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Sample records for kavalactone derivative protects

  1. Fatal kavalactone intoxication by suicidal intravenous injection.

    PubMed

    Ketola, Raimo A; Viinamäki, Jenni; Rasanen, Ilpo; Pelander, Anna; Goebeler, Sirkka

    2015-04-01

    Kavalactones are a group of compounds found in kava, a beverage or extract prepared from the rhizome of the kava plant (Piper methysticum). Traditionally kava extracts have been used for their anxiolytic and sedative properties. Sales of kava extracts were severely restricted or prohibited in European countries in 2002 following several cases of serious hepatotoxicity. Here we report a case where high concentrations of kavalactones and ethanol were detected in post mortem femoral blood. An injection needle with a 10-mL syringe containing 7.5 mL of slightly yellowish liquid was found next to the victim, and there were numerous needle prints on both lower arms following the venous tracks. No evidence of other cause of death was found in the medico-legal investigation. The case was therefore classified as suicide using an injection of kavalactones intravenously together with alcohol poisoning. PMID:25684328

  2. Kavalactone metabolism in rat liver microsomes.

    PubMed

    Fu, Shuang; Rowe, Anthony; Ramzan, Iqbal

    2012-07-01

    The specific CYP enzymes involved in kavalactone (KLT) metabolism and their kinetics have not been fully examined. This study used rat liver microsomes (RLM) to determine kavain (KA), methysticin (MTS) and desmethoxyyangonin (DMY) enzyme kinetic parameters, to elucidate the major CYP450 isoforms involved in KLT metabolism and to examine gender differences in KLT metabolism. Formation of the major KLT metabolites was first-order, consistent with classic enzyme kinetics. In both male and female RLM, clotrimazole (CLO) was the most potent inhibitor of KA and MTS metabolism. This suggests CYP3A1/3A23 (females) and CYP3A2 (males) are the main isoenzymes involved in the metabolism of these KLTs in rats, while the roles of CYP1A2, -2 C6, -2 C9, -2E1 and -3A4 are limited. Desmethoxyyangonin metabolism was equally inhibited by cimetidine (CIM) and CLO in females, and CIM and nortriptyline in males. This implies that DMY metabolism involves CