growth reassortants for egg-based production. PMID:20161790

Increased leptin by hypoxic-preconditioning promotes autophagy of mesenchymal stem cells and protects them from apoptosis.

PubMed

Wang, LiHan; Hu, XinYang; Zhu, Wei; Jiang, Zhi; Zhou, Yu; Chen, PanPan; Wang, JianAn

2014-02-01

Autophagy is the basic catabolic progress involved in cell degradation of unnecessary or dysfunctional cellular components. It has been proven that autophagy could be utilized for cell survival under stresses. Hypoxic-preconditioning (HPC) could reduce apoptosis induced by ischemia and hypoxia/serum deprivation (H/SD) in bone marrow-derived mesenchymal stem cells (BMSCs). Previous studies have shown that both leptin signaling and autophagy activation were involved in the protection against apoptosis induced by various stress, including ischemia-reperfusion. However, it has never been fully understood how leptin was involved in the protective effects conferred by autophagy. In the present study, we demonstrated that HPC can induce autophagy in BMSCs by increased LC3-II/LC3-I ratio and autophagosome formation. Interestingly, similar effects were also observed when BMSCs were pretreated with rapamycin. The beneficial effects offered by HPC were absent when BMSCs were incubated with autophagy inhibitor, 3-methyladenine (3-MA). In addition, down-regulated leptin expression by leptin-shRNA also attenuated HPC-induced autophagy in BMSCs, which in turn was associated with increased apoptosis after exposed to sustained H/SD. Furthermore, increased AMP-activated protein kinase phosphorylation and decreased mammalian target of rapamycin phosphorylation that were observed in HPC-treated BMSCs can also be attenuated by down-regulation of leptin expression. Our data suggests that leptin has impact on HPC-induced autophagy in BMSCs which confers protection against apoptosis under H/SD, possibly through modulating both AMPK and mTOR pathway.

Causal Inference in Educational Effectiveness Research: A Comparison of Three Methods to Investigate Effects of Homework on Student Achievement

ERIC Educational Resources Information Center

Gustafsson, Jan-Eric

2013-01-01

In educational effectiveness research, it frequently has proven difficult to make credible inferences about cause and effect relations. The article first identifies the main categories of threats to valid causal inference from observational data, and discusses designs and analytic approaches which protect against them. With the use of data from 22…

Missense Mutations in LRP5 Associated with High Bone Mass Protect the Mouse Skeleton from Disuse- and Ovariectomy-Induced Osteopenia.

PubMed

Niziolek, Paul J; Bullock, Whitney; Warman, Matthew L; Robling, Alexander G

2015-01-01

The low density lipoprotein receptor-related protein-5 (LRP5), a co-receptor in the Wnt signaling pathway, modulates bone mass in humans and in mice. Lrp5 knock-out mice have severely impaired responsiveness to mechanical stimulation whereas Lrp5 gain-of-function knock-in and transgenic mice have enhanced responsiveness to mechanical stimulation. Those observations highlight the importance of Lrp5 protein in bone cell mechanotransduction. It is unclear if and how high bone mass-causing (HBM) point mutations in Lrp5 alter the bone-wasting effects of mechanical disuse. To address this issue we explored the skeletal effects of mechanical disuse using two models, tail suspension and Botulinum toxin-induced muscle paralysis, in two different Lrp5 HBM knock-in mouse models. A separate experiment employing estrogen withdrawal-induced bone loss by ovariectomy was also conducted as a control. Both disuse stimuli induced significant bone loss in WT mice, but Lrp5 A214V and G171V were partially or fully protected from the bone loss that normally results from disuse. Trabecular bone parameters among HBM mice were significantly affected by disuse in both models, but these data are consistent with DEXA data showing a failure to continue growing in HBM mice, rather than a loss of pre-existing bone. Ovariectomy in Lrp5 HBM mice resulted in similar protection from catabolism as was observed for the disuse experiments. In conclusion, the Lrp5 HBM alleles offer significant protection from the resorptive effects of disuse and from estrogen withdrawal, and consequently, present a potential mechanism to mimic with pharmaceutical intervention to protect against various bone-wasting stimuli.

Nephrotoxic effects of lead nitrate exposure in diabetic and nondiabetic rats: Involvement of oxidative stress and the protective role of sodium selenite.

PubMed

Baş, Hatice; Kalender, Yusuf

2016-10-01

Heavy metals are known to be toxic to organisms. The present study was undertaken to evaluate the protective effect of sodium selenite against lead nitrate (LN)-induced nephrotoxicity in diabetic and nondiabetic rats. Animals were divided into eight groups where the first was served as a control, whereas the remaining groups were treated with sodium selenite (1 mg/kg b.w.), LN (22.5 mg/kg b.w.) and a combination of LN and sodium selenite and diabetic forms of these groups. Changes in antioxidant enzyme activities, malondialdehide levels, serum urea, uric acid, creatinine levels, body, and kidney weights and histopathological changes were determined after 28 days. LN caused severe histopathological changes, increment in urea, uric acid, creatinine, and MDA levels, also decreasing in antioxidant enzyme activities, body, and kidney weights. In sodium selenite + LN group, we observed the protective effect of sodium selenite on examining parameters. Also diabetes caused alterations on these parameters compared with nondiabetic animals. We found that sodium selenite did not show protective effect on diabetes caused damages. As a result, LN caused nephrotoxicity and sodium selenite alleviated this toxicity but sodium selenite did not protect kidneys against diabetes mediated toxicity. Also, LN caused more harmfull effects in diabetic groups compared with nondiabetic groups. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1229-1240, 2016. © 2015 Wiley Periodicals, Inc.

Short- and long-term immunogenicity and protection induced by non-replicating smallpox vaccine candidates in mice and comparison with the traditional 1st generation vaccine.

PubMed

Ferrier-Rembert, Audrey; Drillien, Robert; Tournier, Jean-Nicolas; Garin, Daniel; Crance, Jean-Marc

2008-03-25

This study assessed three non-replicating smallpox vaccine candidates (modified vaccinia Ankara (MVA), NYVAC and HR) for their immunogenicity and ability to protect mice against an intranasal cowpox virus challenge and compared them with the traditional replicating vaccine. A single immunisation with the non-replicating vaccines induced a complete protection from death at short-term, but was not fully protective when mice were challenged 150 days post-vaccination with protection correlated with the specific neutralizing antibodies and CD4(+) T-cells responses. Prime-boost vaccination enabled effective long-term protection from death for mice vaccinated with MVA, but protection from disease and CD4(+) T-cell level were lower than the ones induced by the traditional vaccine over the long-term period. Further investigations are necessary with MVA to determine the optimal conditions of immunisation to induce at long-term immunogenicity and protection observed with the 1st generation smallpox vaccine.

Frying oils with high natural or added antioxidants content, which protect against postprandial oxidative stress, also protect against DNA oxidation damage.

PubMed

Rangel-Zuñiga, Oriol A; Haro, Carmen; Tormos, Carmen; Perez-Martinez, Pablo; Delgado-Lista, Javier; Marin, Carmen; Quintana-Navarro, Gracia M; Cerdá, Concha; Sáez, Guillermo T; Lopez-Segura, Fernando; Lopez-Miranda, Jose; Perez-Jimenez, Francisco; Camargo, Antonio

2017-06-01

Using sunflower oil as frying oil increases postprandial oxidative stress, which is considered the main endogenous source of DNA oxidative damage. We aimed to test whether the protective effect of virgin olive oil and oil models with added antioxidants against postprandial oxidative stress may also protect against DNA oxidative damage. Twenty obese people received four breakfasts following a randomized crossover design consisting of different oils [virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)], which were subjected to 20 heating cycles. We observed the postprandial increase in the mRNA levels of p53, OGG1, POLB, and GADD45b after the intake of the breakfast prepared with SFO and SOX, and an increase in the expression of MDM2, APEX1, and XPC after the intake of the breakfast prepared with SFO, whereas no significant changes at the postprandial state were observed after the intake of the other breakfasts (all p values <0.05). We observed lower 8-OHdG postprandial levels after the intake of the breakfast prepared with VOO and SOP than after the intake of the breakfast prepared with SFO and SOX (all p values <0.05). Our results support the beneficial effect on DNA oxidation damage of virgin olive oil and the oil models with added antioxidants, as compared to the detrimental use of sunflower oil, which induces p53-dependent DNA repair pathway activation.

Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats

PubMed Central

Lim, Tong-Hye; Nor-Amdan, Nur-Asyura

2017-01-01

Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08) were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA). These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM) proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x) and level of GGT (more than 2x) in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver. PMID:28280515

[Effect of Huperzine A on neural lesion of acute organophosphate poisoning in mice].

PubMed

Liu, Li; Wang, Jian; Xie, Guangyun; Sun, Jinxiu

2013-05-01

Effects of neurophathologic changes and expression of Glu and 60 nNOS were observed in acute isocarbophos and phoxim poisoning in mice. KM male mice were randomly divided into three groups, which were control, non-treated and Huperzine A (HupA)-treated groups. The control group was given tween-80. Nontreated group was given isocarbophos (14.7 mg/kg) or phoxim (1702 mg/kg). HupA-treated group was given HupA 2h before phoxim or isocarbophos. Twenty-four hours after exposure, the whole brain was removed and adjacent coronal sections was obtained. One part of sections were stained with toluidine blue. The part of sections were used to assessed the expression of Glu and nNOS in the cortex and hippocampal of brain by immunohistochemistry. Compared to control group, non-treated group was observed nissal body nembers reduced and dyeing light. The animals of HupA protective group were observed nissal body nembers reduced, but the lesional degree was lighter obviously than non-treated group. The statistically reduced of the expression of Glu (P<0.01), the elevation of nNOS (P<0.01), after Isocarbophos intoxication were observed. Compared to non-treated group, the significant elevation of Glu (P<0.01) and reduced of nNOS (P<0.01) was observed on HupA-treated groups. Whereas for phoxim treatment, no changes were observed. HupA have protective effect against glutamatergic systems disorder caused by Isocarbophos poisoning. Administration of HupA have no effects of the neurotransmitter changes induces by acute poisoning of phoxim. It is different for the toxic effect mechanism of the two organophosphate.

Does Breastfeeding Protect Against Childhood Obesity? Moving Beyond Observational Evidence.

PubMed

Woo, Jessica G; Martin, Lisa J

2015-06-01

Human milk is the optimal feeding choice for infants, as it dynamically provides the nutrients, immunity support, and other bioactive factors needed for infants at specific stages during development. Observational studies and several meta-analyses have suggested that breastfeeding is protective against development of obesity in childhood and beyond. However, these findings are not without significant controversy. This review includes an overview of observational findings to date, then focuses on three specific pathways that connect human milk and infant physiology: maternal obesity, microbiome development in the infant, and the development of taste preference and diet quality. Each of these pathways involves complex interactions between mother and infant, includes both biologic and non-biologic factors, and may have both direct and indirect effects on obesity risk in the offspring. This type of integrated approach to examining breastfeeding and childhood obesity is necessary to advance research in this area beyond observational findings.

Protection against Recurrent Stroke with Resveratrol: Endothelial Protection

PubMed Central

Clark, Darren; Tuor, Ursula I.; Thompson, Roger; Institoris, Adam; Kulynych, Angela; Zhang, Xu; Kinniburgh, David W.; Bari, Ferenc; Busija, David W.; Barber, Philip A.

2012-01-01

Despite increased risk of a recurrent stroke following a minor stroke, information is minimal regarding the interaction between injurious mild cerebral ischemic episodes and the possible treatments which might be effective. The aim of the current study was to investigate recurrent ischemic stroke and whether resveratrol, a nutritive polyphenol with promising cardio- and neuro- protective properties, could ameliorate the associated brain damage. Experiments in adult rats demonstrated that a mild ischemic stroke followed by a second mild cerebral ischemia exacerbated brain damage, and, daily oral resveratrol treatment after the first ischemic insult reduced ischemic cell death with the recurrent insult (P<0.002). Further investigation demonstrated reduction of both inflammatory changes and markers of oxidative stress in resveratrol treated animals. The protection observed with resveratrol treatment could not be explained by systemic effects of resveratrol treatment including effects either on blood pressure or body temperature measured telemetrically. Investigation of resveratrol effects on the blood-brain barrier in vivo demonstrated that resveratrol treatment reduced blood-brain barrier disruption and edema following recurrent stroke without affecting regional cerebral blood flow. Investigation of the mechanism in primary cell culture studies demonstrated that resveratrol treatment significantly protected endothelial cells against an in vitro ‘ischemia’ resulting in improved viability against oxygen and glucose deprivation (39.6±6.6% and 81.3±9.5% in vehicle and resveratrol treated cells, respectively). An inhibition of nitric oxide synthesis did not prevent the improved cell viability following oxygen glucose deprivation but SIRT-1 inhibition with sirtinol partially blocked the protection (P<0.001) suggesting endothelial protection is to some extent SIRT-1 dependent. Collectively, the results support that oral resveratrol treatment provides a low risk strategy to protect the brain from enhanced damage produced by recurrent stroke which is mediated in part by a protective effect of resveratrol on the endothelium of the cerebrovasculature. PMID:23082218

Protective roles of single-wall carbon nanotubes in ultrasonication-induced DNA base damage.

PubMed

Petersen, Elijah J; Tu, Xiaomin; Dizdaroglu, Miral; Zheng, Ming; Nelson, Bryant C

2013-01-28

The overall level of ultrasonication-induced DNA damage is reduced in the presence of single-wall carbon nanotubes (SWCNTs), particularly for DNA lesions formed by one-electron reduction of intermediate radicals. The protective role of SWCNTs observed in this work suggests a contrary view to the general idea that carbon nanotubes have damaging effects on biomolecules. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity.

PubMed

Jadoon, Saima; Karim, Sabiha; Bin Asad, Muhammad Hassham Hassan; Akram, Muhammad Rouf; Khan, Abida Kalsoom; Malik, Arif; Chen, Chunye; Murtaza, Ghulam

2015-01-01

The exposure to ultraviolet radiations (UVR) is the key source of skin sunburn; it may produce harmful entities, reactive oxygen species (ROS), leading to aging. The skin can be treated and protected from the injurious effects of ROS by using various pharmaceutical formulations, such as cream. Cream can be loaded with antioxidants to quench ROS leading to photo-protective effects. Moreover, modern medicines depend on ethnobotanicals for protection or treatment of human diseases. This review article summarizes various in vivo antioxidant studies on herbal creams loaded with phyto-extracts. These formulations may serve as cosmeceuticals to protect skin against injurious effects of UVR. The botanicals studied for dermatologic use in cream form include Acacia nilotica, Benincasa hispida, Calendula officinalis, Camellia sinensis, Camellia sinensis, Nelumbo nucifera, Capparis decidua, Castanea sativa, Coffea arabica, Crocus sativus, Emblica officinalis Gaertn, Foeniculum vulgare, Hippophae rhamnoides, Lithospermum erythrorhizon, Malus domestica, Matricaria chamomilla L., Moringa oleifera, Morus alba, Ocimum basilicum, Oryza sativa, Polygonum minus, Punica granatum, Silybum marianum, Tagetes erecta Linn., Terminalia chebula, Trigonella foenum-graecum, and Vitis vinifera. The observed anti-aging effects of cream formulations could be an outcome of a coordinating action of multiple constituents. Of numerous botanicals, the phenolic acids and flavonoids appear effective against UVR-induced damage; however the evidence-based studies for their anti-aging effects are still needed.

Angiogenin in Parkinson Disease Models: Role of Akt Phosphorylation and Evaluation of AAV-Mediated Angiogenin Expression in MPTP Treated Mice

PubMed Central

Steidinger, Trent U.; Slone, Sunny R.; Ding, Huiping; Standaert, David G.; Yacoubian, Talene A.

2013-01-01

The angiogenic factor, angiogenin, has been recently linked to both Amyotrophic Lateral Sclerosis (ALS) and Parkinson Disease (PD). We have recently shown that endogenous angiogenin levels are dramatically reduced in an alpha-synuclein mouse model of PD and that exogenous angiogenin protects against cell loss in neurotoxin-based cellular models of PD. Here, we extend our studies to examine whether activation of the prosurvival Akt pathway is required for angiogenin's neuroprotective effects against 1-methyl-4-phenylpyridinium (MPP+), as observed in ALS models, and to test the effect of virally-mediated overexpression of angiogenin in an in vivo PD model. Using a dominant negative Akt construct, we demonstrate that inhibition of the Akt pathway does not reduce the protective effect of angiogenin against MPP+ toxicity in the dopaminergic SH-SY5Y cell line. Furthermore, an ALS-associated mutant of angiogenin, K40I, which fails to induce Akt phosphorylation, was similar to wildtype angiogenin in protection against MPP+. These results confirm previous work showing neuroprotective effects of angiogenin against MPP+, and indicate that Akt is not required for this protective effect. We also investigated whether adeno-associated viral serotype 2 (AAV2)-mediated overexpression of angiogenin protects against dopaminergic neuron loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. We found that angiogenin overexpression using this approach does not reduce the MPTP-induced degeneration of dopaminergic cells in the substantia nigra, nor limit the depletion of dopamine and its metabolites in the striatum. Together, these findings extend the evidence for protective effects of angiogenin in vitro, but also suggest that further study of in vivo models is required to translate these effects into meaningful therapies. PMID:23409128

Effect of an Intervention on Observed Sun Protection by Vacationers in a Randomized Controlled Trial at North American Resorts

PubMed Central

Buller, David B.; Andersen, Peter A.; Walkosz, Barbara J.; Scott, Michael D.; Beck, Larry; Cutter, Gary R.

2017-01-01

During vacations, many individuals receive high-risk sun exposure that is associated with skin cancer. Vacationers in outdoor recreation venues (pretest n=4,347; posttest n=3,986) at warm-weather destination resorts in North America (n=41) were enrolled in a pair-matched, group-randomized pretest-posttest controlled quasi-experimental design in 2012-14. Print, audiovisual, and online messages based on Transportation Theory and Diffusion of Innovation Theory and promoting advanced sun protection (e.g., use of clothing, hats, shade and pre-application/reapplication of sunscreen and reliable cues to high UV) were delivered through resort channels. Vacationers' sun protection practices observed by trained research staff (i.e., body coverage and shade use analyzed individually and in combined scores) did not differ by experimental condition (p>0.05) or intervention implementation (p>0.05). However, recreation venue moderated intervention impact. The intervention improved sun protection at waterside recreation venues (z-score composite: intervention pre=-22.74, post=-15.77; control pre=-27.24, post=-23.24) but not non-waterside venues (z-score composite: intervention pre=20.43, post=20.53; control pre=22.94, post=18.03, p<0.01). An additional analysis showed that resorts with greater program implementation showed more improvements in sun protection by vacationers at waterside (z=score composite: high implementation pre=-25.45, post=-14.05; low implementation pre=-24.70, post=-21.40) compared to non-waterside (z-score composite: high implementation pre=14.51, post=19.98; low implementation pre=24.03, post=18.98, p<0.01) recreation venues. The intervention appeared effective with the vacationers in recreation venues with the highest-risk for sun exposure, waterside venues. However, it was not effective throughout all the resort venues, possibly because of the sun-seeking desires of vacationers, information overload at the resorts, and constraints on clothing styles and sun protection by recreation activity. PMID:28189810

Inhibition of UV-B induced apoptosis in corneal epithelial cells by potassium channel modulators.

PubMed

Ubels, John L; Schotanus, Mark P; Bardolph, Susan L; Haarsma, Loren D; Koetje, Leah R; Louters, Julienne R

2010-02-01

The goal of this study was to determine whether prevention of K(+) loss can protect human corneal-limbal epithelial (HCLE) cells from UV-B induced apoptosis. Immunostaining for activated caspase-3 of HCLE cells exposed to 150-200 mJ/cm(2) UV-B demonstrated induction of apoptosis 6 h after exposure. The number of apoptotic cells was decreased by incubation in medium with 25 or 100 mM K(+). If this protection is due to a reduction of UV-induced K(+) loss then K(+) channel blockers should also protect HCLE cells from UV-B. Caspase-8 activity induced by exposure to UV-B at 150 mJ/cm(2) was significantly reduced when the cells were incubated in 0.3 microM BDS-I or 0.05-1 mM quinidine. Caspase-3 was also activated by UV-B and a reduction in activity was observed after incubation in 0.1-0.3 microM BDS-I and 0.1-1 mM quinidine. Induction of DNA fragmentation, as measured by the TUNEL assay, was decreased by treatment with 0.3 microM BDS-I and 0.01-0.05 mM quinidine. Patch-clamp recording showed activation of K(+) channels after exposure to UV-B and a decrease in outward K(+) current was observed following application of BDS-I. Quinidine did not block K(+) currents in HCLE cells, suggesting that the protective effect of quinidine occurs by a mechanism other than via K(+) channels. The effect of the K(+) channel blocker BDS-1 on HCLE cells exposed to UV-B confirms that preventing K(+) efflux protects corneal epithelial cells from apoptosis. This suggests the elevated [K(+)] in tears may protect the corneal epithelium from effects of ambient UV-B. Copyright 2009 Elsevier Ltd. All rights reserved.

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem.

PubMed

Kabiru, Caroline W; Elung'ata, Patricia; Mojola, Sanyu A; Beguy, Donatien

2014-01-01

Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? We used cross-sectional data from 3,064 males and females aged 12-19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries.

Inhibition of UV-B Induced Apoptosis in Corneal Epithelial Cells by Potassium Channel Modulators

PubMed Central

Ubels, John L.; Schotanus, Mark P.; Bardolph, Susan L.; Haarsma, Loren D.; Koetje, Leah R.; Louters, Julienne R.

2009-01-01

The goal of this study was to determine whether prevention of K+ loss can protect human corneal-limbal epithelial (HCLE) cells from UV-B induced apoptosis. Immunostaining for activated caspase-3 of HCLE cells exposed to 150 – 200 mJ/cm2 UV-B demonstrated induction of apoptosis 6 hrs after exposure. The number of apoptotic cells was decreased by incubation in medium with 25 or 100 mM K+. If this protection is due to a reduction of UV induced K+ loss then K+ channel blockers should also protect HCLE cells from UV-B. Caspase-8 activity induced by exposure to UV-B at 150 mJ/cm2 was significantly reduced when the cells were incubated in 0.3 µM BDS-I or 0.05–1 mM quinidine. Caspase-3 was also activated by UV-B and a reduction in activity was observed after incubation in 0.1–0.3 µM BDS-I and 0.1–1mM quinidine. Induction of DNA fragmentation, as measured by the TUNEL assay, was decreased by treatment with 0.3 µM BDS-I and 0.01–0.05 mM quinidine. Patch-clamp recording showed activation of K+ channels after exposure to UV-B and a decrease in outward K+ current was observed following application of BDS-I. Quinidine did not block K+ currents in HCLE cells, suggesting that the protective effect of quinidine occurs by a mechanism other than via K+ channels. The effect of the K+ channel blocker BDS-1 on HCLE cells exposed to UV-B confirms that preventing K+ efflux protects corneal epithelial cells from apoptosis. This suggests the elevated [K+] in tears may protect the corneal epithelium from effects of ambient UV-B. PMID:19874821

Effect of an intervention on observed sun protection by vacationers in a randomized controlled trial at North American resorts.

PubMed

Buller, David B; Andersen, Peter A; Walkosz, Barbara J; Scott, Michael D; Beck, Larry; Cutter, Gary R

2017-06-01

During vacations, many individuals receive high-risk sun exposure that is associated with skin cancer. Vacationers in outdoor recreation venues (pretest n=4347; posttest n=3986) at warm-weather destination resorts in North America (n=41) were enrolled in a pair-matched, group-randomized pretest-posttest controlled quasi-experimental design in 2012-14. Print, audiovisual, and online messages based on Transportation Theory and Diffusion of Innovation Theory and promoting advanced sun protection (e.g., use of clothing, hats, shade and pre-application/reapplication of sunscreen and reliable cues to high UV) were delivered through resort channels. Vacationers' sun protection practices observed by trained research staff (i.e., body coverage and shade use analyzed individually and in combined scores) did not differ by experimental condition (p>0.05) or intervention implementation (p>0.05). However, recreation venue moderated intervention impact. The intervention improved sun protection at waterside recreation venues (z-score composite: intervention pre=-22.74, post=-15.77; control pre=-27.24, post=-23.24) but not non-waterside venues (z-score composite: intervention pre=20.43, post=20.53; control pre=22.94, post=18.03, p<0.01). An additional analysis showed that resorts with greater program implementation showed more improvements in sun protection by vacationers at waterside (z=score composite: high implementation pre=-25.45, post=-14.05; low implementation pre=-24.70, post=-21.40) compared to non-waterside (z-score composite: high implementation pre=14.51, post=19.98; low implementation pre=24.03, post=18.98, p<0.01) recreation venues. The intervention appeared effective with the vacationers in recreation venues with the highest-risk for sun exposure, waterside venues. However, it was not effective throughout all the resort venues, possibly because of the sun-seeking desires of vacationers, information overload at the resorts, and constraints on clothing styles and sun protection by recreation activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluating the first introduction of rotavirus vaccine in Thailand: Moving from evidence to policy.

PubMed

Tharmaphornpilas, Piyanit; Jiamsiri, Suchada; Boonchaiya, Somchit; Rochanathimoke, Onwipa; Thinyounyong, Wiravan; Tuntiwitayapun, Sumana; Guntapong, Ratigorn; Riewpaiboon, Arthorn; Rasdjarmrearnsook, Aim-On; Glass, Roger I

2017-02-01

We assessed the effectiveness and possible impact of introducing rotavirus vaccine into the routine immunization program. Two provinces were selected for an observational study, one where vaccine was introduced and another where vaccine was not available. In these areas, two sub-studies were linked. The prospective cohort study enrolled children 2month old and followed them to the age of 18months to detect all diarrhea episodes. The hospital surveillance study enrolled all children up to age 5 hospitalized with diarrhea whose fecal samples were tested for rotavirus. Rates of rotavirus hospitalizations in older children who had not been vaccinated in both settings provided data to determine whether immunization had an indirect herd effect. The key endpoints for the study were both vaccine effectiveness (VE) based upon hospitalized rotavirus diarrhea and herd protection. From the cohort study, the overall VE for hospitalized rotavirus diarrhea was 88% (95%CI 76-94). Data from hospital surveillance indicated that for 2 consecutive years, the seasonal peak of rotavirus admissions was no longer present in the vaccinated area. Herd protection was observed among older children born before the rotavirus vaccine program was introduced, who experienced a 40-69% reduction in admission for rotavirus. Rotavirus vaccine was highly effective in preventing diarrheal hospitalizations and in conferring herd protection among older children who had not been vaccinated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of antimutagenic and protective effects of Parkinsonia aculeata L. leaves against H2O2 induced damage in pBR322 DNA.

PubMed

Sharma, Sonia; Sharma, Sushant; Vig, Adarsh Pal

2016-01-01

The in vitro antimutagenic and DNA protecting potential of organic (methanol, hexane, n-butanol) and aqueous extract/fractions of Parkinsonia aculeata L. (Fabaceae) was investigated by employing Ames assay and DNA nicking assay. DNA damage by hydroxyl radicals was effectively inhibited by all the extract/fractions. A marked antimutagenic effect was observed against 4-Nitro-o-phenylenediamine and sodium azide (direct acting mutagens) and 2-Aminofluorene (indirect acting mutagen) in TA98 and TA100 strains of Salmonella typhimurium. In Ames assay, two different modes of experiments i.e. pre-incubation and co-incubation were performed and it was observed that all the extract/fractions showed better results in the pre-incubation as compared to co- incubation mode. Out of all the extract/fractions tested, n-butanol fraction was found to be the most effective in preventing DNA damage and inhibiting mutagenesis. UHPLC analysis of extract/fractions revealed presence of polyphenols such as gallic acid, catechin, chlorogenic acid, caffeic acid, umbelliferone, coumaric acid, rutin, and ellagic acid etc. DNA protecting and antimutagenic activity of this plant could be attributed to presence of these polyphenols. The results of this study indicate the presence of potent antioxidant factors in Parkinsonia aculeata L, which are being explored further for their mechanism of action.

Lower Plasma Creatinine and Urine Albumin in Individuals at Increased Risk of Type 2 Diabetes with Factor V Leiden Mutation

PubMed Central

Fritsche, Andreas; Machicao, Fausto; Nawroth, Peter P.; Häring, Hans-Ulrich; Isermann, Berend

2014-01-01

The factor V Leiden (FVL) mutation is the most frequent genetic cause of venous thrombosis in Caucasians. However, protective effects have been suggested to balance the disadvantages. We have recently observed protective effects of FVL mutation on experimental diabetic nephropathy in mice as well as an association with reduced albuminuria in two human cohorts of diabetic patients. In the present study we aimed to reevaluate these findings in an independent, larger cohort of 1905 Caucasians at risk of developing type 2 diabetes and extend possible associations to earlier disease stages of nephropathy. Carriers of FVL mutation had a significantly lower urine albumin excretion (P = 0.03) and tended to have lower plasma creatinine concentrations (P = 0.07). The difference in plasma creatinine concentrations was significant after adjustment for the influencing factors: age, gender, and lean body mass (P = 0.048). These observations at a very early “disease” stage are an important extension of previous findings and suggest that modification of glomerular dysfunction by FVL mutation is relevant during very early stages of diabetic nephropathy. This makes the underlying mechanism an interesting therapeutic target and raises the question whether FVL mutation may also exert protective effects in other glomerulopathies. PMID:24729885

Protective role of catechin and quercetin in sodium benzoate-induced lipid peroxidation and the antioxidant system in human erythrocytes in vitro.

PubMed

Yetuk, Gamze; Pandir, Dilek; Bas, Hatice

2014-01-01

The aim of this study was to evaluate the protective effect of catechin and quercetin in sodium benzoate- (SB-) induced oxidative stress in human erythrocytes in vitro. For this, the effects of SB (6.25, 12.5, 25, 50, and 100 μg/mL), catechin (10 μM), and quercetin (10 μM) on lipid peroxidation (LPO) and the activities of SOD, CAT, GPx, and GST were studied. Significantly higher LPO and lower activities of antioxidant enzymes were observed with the increasing concentrations of SB. Catechin or quercetin protected the erythrocytes against SB-induced toxicity only at low concentrations of SB. The presence of catechin or quercetin at 10 μM have no effect on SB-induced toxicity at high concentrations of SB (50 and 100 μg/mL). In conclusion, SB may cause oxidative stress as food additive in human erythrocytes in vitro. So, it appears that our findings provide evidence for the protection of erythrocytes from SB that could be considered for further studies.

Selenomethionine protects against neuronal degeneration by methylmercury in the developing rat cerebrum.

PubMed

Sakamoto, Mineshi; Yasutake, Akira; Kakita, Akiyoshi; Ryufuku, Masae; Chan, Hing Man; Yamamoto, Megumi; Oumi, Sanae; Kobayashi, Sayaka; Watanabe, Chiho

2013-03-19

Although many experimental studies have shown that selenium protects against methylmercury (MeHg) toxicity at different end points, the direct interactive effects of selenium and MeHg on neurons in the brain remain unknown. Our goal is to confirm the protective effects of selenium against neuronal degeneration induced by MeHg in the developing postnatal rat brain using a postnatal rat model that is suitable for extrapolating the effects of MeHg to the fetal brain of humans. As an exposure source of selenium, we used selenomethionine (SeMet), a food-originated selenium. Wistar rats of postnatal days 14 were orally administered with vehicle (control), MeHg (8 mg Hg/kg/day), SeMet (2 mg Se/kg/day), or MeHg plus SeMet coexposure for 10 consecutive days. Neuronal degeneration and reactive astrocytosis were observed in the cerebral cortex of the MeHg-group but the symptoms were prevented by coexposure to SeMet. These findings serve as a proof that dietary selenium can directly protect neurons against MeHg toxicity in the mammalian brain, especially in the developing cerebrum.

The Effects of Sacred Value Networks Within an Evolutionary, Adversarial Game

NASA Astrophysics Data System (ADS)

McCalla, Scott G.; Short, Martin B.; Brantingham, P. Jeffrey

2013-05-01

The effects of personal relationships and shared ideologies on levels of crime and the formation of criminal coalitions are studied within the context of an adversarial, evolutionary game first introduced in Short et al. (Phys. Rev. E 82:066114, 2010). Here, we interpret these relationships as connections on a graph of N players. These connections are then used in a variety of ways to define each player's "sacred value network"—groups of individuals that are subject to special consideration or treatment by that player. We explore the effects on the dynamics of the system that these networks introduce, through various forms of protection from both victimization and punishment. Under local protection, these networks introduce a new fixed point within the game dynamics, which we find through a continuum approximation of the discrete game. Under more complicated, extended protection, we numerically observe the emergence of criminal coalitions, or "gangs". We also find that a high-crime steady state is much more frequent in the context of extended protection networks, in both the case of Erdős-Rényi and small world random graphs.

Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice.

PubMed

Bektur, Nuriye Ezgi; Sahin, Erhan; Baycu, Cengiz; Unver, Gonul

2016-04-01

This study was designed to estimate protective effects of silymarin on acetaminophen (N-acetyl-p-aminophenol, paracetamol; APAP)-induced hepatotoxicity and nephrotoxicity in mice. Treatment of mice with overdose of APAP resulted in the elevation of aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) levels in serum, liver, and kidney nitric oxide (NO) levels and significant histological changes including decreased body weight, swelling of hepatocytes, cell infiltration, dilatation and congestion, necrosis and apoptosis in liver, and dilatation of Bowman's capsular space and glomerular capillaries, pale-stained tubules epithelium, cell infiltration, and apoptosis in kidney. Posttreatment with silymarin 1 h after APAP injection for 7 days, however, significantly normalized the body weight, histological damage, serum ALT, AST, BUN, SCr, and tissue NO levels. Our observation suggested that silymarin ameliorated the toxic effects of APAP-induced hepatotoxicity and nephrotoxicity in mice. The protective role of silymarin against APAP-induced damages might result from its antioxidative and anti-inflammatory effects. © The Author(s) 2013.

Protective effect of ferulic acid on cisplatin induced nephrotoxicity in rats.

PubMed

Bami, Erliasa; Ozakpınar, Ozlem Bingol; Ozdemir-Kumral, Zarife Nigar; Köroglu, Kutay; Ercan, Feriha; Cirakli, Zeynep; Sekerler, Turgut; Izzettin, Fikret Vehbi; Sancar, Mesut; Okuyan, Betul

2017-09-01

This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels (p<0.05). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals (p<0.05). All parameters showed improvement in groups treated with ferulic acid (p<0.05). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound. Copyright © 2017 Elsevier B.V. All rights reserved.

Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats

PubMed Central

Bonior, Joanna; Warzecha, Zygmunt; Ceranowicz, Piotr; Gajdosz, Ryszard; Pierzchalski, Piotr; Kot, Michalina; Leja-Szpak, Anna; Nawrot-Porąbka, Katarzyna; Link-Lenczowski, Paweł; Olszanecki, Rafał; Bartuś, Krzysztof; Trąbka, Rafał; Kuśnierz-Cabala, Beata; Dembiński, Artur; Jaworek, Jolanta

2017-01-01

Ghrelin was shown to exhibit protective and therapeutic effect in the gut. Aim of the study was to investigate the role of sensory nerves (SN) in the protective effect of ghrelin in acute pancreatitis (AP). Studies were performed on male Wistar rats or isolated pancreatic acinar cells. After capsaicin deactivation of sensory nerves (CDSN) or treatment with saline, rats were pretreated intraperitoneally with ghrelin or saline. In those rats, AP was induced by cerulein or pancreases were used for isolation of pancreatic acinar cells. Pancreatic acinar cells were incubated in cerulein-free or cerulein containing solution. In rats with intact SN, pretreatment with ghrelin led to a reversal of the cerulein-induced increase in pancreatic weight, plasma activity of lipase and plasma concentration of tumor necrosis factor-α (TNF-α). These effects were associated with an increase in plasma interleukin-4 concentration and reduction in histological signs of pancreatic damage. CDSN tended to increase the severity of AP and abolished the protective effect of ghrelin. Exposure of pancreatic acinar cells to cerulein led to increase in cellular expression of mRNA for TNF-α and cellular synthesis of this cytokine. Pretreatment with ghrelin reduced this alteration, but this effect was only observed in acinar cells obtained from rats with intact SN. Moreover, CDSN inhibited the cerulein- and ghrelin-induced increase in gene expression and synthesis of heat shock protein 70 (HSP70) in those cells. Ghrelin exhibits the protective effect in cerulein-induced AP on the organ and pancreatic acinar cell level. Sensory nerves ablation abolishes this effect. PMID:28665321

Endogenous and Exogenous Estrogen, Cognitive Function and Dementia in Postmenopausal Women: Evidence from Epidemiologic Studies and Clinical Trials

PubMed Central

Laughlin, Gail A.

2009-01-01

There are more than 200 published scientific papers showing that estrogen has favorable effects on brain tissue and physiology in cell culture and animal models including nonhuman primates. The biological plausibility for a neuroprotective estrogen effect is overwhelming. However, most studies of endogenous estrogen and cognitive decline or dementia fail to show protection, and some suggest harm. Failure to find any consistent association might reflect the limitations of a single time of estrogen assay or poor assay sensitivity. More than half of the observational studies of hormone therapy suggest benefit. Nearly all long term clinical trials fail to show benefit and the longer trials tend to show harm. Failure to adequately adjust for self-selection of healthier and wealthier women and publication bias could account for some, or all, of the protective effect attributed to estrogen in observational studies. Overall, the evidence does not convincingly support the prescription of early or late postmenopausal estrogen therapy to preserve cognitive function or prevent dementia. PMID:19401958

Protective effect of magnolol on lipopolysaccharide-induced acute lung injury in mice.

PubMed

Ni, Yun Feng; Jiang, Tao; Cheng, Qing Shu; Gu, Zhong Ping; Zhu, Yi Fang; Zhang, Zhi Pei; Wang, Jian; Yan, Xiao Long; Wang, Wu Ping; Ke, Chang Kang; Han, Yong; Li, Xiao Fei

2012-12-01

Magnolol, a tradition Chinese herb, displays an array of activities including antifungal, antibacterial, and antioxidant effects. To investigate the protective effect of magnolol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg). The mice received intratracheal instillation of magnolol (5 μg/kg) 30 min before LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and myeloperoxidase (MPO) activity were measured by enzyme-linked immunosorbent assay. Expression of cyclooxygenase (COX)-2 in lung tissues was determined by Western blot analysis. Magnolol pretreatment significantly attenuated the severity of lung injury and inhibited the production of TNF-α and IL-1β in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by magnolol pretreatment. The expression of COX-2 was significantly suppressed by magnolol pretreatment. Magnolol potently protected against LPS-induced ALI and the protective effects of magnolol may attribute partly to the suppression of COX-2 expression.

Interactions between smoking and other exposures associated with lung cancer risk in women: diet and physical activity.

PubMed

Kubík, A; Zatloukal, P; Tomásek, L; Pauk, N; Havel, L; Dolezal, J; Plesko, I

2007-01-01

The objective of the study is to estimate the differences in the impact of diet and physical exercise on lung cancer risk in female nonsmokers vs. smokers, and reveal interactions, if any. In a hospital based case-control study, data collected by in-person interviews from 569 female lung cancer cases and 2120 controls were analyzed using unconditional logistic regression stratifying by appropriate factors. Protective effects were observed for intake of milk/dairy products (OR=0.57, 95%CI 0.35-0.94), vegetables (OR=0.60, 95%CI 0.40-0.91), apples (OR=0.69), wine (OR=0.77), and physical exercise (OR=0.59, 95%CI 0.42-0.83) among smokers only, while no similar effects were found among nonsmokers. In contrast, the intake of black tea was associated with a protective effect (OR=0.66, 95%CI 0.47-0.94) among nonsmokers only. Comparing the effects of dietary items and physical activity on lung cancer risk among nonsmokers versus smokers, statistically significant effect modifications were found for black tea (P 0.005), and milk/dairy products (P 0.047). Borderline effect modifications emerged for physical exercise (P 0.077). These results indicate protective effects of some components of healthful diet and physical exercise among smokers, and of the intake of black tea among nonsmokers. The observed interactions of the impact of black tea, milk/dairy products and physical activity upon lung cancer risk in women at different levels of the smoking habit deserve further studies.

Enhancement of preoxygenation for decompression sickness protection: effect of exercise duration

NASA Technical Reports Server (NTRS)

Webb, James T.; Pilmanis, Andrew A.; Fischer, Michele D.; Kannan, Nandini

2002-01-01

INTRODUCTION: Since strenuous exercise for 10 min during preoxygenation was shown to provide better protection from decompression sickness (DCS) incidence than resting preoxygenation, a logical question was: would a longer period of strenuous exercise improve protection even further? HYPOTHESIS: Increased strenuous exercise duration during preoxygenation increases DCS protection. METHODS: There were 60 subjects, 30 men and 30 women, who were exposed to 9,144 m (4.3 psia) for 4 h while performing mild, upper body exercise. Before the exposures, each subject performed three preoxygenation profiles on different days in balanced order: a 90-min resting preoxygenation control; a 240-min resting preoxygenation control; and a 90-min preoxygenation including exercise during the first 15 min. The subjects were monitored at altitude for venous gas emboli (VGE) with an echo-imaging system and observed for signs and symptoms of DCS. RESULTS: There were no significant differences in occurrence of DCS following any of the three preoxygenation procedures. Results were also comparable to an earlier report of 42% DCS with a 60-min preoxygenation including a 10-min exercise. There was no difference between VGE incidence in the comparison of protection offered by a 90-min preoxygenation with or without 13 min of strenuous exercise. The DCS incidence following a 240-min resting preoxygenation, 40%, was higher than observed during NASA studies and nearly identical with the earlier 42% DCS after a 60-min preoxygenation including exercise during the first 10 min. CONCLUSION: The protection offered by a 10 min exercise in a 60-min preoxygenation was not increased with extension of the preoxygenation exercise period to 15 min in a 90-min preoxygenation, indicating an upper time limit to the beneficial effects of strenuous exercise.

A Preliminary Study of a Spanish Graphic Novella Targeting Hearing Loss Prevention.

PubMed

Guiberson, Mark; Wakefield, Emily

2017-09-18

This preliminary study developed a digital graphic novella targeting hearing protection beliefs of Spanish-speaking agricultural workers. Researchers used pretest-posttest interview surveys to establish if the novella had an immediate influence on the participants' beliefs about noise-induced hearing loss and usage of hearing protection devices. Researchers developed a digital graphic novella directed to increase knowledge about noise-induced hearing loss and increase the proper use of hearing protection devices. The novella was tailored to meet the specific linguistic and literacy needs of Spanish-speaking agricultural workers. Thirty-one Spanish-speaking farmworkers of Mexican nationality participated. This study included an interview survey with specific questions on noise-induced hearing loss, myths, and hearing protection device usage. A pretest-posttest design was applied to measure the graphic novella's immediate influence on workers. The posttest scores on Hearing Protection Beliefs statements were significantly better than pretest scores, with a large effect size observed. Digital media may be an effective way to overcome language and literacy barriers with Spanish-speaking workers when providing health education and prevention efforts.

A Preliminary Study of a Spanish Graphic Novella Targeting Hearing Loss Prevention

PubMed Central

Wakefield, Emily

2017-01-01

Purpose This preliminary study developed a digital graphic novella targeting hearing protection beliefs of Spanish-speaking agricultural workers. Researchers used pretest–posttest interview surveys to establish if the novella had an immediate influence on the participants' beliefs about noise-induced hearing loss and usage of hearing protection devices. Method Researchers developed a digital graphic novella directed to increase knowledge about noise-induced hearing loss and increase the proper use of hearing protection devices. The novella was tailored to meet the specific linguistic and literacy needs of Spanish-speaking agricultural workers. Thirty-one Spanish-speaking farmworkers of Mexican nationality participated. This study included an interview survey with specific questions on noise-induced hearing loss, myths, and hearing protection device usage. A pretest–posttest design was applied to measure the graphic novella's immediate influence on workers. Results The posttest scores on Hearing Protection Beliefs statements were significantly better than pretest scores, with a large effect size observed. Conclusion Digital media may be an effective way to overcome language and literacy barriers with Spanish-speaking workers when providing health education and prevention efforts. PMID:28651254

A method for deriving water-quality benchmarks using field data.

PubMed

Cormier, Susan M; Suter, Glenn W

2013-02-01

The authors describe a methodology that characterizes effects to individual genera observed in the field and estimate the concentration at which 5% of genera are adversely affected. Ionic strength, measured as specific conductance, is used to illustrate the methodology. Assuming some resilience in the population, 95% of the genera are afforded protection. The authors selected an unambiguous effect, the presence or absence of a genus from sampling locations. The absence of a genus, extirpation, is operationally defined as the point above which only 5% of the observations of a genus occurs. The concentrations that cause extirpation of each genus are rank-ordered from least to greatest, and the benchmark is estimated at the 5th percentile of the distribution using two-point interpolation. When a full range of exposures and many taxa are included in the model of taxonomic sensitivity, the model broadly characterizes how species in general respond to a concentration gradient of the causal agent. This recognized U.S. Environmental Protection Agency methodology has many advantages. Observations from field studies include the full range of conditions, effects, species, and interactions that occur in the environment and can be used to model some causal relationships that laboratory studies cannot. Copyright © 2012 SETAC.

[Alcohol and cardiovascular system: mechanisms of the protective effects].

PubMed

Schlienger, J L

2001-11-01

Moderate and regularly alcohol consumption reduces death rate from coronary heart disease and thrombotic stroke. This beneficial correlation observed with several alcoholic beverages seems to be mainly due to an ethanol effect. However the particular role of microconstituants contained in red wine must be considered. The mechanism of the putative protective effect of alcohol intake is mediated through the elevation of HDL cholesterol and through the aintioxydative effect of polyphenolic compounds. In addition, alcohol acts favourably on platelets agregation, fibrinolysis and several other coagulation parameters. Despite these explanations are yet speculative and there is no causal relation between alcohol and reduced coronary death, epidemiological data are consistent with the belief that daily consumption of one or two glasses of an alcoholic beverage has salutary effect on health.

The effect of protected sardine fish oil as feed supplement on ruminal fermentation

NASA Astrophysics Data System (ADS)

Pramono, A.; Widayati, D. T.; Handayanta, E.

2018-03-01

The research aims to evaluate the influence of protected sardine fish oil as feed supplement on ruminal fermentation (pH rumen fluid, ammonia concentration and volatile fatty acids production in the rumen). Protected feed supplement was produced from sardine fish oil and soybean meal, through two protection methods, they were saponification and microencapsulation. The experiment consists of two treatments i.e. P0: basal diet (control) and P1: basal diet + 3 % protected feed supplement. Each treatment was repeated 10 times. The kinetics observation of the pH rumen fluid, ammonia concentration and volatile fatty acids production were performed at incubation times 0, 2, 4 and 6 hours respectively. Data were analyzed using independent samples t-test. Results in cow with protected feed supplement showed that kinetics of pH rumen fluid: 7.23; 7.13; 6.90 and 6.76 respectively; ruminal ammonia concentration: 26.70; 31.06; 19.75 and 15.52 respectively; and volatile fatty acids production: 22.75; 26.08; 29.19 and 25.79 respectively. The results could be concluded that the effect of supplementation of protected sardine fish oil have an optimal of pH rumen fluid, ammonia concentration, and volatile fatty acids production so it did not interfere the ruminal fermentation in the rumen.

Validity and sensitivity of a model for assessment of impacts of river floodplain reconstruction on protected and endangered species

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

Nooij, R.J.W. de; Lotterman, K.M.; Sande, P.H.J. van de

Environmental Impact Assessment (EIA) must account for legally protected and endangered species. Uncertainties relating to the validity and sensitivity of EIA arise from predictions and valuation of effects on these species. This paper presents a validity and sensitivity analysis of a model (BIO-SAFE) for assessment of impacts of land use changes and physical reconstruction measures on legally protected and endangered river species. The assessment is based on links between species (higher plants, birds, mammals, reptiles and amphibians, butterflies and dragon- and damselflies) and ecotopes (landscape ecological units, e.g., river dune, soft wood alluvial forests), and on value assignment to protectedmore » and endangered species using different valuation criteria (i.e., EU Habitats and Birds directive, Conventions of Bern and Bonn and Red Lists). The validity of BIO-SAFE has been tested by comparing predicted effects of landscape changes on the diversity of protected and endangered species with observed changes in biodiversity in five reconstructed floodplains. The sensitivity of BIO-SAFE to value assignment has been analysed using data of a Strategic Environmental Assessment concerning the Spatial Planning Key Decision for reconstruction of the Dutch floodplains of the river Rhine, aimed at flood defence and ecological rehabilitation. The weights given to the valuation criteria for protected and endangered species were varied and the effects on ranking of alternatives were quantified. A statistically significant correlation (p < 0.01) between predicted and observed values for protected and endangered species was found. The sensitivity of the model to value assignment proved to be low. Comparison of five realistic valuation options showed that different rankings of scenarios predominantly occur when valuation criteria are left out of the assessment. Based on these results we conclude that linking species to ecotopes can be used for adequate impact assessments. Quantification of sensitivity of impact assessment to value assignment shows that a model like BIO-SAFE is relatively insensitive to assignment of values to different policy and legislation based criteria. Arbitrariness of the value assignment therefore has a very limited effect on assessment outcomes. However, the decision to include valuation criteria or not is very important.« less

Activation of the innate immune system provides broad-spectrum protection against influenza A viruses with pandemic potential in mice

PubMed Central

Lau, Yuk-Fai; Tang, Lay-Hoon; Ooi, Eng-Eong; Subbarao, Kanta

2010-01-01

The efficacy of a stabilized chemical analog of double-stranded ribonucleic acid (RNA), PIKA, as prophylaxis against infection with 5 different influenza A virus subtypes, including the 2009 swine-origin pandemic H1N1 virus, was evaluated in mice. Intranasal treatment with PIKA resulted in significant reduction of viral replication in the respiratory tract. The inhibitory effect was mediated by rapid infiltration of immune cells into the lungs, and production of inflammatory cytokines. While TLR3 is important for the optimal production of these inflammatory cytokines, inhibition of viral replication was still observed in TLR3−/− mice. In addition, a significant synergistic effect in inhibiting H5N1 virus replication was observed when PIKA was co-administered with oseltamivir. The broad-spectrum protection provided by PIKA makes it an attractive option for prophylaxis from infection with influenza A viruses. PMID:20667572

Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist

PubMed Central

Hu, Zhiqiang; Xing, Yaling; Qian, Yuanyu; Chen, Xiaojuan; Tu, Jian; Ren, Lening; Wang, Kai; Chen, Zhongbin

2013-01-01

A number of agents are now available for use in protecting against ionizing radiation. These radiation-protective agents, however, have many adverse effects. Efforts have been made to develop new radiation-protective agents for medical application. Here, we investigated whether a compound, polyethylenimine (PEI), which activates Toll-like receptor 5 (TLR5)-mediated NF-kB signaling pathways, could have an anti-radiation effect on a mouse model. First, a cell-based screening model for an agonist of TLR5-mediated NF-kB pathway was established and then validated by activation of TLR5-mediated NF-kB luciferase reporter activity with a known TLR5 agonist, flagellin. We found that PEI induced dose-dependent activation of the TLR5-mediated NF-kB pathway, indicating that PEI is indeed a TLR5 agonist. Furthermore, the anti-radiation effect of polyethylenimine was assessed using a γ-ray total body irradiation (TBI) mouse model. Compared with the irradiation control, both survival time and survival rate were significantly improved in mice that received either a low dose of polyethylenimine (P= 0.019) or a high dose of polyethylenimine (P< 0.001). We also observed a positive correlation between animal body weight and survival time in mice that received a low dose of polyethylenimine, a high dose of polyethylenimine and amifostine, over a period of 30 days, r= 0.42 (P< 0.02), 0.72 (P< 0.0001) and 0.95 (P< 0.0001), respectively, while a negative correlation between animal body weight and survival time was observed in the irradiation control (r= –0.89; P< 0.0001). These results indicate that polyethylenimine is a new TLR5 agonist with potential application in offering protection for patients receiving radiotherapy or in radiation-related accidents. PMID:23104900

Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist.

PubMed

Hu, Zhiqiang; Xing, Yaling; Qian, Yuanyu; Chen, Xiaojuan; Tu, Jian; Ren, Lening; Wang, Kai; Chen, Zhongbin

2013-03-01

A number of agents are now available for use in protecting against ionizing radiation. These radiation-protective agents, however, have many adverse effects. Efforts have been made to develop new radiation-protective agents for medical application. Here, we investigated whether a compound, polyethylenimine (PEI), which activates Toll-like receptor 5 (TLR5)-mediated NF-kB signaling pathways, could have an anti-radiation effect on a mouse model. First, a cell-based screening model for an agonist of TLR5-mediated NF-kB pathway was established and then validated by activation of TLR5-mediated NF-kB luciferase reporter activity with a known TLR5 agonist, flagellin. We found that PEI induced dose-dependent activation of the TLR5-mediated NF-kB pathway, indicating that PEI is indeed a TLR5 agonist. Furthermore, the anti-radiation effect of polyethylenimine was assessed using a γ-ray total body irradiation (TBI) mouse model. Compared with the irradiation control, both survival time and survival rate were significantly improved in mice that received either a low dose of polyethylenimine (P= 0.019) or a high dose of polyethylenimine (P< 0.001). We also observed a positive correlation between animal body weight and survival time in mice that received a low dose of polyethylenimine, a high dose of polyethylenimine and amifostine, over a period of 30 days, r= 0.42 (P< 0.02), 0.72 (P< 0.0001) and 0.95 (P< 0.0001), respectively, while a negative correlation between animal body weight and survival time was observed in the irradiation control (r= -0.89; P< 0.0001). These results indicate that polyethylenimine is a new TLR5 agonist with potential application in offering protection for patients receiving radiotherapy or in radiation-related accidents.

Alcohol, wine and platelet function.

PubMed

Ruf, Jean-Claude

2004-01-01

Epidemiological studies have demonstrated an inverse correlation between moderate wine and alcohol consumption and morbidity and mortality from coronary heart disease. The protective effect has been associated with an increase in the plasma level of HDL cholesterol, as it is well recognized that plasma HDL is inversely correlated with CHD. In addition, it has become evident that blood platelets contribute to the rate of development of atherosclerosis and CHD through several mechanisms. In recent studies it has been shown that the level of HDL cholesterol can explain only 50% of the protective effect of alcoholic beverages; the other 50% may be partly related to a decrease in platelet activity. This anti-platelet activity of wine is explained by ethanol but also by the polyphenolic components with which red wines are richly endowed. Several studies carried out on humans and animals have shown that wine phenolics could exert their effects by reducing prostanoid synthesis from arachidonate. In addition, it has been suggested that wine phenolics could reduce platelet activity mediated by nitric oxide. Moreover, wine phenolics increase vitamin E levels while decreasing the oxidation of platelets submitted to oxidative stress. However, a rebound phenomenon of hyperaggregability is observed after an acute alcohol consumption which is not observed with wine consumption. This protection afforded by wine has been duplicated in animals with grape phenolics added to alcohol. The rebound phenomenon may explain ischemic strokes or sudden deaths known to occur after episodes of drunkenness. It appears that wine, and wine phenolics in particular, could have a more significant inhibitory effect on platelet aggregation and could explain, in part, the hypothesis that red wine is more protective against atherosclerosis and coronary heart disease.

Treatment of yellow fever virus with an adenovirus-vectored interferon, DEF201, in a hamster model.

PubMed

Julander, Justin G; Ennis, Jane; Turner, Jeffrey; Morrey, John D

2011-05-01

Interferon (IFN) is an innate immune response protein that is involved in the antiviral response during viral infection. Treatment of acute viral infections with exogenous interferon may be effective but is generally not feasible for clinical use due to many factors, including cost, stability, and availability. To overcome these limitations, an adenovirus type 5-vectored consensus alpha IFN, termed DEF201, was constructed as a potential way to deliver sustained therapeutic levels of systemic IFN. To demonstrate the efficacy of DEF201 against acute flaviviral disease, various concentrations of the construct were administered as a single intranasal dose prior to virus infection, which resulted in a dose-responsive, protective effect in a hamster model of yellow fever virus (YFV) disease. A DEF201 dose of 5×10(7) PFU/animal administered intranasally just prior to YFV challenge protected 100% of the animals, while a 10-fold lower DEF201 dose exhibited lower, although significant, levels of protection. Virus titers in the liver and serum and levels of serum alanine aminotransferase were all significantly reduced as a result of DEF201 administration at all doses tested. No toxicity, as indicated by weight loss or gross morbidity, was observed in non-YFV-infected animals treated with DEF201. Protection of YFV-infected animals was observed when DEF201 was delivered as early as 7 days prior to virus challenge and as late as 2 days after virus challenge, demonstrating effective prophylaxis and therapy in a hamster model of disease. Overall, it appears that DEF201 is effective in the treatment of YFV in a hamster model.

Single-Dose Hepatitis A Immunization: 7.5-Year Observational Pilot Study in Nicaraguan Children to Assess Protective Effectiveness and Humoral Immune Memory Response.

PubMed

Mayorga, Orlando; Bühler, Silja; Jaeger, Veronika K; Bally, Seraina; Hatz, Christoph; Frösner, Gert; Protzer, Ulrike; Van Damme, Pierre; Egger, Matthias; Herzog, Christian

2016-11-15

 Universal 2-dose hepatitis A virus (HAV) vaccination of toddlers effectively controls hepatitis A. High vaccine costs, however, impede implementation in endemic countries. To test single-dose vaccination as a possible alternative, we initiated an observational, longitudinal study in Nicaragua, to assess protective effectiveness and-through challenge vaccination-humoral immune memory response.  After a 2003 serosurvey, 130 originally seronegative children received one dose of virosomal HAV vaccine in 2005, followed by yearly serological and clinical assessments until 2012. After 7.5 years, a vaccine booster was administered. Concurrent antibody screening of patients presenting with hepatitis symptoms documented persistent HAV circulation in the communities studied.  Between serosurvey and vaccination, 25 children contracted hepatitis A subclinically (>8000 mIU/mL anti-HAV). In the remaining 105 children, immunization resulted in anti-HAV levels of 17-572 mIU/mL. Based on the ≥15% annual infection risk, an estimated 60% of children were exposed to HAV encounters during follow-up. No child presented with hepatitis symptoms. Serological breakthrough infection (7106 mIU/mL) was documented in 1 child, representing an estimated protective effectiveness of 98.3% (95% confidence interval, 87.9-99.8). Boosting elicited an average 29.7-fold increase of anti-HAV levels.  In children living in hyperendemic settings, a single dose of virosomal HAV vaccine is sufficient to activate immune memory and may provide long-term protection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Influence of Route of Administration on Immediate and Extended Protection in Rats Immunized with Escherichia coli Heat-Labile Enterotoxin

PubMed Central

Klipstein, Frederick A.; Engert, Richard F.

1980-01-01

The effect of route of administration, dosage, and number of boosts employed during immunization with the polymyxin-release form of Escherichia coli heat-labile (LT) enterotoxin on the degree and duration of protection afforded was evaluated in rats which were challenged by the ligated loop technique. Increasing the boosting dosage by fivefold from 50 to 250 μg resulted in a marked increase in protection against challenge with toxin in rats immunized either just by the parenteral route (i.p./i.p.) or by a parenteral prime, followed by peroral boosts (i.p./p.o.) in rats pretreated with cimetidine to ablate gastric secretions; such was not the case, however, even with a 50-fold increase in dosage in rats immunized just by the peroral route (p.o./p.o.). Four weekly peroral boosts were required to achieve the strongest degree of protection. Increasing the boosting dosage also increased the degree of protection against challenge with viable LT+/ST− and LT+/ST+ strains (ST indicates heat-stable enterotoxin) in rats immunized by the i.p./p.o., but not by the i.p./i.p., route; no protection was evident against an LT−/ST+ strain. Protection was lost within 3 weeks after immunization in rats immunized by the i.p./i.p. route. In contrast, protection was extended over the 3-month observation period in those immunized by the i.p./p.o. route; the degree of protection was enhanced in rats which received an additional boost at 2 months. These observations establish the fact that immunization with LT is similar to that with cholera toxin in that arousal of the local immune intestinal response by means of peroral immunization provides maximal extended protection. PMID:6987180

17β-Estradiol enhances sulforaphane cardioprotection against oxidative stress.

PubMed

Angeloni, Cristina; Teti, Gabriella; Barbalace, Maria Cristina; Malaguti, Marco; Falconi, Mirella; Hrelia, Silvana

2017-04-01

The lower incidence of ischemic heart disease in female with respect to male gender suggests the possibility that female sex hormones could have specific effects in cardiovascular protection. 17β-Estradiol is the predominant premenopausal circulating form of estrogen and has a protective role on the cardiovascular system. Recent evidences suggest that gender can influence the response to cardiovascular medications; therefore, we hypothesized that sex hormones could also modulate the cardioprotective effects of nutraceutical compounds, such as the isothiocyanate sulforaphane, present in Brassica vegetables. This study was designed to explore the protective effects of sulforaphane in the presence of 17β-estradiol against H 2 O 2 -induced oxidative stress in primary cultures of rat cardiomyocytes. Interestingly, 17β-estradiol enhanced sulforaphane protective activity against H 2 O 2 -induced cell death with respect to sulforaphane or 17β-estradiol alone as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-tetrazolium bromide and lactate dehydrogenase assays. Moreover, 17β-estradiol boosted sulforaphane ability to counteract oxidative stress, reducing intracellular reactive oxygen species and 8-hydroxy-2'-deoxyguanosine levels and increasing the expression of phase II enzymes. Using specific antagonists of estrogen receptor α and β, we observed that these effects are not mediated by estrogen receptors. Otherwise, ERK1/2 and Akt signaling pathways seem to be involved, as the presence of specific inhibitors of these kinases reduced the protective effect of sulforaphane in the presence of 17β-estradiol. Sulforaphane and 17β-estradiol co-treatment counteracted cell morphology alterations induced by H 2 O 2 as evidenced by transmission electron microscopy. Our results demonstrated, for the first time, that estrogens could enhance sulforaphane protective effects, suggesting that nutraceutical efficacy might be modulated by sex hormones. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanism of protection of transepithelial barrier function by Lactobacillus salivarius: strain dependence and attenuation by bacteriocin production.

PubMed

Miyauchi, Eiji; O'Callaghan, John; Buttó, Ludovica F; Hurley, Gráinne; Melgar, Silvia; Tanabe, Soichi; Shanahan, Fergus; Nally, Kenneth; O'Toole, Paul W

2012-11-01

Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, barrier protection is not exhibited by all probiotic or commensals and the strain-specific molecules involved remain to be clarified. We evaluated the effects of 33 individual Lactobacillus salivarius strains on the hydrogen peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells. These strains showed markedly different effects on H(2)O(2)-induced reduction in transepithelial resistance (TER). The effective strains such as UCC118 and CCUG38008 attenuated H(2)O(2)-induced disassembly and relocalization of tight junction proteins, but the ineffective strain AH43324 did not. Strains UCC118 and CCUG38008 induced phosphorylation of extracellular signal-regulated kinase (ERK) in Caco-2 cells, and the ERK inhibitor U0126 attenuated the barrier-protecting effect of these strains. In contrast, the AH43324 strain induced phosphorylation of Akt and p38, which was associated with an absence of a protective effect. Global transcriptome analysis of UCC118 and AH43324 revealed that some genes in a bacteriocin gene cluster were upregulated in AH43324 under TER assay conditions. A bacteriocin-negative UCC118 mutant displayed significantly greater suppressive effect on H(2)O(2)-induced reduction in TER compared with wild-type UCC118. The wild-type strain augmented H(2)O(2)-induced phosphorylation of Akt and p38, whereas a bacteriocin-negative UCC118 mutant did not. These observations indicate that L. salivarius strains are widely divergent in their capacity for barrier protection, and this is underpinned by differences in the activation of intracellular signaling pathways. Furthermore, bacteriocin production appears to have an attenuating influence on lactobacillus-mediated barrier protection.

Linking Meteorology, Air Quality Models and Observations to Characterize Human Exposures in Support of the Environmental Health Studies

EPA Science Inventory

Epidemiologic studies are critical in establishing the association between exposure to air pollutants and adverse health effects. Results of epidemiologic studies are used by U.S. EPA in developing air quality standards to protect the public from the health effects of air polluta...

RELATIVE EFFECTS OF OBSERVATIONALLY-NUDGED MODEL METEOROLOGY AND DOWN-SCALED GLOBAL CLIMATE MODEL METEOROLOGY ON BIOGENIC EMISSIONS FOR THE UNITED STATES

EPA Science Inventory

The United States Environmental Protection Agency (USEPA) and National Oceanic and Atmospheric Administration (NOAA) participate in a multi-agency examination of the effects of climate change through the U.S. Climate Change Science Program (CCSP, 2003). The EPA Global Change Rese...

Protective effects of osthole, a natural derivative of coumarin, against intestinal ischemia-reperfusion injury in mice.

PubMed

Dong, Wenpeng; Zhang, Zhen; Liu, Zhengjun; Liu, Hao; Wang, Xianyue; Bi, Shenghui; Wang, Xiaowu; Ma, Tao; Zhang, Weida

2013-06-01

Intestinal ischemia/reperfusion (I/R) injury is considered to be associated with high morbidity and mortality rates. Osthole, a natural derivative of coumarin, has been shown to exert a variety of pharmacological and therapeutic effects under physiological and pathological conditions. In the present study, to investigate the protective effects of osthole against intestinal I/R injury, various doses of osthole (5, 10, 25 and 50 mg/kg) were pre-administered to mice subjected to intestinal I/R injury. A dose-dependent increase in the survival rate was observed in the osthole-treated mice. Pre-treatment with osthole (50 mg/kg) attenuated the destruction of epithelial cells within the villi induced by intestinal I/R injury, and suppressed oxidative stress, neutrophil infiltration and modulated nitric oxide (NO) levels. Moreover, the increased IκBα phosphorylation and nuclear factor (NF)-κB nuclear translocation induced by I/R injury were significantly decreased following pre-treatment with osthole. Taken together, our data demonstrate that osthole exerts protective effects against intestinal I/R injury in mice by suppressing oxidative stress, neutrophil infiltration and NO levels, partly through the inhibition of NF-κB nuclear translocation. Hence, the findings of the present study provide insight into the mechanisms through which osthole exerts its protective effects against intestinal I/R injury.

Luteolin: A Flavonoid that Has Multiple Cardio-Protective Effects and Its Molecular Mechanisms

PubMed Central

Luo, Yuanyuan; Shang, Pingping; Li, Dongye

2017-01-01

Cardiovascular disease (CVD) has become the leading cause of morbidity and mortality worldwide. A well-monitored diet with a sufficient intake of fruits and vegetables has been confirmed as a primary prevention of CVD. Plant constituents such as flavonoids have been shown to confer healthy benefits. Luteolin (Lut), a kind of flavonoid, possesses anti-oxidative, anti-tumor, and anti-inflammatory properties. Recent scientific literature has reported the cardiac protective effects of Lut in vitro and in vivo. Therefore, the aim of this review is to provide an update and detailed overview with cardio-protective molecular mechanisms of Lut with a focus on multiple intrinsic and extrinsic effectors. We further explore how these mechanisms participate in ischemia/reperfusion (I/R) injury, heart failure (HF) and atherosclerosis (AS). A proper understanding of the cardiovascular protective effects and the relative mechanisms of Lut may provide the possibility of new drug design and development for CVD. With the previous studies mainly focused on basic research, we need to advance the prospects of its further clinical utilization against CVD, large prospective clinical trials of Lut are needed to observe its therapeutic effects on patients with I/R injury, HF and AS, especially on the effective therapeutic dosage, and safety of long-term administration. PMID:29056912

Histopathological observation of immunized rhesus macaques with plague vaccines after subcutaneous infection of Yersinia pestis.

PubMed

Tian, Guang; Qiu, Yefeng; Qi, Zhizhen; Wu, Xiaohong; Zhang, Qingwen; Bi, Yujing; Yang, Yonghai; Li, Yuchuan; Yang, Xiaoyan; Xin, Youquan; Li, Cunxiang; Cui, Baizhong; Wang, Zuyun; Wang, Hu; Yang, Ruifu; Wang, Xiaoyi

2011-04-29

In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270) and SV2 (200 µg F1 and 100 µg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6) CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.

Cocoa flavonoids protect hepatic cells against high-glucose-induced oxidative stress: relevance of MAPKs.

PubMed

Cordero-Herrera, Isabel; Martín, María Angeles; Goya, Luis; Ramos, Sonia

2015-04-01

Oxidative stress plays a main role in the pathogenesis of type 2 diabetes mellitus. Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in type 2 diabetes mellitus because of their protective effects against oxidative stress and insulin-like properties. In this study, the protective effect of EC and a cocoa phenolic extract (CPE) against oxidative stress induced by a high-glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells. Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs), nuclear factor E2 related factor 2 (Nrf2) and p-(Ser)-IRS-1 expression, and glucose uptake were evaluated. EC and CPE regulated antioxidant enzymes and activated extracellular-regulated kinase and Nrf2. EC and CPE pre-treatment prevented high-glucose-induced antioxidant defences and p-MAPKs, and maintained Nrf2 stimulation. The presence of selective MAPK inhibitors induced changes in redox status, glucose uptake, p-(Ser)- and total IRS-1 levels that were observed in CPE-mediated protection. EC and CPE recovered redox status of insulin-resistant HepG2 cells, suggesting that the functionality in EC- and CPE-treated cells was protected against high-glucose-induced oxidative insult. CPE beneficial effects on redox balance and insulin resistance were mediated by targeting MAPKs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway

PubMed Central

Gu, Anxin; Jie, Yamin; Sun, Liang; Zhao, Shuping; E, Mingyan; You, Qingshan

2015-01-01

Radiation-induced heart disease (RIHD), which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF)-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway. PMID:26332771

Protective effect of N-acetylcysteine against ethanol-induced gastric ulcer: A pharmacological assessment in mice

PubMed Central

Jaccob, Ausama Ayoob

2015-01-01

Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-acetylcysteine (NAC) against ethanol-induced gastric ulcer models in mice. Materials and Methods: A total of 41 mice were allocated into six groups consisted of 7 mice each. Groups 1 (normal control) and 2 (ulcer control) received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg). All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg) was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by anti-secretory, cytoprotective, histological and biochemical data, but the molecular mechanisms behind such protection are complex. PMID:26401392

Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

PubMed Central

Rajkumar, Lakshmanaswamy; Guzman, Raphael C; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

2004-01-01

Introduction Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. Methods Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. Results In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. Conclusions The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations. PMID:14680498

Protective Effect of Urtica dioica L. (Urticaceae) on Morphometric and Morphologic Alterations of Seminiferous Tubules in STZ Diabetic Rats.

PubMed

Golalipour, Mohammad Jafar; Kabiri Balajadeh, Babak; Ghafari, Soraya; Azarhosh, Ramin; Khori, Vahid

2011-09-01

Urtica dioica L. has been known as a medicinal plant in the world. This study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on seminiferous tubules of diabetic rats. Animals were allocated to control, diabetic and protective groups. Treated animals received extract of U. dioica (100 mg/ kg/ day) IP for the first 5 days and STZ injection on the 6th day. After 5 weeks, testes removed and stained with H&E technique. Tubular cell disintegration, sertoli and spermatogonia cell vacuolization, and decrease in sperm concentration observed in diabetic in comparison with control and protective groups. External seminiferous tubular diameter and seminiferous epithelial height significantly reduced (P< 0.05) in diabetic compared with controls, and these parameters increased (P< 0.05) in the treated compared with diabetics. Hydroalcoholic extract of U. dioica, before induction of diabetes; has protective role on seminiferous tubules alterations.

Measuring protection of aromatic wine thiols from oxidation by competitive reactions vs wine preservatives with ortho-quinones.

PubMed

Nikolantonaki, Maria; Magiatis, Prokopios; Waterhouse, Andrew L

2014-11-15

Quinones are central intermediates in wine oxidation that can degrade the quality of wine by reactions with varietal thiols, such as 3-sulfanylhexanol, decreasing desirable aroma. Protection by wine preservatives (sulphur dioxide, glutathione, ascorbic acid and model tannin, phloroglucinol) was assessed by competitive sacrificial reactions with 4-methyl-1,2-benzoquinone, quantifying products and ratios by HPLC-UV-MS. Regioselectivity was assessed by product isolation and identification by NMR spectroscopy. Nucleophilic addition reactions compete with two electron reduction of quinones by sulphur dioxide or ascorbic acid, and both routes serve as effective quenching pathways, but minor secondary products from coupled redox reactions between the products and reactants are also observed. The wine preservatives were all highly reactive and thus all very protective against 3-sulfanylhexanol loss to the quinone, but showed only additive antioxidant effects. Confirmation of these reaction rates and pathways in wine is needed to assess the actual protective action of each tested preservative. Copyright © 2014 Elsevier Ltd. All rights reserved.

Protective Effect of Urtica dioica L. (Urticaceae) on Morphometric and Morphologic Alterations of Seminiferous Tubules in STZ Diabetic Rats

PubMed Central

Golalipour, Mohammad Jafar; Kabiri Balajadeh, Babak; Ghafari, Soraya; Azarhosh, Ramin; Khori, Vahid

2011-01-01

Objective(s) Urtica dioica L. has been known as a medicinal plant in the world. This study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on seminiferous tubules of diabetic rats. Materials and Methods Animals were allocated to control, diabetic and protective groups. Treated animals received extract of U. dioica (100 mg/ kg/ day) IP for the first 5 days and STZ injection on the 6th day. After 5 weeks, testes removed and stained with H&E technique. Results Tubular cell disintegration, sertoli and spermatogonia cell vacuolization, and decrease in sperm concentration observed in diabetic in comparison with control and protective groups. External seminiferous tubular diameter and seminiferous epithelial height significantly reduced (P< 0.05) in diabetic compared with controls, and these parameters increased (P< 0.05) in the treated compared with diabetics. Conclusion Hydroalcoholic extract of U. dioica, before induction of diabetes; has protective role on seminiferous tubules alterations. PMID:23493848

Protective effects of anethole dithiolethione against oxidative stress-induced cytotoxicity in human Jurkat T cells.

PubMed

Khanna, S; Sen, C K; Roy, S; Christen, M O; Packer, L

1998-07-01

The protective effects of anethole dithiolethione (ADT) against H2O2- or 4-hydroxynonenal (HNE)-induced cytotoxicity in human Jurkat T cells were investigated. Jurkat T cells were pretreated with ADT (10-50 microM) for 18 hr and then challenged with H202 or HNE for up to 4 hr. Cytotoxicity was assessed by measuring: 1) leakage of lactate dehydrogenase from cells to medium; and 2) exclusion of the DNA intercalating fluorescent probe propidium iodide by viable cells. Pretreatment of cells with ADT (10 or 25 microM) for 18 hr significantly protected cells against H202- or HNE-induced cytotoxicity. Treatment of cells with ADT (10-50 microM) for 72 hr significantly increased the activities of catalase and glutathione reductase. The maximum effect of ADT treatment on the activity of these enzymes was observed when cells were treated with 25 microM of ADT for 72 hr. A significant increase in cellular GSH was observed in cells that were treated with ADT for 72 hr. Using monobromobimane as a thiol probe, we consistently observed that cells pretreated for 18 hr with ADT (25 or 50 microM) had also increased total thiol content. Exposure of Jurkat T cells to H202 or HNE resulted in a time-dependent decrease in cellular GSH. ADT (10-50 microM, 18 hr) pretreatment circumvented H202-dependent lowering of cellular GSH. In conclusion, ADT proved to be a potent cytoprotective thiol antioxidant with multifaceted mechanisms of action, suggesting that the drug has a remarkable therapeutic potential.

Protective effect of acetyl-L-carnitine on propofol-induced toxicity in embryonic neural stem cells.

PubMed

Liu, Fang; Rainosek, Shuo W; Sadovova, Natalya; Fogle, Charles M; Patterson, Tucker A; Hanig, Joseph P; Paule, Merle G; Slikker, William; Wang, Cheng

2014-05-01

Propofol is a widely used general anesthetic. A growing body of data suggests that perinatal exposure to general anesthetics can result in long-term deleterious effects on brain function. In the developing brain there is evidence that general anesthetics can cause cell death, synaptic remodeling, and altered brain cell morphology. Acetyl-L-carnitine (L-Ca), an anti-oxidant dietary supplement, has been reported to prevent neuronal damage from a variety of causes. To evaluate the ability of L-Ca to protect against propofol-induced neuronal toxicity, neural stem cells were isolated from gestational day 14 rat fetuses and on the eighth day in culture were exposed for 24h to propofol at 10, 50, 100, 300 and 600 μM, with or without L-Ca (10 μM). Markers of cellular proliferation, mitochondrial health, cell death/damage and oxidative damage were monitored to determine: (1) the effects of propofol on neural stem cell proliferation; (2) the nature of propofol-induced neurotoxicity; (3) the degree of protection afforded by L-Ca; and (4) to provide information regarding possible mechanisms underlying protection. After propofol exposure at a clinically relevant concentration (50 μM), the number of dividing cells was significantly decreased, oxidative DNA damage was increased and a significant dose-dependent reduction in mitochondrial function/health was observed. No significant effect on lactase dehydrogenase (LDH) release was observed at propofol concentrations up to 100 μM. The oxidative damage at 50 μM propofol was blocked by L-Ca. Thus, clinically relevant concentrations of propofol induce dose-dependent adverse effects on rat embryonic neural stem cells by slowing or stopping cell division/proliferation and causing cellular damage. Elevated levels of 8-oxoguanine suggest enhanced oxidative damage [reactive oxygen species (ROS) generation] and L-Ca effectively blocks at least some of the toxicity of propofol, presumably by scavenging oxidative species and/or reducing their production. Published by Elsevier B.V.

Methanol extract of Ocimum gratissimum protects murine peritoneal macrophages from nicotine toxicity by decreasing free radical generation, lipid and protein damage and enhances antioxidant protection

PubMed Central

Mahapatra, Santanu Kar; Chakraborty, Subhankari Prasad; Das, Subhasis

2009-01-01

In the present study, methanol extract of Ocimum gratissimum Linn (ME-Og) was tested against nicotine-induced murine peritoneal macrophage in vitro. Phytochemical analysis of ME-Og shown high amount of flavonoid and phenolic compound present in it. The cytotoxic effect of ME-Og was studied in murine peritoneal macrophages at different concentrations (0.1 to 100 µg/ml) using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) method. To establish the protective role of ME-Og against nicotine toxicity, peritoneal macrophages from mice were treated with nicotine (10 mM), nicotine + ME-Og (1 to 25 µg/ml) for 12 h in culture media. The significantly (p < 0.05) increased super oxide anion generation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, myeloperoxidase (MPO) activity, lipid peroxidation, protein carbonyls, oxidized glutathione levels were observed in nicotine-treated group as compared to control group; those were significantly (p < 0.05) reduced in ME-Og supplemented groups in concentration dependent manner. More over, significantly (p < 0.05) reduced antioxidant status due to nicotine exposure was effectively ameliorated by ME-Og supplementation in murine peritoneal macrophages. Among the different concentration of ME-Og, maximum protective effect was observed by 25 µg/ml, which does not produce significant cell cytotoxicity in murine peritoneal macrophages. These findings suggest the potential use and beneficial role of O. gratissimum as a modulator of nicotine-induced free radical generation, lipid-protein damage and antioxidant status in important immune cell, peritoneal macrophages. PMID:20716908

Pemphigus and smoking- insights from a big data analysis.

PubMed

Kridin, Khalaf; Comaneshter, Doron; Batat, Erez; Cohen, Arnon D

2018-04-28

We have read with great interest the manuscript written by Lai et al.(1). The authors performed a systematic review and pooled-analysis aiming to summarize the current knowledge regarding the prevalence of smoking among patients with pemphigus relative to control subjects. By summarizing the findings of 13 observational studies comprising 3046 pemphigus patients, a pooled OR of 0.9 (95% CI, 0.82-0.99; P<0.05) was revealed indicating that smoking may exert a protective effect against the development of pemphigus(1). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Repellent action of neem cream against mosquitoes.

PubMed

Dua, V K; Nagpal, B N; Sharma, V P

1995-06-01

Neem cream was used as mosquito repellent to provide protection against Aedes albopictus, Ae. aegypti, Culex quinquefasciatus, Anopheles culicifacies and An. subpictus mosquitoes. The application of neem cream on exposed body parts @2.0 gm/person showed 78 (range 65-95), 89 (range 66-100) and 94.4 (range 66-100) per cent protection against Aedes, Culex and Anopheles mosquitoes respectively. Significant difference was observed between neem cream treated and untreated group of population for Aedes mosquitoes (p < 0.001). Application of neem cream was found to be a safe and suitable alternative to insecticide impregnated coils for personal protection against mosquitoes and one application was 68% effective for four hours.

Lipid oxidation in base algae oil and water-in-algae oil emulsion: Impact of natural antioxidants and emulsifiers.

PubMed

Chen, Bingcan; Rao, Jiajia; Ding, Yangping; McClements, David Julian; Decker, Eric Andrew

2016-07-01

The impact of natural hydrophilic antioxidants, metal chelators, and hydrophilic antioxidant/metal chelator mixture on the oxidative stability of base algae oil and water-in-algae oil emulsion was investigated. The results showed that green tea extract and ascorbic acid had greatest protective effect against algae oil oxidation and generated four day lag phase, whereas rosmarinic acid, grape seed extract, grape seed extract polymer, deferoxamine (DFO), and ethylenediaminetetraacetic acid (EDTA) had no significant protective effect. Besides, there was no synergistic effect observed between natural antioxidants and ascorbic acid. The emulsifiers are critical to the physicochemical stability of water-in-algae oil emulsions. Polyglycerol polyricinoleate (PGPR) promoted the oxidation of emulsion. Conversely, the protective effect on algae oil oxidation was appreciated when defatted soybean lecithin (PC 75) or defatted lyso-lecithin (Lyso-PC) was added. The role of hydrophilic antioxidants in emulsion was similar to that in algae oil except EDTA which demonstrated strong antioxidative effect in emulsion. The results could provide information to build up stable food products containing polyunsaturated fatty acids (PUFA). Copyright © 2016 Elsevier Ltd. All rights reserved.

Variability in Non-Target Terrestrial Plant Studies Should Inform Endpoint Selection.

PubMed

Staveley, J P; Green, J W; Nusz, J; Edwards, D; Henry, K; Kern, M; Deines, A M; Brain, R; Glenn, B; Ehresman, N; Kung, T; Ralston-Hooper, K; Kee, F; McMaster, S

2018-05-04

Inherent variability in Non-Target Terrestrial Plant (NTTP) testing of pesticides creates challenges for using and interpreting these data for risk assessment. Standardized NTTP testing protocols were initially designed to calculate the application rate causing a 25% effect (ER25, used in the U.S.) or a 50% effect (ER50, used in Europe) for various measures based on the observed dose-response. More recently, the requirement to generate a no-observed-effect rate (NOER), or, in the absence of a NOER, the rate causing a 5% effect (ER05), has raised questions about the inherent variability in, and statistical detectability of, these tests. Statistically significant differences observed between test and control groups may be a product of this inherent variability and may not represent biological relevance. Attempting to derive an ER05 and the associated risk assessment conclusions drawn from these values can overestimate risk. To address these concerns, we evaluated historical data from approximately 100 seedling emergence and vegetative vigor guideline studies on pesticides to assess the variability of control results across studies for each plant species, examined potential causes for the variation in control results, and defined the minimum percent effect that can be reliably detected. The results indicate that with current test design and implementation, the ER05 cannot be reliably estimated. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

In Vivo Protection against Strychnine Toxicity in Mice by the Glycine Receptor Agonist Ivermectin

PubMed Central

Radwan, Rasha

2014-01-01

The inhibitory glycine receptor, a ligand-gated ion channel that mediates fast synaptic inhibition in mammalian spinal cord and brainstem, is potently and selectively inhibited by the alkaloid strychnine. The anthelminthic and anticonvulsant ivermectin is a strychnine-independent agonist of spinal glycine receptors. Here we show that ivermectin is an effective antidote of strychnine toxicity in vivo and determine time course and extent of ivermectin protection. Mice received doses of 1 mg/kg and 5 mg/kg ivermectin orally or intraperitoneally, followed by an intraperitoneal strychnine challenge (2 mg/kg). Ivermectin, through both routes of application, protected mice against strychnine toxicity. Maximum protection was observed 14 hours after ivermectin administration. Combining intraperitoneal and oral dosage of ivermectin further improved protection, resulting in survival rates of up to 80% of animals and a significant delay of strychnine effects in up to 100% of tested animals. Strychnine action developed within minutes, much faster than ivermectin, which acted on a time scale of hours. The data agree with a two-compartment distribution of ivermectin, with fat deposits acting as storage compartment. The data demonstrate that toxic effects of strychnine in mice can be prevented if a basal level of glycinergic signalling is maintained through receptor activation by ivermectin. PMID:25317421

The effect of doping (Mn,B)3O4 materials as protective layers in different metallic interconnects for Solid Oxide Fuel Cells

NASA Astrophysics Data System (ADS)

Miguel-Pérez, Verónica; Martínez-Amesti, Ana; Nó, María Luisa; Larrañaga, Aitor; Arriortua, María Isabel

2013-12-01

Spinel oxides with the general formula of (Mn,B)3O4 (B = Co, Fe) were used as barrier materials between the cathode and the metallic interconnect to reduce the rate of cathode degradation by Cr poisoning. The effect of doping at the B position was investigated terms of microstructure and electrical conductivity to determine its behaviour and effectiveness as a protective layer in contact with three metallic materials (Crofer 22 APU, SS430 and Conicro 4023 W 188). The analysis showed that the use of these materials considerably decreased the reactivity and diffusion of Cr between the cathode and the metallic interconnects. The protective layer doped with Fe at the B position exhibited the least amount of reactivity with the interconnector and cathode materials. The worst results were observed for SS430 cells coated with a protective layer perhaps due to their low Cr content. The Crofer 22 APU and Conicro 4023 W 188 samples exhibited very similar conductivity results in the presence of the MnCo1.9Fe0.1O4 protective coating. As a result, these two material combinations are a promising option for use as bipolar plates in SOFC.

Assessment of nutrient supplement to reduce gentamicin-induced ototoxicity.

PubMed

Le Prell, C G; Ojano-Dirain, C; Rudnick, E W; Nelson, M A; DeRemer, S J; Prieskorn, D M; Miller, J M

2014-06-01

Gentamicin is an aminoglycoside antibiotic used to treat gram-negative bacterial infections. Treatment with this antibiotic carries the potential for adverse side effects, including ototoxicity and nephrotoxicity. Ototoxic effects are at least in part a consequence of oxidative stress, and various antioxidants have been used to attenuate gentamicin-induced hair cell death and hearing loss. Here, a combination of nutrients previously shown to reduce oxidative stress in the hair cells and attenuate hearing loss after other insults was evaluated for potential protection against gentamicin-induced ototoxicity. Guinea pigs were maintained on a nutritionally complete standard laboratory animal diet or a diet supplemented with β-carotene, vitamins C and E, and magnesium. Three diets with iterative increases in nutrient levels were screened; the final diet selected for study use was one that produced statistically reliable increases in plasma levels of vitamins C and E and magnesium. In two separate studies, significant decreases in gentamicin-induced hearing loss at frequencies including 12 kHz and below were observed, with less benefit at the higher frequencies. Consistent with the functional protection, robust protection of both the inner and outer hair cell populations was observed, with protection largely in the upper half of the cochlea. Protection was independently assessed in two different laboratories, using two different strains of guinea pigs. Additional in vitro tests did not reveal any decrease in antimicrobial activity with nutrient additives. Currently, there are no FDA-approved treatments for the prevention of gentamicin-induced ototoxicity. The current data provide a rationale for continued investigations regarding translation to human patients.

Change in bone mineral density and its determinants in pre- and perimenopausal Chinese women: the Hong Kong Perimenopausal Women Osteoporosis Study.

PubMed

Ho, S C; Chan, S G; Yip, Y B; Chan, C S Y; Woo, J L F; Sham, A

2008-12-01

This 30-month study investigating bone change and its determinants in 438 perimenopausal Chinese women revealed that the fastest bone loss occurred in women undergoing menopausal transition but maintenance of body weight and physical fitness were beneficial for bone health. Soy protein intake also seemed to exert a protective effect. This 30-month follow-up study aims to investigate change in bone mineral density and its determinants in Hong Kong Chinese perimenopausal women. Four hundred and thirty-eight women aged 45 to 55 years were recruited through random telephone dialing and primary care clinic. Bone mass, body composition, lifestyle measurements were obtained at baseline and at 9-, 18- and 30-month follow-ups. Univariate and stepwise multiple regression analyses were performed with the regression coefficients of BMD/C (derived from baseline and follow-up measurements) as the outcome variables. Menopausal status was classified as pre- or postmenopausal or transitional. Menopausal status was the strongest determinant of bone changes. An annual bone loss of about 0.5% was observed among premenopausal, 2% to 2.5% among transitional, and about 1.5% in postmenopausal women. Multiple regression analyses, revealed that a positive regression slope of body weight was protective for follow-up bone loss at all sites. Number of pregnancy, soy protein intake and walking were protective for total body BMC. Higher baseline LM was also protective for neck of femur BMD. Maintenance of body weight and physical fitness were observed to have a protective effect on for bone loss in Chinese perimenopausal women.

Protective Effect of Active Immunization with Purified Escherichia coli Heat-Labile Enterotoxin in Rats

PubMed Central

Klipstein, Frederick A.; Engert, Richard F.

1979-01-01

The protective effect of active immunization by different routes with a purified preparation of the polymyxin-release form of Escherichia coli heat-labile toxin was evaluated in rats. Immunized animals were challenged by placing toxin into ligated ileal loops at dosages which produced either 50% or the maximum secretory response in unimmunized rats. Immunization exclusively by the parenteral route yielded significant protection. Rats were also protected when parenteral priming was followed by boosting given either directly into the duodenum or perorally 2 h after intragastric cimetidine, but not when the peroral boosts were given with bicarbonate. Immunization administered entirely by the peroral route with cimetidine yielded protection but only when the immunizing dosage was fivefold greater than that found effective in the parenteral-peroral approach. Rats immunized exclusively by the parenteral route and those boosted perorally with cimetidine were also tested, and found to be protected, against challenge with viable organisms of strains that produce either heat-labile toxin alone or both heat-labile and heat-stable toxin, but they were not protected against a strain which produces just heat-stable toxin. Geometric mean serum antibody titers were increased by 16-fold or more over control values in those groups of rats in which protection was achieved, with the exception of those immunized exclusively by the peroral route. These observations demonstrate that (i) active immunization with purified E. coli heat-labile toxin results in significant protection against both this toxin as well as viable organisms which produce it, but not against viable strains which produce heat-stable toxin only, and (ii) concomitant ablation of gastric secretion by the use of cimetidine renders the peroral route of immunization effective. They suggest that prophylactic immunization against diarrheal disease caused by heat-labile toxin-producing strains of E. coli may be feasible in humans. PMID:378831

Improving health care workers' protection against infection of Ebola hemorrhagic fever through video surveillance.

PubMed

Xi, Huijun; Cao, Jie; Liu, Jingjing; Li, Zhaoshen; Kong, Xiangyu; Wang, Yonghua; Chen, Jing; Ma, Su; Zhang, Lingjuan

2016-08-01

The purpose of this study was to investigate the importance of supervision through video surveillance in improving the quality of personal protection in preparing health care workers working in Ebola treatment units. Wardens supervise, remind, and guide health care workers' behavior through onsite voice and video systems when they are in the suspected patient observation ward and in the patient diagnosed ward of the Ebola treatment center. The observation results were recorded, and timely feedback was given to the health care workers. After 2 months of supervision, 1,797 cases of incorrect personal protection behaviors were identified and corrected. The error rate continuously declined. The declined rate of the first 2 weeks was statistically different from other time periods. Through reminding and supervising, nonstandard personal protective behaviors can be discovered and corrected, which can help health care workers standardize personal protection. The timely feedback from video surveillance can also offer psychologic support and encouragement promptly to ease psychologic pressure. Finally, this can ensure health care workers stay at a zero infection rate during patient treatment. Personal protective equipment protocol supervised by wardens through a video monitoring process can be used as an effective complement to conventional mutual supervision methods and can help health care workers avoid Ebola infection during treatment. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Impact of Past Land Use Changes on Drinking Water Quantity and Quality in Ljubljana Aquifer

NASA Astrophysics Data System (ADS)

Bracic Zeleznik, Branka; Cencur Curk, Barbara

2010-05-01

Most of the practical problems that we face today with the on-site management of drinking water sources and distribution of healthy drinking water, originate from past actions, interventions and political decisions. In Ljubljana, the capital of the Republic of Slovenia, underlying groundwater is the main drinking water source. The main threat to drinking water sources is constant input of pollutant loads from roads, roofs, sewers, industry and agricultural areas. The main problems are directly and indirectly related to the significant decrease of groundwater level and deterioration of groundwater quality observed in the last decades as an effect of land use practices under varying climate conditions. The Vodovod-Kanalizacija Public Utility is responsible for water supply of the city residents as well as for management of the water supply system, its surveillance and maintenance. In the past, the Ljubljana Municipality was responsible for the protection of water resources and the first delineation of groundwater protection areas was issued in Decree in 1955. In 2004 a Decree on the water protection zones for the aquifer of Ljubljansko polje on the state level was issued and passed the competences of proclamation of the water protection zones to the state. Spatial planning is a domain of The Municipality and land use is limited according to water protection legislation. For several observation wells long-time data sets about groundwater levels and quality are available, which enable us to analyse changes in groundwater quantity and quality parameters. From the data it is obvious that climate variations are affecting groundwater recharge. In addition, changing of land use affects groundwater quality. In spite of the Decree on the water protection there is a heavy pressure of investors to change land use plans and regulations on protection zones, which causes every day problems in managing the drinking water source. Groundwater management in Ljubljana demands strong and effective co-operation between state, municipality, public water supply company and consumers.

Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1.

PubMed

Zhang, Meijuan; Wang, Suping; Mao, Leilei; Leak, Rehana K; Shi, Yejie; Zhang, Wenting; Hu, Xiaoming; Sun, Baoliang; Cao, Guodong; Gao, Yanqin; Xu, Yun; Chen, Jun; Zhang, Feng

2014-01-29

Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies.

The complexity of child protection recurrence: The case for a systems approach.

PubMed

Jenkins, Brian Q; Tilbury, Clare; Mazerolle, Paul; Hayes, Hennessey

2017-01-01

Research on child protection recurrence has found consistent child, family, and case characteristics associated with repeated involvement with the child protection system. Despite the considerable body of empirical research, knowledge about why recurrence occurs, and what can be done to reduce it, is limited. This paper reviews the empirical literature and analyses the approaches of prior recurrence research. Four related conceptual challenges are identified: (1) a tendency to conflate child protection recurrence with repeated child maltreatment; (2) uncertainty about how best to operationalize and measure child protection recurrence in research; (3) inconsistency between prevailing explanations for the most frequently observed patterns of recurrence; and (4) difficulty in developing coherent strategies to address child protection recurrence based on research. Addressing these challenges requires a greater consideration of the effects of decision-making in the child protection system on recurrence. This paper proposes a methodology based in systems theory and drawing on existing administrative data to examine the characteristics of the child protection system that may also produce recurrence. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity

PubMed Central

Karim, Sabiha; Asad, Muhammad Hassham Hassan Bin; Kalsoom Khan, Abida; Malik, Arif; Chen, Chunye

2015-01-01

The exposure to ultraviolet radiations (UVR) is the key source of skin sunburn; it may produce harmful entities, reactive oxygen species (ROS), leading to aging. The skin can be treated and protected from the injurious effects of ROS by using various pharmaceutical formulations, such as cream. Cream can be loaded with antioxidants to quench ROS leading to photo-protective effects. Moreover, modern medicines depend on ethnobotanicals for protection or treatment of human diseases. This review article summarizes various in vivo antioxidant studies on herbal creams loaded with phyto-extracts. These formulations may serve as cosmeceuticals to protect skin against injurious effects of UVR. The botanicals studied for dermatologic use in cream form include Acacia nilotica, Benincasa hispida, Calendula officinalis, Camellia sinensis, Camellia sinensis, Nelumbo nucifera, Capparis decidua, Castanea sativa, Coffea arabica, Crocus sativus, Emblica officinalis Gaertn, Foeniculum vulgare, Hippophae rhamnoides, Lithospermum erythrorhizon, Malus domestica, Matricaria chamomilla L., Moringa oleifera, Morus alba, Ocimum basilicum, Oryza sativa, Polygonum minus, Punica granatum, Silybum marianum, Tagetes erecta Linn., Terminalia chebula, Trigonella foenum-graecum, and Vitis vinifera. The observed anti-aging effects of cream formulations could be an outcome of a coordinating action of multiple constituents. Of numerous botanicals, the phenolic acids and flavonoids appear effective against UVR-induced damage; however the evidence-based studies for their anti-aging effects are still needed. PMID:26448818

[Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

PubMed

Mu, F H; Hu, F L; Wei, H; Zhang, Y Y; Yang, G B; Lei, X Y; Yang, Y P; Sun, W N; Cui, M H

2016-02-01

To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all P<0.01), and content of NO in the compound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, P<0.05). The gastric mucosal lesion index, contents of TNF, and IL-1, 2, 8 were significantly lower in all the protection groups than in the injury group (all P<0.01), and contents of IL-2 and IL-8 in the compound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, P<0.01; (170.82±7.31) vs(179.31±7.80)pg/ml, P<0.05). Tissue injury and inflammatory reaction in all the protection groups were obviously mitigated compared with the injury group. Compound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

Oleocanthal Enhances Amyloid-β Clearance from the Brains of TgSwDI Mice and in Vitro across a Human Blood-Brain Barrier Model

PubMed Central

2015-01-01

Numerous clinical and preclinical studies have suggested several health promoting effects for the dietary consumption of extra-virgin olive oil (EVOO) that could protect and decrease the risk of developing Alzheimer’s disease (AD). Moreover, recent studies have linked this protective effect to oleocanthal, a phenolic secoiridoid component of EVOO. This protective effect of oleocanthal against AD has been related to its ability to prevent amyloid-β (Aβ) and tau aggregation in vitro, and enhance Aβ clearance from the brains of wild type mice in vivo; however, its effect in a mouse model of AD is not known. In the current study, we investigated the effect of oleocanthal on pathological hallmarks of AD in TgSwDI, an animal model of AD. Mice treatment for 4 weeks with oleocanthal significantly decreased amyloid load in the hippocampal parenchyma and microvessels. This reduction was associated with enhanced cerebral clearance of Aβ across the blood-brain barrier (BBB). Further mechanistic studies demonstrated oleocanthal to increase the expression of important amyloid clearance proteins at the BBB including P-glycoprotein and LRP1, and to activate the ApoE-dependent amyloid clearance pathway in the mice brains. The anti-inflammatory effect of oleocanthal in the brains of these mice was also obvious where it was able to reduce astrocytes activation and IL-1β levels. Finally, we could recapitulate the observed protective effect of oleocanthal in an in vitro human-based model, which could argue against species difference in response to oleocanthal. In conclusion, findings from in vivo and in vitro studies provide further support for the protective effect of oleocanthal against the progression of AD. PMID:26348065

State transitions and physicochemical aspects of cryoprotection and stabilization in freeze-drying of Lactobacillus rhamnosus GG (LGG).

PubMed

Pehkonen, K S; Roos, Y H; Miao, S; Ross, R P; Stanton, C

2008-06-01

The frozen and dehydrated state transitions of lactose and trehalose were determined and studied as factors affecting the stability of probiotic bacteria to understand physicochemical aspects of protection against freezing and dehydration of probiotic cultures. Lactobacillus rhamnosus GG was frozen (-22 or -43 degrees C), freeze-dried and stored under controlled water vapour pressure (0%, 11%, 23% and 33% relative vapour pressure) conditions. Lactose, trehalose and their mixture (1 : 1) were used as protective media. These systems were confirmed to exhibit relatively similar state transition and water plasticization behaviour in freeze-concentrated and dehydrated states as determined by differential scanning calorimetry. Ice formation and dehydrated materials were studied using cold-stage microscopy and scanning electron microscopy. Trehalose and lactose-trehalose gave the most effective protection of cell viability as observed from colony forming units after freezing, dehydration and storage. Enhanced cell viability was observed when the freezing temperature was -43 degrees C. State transitions of protective media affect ice formation and cell viability in freeze-drying and storage. Formation of a maximally freeze-concentrated matrix with entrapped microbial cells is essential in freezing prior to freeze-drying. Freeze-drying must retain a solid amorphous state of protectant matrices. Freeze-dried matrices contain cells entrapped in the protective matrices in the freezing process. The retention of viability during storage seems to be controlled by water plasticization of the protectant matrix and possibly interactions of water with the dehydrated cells. Highest cell viability was obtained in glassy protective media. This study shows that physicochemical properties of protective media affect the stability of dehydrated cultures. Trehalose and lactose may be used in combination, which is particularly important for the stabilization of probiotic bacteria in dairy systems.

Maternal antibodies protect offspring from severe influenza infection and do not lead to detectable interference with subsequent offspring immunization.

PubMed

van der Lubbe, Joan E M; Vreugdenhil, Jessica; Damman, Sarra; Vaneman, Joost; Klap, Jaco; Goudsmit, Jaap; Radošević, Katarina; Roozendaal, Ramon

2017-06-26

Various studies have shown that infants under the age of 6 months are especially vulnerable for complications due to influenza. Currently there are no vaccines licensed for use in this age group. Vaccination of pregnant women during the last trimester, recommended by the WHO as protective measure for this vulnerable female population, may provide protection of newborns at this early age. Although it has been observed that maternal vaccination can passively transfer protection, maternal antibodies could possibly also interfere with subsequent active vaccination of the offspring. Using a mouse model, we evaluated in depth the ability of maternal influenza vaccination to protect offspring and the effect of maternal immunization on the subsequent influenza vaccination of the offspring. By varying the regimen of maternal immunization we explored the impact of different levels of maternal antibodies on the longevity of these antibodies in their progeny. We subsequently assessed to what extent maternal antibodies can mediate direct protection against influenza in their offspring, and whether these antibodies interfere with protection induced by active vaccination of the offspring. The number of immunizations of pregnant mice correlates to the level and longevity of maternal antibodies in the offspring. When these antibodies are present at time of influenza challenge they protect offspring against lethal influenza challenge, even in the absence of detectable HAI titers. Moreover, no detectable interference of passively-transferred maternal antibodies on the subsequent vaccination of the offspring was observed. In the absence of a licensed influenza vaccine for young children, vaccination of pregnant women is a promising measure to provide protection of young infants against severe influenza infection.

Protection against renal ischemia-reperfusion injury through hormesis? Dietary intervention versus cold exposure.

PubMed

Shushimita, Shushimita; Grefhorst, Aldo; Steenbergen, Jacobie; de Bruin, Ron W F; Ijzermans, Jan N M; Themmen, Axel P N; Dor, Frank J M F

2016-01-01

Dietary restriction (DR) and fasting (FA) induce robust protection against the detrimental effects of renal ischemia-reperfusion injury (I/RI). Several mechanisms of protection have been proposed, such as hormesis. Hormesis is defined as a life-supporting beneficial effect resulting from the cellular responses to single or multiple rounds of (mild) stress. The cold exposure (CE) model is a stress model similar to DR, and has been shown to have hormetic effects and has proved to increase longevity. CE is considered to be the most robust method to increase metabolism through activation of brown adipocytes. BAT has been considered important in etiology of obesity and its metabolic consequences. Since DR, FA, and CE models are proposed to work through hormesis, we investigated physiology of adipose tissue and effect on BAT in these models and compared them to ad libitum (AL) fed mice. We also studied the differential effect of these stress models on immunological changes, and effect of CE on renal I/RI. We show similar physiological changes in adiposity in male C57Bl/6 mice due to DR, FA and CE, but the CE mice were not protected against renal I/RI. The immunophenotypic changes observed in the CE mice were similar to the AL animals, in contrast to FA mice, that showed major immunophenotypic changes in the B and T cell development stages in primary and secondary lymphoid organs. Our findings thus demonstrate that DR, FA and CE are hormetic stress models. DR and FA protect against renal I/IR, whereas CE could not. Copyright © 2015 Elsevier Inc. All rights reserved.

The recent Italian Consolidation Act on privacy: new measures for data protection.

PubMed

Conti, A

2006-03-01

In the light of the new Consolidation Act on privacy, in effect since January 2004, the author has made some observations in relation to the protection of data concerning health. Special focus has been given to an overall view of the new regulations. "Sensitive data" are seen as differing from health data, while always respecting the rights, the fundamental freedom and the dignity of the person involved. A central role continues to be played by the Controller, who has regulating and control powers.

A Protection And Detection Surface (PADS) for damage tolerance

NASA Technical Reports Server (NTRS)

Shuart, M. J.; Prasad, C. B.; Biggers, S. B.

1990-01-01

A protection and detection surface (PADS) concept was studied for application to composite primary aircraft structures. A Kevlar-epoxy woven face sheet with a Rohacell foam core was found to be the most effective PADS configuration among the configurations evaluated. The weight of the PADS configuration was estimated to be approximately 17 percent of the structural weight. The PADS configuration was bonded to graphite-epoxy base laminates, and up to a 70 percent improvement in compression-after-impact failure strains was observed.

A Protection And Detection Surface (PADS) for damage tolerance

NASA Technical Reports Server (NTRS)

Shuart, Mark J.; Prasad, Chunchu B.; Biggers, Sherrill B.

1990-01-01

A protection and detection surface (PADS) concept was studied for application to composite primary aircraft structures. A Kevlar-epoxy woven face sheet with a Rohacell foam core was found to be the most effective PADS configuration among the configurations evaluated. The weight of the PADS configuration was estimated to be approximately 17 pct of the structural weight. The PADS configuration was bonded to graphite-epoxy base laminates, and up to a 70 pct improvement in compression-after-impact failure strains was observed.

Recent developments in aircraft protection systems for laser guide star operations

NASA Astrophysics Data System (ADS)

Stomski, Paul J.; Murphy, Thomas W.; Campbell, Randy

2012-07-01

The astronomical community's use of high power laser guide star adaptive optics (LGS-AO) systems presents a potential hazard to aviation. Historically, the most common and trusted means of protecting aircraft and their occupants has been the use of safety observers (aka spotters) armed with shut-off switches. These safety observers watch for aircraft at risk and terminate laser propagation before the aircraft can be adversely affected by the laser. Efforts to develop safer and more cost-effective automated aircraft protection systems for use by the astronomical community have been inhibited by both technological and regulatory challenges. This paper discusses recent developments in these two areas. Specifically, with regard to regulation and guidance we discuss the 2011 release of AS-6029 by the SAE as well as the potential impact of RTCA DO-278A. With regard to the recent developments in the technology used to protect aircraft from laser illumination, we discuss the novel Transponder Based Aircraft Detection (TBAD) system being installed at W. M. Keck Observatory (WMKO). Finally, we discuss our strategy for evaluating TBAD compliance with the regulations and for seeking appropriate approvals for LGS operations at WMKO using a fully automated, flexibly configured, multi-tier aircraft protection system incorporating this new technology.

Determination of the radioprotective effects of topical applications of MEA, WR-2721, and N-acetylcysteine on murine skin

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

Verhey, L.J.; Sedlacek, R.

1983-01-01

Topical applications of MEA (beta-mercaptoethylamine or cysteamine), WR-2721 (S-2-(3-aminopropylamino)-ethylphosphorothioic acid), and N-acetylcysteine (NAC) were tested for their ability to protect the normal skin of the hind legs of mice against acute and late damage from single doses of /sup 137/Cs radiation. No significant protection was observed with either WR-2721 or NAC. MEA was shown to offer significant protection against acute skin damage in both buffered and unbuffered forms, but no significant protection against late contraction. The use of topical MEA on unanesthetized animals breathing carbogen (95% O2, 5% CO2) appears to give an enhanced level of radioprotection over that shownmore » for anesthetized, air-breathing animals.« less

Protect sensitive data with lightweight memory encryption

NASA Astrophysics Data System (ADS)

Zhou, Hongwei; Yuan, Jinhui; Xiao, Rui; Zhang, Kai; Sun, Jingyao

2018-04-01

Since current commercial processor is not able to deal with the data in the cipher text, the sensitive data have to be exposed in the memory. It leaves a window for the adversary. To protect the sensitive data, a direct idea is to encrypt the data when the processor does not access them. On the observation, we have developed a lightweight memory encryption, called LeMe, to protect the sensitive data in the application. LeMe marks the sensitive data in the memory with the page table entry, and encrypts the data in their free time. LeMe is built on the Linux with a 3.17.6 kernel, and provides four user interfaces as dynamic link library. Our evaluations show LeMe is effective to protect the sensitive data and incurs an acceptable performance overhead.

Appearance matters: the frame and focus of health messages influences beliefs about skin cancer.

PubMed

Thomas, Kevin; Hevey, David; Pertl, Maria; Ní Chuinneagáin, Siobhán; Craig, Agnella; Maher, Laura

2011-05-01

This study sought to ascertain whether the health message 'framing effect', which has been observed for several diseases, occurs for messages concerning the consequences of skin cancer for one's appearance or one's health. Specifically, the effect of the frame and focus of health messages on intentions to perform skin protection behaviours and the perceived threat of skin cancer was investigated. Consistent with previous research and to avoid carry-over effects, a two-factor, between-groups (message frame: gain vs. loss × message focus: appearance vs. health) design was used. Participants (N= 390) were recruited using convenience sampling and presented with one of four health messages, which were embedded in a questionnaire concerning beliefs about skin cancer (intentions to perform different skin protection behaviours, the perceived threat of skin cancer) and body consciousness. The health messages were framed in terms of loss (risks of sun exposure) or gain (benefits of skin protection) and focused on the consequences of sun exposure for one's appearance or one's health. The primary outcome measures were responses on rating scales concerning the perceived threat of skin cancer, intentions to perform different skin cancer protection behaviours, and body consciousness. Perceived threat of skin cancer was found to be greater for appearance-focused messages and intentions to perform different skin protection behaviours were greater for loss-framed messages. These findings held when individual differences in body consciousness were controlled for. These findings suggest that, for the communication of information about skin cancer to be effective, messages must focus on the impact of sun exposure and inadequate skin protection for people's appearance, not just their health. Moreover, to maximize effectiveness, health messages about skin cancer should take account of dispositional differences in the importance placed upon one's appearance. ©2010 The British Psychological Society.

Evidence of the rapid protective effect of formoterol dry-powder inhalation against exercise-induced bronchospasm in athletes with asthma.

PubMed

Ferrari, M; Balestreri, F; Baratieri, S; Biasin, C; Oldani, V; Lo Cascio, V

2000-01-01

Although formoterol, a new long-acting beta(2)-adrenergic agonist, has a rapid bronchodilating action, no studies have previously examined whether it can provide equally rapid protection against exercise-induced bronchospasm (EIB). The aim of the study was to assess the effect of inhaled formoterol against EIB 15 min and 4 h after administration in asthmatic athletes. The protective effect of a formoterol (12 microg) dry-powder inhalation was evaluated in 14 EIB-positive asthmatic athletes (13 males, mean age 16.8 years), in a double-blind, placebo-controlled, two-period cross-over study. On each treatment day, the subjects underwent two cycloergometric exercise tests 15 min and 4 h after receiving formoterol or placebo. Formoterol induced significant bronchodilation in comparison with placebo both 15 min and 4 h after administration (p = 0.007 and p = 0.004); placebo treatment had no effect on EIB, the maximum percent fall in FEV(1) after exercise being 29.3 +/- 14.3% and 22.9 +/- 13. 7% at 15 min and 4 h, respectively. Formoterol offered good protection against EIB in 12 athletes (86%) who experienced a decrease in FEV(1) after exercise <10% both 15 min and 4 h after administration. The mean maximum percent fall in FEV(1) after formoterol was 5.9+/-7.2% at 15 min (p < 0.0001), and 5.8 +/- 6.9% at 4 h (p < 0.0001). There was no statistically significant difference in resting heart rate before and after medication with placebo or formoterol, nor was the heart rate at the end of exercise significantly different on the 2 treatment days. No side effect was observed in either group. This study demonstrates that formoterol dry powder inhalation is effective in protecting asthmatic athletes as early as 15 min after dosing. Furthermore, the data confirm the long duration of its protective effect and the absence of any significant adverse effects after acute administration. Copyright 2000 S. Karger AG, Basel

The principal phenolic and alcoholic components of wine protect human lymphocytes against hydrogen peroxide- and ionizing radiation-induced DNA damage in vitro.

PubMed

Greenrod, William; Fenech, Michael

2003-03-01

We have tested the hypothesis that the alcoholic and phenolic components of wine are protective against the DNA-damaging and cytotoxic effects of hydrogen peroxide and gamma-radiation in vitro. The components of wine tested were ethanol, glycerol, a mixture of the phenolic compounds catechin and caffeic acid and tartaric acid, all at concentrations that were 2.5 or 10.0% of the concentration in a typical Australian white wine (Riesling). These components were tested individually or combined as a mixture and compared to a white wine stripped of polyphenols, as well as a Hanks balanced salt solution control, which was the diluent for the wine components. The effect of the components was tested in lymphocytes, using the cytokinesis-block micronucleus assay, after 30 min incubation in plasma or whole blood for the hydrogen peroxide or gamma-radiation challenge, respectively. The results obtained showed that ethanol, glycerol, the catechin-caffeic acid mixture, the mixture of all components and the stripped white wine significantly reduced the DNA-damaging effects of hydrogen peroxide and gamma-radiation (P = 0.043-0.001, ANOVA). The strongest protective effect against DNA damage by gamma-irradiation was observed for the catechin-caffeic acid mixture and the mixture of all components (30 and 32% reduction, respectively). These two treatments as well as ethanol produced the strongest protective effects against DNA damage by hydrogen peroxide (24, 25 and 18%, respectively). The protection provided by the mixture did not account for the expected additive protective effects of the individual components. Ethanol was the only component that significantly increased baseline DNA damage rate, however, this effect was negated in the mixture. In conclusion, our results suggest that the main phenolic and alcoholic components of wine can reduce the DNA-damaging effects of two important oxidants, i.e. hydrogen peroxide and ionizing radiation, in this physiologically relevant in vitro system.

GENERATING PARTICIPANT SPECIFIC FIGURES USING SAS GRAPHIC PROCEDURES

EPA Science Inventory

An important part of our research at the U.S. Environmental Protection Agency (EPA) is to effectively communicate the results from observational studies to the study participants. This can be particularly challenging where participants are from different socio-economic background...

Protective effects of Petroselinum crispum (Mill) Nyman ex A. W. Hill leaf extract on D-galactose-induced oxidative stress in mouse brain.

PubMed

Vora, Shreya R; Patil, Rahul B; Pillai, Meena M

2009-05-01

With an aim to examine the effect of ethanolic extract of P. crispum (Parsley) leaves on the D-galactose-induced oxidative stress in the brain of mouse, the activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) involved in oxygen radical (OR)-detoxification and antiperoxidative defense were measured in conjunction with an index of lipid peroxidation in mitochondrial fraction of various regions of the mouse brain. A significant decrease in superoxide dismutase and glutathione peroxidase activity was observed in D-galactose-stressed mice, while catalase activity was increased. Treatment of D-galactose-stressed mice with the ethanolic extract of P. crispum showed protection against the induced oxidative stress in brain regions. Concentration of thiobarbituric acid-reactive product was greatly elevated in D-galactose stress-induced mice and was significantly reduced in the brain regions of these mice upon treatment with P. crispum. It is postulated that parsley shows a protective effect against mitochondrial oxidative damage in the mouse brain.

Protection of Arabidopsis thaliana against Leaf-Pathogenic Pseudomonas syringae by Sphingomonas Strains in a Controlled Model System ▿ †

PubMed Central

Innerebner, Gerd; Knief, Claudia; Vorholt, Julia A.

2011-01-01

Diverse bacterial taxa live in association with plants without causing deleterious effects. Previous analyses of phyllosphere communities revealed the predominance of few bacterial genera on healthy dicotyl plants, provoking the question of whether these commensals play a particular role in plant protection. Here, we tested two of them, Methylobacterium and Sphingomonas, with respect to their ability to diminish disease symptom formation and the proliferation of the foliar plant pathogen Pseudomonas syringae pv. tomato DC3000 on Arabidopsis thaliana. Plants were grown under gnotobiotic conditions in the absence or presence of the potential antagonists and then challenged with the pathogen. No effect of Methylobacterium strains on disease development was observed. However, members of the genus Sphingomonas showed a striking plant-protective effect by suppressing disease symptoms and diminishing pathogen growth. A survey of different Sphingomonas strains revealed that most plant isolates protected A. thaliana plants from developing severe disease symptoms. This was not true for Sphingomonas strains isolated from air, dust, or water, even when they reached cell densities in the phyllosphere comparable to those of the plant isolates. This suggests that plant protection is common among plant-colonizing Sphingomonas spp. but is not a general trait conserved within the genus Sphingomonas. The carbon source profiling of representative isolates revealed differences between protecting and nonprotecting strains, suggesting that substrate competition plays a role in plant protection by Sphingomonas. However, other mechanisms cannot be excluded at this time. In conclusion, the ability to protect plants as shown here in a model system may be an unexplored, common trait of indigenous Sphingomonas spp. and may be of relevance under natural conditions. PMID:21421777

Rodent malaria: BCG-induced protection and immunosuppression. [Mice, gamma radiation, Plasmodium berghei

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

Smrkovski, L.L.; Strickland, G.T.

1978-10-01

One dose of 10/sup 7/ viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10/sup 4/ thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites onlymore » if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge.« less

Use of protective equipment by in-line skaters: an observational study

PubMed Central

Beirness, D; Foss, R; Desmond, K

2001-01-01

Objective—To determine the extent of protective equipment use (that is, helmets, wrist guards, elbow pads, knee pads) in a representative sample of in-line skaters. Setting—Fifteen municipalities throughout the province of British Columbia. Method—A province-wide observational survey was conducted in the summer of 1999. Skaters were observed at four types of sites (commuter, recreational, neighbourhood, general community) in 15 municipalities to provide a representative sample of in-line skaters. Results—The observed use of protective equipment by the 877 in-line skaters was relatively low: wrist guards 25%, helmets 13%, elbow pads 14%, and knee pads 10%. Conclusion—Despite the availability of relatively inexpensive protective equipment, few in-line skaters take advantage of the opportunity to protect themselves from injury. Policies and programs that serve to increase the use of protective equipment by in-line skaters are needed to help reduce the frequency of skating related injuries. PMID:11289536

Epigallocatechin-3-Gallate Reduces Neuronal Apoptosis in Rats after Middle Cerebral Artery Occlusion Injury via PI3K/AKT/eNOS Signaling Pathway

PubMed Central

Zhonghang, Xu; Tongtong, Liu; Wanshu, Guo

2018-01-01

Background/Aims Epigallocatechin-3-gallate (EGCG) has neuroprotective effects and the ability to resist amyloidosis. This study observed the protective effect of EGCG against neuronal injury in rat models of middle cerebral artery occlusion (MCAO) and investigated the mechanism of action of PI3K/AKT/eNOS signaling pathway. Methods Rat models of permanent MCAO were established using the suture method. Rat behavior was measured using neurological deficit score. Pathology and apoptosis were measured using HE staining and TUNEL. Oxidative stress and brain injury markers were examined using ELISA. Apoptosis-related proteins and PI3K/AKT/eNOS signaling pathway were determined using western blot assay and immunohistochemistry. Results EGCG decreased neurological function score, protected nerve cells, inhibited neuronal apoptosis, and inhibited oxidative stress injury and brain injury markers level after MCAO. EGCG reduced the apoptotic rate of neurons, increased the expression of Bcl-2, and decreased the expression of Caspase-3 and Bax. After LY294002 suppressed the PI3K pathway, the protective effect of EGCG decreased after administration of PI3K inhibitors. Conclusion EGCG has a protective effect on rat brain injury induced by MCAO, possibly by modulating the PI3K/AKT/eNOS signaling pathway. PMID:29770336

Protective Role of Dietary Berries in Cancer

PubMed Central

Kristo, Aleksandra S.; Klimis-Zacas, Dorothy; Sikalidis, Angelos K.

2016-01-01

Dietary patterns, including regular consumption of particular foods such as berries as well as bioactive compounds, may confer specific molecular and cellular protection in addition to the overall epidemiologically observed benefits of plant food consumption (lower rates of obesity and chronic disease risk), further enhancing health. Mounting evidence reports a variety of health benefits of berry fruits that are usually attributed to their non-nutritive bioactive compounds, mainly phenolic substances such as flavonoids or anthocyanins. Although it is still unclear which particular constituents are responsible for the extended health benefits, it appears that whole berry consumption generally confers some anti-oxidant and anti-inflammatory protection to humans and animals. With regards to cancer, studies have reported beneficial effects of berries or their constituents including attenuation of inflammation, inhibition of angiogenesis, protection from DNA damage, as well as effects on apoptosis or proliferation rates of malignant cells. Berries extend effects on the proliferation rates of both premalignant and malignant cells. Their effect on premalignant cells is important for their ability to cause premalignant lesions to regress both in animals and in humans. The present review focuses primarily on in vivo and human dietary studies of various berry fruits and discusses whether regular dietary intake of berries can prevent cancer initiation and delay progression in humans or ameliorate patients’ cancer status. PMID:27775562

Protective Role of Dietary Berries in Cancer.

PubMed

Kristo, Aleksandra S; Klimis-Zacas, Dorothy; Sikalidis, Angelos K

2016-10-19

Dietary patterns, including regular consumption of particular foods such as berries as well as bioactive compounds, may confer specific molecular and cellular protection in addition to the overall epidemiologically observed benefits of plant food consumption (lower rates of obesity and chronic disease risk), further enhancing health. Mounting evidence reports a variety of health benefits of berry fruits that are usually attributed to their non-nutritive bioactive compounds, mainly phenolic substances such as flavonoids or anthocyanins. Although it is still unclear which particular constituents are responsible for the extended health benefits, it appears that whole berry consumption generally confers some anti-oxidant and anti-inflammatory protection to humans and animals. With regards to cancer, studies have reported beneficial effects of berries or their constituents including attenuation of inflammation, inhibition of angiogenesis, protection from DNA damage, as well as effects on apoptosis or proliferation rates of malignant cells. Berries extend effects on the proliferation rates of both premalignant and malignant cells. Their effect on premalignant cells is important for their ability to cause premalignant lesions to regress both in animals and in humans. The present review focuses primarily on in vivo and human dietary studies of various berry fruits and discusses whether regular dietary intake of berries can prevent cancer initiation and delay progression in humans or ameliorate patients' cancer status.

Investigation of Effectiveness of Air-Heating a Hollow Steel Propeller for Protection Against Icing. 2: 50% Impartitioned Blades

NASA Technical Reports Server (NTRS)

Perkins, Porter J.; Mulholland, Donald R.

1948-01-01

The icing protection afforded an internal air-heated propeller blade by radial partitioning at 50-percent chord to confine the heated air to the forward half of the blade was determined in the NACA Cleveland icing research tunnel. A modified production-model hollow steel propeller, was used for the investigation. Temperatures of the blade surfaces for several heating rates were measured under various tunnel Icing' conditions. Photographic observations of ice formations on blade surfaces and blade heat-exchanger effectiveness were obtained. With 50-percent partitioning of the blades, adequate icing protection at 1050 rpm was obtained with a heating rate of 26,000 Btu per hour per blade at the blade shank using an air temperature of 400 F with a flow rate of 280 pounds per hour per blade, which is one-third less heat than was found necessary for similar Ice protection with unpartitioned blades. The chordwise distribution of the applied heat, as determined by surface temperature measurements, was considered unsatisfactory with much of the heat dissipated well back of the leading edge. Heat-exchanger effectiveness of approximately 56 percent also Indicated poor utilization of available heat. This effectiveness was, however, 9 percent greater than that obtained from unpartitioned blades.

Protective Effects of Extracellular and Intracellular Polysaccharides on Hepatotoxicity by Hericium erinaceus SG-02.

PubMed

Cui, Fangyuan; Gao, Xia; Zhang, Jianjun; Liu, Min; Zhang, Chen; Xu, Nuo; Zhao, Huajie; Lin, Lin; Zhou, Meng; Jia, Le

2016-09-01

The protective effects of extracellular and intracellular polysaccharides from Hericium erinaceus SG-02 on the CCl4-induced hepatic injury of mice were investigated in this work. By the analysis of GC, the extracellular polysaccharides (EPS) were composed of arabinose, mannose, galactose, and glucose with a ratio of 1:7:14:52, and the composition of intracellular polysaccharides (IPS) was rhamnose, xylose, mannose, galactose, and glucose with a ratio of 3:4:7:14:137. The model of hepatic injury of mice was induced by CCl4 and three tested levels (200, 400, and 800 mg/kg) of EPS and IPS were set as the experimental group. Results showed that the aspartate aminotransferase and glutamic pyruvic transaminase activities in serum were reduced by the supplement of EPS and IPS, while the blood lipid levels including cholesterol, triglyceride, and albumin were improved. In liver tissue, the lipid peroxidation and malondialdehyde were largely decreased, and the superoxide dismutase and catalase activities were significantly increased. The evidence demonstrated that the EPS and IPS of H. erinaceus SG-02 were protective for liver injury. The histopathological observations of mice liver slices indicated that EPS and IPS had obvious effects on liver protection.

Assessing different measures of population-level vaccine protection using a case-control study.

PubMed

Ali, Mohammad; You, Young Ae; Kanungo, Suman; Manna, Byomkesh; Deen, Jacqueline L; Lopez, Anna Lena; Wierzba, Thomas F; Bhattacharya, Sujit K; Sur, Dipika; Clemens, John D

2015-11-27

Case-control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials. We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case-control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding "virtual" cluster. Specific selection strategies were used to evaluate the vaccine protective effects. 66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47-91%) protection in a cohort analysis and 84% (95% CI: 60-94%) in case-control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10-74%) in cohort and 76% (95% CI: 47-89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case-control analyses. The findings show that case-control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection. Copyright © 2015. Published by Elsevier Ltd.

Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity.

PubMed

Tristão, Vivian Regina; Pessoa, Edson A; Nakamichi, Renata; Reis, Luciana A; Batista, Marcelo Costa; Durão Junior, Marcelino de Souza; Monte, Júlio Cesar Martins

2016-01-01

Necroptosis is a nonapoptotic cell death pathway. We aim to study the effect of necrostatin-1 (a specific necroptosis inhibitor) in cisplatin-induced injury. We analyzed the effect of the combined use of inhibitors of apoptosis (z-vad) and necroptosis (necrostatin-1) in acute kidney injury by cisplatin in human proximal tubule cells. Our results showed moderate effectiveness in cytoprotection after treatment with z-vad. But the concomitant use of inhibitors (z-vad and necrostatin-1) presented synergistic and additive protection. The present study analyzed the caspase-3 activity and we observed a significant decrease in the group treated with z-vad and cisplatin. However we did not observe changes in the group treated with both inhibitors (z-vad and necrostatin-1) and cisplatin. Thus, demonstrating that necroptosis is a caspase-independent mechanism. We also analyzed the effect of necrostatin-1 in vivo model. C57BL/6 mice were treated with cisplatin and/or inhibitors. The concomitant use of inhibitors (z-vad and necrostatin-1) recovered renal function and decreased levels of urinary Ngal. Additionally, we analyzed the expression of RIP-1, a specific marker for necroptosis. In animals treated with cisplatin and z-VAD levels of RIP-1 were higher. This result reinforces that necroptosis occurs only in conditions where apoptosis was blocked. However, the use of both inhibitors (z-vad and necrostatin-1) provided additional protection. In conclusion, our study has a significant potential to show in vitro and in vivo protection obtained by necrostatin-1. Therefore, our results suggest that necroptosis may be an important mechanism of cell death after kidney injury.

Effect of Priming with H1N1 Influenza Viruses of Variable Antigenic Distances on Challenge with 2009 Pandemic H1N1 Virus

PubMed Central

O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice N.; Wei, Chih-Jen; Nabel, Gary J.

2012-01-01

Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic. PMID:22674976

Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus.

PubMed

O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice N; Wei, Chih-Jen; Nabel, Gary J; Subbarao, Kanta

2012-08-01

Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.

Dissemination of go sun smart in outdoor recreation: effect of program exposure on sun protection of guests at high-altitude ski areas.

PubMed

Walkosz, Barbara J; Buller, David B; Andersen, Peter A; Scott, Michael D; Dignan, Mark B; Cutter, Gary R; Liu, Xia; Maloy, Julie A

2014-09-01

Go Sun Smart is a theory-based health communication program designed to influence sun-protection behaviors of employees and guests at high-altitude ski areas to reduce skin cancer risk. The effects of Go Sun Smart, in a Phase IV dissemination randomized posttest-only trial, on sun-protection behaviors of ski area guests are reported. Program use was assessed by on-site observation and guest message exposure, and sun protection was measured in intercept surveys at ski areas. Dissemination strategy-enhanced versus basic-was not significantly related to sun safety practices. Additional analyses examined the relation between message exposure and guests' sun safety practices. Ski areas displaying at least 6 Go Sun Smart materials in guest-only areas and 9 Go Sun Smart materials throughout the area increased guests' message exposure. Higher message exposure within the high-use ski areas was associated with improved sun protection by guests but not within the low-use ski areas. The authors underscore the importance of program implementation and message exposure on the success of evidence-based health communication efforts applied industrywide.

Nuclear aggregates of polyamines in a radiation-induced DNA damage model.

PubMed

Iacomino, Giuseppe; Picariello, Gianluca; Stillitano, Ilaria; D'Agostino, Luciano

2014-02-01

Polyamines (PA) are believed to protect DNA minimizing the effect of radiation damage either by inducing DNA compaction and aggregation or acting as scavengers of free radicals. Using an in vitro pDNA double strand breakage assay based on gel electrophoretic mobility, we compared the protective capability of PA against γ-radiation with that of compounds generated by the supramolecular self-assembly of nuclear polyamines and phosphates, named Nuclear Aggregates of Polyamines (NAPs). Both unassembled PA and in vitro produced NAPs (ivNAPs) were ineffective in conferring pDNA protection at the sub-mM concentration. Single PA showed an appreciable protective effect only at high (mM) concentrations. However, concentrations of spermine (4+) within a critical range (0.481 mM) induced pDNA precipitation, an event that was not observed with NAPs-pDNA interaction. We conclude that the interaction of individual PA is ineffective to assure DNA protection, simultaneously preserving the flexibility and charge density of the double strand. Furthermore, data obtained by testing polyamine and ivNAPS with the current radiation-induced DNA damage model support the concept that PA-phosphate aggregates are the only forms through which PA interact with DNA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Stress-induced thermotolerance of ventilatory motor pattern generation in the locust, Locusta migratoria.

PubMed

Newman, Amy E M; Foerster, Melody; Shoemaker, Kelly L; Robertson, R Meldrum

2003-11-01

Ventilation is a crucial motor activity that provides organisms with an adequate circulation of respiratory gases. For animals that exist in harsh environments, an important goal is to protect ventilation under extreme conditions. Heat shock, anoxia, and cold shock are environmental stresses that have previously been shown to trigger protective responses. We used the locust to examine stress-induced thermotolerance by monitoring the ability of the central nervous system to generate ventilatory motor patterns during a subsequent heat exposure. Preparations from pre-stressed animals had an increased incidence of motor pattern recovery following heat-induced failure, however, prior stress did not alter the characteristics of the ventilatory motor pattern. During constant heat exposure at sub-lethal temperatures, we observed a protective effect of heat shock pre-treatment. Serotonin application had similar effects on motor patterns when compared to prior heat shock. These studies are consistent with previous studies that indicate prior exposure to extreme temperatures and hypoxia can protect neural operation against high temperature stress. They further suggest that the protective mechanism is a time-dependent process best revealed during prolonged exposure to extreme temperatures and is mediated by a neuromodulator such as serotonin.

Advax-Adjuvanted Recombinant Protective Antigen Provides Protection against Inhalational Anthrax That Is Further Enhanced by Addition of Murabutide Adjuvant

PubMed Central

Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita

2014-01-01

Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy. PMID:24554695

Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

PubMed

Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Merkel, Tod J

2014-04-01

Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

Exterior spacecraft subsystem protective shielding analysis and design

NASA Technical Reports Server (NTRS)

Schonberg, William P.; Taylor, Roy A.

1990-01-01

All spacecraft are susceptible to impacts by meteoroids and pieces of orbiting space debris. An effective mechanism is developed to protect external spacecraft subsystems against damage by ricochet particles formed during such impacts. Equations and design procedures for protective shield panels are developed based on observed ricochet phenomena and calculated ricochet particle sizes and speeds. It is found that the diameter of the most damaging ricochet debris particle can be as large as 40 percent of the original project tile diameter, and can travel at speeds between 24 and 36 percent of the original projectile impact velocity. Panel dimensions are shown to be strongly dependent on their inclination to the impact velocity vector and on their distribution around a spacecraft module. It is concluded that obliquity effects of high-speed impacts must be considered in the design of any structure exposed to the meteoroid and space debris environment.

Acorus tatarinowii Schott extract protects PC12 cells from amyloid-beta induced neurotoxicity.

PubMed

An, Hong-Mei; Li, Guo-Wen; Lin, Chen; Gu, Chao; Jin, Miao; Sun, Wen-Xian; Qiu, Ming-Feng; Hu, Bing

2014-05-01

Amyloid-beta induced neurotoxicity has been identified as a major cause of Alzheimer's disease. Acorus tatarinowii Schott is one of the most frequently used Chinese herbs for Alzheimer's disease treatment. However, the effects of Acorus tatarinowii Schott on amyloid-beta mediated nerve cell damage remains unknown. In the present study, neuronal differentiated PC12 cells were used as a model to evaluate the effects of A. tatarinowii Schott extract (ATSE) against Abeta25-35 induced neurotoxicity. The results showed pretreatment with ATSE significantly protected PC12 cells from Abeta25-35 induced cell death, lactate dehydrogenase release, DNA damage, mitochondrial dysfunction and cytochrome c release from mitochondria. In addition, pretreatment with ATSE also significantly inhibited Abeta25-35 induced caspase-3 activation and reactive oxygen species generation in PC12 cells. These observations suggested that ATSE protects PC12 cells from amyloid-beta induced neurotoxicity.

Freeze-drying of silica nanoparticles: redispersibility toward nanomedicine applications.

PubMed

Picco, Agustin S; Ferreira, Larissa F; Liberato, Michelle S; Mondo, Gabriela B; Cardoso, Mateus B

2018-01-01

To study freeze-drying of silica nanoparticles (SiO 2 NPs) in order to find suitable conditions to produce lyophilized powders with no aggregation after resuspension and storage. SiO 2 NPs were synthesized using a Stöber-based procedure, and characterized by scanning electron microscopy, dynamic light scattering and nitrogen adsorption/desorption isotherms. SiO 2 NPs hydrodynamic diameters were compared prior and after freeze-drying in the presence/absence of carbohydrate protectants. Glucose was found to be the most suitable protectant against the detrimental effects of lyophilization. The minimum concentration of carbohydrate required to effectively protect SiO 2 NPs from aggregation during freeze-drying is influenced by the nanoparticle's size and texture. Negligible aggregation was observed during storage. Carbohydrates can be used during SiO 2 NPs freeze-drying process to obtain redispersable solids that maintain original sizes without residual aggregation.

Correlates of sun protection behaviors among Hispanic children residing in a high UVR environment.

PubMed

Miller, Kimberly A; Huh, Jimi; Unger, Jennifer B; Richardson, Jean L; Allen, Martin W; Peng, David H; Cockburn, Myles G

2017-03-01

Rates of melanoma are rising in Hispanics in the United States. Excessive sun exposure in childhood increases the risk of melanoma in adulthood, and little is known about the factors motivating sun protection behaviors among Hispanic youth. Correlates of sun protection were examined among Hispanic children residing in Los Angeles, California (N = 1891). Associations between multiple constructs (psychosocial, familial, and cultural) and sun protection outcomes (use of sunscreen, protective clothing, and shade seeking/sun avoidance) were examined. Family variables were associated with more frequent sun protection among Hispanic children across outcomes, as were perceived peer norms, perceived self-efficacy, and fewer sun protection barriers. Skin cancer risk factors such as lighter skin and sunburn experience, and level of acculturation were not associated with greater sun protection. Family sun protection habits are instrumental to Hispanic children's sun safe behaviors, and interventions that engage the family may be most effective. Increasing risk communication to high-risk subgroups of Hispanic children (those with lighter, more sun reactive skin) is important when developing intervention strategies. However, there is overlap between Hispanic children's sun protection correlates and those observed among non-Hispanic white children, suggesting that interventions to improve sun protection may generalize across cultural contexts. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Protective effect of carbachol postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells.

PubMed

Han, Hongxia; Yang, Jun; Fei, Sujuan; Liu, Zhangbo; Zhu, Shengping; Dong, Qiuju; Gao, Zhifeng; Wang, Shihui; Zhang, Jianfu

2016-01-01

We investigated the protective effects of carbachol postconditioning (CAR-P) on acute gastric mucosal injury induced by hypoxia/reoxygenation (H/R) and its possible mechanisms. Cell viability was detected by methyl thiazolyl tetrazolium (MTT). The apoptotic cells were examined by Hoechst 33258 staining. Flow cytometric analysis, lactate dehydrogenate (LDH) release assay, immunocytochemistry, and western blotting were used to investigate the effects of CAR-P on acute gastric mucosal injury induced by H/R. The model of H/R was established by hypoxia induction(94% N2+1% O2+5% CO2 for 2 h) and reoxygenation (normoxic condition for 4 h, 8 h and 16 h). Our study observed the protective effect of carbachol postconditioning on H/R-induced injury in human gastric epithelial cell lines (hGES-1) cells, which is achieved by direct activation of vanilloid receptor subtype 1 (VR1) and production of calcitonin gene-related peptide (CGRP), and in the inhibition of cell apoptosis. In the study, we demonstrate that CAR-P has protective effects on the H/R-induced injury in hGES-1 cells, and these effects are associated with cholinergic muscarinic receptors (CMR), VR1, and extracellular signal-regulated kinase (ERK) signaling pathway. Our findings might provide a new and improved understanding of CAR-P function and an effective treatment strategy for acute gastric mucosal injury induced by H/R. Copyright © 2015 Elsevier Inc. All rights reserved.

The test about blood serum capabilities in maintaining the quality of bull spermatozoa during storage in cep diluent at refrigerator temperature

NASA Astrophysics Data System (ADS)

Ducha, Nur

2018-03-01

The storage of spermatozoa requires a protective material from cold shock events and the presence of free radicals.In CEP diluent contain BSA, that was used as spermatozoa protection. This study aim was to examine the ability of cow blood serum in replacing BSA as spermatozoa protective in CEP diluent. Fresh semen from Limousin bull was diluted with CEP diluent + BSA as control, in the treatment group were CEP without BSA, but replaced with 3%, 5%, and 7% serum from fresh blood. Spermatozoa quality tests included motility and viability. The motility of spermatozoa was observed by two people using a light microscope with 200 X magnification at temperature of 37°C. The method of viability observation was eosin nigrosin staining, and observed under a light microscope with 400 X magnification. The results showed that the replacement of cow blood serum with various concentrations gave different effects on the quality of spermatozoa. The best motility and viability of the treatment group was at serum concentrations of 5% after eight days storage and was not significantly different from the controls. The conclusion in this study was cow blood serum can replace BSA in CEP diluents.

Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

PubMed Central

Silva-Pereira, Liz Carmem; da Rocha, Carlos Alberto Machado; Cunha, Luiz Raimundo Campos da Silva e; da Costa, Edmar Tavares; Guimarães, Ana Paula Araújo; Pontes, Thais Brilhante; Diniz, Domingos Luiz Wanderley Picanço; Leal, Mariana Ferreira; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodríguez

2014-01-01

Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg. PMID:25247425

Coffee, tea, caffeine and risk of depression: A systematic review and dose-response meta-analysis of observational studies.

PubMed

Grosso, Giuseppe; Micek, Agnieszka; Castellano, Sabrina; Pajak, Andzrej; Galvano, Fabio

2016-01-01

The aim of the study was to systematically review and analyze results from observational studies on coffee, caffeine, and tea consumption and association or risk of depression. Embase and PubMed databases were searched from inception to June 2015 for observational studies reporting the odds ratios or relative risks (RRs) and 95% confidence intervals (CI) of depression by coffee/tea/caffeine consumption. Random effects models, subgroup analyses, and dose-response analyses were performed. Twelve studies with 23 datasets were included in the meta-analysis, accounting for a total of 346 913 individuals and 8146 cases of depression. Compared to individuals with lower coffee consumption, those with higher intakes had pooled RR of depression of 0.76 (95% CI: 0.64, 0.91). Dose-response effect suggests a nonlinear J-shaped relation between coffee consumption and risk of depression with a peak of protective effect for 400 mL/day. A borderline nonsignificant association between tea consumption and risk of depression was found (RR 0.70, 95% CI: 0.48, 1.01), while significant results were found only for analysis of prospective studies regarding caffeine consumption (RR = 0.84, 95% CI: 0.75, 0.93). This study suggests a protective effect of coffee and, partially, of tea and caffeine on risk of depression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lifestyle factors and risk of leukemia and non-Hodgkin's lymphoma: a case-control study.

PubMed

Parodi, Stefano; Santi, Irene; Marani, Enza; Casella, Claudia; Puppo, Antonella; Garrone, Elsa; Fontana, Vincenzo; Stagnaro, Emanuele

2016-03-01

Risk factors for leukemia and lymphomas in adults are largely unknown. This study was aimed at evaluating the association between lifestyle factors and the risk of hematological malignancies in an adult population. Data were drawn from a population-based case-control study carried out in Italy and included 294 cases (199 lymphoid and 95 myeloid) and 279 controls. Analyses were performed using standard multivariable logistic regression. Hair dye use for at least 15 years was associated with a higher risk of lymphoid malignancies among females (OR 2.3, 95 % CI 1.0-4.9, p = 0.036, test for trend). Furthermore, a protective effect of a moderate to heavy tea consumption on the risk of myeloid malignancies was observed (OR 0.4, 95 % CI 0.2-0.9, p = 0.017). No association was found for the use of alcoholic beverages and tobacco smoking. Our results confirm the potential carcinogenic effect of prolonged hair dye use observed in previous investigations. The excess risk could be explained by exposure to a higher concentration of toxic compounds in hair products used in the past. The protective effect of regular tea consumption observed in an area with a very high prevalence of black tea consumers deserves further investigation.

Dispelling urban myths about default uncertainty factors in chemical risk assessment – sufficient protection against mixture effects?

PubMed Central

2013-01-01

Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. PMID:23816180

Dispelling urban myths about default uncertainty factors in chemical risk assessment--sufficient protection against mixture effects?

PubMed

Martin, Olwenn V; Martin, Scholze; Kortenkamp, Andreas

2013-07-01

Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment.

Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination.

PubMed

Defaux, Antoinette; Zurich, Marie-Gabrielle; Braissant, Olivier; Honegger, Paul; Monnet-Tschudi, Florianne

2009-05-07

Brain inflammation plays a central role in numerous brain pathologies, including multiple sclerosis (MS). Microglial cells and astrocytes are the effector cells of neuroinflammation. They can be activated also by agents such as interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Peroxisome proliferator-associated receptor (PPAR) pathways are involved in the control of the inflammatory processes, and PPAR-beta seems to play an important role in the regulation of central inflammation. In addition, PPAR-beta agonists were shown to have trophic effects on oligodendrocytes in vitro, and to confer partial protection in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the present work, a three-dimensional brain cell culture system was used as in vitro model to study antibody-induced demyelination and inflammatory responses. GW 501516, a specific PPAR-beta agonist, was examined for its capacity to protect from antibody-mediated demyelination and to prevent inflammatory responses induced by IFN-gamma and LPS. Aggregating brain cells cultures were prepared from embryonal rat brain, and used to study the inflammatory responses triggered by IFN-gamma and LPS and by antibody-mediated demyelination induced by antibodies directed against myelin-oligodendrocyte glycoprotein (MOG). The effects of GW 501516 on cellular responses were characterized by the quantification of the mRNA expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), inducible NO synthase (i-NOS), PPAR-beta, PPAR-gamma, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and high molecular weight neurofilament protein (NF-H). GFAP expression was also examined by immunocytochemistry, and microglial cells were visualized by isolectin B4 (IB4) and ED1 labeling. GW 501516 decreased the IFN-gamma-induced up-regulation of TNF-alpha and iNOS in accord with the proposed anti-inflammatory effects of this PPAR-beta agonist. However, it increased IL-6 m-RNA expression. In demyelinating cultures, reactivity of both microglial cells and astrocytes was observed, while the expression of the inflammatory cytokines and iNOS remained unaffected. Furthermore, GW 501516 did not protect against the demyelination-induced changes in gene expression. Although GW 501516 showed anti-inflammatory activity, it did not protect against antibody-mediated demyelination. This suggests that the protective effects of PPAR-beta agonists observed in vivo can be attributed to their anti-inflammatory properties rather than to a direct protective or trophic effect on oligodendrocytes.

Effects of the PPAR-β agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination

PubMed Central

Defaux, Antoinette; Zurich, Marie-Gabrielle; Braissant, Olivier; Honegger, Paul; Monnet-Tschudi, Florianne

2009-01-01

Background Brain inflammation plays a central role in numerous brain pathologies, including multiple sclerosis (MS). Microglial cells and astrocytes are the effector cells of neuroinflammation. They can be activated also by agents such as interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Peroxisome proliferator-associated receptor (PPAR) pathways are involved in the control of the inflammatory processes, and PPAR-β seems to play an important role in the regulation of central inflammation. In addition, PPAR-β agonists were shown to have trophic effects on oligodendrocytes in vitro, and to confer partial protection in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the present work, a three-dimensional brain cell culture system was used as in vitro model to study antibody-induced demyelination and inflammatory responses. GW 501516, a specific PPAR-β agonist, was examined for its capacity to protect from antibody-mediated demyelination and to prevent inflammatory responses induced by IFN-γ and LPS. Methods Aggregating brain cells cultures were prepared from embryonal rat brain, and used to study the inflammatory responses triggered by IFN-γ and LPS and by antibody-mediated demyelination induced by antibodies directed against myelin-oligodendrocyte glycoprotein (MOG). The effects of GW 501516 on cellular responses were characterized by the quantification of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), inducible NO synthase (i-NOS), PPAR-β, PPAR-γ, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and high molecular weight neurofilament protein (NF-H). GFAP expression was also examined by immunocytochemistry, and microglial cells were visualized by isolectin B4 (IB4) and ED1 labeling. Results GW 501516 decreased the IFN-γ-induced up-regulation of TNF-α and iNOS in accord with the proposed anti-inflammatory effects of this PPAR-β agonist. However, it increased IL-6 m-RNA expression. In demyelinating cultures, reactivity of both microglial cells and astrocytes was observed, while the expression of the inflammatory cytokines and iNOS remained unaffected. Furthermore, GW 501516 did not protect against the demyelination-induced changes in gene expression. Conclusion Although GW 501516 showed anti-inflammatory activity, it did not protect against antibody-mediated demyelination. This suggests that the protective effects of PPAR-β agonists observed in vivo can be attributed to their anti-inflammatory properties rather than to a direct protective or trophic effect on oligodendrocytes. PMID:19422681

Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis

PubMed Central

Oz, Helieh S.

2014-01-01

Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis. Methods Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied. Results Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were observed amongst varied treatments during high-dose (600) infection and severe related- toxoplasmosis complications as follows. Dams developed hydrothorax, ascities and excess weight gain. Combined therapy (P < 0.01) and to a lesser extent diclazuril monotherapy (P < 0.05) protected dams from excess weight, hydrothorax, and ascities. Infected dams exhibited splenomegaly, hepatomegaly and severe hepatitis. Combined therapy synergistically normalized pathology (P < 0.001) and to a lesser degree monotherapy (diclazuril P < 0.01, and atovaquone P < 0.05) protected dams from hepatitis and splemomegaly. Additionally, behavioral response to pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams Conclusions This is the first report describing combined atovaquone and diclazuril therapy (a) to be safe in pregnancy, (b) to exert novel synergistic effects, and (c) to protect dams and their nested fetuses against adverse effects of severe toxoplasmosis. PMID:25210646

Naringin ameliorates pentylenetetrazol-induced seizures and associated oxidative stress, inflammation, and cognitive impairment in rats: possible mechanisms of neuroprotection.

PubMed

Golechha, Mahaveer; Sarangal, Vikas; Bhatia, Jagriti; Chaudhry, Uma; Saluja, Daman; Arya, Dharmveer Singh

2014-12-01

Oxidative stress and cognitive impairment are associated with PTZ-induced convulsions. Naringin is a bioflavonoid present in the grapefruit. It is a potent antioxidant, and we evaluated its effect on PTZ-induced convulsions. Rats were pretreated with normal saline, naringin (20, 40, and 80 mg/kg, i.p.), or diazepam (5mg/kg, i.p.) 30 min prior to the administration of PTZ. The administration of PTZ induced myoclonic jerks and generalized tonic-clonic seizures (GTSs). We observed that naringin significantly prolonged the induction of myoclonic jerks dose-dependently. Naringin (80 mg/kg, i.p.) pretreatment protected all rats, and this protective effect was annulled by the GABAA receptor antagonist, flumazenil. In addition, naringin reduced brain MDA and TNF-α levels and conserved GSH. The pretreatment also enhanced the performance of rats in the passive avoidance task. Our observations highlight the antioxidant, antiinflammatory, and anticonvulsant potential of naringin. Also, naringin modulates the GABAA receptor to produce anticonvulsant effects and to ameliorate cognitive impairment. Copyright © 2014 Elsevier Inc. All rights reserved.

Protective effects of tea polyphenols and β-carotene against γ-radiation induced mutation and oxidative stress in Drosophila melanogaster.

PubMed

Nagpal, Isha; Abraham, Suresh K

2017-01-01

The commonly consumed antioxidants β-carotene and tea polyphenols were used to assess their protective effects against γ-radiation induced sex-linked recessive lethal (SLRL) mutation and oxidative stress in Drosophila melanogaster . Third instar larvae and adult males of wild-type Oregon-K (ORK) were fed on test agents for 24 and 72 h respectively before exposure to 10Gy γ-irradiation. The treated/control flies were used to assess the induction of SLRLs. We also evaluated antioxidant properties of these phytochemicals in the third instar larvae. Different stages of spermatogenesis in adult males showed a decrease in γ-radiation induced SLRL frequencies upon co-treatment with test agents. A similar trend was observed in larvae. Furthermore, a significant increase in antioxidant enzymatic activities with a decrease in malondialdehyde content was observed. β-carotene and tea polyphenols have exerted antigenotoxic and antioxidant effects in Drosophila . This study demonstrated the suitability of Drosophila as an alternative to mammalian testing for evaluating the antigenotoxic and antioxidant activity of natural products.

Acoustic Issues in Human Spaceflight

NASA Technical Reports Server (NTRS)

Clark, Jonathan B.

2001-01-01

NASA is concerned about acute effect of sound on crew performance on International Space Station (ISS), and is developing strategies to assess and reduce acute, chronic, and delayed effects of sound. High noise levels can cause headaches, irritation, fatigue, impaired sleep, headache, and tinnitus and have resulted in an inability to hear alarms. Speech intelligibility may be more impaired for crew understanding non-native language in a noisy environment. No hearing loss occurred, but significant effects on crew performance and communication occurred. Permanent Threshold Shifts (PTS) have not been observed in the US shuttle program. Russian specification for noise in spacecraft is 60 dBA (awake) and 50 dBA (asleep) while the U.S. noise specification on ISS is NC 50 (awake) and NC 40 (asleep) with a 85 dBA hazard limit. Background noise levels of ISS modules have measured 56-69 dBA. Treadmill exercise operations measure 77 dBA. Alarms are required to be 20 dBA above ambient. Hearing protection is recommended when noise exceeds 60 dB 24 hour Leq. Countermeasures include hearing protection and design/ engineering controls. Advanced composite materials with excellent low frequency attenuation properties could be applied as a barrier protection around noisy equipment, or used on personal protective equipment worn by the crew. Hearing protection countermeasures include foam ear inserts, passive muff headsets, and active noise reduction headsets. Oto-acoustic emissions (OAE) could be used to monitor effectiveness of hearing protection countermeasures and tailor hearing protection countermeasures to individual crewmembers. Micro-gravity, vibration, toxic fumes, air quality/composition, stress, temperature, physical exertion or some combination of the above factors may have interacted with moderate long-term noise exposure to cause significant hearing loss. Longitudinal studies will need to address what co-morbidity factors, such as radiation, toxicology, microgravity effects (fluid shift), aging, are involved with hearing loss.

Planning for the worst in Washington State: initial response planning for improvised nuclear device explosions.

PubMed

Poeton, Richard W; Glines, Wayne M; McBaugh, Debra

2009-01-01

Since 11 September 2001, improvised nuclear devices have become recognized as an important radiological threat requiring emergency response planning. Although Protective Action Guidance is well established for fixed nuclear facilities, correspondingly well-developed guidance does not exist for nuclear explosions. The Washington State Department of Health has developed preplanned Protective Action Recommendations for improvised nuclear device explosions. These recommendations recognize the need for advice to the public soon after such an event, before significant data are available. They can be used before significant outside support is available locally, and reference observable effects so people can use them if communications were disabled. The recommendations focus on early actions (24-48 h) and place priority on actions to avoid deterministic health effects due to residual fallout. Specific emphasis is placed on determining recommendations for evacuation, as well as the extent of the area for sheltering. The key recommendations developed for an initial public response are: (1) if there is ready access to robust shelter such as an underground basement or interior spaces in a multi-story structure, immediate sheltering in these areas is the best action, regardless of location; (2) if robust shelter is not available, and if fallout is observed in the area, then evacuation is the best general recommendation for locations within 16 km (10 miles) of the explosion; and (3) beyond 16 km (10 miles), the generally recommended protective action is to shelter in the best-protected location which is readily available.

Targeting Oct2 and P53: Formononetin prevents cisplatin-induced acute kidney injury

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

Huang, Di

Nephrotoxicity is one of major side effects of cisplatin in chemotherapy. Therefore, there is an urgent medical need to develop drugs that may protect kidney from toxicity. In previous study, we found that it showed the protective effects of formononetin against apoptosis by upregulating Nrf2. In this study, we investigated the renoprotective effect of formononetin against cisplatin-induced AKI and tried to elucidate the possible mechanisms. The amelioration of renal function, histopathological changes, and apoptosis in tubular cells was observed after formononetin treatment. Formononetin decreased expression of organic cation transporter 2 (Oct2) and increased the expressions of multidrug resistance-associated proteins (Mrps),more » which might result in a decrease accumulation of cisplatin in tubular cells after AKI. 5-Bromo-2-deoxyuridine (BrdU) and Ki-67 staining assay indicated that formononetin could promote the renal tubular cells proliferation after cisplatin nephrotoxicity. Moreover, formononetin regulated cyclins and pro-apoptotic proteins to involve the regulation of cell cycle. Furthermore, formononetin decreased p53 expression via promoting the overexpression of murine double minute 2 (MDM2) and MDMX. Taken together, formononetin provided protective effects by promoting proliferation of surviving renal tubular cells and inhibiting apoptosis after cisplatin-induced AKI. - Highlights: • Formononetin ameliorated the cisplatin-induced AKI. • Oct2 were reduced by formononetin. • Protective effect of formononetin was closely related to the reduction of cisplatin.« less

Flight set 360L007 (STS-33R) field joint protection system, thermal protection system, and systems tunnel components, volume 7

NASA Technical Reports Server (NTRS)

1990-01-01

The performance of the thermal protection system, field joint protection system, and systems tunnel components of flight set 360L007 is presented as evaluated by postflight hardware inspection. The condition of both motors was similar to previous flights. Four aft edge strikes were noted on the ground environment instrumentation thermal protection system. The hits all left a clean substrate, indicating that the damage was caused by nozzle severance debris and/or water impact. No National Space Transportation System debris criteria for missing thermal protection system were violated. Two problem reports were written against the field joint protection system. The first concerned two cracks in the K5NA closeout over the trunnion/vent valve location on the left-hand aft field joint. A similar condition was observed on Flight 5 (360H005). The second problem report referred to a number of small surface cracks between two impact marks on the left-hand forward field joint. Neither area exhibited loose material or any abnormal heat effects, and they have no impact on flight safety.

Research subject privacy protection in otolaryngology.

PubMed

Noone, Michael C; Walters, K Christian; Gillespie, M Boyd

2004-03-01

Health Insurance Portability and Accountability Act regulations, which took effect on April 14, 2003, placed new constraints on the use of protected health information for research purposes. To review practices of research subject privacy protection in otolaryngology in order to determine steps necessary to achieve compliance with Health Insurance Portability and Accountability Act regulations. Literature review. Articles appearing in 2001 in 3 widely circulated otolaryngology journals were classified according to study design. The "Methods" section of each article was reviewed to determine whether the informed consent and institutional review board processes were clearly documented. Descriptive studies involving case reports and case series were more common than observational studies that include a control group (66% vs 11%). Few case series documented the consent process (18%) and institutional review board process (19%). Observational designs demonstrated better documentation of the consent process (P<.001) and the institutional review board exemption and approval process (P<.001). Methods used to protect subject privacy are not commonly documented in case series in otolaryngology. More attention needs to be given to research subject privacy concerns in the otolaryngology literature in order to comply with Health Insurance Portability and Accountability Act regulations.

Age Differences in Prenatal Testosterone's Protective Effects on Disordered Eating Symptoms: Developmental Windows of Expression?

PubMed Central

Culbert, Kristen M.; Breedlove, S. Marc; Sisk, Cheryl L.; Keel, Pamela K.; Neale, Michael C.; Boker, Steven M.; Burt, S. Alexandra; Klump, Kelly L.

2015-01-01

Prenatal testosterone exposure may be protective against disordered eating. However, prior studies have produced mixed results. Developmental differences in prenatal testosterone's protective effects on disordered eating may explain these discrepancies. Indeed, studies have differed in the age of participants assessed, with data supporting prenatal testosterone effects on disordered eating in early adolescent and young adult samples but not in late adolescence. The present series of studies are the first to investigate age differences in prenatal testosterone's protective effects on disordered eating. Two indirect markers of higher prenatal testosterone were examined: 1) lower finger-length ratios [index (2D)/ring (4D) finger] (Study 1), and 2) lower disordered eating in females from opposite-sex twin pairs (who are thought to be exposed to higher prenatal testosterone from their male co-twin) relative to female controls (Study 2). Participants were twins from the Michigan State University Twin Registry (Study 1: n = 409; Study 2: n = 1,538) in early adolescence, late adolescence, or young adulthood. Disordered eating was assessed with well-validated questionnaires. Finger-length ratios were measured from hand scans, using electronic computer calipers. Findings were consistent across both studies. Higher prenatal testosterone (lower 2D:4D; females from opposite-sex twin pairs vs. controls) predicted lower disordered eating in early adolescence and young adulthood only. Prenatal testosterone-disordered eating associations were not observed during late adolescence. Results point to the possibility of developmental windows of expression for prenatal testosterone's protective effects on disordered eating and suggest that prior discrepant results may reflect age differences across samples. PMID:25621790

Relationship between drugs affecting the renin-angiotensin system and colorectal cancer: The MCC-Spain study.

PubMed

Dierssen-Sotos, Trinidad; Gómez-Acebo, Inés; Palazuelos, Camilo; Rodriguez-Moranta, Francisco; Pérez-Gómez, Beatriz; Fernández Vazquez, José Pedro; Amiano, Pilar; Barricarte, Aurelio; Mirón-Pozo, Benito; Tardon, Adonina; Capelo, Rocío; Peiro Pérez, Rosana; Huerta, José María; Andreu, Montserrat; Sierra, Mª Ángeles; Castañón López, Carmen; Ruiz, Irune; Moreno-Iribas, Concepción; Olmedo-Requena, Rocío; Castaño-Vinyals, Gemma; Aragonés, Nuria; Kogevinas, Manolis; Pollán, Marina; Llorca, Javier

2017-06-01

The potential protective effect of renin-angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). To evaluate this association, we conducted a case-control study with 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65years group (OR=0.65 95%CI (0.48-0.89)) and to a lesser degree to men (OR=0.81 95%CI (0.66-0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of Carotid Artery Stenting by the Universal Protection Method.

PubMed

Goto, Shunsaku; Ohshima, Tomotaka; Kato, Kyozo; Izumi, Takashi; Wakabayashi, Toshihiko

2018-04-18

To avoid distal plaques embolization during carotid artery stenting, we developed Universal Protection Method that combined the use of a proximal common carotid artery balloon, an external carotid artery balloon, and a distal internal carotid artery filter, with continuous flow reversal to the femoral vein. Herein, we assessed the efficacy of the Universal Protection Method by comparing stenting outcomes before and after its introduction. We assessed outcomes for 115 cases before and 41 cases after the Universal Protection Method was adopted (non-Universal Protection Method and Universal Protection Method groups, respectively). We then compared procedure details, magnetic resonance imaging (within 48 hours after the procedure), intraprocedural complications, and postoperative stroke rates. Ischemic stroke was not observed in the Universal Protection Method group, but 1 major stroke and 2 minor strokes were observed in the non-Universal Protection Method group. High-intensity areas were seen in 6 (15.0%) and 49 (42.6%) cases in the Universal Protection Method and non-Universal Protection Method groups, respectively (P = .001). Contrastingly, intraprocedural complications were observed in 9 (22.5%) and 21 (18.3%) cases in the Universal Protection Method and non-Universal Protection Method groups, respectively. Among these intraprocedural complication cases, high-intensity areas were observed in 1 case (11.1%) in the Universal Protection Method group and in 15 cases (71.4%) in the non-Universal Protection Method group. Universal Protection Method is a safe technique that is applicable to all patients undergoing carotid artery stenting, irrespective of individual risk factors. Notably, the incidence rates of both distal embolization and unexpected intraprocedural complications are low. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The possible protective effects of dipyridamole on ischemic reperfusion injury of priapism

PubMed Central

Karaguzel, Ersagun; Bayraktar, Cemil; Kutlu, Omer; Yulug, Esin; Mentese, Ahmet; Okatan, Ali Ertan; Colak, Fatih; Ozer, Serap; O.Kazaz, Ilke

2016-01-01

ABSTRACT Purpose To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. Materials and Methods Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. Results Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. Conclusions The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis. PMID:27136481

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem

PubMed Central

2014-01-01

Background Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? Methods We used cross-sectional data from 3,064 males and females aged 12–19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Results Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Conclusions Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries. PMID:25210535

Effects of natural mineral-rich water consumption on the expression of sirtuin 1 and angiogenic factors in the erectile tissue of rats with fructose-induced metabolic syndrome

PubMed Central

Pereira, Cidália D; Severo, Milton; Rafael, Luísa; Martins, Maria João; Neves, Delminda

2014-01-01

Consuming a high-fructose diet induces metabolic syndrome (MS)-like features, including endothelial dysfunction. Erectile dysfunction is an early manifestation of endothelial dysfunction and systemic vascular disease. Because mineral deficiency intensifies the deleterious effects of fructose consumption and mineral ingestion is protective against MS, we aimed to characterize the effects of 8 weeks of natural mineral-rich water consumption on the structural organization and expression of vascular growth factors and receptors on the corpus cavernosum (CC) in 10% fructose-fed Sprague-Dawley rats (FRUCT). Differences were not observed in the organization of the CC either on the expression of vascular endothelial growth factor (VEGF) or the components of the angiopoietins/Tie2 system. However, opposing expression patterns were observed for VEGF receptors (an increase and a decrease for VEGFR1 and VEGFR2, respectively) in FRUCT animals, with these patterns being strengthened by mineral-rich water ingestion. Mineral-rich water ingestion (FRUCTMIN) increased the proportion of smooth muscle cells compared with FRUCT rats and induced an upregulatory tendency of sirtuin 1 expression compared with the control and FRUCT groups. Western blot results were consistent with the dual immunofluorescence evaluation. Plasma oxidized low-density lipoprotein and plasma testosterone levels were similar among the experimental groups, although a tendency for an increase in the former was observed in the FRUCTMIN group. The mineral-rich water-treated rats presented changes similar to those observed in rats treated with MS-protective polyphenol-rich beverages or subjected to energy restriction, which led us to hypothesize that the effects of mineral-rich water consumption may be more vast than those directly observed in this study. PMID:24625878

The human milk oligosaccharide 2'-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine.

PubMed

Good, Misty; Sodhi, Chhinder P; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B; Martin, Laura Y; Prindle, Thomas; Nino, Diego F; Zhou, Qinjie; Ma, Congrong; Ozolek, John A; Buck, Rachael H; Goehring, Karen C; Hackam, David J

2016-10-01

Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2'FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2'FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2'FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2'FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2'FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2'FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.

The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine

PubMed Central

Good, Misty; Sodhi, Chhinder P.; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B.; Martin, Laura Y.; Prindle, Thomas; Nino, Diego F.; Zhou, Qinjie; Ma, Congrong; Ozolek, John A.; Buck, Rachael H.; Goehring, Karen C.; Hackam, David J.

2016-01-01

Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2′-fucosyllactose (2′FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2′FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2′FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2′FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2′FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2′FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2′FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC. PMID:27609061

Effects of oral and intraperitoneal magnesium treatment against cadmium-induced oxidative stress in plasma of rats.

PubMed

Buha, Aleksandra; Bulat, Zorica; Dukić-Ćosić, Danijela; Matović, Vesna

2012-09-01

Cadmium (Cd) has been recognised as one of the most important environmental and industrial pollutants, and up-to-date investigations have shown that one of the mechanisms of its toxicity is associated with the induction of oxidative stress. The aim of this study was to determine the connection between acute oral and intraperitoneal exposure to Cd and parameters indicative of oxidative stress in the plasma of rats, as well as to examine the potential protective effect of magnesium (Mg) in conditions of acute oral and intraperitoneal Cd poisoning. The experiment was performed on male albino Wistar rats (n=40) randomly divided into control group, Cdor group that received 30 mg kg-1 b.w. Cd by oral gavage, Cd+Mgor group that orally received 50 mg kg-1 b.w. Mg one hour before oral Cd, Cdip group that received 1.5 mg kg-1 b.w. Cd intraperitoneally, and Cd+Mgip group that intraperitoneally received 3 mg kg-1 b.w. Mg 10 min before intraperitoneal Cd. The animals were sacrificed 24 h after treatment and the following parameters were measured: superoxide dismutase activity, superoxide anion, total oxidative status, advanced oxidation protein products, and malondialdehyde. All parameters of oxidative stress in rat plasma were negatively affected by Cd treatment with more pronounced negative effects after intraperitoneal treatment, with the exception of superoxide dismutase (SOD) activity. Although both oral and intraperitoneal Mg pretreatment had protective effects, more pronounced beneficial effects were observed after oral administration, since it managed to completely prevent Cd-induced changes in the investigated parameters. The observed results support the use of Mg as potential protective agent against toxic effects caused by Cd.

Possible biochemical effects following inhibition of ethanol-induced gastric mucosa damage by Gymnema sylvestre in male Wistar albino rats.

PubMed

Al-Rejaie, Salim S; Abuohashish, Hatem M; Ahmed, Mohammed M; Aleisa, Abdulaziz M; Alkhamees, Osama

2012-12-01

Gymnema sylvestre (GS) R. Br. (Gymnema) (Asclepiadaceae) has been used from ancient times as a folk medicine for the treatment of diabetes, obesity, urinary disorder, and stomach stimulation. The present study was designed to investigate the effects of G. sylvestre leaves ethanol extract on gastric mucosal injury in rats. Gastric mucosal damage was induced by 80% ethanol in 36 h fasted rats. The effect of G. sylvestre on gastric secretions induced in Shay rats was estimated. In stomach, wall mucus, non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), total proteins and nucleic acids levels were estimated. Histopathological changes were observed. G. sylvestre pretreatment at doses of 100, 200 and 400 mg/kg provided 27, 49, and 63% protection against the ulcerogenic effect of ethanol, respectively. Pylorus ligation accumulated 10.24 mL gastric secretions with 66.56 mEq of acidity in control rats. Pretreatment with G. sylvestre significantly inhibited the secretions volume and acidity in dose-dependent manner. Ethanol caused significant depletion in stomach-wall mucus (p < 0.001), total proteins (p < 0.01), nucleic acids (p < 0.001), and NP-SH (p < 0.001) levels. Pretreatment with G. sylvestre showed protection against these depleted levels in dose-dependent manner. The MDA levels increased from 19.02 to 29.22 nmol/g by ethanol ingestion and decreased with G. sylvestre pretreatments in dose-dependent manner. The protective effect of G. sylvestre observed in the present study is attributed to its effect on mucus production, increase in nucleic acid and NP-SH levels, which appears to be mediated through its free radical scavenging ability and/or possible cytoprotective properties.

Examination of the effect of changing to azilsartan from candesartan in renal transplant patients.

PubMed

Ishii, T; Yasuda, M; Saito, Y; Mori, Y; Hayashi, T; Uemura, H; Nose, K; Nishioka, T

2014-01-01

Azilsartan, an angiotensin receptor blocker (ARB), was administered to renal transplant recipients to investigate the safety and antihypertensive effect in addition to its ARB-characteristic organ-protective effect. The subjects were 20 patients (18 males, 2 females; baseline serum creatinine 2.39 ± 1.33 mg/dL) responding poorly to candesartan, who suffered albuminuria (>0.3 g/g creatinine) and hypertension (>140/90 mm Hg) following renal transplantation. Three months after candesartan was switched to azilsartan 20 mg/d, blood pressure, creatinine-corrected urinary albumin excretion, urinary L-type acid binding protein, urinary 8-hydroxydeoxyguano-sine, serum creatinine, and estimated glomerular filtration rate were evaluated. Thirteen patients received cyclosporine (65.0%) and 7 received tacrolimus (35.0%). Another hypertensive (calcium antagonist) agent was combined in 7 (35.0%). Systolic blood pressure significantly decreased from 139.5 mm Hg (baseline) from 128.7 mm Hg (at 3 months), whereas no significant changes were observed for diastolic blood pressure. The percentage of patients achieving the target level of antihypertensive effect (blood pressure < 130/80 mm Hg) significantly improved from 30.0% (baseline) to 70.0% (at 3 months). No significant changes were observed in renal graft function, oxidative stress marker level, or biochemical examination findings. Sufficient antihypertensive effect was demonstrated soon after switching to azilsartan. However, no significant change was found in renal damage markers. Long-term study must be conducted to confirm the protective effect azilsartan on the transplanted kidney, as found with candesartan. The safety of azilsartan was demonstrated. If the transplanted kidney protection is demonstrated, this drug is expected to contribute to the improved long-term prognosis of renal transplant recipients. Copyright © 2014 Elsevier Inc. All rights reserved.

ABCC1 is related to the protection of the distal nephron against hyperosmolality and high sodium environment: possible implications for cancer chemotherapy.

PubMed

Fonseca, Leonardo M; Alvarez, Adriana B; Rodrigues, Rachel C; Santos, Diego H F; Lopes, Anibal G; Capella, Marcia A M

2013-01-01

Glutathione (GSH) plays an important role in protecting cells against oxidative damage. ABCC1 protein transports GSH. Although this protein is largely studied in cancer, due to multidrug resistance phenotype, its role in the tubular cells of the kidney is unknown. The goal of this study was to find out whether ABCC1 has a role in protecting cells from the distal nephron against the stress caused by high medullar osmolality. MA104 cells were treated with high concentrations of sodium chloride, urea, or both to raise the osmolality of the culture medium. Cell viability was accessed by MTT and trypan blue assays. ABCC1 expression and extrusion of carboxi-fluorescein (CF), a fluorescent ABCC1 substrate, were measured by flow cytometry. Incubation of MA104 cells in a high sodium concentration medium resulted in changes in cell granularity and altered expression and activity of ABCC1. Urea did not alter ABCC1 expression or activity, but reversed the observed NaCl effects. High sodium concentrations also had a negative effect on cell viability and urea also protected cells against this effect. Our findings demonstrate that ABCC1 plays a significant role in the protection of kidney epithelial cells against the stress caused by high sodium environment present in renal medulla.

The crypto-OH radical in the damage of DNA by bleomycin-Fe2+?

PubMed

Bartkowiak, A; Grzelinska, E; Bartosz, G; Zabłocka, J; Leyko, W

1982-01-01

1. Effects of various OH scavengers, superoxide dismutase and catalase on the formation of malondialdehyde-like products from DNA by bleomycin-Fe2+ were studied. In no case was a protective effect observed. 2. These results can be interpreted on the basis that a crypto-OH radical mediates the damage to DNA by bleomycin-Fe2+.

Evaluation of food protective property of five natural products using fresh-cut apple slice model.

PubMed

Hakkim, Faruk Lumanul; Mathiraj; Essa, Musthafa Mohamed; Arivazhagan, Girija; Guizani, Nejib; Hyuk, Song

2012-01-01

The present study evaluated the antioxidant (AA), antimicrobial and preservation effects of five plant derived natural products viz., Rosmarinic Acid (RA), p-Coumaric Acid (pCA), Trans-Cinnamic Acid (TCA), Hydroxyphenyllactic Acid (HPA) and Caffeic acid (CA) along with synthetic compounds (Ascorbic acid, gallic acid, citric acid and BHA) on fresh cut apple slices. Antimicrobial efficacy of these compounds against Bacillus licheniformis, Pseudomonas vulgaris, Shigella boydii, Salmonella typhi, Staphylococcus aureus, Listeria monocytogenes and Escherichia coli was found to be concentration dependent with the maximum inhibition observed at 500 microg mL(-1). A considerable AA potential of these compounds was observed in in vitro based assay system, with RA exhibiting significantly higher effect than the other compounds at 500 microg mL(-1). Furthermore the compounds at 500 microg mL(-1) significantly reduced the browning, maintained the acidic pH and restricted growth of L. monocytogenes even after 10 days of treatment. Ethanol accumulation in fresh cut apple slices increased significantly throughout the experimental period. Over all RA exhibited maximum effect in all the food preservation parameters studied suggesting that it has synchronized food protection effect and can be recommended as food additive.

Physicochemical properties, antioxidant activities and protective effect against acute ethanol-induced hepatic injury in mice of foxtail millet (Setaria italica) bran oil.

PubMed

Pang, Min; He, Shujian; Wang, Lu; Cao, Xinmin; Cao, Lili; Jiang, Shaotong

2014-08-01

This study was designed to investigate physicochemical characterization of the oil extracted from foxtail millet bran (FMBO), and the antioxidant and hepatoprotective effects against acute ethanol-induced hepatic injury in mice. GC-MS analysis revealed that unsaturated fatty acids (UFAs) account for 83.76% of the total fatty acids; in particular, the linoleic acid (C18:2) is the predominant polyunsaturated fatty acid (PUFA), and the compounds of squalene and six phytosterols (or phytostanols) were identified in unsaponifiable matter of FMBO. The antioxidant activity examination of FMBO in vitro showed highly ferric-reducing antioxidant power and scavenging effects against DPPH· and HO· radicals. Furthermore, the protective effect of FMBO against acute hepatic injuries induced by ethanol was verified in mice. In this, intragastric administration with different dosages of FMBO in mice ahead of acute ethanol administration could observably antagonize the ethanol-induced increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and the hepatic malondialdehyde (MDA) levels, respectively, along with enhanced hepatic superoxide dismutase (SOD) levels relative to the control. Hepatic histological changes were also observed and confirmed that FMBO is capable of attenuating ethanol-induced hepatic injury.

The Synergetic Effect of Cash Transfers for Families, Child Sensitive Social Protection Programs, and Capacity Building for Effective Social Protection on Children's Nutritional Status in Nepal.

PubMed

Renzaho, Andre M N; Chitekwe, Stanley; Chen, Wen; Rijal, Sanjay; Dhakal, Thakur; Dahal, Pradiumna

2017-12-04

The aim of this study was to evaluate the effectiveness of the synergetic effect of child sensitive social protection programs, augmented by a capacity building for social protection and embedded within existing government's targeted resource transfers for families on child nutritional status. A repeat cross-sectional quasi-experimental design with measures taken pre- (October-December 2009) and post- (December 2014-February 2015) intervention in the intervention and comparison district. The comparison district received standard social welfare services in the form of targeted resource transfers (TRTs) for eligible families. The intervention district received the TRTs plus a child cash payment, augmented by a capacity building for effective social protection outcomes. Propensity scores were used in difference-in-differences models to compare the changes over time between the intervention and control groups. Propensity score matched/weighted models produced better results than the unmatched analyses, and hence we report findings from the radius matching. The intervention resulted in a 5.16 (95% CI: 9.55, 0.77), 7.35 (95% CI: 11.62, 3.08) and 2.84 (95% CI: 5.58, 0.10) percentage point reduction in the prevalence of stunting, underweight, and wasting among children under the age, respectively. The intervention impact was greater in boys than girls for stunting and wasting; and greater in girls than boys for underweight. The intervention also resulted in a 6.66 (95% CI: 2.13, 3.18), 11.40 (95% CI: 16.66, 6.13), and 4.0 (95% CI: 6.43, 1.78) percentage point reduction in the prevalence of stunting, underweight, and wasting among older children (≥24 months). No impact was observed among younger children (<24 months). Targeted resource transfers for families, augmented with a child sensitive social protection program and capacity building for social protection can address effectively child malnutrition. To increase the intervention effectiveness on younger children, the child cash payment amount needs to be revisited and closely embedded into infant and young child feeding initiatives, but also adjusted to equate to 20% of household expenditure or more to maximize the diversity of food available to young children.

Protective activity of Lentinan in experimental tuberculosis.

PubMed

Markova, Nadya; Kussovski, Vesselin; Drandarska, Ivanka; Nikolaeva, Sascha; Georgieva, Neli; Radoucheva, Tatyana

2003-10-01

Protective effects of Lentinan (Ajinomoto, Japan) against Mycobacterium tuberculosis infection were studied by in vitro and in vivo mouse models. The effectiveness of Lentinan administrated intraperitoneally (i.p.) before infection at a dose of 1 mg/kg three times at 2-day intervals was monitored in vivo by several parameters (body temperature; spleen weight; CFU counts of M. tuberculosis in spleen, liver and lung; and histomorphological observations). Peritoneal macrophages obtained from animals treated with Lentinan were greatly stimulated, as assayed by establishing their number, acid phosphatase activity, H2O2 production and killing ability against M. tuberculosis in vitro. The in vivo model demonstrated that administration of Lentinan before infection can mobilize host defense potential and reduce mycobacterial infection.

HLA class I-mediated control of HIV-1 in the Japanese population, in which the protective HLA-B*57 and HLA-B*27 alleles are absent.

PubMed

Naruto, Takuya; Gatanaga, Hiroyuki; Nelson, George; Sakai, Keiko; Carrington, Mary; Oka, Shinichi; Takiguchi, Masafumi

2012-10-01

We investigated the effect of HLA class I alleles on clinical parameters for HIV-1 disease progression in the Japanese population, where two strongly protective alleles, HLA-B*57 and HLA-B*27, are virtually nonexistent. HLA-B alleles showed a dominant role, primarily through HLA-B*67:01 and the HLA-B*52:01-C*12:02 haplotype. Neither a rare-allele nor a heterozygote advantage was found, suggesting that the effect of HLA alleles in the Japanese population is either different from those observed in Africans and Caucasians or undetectable due to limited power.

HLA Class I-Mediated Control of HIV-1 in the Japanese Population, in Which the Protective HLA-B*57 and HLA-B*27 Alleles Are Absent

PubMed Central

Naruto, Takuya; Gatanaga, Hiroyuki; Nelson, George; Sakai, Keiko; Carrington, Mary; Oka, Shinichi

2012-01-01

We investigated the effect of HLA class I alleles on clinical parameters for HIV-1 disease progression in the Japanese population, where two strongly protective alleles, HLA-B*57 and HLA-B*27, are virtually nonexistent. HLA-B alleles showed a dominant role, primarily through HLA-B*67:01 and the HLA-B*52:01-C*12:02 haplotype. Neither a rare-allele nor a heterozygote advantage was found, suggesting that the effect of HLA alleles in the Japanese population is either different from those observed in Africans and Caucasians or undetectable due to limited power. PMID:22811530

Antiulcerogenic effects of coconut (Cocos nucifera) extract in rats.

PubMed

Nneli, R O; Woyike, O A

2008-07-01

A warm water crude extract of coconut milk and a coconut water dispersion were investigated for their antiulcerogenic effects in male Wistar albino rats. Ulcers were induced in the male rats by subcutaneous administration of indomethacin (40 mg/kg) using standard procedures. The ulcer inhibition rate (UIR) was taken as a measure of the cytoprotection offered by test substances. Coconut milk (2 mL daily oral feeding) produced a stronger percentage (54%) reduction in the mean ulcer area than coconut water (39%). The effect of coconut milk was similar to the effect of sucralfate that reduced the mean ulcer area by 56% in this study. Sucralfate is a conventional cytoprotective agent. The results showed that coconut milk and water via macroscopic observation had protective effects on the ulcerated gastric mucosa. It is concluded that coconut milk offered stronger protection on indomethacin-induced ulceration than coconut water in rats.

Effect of antioxidant protection of must on volatile compounds and aroma shelf life of Falanghina (Vitis vinifera L.) wine.

PubMed

Moio, Luigi; Ugliano, Maurizio; Genovese, Alessandro; Gambuti, Angelita; Pessina, Rita; Piombino, Paola

2004-02-25

Two vinification methods involving different degrees of antioxidant protection of Falanghina must during prefermentative steps, and referred as HAMP (high antioxidant must protection) and LAMP (low antioxidant must protection), were compared in terms of fermentation performances of four different yeast strains, composition of the volatile fraction of wines at the end of alcoholic fermentation, and shelf life of wines during storage. The use of HAMP technology resulted in wines with lower volatile acidity and higher concentrations of medium-chain fatty acid ethyl esters, acetates, and volatile fatty acids. For two of the four strains a lower concentration of isoamyl alcohol was also observed. HAMP wines also revealed increased shelf life because of the higher concentration of odor active esters at the end of storage and better preservation of varietal aromas.

Oxidative Hemolysis of Erythrocytes

ERIC Educational Resources Information Center

Wlodek, Lidia; Kusior, Dorota

2006-01-01

This exercise for students will allow them to simultaneously observe lipid peroxidation and consequent hemolysis of rat erythrocytes and the effect of sodium azide, a catalase inhibitor, on these processes. It will also demonstrate a protective action of antioxidants, the therapeutically used N-acetylcysteine and albumins present in plasma.

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.

[HPLC specific chromatogram spectrum-effect relationship for Shuanghuanglian on MDCK cell injury induced by influenza A virus (H1N1)].

PubMed

Liu, Ting; Wang, Hai-dan; Di, Liu-qing; Kang, An; Zhao, Xiao-li; Zhu, Xuan-xuan; Li, Jun-song

2015-11-01

To establish HPLC specific chromatogram and its correlation with the protection effect of Shuanghuanglian on MDCK (Madin-Darby canine kidney) cell injury induced by influenza A virus( H1N1). Nine recipes of Shuanghuanglian based on the official prescription were prepared according to orthogonal test for HPLC analysis and MDCK cells protection experiment separately (cytopathic effect (CPE) method was used for observing the virus infectivity and MTT staining results were used as the determining indexes for drug concentration selection and analyzing cell viability). The results suggested that all the other Shuang-Huang-Lian recipes except recipe1 demonstrate protecting effect on MDCK cell injury induced by influenza A virus (P < 0.01, P < 0.001). Stepwise regression analysis was used for analyzing the relationships between HPLC fingerprint and the protecting effect of Shuanghuanglian on influenza A virus induced MDCK cell injury. Peak 2, 3, 6, 8 and 12 were found to be strongly related with anti-influenza A virus efficacy. Stepwise regression analysis of recipes data and efficacy data showed that Lonicerae Japonicae Flos and Forsythiae Fructus were positively associated with the protecting effect of cells injury. From HPLC fingerprints, we found that peak 2, 3, 12 were from Lonicerae Japonicae Flos and peak 6, 8 were from Forsythiae Fructus. Four peaks were identified through comparing the retention time between the standard and Shuanghuanglian recipes, and they were chlorogenicacid, cryptochlorogenic acid, forsythoside B and 3,4-dicaffeoylquinic acid respectively. Caffeic acid derivatives in Lonicerae Japonicae Flos and Forsythiae Fructus were found to be greatly correlated with anti-influenza A virus efficacy and maybe the substance basis of Shuanghuanglian.

[Tick-borne encephalitis (TBE) and TBE-vaccination in Austria: Update 2014].

PubMed

Kunze, Ursula; Böhm, Gabriela

2015-07-01

TBE is a public health problem well under control in Austria because of a mass vaccination programme. There have been 50-100 registered cases per year for many years, the vaccination rate of the population is currently 85 %. Special attention has to be given to the "older" generation 40 plus as this is the segment of the population where the majority of cases are observed annually. In comparison of the counties, Tyrol and Upper Austria finished first and second after a long time when Styria and Carynthia had observed most of the cases. For TBE applies the same as for Tetanus, namely the principle of disease control or disease elimination: The virus cannot be eliminated and vaccination provides individual protection. The both available TBE vaccines have proven to be very effective with an effectivity of 96-99 %, also when given irregular vaccinations the protection rate is still very high (>90 %). More than 4000 prevented cases between 2000 and 2011 prove this impressively.

Mitigating Infectious Disease Outbreaks

NASA Astrophysics Data System (ADS)

Davey, Victoria

The emergence of new, transmissible infections poses a significant threat to human populations. As the 2009 novel influenza A/H1N1 pandemic and the 2014-2015 Ebola epidemic demonstrate, we have observed the effects of rapid spread of illness in non-immune populations and experienced disturbing uncertainty about future potential for human suffering and societal disruption. Clinical and epidemiologic characteristics of a newly emerged infectious organism are usually gathered in retrospect as the outbreak evolves and affects populations. Knowledge of potential effects of outbreaks and epidemics and most importantly, mitigation at community, regional, national and global levels is needed to inform policy that will prepare and protect people. Study of possible outcomes of evolving epidemics and application of mitigation strategies is not possible in observational or experimental research designs, but computational modeling allows conduct of `virtual' experiments. Results of well-designed computer simulations can aid in the selection and implementation of strategies that limit illness and death, and maintain systems of healthcare and other critical resources that are vital to public protection. Mitigating Infectious Disease Outbreaks.

Protective Effect of ECQ on Rat Reflux Esophagitis Model.

PubMed

Jang, Hyeon-Soon; Han, Jeong Hoon; Jeong, Jun Yeong; Sohn, Uy Dong

2012-12-01

This study was designed to determine the protective effect of Rumex Aquaticus Herba extracts containing quercetin-3-β-D-glucuronopyranoside (ECQ) on experimental reflux esophagitis. Reflux esophagitis was induced by surgical procedure. The rats were divided into seven groups, namely normal group, control group, ECQ (1, 3, 10, 30 mg/kg) group and omeprazole (30 mg/kg) group. ECQ and omeprazole groups received intraduodenal administration. The Rats were starved for 24 hours before the experiments, but were freely allowed to drink water. ECQ group attenuated the gross esophagitis significantly compared to that treated with omeprazole in a dose-dependent manner. ECQ decreased the volume of gastric juice and increased the gastric pH, which are similar to those of omeprazole group. In addition, ECQ inhibited the acid output effectively in reflux esophagitis. Significantly increased amounts of malondialdehyde (MDA), myeloperoxidase (MPO) activity and the mucosal depletion of reduced glutathione (GSH) were observed in the reflux esophagitis. ECQ administration attenuated the decrement of the GSH levels and affected the MDA levels and MPO activity. These results suggest that the ECQ has a protective effect which may be attributed to its multiple effects including anti-secretory, anti-oxidative and anti-inflammatory actions on reflux esophagitis in rats.

Prevention of murine cerebral malaria by low-dose cyclosporin A.

PubMed Central

Grau, G E; Gretener, D; Lambert, P H

1987-01-01

The effects of cyclosporin A (CsA) were investigated in an experimental model of cerebral malaria. In this model, Plasmodium berghei ANKA-infected CBA/Ca mice develop a clinically and histologically characterized neurological syndrome which is considered to be the result of immunopathological reactions mediated by L3T4+ T cells. It was shown that CsA displayed a strong protective effect on neurological complications when given at a dose 1 mg/kg/day for 5 consecutive days (Days 4-8), which had no effect on the parasite. Paradoxically, this protection against neurological complications was not seen when parasiticidal doses were used during this limited 5-day period. A similar protective effect was observed with two CsA derivatives, C5-34 and H7-94. The mechanisms by which CsA and the two derivatives could prevent murine cerebral malaria are unknown but can be related to exquisite effects on some lymphocyte functions. In view of these results, it might be conceivable to investigate the benefits of using low doses of CsA in man, in conjunction with the classical antiparasite therapy, for the management of cerebral malaria. PMID:3327806

Prevention of murine cerebral malaria by low-dose cyclosporin A.

PubMed

Grau, G E; Gretener, D; Lambert, P H

1987-08-01

The effects of cyclosporin A (CsA) were investigated in an experimental model of cerebral malaria. In this model, Plasmodium berghei ANKA-infected CBA/Ca mice develop a clinically and histologically characterized neurological syndrome which is considered to be the result of immunopathological reactions mediated by L3T4+ T cells. It was shown that CsA displayed a strong protective effect on neurological complications when given at a dose 1 mg/kg/day for 5 consecutive days (Days 4-8), which had no effect on the parasite. Paradoxically, this protection against neurological complications was not seen when parasiticidal doses were used during this limited 5-day period. A similar protective effect was observed with two CsA derivatives, C5-34 and H7-94. The mechanisms by which CsA and the two derivatives could prevent murine cerebral malaria are unknown but can be related to exquisite effects on some lymphocyte functions. In view of these results, it might be conceivable to investigate the benefits of using low doses of CsA in man, in conjunction with the classical antiparasite therapy, for the management of cerebral malaria.

Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury

PubMed Central

Thangavel, Jayakumar; Samanta, Saheli; Rajasingh, Sheeja; Barani, Bahar; Xuan, Yu-Ting; Dawn, Buddhadeb; Rajasingh, Johnson

2015-01-01

ABSTRACT Acute lung injury (ALI) during sepsis is characterized by bilateral alveolar infiltrates, lung edema and respiratory failure. Here, we examined the efficacy the DNA methyl transferase (DNMT) inhibitor 5-Aza 2-deoxycytidine (Aza), the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), as well as the combination therapy of Aza and TSA (Aza+TSA) provides in the protection of ALI. In LPS-induced mouse ALI, post-treatment with a single dose of Aza+TSA showed substantial attenuation of adverse lung histopathological changes and inflammation. Importantly, these protective effects were due to substantial macrophage phenotypic changes observed in LPS-stimulated macrophages treated with Aza+TSA as compared with untreated LPS-induced macrophages or LPS-stimulated macrophages treated with either drug alone. Further, we observed significantly lower levels of pro-inflammatory molecules and higher levels of anti-inflammatory molecules in LPS-induced macrophages treated with Aza+TSA than in LPS-induced macrophages treated with either drug alone. The protection was ascribed to dual effects by an inhibition of MAPK–HuR–TNF and activation of STAT3–Bcl2 pathways. Combinatorial treatment with Aza+TSA reduces inflammation and promotes an anti-inflammatory M2 macrophage phenotype in ALI, and has a therapeutic potential for patients with sepsis. PMID:26116574

Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis.

PubMed

Villamor-Martínez, Eduardo; Pierro, Maria; Cavallaro, Giacomo; Mosca, Fabio; Kramer, Boris W; Villamor, Eduardo

2018-02-20

Bronchopulmonary dysplasia (BPD) is the most common complication after preterm birth. Pasteurized donor human milk (DHM) has increasingly become the standard of care for very preterm infants over the use of preterm formula (PF) if the mother's own milk (MOM) is unavailable. Studies have reported beneficial effects of DHM on BPD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies on the effects of DHM on BPD and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta-analysis of RCTs could not demonstrate that supplementation of MOM with DHM reduced BPD when compared to PF (three studies, risk ratio (RR) 0.89, 95% confidence interval (CI) 0.60-1.32). However, meta-analysis of observational studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI 0.67-0.90). An exclusive human milk diet reduced the risk of BPD, compared to a diet with PF and/or bovine milk-based fortifier (three studies, RR 0.80, 95% CI 0.68-0.95). Feeding raw MOM, compared to feeding pasteurized MOM, protected against BPD (two studies, RR 0.77, 95% CI 0.62-0.96). In conclusion, our data suggest that DHM protects against BPD in very preterm infants.

Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

PubMed Central

Mosca, Fabio; Kramer, Boris W.

2018-01-01

Bronchopulmonary dysplasia (BPD) is the most common complication after preterm birth. Pasteurized donor human milk (DHM) has increasingly become the standard of care for very preterm infants over the use of preterm formula (PF) if the mother’s own milk (MOM) is unavailable. Studies have reported beneficial effects of DHM on BPD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies on the effects of DHM on BPD and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta-analysis of RCTs could not demonstrate that supplementation of MOM with DHM reduced BPD when compared to PF (three studies, risk ratio (RR) 0.89, 95% confidence interval (CI) 0.60–1.32). However, meta-analysis of observational studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI 0.67–0.90). An exclusive human milk diet reduced the risk of BPD, compared to a diet with PF and/or bovine milk-based fortifier (three studies, RR 0.80, 95% CI 0.68–0.95). Feeding raw MOM, compared to feeding pasteurized MOM, protected against BPD (two studies, RR 0.77, 95% CI 0.62–0.96). In conclusion, our data suggest that DHM protects against BPD in very preterm infants. PMID:29461479

Evaluation of the protective effect of α-lipoic acid on cisplatin ototoxicity using distortion-product otoacoustic emission measurements: an experimental animal study.

PubMed

Ozkul, Yilmaz; Songu, Murat; Basoglu, Mehmet Sinan; Ozturkcan, Sedat; Katilmis, Huseyin

2014-07-01

The aim of our study was to determine the effectiveness of intratympanic α-lipoic acid injection as an otoprotective agent against cisplatin-induced ototoxicity in guinea pigs. Twenty-four adult male albino guinea pigs with normal hearing were divided into 4 groups. The guinea pigs received intraperitoneal cisplatin in group 1, intraperitoneal cisplatin and intratympanic α-lipoic acid in group 2, intratympanic α-lipoic acid in group 3, as well as intraperitoneal cisplatin and intratympanic saline in group 4. Distortion-product otoacoustic emission measurements were obtained for both ears at the following time points: before administration (baseline recording) and on day 3 (72 h later). In group 1 (cisplatin), significant deterioration was observed at all frequencies on day 3 (P < 0.05). In group 2 (cisplatin + α-lipoic acid), deterioration was observed at all frequencies on day 3; however, this deterioration did not reach a statistical significance (P > 0.05). In group 3 (α-lipoic acid), no significant difference was observed between baseline and day 3 (P > 0.05). In group 4 (cisplatin + saline), deterioration was observed at all frequencies on day 3; however, this deterioration did not reach a statistical significance (P > 0.05). Cisplatin-induced hearing loss in the guinea pigs may be limited to some extent by the concomitant use of α-lipoic acid. Dose-dependent changes in the possible effects of α-lipoic acid need further investigation. Future morphologic studies may contribute to expose clearly the protective effect of α-lipoic acid.

Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist.

PubMed

Sato, Atsuhisa; Fukuda, Seiichi

2013-10-01

We have reported observing aldosterone breakthrough in the course of relatively long-term treatment with renin-angiotensin (RA) system inhibitors, where the plasma aldosterone concentration (PAC) increased following an initial decrease. Aldosterone breakthrough has the potential to eliminate the organ-protective effects of RA system inhibitors. We therefore conducted a study in essential hypertensive patients to determine whether aldosterone breakthrough occurred during treatment with the direct renin inhibitor (DRI) aliskiren and to ascertain its clinical significance. The study included 40 essential hypertensive patients (18 men and 22 women) who had been treated for 12 months with aliskiren. Aliskiren significantly decreased blood pressure and plasma renin activity (PRA). The PAC was also decreased significantly at 3 and 6 months; however, the significant difference disappeared after 12 months. Aldosterone breakthrough was observed in 22 of the subjects (55%). Urinary albumin excretion differed depending on whether breakthrough occurred. For the subjects in whom aldosterone breakthrough was observed, eplerenone was added. A significant decrease in urinary albumin excretion was observed after 1 month, independent of changes in blood pressure. In conclusion, this study demonstrated that aldosterone breakthrough occurs in some patients undergoing DRI therapy. Aldosterone breakthrough affects the drug's ability to improve urinary albumin excretion, and combining a mineralocorticoid receptor antagonist with the DRI may be useful for decreasing urinary albumin excretion. When the objective is organ protection in hypertensive patients, a two-pronged approach using combination therapy to inhibit both the RA system and aldosterone may be highly effective.

Mechanisms of gender-linked ischemic brain injury

PubMed Central

Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.

2010-01-01

Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872

Setting limits: Using air pollution thresholds to protect and restore US ecosystems

USGS Publications Warehouse

Fenn, Mark E.; Lambert, Kathleen F.; Blett, Tamara F.; Burns, Douglas A.; Pardo, Linda H.; Lovett, Gary M.; Haeuber, Richard A.; Evers, David C.; Driscoll, Charles T.; Jeffries, Dean S.

2011-01-01

More than four decades of research provide unequivocal evidence that sulfur, nitrogen, and mercury pollution have altered, and will continue to alter, our nation's lands and waters. The emission and deposition of air pollutants harm native plants and animals, degrade water quality, affect forest productivity, and are damaging to human health. Many air quality policies limit emissions at the source but these control measures do not always consider ecosystem impacts. Air pollution thresholds at which ecological effects are observed, such as critical loads, are effective tools for assessing the impacts of air pollution on essential ecosystem services and for informing public policy. U.S. ecosystems can be more effectively protected and restored by using a combination of emissions-based approaches and science-based thresholds of ecosystem damage.

DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice.

PubMed

Oršolić, Nada; Gajski, Goran; Garaj-Vrhovac, Vera; Dikić, Domagoj; Prskalo, Zvjezdana Špacir; Sirovina, Damir

2011-04-10

Diabetes mellitus is associated with a high production of reactive oxygen species, which may cause oxidative DNA damage. High levels of genomic damage have been associated with liver and renal failure as well as immune-system decline. Flavonoids are effective antioxidants and may protect against several chronic diseases including diabetes. This study used the comet assay to assess the levels of DNA damage in the blood, liver and kidney cells in untreated and quercetin (QU) or naringenin treated diabetic mice. In addition, the study was designed to establish whether QU or naringenin might have a biological effect in protecting diabetic mice against oxidative stress by using survival studies to observe total body injury at the level of the organism. QU or naringenin were injected to mice intraperitoneally (i.p.) at a dose of 50mg/kg for 7days starting 2days after a single dose (75mg/kg, i.v.) alloxan injection. These findings suggest that QU or naringenin treatment resulted in a significant increase in the body weight, the haematological and immunological parameters of blood, as well as leading to 100% survival of diabetic mice. The tested flavonoids have protective effects against alloxan-induced DNA-damage in peripheral lymphocytes but not in the liver and kidney cells of diabetic mice. It might be hypothesised that diabetic mice with a high intake of flavonoid-rich foods, and specifically foods rich in quercetin or naringenin, might be relatively protected against long-term complications of diabetes due to decreased oxidative stress. Various co-operative and synergistic action mechanisms of the tested flavonoids may lead to the protection of the whole organism against diabetes. Copyright © 2011 Elsevier B.V. All rights reserved.

Examining the effect of intramammary infections with minor mastitis pathogens on the acquisition of new intramammary infections with major mastitis pathogens--a systematic review and meta-analysis.

PubMed

Reyher, K K; Haine, D; Dohoo, I R; Revie, C W

2012-11-01

Major mastitis pathogens such as Staphylococcus aureus, Streptococcus agalactiae, Streptococcus uberis, Streptococcus dysgalactiae, and the coliforms are usually considered more virulent and damaging to the udder than minor mastitis pathogens such as Corynebacterium bovis and coagulase-negative staphylococci (CNS). The current literature contains several studies detailing analyses with conflicting results as to whether intramammary infection (IMI) with the minor pathogens decreases, increases, or has no effect on the risk of a quarter acquiring a new intramammary infection (NIMI) with a major pathogen. To investigate the available scientific evidence regarding the effect of IMI with minor pathogens on the acquisition of NIMI with major pathogens, a systematic review and meta-analysis were conducted. The total extant English- and French-language literature in electronic databases was searched and all publications cited by relevant papers were investigated. Results from 68 studies were extracted from 38 relevant papers. Random-effects models were used to investigate the effects of CNS and C. bovis on acquisition of new IMI with any of the major pathogens, as well as individually for the minor pathogens and Staph. aureus. Significant heterogeneity among studies exists, some of which could be accounted for by using meta-regression. Overall, observational studies showed no effect, whereas challenge studies showed strong and significant protective effects, specifically when major pathogens were introduced into the mammary gland via methods bypassing the teat end. Underlying risk can account for several unmeasured factors, and studies with higher underlying risk found more protective effects of minor pathogens. Larger doses of challenge organisms reduced the protective effect of minor pathogens, and studies with more stringent diagnostic criteria for pathogen IMI identified less protection. Smaller studies (those utilizing fewer than 40 cows) also showed a greater protective effect than larger studies. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

An evaluation of UV protection imparted by cotton fabrics dyed with natural colorants.

PubMed

Sarkar, Ajoy K

2004-10-27

The ultraviolet properties of textiles dyed with synthetic dyes have been widely reported in literature. However, no study has investigated the ultraviolet properties of natural fabrics dyed with natural colorants. This study reports the Ultraviolet Protection Factor (UPF) of cotton fabrics dyed with colorants of plant and insect origins. Three cotton fabrics were dyed with three natural colorants. Fabrics were characterized with respect to fabric construction, weight, thickness and thread count. Influence of fabric characteristics on Ultraviolet Protection Factor was studied. Role of colorant concentration on the ultraviolet protection factor was examined via color strength analysis. A positive correlation was observed between the weight of the fabric and their UPF values. Similarly, thicker fabrics offered more protection from ultraviolet rays. Thread count appears to negatively correlate with UPF. Dyeing with natural colorants dramatically increased the protective abilities of all three fabric constructions. Additionally, within the same fabric type UPF values increased with higher depths of shade. Dyeing cotton fabrics with natural colorants increases the ultraviolet protective abilities of the fabrics and can be considered as an effective protection against ultraviolet rays. The UPF is further enhanced with colorant of dark hues and with high concentration of the colorant in the fabric.

Further Characterization of the Mitigation of Radiation Lethality by Protective Wounding

PubMed Central

Dynlacht, Joseph R.; Garrett, Joy; Joel, Rebecca; Lane, Katharina; Mendonca, Marc S.; Orschell, Christie M.

2017-01-01

There continues to be a major effort in the United States to develop mitigators for the treatment of mass casualties that received high-intensity acute ionizing radiation exposures from the detonation of an improvised nuclear device during a radiological terrorist attack. The ideal countermeasure should be effective when administered after exposure, and over a wide range of absorbed doses. We have previously shown that the administration of a subcutaneous incision of a defined length, if administered within minutes after irradiation, protected young adult female C57BL/6 mice against radiation-induced lethality, and increased survival after total-body exposure to an LD50/30 X-ray dose from 50% to over 90%. We refer to this approach as “protective wounding”. In this article, we report on our efforts to further optimize, characterize and demonstrate the validity of the protective wounding response by comparing the response of female and male mice, varying the radiation dose, the size of the wound, and the timing of wounding with respect to administration of the radiation dose. Both male and female mice that received a subcutaneous incision after irradiation were significantly protected from radiation lethality. We observed that the extent of protection against lethality after an LD50/30 X-ray dose was independent of the size of the subcutaneous cut, and that a 3 mm subcutaneous incision is effective at enhancing the survival of mice exposed to a broad range of radiation doses (LD15–LD100). Over the range of 6.2–6.7 Gy, the increase in survival observed in mice that received an incision was associated with an enhanced recovery of hematopoiesis. The enhanced rate of recovery of hematopoiesis was preceded by an increase in the production of a select group of cytokines. Thus, a thorough knowledge of the timing of the cytokine cascade after wounding could aid in the development of novel pharmacological radiation countermeasures that can be administered several days after the actual radiation exposure. PMID:28437188

The rapid suicide protection of mood stabilizers on patients with bipolar disorder: A nationwide observational cohort study in Taiwan.

PubMed

Tsai, Chia-Jui; Cheng, Chin; Chou, Po-Han; Lin, Ching-Heng; McInnis, Melvin G; Chang, Chia-Li; Lan, Tsuo-Hung

2016-05-15

The suicide rate is high among bipolar disorder (BD) patients. Previous studies have focused on the anti-suicidal effect of long-term treatment with mood stabilizers but less on the immediate preventive effects of interventions. The aim of the study was to evaluate the short-term and immediate anti-suicidal effects of mood stabilizers on recent-onset BD patients. The National Health Insurance Database (NHID) of Taiwan was used to perform a nationwide cohort observation study of suicide behaviors in bipolar disorder. All the recent-onset BD patients (ICD-9-CM code 296 except 296.2 and 296.3) diagnosed between 2000-2005 were collected (n=5091) and followed through 2009. The primary endpoint was the presence of a suicide code or the end of observation; exposure to mood stabilizers in the final month of observation was the independent variable. The hazard ratios (HRs) of suicide-related events, completed suicide, and all-cause mortality were significantly lower for those treated with lithium, divalproex, or carbamazepine compared with no use in the last month (HRs of suicide-related events were 0.10, 0.14 and 0.10, respectively, and all-cause mortality HRs were 0.03; P<0.0001); there was no significant difference in HR between the mood stabilizers. The NIHD does not provide information on the severity, mood status, or treatment adherence of BD patients. Neither substance-related disorder nor personality disorder were included in the analysis. We focused on the effect of the final prescription time period, not the long-term protective effect. The immediate recent use of any mood stabilizer significantly lowers the rate of death, suicide, or suicidal behavior in BD. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl4 induced toxicity in rats.

PubMed

Abdel-Kader, Maged S; Abulhamd, Ashraf T; Hamad, Abubaker M; Alanazi, Abdullah H; Ali, Rizwan; Alqasoumi, Saleh I

2018-05-01

Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in  Glycyrrhiza glabra  (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011–2012 season in Spain, among population targeted for vaccination

PubMed Central

2013-01-01

Background In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011–2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. Results The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0–69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions The 2011–2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season. PMID:24053661

New keratin isolates: actives for natural hair protection.

PubMed

Roddick-Lanzilotta, Alisa; Kelly, Rob; Scott, Sonya; Chahal, Surinder

2007-01-01

Hair is primarily composed of keratin proteins and it is well established that peptides and proteins bestow desirable effects on the hair, for example improving moisturization and softness. In the present work we describe how keratin actives with unique properties convey a range of beneficial properties to a variety of hair types. It has been observed that these functional keratins protect hair from damage associated with chemical treatments such as perming and relaxation, help to restore the mechanical strength of damaged fibers and decrease fading of colored hair.

Chirality-induced magnon transport in AA-stacked bilayer honeycomb chiral magnets.

PubMed

Owerre, S A

2016-11-30

In this Letter, we study the magnetic transport in AA-stacked bilayer honeycomb chiral magnets coupled either ferromagnetically or antiferromagnetically. For both couplings, we observe chirality-induced gaps, chiral protected edge states, magnon Hall and magnon spin Nernst effects of magnetic spin excitations. For ferromagnetically coupled layers, thermal Hall and spin Nernst conductivities do not change sign as function of magnetic field or temperature similar to single-layer honeycomb ferromagnetic insulator. In contrast, for antiferromagnetically coupled layers, we observe a sign change in the thermal Hall and spin Nernst conductivities as the magnetic field is reversed. We discuss possible experimental accessible honeycomb bilayer quantum materials in which these effects can be observed.

Protective efficacy of 2-PAMCl, atropine and curcumin against dichlorvos induced toxicity in rats

PubMed Central

Yadav, Preeti; Jadhav, Sunil E.; Kumar, Vinesh; Kaul, Kirtee K.; Pant, Satish C.; Flora, Swaran J.S.

2012-01-01

The effect of 2- pyridine aldoxime methyl chloride (2-PAMCl) and atropine with or without curcumin was investigated in dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP) induced toxicity in rats. Rats were exposed to DDVP (2 mg/kg sub-cutaneously) once daily for the period of 21 days. Post DDVP exposure, rats were further treated with 2-PAMCl (50 mg/kg intramuscular, once daily) + atropine (10 mg/kg, i.m. once daily) with or without curcumin (200 mg/kg; oral; once daily) for further 21 days. We observed a significant increase in lipid peroxidation (LPO), reactive oxygen species (ROS), oxidized glutathione (GSSG), while there was a significant decrease in antioxidant enzymes, brain acetylcholinesterase (AChE) and 5-hydroxy tryptamine (5-HT) activity on DDVP exposure of rats. These alterations were restored significantly by co-administration of 2-PAMCl + atropine in DDVP exposed rats. Curcumin when co-supplemented with 2-PAMCl + atropine also significantly protected serum aspartate aminotransferase (AST) and restored brain AChE activity and 5-HT level in animals sub-chronically exposed to DDVP. Histopathological observations along with biochemical changes in rat blood and tissues revealed significant protection offered by 2-PAMCl + atropine against DDVP. The results indicate that DDVP-induced toxicity can be significantly protected by co-administration of 2-PAMCl + atropine individually, however, curcumin co-supplementation with 2-PAMCl + atropine provides more pronounced protection, concerning particularly neurological disorders. PMID:22783142

T cells play an essential role in anti-F1 mediated rapid protection against bubonic plague.

PubMed

Levy, Yinon; Flashner, Yehuda; Tidhar, Avital; Zauberman, Ayelet; Aftalion, Moshe; Lazar, Shirley; Gur, David; Shafferman, Avigdor; Mamroud, Emanuelle

2011-09-16

Plague, which is initiated by Yersinia pestis infection, is a fatal disease that progresses rapidly and leads to high mortality rates if not treated. Antibiotics are an effective plague therapy, but antibiotic-resistant Y. pestis strains have been reported and therefore alternative countermeasures are needed. In the present study, we assessed the potential of an F1 plus LcrV-based vaccine to provide protection shortly pre- or post-exposure to a lethal Y. pestis infection. Mice vaccinated up to one day before or even several hours after subcutaneous challenge were effectively protected. Mice immunized one or three days pre-challenge were protected even though their anti-F1 and anti-LcrV titers were below detection levels at the day of challenge. Moreover, using B-cell deficient μMT mice, we found that rapidly induced protective immunity requires the integrity of the humoral immune system. Analysis of the individual contributions of vaccine components to protection revealed that rF1 is responsible for the observed rapid antibody-mediated immunity. Applying anti-F1 passive therapy in the mouse model of bubonic plague demonstrated that anti-F1 F(ab')(2) can delay mortality, but it cannot provide long-lasting protection, as do intact anti-F1 molecules. Fc-dependent immune components, such as the complement system and (to a lesser extent) neutrophils, were found to contribute to mouse survival. Interestingly, T cells but not B cells were found to be essential for the recovery of infected animals following passive anti-F1 mediated therapy. These data extend our understanding of the immune mechanisms required for the development of a rapid and effective post-exposure therapy against plague. Copyright © 2011 Elsevier Ltd. All rights reserved.

Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats

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

Peng, Qiuxian; Department of Biology, Hong Kong Baptist University, Kowloon Tong; Zhang, Qin

Highlights: • AESM is able to prevent the elevation of ALT and AST, and to decreased LDL-C level. • AESM demonstrates the effects of down-regulating blood fat level and protecting liver. • AESM consistent with the efficacy of simvastatin in NAFLD. - Abstract: Objectives: Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Methods: Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertnmore » group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. Results: High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Conclusions: Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver.« less

Evaluation of a Wildfire Smoke Forecasting System as a Tool for Public Health Protection

PubMed Central

Brauer, Michael; Henderson, Sarah B.

2013-01-01

Background: Exposure to wildfire smoke has been associated with cardiopulmonary health impacts. Climate change will increase the severity and frequency of smoke events, suggesting a need for enhanced public health protection. Forecasts of smoke exposure can facilitate public health responses. Objectives: We evaluated the utility of a wildfire smoke forecasting system (BlueSky) for public health protection by comparing its forecasts with observations and assessing their associations with population-level indicators of respiratory health in British Columbia, Canada. Methods: We compared BlueSky PM2.5 forecasts with PM2.5 measurements from air quality monitors, and BlueSky smoke plume forecasts with plume tracings from National Oceanic and Atmospheric Administration Hazard Mapping System remote sensing data. Daily counts of the asthma drug salbutamol sulfate dispensations and asthma-related physician visits were aggregated for each geographic local health area (LHA). Daily continuous measures of PM2.5 and binary measures of smoke plume presence, either forecasted or observed, were assigned to each LHA. Poisson regression was used to estimate the association between exposure measures and health indicators. Results: We found modest agreement between forecasts and observations, which was improved during intense fire periods. A 30-μg/m3 increase in BlueSky PM2.5 was associated with an 8% increase in salbutamol dispensations and a 5% increase in asthma-related physician visits. BlueSky plume coverage was associated with 5% and 6% increases in the two health indicators, respectively. The effects were similar for observed smoke, and generally stronger in very smoky areas. Conclusions: BlueSky forecasts showed modest agreement with retrospective measures of smoke and were predictive of respiratory health indicators, suggesting they can provide useful information for public health protection. Citation: Yao J, Brauer M, Henderson SB. 2013. Evaluation of a wildfire smoke forecasting system as a tool for public health protection. Environ Health Perspect 121:1142–1147; http://dx.doi.org/10.1289/ehp.1306768 PMID:23906969

Current desires of conspecific observers affect cache-protection strategies in California scrub-jays and Eurasian jays.

PubMed

Ostojić, Ljerka; Legg, Edward W; Brecht, Katharina F; Lange, Florian; Deininger, Chantal; Mendl, Michael; Clayton, Nicola S

2017-01-23

Many corvid species accurately remember the locations where they have seen others cache food, allowing them to pilfer these caches efficiently once the cachers have left the scene [1]. To protect their caches, corvids employ a suite of different cache-protection strategies that limit the observers' visual or acoustic access to the cache site [2,3]. In cases where an observer's sensory access cannot be reduced it has been suggested that cachers might be able to minimise the risk of pilfering if they avoid caching food the observer is most motivated to pilfer [4]. In the wild, corvids have been reported to pilfer others' caches as soon as possible after the caching event [5], such that the cacher might benefit from adjusting its caching behaviour according to the observer's current desire. In the current study, observers pilfered according to their current desire: they preferentially pilfered food that they were not sated on. Cachers adjusted their caching behaviour accordingly: they protected their caches by selectively caching food that observers were not motivated to pilfer. The same cache-protection behaviour was found when cachers could not see on which food the observers were sated. Thus, the cachers' ability to respond to the observer's desire might have been driven by the observer's behaviour at the time of caching. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

How TK-TD and population models for aquatic macrophytes could support the risk assessment for plant protection products.

PubMed

Hommen, Udo; Schmitt, Walter; Heine, Simon; Brock, Theo Cm; Duquesne, Sabine; Manson, Phil; Meregalli, Giovanna; Ochoa-Acuña, Hugo; van Vliet, Peter; Arts, Gertie

2016-01-01

This case study of the Society of Environmental Toxicology and Chemistry (SETAC) workshop MODELINK demonstrates the potential use of mechanistic effects models for macrophytes to extrapolate from effects of a plant protection product observed in laboratory tests to effects resulting from dynamic exposure on macrophyte populations in edge-of-field water bodies. A standard European Union (EU) risk assessment for an example herbicide based on macrophyte laboratory tests indicated risks for several exposure scenarios. Three of these scenarios are further analyzed using effect models for 2 aquatic macrophytes, the free-floating standard test species Lemna sp., and the sediment-rooted submerged additional standard test species Myriophyllum spicatum. Both models include a toxicokinetic (TK) part, describing uptake and elimination of the toxicant, a toxicodynamic (TD) part, describing the internal concentration-response function for growth inhibition, and a description of biomass growth as a function of environmental factors to allow simulating seasonal dynamics. The TK-TD models are calibrated and tested using laboratory tests, whereas the growth models were assumed to be fit for purpose based on comparisons of predictions with typical growth patterns observed in the field. For the risk assessment, biomass dynamics are predicted for the control situation and for several exposure levels. Based on specific protection goals for macrophytes, preliminary example decision criteria are suggested for evaluating the model outputs. The models refined the risk indicated by lower tier testing for 2 exposure scenarios, while confirming the risk associated for the third. Uncertainties related to the experimental and the modeling approaches and their application in the risk assessment are discussed. Based on this case study and the assumption that the models prove suitable for risk assessment once fully evaluated, we recommend that 1) ecological scenarios be developed that are also linked to the exposure scenarios, and 2) quantitative protection goals be set to facilitate the interpretation of model results for risk assessment. © 2015 SETAC.

Effects of taurine supplementation on hepatic markers of inflammation and lipid metabolism in mothers and offspring in the setting of maternal obesity.

PubMed

Li, Minglan; Reynolds, Clare M; Sloboda, Deborah M; Gray, Clint; Vickers, Mark H

2013-01-01

Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may ameliorate the adverse effects observed in offspring following a maternal obesogenic diet but these effects are dependent upon prior maternal nutritional background.

Histological Observation of the Retinacula of Weitbrecht and Its Clinical Significance: A cadaveric study.

PubMed

Dou, Bang; Mei, Jiong; Wang, Zhiyuan; Ni, Ming; Jia, Guangyao; Liu, Shiwei

2018-01-01

The retinacular arteries provide major supply to the femoral head, their injuries may lead to the femoral head necrosis (FHN) in femoral neck fractures. Although the femoral neck fracture was seriously displaced in some patients, FHN did not occur, which suggests that the blood supply is not fully blocked. This study was aimed to find the association between the structure of the retinacula of Weitbrecht and the mechanism of protecting retinacular arteries from being injured. Fourteen formalin-fixed cadaveric specimens (in 28 hips) with no significant vascular disease were observed. The retinacula were cut longitudinally and then cut into three parts: medial, middle, and lateral. These specimens were stained using hematoxylin and eosin and improved Masson Trichrome stain. The microstructure and tightness of the retinacula fixed to the bone and the distribution of vessels were examined under a stereoscope, an optical microscope, and a scanning electron microscope. The microstructure and compactness in each part of retinacula were different, and the tightness of the fibers of the retinacula fixed to the bone in each part were different. A particular structure which resembled a Sandwich panels was observed, and it may be an effective mechanism of protecting retinacular arteries. The Sandwich panels structure existed generally in the retinacula of Weitbrecht, and this sandwich panelture may play very important role in protecting the retinaculum artery from being injured, which show the importance of protecting the retinacular artery in the treatment of femoral neck fractures.

The effect of resveratrol on protecting corneal epithelial cells from cytotoxicity caused by moxifloxacin and benzalkonium chloride.

PubMed

Tsai, Tzu-Yun; Chen, Ta-Ching; Wang, I-Jong; Yeh, Chao-Yuan; Su, Ming-Jai; Chen, Ruey-Hua; Tsai, Tzu-Hsun; Hu, Fung-Rong

2015-02-10

Moxifloxacin (MOX), a fourth generation fluoroquinolone (FQ), has a wide antibacterial spectrum, but may show cytotoxicity characterized by high productions of reactive oxygen species (ROS). This study investigated the protective role of a common antioxidant agent, resveratrol (trans-3,5,4'-trihydroxystilbene), against the cytotoxicity caused by MOX. Experiments were performed with a human corneal epithelial cell line (HCECs; ATCC-CRL-11515). Another commonly used FQ, levofloxacin (LEV), and the most commonly used preservatives, benzalkonium chloride (BAC), were also used for comparison with MOX. Cell viability and morphologic changes after treatment were evaluated with trypan blue exclusion assay, propidium iodine/annexin V-FITC staining, and flow cytometry. Chemiluminescence immunoassay was used for ROS quantification. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, wound healing assay, and intracellular detections of oxidative stress were performed to evaluate the effects of resveratrol. The MOX group, similar to the BAC group, showed significant cell shrinkage and death compared with the LEV group. High ROS production in HCECs of MOX group was observed both by chemiluminescence immunoassay and intracellular images. Within the observations of MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, live cell images, and wound healing process in vitro, the cytotoxic effects of the MOX and BAC groups were opposed by resveratrol. Human corneal epithelial cells pretreated with resveratrol demonstrated better cell viability and healing rate in the early stage. The protective effects of antioxidant agents indicate that MOX, similar to BAC, causes oxidative stress-related cell damage. The results also inspired us to think about a "supplementary regimen" to increase safety and decrease the adverse effect in the treatment of corneal infections. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

In Vitro Skin Penetration of Petrolatum and Soybean Oil and Effects of Glyceryl Monooleate.

PubMed

Intarakumhaeng, Rattikorn; Shi, Zhanquan; Wanasathop, Apipa; Stella, Q Ching; Wei, Karl S; Styczynski, P B; Li, Chuiying; Smith, Edward D; Li, S Kevin

2018-06-06

Petrolatum and soybean oil are common ingredients incorporated in topical skin formulations for skin protection and moisturization. However, the stratum corneum (SC) penetration kinetics of these two cosmetic ingredients has not been systematically studied. Glyceryl monooleate (GlyMOle) has been shown to enhance skin penetration of various compounds. It was hypothesized that GlyMOle could enhance skin penetration of petrolatum and soybean oil. The present study aimed to examine the in vitro skin penetration of petrolatum and soybean oil in the presence or absence of GlyMOle. Skin permeation experiments were conducted using the in vitro Franz diffusion cell model with split-thickness human skin and human epidermal membrane (HEM). The effect of permeant dose and the kinetics of permeant penetration were examined with and without GlyMOle in vitro. Petrolatum and soybean oil were found to permeate across HEM, and no effect of GlyMOle on skin permeation into the receptor chamber was observed. GlyMOle enhanced the penetration of petrolatum into the split-thickness skin at 50 μg dose (petrolatum:GlyMOle, 49:1, w/w). However, no effect of GlyMOle on petrolatum penetration was observed at 200 μg dose (petrolatum:GlyMOle, 49:1, w/w), indicating a dose-dependent effect. GlyMOle at the level used in the study did not enhance the penetration of soybean oil with 50 and 200 μg doses at any time points. GlyMOle was a skin penetration enhancer for petrolatum under the in vitro conditions identified in the present study. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Caffeic acid protects rat heart mitochondria against isoproterenol-induced oxidative damage

PubMed Central

Kumaran, Kandaswamy Senthil

2010-01-01

Cardiac mitochondrial dysfunction plays an important role in the pathology of myocardial infarction. The protective effects of caffeic acid on mitochondrial dysfunction in isoproterenol-induced myocardial infarction were studied in Wistar rats. Rats were pretreated with caffeic acid (15 mg/kg) for 10 days. After the pretreatment period, isoproterenol (100 mg/kg) was subcutaneously injected to rats at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-induced rats showed considerable increased levels of serum troponins and heart mitochondrial lipid peroxidation products and considerable decreased glutathione peroxidase and reduced glutathione. Also, considerably decreased activities of isocitrate, succinate, malate, α-ketoglutarate, and NADH dehydrogenases and cytochrome-C-oxidase were observed in the mitochondria of myocardial-infarcted rats. The mitochondrial calcium, cholesterol, free fatty acids, and triglycerides were considerably increased and adenosine triphosphate and phospholipids were considerably decreased in isoproterenol-induced rats. Caffeic acid pretreatment showed considerable protective effects on all the biochemical parameters studied. Myocardial infarct size was much reduced in caffeic acid pretreated isoproterenol-induced rats. Transmission electron microscopic findings also confirmed the protective effects of caffeic acid. The possible mechanisms of caffeic acid on cardiac mitochondria protection might be due to decreasing free radicals, increasing multienzyme activities, reduced glutathione, and adenosine triphosphate levels and maintaining lipids and calcium. In vitro studies also confirmed the free-radical-scavenging activity of caffeic acid. Thus, caffeic acid protected rat’s heart mitochondria against isoproterenol-induced damage. This study may have a significant impact on myocardial-infarcted patients. PMID:20376586

Caffeic acid protects rat heart mitochondria against isoproterenol-induced oxidative damage.

PubMed

Kumaran, Kandaswamy Senthil; Prince, Ponnian Stanely Mainzen

2010-11-01

Cardiac mitochondrial dysfunction plays an important role in the pathology of myocardial infarction. The protective effects of caffeic acid on mitochondrial dysfunction in isoproterenol-induced myocardial infarction were studied in Wistar rats. Rats were pretreated with caffeic acid (15 mg/kg) for 10 days. After the pretreatment period, isoproterenol (100 mg/kg) was subcutaneously injected to rats at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-induced rats showed considerable increased levels of serum troponins and heart mitochondrial lipid peroxidation products and considerable decreased glutathione peroxidase and reduced glutathione. Also, considerably decreased activities of isocitrate, succinate, malate, α-ketoglutarate, and NADH dehydrogenases and cytochrome-C-oxidase were observed in the mitochondria of myocardial-infarcted rats. The mitochondrial calcium, cholesterol, free fatty acids, and triglycerides were considerably increased and adenosine triphosphate and phospholipids were considerably decreased in isoproterenol-induced rats. Caffeic acid pretreatment showed considerable protective effects on all the biochemical parameters studied. Myocardial infarct size was much reduced in caffeic acid pretreated isoproterenol-induced rats. Transmission electron microscopic findings also confirmed the protective effects of caffeic acid. The possible mechanisms of caffeic acid on cardiac mitochondria protection might be due to decreasing free radicals, increasing multienzyme activities, reduced glutathione, and adenosine triphosphate levels and maintaining lipids and calcium. In vitro studies also confirmed the free-radical-scavenging activity of caffeic acid. Thus, caffeic acid protected rat's heart mitochondria against isoproterenol-induced damage. This study may have a significant impact on myocardial-infarcted patients.

Supplementation of soft drinks with metallic ions reduces dissolution of bovine enamel

PubMed Central

PEREIRA, Heloisa Aparecida Barbosa da Silva; LEITE, Aline de Lima; ITALIANI, Flávia de Moraes; KATO, Melissa Thiemi; PESSAN, Juliano Pelim; BUZALAF, Marília Afonso Rabelo

2013-01-01

Objective The aim of this study was to evaluate the effect of the addition of metallic ions to carbonated drinks on their erosive potential. Material and Methods Powdered enamel was added to carbonated beverages (Coca-ColaTM or Sprite ZeroTM and shaken for 30 s. The samples were then immediately centrifuged and the supernatant removed. This procedure was repeated 5 times with the beverages containing Cu2+, Mg2+, Mn2+ or Zn2+ (1.25-60 mmol/L). For Coca-ColaTM, the concentration of each ion that exhibited the highest protection was also evaluated in combination with Fe2+. The phosphate or calcium released were analyzed spectrophotometrically. Data were analyzed using ANOVA and Tukey's test (p<0.05). Results For Coca-ColaTM, the best protective effect was observed for Zn2+ alone (10 mmol/L) or in combination (1 mmol/L) with other ions (12% and 27%, respectively, when compared with the control). Regarding Sprite ZeroTM, the best protective effect was observed for Cu2+ at 15 and 30 mmol/L, which decreased the dissolution by 22-23%. Zn2+ at 2.5 mmol/L also reduced the dissolution of powdered enamel by 8%. Conclusions The results suggest that the combination of metallic ions can be an alternative to reduce the erosive potential of Coca-ColaTM. Regarding Sprite ZeroTM, the addition of Cu2+ seems to be the best alternative. PMID:24037077

Protective effect of CMV reactivation on relapse after allogeneic hematopoietic cell transplantation in AML patients is influenced by their conditioning regimen

PubMed Central

Manjappa, Shivaprasad; Bhamidipati, Pavan Kumar; Stokerl-Goldstein, Keith E.; DiPersio, John F.; Uy, Geoffrey L.; Westervelt, Peter; Liu, Jingxia; Schroeder, Mark A.; Vij, Ravi; Abboud, Camille N.; Fehniger, Todd A; Cashen, Amanda F.; Pusic, Iskra; Jacoby, Meagan; Meera, Srinidhi J.; Romee, Rizwan

2014-01-01

Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplant (allo-HCT) has been associated with reduced risk of relapse in patients with acute myeloid leukemia (AML). However the influence of the conditioning regimen on this protective effect of CMV reactivation after allo-HCT is relatively unexplored. To address this, we evaluated the risk of relapse in 264 AML patients who received T cell replete, 6/6 HLA matched sibling or 10/10 HLA matched unrelated donor transplantation at a single institution between 2006 and 2011. Out of these 264 patients, 206 received myeloablative (MA) and 58 received reduced intensity conditioning (RIC) regimens. CMV reactivation was observed in 88 patients with MA conditioning and 37 patients with RIC. At a median follow up of 299 days, CMV reactivation was associated with significantly lower risk of relapse in patients who received MA conditioning both in univariate (P= .01) and multivariate analyses (hazard ratio of 0.5246, P= .006), however CMV reactivation did not significantly affect the risk of relapse in our RIC cohort. These results confirm the protective effect of CMV reactivation on relapse in AML patients after allo-HCT reported by previous studies, however they suggest that this protective effect of CMV reactivation on relapse is influenced by the conditioning regimen used with the transplant. PMID:24120526

Prion Protein Does Not Confer Resistance to Hippocampus-Derived Zpl Cells against the Toxic Effects of Cu2+, Mn2+, Zn2+ and Co2+ Not Supporting a General Protective Role for PrP in Transition Metal Induced Toxicity

PubMed Central

Cingaram, Pradeep Kumar Reddy; Nyeste, Antal; Dondapati, Divya Teja; Fodor, Elfrieda; Welker, Ervin

2015-01-01

The interactions of transition metals with the prion protein (PrP) are well-documented and characterized, however, there is no consensus on their role in either the physiology of PrP or PrP-related neurodegenerative disorders. PrP has been reported to protect cells from the toxic stimuli of metals. By employing a cell viability assay, we examined the effects of various concentrations of Cu2+, Zn2+, Mn2+, and Co2+ on Zpl (Prnp -/-) and ZW (Prnp +/+) hippocampus-derived mouse neuronal cells. Prnp -/- Zpl cells were more sensitive to all four metals than PrP-expressing Zw cells. However, when we introduced PrP or only the empty vector into Zpl cells, we could not discern any protective effect associated with the presence of PrP. This observation was further corroborated when assessing the toxic effect of metals by propidium-iodide staining and fluorescence activated cell sorting analysis. Thus, our results on this mouse cell culture model do not seem to support a strong protective role for PrP against transition metal toxicity and also emphasize the necessity of extreme care when comparing cells derived from PrP knock-out and wild type mice. PMID:26426582

Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review.

PubMed

Warren-Gash, Charlotte; Smeeth, Liam; Hayward, Andrew C

2009-10-01

Cardiac complications of influenza infection, such as myocarditis, are well recognised, but the role of influenza as a trigger of acute myocardial infarction is less clear. We did a systematic review of the evidence that influenza (including influenza-like illness and acute respiratory infection) triggers acute myocardial infarction or cardiovascular death. We examined the effectiveness of influenza vaccines at protecting against cardiac events and did a meta-analysis of data from randomised controlled trials. 42 publications describing 39 studies were identified. Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction. There was weaker evidence of an association with cardiovascular death. Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a protective, though non-significant, effect (relative risk 0.51, 95% CI 0.15-1.76). We believe influenza vaccination should be encouraged wherever indicated, especially in people with existing cardiovascular disease, among whom there is often suboptimum vaccine uptake. Further evidence is needed on the effectiveness of influenza vaccines to reduce the risk of cardiac events in people without established vascular disease.

Opportunities for Cost-Sharing in Conservation: Variation in Volunteering Effort across Protected Areas

PubMed Central

Armsworth, Paul R.; Cantú-Salazar, Lisette; Parnell, Mark; Booth, Josephine E.; Stoneman, Rob; Davies, Zoe G.

2013-01-01

Efforts to expand protected area networks are limited by the costs of managing protected sites. Volunteers who donate labor to help manage protected areas can help defray these costs. However, volunteers may be willing to donate more labor to some protected areas than others. Understanding variation in volunteering effort would enable conservation organizations to account for volunteer labor in their strategic planning. We examined variation in volunteering effort across 59 small protected areas managed by Yorkshire Wildlife Trust, a regional conservation nonprofit in the United Kingdom. Three surveys of volunteering effort reveal consistent patterns of variation across protected areas. Using the most detailed of these sources, a survey of site managers, we estimate that volunteers provided 3200 days of labor per year across the 59 sites with a total value exceeding that of paid staff time spent managing the sites. The median percentage by which volunteer labor supplements management costs on the sites was 36%. Volunteering effort and paid management costs are positively correlated, after controlling for the effect of site area. We examined how well a range of characteristics of the protected areas and surrounding communities explain variation in volunteering effort. Protected areas that are larger have been protected for longer and that are located near to denser conurbations experience greater volunteering effort. Together these factors explain 38% of the observed variation in volunteering effort across protected areas. PMID:23383176

Opportunities for cost-sharing in conservation: variation in volunteering effort across protected areas.

PubMed

Armsworth, Paul R; Cantú-Salazar, Lisette; Parnell, Mark; Booth, Josephine E; Stoneman, Rob; Davies, Zoe G

2013-01-01

Efforts to expand protected area networks are limited by the costs of managing protected sites. Volunteers who donate labor to help manage protected areas can help defray these costs. However, volunteers may be willing to donate more labor to some protected areas than others. Understanding variation in volunteering effort would enable conservation organizations to account for volunteer labor in their strategic planning. We examined variation in volunteering effort across 59 small protected areas managed by Yorkshire Wildlife Trust, a regional conservation nonprofit in the United Kingdom. Three surveys of volunteering effort reveal consistent patterns of variation across protected areas. Using the most detailed of these sources, a survey of site managers, we estimate that volunteers provided 3200 days of labor per year across the 59 sites with a total value exceeding that of paid staff time spent managing the sites. The median percentage by which volunteer labor supplements management costs on the sites was 36%. Volunteering effort and paid management costs are positively correlated, after controlling for the effect of site area. We examined how well a range of characteristics of the protected areas and surrounding communities explain variation in volunteering effort. Protected areas that are larger have been protected for longer and that are located near to denser conurbations experience greater volunteering effort. Together these factors explain 38% of the observed variation in volunteering effort across protected areas.

Evaluation of a wildfire smoke forecasting system as a tool for public health protection.

PubMed

Yao, Jiayun; Brauer, Michael; Henderson, Sarah B

2013-10-01

Exposure to wildfire smoke has been associated with cardiopulmonary health impacts. Climate change will increase the severity and frequency of smoke events, suggesting a need for enhanced public health protection. Forecasts of smoke exposure can facilitate public health responses. We evaluated the utility of a wildfire smoke forecasting system (BlueSky) for public health protection by comparing its forecasts with observations and assessing their associations with population-level indicators of respiratory health in British Columbia, Canada. We compared BlueSky PM2.5 forecasts with PM2.5 measurements from air quality monitors, and BlueSky smoke plume forecasts with plume tracings from National Oceanic and Atmospheric Administration Hazard Mapping System remote sensing data. Daily counts of the asthma drug salbutamol sulfate dispensations and asthma-related physician visits were aggregated for each geographic local health area (LHA). Daily continuous measures of PM2.5 and binary measures of smoke plume presence, either forecasted or observed, were assigned to each LHA. Poisson regression was used to estimate the association between exposure measures and health indicators. We found modest agreement between forecasts and observations, which was improved during intense fire periods. A 30-μg/m3 increase in BlueSky PM2.5 was associated with an 8% increase in salbutamol dispensations and a 5% increase in asthma-related physician visits. BlueSky plume coverage was associated with 5% and 6% increases in the two health indicators, respectively. The effects were similar for observed smoke, and generally stronger in very smoky areas. BlueSky forecasts showed modest agreement with retrospective measures of smoke and were predictive of respiratory health indicators, suggesting they can provide useful information for public health protection.

Human Perceptions Mirror Realities of Carnivore Attack Risk for Livestock: Implications for Mitigating Human-Carnivore Conflict

PubMed Central

Miller, Jennifer R. B.; Jhala, Yadvendradev V.; Schmitz, Oswald J.

2016-01-01

Human-carnivore conflict is challenging to quantify because it is shaped by both the realities and people’s perceptions of carnivore threats. Whether perceptions align with realities can have implications for conflict mitigation: misalignments can lead to heightened and indiscriminant persecution of carnivores whereas alignments can offer deeper insights into human-carnivore interactions. We applied a landscape-scale spatial analysis of livestock killed by tigers and leopards in India to model and map observed attack risk, and surveyed owners of livestock killed by tigers and leopards for their rankings of threats across habitats to map perceived attack risk. Observed tiger risk to livestock was greatest near dense forests and at moderate distances from human activity while leopard risk was greatest near open vegetation. People accurately perceived spatial differences between tiger and leopard hunting patterns, expected greater threat in areas with high values of observed risk for both carnivores. Owners’ perception of threats largely did not depend on environmental conditions surrounding their village (spatial location, dominant land-use or observed carnivore risk). Surveys revealed that owners who previously lost livestock to carnivores used more livestock protection methods than those who had no prior losses, and that owners who had recently lost livestock for the first time expressed greater interest in changing their protection methods than those who experienced prior losses. Our findings suggest that in systems where realities and perceptions of carnivore risk align, conservation programs and policies can optimize conservation outcomes by (1) improving the effectiveness of livestock protection methods and (2) working with owners who have recently lost livestock and are most willing to invest effort in adapting protection strategies to mitigate human-carnivore conflict. PMID:27617831

Human Perceptions Mirror Realities of Carnivore Attack Risk for Livestock: Implications for Mitigating Human-Carnivore Conflict.

PubMed

Miller, Jennifer R B; Jhala, Yadvendradev V; Schmitz, Oswald J

2016-01-01

Human-carnivore conflict is challenging to quantify because it is shaped by both the realities and people's perceptions of carnivore threats. Whether perceptions align with realities can have implications for conflict mitigation: misalignments can lead to heightened and indiscriminant persecution of carnivores whereas alignments can offer deeper insights into human-carnivore interactions. We applied a landscape-scale spatial analysis of livestock killed by tigers and leopards in India to model and map observed attack risk, and surveyed owners of livestock killed by tigers and leopards for their rankings of threats across habitats to map perceived attack risk. Observed tiger risk to livestock was greatest near dense forests and at moderate distances from human activity while leopard risk was greatest near open vegetation. People accurately perceived spatial differences between tiger and leopard hunting patterns, expected greater threat in areas with high values of observed risk for both carnivores. Owners' perception of threats largely did not depend on environmental conditions surrounding their village (spatial location, dominant land-use or observed carnivore risk). Surveys revealed that owners who previously lost livestock to carnivores used more livestock protection methods than those who had no prior losses, and that owners who had recently lost livestock for the first time expressed greater interest in changing their protection methods than those who experienced prior losses. Our findings suggest that in systems where realities and perceptions of carnivore risk align, conservation programs and policies can optimize conservation outcomes by (1) improving the effectiveness of livestock protection methods and (2) working with owners who have recently lost livestock and are most willing to invest effort in adapting protection strategies to mitigate human-carnivore conflict.

Protection and Sensitization of Human Cells to Proton Radiation by Cerium Oxide Nanoparticles

NASA Astrophysics Data System (ADS)

Carlson, Nathan B.

In radiation therapy for the treatment of cancer, there is demand for novel approaches that will improve tumor cell killing while protecting healthy tissue. One such approach that has shown considerable promise is the application of nanoparticles as radiation sensitizers for tumor cells and as radiation protectants for healthy tissue. In this investigation, cerium oxide nanoparticles (CNPs) obtained from the University of Central Florida's NanoScience Technology Center were studied for their protective effect to charged particle radiation in non-malignant breast cells, and for their sensitizing effect in breast and prostate cancer cell lines. These experiments were conducted at East Carolina University, where human cells were grown in the cell culture facility in the Department of Biology and then irradiated with energetic protons in the Accelerator Laboratory in the Department of Physics. Prior to irradiation, the cells were treated with distinct CNP preparations ranging in concentrations from 10 nanomolar to 10 micromolar, and cell viability was assessed using multiple assays post-irradiation. Radioprotection and radiosensitization were observed for several of the CNP treatments tested. Ultimately, the goal is to find a specific nanoparticle treatment that holds the synergistic effect of enhancing the rate of killing in tumor cells while simultaneously improving the survival of normal cells.

An Evaluation of Root Phytochemicals Derived from Althea officinalis (Marshmallow) and Astragalus membranaceus as Potential Natural Components of UV Protecting Dermatological Formulations

PubMed Central

Curnow, Alison; Owen, Sara J.

2016-01-01

As lifetime exposure to ultraviolet (UV) radiation has risen, the deleterious effects have also become more apparent. Numerous sunscreen and skincare products have therefore been developed to help reduce the occurrence of sunburn, photoageing, and skin carcinogenesis. This has stimulated research into identifying new natural sources of effective skin protecting compounds. Alkaline single-cell gel electrophoresis (comet assay) was employed to assess aqueous extracts derived from soil or hydroponically glasshouse-grown roots of Althea officinalis (Marshmallow) and Astragalus membranaceus, compared with commercial, field-grown roots. Hydroponically grown root extracts from both plant species were found to significantly reduce UVA-induced DNA damage in cultured human lung and skin fibroblasts, although initial Astragalus experimentation detected some genotoxic effects, indicating that Althea root extracts may be better suited as potential constituents of dermatological formulations. Glasshouse-grown soil and hydroponic Althea root extracts afforded lung fibroblasts with statistically significant protection against UVA irradiation for a greater period of time than the commercial field-grown roots. No significant reduction in DNA damage was observed when total ultraviolet irradiation (including UVB) was employed (data not shown), indicating that the extracted phytochemicals predominantly protected against indirect UVA-induced oxidative stress. Althea phytochemical root extracts may therefore be useful components in dermatological formulations. PMID:26953144

An Evaluation of Root Phytochemicals Derived from Althea officinalis (Marshmallow) and Astragalus membranaceus as Potential Natural Components of UV Protecting Dermatological Formulations.

PubMed

Curnow, Alison; Owen, Sara J

2016-01-01

As lifetime exposure to ultraviolet (UV) radiation has risen, the deleterious effects have also become more apparent. Numerous sunscreen and skincare products have therefore been developed to help reduce the occurrence of sunburn, photoageing, and skin carcinogenesis. This has stimulated research into identifying new natural sources of effective skin protecting compounds. Alkaline single-cell gel electrophoresis (comet assay) was employed to assess aqueous extracts derived from soil or hydroponically glasshouse-grown roots of Althea officinalis (Marshmallow) and Astragalus membranaceus, compared with commercial, field-grown roots. Hydroponically grown root extracts from both plant species were found to significantly reduce UVA-induced DNA damage in cultured human lung and skin fibroblasts, although initial Astragalus experimentation detected some genotoxic effects, indicating that Althea root extracts may be better suited as potential constituents of dermatological formulations. Glasshouse-grown soil and hydroponic Althea root extracts afforded lung fibroblasts with statistically significant protection against UVA irradiation for a greater period of time than the commercial field-grown roots. No significant reduction in DNA damage was observed when total ultraviolet irradiation (including UVB) was employed (data not shown), indicating that the extracted phytochemicals predominantly protected against indirect UVA-induced oxidative stress. Althea phytochemical root extracts may therefore be useful components in dermatological formulations.

Genetic Structure, Diversity and Long Term Viability of a Medicinal Plant, Nothapodytes nimmoniana Graham. (Icacinaceae), in Protected and Non-Protected Areas in the Western Ghats Biodiversity Hotspot

PubMed Central

Shivaprakash, K. Nagaraju; Ramesha, B. Thimmappa; Uma Shaanker, Ramanan; Dayanandan, Selvadurai; Ravikanth, Gudasalamani

2014-01-01

Background and Question The harvesting of medicinal plants from wild sources is escalating in many parts of the world, compromising the long-term survival of natural populations of medicinally important plants and sustainability of sources of raw material to meet pharmaceutical industry needs. Although protected areas are considered to play a central role in conservation of plant genetic resources, the effectiveness of protected areas for maintaining medicinal plant populations subject to intense harvesting pressure remain largely unknown. We conducted genetic and demographic studies of Nothapodytes nimmoniana Graham, one of the extensively harvested medicinal plant species in the Western Ghats biodiversity hotspot, India to assess the effectiveness of protected areas in long-term maintenance of economically important plant species. Methodology/Principal Findings The analysis of adults and seedlings of N. nimmoniana in four protected and four non-protected areas using 7 nuclear microsatellite loci revealed that populations that are distributed within protected areas are subject to lower levels of harvesting and maintain higher genetic diversity (He = 0.816, Ho = 0.607, A = 18.857) than populations in adjoining non-protected areas (He = 0.781, Ho = 0.511, A = 15.571). Furthermore, seedlings in protected areas had significantly higher observed heterozygosity (Ho = 0.630) and private alleles as compared to seedlings in adjoining non-protected areas (Ho = 0.426). Most populations revealed signatures of recent genetic bottleneck. The prediction of long-term maintenance of genetic diversity using BOTTLESIM indicated that current population sizes of the species are not sufficient to maintain 90% of present genetic diversity for next 100 years. Conclusions/Significance Overall, these results highlight the need for establishing more protected areas encompassing a large number of adult plants in the Western Ghats to conserve genetic diversity of economically and medicinally important plant species. PMID:25493426

The IMI PROTECT project: purpose, organizational structure, and procedures.

PubMed

Reynolds, Robert F; Kurz, Xavier; de Groot, Mark C H; Schlienger, Raymond G; Grimaldi-Bensouda, Lamiae; Tcherny-Lessenot, Stephanie; Klungel, Olaf H

2016-03-01

The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) initiative was a collaborative European project that sought to address limitations of current methods in the field of pharmacoepidemiology and pharmacovigilance. Initiated in 2009 and ending in 2015, PROTECT was part of the Innovative Medicines Initiative, a joint undertaking by the European Union and pharmaceutical industry. Thirty-five partners including academics, regulators, small and medium enterprises, and European Federation of Pharmaceuticals Industries and Associations companies contributed to PROTECT. Two work packages within PROTECT implemented research examining the extent to which differences in the study design, methodology, and choice of data source can contribute to producing discrepant results from observational studies on drug safety. To evaluate the effect of these differences, the project applied different designs and analytic methodology for six drug-adverse event pairs across several electronic healthcare databases and registries. This papers introduces the organizational structure and procedures of PROTECT, including how drug-adverse event and data sources were selected, study design and analyses documents were developed, and results managed centrally. Copyright © 2016 John Wiley & Sons, Ltd.

Protective effect of vanilloids against tert-butyl hydroperoxide-induced oxidative stress in vero cells culture.

PubMed

Rosa, Antonella; Atzeri, Angela; Deiana, Monica; Melis, M Paola; Incani, Alessandra; Corona, Giulia; Loru, Debora; Appendino, Giovanni; Dessì, M Assunta

2008-05-28

This study investigated the effect of synthetic capsiate, a simplified analogue of capsiate, and vanillyl alcohol on the oxidative stress induced by tert-butyl hydroperoxide (TBH) in a line of fibroblasts derived from monkey kidney (Vero cells). In response to the TBH-mediated oxidative stress, a reduction of the levels of total unsaturated fatty acids and cholesterol was observed, and a rise in the concentrations of conjugated dienes fatty acids hydroperoxides and 7-ketocholesterol. Pretreatment with both synthetic capsiate and vanillyl alcohol preserved Vero cells from oxidative damage and showed a remarkable protective effect on the reduction of the levels of total unsaturated fatty acids and cholesterol, inhibiting the increase of MDA, conjugated dienes fatty acids hydroperoxides, and 7-ketocholesterol. Both compounds were effective against peroxidation of cell membrane lipids induced by TBH, with synthetic capsiate essentially acting as a pro-drug of vanillyl alcohol, its hydrophilic hydrolytic derivative.

Effects of Cell-Free Spleen Extract Treatment on the Hematopoietic Tissues of Irradiated Guinea-Pigs

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

Ellinger, Friedrigh; Strike, Thomas A.

2004-07-01

Guinea pigs were given whole-body Co 60 irradiation (650 r) and injected daily thereafter with cell-free extracts of homologous and heterologous spleen. Spleen of irradiated control guinea pigs showed a progressive reduction of alkaline phosphatase staining commencing after the 3rd postirradiation day and reaching a maximum on or about the 9th day. Treatment of the animals with spleen extracts modified the radioinduced changes in alkaline phosphatase staining, so that an almost normal appearance was noted over the entire 14-day observation period. Most of the alkaiine phosphatase-staining spleen elements were mature neutrophils. It was concluded that spleen extract treatment affects apparentlymore » various celluiar elements of spleen in a different way. The results support the hypothesis that protection of phosphorylization processes against effects of irradiation represent one of the mechanisms by which the radiation protective effect of spleen extracts is effected.« less

Antiviral Effect of Pyran Against Systemic Infection of Mice with Herpes Simplex Virus Type 2

PubMed Central

McCord, Ronald S.; Breinig, Mary K.; Morahan, Page S.

1976-01-01

The immunomodulator pyran markedly protected 5-week-old mice from lethal intravenous infection with herpes simplex virus type 2. The 50% lethal dose was increased almost 100-fold in pyran-treated mice as compared with controls. Although the protection was not as marked in older mice (10 and 16 weeks old), there was a significant increase in mean survival time. When the pathogenesis of herpesvirus disease was monitored in control and drug-treated mice, the effect of pyran was most evident in the spinal cord, where virus was recovered from 20 of 25 control mice and from only 6 of 25 pyran-treated mice. There was also a significant reduction in the titer of virus present, and virus appeared later in the spinal cord of pyran-treated mice than in control mice. The protective effect of pyran was observed only when the drug was administered 24 h before viral challenge, was seen after both intraperitoneal and intravenous injection, and was not due to direct inactivation of the virus. PMID:185945

Protective effect of U74500A on phorbol myristate acetate-induced acute lung injury.

PubMed

Chu, Shi-Jye; Chang, Deh-Ming; Wang, David; Lin, Hen-I; Lin, Shih-Hua; Hsu, Kang

2004-08-01

1. The present study was designed to determine whether U74500A could ameliorate acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in our rat isolated lung model compared with any amelioration induced by dimethylthiourea (DMTU), superoxide dismutase (SOD) and catalase. 2. Acute lung injury was induced successfully by PMA during 60 min of observation. At 2 microg/kg, PMA elicited a significant increase in microvascular permeability (measured using the capillary filtration coefficient Kfc), lung weight gain, the lung weight/bodyweight ratio, pulmonary arterial pressure and protein concentration of the bronchoalveolar lavage fluid. 3. Pretreatment with 1.5 mg/kg U74500A significantly attenuated ALI; there was no significant increase in any parameters measured, except for pulmonary arterial pressure. The protective effect of U74500A was approximately the same as that of 600 mg/kg DMTU. However, 6000 U/kg SOD, 50,000 U/kg catalase and 6000 U/kg SOD + 50,000 U/kg catalase had no protective effect. 4. These experimental data suggest that U74500A significantly ameliorates ALI induced by PMA in rats.

Methamphetamine induces apoptosis in immortalized neural cells: protection by the proto-oncogene, bcl-2.

PubMed

Cadet, J L; Ordonez, S V; Ordonez, J V

1997-02-01

Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2 could protect against METH-induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA laddering. All these changes were prevented by bcl-2 expression. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway.

The roles of contact conformity, temperature and displacement amplitude on the lubricated fretting wear of a steel-on-steel contact

PubMed Central

Warmuth, A. R.; Sun, W.; Shipway, P. H.

2016-01-01

This paper investigates the effect of contact geometry, temperature and displacement amplitude on the fretting behaviour of an aero-turbo oil lubricated cylinder-on-flat contact. To be effective, the lubricant needed both to penetrate the contact and then offer protection. Lubricant penetration into the fretting contact is found to be controlled by two physical parameters, namely (i) the width of the contact that remains covered throughout the fretting test and (ii) the lubricant viscosity. The protection offered by the lubricant (assuming that it has successfully penetrated the contact) is influenced by four physical parameters, namely (i) lubricant viscosity, (ii) traverse velocity, (iii) nominal contact pressure, and (iv) chemical effects. The relationship between the three experimental parameters which were varied in the programme of work (temperature, fretting displacement and cylinder radius) and physical parameters which influence the protection offered by the lubricant film can be competing, and therefore complex wear behaviour is observed. The roles of the various parameters in controlling the wear behaviour are presented in a coherent physical framework. PMID:27853530

Phycocyanin and phycocyanobilin from Spirulina platensis protect against diabetic nephropathy by inhibiting oxidative stress.

PubMed

Zheng, Jing; Inoguchi, Toyoshi; Sasaki, Shuji; Maeda, Yasutaka; McCarty, Mark F; Fujii, Masakazu; Ikeda, Noriko; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

2013-01-15

We and other investigators have reported that bilirubin and its precursor biliverdin may have beneficial effects on diabetic vascular complications, including nephropathy, via its antioxidant effects. Here, we investigated whether phycocyanin derived from Spirulina platensis, a blue-green algae, and its chromophore phycocyanobilin, which has a chemical structure similar to that of biliverdin, protect against oxidative stress and renal dysfunction in db/db mice, a rodent model for Type 2 diabetes. Oral administration of phycocyanin (300 mg/kg) for 10 wk protected against albuminuria and renal mesangial expansion in db/db mice, and normalized tumor growth factor-β and fibronectin expression. Phycocyanin also normalized urinary and renal oxidative stress markers and the expression of NAD(P)H oxidase components. Similar antioxidant effects were observed following oral administration of phycocyanobilin (15 mg/kg) for 2 wk. Phycocyanobilin, bilirubin, and biliverdin also inhibited NADPH dependent superoxide production in cultured renal mesangial cells. In conclusion, oral administration of phycocyanin and phycocyanobilin may offer a novel and feasible therapeutic approach for preventing diabetic nephropathy.

The protective effect of marriage for survival: a review and update.

PubMed

Rendall, Michael S; Weden, Margaret M; Favreault, Melissa M; Waldron, Hilary

2011-05-01

The theory that marriage has protective effects for survival has itself lived for more than 100 years since Durkheim's groundbreaking study of suicide (Durkheim 1951 [1897]). Investigations of differences in this protective effect by gender, by age, and in contrast to different unmarried statuses, however, have yielded inconsistent conclusions. These investigations typically either use data in which marital status and other covariates are observed in cross-sectional surveys up to 10 years before mortality exposure, or use data from panel surveys with much smaller sample sizes. Their conclusions are usually not based on formal statistical tests of contrasts between men and women or between never-married, divorced/separated, and widowed statuses. Using large-scale pooled panel survey data linked to death registrations and earnings histories for U.S. men and women aged 25 and older, and with appropriate contrast tests, we find a consistent survival advantage for married over unmarried men and women, and an additional survival "premium" for married men. We find little evidence of mortality differences between never-married, divorced/separated, and widowed statuses.

MP-12 virus containing the clone 13 deletion in the NSs gene prevents lethal disease when administered after Rift Valley fever virus infection in hamsters.

PubMed

Gowen, Brian B; Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Nishiyama, Shoko; Wandersee, Luci; Scharton, Dionna; Jung, Kie-Hoon; Ikegami, Tetsuro

2015-01-01

Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) causes a range of illnesses that include retinitis, fulminant hepatitis, neurologic disease, and hemorrhagic fever. In hospitalized individuals, case fatality rates can be as high as 10-20%. There are no vaccines or antivirals approved for human use to prevent or treat severe RVFV infections. We previously tested the efficacy of the MP-12 vaccine strain and related variants with NSs truncations as a post-exposure prophylaxis in mice infected with wild-type pathogenic RVFV strain ZH501. Post-exposure efficacy of the rMP12-C13type, a recombinant MP-12 vaccine virus which encodes an in-frame truncation removing 69% of the NSs protein, resulted in 30% survival when administering the virus within 30 min of subcutaneous ZH501 challenge in mice, while the parental MP-12 virus conferred no protection by post-exposure vaccination. Here, we demonstrate uniform protection of hamsters by post-exposure vaccination with rMP12-C13type administered 6 h post-ZH501 infection while no efficacy was observed with the parental MP-12 virus. Notably, both the MP-12 and rMP12-C13type viruses were highly effective (100% protection) when administered 21 days prior to challenge. In a subsequent study delaying vaccination until 8, 12, and 24 h post-RVFV exposure, we observed 80, 70, and 30% survival, respectively. Our findings indicate that the rapid protective innate immune response elicited by rMP12-C13type may be due to the truncated NSs protein, suggesting that the resulting functional inactivation of NSs plays an important role in the observed post-exposure efficacy. Taken together, the data demonstrate that post-exposure vaccination with rMP12-C13type is effective in limiting ZH501 replication and associated disease in standard pre-exposure vaccination and post-challenge treatment models of RVFV infection, and suggest an extended post-exposure prophylaxis window beyond that initially observed in mice.

Evaluating the efficacy of breastfeeding guidelines on long-term outcomes for allergic disease.

PubMed

Bion, V; Lockett, G A; Soto-Ramírez, N; Zhang, H; Venter, C; Karmaus, W; Holloway, J W; Arshad, S H

2016-05-01

WHO guidelines advocate breastfeeding for 6 months, and EAACI guideline recommends exclusive breastfeeding for 4-6 months. However, evidence for breastfeeding to prevent asthma and allergic disease is conflicting. We examined whether following recommended breastfeeding guidelines alters the long-term risks of asthma, eczema, rhinitis or atopy. The effect of nonexclusive (0, >0-6, >6 months) and exclusive breastfeeding (0, >0-4, >4 months) on repeated measures of asthma (10, 18 years), eczema, rhinitis, and atopy (1-or-2, 4, 10, 18 years) risks was estimated in the IoW cohort (n = 1456) using log-linear models with generalized estimating equations. The Food Allergy and Intolerance Research (FAIR) cohort (n = 988), also from the IoW, was examined to replicate results. Breastfeeding (any or exclusive) had no effect on asthma and allergic disease in the IoW cohort. In the FAIR cohort, any breastfeeding for >0-6 months protected against asthma at 10 years (RR = 0.50, 95% CI = 0.32-0.79, P = 0.003), but not other outcomes, whilst exclusive breastfeeding for >4 months protected against repeated rhinitis (RR = 0.36, 95% CI = 0.18-0.71, P = 0.003). Longer breastfeeding was protective against late-onset wheeze in the IoW cohort. The protective effects of nonexclusive and exclusive breastfeeding against long-term allergic outcomes were inconsistent between these colocated cohorts, agreeing with previous observations of heterogeneous effects. Although breastfeeding should be recommended for other health benefits, following breastfeeding guidelines did not appear to afford a consistent protection against long-term asthma, eczema, rhinitis or atopy. Further research is needed into the long-term effects of breastfeeding on allergic disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluating the efficacy of breastfeeding guidelines on long-term outcomes for allergic disease

PubMed Central

Bion, Victoria; Lockett, Gabrielle A.; Soto-Ramírez, Nelís; Zhang, Hongmei; Venter, Carina; Karmaus, Wilfried; Holloway, John W.; Arshad, S. Hasan

2015-01-01

Background WHO guidelines advocate breastfeeding for six months, and EAACI recommends exclusive breastfeeding for 4–6 months. However, evidence for breastfeeding to prevent asthma and allergic disease is conflicting. We examined whether following recommended breastfeeding guidelines alters the long-term risks of asthma, eczema, rhinitis, or atopy. Methods The effect of non-exclusive (0, >0–6, >6 months), and exclusive breastfeeding (0, >0–4, >4 months) on repeated measures of asthma (10, 18 years), eczema, rhinitis, and atopy (1-or-2, 4, 10, 18 years) risks were estimated in the IoW cohort (n=1456) using log-linear models with generalised estimating equations. The Food Allergy and Intolerance Research (FAIR) cohort (n=988), also from the IoW, was examined to replicate results. Results Breastfeeding (any or exclusive) had no effect on asthma and allergic disease in the IoW cohort. In the FAIR cohort, any breastfeeding for >0–6 months protected against asthma at 10 years (RR=0.50, 95%CI=0.32–0.79, p=0.003) but not other outcomes, while exclusive breastfeeding for >4 months protected against repeated rhinitis (RR=0.36, 95%CI=0.18–0.71, p=0.003). Longer breastfeeding was protective against late-onset wheeze in the IoW cohort. Conclusion The protective effects of non-exclusive and exclusive breastfeeding against long-term allergic outcomes were inconsistent between these co-located cohorts, agreeing with previous observations of heterogeneous effects. Although breastfeeding should be recommended for other health benefits, following breastfeeding guidelines did not appear to afford consistent protection against long-term asthma, eczema, rhinitis or atopy. Further research is needed into the long-term effects of breastfeeding on allergic disease. PMID:26714430

Inflammatory Effects of the Plant Protection Product Stifenia (FEN560) on Vertebrates.

PubMed

Teyssier, Lény; Colussi, Julie; Delemasure, Stéphanie; Chluba, Johanna; Wendehenne, David; Lamotte, Olivier; Connat, Jean-Louis

2017-01-01

Plant defense stimulators (PDSs) rely on the activation of plant innate immunity in order to protect crops against various pests. These molecules are thought to be a safer alternative to classical plant protection products. Given that innate immune systems share common features in plants and vertebrates, PDS can potentially cross-react with innate immunity of non-target organisms. To test this hypothesis, we studied effects of the commercial PDS Stifenia (FEN560), which is composed of crushed fenugreek seeds. We tested various concentrations of Stifenia (0.03-1 mg mL -1 ) on human peripheral blood mononuclear cells and checked, 20 h later, cell metabolic activity (MA) using XTT assay, cell death by flow cytometry analysis, and IL-1β inflammatory cytokine released in the culture medium using ELISA. Stifenia induced a general decrease of the cell MA, which was concomitant with a dose-dependent release of IL-1β. Our results highlight the activation of human immune cells. The inflammatory effect of Stifenia was partially inhibited by pan-caspase inhibitor. Accordingly, Stifenia induced the release of p20 caspase-1 fragment into the culture medium suggesting the involvement of the NLRP3 inflammasome. Furthermore, we observed that Stifenia can induce cell death. We also tested the effect of Stifenia on Zebrafish larvae. After 24 h of exposure, Stifenia induced a dose-dependent IL-1β and TNFα gene expression. The human-cell-based approach developed in this work revealed a high sensitivity concerning inflammatory properties of a plant protection product. These tests could be routinely used to screen the potential adverse effects of this type of compounds. Finally, our results suggest a potential danger of using extensively certain PDS for crop protection.

Inflammatory Effects of the Plant Protection Product Stifenia (FEN560) on Vertebrates

PubMed Central

Teyssier, Lény; Colussi, Julie; Delemasure, Stéphanie; Chluba, Johanna; Wendehenne, David; Lamotte, Olivier; Connat, Jean-Louis

2017-01-01

Plant defense stimulators (PDSs) rely on the activation of plant innate immunity in order to protect crops against various pests. These molecules are thought to be a safer alternative to classical plant protection products. Given that innate immune systems share common features in plants and vertebrates, PDS can potentially cross-react with innate immunity of non-target organisms. To test this hypothesis, we studied effects of the commercial PDS Stifenia (FEN560), which is composed of crushed fenugreek seeds. We tested various concentrations of Stifenia (0.03–1 mg mL−1) on human peripheral blood mononuclear cells and checked, 20 h later, cell metabolic activity (MA) using XTT assay, cell death by flow cytometry analysis, and IL-1β inflammatory cytokine released in the culture medium using ELISA. Stifenia induced a general decrease of the cell MA, which was concomitant with a dose-dependent release of IL-1β. Our results highlight the activation of human immune cells. The inflammatory effect of Stifenia was partially inhibited by pan-caspase inhibitor. Accordingly, Stifenia induced the release of p20 caspase-1 fragment into the culture medium suggesting the involvement of the NLRP3 inflammasome. Furthermore, we observed that Stifenia can induce cell death. We also tested the effect of Stifenia on Zebrafish larvae. After 24 h of exposure, Stifenia induced a dose-dependent IL-1β and TNFα gene expression. The human-cell-based approach developed in this work revealed a high sensitivity concerning inflammatory properties of a plant protection product. These tests could be routinely used to screen the potential adverse effects of this type of compounds. Finally, our results suggest a potential danger of using extensively certain PDS for crop protection. PMID:28484691

A protein chimera including PspA in fusion with PotD is protective against invasive pneumococcal infection and reduces nasopharyngeal colonization in mice.

PubMed

Converso, T R; Goulart, C; Darrieux, M; Leite, L C C

2017-09-12

Despite the success of the available polysaccharide-based vaccines against Streptococcus pneumoniae in preventing invasive diseases, this bacterium remains a major cause of death in many parts of the world. New vaccine strategies are needed in order to increase protection. Thus, the utilization of fusion proteins is being investigated as an alternative to the current formulations. In the present work, we demonstrate that a chimeric protein, composed of PspA and PotD in fusion is able to maintain the protective characteristics of both parental proteins, providing protection against systemic infection while reducing nasal colonization. The hybrid was not able to improve the response against invasive disease elicited by PspA alone, but the inclusion of PotD was able to reduce colonization, an effect never observed using subcutaneous immunization with PspA. The mechanisms underlying the protective efficacy of the rPspA-PotD hybrid protein were investigated, revealing the production of antibodies with an increased binding capacity to pneumococcal strains of diverse serotypes and genetic backgrounds, enhanced opsonophagocytosis, and secretion of IL-17 by splenocytes. These findings reinforce the use of chimeric proteins based on surface antigens as an effective strategy against pneumococcal infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enteric coated spheres produced by extrusion/spheronization provide effective gastric protection and efficient release of live therapeutic bacteria.

PubMed

de Barros, João M S; Lechner, Tabea; Charalampopoulos, Dimitrios; Khutoryanskiy, Vitaliy V; Edwards, Alexander D

2015-09-30

We present a novel but simple enteric coated sphere formulation containing probiotic bacteria (Lactobacillus casei). Oral delivery of live bacterial cells (LBC) requires live cells to survive firstly manufacturing processes and secondly GI microbicidal defenses including gastric acid. We incorporated live L. casei directly in the granulation liquid, followed by granulation, extrusion, spheronization, drying and spray coating to produce dried live probiotic spheres. A blend of MCC, calcium-crosslinked alginate, and lactose was developed that gave improved live cell survival during manufacturing, and gave excellent protection from gastric acid plus rapid release in intestinal conditions. No significant loss of viability was observed in all steps except drying, which resulted in approximately 1 log loss of viable cells. Eudragit coating was used to protect dried live cells from acid, and microcrystalline cellulose (MCC) was combined with sodium alginate to achieve efficient sphere disintegration leading to rapid and complete bacterial cell release in intestinal conditions. Viability and release of L. casei was evaluated in vitro in simulated GI conditions. Uncoated spheres gave partial acid protection, but enteric coated spheres effectively protected dried probiotic LBC from acid for 2h, and subsequently released all viable cells within 1h of transfer into simulated intestinal fluid. Copyright © 2015 Elsevier B.V. All rights reserved.

How Much and What Type of Protein Should a Critically Ill Patient Receive?

PubMed

Ochoa Gautier, Juan B; Martindale, Robert G; Rugeles, Saúl J; Hurt, Ryan T; Taylor, Beth; Heyland, Daren K; McClave, Stephen A

2017-04-01

Protein loss, manifested as loss of muscle mass, is observed universally in all critically ill patients. Depletion of muscle mass is associated with impaired function and poor outcomes. In extreme cases, protein malnutrition is manifested by respiratory failure, lack of wound healing, and immune dysfunction. Protecting muscle loss focused initially on meeting energy requirements. The assumption was that protein was being used (through oxidation) as an energy source. In healthy individuals, small amounts of glucose (approximately 400 calories) protect muscle loss and decrease amino acid oxidation (protein-sparing effect of glucose). Despite expectations of the benefits, the high provision of energy (above basal energy requirements) through the delivery of nonprotein calories has failed to demonstrate a clear benefit at curtailing protein loss. The protein-sparing effect of glucose is not clearly observed during illness. Increasing protein delivery beyond the normal nutrition requirements (0.8 g/k/d) has been investigated as an alternative solution. Over a dozen observational studies in critically ill patients suggest that higher protein delivery is beneficial at protecting muscle mass and associated with improved outcomes (decrease in mortality). Not surprisingly, new Society of Critical Care Medicine/American Society for Parenteral and Enteral Nutrition guidelines and expert recommendations suggest higher protein delivery (>1.2 g/kg/d) for critically ill patients. This article provides an introduction to the concepts that delineate the basic principles of modern medical nutrition therapy as it relates to the goal of achieving an optimal management of protein metabolism during critical care illness, highlighting successes achieved so far but also placing significant challenges limiting our success in perspective.

Protective Effect of Neuropeptide Apelin-13 on 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Dopaminergic Cells: Involvement of Its Antioxidant and Antiapoptotic Properties.

PubMed

Pouresmaeili-Babaki, Elham; Esmaeili-Mahani, Saeed; Abbasnejad, Mehdi; Ravan, Hadi

2018-04-01

Parkinson's disease (PD) is a severe neurodegenerative disorder characterized by the loss of brain dopaminergic neurons. Beside pharmacologic and symptomatic treatment of PD the neuroprotective therapy has recently attracted more attention. Apelin, a novel neuropeptide, and its receptors have numerous reported roles in regulating brain functions. In addition, this peptide has potent neuroprotective effects in some neurodegenerative situations. In this study, the effects of apelin-13 were investigated in a cell model of PD. Human neuroblastoma SH-SY5Y cell damage was induced by 150 μM 6-hydroxydopamine (6-OHDA) and the cells viability was examined by MTT assay. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were determined by fluorescence spectrophotometry method. Immunoblotting analysis was also employed to evaluate cytochrome c release and caspase-3 activity. Data showed that 6-OHDA could decrease cell viability and mitochondrial membrane potential and increase intracellular ROS, cytochrome c, and cleaved caspase-3 levels. Pretreatment of SH-SY5Y cells with apelin-13 (5 and 10 nM) significantly prevented the mentioned biochemical and molecular markers of 6-OHDA-induced neurotoxicity. Furthermore, the results showed that apelin receptor and PI3K signaling contributed to the observed protective effects of apelin. The results suggest that apelin-13 has protective effects against dopaminergic neural toxicity and its antioxidant and antiapoptotic properties are involved, at least in part, in such protection.

Is influenza vaccination in asthma helpful?

PubMed

Bueving, Herman J; Thomas, Siep; Wouden, Johannes C van der

2005-02-01

Influenza infections are frequently involved in asthma exacerbations. During influenza epidemics substantial excess morbidity due to respiratory tract complications is reported in all age categories as well as excess mortality among the elderly. Vaccines are available for protection against influenza. Worldwide, vaccination is advised and considered a quality point for asthma care. However, the protective effect of influenza vaccination in patients with asthma is still disputed. In order to establish the current state of affairs we reviewed the recent literature on the protective effect of influenza vaccination and its usefulness in patients with asthma. Several studies were found addressing influenza and the protective aspects of vaccination. They discussed the incidence, the adverse effects of vaccination, the coverage of influenza vaccination among patients with asthma and the effectiveness of the vaccine. Influenza vaccination can safely be used in patients with asthma. Allegations that vaccination could provoke asthma exacerbations are convincingly invalidated by previous and recent research. Although patients with asthma are one of the major target groups for immunization, vaccine coverage in all age categories remains low. So far, no unequivocal beneficial effect of influenza vaccination in patients with asthma was found in observational and experimental studies in the sense of reduction of asthma exacerbations and other complications. Recent studies confirm these negative findings. More long-term randomized, placebo-controlled studies, focusing on influenza- proven illness in patients with asthma, are needed to address the question of how helpful influenza vaccination is in these patients.

The RS4939827 polymorphism in the SMAD7 GENE and its association with Mediterranean diet in colorectal carcinogenesis.

PubMed

Alonso-Molero, Jéssica; González-Donquiles, Carmen; Palazuelos, Camilo; Fernández-Villa, Tania; Ramos, Elena; Pollán, Marina; Aragonés, Nuria; Llorca, Javier; Henar Alonso, M; Tardón, Adonina; Amiano, Pilar; Moleon, José Juan Jiménez; Pérez, Rosana Peiró; Capelo, Rocío; Molina, Antonio J; Acebo, Inés Gómez; Guevara, Marcela; Perez-Gomez, Beatriz; Lope, Virginia; Huerta, José María; Castaño-Vinyals, Gemma; Kogevinas, Manolis; Moreno, Victor; Martín, Vicente

2017-10-30

The objective of our investigation is to study the relationship between the rs4939827 SNP in the SMAD7 gene, Mediterranean diet pattern and the risk of colorectal cancer. We examined 1087 cases of colorectal cancer and 2409 population controls with available DNA samples from the MCC-Spain study, 2008-2012. Descriptive statistical analyses, and multivariate logistic mixed models were performed. The potential synergistic effect of rs4939827 and the Mediterranean diet pattern was evaluated with logistic regression in different strata of of adherence to the Mediterranean diet and the genotype. High adherence to Mediterrenean diet was statistically significantly associated with colorectal cancer risk. A decreased risk for CRC cancer was observed for the CC compared to the TT genotype (OR = 0.65 and 95% CI = 0.51-0.81) of the rs4939827 SNP Also, we could show an association between the Mediterranean diet pattern (protective factor) and rs4939827. Although the decreased risk for the CC genotype was slightly more pronounced in subjects with high adherence to Mediterrenean diet, there was no statistically significant synergistic effect between genotype CC and adherence to the Mediterranean dietary pattern factors. The SMAD7 gene and specifically the allele C could be protective for colorectal cancer. An independent protective association was also observed between high adherence Mediterranean diet pattern and CRC risk. Findings form this study indicate that high adherence to Mediterranean diet pattern has a protective role for CRC cancer probably involving the Tumor Growth Factor- β pathway in this cancer.

Children With Serious Illness: Behavioral Correlates of Separation and Isolation.

ERIC Educational Resources Information Center

Hollenbeck, A. R.; And Others

The deleterious effects of separation and deprivation using children who were undergoing chemotherapy for childhood cancer was investigated. Extensive observational and physiological records were obtained on four children under five years of age during six weeks of treatment in a protected environment. In general, findings parallel those reported…

A GIS APPLICATION AND RESOURCE TOOL FOR USE ON STUDIES OF THE LAKE TEXOMA ECOLOGICAL SYSTEM

EPA Science Inventory

Investigations are underway at Lake Texoma to develop tools and information needed to evaluate the transport and attenuation of contaminants and stressors in a lake ecosystem, and link them to observable ecological effects. The U. S. Environmental Protection Agency (USEPA),
...

40 CFR 159.170 - Human epidemiological and exposure studies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in humans...

40 CFR 159.170 - Human epidemiological and exposure studies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in humans...

40 CFR 159.170 - Human epidemiological and exposure studies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in humans...

40 CFR 159.170 - Human epidemiological and exposure studies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in humans...

Synthesis and characterization of an effective organic/inorganic hybrid green corrosion inhibitive complex based on zinc acetate/Urtica Dioica

NASA Astrophysics Data System (ADS)

Salehi, E.; Naderi, Reza; Ramezanzadeh, B.

2017-02-01

This study aims at synthesis and characterization of an effective corrosion inhibitive complex based on zinc acetate/Urtica Dioica (ZnA-U.D) for corrosion protection of mild steel in chloride solution. The chemical structure and morphology of the complex were characterized by Fourier transform infrared spectroscopy (FT-IR), UV-vis, thermal gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The corrosion protection performance of the mild steel samples dipped in 3.5 wt.% NaCl solutions with and without ZnA-U.D extract was investigated by visual observations, open circuit potential (OCP) measurements, electrochemical impedance spectroscopy (EIS) and polarization test. Results revealed that the ZnA successfully chelated with organic inhibitive compounds (i.e Quercetin, Quinic acid, Caffeic acid, Hystamine and Serotonin) present in the U.D extract. The electrochemical measurements revealed the effective inhibition action of ZnA-U.D complex in the sodium chloride solution on the mild steel. The synergistic effect between Zn2+ and organic compounds present in the U.D extract resulted in protective film deposition on the steel surface, which was proved by SEM and XPS analyses.

Stimulation or Inhibition: Conflicting evidence for (+/-)-catechin's role as a chemical facilitator and disease protecting agent.

PubMed

Bais, Harsh P; Venkatachalam, L; Biedrzycki, Meredith L

2010-03-01

The occurrence of plant hormesis is a poorly understood phenomenon, wherein low doses of phytotoxins unusually promote growth responses in higher plants. In contrast, negative plant-plant interactions mediated through secreted small molecular weight compounds initiate growth inhibitory responses. Studies related to (+/-)-catechin mediated allelopathy have transpired both novel information and generated significant controversy. Specifically, studies related to the phytotoxicity responses mediated by (+/-)-catechins have been seriously debated. The pronged opinion that (+/-)-catechin is phytotoxic versus non-phytotoxic relies more on the target plant systems and the conditions used to test phytotoxic responses. It is reported that lower than MIC dosage supplementation of (+/-)-catechin could promote growth responses in the model plant Arabidopsis thaliana. Furthermore, it was shown that sub-MIC levels of (+/-)-catechin supplementation leads to elicitation of disease resistance against Pseudomonas syringae DC3000 (hereafter DC3000). Intrigued by the unique hormesis response observed, we tested whether (+/-)-catechin indeed promotes growth responses in A. thaliana. In our hands, we observed no growth promotion responses of (+/-)-catechin against A. thaliana under in vitro or in soil conditions. We also evaluated the previously reported disease protecting properties of (+/-)-catechin in A. thaliana against DC3000. The systematic observations to evaluate disease protecting properties entailing colony counts, disease incidences and loss of chlorophyll studies showed no disease protecting properties of (+/-)-catechin. The transcriptional response for a marker pathogenesis related PR1 defense gene showed no induction post (+/-)-catechin supplementation. The cell death genes (ACD2 and CAD1) associated with programmed cell death revealed unchanged expression levels in plants treated with sub-MIC levels of (+/-)-catechin. Further, we report supplementation of sub-MIC levels of (+/-)-catechin negates any change in the expression of an auxin responsive gene. Our results refute the previous claims of growth and defense inducing effects of (+/-)-catechin, thus suggesting that a thorough reexamination is required to evaluate the hormetic effect of (+/-)-catechin under both controlled and natural conditions.

Effect of untreated bed nets on blood-fed Phlebotomus argentipes in kala-azar endemic foci in Nepal and India.

PubMed

Picado, Albert; Kumar, Vijay; Das, Murari; Burniston, Ian; Roy, Lalita; Suman, Rijal; Dinesh, Diwakar; Coosemans, Marc; Sundar, Shyam; Shreekant, Kesari; Boelaert, Marleen; Davies, Clive; Cameron, Mary

2009-12-01

Observational studies in the Indian subcontinent have shown that untreated nets may be protective against visceral leishmaniasis (VL). In this study, we evaluated the effect of untreated nets on the blood feeding rates of Phlebotomus argentipes as well as the human blood index (HBI) in VL endemic villages in India and Nepal. The study had a 'before and after intervention' design in 58 households in six clusters. The use of untreated nets reduced the blood feeding rate by 85% (95% CI 76.5-91.1%) and the HBI by 42.2% (95% CI 11.1-62.5%). These results provide circumstantial evidence that untreated nets may provide some degree of personal protection against sand fly bites.

Analysis of Vaginal Cell Populations during Experimental Vaginal Candidiasis

PubMed Central

Fidel, Paul L.; Luo, Wei; Steele, Chad; Chabain, Joseph; Baker, Marc; Wormley, Floyd

1999-01-01

Studies with an estrogen-dependent murine model of vaginal candidiasis suggest that local cell-mediated immunity (CMI) is more important than systemic CMI for protection against vaginitis. The present study, however, showed that, compared to uninfected mice, little to no change in the percentage or types of vaginal T cells occurred during a primary vaginal infection or during a secondary vaginal infection where partial protection was observed. Furthermore, depletion of polymorphonuclear leukocytes (PMN) had no effect on infection in the presence or absence of pseudoestrus. These results indicate a lack of demonstrable effects by systemic CMI or PMN against vaginitis and suggest that if local T cells are important, they are functioning without showing significant increases in numbers within the vaginal mucosa during infection. PMID:10338532

Cross linking in the radiolysis of some enzymes and related proteins

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

Lynn, K.R.

1977-01-01

In non-covalently bound complexes of several serine proteases and of ribonuclease with DNA the enzymes were protected against the effects of ionizing radiation. No scavenging by the nucleic acids was observed. Similarly, complexing trypsin with silica protected the enzyme from radiolytic destruction. Irradiation of solutions of serine proteases required about twice the D37 dose to produce about 10% polymerization: significantly lower relative doses were effective in causing polymerization in both lima bean protease inhibitor and in the octapeptidal hormone oxytocin. Several sulfhydryl enzymes which have been examined were very efficiently inactivated by ionizing radiation. There was, at the same time,more » apparent formation of novel intra-molecular -S-S- bonds.« less

Redox-active cerium oxide nanoparticles protect human dermal fibroblasts from PQ-induced damage.

PubMed

von Montfort, Claudia; Alili, Lirija; Teuber-Hanselmann, Sarah; Brenneisen, Peter

2015-01-01

Recently, it has been published that cerium (Ce) oxide nanoparticles (CNP; nanoceria) are able to downregulate tumor invasion in cancer cell lines. Redox-active CNP exhibit both selective pro-oxidative and antioxidative properties, the first being responsible for impairment of tumor growth and invasion. A non-toxic and even protective effect of CNP in human dermal fibroblasts (HDF) has already been observed. However, the effect on important parameters such as cell death, proliferation and redox state of the cells needs further clarification. Here, we present that nanoceria prevent HDF from reactive oxygen species (ROS)-induced cell death and stimulate proliferation due to the antioxidative property of these particles. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Cancer prevention by green tea: evidence from epidemiologic studies.

PubMed

Yuan, Jian-Min

2013-12-01

In contrast to the consistent results of an inhibitory effect of green tea extracts and tea polyphenols on the development and growth of carcinogen-induced tumors in experimental animal models, results from human studies are mixed. Both observational and intervention studies have provided evidence in support of a protective role of green tea intake in the development of oral-digestive tract cancer or an inhibitory role of oral supplementation of green tea extract on a precancerous lesion of oral cavity. Evidence in support of green tea intake against the development of liver cancer risk is limited and inconsistent. An inverse association between green tea intake and lung cancer risk has been observed among never smokers but not among smokers. Although observational studies do not support a beneficial role of tea intake against the development of prostate cancer, several phase 2 clinical trials have shown an inhibitory effect of green tea extract against the progression of prostate premalignant lesions to malignant tumors. Prospective epidemiologic studies so far have not provided evidence for a protective effect of green tea consumption on breast cancer development. Current data neither confirm nor refute a definitive cancer-preventive role of green tea intake. Large randomized intervention trials on the efficacy of green tea polyphenols or extracts are required before a recommendation for green tea consumption for cancer prevention should be made.

Analytical template protection performance and maximum key size given a Gaussian-modeled biometric source

NASA Astrophysics Data System (ADS)

Kelkboom, Emile J. C.; Breebaart, Jeroen; Buhan, Ileana; Veldhuis, Raymond N. J.

2010-04-01

Template protection techniques are used within biometric systems in order to protect the stored biometric template against privacy and security threats. A great portion of template protection techniques are based on extracting a key from or binding a key to a biometric sample. The achieved protection depends on the size of the key and its closeness to being random. In the literature it can be observed that there is a large variation on the reported key lengths at similar classification performance of the same template protection system, even when based on the same biometric modality and database. In this work we determine the analytical relationship between the system performance and the theoretical maximum key size given a biometric source modeled by parallel Gaussian channels. We consider the case where the source capacity is evenly distributed across all channels and the channels are independent. We also determine the effect of the parameters such as the source capacity, the number of enrolment and verification samples, and the operating point selection on the maximum key size. We show that a trade-off exists between the privacy protection of the biometric system and its convenience for its users.

Organization of food protection behavior is differentially influenced by 192 IgG-saporin lesions of either the medial septum or the nucleus basalis magnocellularis

PubMed Central

Martin, Megan M.; Winter, Shawn S.; Cheatwood, Joseph L.; Carter, Lynniece A.; Jones, Jeana L.; Weathered, Scott L.; Wagner, Steven J.; Wallace, Douglas G.

2008-01-01

Converging lines of evidence have supported a role for the nucleus basalis magnocellularis (NB) in attentional mechanisms; however, debate continues regarding the role of the medial septum in behavior (MS). Recent studies have supported a role for the septohippocampal system in the online processing of internally generated cues. The current study was designed to investigate a possible double dissociation in rat food protection behavior, a natural behavior that has been shown to depend on external and internal sources of information. The study examined the effects of intraparenchymal injections of 192 IgG-saporin into either the MS or NB on the organization of food protection behavior. NB cholinergic lesions reduced the number of successful food protection behaviors while sparing the temporal organization of food protection behavior. In contrast, MS cholinergic lesions disrupted the temporal organization of food protection behavior while sparing the ability to successfully protect food items. These observations are consistent with a double dissociation of NB and MS cholinergic systems' contributions to processing external and internal sources of information and provide further evidence for the septohippocampal system's involvement in processing internally generated cues. PMID:18823954

40 CFR 26.303 - Duties of IRBs in connection with observational research involving pregnant women and fetuses.

Code of Federal Regulations, 2013 CFR

2013-07-01

... observational research involving pregnant women and fetuses. 26.303 Section 26.303 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.303 Duties of IRBs in connection with observational research involving pregnant women...

40 CFR 26.303 - Duties of IRBs in connection with observational research involving pregnant women and fetuses.

Code of Federal Regulations, 2012 CFR

2012-07-01

... observational research involving pregnant women and fetuses. 26.303 Section 26.303 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.303 Duties of IRBs in connection with observational research involving pregnant women...

40 CFR 26.303 - Duties of IRBs in connection with observational research involving pregnant women and fetuses.

Code of Federal Regulations, 2010 CFR

2010-07-01

... observational research involving pregnant women and fetuses. 26.303 Section 26.303 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.303 Duties of IRBs in connection with observational research involving pregnant women...

40 CFR 26.303 - Duties of IRBs in connection with observational research involving pregnant women and fetuses.

Code of Federal Regulations, 2011 CFR

2011-07-01

... observational research involving pregnant women and fetuses. 26.303 Section 26.303 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.303 Duties of IRBs in connection with observational research involving pregnant women...

40 CFR 26.303 - Duties of IRBs in connection with observational research involving pregnant women and fetuses.

Code of Federal Regulations, 2014 CFR

2014-07-01

... observational research involving pregnant women and fetuses. 26.303 Section 26.303 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.303 Duties of IRBs in connection with observational research involving pregnant women...

The Possible Pre- and Post-UVA Radiation Protective Effect of Amaranth Oil on Human Skin Fibroblast Cells.

PubMed

Wolosik, Katarzyna; Zareba, Ilona; Surazynski, Arkadiusz; Markowska, Agnieszka

2017-07-01

The health effects of Amaranth Oil (AO) are attributed to its specific chemical composition. That makes it an outstanding natural product for the prevention and treatment of ultraviolet (UV) irradiation-related pathologies such as sunburn, photoaging, photoimmunosuppression, and photocarcinogenesis. Most of the studies are taken on animal model, and there is a lack of research on the endogenous effect of AO on fibroblast level, where UVA takes it harmful place. The aim of this study was evaluation if AO can protect or abolish UVA exposure effect on human skin fibroblast. The 0.1% AO, 0.25% AO, and 0.5% AO concentration and irradiation for 15 min under UVA-emitting lamp were studied in various condition. In all experiments, the mean values for six assays ± standard deviations were calculated. Pretreatment with various concentrations of AO was tested. The highest concentration of AO where cell survival was observed was 0.5%. Cytotoxicity assays provided evidence for pre- and post-UVA protective effect of 0.1% AO among three tested concentrations. The results also provide evidence that UVA has inhibitory effect on collagen biosynthesis in confluent skin fibroblast, but presence of 0.1% AO abolishes pre- and post-UVA effect comparing to other used AO concentration. The assessment results on DNA biosynthesis show the significant abolished post-UVA effect when 0.1% and 0.5% of AO were added. AO gives pre- and post-UVA protection in low concentration. This provides the evidence for using it not as a main protective factor against UV but as one of the combined components in cosmetic formulation. The recommended Amaranth Oil (AO) concentration in cosmetic formulation is between 0.1 and 5%Pretreatment with various concentrations of AO suggests to use the highest 0.5% concentration of AO in human skin fibroblast culturesThe 0.1% of AO in fibroblast cultures, protects and abolishes effect of ultraviolet A (UVA) exposureUVA has inhibitory effect on collagen biosynthesis in skin fibroblast, but presence of 0.1% AO abolishes pre- and post-UVA effectThe abolished post-UVA effect occurs when 0.1% and 0.5% of AO were added on DNA biosynthesis. Abbreviations used: AO: Amaranth Oil.

Space Station MMOD Shielding

NASA Technical Reports Server (NTRS)

Christiansen, Eric

2006-01-01

This paper describes International Space Station (ISS) shielding for micrometeoroid orbital debris (MMOD) protection, requirements for protection, and the technical approach to meeting requirements. Current activities in MMOD protection for ISS will be described, including efforts to augment MMOD protection by adding shields on-orbit. Observed MMOD impacts on ISS elements such as radiators, modules and returned hardware will be described. Comparisons of the observed damage with predicted damage using risk assessment software will be made.

Protective Effect of a Synbiotic against Multidrug-Resistant Acinetobacter baumannii in a Murine Infection Model

PubMed Central

Takahashi, Akira; Yuki, Norikatsu; Kaji, Rumi; Takahashi, Takuya; Nomoto, Koji

2016-01-01

This study investigated the ability of the probiotic Bifidobacterium breve strain Yakult (BbY) to protect against infection, as well as the potentiation of BbY activity by the synbiotic combination of BbY and prebiotic galactooligosaccharides (GOS). The study employed a mouse model of lethal intestinal multidrug-resistant Acinetobacter baumannii (MDRAb) infection. The endogenous intestinal microbiota was disrupted by the administration of multiple antibiotics, causing the loss of endogenous Bifidobacterium. Oral infection of these mice with MDRAb resulted in marked growth of this organism. Additional treatment of the infected mice with a sublethal dose of 5-fluorouracil (5-FU) induced systemic invasion by MDRAb and subsequent animal death. The continuous oral administration of BbY increased the survival rate and inhibited the intestinal growth and invasion by MDRAb in the infection model. Disruptions of the intestinal environment and barrier function in the infected mice were attenuated by BbY. Protection against the MDRAb infection was markedly potentiated by a synbiotic combination of BbY and GOS, although GOS by itself did not provide protection. Negative correlations were observed between intestinal MDRAb and BbY counts or acetic acid levels; positive correlations were observed between acetic acid levels and intestinal epithelium expression of tight-junction-related genes. These results demonstrated that the probiotic and synbiotic markedly potentiated protection against fatal intestinal infection caused by a multidrug-resistant bacterium. Probiotics and synbiotics are presumed to provide protection by compensation for the disrupted indigenous populations, thereby maintaining the intestinal environments and barrier functions otherwise targeted during opportunistic infection by MDRAb. PMID:26953197

No evidence for cross-protection of the HPV-16/18 vaccine against HPV-6/11 positivity in female STI clinic visitors.

PubMed

Woestenberg, Petra J; King, Audrey J; van der Sande, Marianne A B; Donken, Robine; Leussink, Suzan; van der Klis, Fiona R M; Hoebe, Christian J P A; Bogaards, Johannes A; van Benthem, Birgit H B

2017-04-01

Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11 positivity and AGW in the Netherlands. We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional study among 16- to 24-year-old sexually transmitted infection (STI) clinic attendants. Vaginal self-swabs were analyzed for type specific HPV and AGW were diagnosed at the STI-clinic. Prevalence of HPV-6 and/or HPV-11 and AGW were compared between self-reported vaccinated and unvaccinated women by log-binomial regression analysis, adjusted for demographics and risk behavior. Of the 1198 women included, 56% reported to be vaccinated at least once. Relative to unvaccinated women, the adjusted prevalence ratio (PR) for HPV-6/11 was 1.03 (95% confidence interval [CI] 0.74-1.43) for women vaccinated at least once. The crude PR for AGW was 0.67 (95% CI 0.22-2.07) for women vaccinated at least once. Adjustment did not change these results. We observed no cross-protective effect of the bivalent vaccine on genital HPV-6/11 positivity and a non-significant partially protective effect on AGW. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of Toxins on Arachidonic Acid Metabolism in Cultured Rat Pulmonary Alveolar Macrophages

DTIC Science & Technology

1988-12-28

response to’toixin exposure, and fluocinolone may protect against .T-2 toxicosis. Some natural toxins are potent a nd powerful inflammtatory agents (1,2...macrophages in the inflammatory response to natural toxins, we examined the effect of T-2, microcystin-LR known inflammatory agents, and also included...effective in inducing the release of arachidonic acid metabolites, probably due to non-inflammatory nature of the toxin. We observed a large increase in

Hadronic uncertainties in B → K ∗ μ + μ -: a state-of-the-art analysis

NASA Astrophysics Data System (ADS)

Capdevila, Bernat; Descotes-Genon, Sébastien; Hofer, Lars; Matias, Joaquim

2017-04-01

In the absence of direct evidence for New Physics at present LHC energies, the focus is set on the anomalies and discrepancies recently observed in rare b → sℓℓ transitions which can be interpreted as indirect hints. Global fits have shown that an economical New Physics solution can simultaneously alleviate the tensions in the various channels and can lead to a significant improvement in the description of the data. Alternative explanations within the Standard Model for part of the observed anomalies have been proposed in terms of (unexpectedly large) hadronic effects at low dilepton invariant mass and attributing tensions in protected observables to statistical fluctuations or experimental errors. We review the treatment of hadronic uncertainties in this kinematic regime for one of the most important channels, B → K ∗ μ + μ -, in a pedagogical way. We provide detailed arguments showing that factorisable power corrections cannot account for the observed anomalies and that an explanation through long-distance charm contributions is disfavoured. Some optimized observables at very low dilepton invariant mass are shown to be protected against contributions from the semileptonic coefficient C 9 (including any associated long-distance charm effects), enhancing their sensitivity to New Physics contributions to other Wilson coefficients. Finally, we discuss how the recent measurement of Q 5 by Belle (and in the future by LHCb and Belle-II) may provide a robust cross-check of our arguments.

Estimating influenza vaccine effectiveness: Evolution of methods to better understand effects of confounding in older adults.

PubMed

McElhaney, Janet E; Andrew, Melissa K; McNeil, Shelly A

2017-11-01

Older adults are at high risk for serious complications of influenza illness and loss of vaccine-mediated protection. It is increasingly recognized that in addition to age, multiple chronic conditions and associated frailty contribute to the decline in vaccine effectiveness in this population. However, observational studies have been fraught with issues of confounding related to the degree of frailty and functional decline, measures of which are not included in standard administrative health care databases that are used to calculate vaccine effectiveness. This issue has led to the identification of confounding by indication or from "healthy vaccinee" bias, which respectively lead to underestimates or overestimates of influenza vaccine effectiveness. In addition, the sensitivity and specificity of the criteria used to define influenza-like illness declines with increasing age due to atypical presentations of illness and the inability to distinguish between influenza and other respiratory viruses. The test-negative case:control design has emerged as a method to estimate influenza vaccine effectiveness by comparing vaccination rates in those with laboratory-confirmed influenza to those with other acute viral respiratory illnesses. This review provides a perspective on how test-negative case:control study designs and new insights into mechanisms of protection have considerably strengthened influenza vaccination policy decisions for older adults that have historically been undermined by the conclusions of observational studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

About the Sterilization of Chitosan Hydrogel Nanoparticles

PubMed Central

Galante, Raquel; Rediguieri, Carolina F.; Kikuchi, Irene Satiko; Vasquez, Pablo A. S.; Colaço, Rogério; Pinto, Terezinha J. A.

2016-01-01

In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP) associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility) with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS) hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation), a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP) hydrogel nanoparticles (CS-HNP), with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol). Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles. PMID:28002493

PF 9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine], a new MAO-B inhibitor, attenuates MPTP-induced depletion of striatal dopamine levels in C57/BL6 mice.

PubMed

Perez, Virgili; Unzeta, Mercedes

2003-02-01

Monoamine oxidase isoform B (MAO-B) is involved in Parkinson's disease (PD) induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxin (MPTP) in human and non-human-primate. MAO-B inhibitors, such as L-deprenyl have shown to prevent against MPTP-toxicity in different species, and it has been used in Parkinson therapy, however, the fact that it is metabolized to (-)-methamphetamine and (-)-amphetamine highlights the need to find out new MAO-B inhibitors without a structural amphetaminic moiety. In this context we herein report, for the first time, anywhere a novel non-amphetamine-like MAO-B inhibitor, PF 9601N, N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine. This attenuates the MPTP-induced striatal dopamine depletion in young-adult and adult-old C57/BL mice, using different schedules of administration, and which behave "ex vivo" as a slightly more potent and selective MAO-B inhibitor than L-deprenyl, assayed for comparative purposes in the same experimental conditions. The MAO-B ID(50) values were calculated from the total MAO-B activity measured against [14C] phenylethylamine (22 microM) as substrate, at each inhibitor concentration. The MAO-B ID(50) values resulted to be 381 and 577 nmol/kg for PF 9601N and L-deprenyl, respectively. The intraperitoneally (i.p.) co-administration to young-adult C57/BL6 mice of MPTP (30 mg/kg), with different concentrations of PF 9601N or L-deprenyl (29.5-0.357 micromol/kg) showed a dose-dependent protective effect against striatal dopamine depletion, measuring the dopamine contents and its metabolites by HPLC. The ED(50) value proved to be 3.07 micromol/kg without any significant differences between either MAO-B inhibitor. Nevertheless, lower doses of PF 9601N (1.5 micromol/kg) were necessary to get almost total protection, without any change in the DOPAC and HVA content, when administered 2 h before MPTP (30 mg/kg), whereas partial protection (45%) against dopamine depletion was observed in the case of L-deprenyl. In both cases, MAO-B inhibition was a necessary condition in order to observe the protective effect. When adult-old (8-10 months) C57/BL6 mice were used, MPTP (25 mg/kg) administration induced 25 days later, an irreversible dopamine depletion. In these conditions, chronic administration with 0.15 micromol/kg of PF 9601N, before the toxin, every 24 h for 10 days, rendered almost total protection of dopamine depletion, whereas L-deprenyl yielded only 50% protection of the dopamine content, assayed in the same conditions. It is worth remarking, that in both cases MAO-B was not affected. From these results, it can be concluded that PF 9601N attenuates MPTP neurotoxicity "in vivo" better than L-deprenyl through different mechanisms, with special relevance to the protective effect, independent of MAO-B inhibition, observed in the irreversibly MPTP-lesioned adult-old mice. Therefore, this novel non-amphetamine MAO-B inhibitor could be potentially effective in PD therapy. Copyright 2003 Elsevier Science Ltd.

Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis.

PubMed

Sperber, Jesper; Lipcsey, Miklós; Larsson, Anders; Larsson, Anders; Sjölin, Jan; Castegren, Markus

2015-05-10

Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome. 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels. TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb. Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia protective ventilation attenuates hepatic inflammatory cytokine output contributing to a reduced total inflammatory burden.

Acylated and unacylated ghrelin confer neuroprotection to mesencephalic neurons.

PubMed

Wagner, Johanna; Vulinović, Franca; Grünewald, Anne; Unger, Marcus M; Möller, Jens C; Klein, Christine; Michel, Patrick P; Ries, Vincent; Oertel, Wolfgang H; Alvarez-Fischer, Daniel

2017-12-04

The polypeptide ghrelin is an endogenous ligand at the growth hormone secretagogue receptor 1a. To ghrelin multiple functions have been ascribed including promotion of gastrointestinal motility. Postprandial ghrelin levels have been reported to be reduced in patients suffering from Parkinson disease (PD). Experimental studies revealed neuroprotective effects of ghrelin in different PD models. The purpose of the present study was (i) to further elucidate the mechanism underlying the neuroprotective action of ghrelin and (ii) to determine whether these effects occur with both the acylated and the unacylated form. The study was conducted in primary mesencephalic cultures treated with mitochondrial complex I and complex II inhibitors. We show that protective effects of ghrelin against complex I inhibition with MPP + were independent of the acylation status of ghrelin, although acylated ghrelin appeared to be more potent. Protection by both forms was also observed when neurons were exposed to the complex II inhibitor 3-NP. Both forms led to higher oxygen consumption rates upon electron transport chain uncoupling, indicating that the two peptides may exert uncoupling effects themselves. We demonstrate that the rescue provided by ghrelin required calcium influx through L-type voltage-gated calcium channels. Whereas the protective effects of acylated ghrelin required receptor binding, effects of the unacylated form remained unaffected by treatment with a ghrelin receptor antagonist. Importantly, inhibition of ghrelin O-acyltransferase failed to reduce the activity of unacylated ghrelin. Overall, our data suggest that both acylated and unacylated ghrelin afford protection to dopamine neurons but through mechanisms that only partially overlap. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis

PubMed Central

Rajkumar, Lakshmanaswamy; Guzman, Raphael C.; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

2001-01-01

It is well established that pregnancy early in life reduces the risk of breast cancer in women and that this effect is universal. This phenomenon of parity protection against mammary cancer is also observed in rodents. Earlier studies have demonstrated that short-term administration of estradiol (E) in combination with progesterone mimics the protective effect of parity in rats. In this study, the lowest effective E dosage for preventing mammary cancer was determined. Rats were injected with N-methyl-N-nitrosourea at 7 weeks of age; 2 weeks later, the rats were subjected to sustained treatment with 20 μg, 100 μg, 200 μg, or 30 mg of E in silastic capsules for 3 weeks. Treatments with 100 μg, 200 μg, and 30 mg of E resulted in serum levels of E equivalent to those of pregnancy and were highly effective in preventing mammary cancer. E treatment (20 μg) did not result in pregnancy levels of E and was not effective in reducing the mammary cancer incidence. In another set of experiments, we determined the effect of different durations of E with or without progesterone treatments on mammary carcinogenesis. These experiments indicate that a period as short as one-third the period of gestation is sufficient to induce protection against mammary carcinogenesis. The pioneering aspect of our study in contrast to long-term estrogen exposure, which is thought to increase the risk of breast cancer, is that short-term sustained treatments with pregnancy levels of E can induce protection against frank mammary cancer. PMID:11573010

Anti-islanding Protection of Distributed Generation Using Rate of Change of Impedance

NASA Astrophysics Data System (ADS)

Shah, Pragnesh; Bhalja, Bhavesh

2013-08-01

Distributed Generation (DG), which is interlinked with distribution system, has inevitable effect on distribution system. Integrating DG with the utility network demands an anti-islanding scheme to protect the system. Failure to trip islanded generators can lead to problems such as threats to personnel safety, out-of-phase reclosing, and degradation of power quality. In this article, a new method for anti-islanding protection based on impedance monitoring of distribution network is carried out in presence of DG. The impedance measured between two phases is used to derive the rate of change of impedance (dz/dt), and its peak values are used for final trip decision. Test data are generated using PSCAD/EMTDC software package and the performance of the proposed method is evaluated in MatLab software. The simulation results show the effectiveness of the proposed scheme as it is capable to detect islanding condition accurately. Subsequently, it is also observed that the proposed scheme does not mal-operate during other disturbances such as short circuit and switching event.

The U. S. Environmental Protection Agency's inhalation RfD methodology: Risk assessment for air toxics

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

Jarabek, A.M.; Menache, M.G.; Overton, J.H. Jr.

1990-10-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. This paper presents a brief background on the development of the inhalation reference dose (RfDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extra-respiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

U. S. Environmental Protection Agency's inhalation RFD methodology: Risk assessment for air toxics

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

Jarabek, A.M.; Menache, M.G.; Overton, J.H.

1989-01-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. The paper presents a brief background on the development of the inhalation reference dose (RFDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extrarespiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

sUAS and their application in observing geomorphological processes

NASA Astrophysics Data System (ADS)

Gallik, Jozef; Bolešová, Lenka

2016-07-01

Methodologies and procedures in processing gained data vary based on possibilities and needs of scientific projects. This paper should help to get a general overview in the choice of small unmanned aircraft systems (sUAS - commonly known as drones) for scientific purposes, namely remote sensing of geomorphologic processes such as soil degradation in high mountainous areas that are hard to access and have unfavourable weather conditions. All high mountain areas in European countries are legislatively protected, and so various permissions and observation of strict procedures are needed in order to not have a negative influence on the environment. Nowadays, several types of UAS exist that could effectively help us in such protection, as well as in full-fledged utilization when answering scientific questions about the alpine lake genesis. We demonstrate it here with selected examples of our photo documentation.

Role of cloned carotenoid genes expressed in Escherichia coli in protecting against inactivation by near-UV light and specific phototoxic molecules

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

Tuveson, R.W.; Larson, R.A.; Kagan, J.

1988-10-01

Genes controlling carotenoid synthesis were cloned from Erwinia herbicola and expressed in an Escherichia coli strain. Carotenoids protect against high fluences of near-UV (NUV; 320 to 400 nm) but not against far-UV (200-300 nm). Protection of E. coli cells was not observed following treatment with either psoralen or 8-methoxypsoralen plus NUV. However, significant protection of cells producing carotenoids was observed with three photosensitizing molecules activated by NUV (alpha-terthienyl, harmine, and phenylheptatriyne) which are thought to have the membrane as an important lethal target. Protection of carotenoid-producing cells against inactivation was not observed with acridine orange plus visible light but wasmore » seen with toluidine blue O plus visible light.« less

Role of cloned carotenoid genes expressed in Escherichia coli in protecting against inactivation by near-UV light and specific phototoxic molecules.

PubMed Central

Tuveson, R W; Larson, R A; Kagan, J

1988-01-01

Genes controlling carotenoid synthesis were cloned from Erwinia herbicola and expressed in an Escherichia coli strain. Carotenoids protect against high fluences of near-UV (NUV; 320 to 400 nm) but not against far-UV (200-300 nm). Protection of E. coli cells was not observed following treatment with either psoralen or 8-methoxypsoralen plus NUV. However, significant protection of cells producing carotenoids was observed with three photosensitizing molecules activated by NUV (alpha-terthienyl, harmine, and phenylheptatriyne) which are thought to have the membrane as an important lethal target. Protection of carotenoid-producing cells against inactivation was not observed with acridine orange plus visible light but was seen with toluidine blue O plus visible light. PMID:3049544

Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.

PubMed

Goheen, M M; Wegmüller, R; Bah, A; Darboe, B; Danso, E; Affara, M; Gardner, D; Patel, J C; Prentice, A M; Cerami, C

2016-12-01

Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection. This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin <11g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12mg/day) as part of a micronutrient powder for 84days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint. Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (p<0.001), paralleling increases in erythropoiesis. These results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria. National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

An evaluation of UV protection imparted by cotton fabrics dyed with natural colorants

PubMed Central

Sarkar, Ajoy K

2004-01-01

Background The ultraviolet properties of textiles dyed with synthetic dyes have been widely reported in literature. However, no study has investigated the ultraviolet properties of natural fabrics dyed with natural colorants. This study reports the Ultraviolet Protection Factor (UPF) of cotton fabrics dyed with colorants of plant and insect origins. Methods Three cotton fabrics were dyed with three natural colorants. Fabrics were characterized with respect to fabric construction, weight, thickness and thread count. Influence of fabric characteristics on Ultraviolet Protection Factor was studied. Role of colorant concentration on the ultraviolet protection factor was examined via color strength analysis. Results A positive correlation was observed between the weight of the fabric and their UPF values. Similarly, thicker fabrics offered more protection from ultraviolet rays. Thread count appears to negatively correlate with UPF. Dyeing with natural colorants dramatically increased the protective abilities of all three fabric constructions. Additionally, within the same fabric type UPF values increased with higher depths of shade. Conclusion Dyeing cotton fabrics with natural colorants increases the ultraviolet protective abilities of the fabrics and can be considered as an effective protection against ultraviolet rays. The UPF is further enhanced with colorant of dark hues and with high concentration of the colorant in the fabric. PMID:15509304

Nutritional supplementation with arginine protects radiation-induced effects. An experimental study.

PubMed

Pinto, Flavia Cristina Morone; Campos-Silva, Pamella; Souza, Diogo Benchimol de; Costa, Waldemar Silva; Sampaio, Francisco José Barcellos

2016-10-01

To investigate the protective effect of L-arginine on the prostate (nonneoplasic) of rats with radiation-induced injury. Twenty-nine Wistar rats, male adult, allocated into three groups: Control group (C) was not exposed to irradiation (n=10); Radiated group (R) had undergone pelvic irradiation (n=10); Supplemented and radiated group (R+S) had undergone pelvic irradiation plus L-arginine supplementation (n=9). The animals were observed for signs of toxicity. After euthanization, the prostate was dissected under magnification and stained by hematoxylin and eosin to study acinar structures and stained with Picrosirius red for collagen analysis. After radiation exposure, all animals presented diarrhea, but supplementation with L-arginine reduced this effect. The weight gain in the R+S group was significantly higher than in the C and R groups. In the R+S group the collagen density and the prostate acinar area was similar to the R and C groups. Epithelial height was significantly reduced in group R compared with group C (p<0.0001). When comparing the group R+S with R, a statistical difference was observed to be present (p<0.0001). Pelvic radiation promotes systemic effects and some structural modifications in the ventral prostate of rats. These modifications can be prevented by oral supplementation with L-arginine.

Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation.

PubMed

Zheng, Hang; Wang, Miao; Wu, Jing; Wang, Zhi-Ming; Nan, Hai-Jun; Sun, He

2016-06-01

Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation.

Chapter 8. Tea and Cancer Prevention: Epidemiological Studies

PubMed Central

Yuan, Jian-Min; Sun, Canlan; Butler, Lesley M.

2011-01-01

Experimental studies have consistently shown the inhibitory activities of tea extracts on tumorigenesis in multiple model systems. Epidemiologic studies, however, have produced inconclusive results in humans. A comprehensive review was conducted to assess the current knowledge on tea consumption and risk of cancers in humans. In general, consumption of black tea was not associated with lower risk of cancer. High intake of green tea was consistently associated with reduced risk of upper gastrointestinal tract cancers after sufficient control for confounders. Limited data support a protective effect of green tea on lung and hepatocellular carcinogenesis. Although observational studies do not support a beneficial role of tea intake on prostate cancer risk, phase II clinical trials have demonstrated an inhibitory effect of green tea extract against the progression of prostate pre-malignant lesions. Green tea may exert beneficial effects against mammary carcinogenesis in premenopausal women and recurrence of breast cancer. There is no sufficient evidence that supports a protective role of tea intake on the development of cancers of the colorectum, pancreas, urinary tract, glioma, lymphoma, and leukemia. Future prospective observational studies with biomarkers of exposure and phase III clinical trials are required to provide definitive evidence for the hypothesized beneficial effect of tea consumption on cancer formation in humans. PMID:21419224

Protective effect of Petroselinum crispum extract in abortion using prostadin-induced renal dysfunction in female rats.

PubMed

Rezazad, Maryam; Farokhi, Farah

2014-09-01

Present study investigated the effects of parsley extract on pregnant rat kidneys which have undergone clinical abortion using prostaglandins. The renal protective effect of parsley extract was evaluated in pregnant rats which had an abortion. Parsley was used due to its antioxidant properties. Fifty-four female rats were divided in 9 groups of 6: control pregnant, two pregnant groups which received parsley extract and prostadin, two non-pregnant groups treated with parsley extract and prostadin, a group administered with both treatments, and three groups which received parsley extract in pre-implantation, implantation, and post-implantation periods of embryos. Ethanolic extract (5 mg/kg) was given daily to animals for 18 days of pregnancy period. Parameters such as malondialdehyde (MDA), total antioxidant statues (TAS), creatinine, and urea were measured using biochemical assays. Histopathologic studies were also done with Hematoxylin-Eosin staining method. After 18 days of treatment, significant differences were observed in serum creatinine, urea, and MDA and TAS levels. Kidney cross-sections showed edema in prostadin-treated rats while improvements in parsley + prostadin -treated rats were observed. These results suggested that ethanolic extract of Petroselinum crispum reduced the dysfunction in rats kidney caused by prostadin-induced abortion and could have beneficial effect in reducing the progression of prostaglandin-induced edema.

Antipyretic and anticonvulsant activity of n-hexane fraction of Viola betonicifolia.

PubMed

Muhammad, Naveed; Saeed, Muhammad; Khan, Haroon; Raziq, Naila; Halimi, Syed Muhammad Ashhad; Abass, Muzaffer

2013-04-01

To investigate the antipyretic and anticonvulsant activities of n-hexane fraction of Viola betonicifolia (V. betonicifolia). The antipyretic effect was scrutinized using brewer's yeast induced pyrexia and anticonvlsion effect was tested using pentylenetetrazol and strychnine induced convulsion in mice. N-hexane fraction of V. betonicifolia demonstrated highly significant antipyretic activity during various assessment times (1-5 h) when challenged in yeast induced pyrexia test. The effect was in a dose dependent manner with maximum attenuation (82.50%) observed at 300 mg/kg i.p. When tested in pentylenetetrazol induced convulsion test, the 1st stage (Ear and facial twitching) and 2nd stage (Convulsive wave through the body) was 100% protected during 24 h at all the test doses (300, 400 and 500 mg/kg i.p.), while the latency time of remaining stages was significantly increased. The maximum effect was observed by n-hexane fraction of V. betonicifolia at 400 and 500 mg/kg i.p., as the latency time for generalized clonic-tonic seizure (5th stage) was increased up to 25.34 min. However, n-hexane fraction of V. betonicifolia had no protection in strychnine induced convulsion test. In conclusion, phytopharmacological studies provide scientific foundation to the folk uses of the plant in the treatment of pyrexia and neurological disorders.

Antipyretic and anticonvulsant activity of n-hexane fraction of Viola betonicifolia

PubMed Central

Muhammad, Naveed; Saeed, Muhammad; Khan, Haroon; Raziq, Naila; Halimi, Syed Muhammad Ashhad

2013-01-01

Objective To investigate the antipyretic and anticonvulsant activities of n-hexane fraction of Viola betonicifolia (V. betonicifolia). Methods The antipyretic effect was scrutinized using brewer's yeast induced pyrexia and anticonvlsion effect was tested using pentylenetetrazol and strychnine induced convulsion in mice. Results N-hexane fraction of V. betonicifolia demonstrated highly significant antipyretic activity during various assessment times (1-5 h) when challenged in yeast induced pyrexia test. The effect was in a dose dependent manner with maximum attenuation (82.50%) observed at 300 mg/kg i.p. When tested in pentylenetetrazol induced convulsion test, the 1st stage (Ear and facial twitching) and 2nd stage (Convulsive wave through the body) was 100% protected during 24 h at all the test doses (300, 400 and 500 mg/kg i.p.), while the latency time of remaining stages was significantly increased. The maximum effect was observed by n-hexane fraction of V. betonicifolia at 400 and 500 mg/kg i.p., as the latency time for generalized clonic-tonic seizure (5th stage) was increased up to 25.34 min. However, n-hexane fraction of V. betonicifolia had no protection in strychnine induced convulsion test. Conclusions In conclusion, phytopharmacological studies provide scientific foundation to the folk uses of the plant in the treatment of pyrexia and neurological disorders. PMID:23620851

Angiotensin II Moderately Decreases Plasmodium Infection and Experimental Cerebral Malaria in Mice.

PubMed

Gallego-Delgado, Julio; Baravian, Charlotte; Edagha, Innocent; Ty, Maureen C; Ruiz-Ortega, Marta; Xu, Wenyue; Rodriguez, Ana

2015-01-01

Angiotensin II, a peptide hormone that regulates blood pressure, has been proposed as a protective factor against cerebral malaria based on a genetic analysis. In vitro studies have documented an inhibitory effect of angiotensin II on Plasmodium growth, while studies using chemical inhibitors of angiotensin II in mice showed protection against experimental cerebral malaria but not major effects on parasite growth. To determine whether the level of angiotensin II affects Plasmodium growth and/or disease outcome in malaria, elevated levels of angiotensin II were induced in mice by intradermal implantation of osmotic mini-pumps providing constant release of this hormone. Mice were then infected with P. berghei and monitored for parasitemia and incidence of cerebral malaria. Mice infused with angiotensin II showed decreased parasitemia seven days after infection. The development of experimental cerebral malaria was delayed and a moderate increase in survival was observed in mice with elevated angiotensin II, as confirmed by decreased number of cerebral hemorrhages compared to controls. The results presented here show for the first time the effect of elevated levels of angiotensin II in an in vivo model of malaria. The decreased pathogenesis observed in mice complements a previous human genetic study, reinforcing the hypothesis of a beneficial effect of angiotensin II in malaria.

Cyber security risk management: public policy implications of correlated risk, imperfect ability to prove loss, and observability of self-protection.

PubMed

Oğüt, Hulisi; Raghunathan, Srinivasan; Menon, Nirup

2011-03-01

The correlated nature of security breach risks, the imperfect ability to prove loss from a breach to an insurer, and the inability of insurers and external agents to observe firms' self-protection efforts have posed significant challenges to cyber security risk management. Our analysis finds that a firm invests less than the social optimal levels in self-protection and in insurance when risks are correlated and the ability to prove loss is imperfect. We find that the appropriate social intervention policy to induce a firm to invest at socially optimal levels depends on whether insurers can verify a firm's self-protection levels. If self-protection of a firm is observable to an insurer so that it can design a contract that is contingent on the self-protection level, then self-protection and insurance behave as complements. In this case, a social planner can induce a firm to choose the socially optimal self-protection and insurance levels by offering a subsidy on self-protection. We also find that providing a subsidy on insurance does not provide a similar inducement to a firm. If self-protection of a firm is not observable to an insurer, then self-protection and insurance behave as substitutes. In this case, a social planner should tax the insurance premium to achieve socially optimal results. The results of our analysis hold regardless of whether the insurance market is perfectly competitive or not, implying that solely reforming the currently imperfect insurance market is insufficient to achieve the efficient outcome in cyber security risk management. © 2010 Society for Risk Analysis.

A review: Development of a microdose model for analysis of adaptive response and bystander dose response behavior.

PubMed

Leonard, Bobby E

2008-02-27

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type (125)I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1. Single Specific Energy Hits initiate Adaptive Response. 2. Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3. For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4. The dose range of the AR protection depends on the value of the Specific Energy per Hit, 1 >. 5. Alpha particle induced deleterious Bystander damage is modulated by low LET radiation.

Chitooligosaccharides protect human embryonic hepatocytes against oxidative stress induced by hydrogen peroxide.

PubMed

Xu, Qingsong; Ma, Pan; Yu, Weiting; Tan, Chengyu; Liu, Hongtao; Xiong, Chuannan; Qiao, Ying; Du, Yuguang

2010-06-01

Chitooligosaccharides (COS) has many biological activities, such as antitumor activity and hepatoprotective effect. Herein, we investigated the protective effect of COS against hydrogen peroxide (H2O2)-induced oxidative stress on human embryonic hepatocytes (L02 cells) and its scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl radical in vitro. The results showed that the lost cell viability induced by H2O2 was markedly restored after 24 h pre-incubation with COS (0.1-0.4 mg/ml). This rescue effect could be related to the antioxidant property of COS, in which we showed that the radical scavenging activity of COS reached 80% at concentration of 2 mg/ml. In addition, COS could prevent cell apoptosis induced by H2O2, as shown by the inhibition of the cleavage of poly (adenosine diphosphate-ribose) polymerase and increased expression of the anti-apoptotic protein Bcl-xL. Furthermore, we have utilized confocal laser microscopy to observe cellular uptake of COS, an important step for COS to exert its effects on target cells. Taken together, our findings suggested that COS could effectively protect L02 cells against oxidative stress, which might be useful in clinical setting during the treatment of oxidative stress-related liver damages.

Protective effect of heat-treated cucumber (Cucumis sativus L.) juice on alcohol detoxification in experimental rats.

PubMed

Bajpai, Vivek K; Kim, Na-Hyung; Kim, Ji-Eun; Kim, Kangmin; Kang, Sun Chul

2016-05-01

In this study, heat-treated cucumber juice was assessed for its protective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats. Initially, during detoxification of alcohol, all groups were orally dosed to 22% alcohol (6ml/kg body weight) along with different concentrations of heat-treated cucumber juice (10, 100 and 500mg/kg) and commercial goods for hangover-removal on sale (2ml/kg). Cucumber juice was dosed before 30 min, and simultaneously after 30min of alcohol administration, and its hepatoprotective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats was evaluated. As a result, after 7h, remarkable reduction was found in the blood alcohol levels for all concentrations of cucumber juice treatment. Treatment with cucumber juice resulted in increasing dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) enzymatic activities in rat liver at 9h after alcohol administration thereby stimulated blood alcohol metabolism as compared with control group. The effect of heat-treated cucumber juice on alcohol detoxification was observed only in the rats treated before 30min from alcohol administration. These findings indicate that heat-treated cucumber juice has significant protective effect on alcohol detoxification in experimental rats, suggesting its usefulness in the treatment of liver injury caused by alcohol consumption.

The protective effect of dexmedetomidine in a rat ex vivo lung model of ischemia-reperfusion injury.

PubMed

Zhou, Yan; Zhou, Xinqiao; Zhou, Wenjuan; Pang, Qingfeng; Wang, Zhiping

2018-01-01

To investigate the effect of dexmedetomidine (Dex) in a rat ex vivo lung model of ischemia-reperfusion injury. An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Drugs were added to the perfusion solution for reperfusion. Lung injury was assessed by histopathological changes, airway pressure (Res), lung compliance (Compl), perfusion flow (Flow), pulmonary venous oxygen partial pressure (PaO2), and lung wet/dry (W/D) weight ratio. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), 78 kDa glucose-regulated protein (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured, respectively. The introduction of Dex attenuated the post-ischemia-reperfusion lung damage and MDA level, improved lung histology, W/D ratio, lung injury scores and SOD activity. Decreased mRNA and protein levels of GRP78 and CHOP compared with the IR group were observed after Dex treatment. The effect of Dex was dosage-dependence and a high dose of Dex (10 nM) was shown to confer the strongest protective effect against lung damage (P<0.05). Yohimbine, an α2 receptor antagonist, significantly reversed the protective effect of Dex in lung tissues (P<0.05). Dex reduced ischemia-reperfusion injury in rat ex vivo lungs.

More Observations in Schools for Promoting Astronomy and Sky Protection

NASA Astrophysics Data System (ADS)

Ros, Rosa M.

2015-03-01

In astronomy it is important to promote observation and the quality of the sky is essential for a good observation impact. It is important that children have a nice memory of their observations in a non-polluted sky. Using students as agents of change it is possible to promote good practice for sky protection in society.

The Interaction between Dietary Fiber and Fat and Risk of Colorectal Cancer in the Women's Health Initiative.

PubMed

Navarro, Sandi L; Neuhouser, Marian L; Cheng, Ting-Yuan David; Tinker, Lesley F; Shikany, James M; Snetselaar, Linda; Martinez, Jessica A; Kato, Ikuko; Beresford, Shirley A A; Chapkin, Robert S; Lampe, Johanna W

2016-11-30

Combined intakes of specific dietary fiber and fat subtypes protect against colon cancer in animal models. We evaluated associations between self-reported individual and combinations of fiber (insoluble, soluble, and pectins, specifically) and fat (omega-6, omega-3, and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), specifically) and colorectal cancer (CRC) risk in the Women's Health Initiative prospective cohort ( n = 134,017). During a mean 11.7 years (1993-2010), 1952 incident CRC cases were identified. Cox regression models computed multivariate adjusted hazard ratios to estimate the association between dietary factors and CRC risk. Assessing fiber and fat individually, there was a modest trend for lower CRC risk with increasing intakes of total and insoluble fiber ( p-trend 0.09 and 0.08). An interaction ( p = 0.01) was observed between soluble fiber and DHA + EPA, with protective effects of DHA + EPA with lower intakes of soluble fiber and an attenuation at higher intakes, however this association was no longer significant after correction for multiple testing. These results suggest a modest protective effect of higher fiber intake on CRC risk, but not in combination with dietary fat subtypes. Given the robust results in preclinical models and mixed results in observational studies, controlled dietary interventions with standardized intakes are needed to better understand the interaction of specific fat and fiber subtypes on colon biology and ultimately CRC susceptibility in humans.

Enzymatic Removal of Diacetyl from Beer 1

PubMed Central

Thompson, Janet W.; Shovers, J.; Sandine, W. E.; Elliker, P. R.

1970-01-01

Use of diacetyl reductase, a reduced nicotinamide adenine dinucleotide (NADH)-requiring enzyme, to eliminate diacetyl off-flavor in beer was studied. The crude enzyme was extracted from Aerobacter aerogenes and partially purified by ammonium sulfate precipitation or Sephadex chromatography. In the semipure state, the enzyme was inactivated by lyophilization; in a crude state, the lyophilized extract remained stable for at least 4 months at — 20 C. A 50% reduction in specific activity within 5 min was observed when crude diacetyl reductase was suspended (5 mg of protein/ml) in phosphate buffer at pH 5.5 or below; a similar inactivation rate was observed when the crude enzyme was dissolved in a 5% aqueous ethyl alcohol solution. Effective crude enzyme activity in beer at a natural pH of 4.1 required protection of the enzyme in 10% gelatin. Incorporation of yeast cells with the gel-protected enzyme provided regeneration of NADH. Combinations of yeast, enzyme, and gelatin were tested to obtain data analyzed by regression analysis to determine the optimal concentration of each component of the system required to reduce the level of diacetyl in spiked (0.5 ppm) beer to less than 0.12 ppm within 48 hr at 5 C. The protected enzyme system was also effective in removing diacetyl from orange juice (pH 3.8) and some distilled liquors. PMID:4318450

Triamcinolone hexacetonide protects against fibrillation and osteophyte formation following chemically induced articular cartilage damage.

PubMed

Williams, J M; Brandt, K D

1985-11-01

Although corticosteroids have been shown to cause articular cartilage degeneration, recent studies of experimentally induced osteoarthritis indicate that under certain conditions they may protect against cartilage damage and osteophyte formation. The present study examines the in vivo effect of triamcinolone hexacetonide on the degeneration of articular cartilage which occurs following intraarticular injection of sodium iodoacetate. Three weeks after a single injection of iodoacetate into the knees of guinea pigs, ipsilateral femoral condylar cartilage exhibited fibrillation, loss of staining with Safranin O, depletion of chondrocytes, and prominent osteophytes. In striking contrast, when triamcinolone hexacetonide was injected into the ipsilateral knee 24 hours after the intraarticular injection of iodoacetate, fibrillation was noted in only 1 of 6 samples, osteophytes were much less prominent, pericellular staining with Safranin O persisted, and cell loss was less extensive. Knees of animals which received only one-tenth as much intraarticular triamcinolone hexacetonide after the iodoacetate injection also exhibited marked reduction in size and extent of osteophytes. However, the degree of fibrillation, loss of Safranin O staining, and chondrocyte depletion was similar to that observed in animals injected with iodoacetate but not treated with intraarticular steroid. No apparent morphologic or histochemical changes were observed after intraarticular injection of the steroid preparation alone. Thus, triamcinolone hexacetonide produced a marked, dose-dependent protective effect in this model of chemically induced articular cartilage damage.

Effects of curcumin on angiotensin-converting enzyme gene expression, oxidative stress and anti-oxidant status in thioacetamide-induced hepatotoxicity.

PubMed

Fazal, Yumna; Fatima, Syeda Nuzhat; Shahid, Syed Muhammad; Mahboob, Tabassum

2015-12-01

This study aimed to evaluate the protective effects of curcumin on angiotensin-converting enzyme (ACE) gene expression, oxidative stress and anti-oxidant status in thioacetamide (TAA)-induced hepatotoxicity in rats. Total 32 albino Wistar rats (male, 200-250 g) were divided into six groups (n=8). Group 1: untreated controls; Group 2: received TAA (200 mg/kg body weight (b.w.); i.p.) for 12 weeks; Group 3: received curcumin (75 mg/kg b.w.) for 24 weeks; Group 4: received TAA (200 mg/kg b.w.; i.p.) for 12 weeks+curcumin (75 mg/kg b.w.) for 12 weeks. A significantly higher ACE gene expression was observed in TAA-induced groups as compared with control, indicating more synthesis of ACE proteins. Treatment with curcumin suppressed ACE expression in TAA liver and reversed the toxicity produced. TAA treatment results in higher lipid peroxidation and lower GSH, SOD and CAT than the normal, and this produces oxidative stress in the liver. Cirrhotic conditions were confirmed by serum enzymes (ALT, AST and ALP) as well as histopathological observations. Curcumin treatment reduced oxidative stress in animals by scavenging reactive oxygen species, protecting the anti-oxidant enzymes from being denatured and reducing the oxidative stress marker lipid peroxidation. Curcumin treatment restores hepatocytes, damaged by TAA, and protects liver tissue approaching cirrhosis. © The Author(s) 2014.

The Synergetic Effect of Cash Transfers for Families, Child Sensitive Social Protection Programs, and Capacity Building for Effective Social Protection on Children’s Nutritional Status in Nepal

PubMed Central

Renzaho, Andre M. N.; Chitekwe, Stanley; Chen, Wen; Rijal, Sanjay; Dhakal, Thakur; Dahal, Pradiumna

2017-01-01

Objective: The aim of this study was to evaluate the effectiveness of the synergetic effect of child sensitive social protection programs, augmented by a capacity building for social protection and embedded within existing government’s targeted resource transfers for families on child nutritional status. Design: A repeat cross-sectional quasi-experimental design with measures taken pre- (October–December 2009) and post- (December 2014–February 2015) intervention in the intervention and comparison district. The comparison district received standard social welfare services in the form of targeted resource transfers (TRTs) for eligible families. The intervention district received the TRTs plus a child cash payment, augmented by a capacity building for effective social protection outcomes. Propensity scores were used in difference-in-differences models to compare the changes over time between the intervention and control groups. Results: Propensity score matched/weighted models produced better results than the unmatched analyses, and hence we report findings from the radius matching. The intervention resulted in a 5.16 (95% CI: 9.55, 0.77), 7.35 (95% CI: 11.62, 3.08) and 2.84 (95% CI: 5.58, 0.10) percentage point reduction in the prevalence of stunting, underweight, and wasting among children under the age, respectively. The intervention impact was greater in boys than girls for stunting and wasting; and greater in girls than boys for underweight. The intervention also resulted in a 6.66 (95% CI: 2.13, 3.18), 11.40 (95% CI: 16.66, 6.13), and 4.0 (95% CI: 6.43, 1.78) percentage point reduction in the prevalence of stunting, underweight, and wasting among older children (≥24 months). No impact was observed among younger children (<24 months). Conclusions: Targeted resource transfers for families, augmented with a child sensitive social protection program and capacity building for social protection can address effectively child malnutrition. To increase the intervention effectiveness on younger children, the child cash payment amount needs to be revisited and closely embedded into infant and young child feeding initiatives, but also adjusted to equate to 20% of household expenditure or more to maximize the diversity of food available to young children. PMID:29207554

Immunogenicity and clinical protection against equine influenza by gene-based DNA vaccination of ponies

PubMed Central

Ault, Alida; Zajac, Alyse M.; Kong, Wing-Pui; Gorres, J. Patrick; Royals, Michael; Wei, Chih-Jen; Bao, Saran; Yang, Zhi-yong; Reedy, Stephanie E.; Sturgill, Tracy L.; Page, Allen E.; Donofrio-Newman, Jennifer; Adams, Amanda A.; Balasuriya, Udeni B.R.; Horohov, David W.; Chambers, Thomas M.; Nabel, Gary J.; Rao, Srinivas S.

2012-01-01

Equine influenza A (H3N8) virus is a leading cause of infectious respiratory disease in horses causing widespread morbidity and economic losses. As with influenza in other species, equine influenza strains continuously mutate, requiring constant re-evaluation of current vaccines and development of new vaccines. Current inactivated (killed) vaccines, while efficacious, only offer limited protection against multiple strains and require frequent boosts. Ongoing research into new vaccine technologies, including gene-based vaccines, aims to increase the neutralization potency, breadth, and duration of protective immunity of new or existing vaccines. In these hypothesis-generating experiments, we demonstrate that a DNA vaccine expressing the hemagglutinin protein of equine H3N8 influenza virus generates homologous and heterologous immune responses, and protects against clinical disease and viral replication following homologous H3N8 infection in horses. Furthermore, we demonstrate that a needle-free delivery device is as efficient and effective as conventional parenteral injection using a needle and syringe. The observed trends in this study drive the hypothesis that DNA vaccines offer a safe, effective, and promising alternative approach for veterinary vaccines against influenza, and applicable to combat equine influenza. PMID:22449425

Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p-transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria model.

PubMed

Cherif, Mahamoud Sama; Shuaibu, Mohammed Nasir; Kodama, Yukinobu; Kurosaki, Tomoaki; Helegbe, Gideon Kofi; Kikuchi, Mihoko; Ichinose, Akitoyo; Yanagi, Tetsuo; Sasaki, Hitoshi; Yui, Katsuyuki; Tien, Nguyen Huy; Karbwang, Juntra; Hirayama, Kenji

2014-04-07

We have previously reported the new formulation of polyethylimine (PEI) with gamma polyglutamic acid (γ-PGA) nanoparticle (NP) to have provided Plasmodium yoelii merozoite surface protein-1 (PyMSP-1) plasmid DNA vaccine with enhanced protective cellular and humoral immunity in the lethal mouse malaria model. PyGPI8p-transamidase-related protein (PyTAM) was selected as a possible candidate vaccine antigen by using DNA vaccination screening from 29 GPI anchor and signal sequence motif positive genes picked up using web-based bioinformatics tools; though the observed protection was not complete. Here, we observed augmented protective effect of PyTAM DNA vaccine by using PEI and γ-PGA complex as delivery system. NP-coated PyTAM plasmid DNA immunized mice showed a significant survival rate from lethal P. yoelii challenge infection compared with naked PyTAM plasmid or with NP-coated empty plasmid DNA group. Antigen-specific IgG1 and IgG2b subclass antibody levels, proportion of CD4 and CD8T cells producing IFN-γ in the splenocytes and IL-4, IFN-γ, IL-12 and TNF-α levels in the sera and in the supernatants from ex vivo splenocytes culture were all enhanced by the NP-coated PyTAM DNA vaccine. These data indicates that NP augments PyTAM protective immune response, and this enhancement was associated with increased DC activation and concomitant IL-12 production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enhancing robustness of multiparty quantum correlations using weak measurement

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

Singh, Uttam, E-mail: uttamsingh@hri.res.in; Mishra, Utkarsh, E-mail: utkarsh@hri.res.in; Dhar, Himadri Shekhar, E-mail: dhar.himadri@gmail.com

Multipartite quantum correlations are important resources for the development of quantum information and computation protocols. However, the resourcefulness of multipartite quantum correlations in practical settings is limited by its fragility under decoherence due to environmental interactions. Though there exist protocols to protect bipartite entanglement under decoherence, the implementation of such protocols for multipartite quantum correlations has not been sufficiently explored. Here, we study the effect of local amplitude damping channel on the generalized Greenberger–Horne–Zeilinger state, and use a protocol of optimal reversal quantum weak measurement to protect the multipartite quantum correlations. We observe that the weak measurement reversal protocol enhancesmore » the robustness of multipartite quantum correlations. Further it increases the critical damping value that corresponds to entanglement sudden death. To emphasize the efficacy of the technique in protection of multipartite quantum correlation, we investigate two proximately related quantum communication tasks, namely, quantum teleportation in a one sender, many receivers setting and multiparty quantum information splitting, through a local amplitude damping channel. We observe an increase in the average fidelity of both the quantum communication tasks under the weak measurement reversal protocol. The method may prove beneficial, for combating external interactions, in other quantum information tasks using multipartite resources. - Highlights: • Extension of weak measurement reversal scheme to protect multiparty quantum correlations. • Protection of multiparty quantum correlation under local amplitude damping noise. • Enhanced fidelity of quantum teleportation in one sender and many receivers setting. • Enhanced fidelity of quantum information splitting protocol.« less

Protective actions of progesterone in the cardiovascular system: potential role of membrane progesterone receptors (mPRs) in mediating rapid effects.

PubMed

Thomas, Peter; Pang, Yefei

2013-06-01

The protective functions of progesterone in the cardiovascular system have received little attention even though evidence has accumulated that progesterone lowers blood pressure, inhibits coronary hyperactivity and has powerful vasodilatory and natriuretic effects. One possible reason why potential beneficial actions of progesterone on cardiovascular functions have not been extensively studied is that divergent effects to those of progesterone have been observed in many clinical trials with synthetic progestins such as medroxyprogesterone acetate which are associated with increased risk of coronary disease. Evidence that progesterone exerts protective effects on cardiovascular functions is briefly reviewed. The finding that progesterone administration decreases blood vessel vasoconstriction in several animal models within a few minutes suggests that rapid, nongenomic progesterone mechanisms are of physiological importance in regulating vascular tone. Rapid activation of second messenger pathways by progesterone has been observed in vascular endothelial and smooth muscle cells, resulting in alterations in endothelial nitric oxide synthase (eNOS) activity and calcium influx, respectively. Both nuclear progesterone receptors (PRs) and novel membrane progesterone receptors (mPRs) are candidates for the intermediaries in these rapid, cell-surface initiated progesterone actions in endothelial and smooth muscle vascular cells. PRs have been detected in both cell types. New data are presented showing mPRα, mPRβ and mPRγ are also present in human endothelial and smooth muscle vascular cells. Preliminary evidence suggests mPRs mediate rapid progestin signaling in these endothelial cells, resulting in down-regulation of cAMP production and increased nitric oxide synthesis. The role of mPRs in progesterone regulation of cardiovascular functions warrants further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats.

PubMed

Gelen, Volkan; Şengül, Emin; Yıldırım, Serkan; Atila, Gözde

2018-04-01

5-fluorouracil-induced (5-FU), an anticarcinogenic agent, is reported to have side-effects that include hepatotoxicity and nephrotoxicity. The study objective was to investigate the protective effects of naringin on 5-FU-induced hepatotoxicity and nephrotoxicity. Thirty rodents were assigned to three groups. The control group received 1 ml of intragastric distilled water for 14 days. The 5-FU group received 1 ml of distilled water for 14 days as a placebo. On day 9, this same group received a 20 mg/kg dose of 5-FU administered intraperitoneally(IP) for a further five days. The naringin+5-FU group received a 100 mg/kg dose of naringin (IP) for 14 days. On day 9, 20 mg/kg of 5-FU was administered (IP) to this group for a further five days. On day 15, the rats were decapitated, and blood and renal and hepatic tissues were taken. It was determined that serum creatinine, BUN, AST, ALT, ALP, and LDH levels, as well as cytokine levels in the liver and kidney tissues were significantly elevated in the 5-FU group, compared to the control group. The comparative values were similar in the control and naringin+5-FU groups. When the liver tissue was examined histopathologically, in the control group it was found to be normal in structure. However, necrosis was observed in the hepatocytes of the pericentric region in the 5-FU group. 8-OHdG cell density was significantly elevated in the 5-FU group, compared to the control and naringin+5-FU groups. Naringin was observed to have a protective effect on 5-FU-induced liver and kidney damage.

The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats

PubMed Central

Gelen, Volkan; Şengül, Emin; Yıldırım, Serkan; Atila, Gözde

2018-01-01

Objective(s): 5-fluorouracil-induced (5-FU), an anticarcinogenic agent, is reported to have side-effects that include hepatotoxicity and nephrotoxicity. The study objective was to investigate the protective effects of naringin on 5-FU-induced hepatotoxicity and nephrotoxicity. Materials and Methods: Thirty rodents were assigned to three groups. The control group received 1 ml of intragastric distilled water for 14 days. The 5-FU group received 1 ml of distilled water for 14 days as a placebo. On day 9, this same group received a 20 mg/kg dose of 5-FU administered intraperitoneally(IP) for a further five days. The naringin+5-FU group received a 100 mg/kg dose of naringin (IP) for 14 days. On day 9, 20 mg/kg of 5-FU was administered (IP) to this group for a further five days. On day 15, the rats were decapitated, and blood and renal and hepatic tissues were taken. Results: It was determined that serum creatinine, BUN, AST, ALT, ALP, and LDH levels, as well as cytokine levels in the liver and kidney tissues were significantly elevated in the 5-FU group, compared to the control group. The comparative values were similar in the control and naringin+5-FU groups. When the liver tissue was examined histopathologically, in the control group it was found to be normal in structure. However, necrosis was observed in the hepatocytes of the pericentric region in the 5-FU group. 8-OHdG cell density was significantly elevated in the 5-FU group, compared to the control and naringin+5-FU groups. Conclusion: Naringin was observed to have a protective effect on 5-FU-induced liver and kidney damage. PMID:29796225

Sun protection at elementary schools: a cluster randomized trial.

PubMed

Hunter, Seft; Love-Jackson, Kymia; Abdulla, Rania; Zhu, Weiwei; Lee, Ji-Hyun; Wells, Kristen J; Roetzheim, Richard

2010-04-07

Elementary schools represent both a source of childhood sun exposure and a setting for educational interventions. Sun Protection of Florida's Children was a cluster randomized trial promoting hat use at (primary outcome) and outside of schools among fourth-grade students during August 8, 2006, through May 22, 2007. Twenty-two schools were randomly assigned to the intervention (1115 students) or control group (1376 students). Intervention schools received classroom sessions targeting sun protection attitudes and social norms. Each student attending an intervention school received two free wide-brimmed hats. Hat use at school was measured by direct observation and hat use outside of school was measured by self-report. A subgroup of 378 students (178 in the intervention group and 200 in the control group) underwent serial measurements of skin pigmentation to explore potential physiological effects of the intervention. Generalized linear mixed models were used to evaluate the intervention effect by accounting for the cluster randomized trial design. All P values were two-sided and were claimed as statistically significant at a level of .05. The percentage of students observed wearing hats at control schools remained essentially unchanged during the school year (baseline = 2%, fall = 0%, and spring = 1%) but increased statistically significantly at intervention schools (baseline = 2%, fall = 30%, and spring = 41%) (P < .001 for intervention effect comparing the change in rate of hat use over time at intervention vs control schools). Self-reported use of hats outside of school did not change statistically significantly during the study (control: baseline = 14%, fall = 14%, and spring = 11%; intervention: baseline = 24%, fall = 24%, and spring = 23%) nor did measures of skin pigmentation. The intervention increased use of hats among fourth-grade students at school but had no effect on self-reported wide-brimmed hat use outside of school or on measures of skin pigmentation.

Ameliorative effects of nano-elemental selenium against hexavalent chromium-induced apoptosis in broiler liver.

PubMed

Xueting, Liu; Rehman, Mujeeb Ur; Mehmood, Khalid; Huang, Shucheng; Tian, Xinxin; Wu, Xiaoxing; Zhou, Donghai

2018-06-01

The current study examined the ameliorative effects of nano-elemental selenium (Nano-Se) against chromium-VI (K 2 Cr 2 O 7 )-induced apoptosis in chickens. The expression of apoptosis-related genes was evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. A total of 60, one-day-old broiler chickens allotted to six equal groups, i.e., control group (standard diet), Cr(VI)-exposed group (K 2 Cr 2 O 7 via drinking water), Nano-Se group (Nano-Se at 0.5 mg/kg via diet), protection group (K 2 Cr 2 O 7  + Nano-Se), cure group (K 2 Cr 2 O 7 for initial 2 weeks and then Nano-Se), and prevention group (opposite to the cure group) and were detected by the activities of pro-apoptosis (Bax, Caspase-3) and anti-apoptosis (Bcl-2) genes expression at day 35 of the experiment. Intense apoptosis was observed in liver tissues of chickens exposed to K 2 Cr 2 O 7 . The Nano-Se supplementation caused a significant decrease (P < 0.01) in the mRNA expression levels of Bax and Caspase-3 genes, while significantly elevated (P < 0.05) mRNA expression level of Bcl-2 gene was observed in Nano-Se experimental groups as compare to control and Cr(VI)-exposed group. The results quantified by the RT-qPCR were further confirmed by the western blot analysis. Altogether, these results suggest anti-apoptotic effects of Nano-Se in the chicken liver, which is interesting for further study. The present findings suggested that Nano-Se has protective effects against K 2 Cr 2 O 7 -induced apoptosis in broilers liver and can serve a key role as a protective agent against apoptosis.

Protective Effect of Thymoquinone against Cyclophosphamide-Induced Hemorrhagic Cystitis through Inhibiting DNA Damage and Upregulation of Nrf2 Expression.

PubMed

Gore, Prashant R; Prajapati, Chaitali P; Mahajan, Umesh B; Goyal, Sameer N; Belemkar, Sateesh; Ojha, Shreesh; Patil, Chandragouda R

2016-01-01

Cyclophosphamide (CYP) induced hemorrhagic cystitis is a dose-limiting side effect involving increased oxidative stress, inflammatory cytokines and suppressed activity of nuclear factor related erythroid 2-related factor (Nrf2). Thymoquinone (TQ), an active constituent of Nigella sativa seeds, is reported to increase the expression of Nrf2, exert antioxidant action, and anti-inflammatory effects in the experimental animals. The present study was designed to explore the effects of TQ on CYP-induced hemorrhagic cystitis in Balb/c mice. Cystitis was induced by a single intraperitoneal injection of CYP (200 mg/kg). TQ was administered intraperitoneally at 5, 10 and 20 mg/kg doses twice a day, for three days before and three days after the CYP administration. The efficacy of TQ was determined in terms of the protection against the CYP-induced histological perturbations in the bladder tissue, reduction in the oxidative stress, and inhibition of the DNA fragmentation. Immunohistochemistry was performed to examine the expression of Nrf2. TQ protected against CYP-induced oxidative stress was evident from significant reduction in the lipid peroxidation, restoration of the levels of reduced glutathione, catalase and superoxide dismutase activities. TQ treatment significantly reduced the DNA damage evident as reduced DNA fragmentation. A significant decrease in the cellular infiltration, edema, epithelial denudation and hemorrhage were observed in the histological observations. There was restoration and rise in the Nrf2 expression in the bladder tissues of mice treated with TQ. These results confirm that, TQ ameliorates the CYP-induced hemorrhagic cystitis in mice through reduction in the oxidative stress, inhibition of the DNA damage and through increased expression of Nrf2 in the bladder tissues.

Protective efficacy of passive immunization with monoclonal antibodies in animal models of H5N1 highly pathogenic avian influenza virus infection.

PubMed

Itoh, Yasushi; Yoshida, Reiko; Shichinohe, Shintaro; Higuchi, Megumi; Ishigaki, Hirohito; Nakayama, Misako; Pham, Van Loi; Ishida, Hideaki; Kitano, Mitsutaka; Arikata, Masahiko; Kitagawa, Naoko; Mitsuishi, Yachiyo; Ogasawara, Kazumasa; Tsuchiya, Hideaki; Hiono, Takahiro; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi; Ito, Mutsumi; Quynh Mai, Le; Kawaoka, Yoshihiro; Miyamoto, Hiroko; Ishijima, Mari; Igarashi, Manabu; Suzuki, Yasuhiko; Takada, Ayato

2014-06-01

Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.

[Face protective patches do not reduce facial pressure ulcers in a simulated model of non-invasive ventilation].

PubMed

Riquelme M, Hugo; Wood V, David; Martínez F, Santiago; Carmona M, Fernando; Peña V, Axel; Wegner A, Adriana

2017-06-01

Noninvasive ventilation (NIV) frequently involves the development of facial pressure ulcers (FPU). Its prevention considers the empirical use of protective patches between skin and mask, in order to reduce the pressure exerted by it. To evaluate the effect of protective patches on the pressure exerted by the facial mask, and its impact on the programmed ventilatory parameters. Bilevel NIV simulated model using full face mask in phantom with a physiological airway (ALS PRO +) in supine position. Forehead, chin and cheekbones pressure were measured using 3 types of standard protective patches versus a control group using pressure sensors (Interlinks Electronics®). The values obtained with the protective patches-mask model were evaluated in the programmed variables maximum inspiratory flow (MIF)), expired tidal volume (Vte) and positive inspiratory pressure (IPAP), with Trilogy 100 ventilator, Respironics®. The programming and recording of the variables was carried out in 8 opportunities in each group by independent operators. There was no decrease in facial pressure with any of the protective patches compared to the control group. Moltopren increased facial pressure at all support points (p < 0.001), increased leakage, it decreased MIF, Vte and IPAP (p < 0.001). Hydrocolloid patches increased facial pressure only in the left cheekbone, increased leakage and decreased MIF. Polyurethane patches did not produce changes in facial pressure or ventilatory variables. The use of protective patches of moltopren, hydrocolloid and polyurethane transparent did not contribute to the decrease of the facial pressure. A deleterious effect of the moltopren and hydrocolloid patches was observed on the administration of ventilatory variables, concluding that the non-use of the protective patches allowed a better administration of the programmed parameters.

Nasal Acai polysaccharides potentiate innate immunity to protect against pulmonary Francisella tularensis and Burkholderia pseudomallei Infections.

PubMed

Skyberg, Jerod A; Rollins, MaryClare F; Holderness, Jeff S; Marlenee, Nicole L; Schepetkin, Igor A; Goodyear, Andrew; Dow, Steven W; Jutila, Mark A; Pascual, David W

2012-01-01

Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens.

In vitro safety evaluation and anticlastogenic effect of BacoMind on human lymphocytes.

PubMed

Deb, Dlpanwita Dutta; Kapoor, Preeti; Dighe, R P; Padmaja, R; Anand, M S; D'Souza, P; Deepak, M; Murali, B; Agarwal, Amit

2008-02-01

BacoMind (BM) is a standardized extract of Bacopa monnieri, which belongs to the family Scrophulariaceae and is a creeping annual plant found throughout the Indian subcontinent. It has been used by Ayurvedic medicinal practitioners in India for almost 3000 years and is classified as a medharasayana, a substance which improves memory and intellect. With the widespread traditional use as well as scientific validation of Bacopa monnieri for nootropic activity, a bioactive-rich unique phytochemical composition-BacoMind was developed from B. monnieri for use as a cognition and memory enhancing agent. The present study aimed to investigate the in vitro toxicity of this formulation of BacoMind on human lymphocytes and to rule out its possible contribution to mutagenicity. In the present investigation the active ingredients present in BM were identified and quantified by high performance liquid chromatography (HPLC) and high performance thin-layer chromatography (HPTLC). Antioxidant and anticlastogenic properties of BM were studied in vitro with and without metabolic activation. Doses of BM were chosen on the basis of mitotic index (MI) and cytokinesis-block proliferation index (CBPI). Clastogenicity assays were performed at 31.2 microg/mL, 62.5 microg/mL, and 125 microg/mL, while the Salmonella reverse mutation assay (Ames test) was performed at doses of 61.72, 185.18, 555.55, 1666.67, and 5000.00 microg/plate. HPLC and HPTLC analysis of BM revealed the presence of bacoside A3, bacopaside I, bacopaside II, jujubogenin isomer of bacopasaponin C, bacosine, luteolin, apigenin, bacosine, and beta-sitosterol D glucoside. BM demonstrated significant antioxidant activity. The number of chromosomal aberrations and the frequency of micronuclei induced by BM were not statistically significant up to a dose of 62.5 microg/mL. A subsequent dose of 125 microg/mL prior to metabolic activation induced mild clastogenicity, but it was found to be biologically insignificant as this effect was not seen post metabolic activation. BM also demonstrated a dose-dependent protection against the clastogens used in this study using the above tests for clastogenicity. Maximum protection was observed in presence of metabolic activation. Moreover, BM demonstrated no mutagenic effect on the tested strains, as observed in the Ames test. BM protected human lymphocytes against various clastogens. BM also exhibited high antioxidant activity which might be responsible for the observed protective effects against the clastogens since the used clastogens are known to induce their clastogenic effects via production of oxidative radicals.

Workplace protection of air-fed visors used in paint spraying operations.

PubMed

Bolsover, J; Rajan-Sithamparanadarajah, B; Vaughan, N

2006-04-01

Air-fed visors are commonly used for protection against exposure to airborne isocyanates during paint spraying. Protection levels for this class of equipment are theoretically adequate, yet isocyanate sensitization in this occupation still occurs. The work reported here set out to establish the level of respiratory protection that is achieved during real paint spraying activities when air-fed visors are used. The work also examined the effects of reduced air supply flow rates on this type of respiratory protection. The workplace study highlighted common problems that occur when attempting to measure protection factors, and process and interpret the collected data. Many of the environments included in this study did not exhibit challenge concentrations high enough to reliably measure the workplace protection factor of this class of device. When detection limits are taken into consideration, the remaining field data suggest that an assigned protection factor in the region of 40 may be appropriate. When well maintained and used in accordance with the manufacturer's instructions, air-fed visors are capable of providing a good level of respiratory protection. The protection given by air-fed visors is strongly dependent on the air flow supplied to them. Laboratory measurements demonstrate that protection falls as the air supply falls. This is a gradual process and does not suddenly occur at any particular air supply flow. Observations made during the field tests indicate that there may be other activities associated with the spraying process that need to be taken into consideration when looking for sources of respiratory sensitization.

Effectiveness of OSHA Outreach Training on carpenters' work-related injury rates, Washington State 2000-2008.

PubMed

Schoenfisch, Ashley L; Lipscomb, Hester; Sinyai, Clayton; Adams, Darrin

2017-01-01

Despite the size and breadth of OSHA's Outreach Training program for construction, information on its impact on work-related injury rates is limited. In a 9-year dynamic cohort of 17,106 union carpenters in Washington State, the effectiveness of OSHA Outreach Training on workers' compensation claims rate was explored. Injury rates were calculated by training status overall and by carpenters' demographic and work characteristics using Poisson regression. OSHA Outreach Training resulted in a 13% non-significant reduction in injury claims rates overall. The protective effect was more pronounced for carpenters in their apprenticeship years, drywall installers, and with increasing time since training. In line with these observed effects and prior research, it is unrealistic to expect OSHA Outreach Training alone to have large effects on union construction workers' injury rates. Standard construction industry practice should include hazard awareness and protection training, coupled with more efficient approaches to injury control. Am. J. Ind. Med. 60:45-57, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Rigid removable cover for dorsal wound protection and tube fixation in pigs.

PubMed

Stynes, G D; Kiroff, G K; Morrison, W A; Edwards, G A; Page, R S; Kirkland, M A

2016-04-01

To report the design and benefits of a rigid polyethylene cover 'shell' for the protection of dorsal torso wounds and tube fixation in pigs. Open C-shaped polyethylene shells were designed to protect wounds and dressings on the dorsum of pigs used in research into negative pressure dressing-assisted wound healing. The shells were designed to resist trauma and contamination, to be comfortable and expansible, and to facilitate tube fixation and management. Strap fixation was optimised during experimentation. Efficacy was assessed by direct observation of dressing and wound protection, tube integrity and by macroscopic and microscopic assessments of wound healing. The shells effectively protected the wounds against blunt and sharp trauma, were simple to remove and reapply, were well tolerated and allowed for growth of the pigs. Circumferential neck straps attached by lateral straps to the shells proved critical. There was no wound infection or inflammation underlying the shells. Porting tubing via mid-dorsal holes in the shells and affixing the tubing just cranial to these holes prevented tube damage and traction, permitted tube management from outside the cages and allowed the pigs to move freely without becoming entangled. These shells effectively protected dorsal skin wounds and dressings, prevented tube damage and facilitated tube management in pigs. Similar systems may be useful for other production animals for wound management and for tube management with negative pressure wound healing, drain tubes or the delivery of nutrition, fluids or medications. © 2016 Australian Veterinary Association.

Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model.

PubMed

Coudeville, Laurent; Bailleux, Fabrice; Riche, Benjamin; Megas, Françoise; Andre, Philippe; Ecochard, René

2010-03-08

Antibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI) assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy. We present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information. A significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B) and the vaccination status of the individuals. Although limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile.

Allicin protects auditory hair cells and spiral ganglion neurons from cisplatin - Induced apoptosis.

PubMed

Wu, Xianmin; Li, Xiaofei; Song, Yongdong; Li, He; Bai, Xiaohui; Liu, Wenwen; Han, Yuechen; Xu, Lei; Li, Jianfeng; Zhang, Daogong; Wang, Haibo; Fan, Zhaomin

2017-04-01

Cisplatin is a broad-spectrum anticancer drug that is commonly used in the clinic. Ototoxicity is one of the major side effects of this drug, which caused irreversible sensorineural hearing loss. Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-apoptotic and anti-oxidative activities in vitro and in vivo studies. We took advantage of C57 mice intraperitoneally injected with cisplatin alone or with cisplatin and allicin combined, to investigate whether allicin plays a protective role in vivo against cisplatin ototoxicity. The result showed that C57 mice in cisplatin group exhibited increased shift in auditory brainstem response, whereas the auditory fuction of mice in allicin + cisplatin group was protected in most frequencies, which was accordance with observed damages of outer hair cells (OHCs) and spiral ganglion neurons (SGNs) in the cochlea. Allicin markedly protected SGN mitochondria from damage and releasing cytochrome c, and significantly reduced pro-apoptosis factor expressions activated by cisplatin, including Bax, cleaved-caspase-9, cleaved-caspase-3and p53. Furthermore, allicin reduced the level of Malondialdehyde (MDA), but increased the level of superoxide dismutase (SOD). All data suggested that allicin could prevent hearing loss induced by cisplatin effectively, of which allicin protected SGNs from apoptosis via mitochondrial pathway while protected OHCs and supporting cells (SCs) from apoptosis through p53 pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exercise and the Prevention of Depression: Results of the HUNT Cohort Study.

PubMed

Harvey, Samuel B; Øverland, Simon; Hatch, Stephani L; Wessely, Simon; Mykletun, Arnstein; Hotopf, Matthew

2018-01-01

The purpose of the present study was to address 1) whether exercise provides protection against new-onset depression and anxiety and 2) if so, the intensity and amount of exercise required to gain protection and, lastly, 3) the mechanisms that underlie any association. A "healthy" cohort of 33,908 adults, selected on the basis of having no symptoms of common mental disorder or limiting physical health conditions, was prospectively followed for 11 years. Validated measures of exercise, depression, anxiety, and a range of potential confounding and mediating factors were collected. Undertaking regular leisure-time exercise was associated with reduced incidence of future depression but not anxiety. The majority of this protective effect occurred at low levels of exercise and was observed regardless of intensity. After adjustment for confounders, the population attributable fraction suggests that, assuming the relationship is causal, 12% of future cases of depression could have been prevented if all participants had engaged in at least 1 hour of physical activity each week. The social and physical health benefits of exercise explained a small proportion of the protective effect. Previously proposed biological mechanisms, such as alterations in parasympathetic vagal tone, did not appear to have a role in explaining the protection against depression. Regular leisure-time exercise of any intensity provides protection against future depression but not anxiety. Relatively modest changes in population levels of exercise may have important public mental health benefits and prevent a substantial number of new cases of depression.

76 FR 78832 - Protection of Stratospheric Ozone: Listing of Substitutes for Ozone-Depleting Substances...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-20

... outside the home. Household freezers offer storage space only at freezing temperatures. Products with both... systems, including cold storage cases, designed to chill food or keep it at a cold temperature for... Administration NOAEL--no observable adverse effect level NPRM--notice of proposed rulemaking NTTAA--National...

Agency Stovepipes vs Strategic Agility: Lessons We Need to Learn from Provincial Reconstruction Teams in Iraq and Afghanistan

DTIC Science & Technology

2008-04-01

soil testing labs, farming cooperatives, flood protection walls, veterinary services, solar meat chillers, poultry industry development, fish farms...measuring a PRT’s performance or effectiveness. Many of our sources observed that PRT operations have been and continue to be a “pick up game

Alkaline phosphatase protects against renal inflammation through dephosphorylation of lipopolysaccharide and adenosine triphosphate.

PubMed

Peters, E; Geraci, S; Heemskerk, S; Wilmer, M J; Bilos, A; Kraenzlin, B; Gretz, N; Pickkers, P; Masereeuw, R

2015-10-01

Recently, two phase-II trials demonstrated improved renal function in critically ill patients with sepsis-associated acute kidney injury treated with the enzyme alkaline phosphatase. Here, we elucidated the dual active effect on renal protection of alkaline phosphatase. The effect of human recombinant alkaline phosphatase (recAP) on LPS-induced renal injury was studied in Sprague-Dawley rats. Renal function was assessed by transcutaneous measurement of FITC-sinistrin elimination in freely moving, awake rats. The mechanism of action of recAP was further investigated in vitro using conditionally immortalized human proximal tubular epithelial cells (ciPTEC). In vivo, LPS administration significantly prolonged FITC-sinistrin half-life and increased fractional urea excretion, which was prevented by recAP co-administration. Moreover, recAP prevented LPS-induced increase in proximal tubule injury marker, kidney injury molecule-1 expression and excretion. In vitro, LPS-induced production of TNF-α, IL-6 and IL-8 was significantly attenuated by recAP. This effect was linked to dephosphorylation, as enzymatically inactive recAP had no effect on LPS-induced cytokine production. RecAP-mediated protection resulted in increased adenosine levels through dephosphorylation of LPS-induced extracellular ADP and ATP. Also, recAP attenuated LPS-induced increased expression of adenosine A2A receptor. However, the A2A receptor antagonist ZM-241385 did not diminish the effects of recAP. These results indicate that the ability of recAP to reduce renal inflammation may account for the beneficial effect observed in septic acute kidney injury patients, and that dephosphorylation of ATP and LPS are responsible for this protective effect. © 2015 The British Pharmacological Society.

Heated naringin mitigate the genotoxicity effect of Mitomycin C in BALB/c mice through enhancing the antioxidant status.

PubMed

Maatouk, Mouna; Mustapha, Nadia; Mokdad-Bzeouich, Imen; Chaaban, Hind; Ioannou, Irina; Ghedira, Kamel; Ghoul, Mohamed; Chekir-Ghedira, Leila

2018-01-01

A major problem with cancer chemotherapy is its severe toxic effects on non-target tissues. Assessment of natural products for their protective effect against anticancer drugs induced toxicity is gaining importance in cancer biology. The aim of the present study was to evaluate the effect of native and thermal treated naringin on the protective effect against mitomycin C (MMC) induced genotoxicity. The genotoxicity in liver kidney and brain cells isolated from Balb/C mice were evaluated by performing the comet assay. Antioxidant and lipid peroxidation assays were carried out to understand the protective effects of these compounds. The comet assay showed that heated and native naringin were not genotoxic at the tested dose (40 mg/kg b.w) on liver, kidney and brain cells. A significant decrease in DNA damages was observed, at the tested doses (20 mg/kg b.w and 40 mg/kg b.w) suggesting a protective role of these molecules against the genotoxicity induced by mitomycin C on liver, kidney and brain cells. Moreover, administration of MMC (6 mg/kg b.w.) altered the activities of glutathione peroxidase and superoxide dismutase accompanied by a significant increase of lipid peroxidation. Pretreatment of mouse with heated and native naringin before MMC administration significantly raised the glutathione peroxidase and superoxide dismutase activities followed by a reduced MMC-induced lipid peroxidation. Our study demonstrated that heat treatment of naringin preserve activities of native naringin. The genoprotective properties of heated and native naringin against MMC could be attributed to its antioxidant activities and its inhibitory effect on lipid peroxidation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Protective effect of Urtica dioica on liver damage induced by biliary obstruction in rats.

PubMed

Oguz, Serhat; Kanter, Mehmet; Erboga, Mustafa; Ibis, Cem

2013-10-01

The aim of this study was to evaluate the possible protective effects of Urtica dioica (UD) against liver damage in the common bile duct-ligated rats. A total of 24 male Sprague Dawley rats were divided into three groups, namely, control, bile duct ligation (BDL) and BDL + received UD groups, containing eight animals in each group. The rats in UD-treated groups were given UD oils (2 ml/kg) once a day intraperitoneally for 2 weeks starting 3 days prior to BDL operation. The change demonstrating the bile duct proliferation and fibrosis in expanded portal tracts includes the extension of proliferated bile ducts into the lobules; inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with UD attenuated alterations in liver histology. The α-smooth muscle actin, cytokeratin-positive ductular proliferation and the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in the BDL were observed to be reduced with the UD treatment. The data indicate that UD attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis.

Protective Effects of Hydrogen against Low-Dose Long-Term Radiation-Induced Damage to the Behavioral Performances, Hematopoietic System, Genital System, and Splenic Lymphocytes in Mice

PubMed Central

Lei, Xiao; Zhao, Hainan; Liu, Pengfei; Xu, Yang; Chen, Yuanyuan; Chuai, Yunhai

2016-01-01

Molecular hydrogen (H2) has been previously reported playing an important role in ameliorating damage caused by acute radiation. In this study, we investigated the effects of H2 on the alterations induced by low-dose long-term radiation (LDLTR). All the mice in hydrogen-treated or radiation-only groups received 0.1 Gy, 0.5 Gy, 1.0 Gy, and 2.0 Gy whole-body gamma radiation, respectively. After the last time of radiation exposure, all the mice were employed for the determination of the body mass (BM) observation, forced swim test (FST), the open field test (OFT), the chromosome aberration (CA), the peripheral blood cells parameters analysis, the sperm abnormality (SA), the lymphocyte transformation test (LTT), and the histopathological studies. And significant differences between the treatment group and the radiation-only groups were observed, showing that H2 could diminish the detriment induced by LDLTR and suggesting the protective efficacy of H2 in multiple systems in mice against LDLTR. PMID:27774116

Protective effect of embelin from Embelia ribes Burm. against transient global ischemia-induced brain damage in rats.

PubMed

Thippeswamy, B S; Nagakannan, P; Shivasharan, B D; Mahendran, S; Veerapur, V P; Badami, S

2011-11-01

Embelia ribes is being used in Indian traditional herbal medicine for the treatment of mental disorders and as brain tonic. The present study was designed to investigate the protective effects of embelin from E. ribes on global ischemia/reperfusion-induced brain injury in rats. Transient global ischemia was induced by occluding bilateral common carotid arteries for 30 min followed by 24-h reperfusion. Neurological functions were measured using sensorimotor tests. Ischemia/reperfusion-induced neuronal injury was assessed by cerebral infarct area, biochemical and histopathological examination. Pretreatment of embelin (25 and 50 mg/kg, p.o.) significantly increased locomotor activity and hanging latency time and decreased beam walking latency when compared with ischemic control. The treatment also reduced significantly the lipid peroxidation and increased the total thiol content and glutathione-S-transferase activity in brain homogenates. The decreased cerebral infarction area in embelin-treated groups and histopathological observations confirmed the above findings. These observations suggested that embelin is a neuroprotective agent and may prove to be useful adjunct in the treatment of stroke.

Killing of tumor cells: a drama in two acts.

PubMed

Giansanti, Vincenzo; Tillhon, Micol; Mazzini, Giuliano; Prosperi, Ennio; Lombardi, Paolo; Scovassi, A Ivana

2011-11-15

Cancer still represents a major health problem worldwide, which urges the development of more effective strategies. Resistance to chemotherapy, a major obstacle for cancer eradication, is mainly related to an intrinsic failure to activate the apoptotic pathways. However, a protective effect of autophagy toward cancer cells has been recently observed, thus adding further complexity to the development of an effective approach counteracting cancer cell growth and improving the response to therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Immortal time bias in observational studies of time-to-event outcomes.

PubMed

Jones, Mark; Fowler, Robert

2016-12-01

The purpose of the study is to show, through simulation and example, the magnitude and direction of immortal time bias when an inappropriate analysis is used. We compare 4 methods of analysis for observational studies of time-to-event outcomes: logistic regression, standard Cox model, landmark analysis, and time-dependent Cox model using an example data set of patients critically ill with influenza and a simulation study. For the example data set, logistic regression, standard Cox model, and landmark analysis all showed some evidence that treatment with oseltamivir provides protection from mortality in patients critically ill with influenza. However, when the time-dependent nature of treatment exposure is taken account of using a time-dependent Cox model, there is no longer evidence of a protective effect of treatment. The simulation study showed that, under various scenarios, the time-dependent Cox model consistently provides unbiased treatment effect estimates, whereas standard Cox model leads to bias in favor of treatment. Logistic regression and landmark analysis may also lead to bias. To minimize the risk of immortal time bias in observational studies of survival outcomes, we strongly suggest time-dependent exposures be included as time-dependent variables in hazard-based analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of 2-[(aminopropyl)amino] ethanethiol on fission-neutron-induced DNA damage and repair.

PubMed Central

Grdina, D. J.; Sigdestad, C. P.; Dale, P. J.; Perrin, J. M.

1989-01-01

The effect(s) of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR 1065) on fission-neutron-induced DNA damage and repair in V79 Chinese hamster cells was determined by using a neutral filter elution procedure (pH 7.2). When required, WR1065, at a final working concentration of 4 mM, was added to the culture medium, either 30 min before and during irradiation with fission spectrum neutrons (beam energy of 0.85 MeV) from the JANUS research reactor, or for selected intervals of time following exposure. The frequency of neutron-induced DNA strand breaks as measured by neutral elution as a function of dose equalled that observed for 60Co gamma-ray-induced damage (relative biological effectiveness of one). In contrast to the protective effect exhibited by WR1065 in reducing 60Co-induced DNA damage, WR1065 was ineffective in reducing or protecting against induction of DNA strand breaks by JANUS neutrons. The kinetics of DNA double-strand rejoining were measured following neutron irradiation. In the absence of WR1065, considerable DNA degradation by cellular enzymes was observed. This process was inhibited when WR1065 was present. These results indicate that, under the conditions used, the quality (i.e. nature), rather than quantity, of DNA lesions (measured by neutral elution) formed by neutrons was significantly different from that formed by gamma-rays. PMID:2667608

Evaluation of the protective effect of agmatine against cisplatin nephrotoxicity with 99mTc-DMSA renal scintigraphy and cystatin-C.

PubMed

Salihoglu, Yavuz Sami; Elri, Tarik; Gulle, Kanat; Can, Murat; Aras, Mustafa; Ozacmak, Hale Sayan; Cabuk, Mehmet

2016-10-01

The aim of the current study was to investigate whether agmatine (AGM) has a protective effect against cisplatin-induced nephrotoxicity. Thirty-two rats were randomly divided into four groups: (1) Saline (control); (2) Cisplatin (CDDP; 7.5 mg/kg intraperitoneally); (3) Agmatine (AGM; 10 mg/kg intraperitoneally); (4) Cisplatin plus agmatine (CDDP + AGM). Agmatine was given before and two consecutive days after cisplatin injection. All the animals underwent renal scintigraphy with 99mTc-DMSA. The levels of serum creatinine, cystatin C, and blood urea nitrogen (BUN) were measured in addition to examination of the tissue samples with light microscopy. Acute renal injury was assessed with biochemical analyses, scintigraphic imaging, and histopathological evaluation. In the cisplatin group, the levels of BUN, creatinine, and cystatin C were significantly higher than that of the controls. Histopathological examination showed remarkable damage of tubular and glomerular structures. Additionally, cisplatin caused markedly decreased renal 99mTc-DMSA uptake. AGM administration improved renal functions. Serum creatinine, BUN, and cystatin C levels had a tendency to normalize and, scintigraphic and histopathological findings showed significantly less evidence of renal toxicity than those observed in animals receiving cisplatin alone. Our data indicate that AGM has a protective effect against cisplatin-induced nephrotoxicity. Therefore, it may improve the therapeutic index of cisplatin. In addition, the early renal damage induced by cisplatin and protective effects of AGM against cisplatin nephrotoxicity was accurately demonstrated with 99mTc-DMSA renal scintigraphy.

Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells.

PubMed

Hirotani, Yoshihiko; Ikeda, Kenji; Kato, Ryuji; Myotoku, Michiaki; Umeda, Takashi; Ijiri, Yoshio; Tanaka, Kazuhiko

2008-09-01

Indirect evidence suggests that lactoferrin (Lf), a major iron-binding protein in human milk, induces enterocyte growth and proliferation, depending on its concentration and affects the function and permeability of the intestinal mucosa. The bacterial endotoxin (lipopolysaccharide, LPS) is known to cause mucosal hyperpermeability in vivo. However, protective effects of Lf against LPS-mediated intestinal mucosal damage and barrier function in epithelial cells are not yet fully clarified. The aim of this study was to investigate whether Lf can reduce the cellular injury and alter epithelial hyperpermeability caused by LPS in human intestinal Caco-2 cells. When cell viability was measured by a WST-1 assay (tetrazolium salt-based assay), the protective effects against LPS-induced damage to Caco-2 cells were observed at doses of 800 and 1000 microg/ml Lf. The barrier function of Caco-2 monolayer tight junctions was assessed by measuring transepithelial electrical resistance (TEER) and permeability of FITC-labeled dextran 4000 (FD-4). The treatment of Caco-2 cells with Lf at doses of 400 and 1000 microg/ml significantly increased TEER as compared to treatment with LPS alone for 2 h (p<0.05). Further, at doses of 400 and 1000 microg/ml, Lf inhibited the enhancement of LPS-mediated permeability in Caco-2 cell monolayer. The results of this study suggest that Lf may have protective effects against LPS-mediated intestinal mucosal damage and impairment of barrier function in intestinal epithelial cells.

Microsomal Glutathione Transferase 1 Protects Against Toxicity Induced by Silica Nanoparticles but Not by Zinc Oxide Nanoparticles

PubMed Central

2012-01-01

Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO2, CeO2, SiO2, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO2 and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO2 and CeO2. We also noted pronounced cytotoxicity for three out of four additional SiO2 nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO2 nanoparticles tested and for one of the supplementary SiO2 nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO2 nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn2+ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn2+ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO2 nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum. PMID:22303956

Xanthohumol Prevents DNA Damage by Dietary Carcinogens: Results of a Human Intervention Trial.

PubMed

Pichler, Christoph; Ferk, Franziska; Al-Serori, Halh; Huber, Wolfgang; Jäger, Walter; Waldherr, Monika; Mišík, Miroslav; Kundi, Michael; Nersesyan, Armen; Herbacek, Irene; Knasmueller, Siegfried

2017-02-01

Xanthohumol (XN) is a hop flavonoid contained in beers and soft drinks. In vitro and animal studies indicated that XN has DNA and cancer protective properties. To find out if it causes DNA protective effects in humans, an intervention trial was conducted in which the participants (n = 22) consumed a XN containing drink (12 mg XN/P/d). We monitored prevention of DNA damage induced by representatives of major groups of dietary carcinogens [i.e., nitrosodimethylamine (NDMA) benzo(a)pyrene (B(a)P) and the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)]. Lymphocytes were collected before, during, and after the intervention and incubated with the carcinogens and with human liver homogenate (S9). We found substantial reduction of B(a)P and IQ (P < 0.001 for both substances) induced DNA damage after consumption of the beverage; also, with the nitrosamine a moderate, but significant protective effect was found. The results of a follow-up trial (n = 10) with XN pills showed that the effects are caused by the flavonoid and were confirmed in γH2AX experiments. To elucidate the underlying mechanisms we measured several parameters of glutathione related detoxification. We found clear induction of α-GST (by 42.8%, P < 0.05), but no alteration of π-GST. This observation provides a partial explanation for the DNA protective effects and indicates that the flavonoid also protects against other carcinogens that are detoxified by α-GST. Taken together, our findings support the assumption that XN has anticarcinogenic properties in humans. Cancer Prev Res; 10(2); 153-60. ©2016 AACR. ©2016 American Association for Cancer Research.

Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats.

PubMed

Martínez-Moya, P; Ortega-González, M; González, R; Anzola, A; Ocón, B; Hernández-Chirlaque, C; López-Posadas, R; Suárez, M D; Zarzuelo, A; Martínez-Augustin, O; Sánchez de Medina, F

2012-08-01

Alkaline phosphatase (AP) inactivates bacterial lipopolysaccharide and may therefore be protective. The small intestine and colon express intestinal (IAP) and tissue nonspecific enzyme (TNAP), respectively. The aim of this study was to assess the therapeutic potential of exogenous AP and its complementarity with endogenous enzyme protection in the intestine, as evidenced recently. IAP was given to rats by the oral or intrarectal route (700U/kgday). Oral budesonide (1mg/kgday) was used as a reference treatment. Treatment with intrarectal AP resulted in a 54.5% and 38.0% lower colonic weight and damage score, respectively, and an almost complete normalization of the expression of S100A8, LCN2 and IL-1β (p<0.05). Oral AP was less efficacious, while budesonide had a more pronounced effect on most parameters. Both oral and intrarectal AP counteracted bacterial translocation effectively (78 and 100%, respectively, p<0.05 for the latter), while budesonide failed to exert a positive effect. AP activity was increased in the feces of TNBS colitic animals, associated with augmented sensitivity to the inhibitor levamisole, suggesting enhanced luminal release of this enzyme. This was also observed in the mouse lymphocyte transfer model of chronic colitis. In a separate time course study, TNAP was shown to increase 2-3 days after colitis induction, while dextran sulfate sodium was a much weaker inducer of this isoform. We conclude that exogenous AP exerts beneficial effects on experimental colitis, which includes protection against bacterial translocation. AP of the tissue-nonspecific isoform is shed in higher amounts to the intestinal lumen in experimental colitis, possibly aiding in intestinal protection. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improving reconstituted HDL composition for efficient post-ischemic reduction of ischemia reperfusion injury.

PubMed

Brulhart-Meynet, Marie-Claude; Braunersreuther, Vincent; Brinck, Jonas; Montecucco, Fabrizio; Prost, Jean-Christophe; Thomas, Aurelien; Galan, Katia; Pelli, Graziano; Pedretti, Sarah; Vuilleumier, Nicolas; Mach, François; Lecour, Sandrine; James, Richard W; Frias, Miguel A

2015-01-01

New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects. The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations. The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo. HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte.

The mitochondrially targeted antioxidant MitoQ protects the intestinal barrier by ameliorating mitochondrial DNA damage via the Nrf2/ARE signaling pathway.

PubMed

Hu, Qiongyuan; Ren, Jianan; Li, Guanwei; Wu, Jie; Wu, Xiuwen; Wang, Gefei; Gu, Guosheng; Ren, Huajian; Hong, Zhiwu; Li, Jieshou

2018-03-14

Disruption of the mucosal barrier following intestinal ischemia reperfusion (I/R) is life threatening in clinical practice. Mitochondrial dysfunction and oxidative stress significantly contribute to the early phase of I/R injury and amplify the inflammatory response. MitoQ is a mitochondrially targeted antioxidant that exerts protective effects following I/R injury. In the present study, we aimed to determine whether and how MitoQ protects intestinal epithelial cells (IECs) from I/R injury. In both in vivo and in vitro studies, we found that MitoQ pretreatment downregulated I/R-induced oxidative stress and stabilized the intestinal barrier, as evidenced by MitoQ-treated I/R mice exhibiting attenuated intestinal hyperpermeability, inflammatory response, epithelial apoptosis, and tight junction damage compared to controls. Mechanistically, I/R elevated mitochondrial 8-hydroxyguanine content, reduced mitochondrial DNA (mtDNA) copy number and mRNA transcription levels, and induced mitochondrial disruption in IECs. However, MitoQ pretreatment dramatically inhibited these deleterious effects. mtDNA depletion alone was sufficient to induce apoptosis and mitochondrial dysfunction of IECs. Mitochondrial transcription factor A (TFAM), a key activator of mitochondrial transcription, was significantly reduced during I/R injury, a phenomenon that was prevented by MitoQ treatment. Furthermore, we observed that thee protective properties of MitoQ were affected by upregulation of cellular antioxidant genes, including HO-1, NQO-1, and γ-GCLC. Transfection with Nrf2 siRNA in IECs exposed to hypoxia/reperfusion conditions partially blocked the effects of MitoQ on mtDNA damage and mitochondrial oxidative stress. In conclusion, our data suggest that MitoQ exerts protective effect on I/R-induced intestinal barrier dysfunction.

Protective effects and mechanisms of curcumin on podophyllotoxin toxicity in vitro and in vivo

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

Li, Juan; Dai, Cai-Xia; Sun, Hua

2012-12-01

Podophyllotoxin (POD) is a naturally occurring lignan with pronounced antineoplastic and antiviral properties. POD binds to tubulin and prevents the formation of mitotic spindle. Although cases of overdose or accidental ingestion are quite often, no specific therapy is currently available to treat the POD intoxication. In the current investigation, the protective effects and mechanisms of curcumin (CUR) on podophyllotoxin toxicity were evaluated in vitro and in vivo. The results showed that CUR could protect POD-induced cytotoxicity by recovering the G2/M arrest and decrease the changes of membrane potential and microtubule structure in Vero cells. A significant decrease of mortality ratesmore » was observed in Swiss mice treated by intragastrical administration of POD + CUR as compared with POD alone. The POD + CUR group also exhibited decreases in plasma transaminases, alkaline phosphatase, lactate dehydrogenase, plasma urea, creatinine and malondialdehyde level but elevated superoxide dismutase and glutathione levels as compared to the POD group. Histological examination of the liver and kidney demonstrated less morphological changes in the treatment of POD + CUR as compared with POD alone. The mechanism of the protective effects might be due to the competitive binding of CUR with POD in the same colchicines binding site as revealed by the tubulin polymerization assay and the molecular docking analysis, and the antioxidant activity against the oxidative stress induced by POD. In summary, both in vitro and in vivo data indicated the promising role of CUR as a protective agent against the POD poisoning. Highlights: ► A potential antidote to treat the podophyllotoxin (POD) intoxication is found. ► Curcumin showed promising effects against POD poisoning in vitro and in vivo. ► The mechanisms lie in the antioxidant activity and competitive binding with tubulin.« less

The protective effect of lycopene on hypoxia/reoxygenation-induced endoplasmic reticulum stress in H9C2 cardiomyocytes.

PubMed

Gao, Yang; Jia, Pengyu; Shu, WenQi; Jia, Dalin

2016-03-05

Nowadays, drugs protecting ischemia/reperfusion (I/R) myocardium become more suitable for clinic. It has been confirmed lycopene has various protections, but lacking the observation of its effect on endoplasmic reticulum stress (ERS)-mediated apoptosis caused by hypoxia/reoxygenation (H/R). This study aims to clarify the protective effect of lycopene on ERS induced by H/R in H9C2 cardiomyocytes. Detect the survival rate, lactic dehydrogenase (LDH) activity, apoptosis ratio, glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP), c-Jun-N-terminal protein Kinase (JNK) and Caspase-12 mRNA and protein expression and phosphorylation of JNK (p-JNK) protein expression. LDH activity, apoptosis ratio and GRP78 protein expression increase in the H/R group, reduced by lycopene. The survival rate reduces in the H/R and thapsigargin (TG) groups; lycopene and 4-phenyl butyric acid (4-PBA) can improve it caused by H/R, lycopene also can improve it caused by TG. The apoptosis ratio, the expression of GRP78, CHOP and Caspase-12 mRNA and protein and p-JNK protein increase in the H/R and TG groups, weaken in the lycopene+H/R, 4-PBA+H/R and lycopene+TG groups. There is no obvious change in the expression of JNK mRNA or protein. Hence, our results provide the evidence that 10 μM lycopene plays an obviously protective effect on H/R H9C2 cardiomyocytes, realized through reducing ERS and apoptosis. The possible mechanism may be related to CHOP, p-JNK and Caspase-12 pathways. Copyright © 2016. Published by Elsevier B.V.

Gata3 hypermethylation and Foxp3 hypomethylation are associated with sustained protection and bystander effect following epicutaneous immunotherapy in peanut-sensitized mice.

PubMed

Mondoulet, Lucie; Dioszeghy, Vincent; Busato, Florence; Plaquet, Camille; Dhelft, Véronique; Bethune, Kevin; Leclere, Laurence; Daviaud, Christian; Ligouis, Mélanie; Sampson, Hugh; Dupont, Christophe; Tost, Jörg

2018-05-19

Epicutaneous immunotherapy (EPIT) is a promising method for treating food allergies. In animal models, EPIT induces sustained unresponsiveness and prevents further sensitization mediated by Tregs. Here, we elucidate the mechanisms underlying the therapeutic effect of EPIT, by characterizing the kinetics of DNA methylation changes in sorted cells from spleen and blood and by evaluating its persistence and bystander effect compared to oral immunotherapy (OIT). BALB/c mice orally sensitized to peanut proteins (PPE) were treated by EPIT using a PPE-patch or by PPE-OIT. Another set of peanut-sensitized mice treated by EPIT or OIT were sacrificed following a protocol of sensitization to OVA. DNA methylation was analysed during immunotherapy and 8 weeks after the end of treatment in sorted cells from spleen and blood by pyrosequencing. Humoral and cellular responses were measured during and after immunotherapy. Analyses showed a significant hypermethylation of the Gata3 promoter detectable only in Th2 cells for EPIT from the 4 th week and a significant hypomethylation of the Foxp3 promoter in CD62L + Tregs, which was sustained only for EPIT. In addition, mice treated with EPIT were protected from subsequent sensitization and maintained the epigenetic signature characteristic for EPIT. Our study demonstrates that EPIT leads to a unique and stable epigenetic signature in specific T cell compartments with down regulation of Th2 key regulators and upregulation of Treg transcription factors, likely explaining the sustainability of protection and the observed bystander effect. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: the role of CD4+ T cells and IFN-gamma.

PubMed

Day, Yuan-Ji; Huang, Liping; Ye, Hong; Li, Li; Linden, Joel; Okusa, Mark D

2006-03-01

A(2A) adenosine receptor (A(2A)R)-expressing bone marrow (BM)-derived cells contribute to the renal protective effect of A(2A) agonists in renal ischemia-reperfusion injury (IRI). We performed IRI in mice lacking T and B cells to determine whether A(2A)R expressed in CD4+ cells mediate protection from IRI. Rag-1 knockout (KO) mice were protected in comparison to wild-type (WT) mice when subjected to IRI. ATL146e, a selective A(2A) agonist, did not confer additional protection. IFN-gamma is an important early signal in IRI and is thought to contribute to reperfusion injury. Because IFN-gamma is produced by kidney cells and T cells we performed IRI in BM chimeras in which the BM of WT mice was reconstituted with BM from IFN-gamma KO mice (IFN-gamma KO-->WT chimera). We observed marked reduction in IRI in comparison to WT-->WT chimeras providing additional indirect support for the role of T cells. To confirm the role of CD4+ A(2A)R in mediating protection from IRI, Rag-1 KO mice were subjected to ischemia-reperfusion. The protection observed in Rag-1 KO mice was reversed in Rag-1 KO mice that were adoptively transferred WT CD4+ cells (WT CD4+-->Rag-1 KO) or A(2A) KO CD4+ cells (A(2A) KO CD4+-->Rag-1 KO). ATL146e reduced injury in WT CD4+-->Rag-1 KO mice but not in A(2A) KO CD4+-->Rag-1 KO mice. Rag-1 KO mice reconstituted with CD4+ cells derived from IFN-gamma KO mice (IFN-gamma CD4+-->Rag-1 KO) were protected from IRI; ATL146e conferred no additional protection. These studies demonstrate that CD4+ IFN-gamma contributes to IRI and that A(2A) agonists mediate protection from IRI through action on CD4+ cells.

Counteraction of oxidative damage in the rat liver by an ancient grain (Kamut brand khorasan wheat).

PubMed

Benedetti, Serena; Primiterra, Mariangela; Tagliamonte, Maria Chiara; Carnevali, Andrea; Gianotti, Andrea; Bordoni, Alessandra; Canestrari, Franco

2012-04-01

We previously demonstrated in rat plasma the antioxidant protective effect of whole-grain bread, particularly when made from Kamut brand khorasan wheat. In the present study, we investigated the effects of the same experimental breads in rat liver using two different bread-making procedures (baker's yeast and sourdough fermentation). Rats were examined in the basal condition and after the administration of doxorubicin, a pro-oxidative agent. The following parameters were measured in liver homogenates: glutathione peroxidase and thioredoxin reductase activities, as antioxidant enzymes containing selenium; glutathione, α-tocopherol and β-carotene, as major non-enzymatic cell antioxidants; malondialdehyde and advanced oxidation protein products, as markers of oxidative damage to lipids and proteins, respectively. A histologic evaluation of liver tissue was also conducted. In agreement with our previous work, we observed a lower oxidative status and a different activity of glutathione peroxidase and thioredoxin reductase in rats fed the whole-grain Kamut khorasan bread than in rats fed the modern whole-grain durum wheat bread. Histologic evaluation of the hepatic tissue showed the onset of inflammation in response to doxorubicin only in rats fed the modern durum wheat bread. Our data confirm that bread made from whole-grain Kamut khorasan protects rats from oxidative stress better than bread made from whole-grain durum wheat. This is consistent with their different antioxidant profiles. The type of wheat used for bread-making appeared to be the main determinant of the observed protective effect. Copyright © 2012 Elsevier Inc. All rights reserved.

Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

PubMed

Facchini, Gustavo; Eberlin, Samara; Clerici, Stefano Piatto; Alves Pinheiro, Ana Lucia Tabarini; Costa, Adilson

2017-12-01

Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients. © 2017 Wiley Periodicals, Inc.

Use of a human skin in vitro model to investigate the influence of 'every-day' clothing and skin surface decontamination on the percutaneous penetration of organophosphates.

PubMed

Moore, C A; Wilkinson, S C; Blain, P G; Dunn, M; Aust, G A; Williams, F M

2014-08-17

Organophosphates (OPs) are widely used in agriculture. Many studies have investigated the capability of personal protective equipment (PPE) to reduce chemical exposure; however, investigations into the protective effect of 'every-day' clothing are rare. The purpose of this study was to investigate the protective effect of 'every-day' clothing against dermal exposure and to measure early decontamination of skin following exposure to chlorpyrifos and dichlorvos. Using human skin in vitro, absorption of (14)C-labelled chlorpyrifos (500 ng/cm(2)), was shown to be significantly reduced when applied to clothed skin (cotton shirt), regardless of application vehicle (isopropanol (IPA) or propylene glycol (PG)). The majority of applied dose was retained within the clothing after 4 h exposure. Significant reduction in absorption of chlorpyrifos (in PG) was seen through clothed skin when supplemented with skin decontamination at 4 h, compared with clothed skin decontaminated after 24 h, however, this was not observed with IPA. Absorption of dichlorvos (5 μg/cm(2)) was greater through unclothed skin than chlorpyrifos for all vehicles (IPA, isopropyl myristate (IPM) and PG). Significant reduction in absorption was observed when decontaminating clothed skin at 30 min, compared with decontamination at 24 h (post-exposure) for all vehicles. indicate that 'every-day' clothing is effective at reducing exposure to chemicals in contact with skin. Washing the skin surface immediately following removal of exposed clothing can further reduce exposure, depending on the properties of the chemical and vehicle applied. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Protection of methamphetamine nigrostriatal toxicity by dietary selenium.

PubMed

Kim, H C; Jhoo, W K; Choi, D Y; Im, D H; Shin, E J; Suh, J H; Floyd, R A; Bing, G

1999-12-18

Multiple dose administration of methamphetamine (MA) results in long-lasting toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased production of hydrogen peroxide or other reactive oxygen species in the dopaminergic system. The present study was designed to determine the protective effects of dietary antioxidant selenium on MA-induced neurotoxicity in the nigrostriatal dopaminergic system. Male C57BL/6J mice were fed either selenium-deficient (< 0.01 ppm Se) or selenium-replete (0.2 ppm Se) diets for 90 days. MA treatment decreased the dopamine (DA) levels in the striatum and substantia nigra (SN) of both Se-replete and Se-deficient animals. However, in Se-replete animals, this DA depletion was significantly attenuated in both the striatum and SN. A novel observation is that MA administration resulted in increased activity of Cu,Zn-SOD in the brains of both Se-deficient and Se-replete animals. However, MA administration to Se-deficient animals exhibited a higher Cu,Zn-SOD activity in the nigrostriatal system than the control animals. Elevated malondialdehyde (MDA) levels in the striatum and SN were also observed in Se-deficient MA-treated animals. Se repletion significantly increased the glutathione peroxidase (GPx) activity and the ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) in the MA-treated animals. In conclusion, we have shown that dietary Se attenuated methamphetamine neurotoxicity and that this protection involves GPx-mediated antioxidant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is not yet clear.

Unique natural exopolysaccharides for biomimetic protective effect against urban pollution.

PubMed

Borel, Magali; Lamarque, Elisabeth; Loing, Estelle

Through natural selection, living organisms have evolved well-adapted survival strategies over time. The shallow salt waters of Moorea lagoon are the site of accumulation of microbial mats called "Kopara," in the native Polynesian language. This unique ecosystem is rich in film-forming exopolysaccharides (EPSs) secreted by microorganisms within the biofilm, as a mean to protect themselves from environmental stress (strong ultraviolet [UV], pH, salinity … ). Using blue biotechnology, a manufacturing process was developed to obtain an EPS with skin benefits. The active ingredient (EPS-229) protects against urban pollution, including free radicals, heavy metals, hydrocarbons, and PM 2.5 (particulate matter with a size lower than 2.5 μm). The anti-lipid peroxidation action of EPS-229 was studied in an in vitro UVB-irradiated keratinocyte culture model, using lipophilic fluorescent probe. The chelating properties of EPS-229 were evaluated in tubo in the presence of cadmium and lead. The protective effect of EPS-229 on pollution-exposed skin explants was investigated through quantification of released malondialdehyde (MDA) and histological observation of skin morphology using optical microscopy. Clinical evaluation of the protective and cleansing efficacy of a water solution containing EPS-229 (0.02% and 0.01% w/v, respectively) was performed, against placebo, on a panel of 18 volunteers. For these studies, the forearms of volunteers were treated with EPS-229 before (anti-adhesion affect) or after (cleansing effect) application of PM 2.5 (iron particles of 1 μm). The presence of skin-adherent particles was observed and quantified by image analysis, using specific digital masks. In vitro , EPS-229 significantly protected keratinocyte cell membranes from lipid peroxidation. A decrease of 28% was achieved when a concentration of 0.001% w/v EPS-229 was applied to the cell culture. In tubo , EPS-229 also presented strong chelating properties. Maximal adsorption was estimated at 154 mg/g (1.37 mmol/g) of EPS-299 for cadmium and at 250 mg/g (1.21 mmol/g) of EPS-229 for lead. In the skin explant model of pollution exposure, EPS-229 (0.03% w/v) reduced MDA production by 44%, preserved cell integrity, improved dermal-epidermal cohesion, and normalized the collagen network. In vivo , treatment of skin with EPS-229 before exposure to PM 2.5 created a protective film limiting particle adhesion. When used in a cleansing solution after exposure to PM 2.5 , EPS-229 formed a mesh that entrapped particles and removed them from the skin surface. Inspired by the French Polynesia Kopara unique ecosystem, a bioactive exopolysaccharide (EPS-229) has been developed that offers protection from environmental aggression. As a biomimetic shield at the surface of the skin, EPS-229 provides an immediate multiprotective action that efficiently fights the harmful effects of urban pollution and smog.

Vaccination with plasmid DNA encoding TSA/LmSTI1 leishmanial fusion proteins confers protection against Leishmania major infection in susceptible BALB/c mice.

PubMed

Campos-Neto, A; Webb, J R; Greeson, K; Coler, R N; Skeiky, Y A W; Reed, S G

2002-06-01

We have recently shown that a cocktail containing two leishmanial recombinant antigens (LmSTI1 and TSA) and interleukin-12 (IL-12) as an adjuvant induces solid protection in both a murine and a nonhuman primate model of cutaneous leishmaniasis. However, because IL-12 is difficult to prepare, is expensive, and does not have the stability required for a vaccine product, we have investigated the possibility of using DNA as an alternative means of inducing protective immunity. Here, we present evidence that the antigens TSA and LmSTI1 delivered in a plasmid DNA format either as single genes or in a tandem digene construct induce equally solid protection against Leishmania major infection in susceptible BALB/c mice. Immunization of mice with either TSA DNA or LmSTI1 DNA induced specific CD4(+)-T-cell responses of the Th1 phenotype without a requirement for specific adjuvant. CD8 responses, as measured by cytotoxic-T-lymphocyte activity, were generated after immunization with TSA DNA but not LmSTI1 DNA. Interestingly, vaccination of mice with TSA DNA consistently induced protection to a much greater extent than LmSTI1 DNA, thus supporting the notion that CD8 responses might be an important accessory arm of the immune response for acquired resistance against leishmaniasis. Moreover, the protection induced by DNA immunization was specific for infection with Leishmania, i.e., the immunization had no effect on the course of infection of the mice challenged with an unrelated intracellular pathogen such as Mycobacterium tuberculosis. Conversely, immunization of BALB/c mice with a plasmid DNA that is protective against challenge with M. tuberculosis had no effect on the course of infection of these mice with L. major. Together, these results indicate that the protection observed with the leishmanial DNA is mediated by acquired specific immune response rather than by the activation of nonspecific innate immune mechanisms. In addition, a plasmid DNA containing a fusion construct of the two genes was also tested. Similarly to the plasmids encoding individual proteins, the fusion construct induced both specific immune responses to the individual antigens and protection against challenge with L. major. These results confirm previous observations about the possibility of DNA immunization against leishmaniasis and lend support to the idea of using a single polygenic plasmid DNA construct to achieve polyspecific immune responses to several distinct parasite antigens.

Reduction of cytotoxicity of benzalkonium chloride and octenidine by Brilliant Blue G.

PubMed

Bartok, Melinda; Tandon, Rashmi; Alfaro-Espinoza, Gabriela; Ullrich, Matthias S; Gabel, Detlef

2015-01-01

The irritative effects of preservatives found in ophthalmologic solution, or of antiseptics used for skin disinfection is a consistent problem for the patients. The reduction of the toxic effects of these compounds is desired. Brilliant Blue G (BBG) has shown to meet the expected effect in presence of benzalkonium chloride (BAK), a well known preservative in ophthalmic solutions, and octenidine dihydrochloride (Oct), used as antiseptic in skin and wound disinfection. BBG shows a significant protective effect on human corneal epithelial (HCE) cells against BAK and Oct toxicity, increasing the cell survival up to 51 % at the highest BAK or Oct concentration tested, which is 0.01 %, both at 30 min incubation. Although BBG is described as a P2x7 receptor antagonist, other selective P2x7 receptor antagonists, OxATP (adenosine 5'-triphosphate-2',3'-dialdehyde) and DPPH (N'-(3,5-dichloropyridin-4-yl)-3-phenylpropanehydrazide), did not reduce the cytotoxicity of neither BAK nor Oct. Therefore we assume that the protective effect of BBG is not due to its action on the P2x7 receptor. Brilliant Blue R (BBR), a dye similar to BBG, was also tested for protective effect on BAK and Oct toxicity. In presence of BAK no significant protective effect was observed. Instead, with Oct a comparable protective effect was seen with that of BBG. To assure that the bacteriostatic effect is not affected by the combinations of BAK/BBG, Oct/BBG and Oct/BBR, bacterial growth inhibition was analyzed on different Gram-negative and Gram-positive bacteria. All combinations of BAK or Oct with BBG hinder growth of Gram-positive bacteria. The combinations of 0.001 % Oct and BBR above 0.025 % do not hinder the growth of B. subtilis. For Gram-negative bacteria, BBG and BBR reduce, but do not abolish, the antimicrobial effect of BAK nor of Oct. In conclusion, the addition of BBG at bacterial inhibitory concentrations is suggested in the ready-to-use ophthalmic preparations and antiseptic solutions.

Reduction of cytotoxicity of benzalkonium chloride and octenidine by Brilliant Blue G

PubMed Central

Bartok, Melinda; Tandon, Rashmi; Alfaro-Espinoza, Gabriela; Ullrich, Matthias S.; Gabel, Detlef

2015-01-01

The irritative effects of preservatives found in ophthalmologic solution, or of antiseptics used for skin disinfection is a consistent problem for the patients. The reduction of the toxic effects of these compounds is desired. Brilliant Blue G (BBG) has shown to meet the expected effect in presence of benzalkonium chloride (BAK), a well known preservative in ophthalmic solutions, and octenidine dihydrochloride (Oct), used as antiseptic in skin and wound disinfection. BBG shows a significant protective effect on human corneal epithelial (HCE) cells against BAK and Oct toxicity, increasing the cell survival up to 51 % at the highest BAK or Oct concentration tested, which is 0.01 %, both at 30 min incubation. Although BBG is described as a P2x7 receptor antagonist, other selective P2x7 receptor antagonists, OxATP (adenosine 5’-triphosphate-2’,3’-dialdehyde) and DPPH (N’-(3,5-dichloropyridin-4-yl)-3-phenylpropanehydrazide), did not reduce the cytotoxicity of neither BAK nor Oct. Therefore we assume that the protective effect of BBG is not due to its action on the P2x7 receptor. Brilliant Blue R (BBR), a dye similar to BBG, was also tested for protective effect on BAK and Oct toxicity. In presence of BAK no significant protective effect was observed. Instead, with Oct a comparable protective effect was seen with that of BBG. To assure that the bacteriostatic effect is not affected by the combinations of BAK/BBG, Oct/BBG and Oct/BBR, bacterial growth inhibition was analyzed on different Gram-negative and Gram-positive bacteria. All combinations of BAK or Oct with BBG hinder growth of Gram-positive bacteria. The combinations of 0.001 % Oct and BBR above 0.025 % do not hinder the growth of B. subtilis. For Gram-negative bacteria, BBG and BBR reduce, but do not abolish, the antimicrobial effect of BAK nor of Oct. In conclusion, the addition of BBG at bacterial inhibitory concentrations is suggested in the ready-to-use ophthalmic preparations and antiseptic solutions. PMID:26417355

Protecting Mammalian Hair Cells from Aminoglycoside-Toxicity: Assessing Phenoxybenzamine's Potential.

PubMed

Majumder, Paromita; Moore, Paulette A; Richardson, Guy P; Gale, Jonathan E

2017-01-01

Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic, causing the death of sensory hair cells in the inner ear. Strategies aimed at developing or discovering agents that protect against aminoglycoside ototoxicity have focused on inhibiting apoptosis or more recently, on preventing antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds using the larval zebrafish lateral line identified phenoxybenzamine as a potential protectant for aminoglycoside-induced hair cell death. Here we used live imaging of FM1-43 uptake as a proxy for aminoglycoside entry, combined with hair-cell death assays to evaluate whether phenoxybenzamine can protect mammalian cochlear hair cells from the deleterious effects of the aminoglycoside antibiotic neomycin. We show that phenoxybenzamine can block FM1-43 entry into mammalian hair cells in a reversible and dose-dependent manner, but pre-incubation is required for maximal inhibition of entry. We observed differential effects of phenoxybenzamine on FM1-43 uptake in the two different types of cochlear hair cell in mammals, the outer hair cells (OHCs) and inner hair cells (IHCs). The requirement for pre-incubation and reversibility suggests an intracellular rather than an extracellular site of action for phenoxybenzamine. We also tested the efficacy of phenoxybenzamine as an otoprotective agent. In mouse cochlear explants the hair cell death resulting from 24 h exposure to neomycin was steeply dose-dependent, with 50% cell death occurring at ~230 μM for both IHC and OHC. We used 250 μM neomycin in subsequent hair-cell death assays. At 100 μM with 1 h pre-incubation, phenoxybenzamine conferred significant protection to both IHCs and OHCs, however at higher concentrations phenoxybenzamine itself showed clear signs of ototoxicity and an additive toxic effect when combined with neomycin. These data do not support the use of phenoxybenzamine as a therapeutic agent in mammalian inner ear. Our findings do share parallels with the observations from the zebrafish lateral line model but they also highlight the necessity for validation in the mammalian system and the potential for differential effects on sensory hair cells from different species, in different systems and even between cells in the same organ.

[Protective effect of Tanreqing injection on acute hepatic injury induced by CCl4 in rats].

PubMed

Lei, Yang; Zhou, Ai-Min; Guo, Tao; Tan, Ye; Tao, Yan-Yan; Liu, Cheng-Hai

2013-04-01

To observe the protective effect of Tanreqing injection(TRQ) on carbon tetrachloride-induced acute hepatic injury in rats. Rats were randomly divided into the normal group and the model group, and injected subcutaneously with 100% CCl4 5 mL x kg(-1) to establish the single CCl4 infection model, in order to observe the changes in rat liver injury after 3 h and 6 h. Subsequently, the multiple CCl4 infection liver injury model was reproduced by subcutaneously injecting 100% CCl4 (5 mL x kg(-1)), 50% CCl4 olive oil solution (2 mL x kg(-1)) and then 20% CCl4 olive oil solution (2 mL x kg(-1)). At 6 h after the first CCl4 injection, the rats were divided into six groups: the model group, the control group, the diammonium glycyrrhizinate-treated group, and TRQ high, middle and low dose groups. They were injected through caudal veins, while a normal control group was set up. Their weight and liver-body ratio were observed. Hepatic inflammation was observed with HE staining. Assay kits were adopted to detect ALT, AST, T. Bil, D. Bil, CHE, TBA, gamma-GT and Alb. According to the single injection model, serum AST and T. Bil of model rats were obviously increased at 6 h after single subcutaneous injection of CCl4, with disordered lobular structure in liver tissues, notable swollen liver cells and remarkable liver injury. According to the results of the multiple injection pharmacological experiment, compared with the normal group, the model group had higher serum ALT, AST, and gamma-GT activities (P < 0. 05), TBA and T. Bil contents (P < 0.05) and lower CHE activity (P < 0.05). HE staining showed disorganized lobular structure in liver tissues and notable ballooning degeneration in liver cells. Compared with the model group, TRQ high and middle dose groups and the diammonium glycyrrhizinate-treated group showed significant charges in serum liver function and inflammation in liver cells. Specifically, TRQ high and middle dose groups were superior to the diammonium glycyrrhizinate-treated group. Tanreqing injection has significant protective effect on CCl4-induced acute hepatic injury in rats.

Repellent effect of Salvia dorisiana, S. longifolia, and S. sclarea (Lamiaceae) essential oils against the mosquito Aedes albopictus Skuse (Diptera: Culicidae).

PubMed

Conti, Barbara; Benelli, Giovanni; Leonardi, Michele; Afifi, Fatma U; Cervelli, Claudio; Profeti, Raffaele; Pistelli, Luisa; Canale, Angelo

2012-07-01

Aedes albopictus (Diptera: Culicidae) has been one of the fastest spreading insects over the past 20 years. Its medical importance is due to the aggressive daytime human-biting behavior and the ability to vector many viruses, including dengue, LaCrosse, Eastern Equine encephalitis and West Nile viruses. In this research, the essential oils (EOs) extracted from fresh air dried leaves of Salvia dorisiana, S. longifolia, and S. sclarea (Lamiaceae) were evaluated for their repellent activity against A. albopictus by using the human-bait technique. The EOs chemical composition was also investigated, and EOs were divided in three different profiles on the basis of their chemical composition: EO with large amount of monoterpenes from S. sclarea, EO rich in oxygenated sesquiterpenes from S. dorisiana, and S. longifolia EO characterized by similar percentages of monoterpenes and sesquiterpenes. The efficacy protection from S. dorisiana, S. longifolia, and S. sclarea EOs, at dosages ranging from 0.004 to 0.4 μL cm(-2) of skin, was evaluated during 120 min of observation. Results indicated that S. dorisiana, S. longifolia, and S. sclarea EOs had a significant repellent activity (RD(50) =0.00035, 0.00049, and 0.00101 μL cm(-2), respectively), with differences in repellency rates, as a function of oil, dosage, and observation time. S. dorisiana was the most effective oil: at the two higher dosages, it gave almost complete protection (with a protective efficacy of 90.99% and 95.62%, respectively) for 90 min. The best protection time was achieved with S. dorisiana essential oil. It ranged from 9.2 to 92.4 min. Protection times of S. longifolia and S. sclarea oils ranged from 3.2 to 60 min, and from 3.6 to 64.2 min, respectively. Our findings clearly reveal that these EOs have a good repellent activity against A. albopictus, therefore they can be proposed to improve the efficacy of repellent formulations against the Asian tiger mosquito.

Do the Emotional Benefits of Optimism Vary Across Older Adulthood? A Life Span Perspective.

PubMed

Wrosch, Carsten; Jobin, Joelle; Scheier, Michael F

2017-06-01

This study examined whether the emotional benefits of dispositional optimism for managing stressful encounters decrease across older adulthood. Such an effect might emerge because age-related declines in opportunities for overcoming stressors could reduce the effectiveness of optimism. This hypothesis was tested in a 6-year longitudinal study of 171 community-dwelling older adults (age range = 64-90 years). Hierarchical linear models showed that dispositional optimism protected relatively young participants from exhibiting elevations in depressive symptoms over time, but that these benefits became increasingly reduced among their older counterparts. Moreover, the findings showed that an age-related association between optimism and depressive symptoms was observed particularly during periods of enhanced, as compared to reduced, stress. These results suggest that dispositional optimism protects emotional well-being during the early phases of older adulthood, but that its effects are reduced in advanced old age. © 2016 Wiley Periodicals, Inc.

Age/Radiation Parallels in the Effects of 56Fe Particle Irradiation and Protection by Berry Diets

NASA Astrophysics Data System (ADS)

Joseph, James; Bielinski, Donna; Carrihill-Knoll, Kirsty; Rabin, Bernard; Shukitt-Hale, Barbara

Exposing young rats to particles of high-energy and charge (HZE particles) enhances indices of oxidative stress and inflammation and disrupts the functioning of the dopaminergic system and behaviors mediated by this system in a manner similar to that seen in aged animals Previous research has shown that diets supplemented with 2% blueberry or strawberry extracts have the ability to retard and even reverse age-related deficits in behavior and signal transduction in rats, perhaps due to their antioxidant and anti-inflammatory properties. A subsequent study has shown that whole-body irradiation with 1.5 Gy of 1 GeV/n high-energy 56 Fe particles impaired performance in the Morris water maze and measures of dopamine release one month following radiation; these deficits were protected by the antioxidant diets. The strawberry diet offered better protection against spatial deficits in the maze because strawberry-fed animals were better able to retain place information, while the blueberry-supplemented animals showed enhanced learning that was dependent on striatal functioning. Additional experiments in cell models to examine possible mechanisms involved in these beneficial effects have shown that, in addition to the well known free radical scavenging effects of berries, it appears that berry fruit can directly reduce stress signaling and enhance protective signals, suggesting the involvement of multiple mechanisms in the beneficial effects observed. Enhancements of "protective" signals (e.g., extracellular signal regulated kinase, ERK) include those that are involved in neuronal communication, neurogenesis, and learning and memory. Reductions in stress signaling include inhibiting nuclear factor kappa B (NF-κB) and cytokines, among others, induced by oxidative and inflammatory stressors. We have found these changes in both BV2 mouse microglial and hippocampal cells. We believe that the possible addition of colorful fruits such as berry fruits to the diet can possibly increase protection against the deleterious effects of HZE particles in long-term space flights and may provide a "longevity dividend" or economic benefit for mitigating possible accelerated aging effects at the end of the mission.

Activation of the Nrf2/HO-1 Antioxidant Pathway Contributes to the Protective Effects of Lycium Barbarum Polysaccharides in the Rodent Retina after Ischemia-Reperfusion-Induced Damage

PubMed Central

Chang, Raymond Chuen-Chung; So, Kwok-Fai; Brecha, Nicholas C.; Pu, Mingliang

2014-01-01

Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are protective to retina after ischemia-reperfusion (I/R). The antioxidant response element (ARE)–mediated antioxidant pathway plays an important role in maintaining the redox status of the retina. Heme oxygenase-1 (HO-1), combined with potent AREs in its promoter, is a highly effective therapeutic target for the protection against neurodegenerative diseases, including I/R-induced retinal damage. The aim of our present study was to investigate whether the protective effect of LBP after I/R damage was mediated via activation of the Nrf2/HO-1-antioxidant pathway in the retina. Retinal I/R was induced by an increase in intraocular pressure to 130 mm Hg for 60 minutes. Prior to the induction of ischemia, rats were orally treated with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. For specific experiments, zinc protoporphyrin (ZnPP, 20 mg/kg), an HO-1 inhibitor, was intraperitoneally administered at 24 h prior to ischemia. The protective effects of LBP were evaluated by quantifying ganglion cell and amacrine cell survival, and by measuring cell apoptosis in the retinal layers. In addition, HO-1 expression was examined using Western blotting and immunofluorescence analyses. Cytosolic and nuclear Nrf2 was measured using immunofluorescent staining. LBP treatment significantly increased Nrf2 nuclear accumulation and HO-1 expression in the retina after I/R injury. Increased apoptosis and a decrease in the number of viable cells were observed in the ganglion cell layer (GCL) and inner nuclear layer (INL) in the I/R retina, which were reversed by LBP treatment. The HO-1 inhibitor, ZnPP, diminished the LBP treatment-induced protective effects in the retina after I/R. Taken together, these results suggested that LBP partially exerted its beneficial neuroprotective effects via the activation of Nrf2 and an increase in HO-1 protein expression. PMID:24400114

Mechanism for Prevention of Alcohol-Induced Liver Injury by Dietary Methyl Donors

PubMed Central

Powell, Christine L.; Bradford, Blair U.; Craig, Christopher Patrick; Tsuchiya, Masato; Uehara, Takeki; O’Connell, Thomas M.; Pogribny, Igor P.; Melnyk, Stepan; Koop, Dennis R.; Bleyle, Lisa; Threadgill, David W.; Rusyn, Ivan

2010-01-01

Alcohol-induced liver injury (ALI) has been associated with, among other molecular changes, abnormal hepatic methionine metabolism, resulting in decreased levels of S-adenosylmethionine (SAM). Dietary methyl donor supplements such as SAM and betaine mitigate ALI in animal models; however, the mechanisms of protection remain elusive. It has been suggested that methyl donors may act via attenuation of alcohol-induced oxidative stress. We hypothesized that the protective action of methyl donors is mediated by an effect on the oxidative metabolism of alcohol in the liver. Male C57BL/6J mice were administered a control high-fat diet or diet enriched in methyl donors with or without alcohol for 4 weeks using the enteral alcohol feeding model. As expected, attenuation of ALI and an increase in reduced glutathione:oxidized glutathione ratio were achieved with methyl donor supplementation. Interestingly, methyl donors led to a 35% increase in blood alcohol elimination rate, and while there was no effect on alcohol metabolism in the stomach, a profound effect on liver alcohol metabolism was observed. The catalase-dependent pathway of alcohol metabolism was induced, yet the increase in CYP2E1 activity by alcohol was blunted, which may be mitigating production of oxidants. Additional factors contributing to the protective effects of methyl donors in ALI were increased activity of low- and high-Km aldehyde dehydrogenases leading to lower hepatic acetaldehyde, maintenance of the efficient mitochondrial energy metabolism, and promotion of peroxisomal β-oxidation. Profound changes in alcohol metabolism represent additional important mechanism of the protective effect of methyl donors in ALI. PMID:20118189

Protection from childhood asthma and allergy in Alpine farm environments-the GABRIEL Advanced Studies.

PubMed

Illi, Sabina; Depner, Martin; Genuneit, Jon; Horak, Elisabeth; Loss, Georg; Strunz-Lehner, Christine; Büchele, Gisela; Boznanski, Andrzej; Danielewicz, Hanna; Cullinan, Paul; Heederik, Dick; Braun-Fahrländer, Charlotte; von Mutius, Erika

2012-06-01

Studies on the association of farm environments with asthma and atopy have repeatedly observed a protective effect of farming. However, no single specific farm-related exposure explaining this protective farm effect has consistently been identified. We sought to determine distinct farm exposures that account for the protective effect of farming on asthma and atopy. In rural regions of Austria, Germany, and Switzerland, 79,888 school-aged children answered a recruiting questionnaire (phase I). In phase II a stratified random subsample of 8,419 children answered a detailed questionnaire on farming environment. Blood samples and specific IgE levels were available for 7,682 of these children. A broad asthma definition was used, comprising symptoms, diagnosis, or treatment ever. Children living on a farm were at significantly reduced risk of asthma (adjusted odds ratio [aOR], 0.68; 95% CI, 0.59-0.78; P< .001), hay fever (aOR, 0.43; 95% CI, 0.36-0.52; P< .001), atopic dermatitis (aOR, 0.80; 95% CI, 0.69-0.93; P= .004), and atopic sensitization (aOR, 0.54; 95% CI, 0.48-0.61; P< .001) compared with nonfarm children. Whereas this overall farm effect could be explained by specific exposures to cows, straw, and farm milk for asthma and exposure to fodder storage rooms and manure for atopic dermatitis, the farm effect on hay fever and atopic sensitization could not be completely explained by the questionnaire items themselves or their diversity. A specific type of farm typical for traditional farming (ie, with cows and cultivation) was protective against asthma, hay fever, and atopy. However, whereas the farm effect on asthma could be explained by specific farm characteristics, there is a link still missing for hay fever and atopy. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Effects of Personal Protective Equipment Use and Good Workplace Hygiene on Symptoms of Neurotoxicity in Solvent-Exposed Vehicle Spray Painters.

PubMed

Keer, Sam; McLean, Dave; Glass, Bill; Douwes, Jeroen

2018-03-12

To assess the association between the use of personal protective equipment (PPE) and good workplace hygiene and symptoms of neurotoxicity in solvent-exposed vehicle spray painters. Exposure control measures including PPE-use and workplace hygiene practices and symptoms of neurotoxicity were assessed in 267 vehicle repair spray painters. Symptoms were assessed using an adapted version of the EUROQUEST Questionnaire. Frequent respirator and glove use was inversely and significantly associated with symptoms of neurotoxicity in a dose-dependent manner (P < 0.05 for trend) with the strongest protective effect found for consistent glove use (odds ratios [OR] 0.1-0.2, P < 0.01, for reporting ≥10 and ≥5 symptoms). A clear dose-response trend was also observed when combining frequency of respirator and glove use (P < 0.05 for reporting ≥5 and ≥10 symptoms), with an overall reduction in risk of 90% (OR, 0.1, P < 0.01) for those who consistently used both types of PPE. Protective effects were most pronounced for the symptom domains of psychosomatic (P < 0.05 for trend, for combined PPE use), mood (P < 0.05), and memory and concentration symptoms combined (P < 0.05), with reductions in risk of >80%. Poor hygiene workplace practices, such as solvent exposure to multiple body parts (OR 3.4, P = 0.11 for reporting ≥10 symptoms), were associated with an increased risk of symptoms. When using a general workplace hygiene score derived from a combination of PPE-use and (good) workplace practice factors an inverse and significant dose-response trend was observed for reporting ≥5 (P < 0.01) and ≥10 symptoms (P < 0.01). This study has shown that PPE-use and good workplace hygiene are associated with a strongly reduced risk of symptoms of neurotoxicity in solvent-exposed vehicle spray painters.

Is the chronic Tier-1 effect assessment approach for insecticides protective for aquatic ecosystems?

PubMed

Brock, Theo Cm; Bhatta, Ranjana; van Wijngaarden, René Pa; Rico, Andreu

2016-10-01

We investigated the appropriateness of several methods, including those recommended in the Aquatic Guidance Document of the European Food Safety Authority (EFSA), for the derivation of chronic Tier-1 regulatory acceptable concentrations (RACs) for insecticides and aquatic organisms. The insecticides represented different chemical classes (organophosphates, pyrethroids, benzoylureas, insect growth regulators, biopesticides, carbamates, neonicotinoids, and miscellaneous). Chronic Tier-1 RACs derived using toxicity data for the standard species Daphnia magna, Chironomus spp., and/or Americamysis bahia, were compared with Tier-3 RACs derived from micro- and mesocosm studies on basis of the ecological threshold option (ETO-RACs). ETO-RACs could be derived for 31 insecticides applied to micro- and mesocosms in single or multiple applications, yielding a total number of 36 cases for comparison. The chronic Tier-1 RACs calculated according to the EFSA approach resulted in a sufficient protection level, except for 1 neonicotinoid (slightly underprotective) and for several pyrethroids if toxicity data for A. bahia were not included. This latter observation can be explained by 1) the fact that A. bahia is the most sensitive standard test species for pyrethroids, 2) the hydrophobic properties of pyrethroids, and 3) the fact that long-term effects observed in (epi) benthic arthropods may be better explained by exposure via the sediment than via overlying water. Besides including toxicity data for A. bahia, the protection level for pyrethroids can be improved by selecting both D. magna and Chironomus spp. as standard test species for chronic Tier-1 derivation. Although protective in the majority of cases, the conservativeness of the recommended chronic Tier-1 RACs appears to be less than an order of magnitude for a relatively large proportion of insecticides when compared with their Tier-3 ETO-RACs. This may leave limited options for refinement of the chronic effect assessment using laboratory toxicity data for additional species. Integr Environ Assess Manag 2016;12:747-758. © 2015 SETAC. © 2015 SETAC.

Intranasal bacille Calmette–Guérin (BCG) vaccine dosage needs balancing between protection and lung pathology

PubMed Central

TREE, J A; WILLIAMS, A; CLARK, S; HALL, G; MARSH, P D; IVANYI, J

2004-01-01

Intranasal vaccination may offer practical benefits and better protection against respiratory infections, including tuberculosis. In this paper, we investigated the persistence of the Mycobacterium bovis-strain bacille Calmette–Guérin (BCG) Pasteur, lung granuloma formation and protection against pathogenic tuberculous challenge in mice. A pronounced BCG dose-dependent granulomatous infiltration of the lungs was observed following intranasal, but not after subcutaneous, vaccination. Corresponding doses of BCG, over a 100-fold range, imparted similar protection against H37Rv challenge when comparing the intranasal and subcutaneous vaccination routes. Interestingly, a BCG dose-dependent reduction of the H37Rv challenge infection was observed in the lungs, but not in the spleens, following both intranasal and subcutaneous vaccination. In the light of the observed concurrence between the extent of granuloma formation and the level of protection of the lungs, we conclude that intranasal vaccination leading to best protective efficacy needs to be balanced with an acceptable safety margin avoiding undue pathology in the lungs. PMID:15544615

Inhibition of lipid peroxidation by extracts/subfractions of Chickrassy ( Chukrasia tabularis A. Juss.)

NASA Astrophysics Data System (ADS)

Kaur, Rajbir; Thind, Tarunpreet Singh; Singh, Bikram; Arora, Saroj

2009-01-01

Polyphenols and polyphenol-rich fractions of plants have been reported to have protective effects against lipid peroxidation, most probably by serving as scavengers of free radicals and/or by chelating metal ions. In the present study, the effect of different extracts/subfractions of Chickrassy ( Chukrasia tabularis) on peroxyl radical mediated damage to the polyunsaturated fatty acids was investigated. Liver homogenate was used as experimental material. The production of malondialdehyde served as a marker of lipid peroxidation and oxidative stress. It was observed that polyphenol-rich fractions, particularly the ethyl acetate fractions of bark and leaves, showed the highest protective activity of 83.02% and 88.62% inhibition, respectively. This study will help in knowing the scientific validation of this plant, for its use in ayurvedic formulations.

Performance evaluation of two protective treatments on salt-laden limestones and marble after natural and artificial weathering.

PubMed

Salvadori, Barbara; Pinna, Daniela; Porcinai, Simone

2014-02-01

Salt crystallization is a major damage factor in stone weathering, and the application of inappropriate protective products may amplify its effects. This research focuses on the evaluation of two protective products' performance (organic polydimethylsiloxane and inorganic ammonium oxalate (NH4)2(COO)2·H2O) in the case of a salt load from behind. Experimental laboratory simulations based on salt crystallization cycles and natural weathering in an urban area were carried out. The effects were monitored over time, applying different methods: weight loss evaluation, colorimetric and water absorption by capillarity measurements, stereomicroscope observations, FTIR and SEM-EDS analyses. The results showed minor impact exerted on the short term on stones, particularly those treated with the water repellent, by atmospheric agents compared to salt crystallization. Lithotypes with low salt load (Gioia marble) underwent minor changes than the heavily salt-laden limestones (Lecce and Ançã stones), which were dramatically damaged when treated with polysiloxane. The results suggest that the ammonium oxalate treatment should be preferred to polysiloxane in the presence of soluble salts, even after desalination procedures which might not completely remove them. In addition, the neo-formed calcium oxalate seemed to effectively protect the stone, improving its resistance against salt crystallization without occluding the pores and limiting the superficial erosion caused by atmospheric agents.

Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

PubMed

Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

2015-02-01

Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.

PubMed

Alvarez, Pedro; Green, Paul G; Levine, Jon D

2018-06-01

Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. Muscle mechanical nociceptive threshold was assessed before and after water avoidance (WA) stress, when they were adults. In contrast to male rats, NH produced only a modest protection against WA stress-induced muscle hyperalgesia in female rats. Gonadectomy completely abolished NH-induced resilience in male rats but produced only a small increase in this protective effect in female rats. The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia. NH induces androgen-dependent resilience to stress-induced muscle pain. Therefore, androgens may contribute to sex differences observed in chronic musculoskeletal pain and its enhancement by stress. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.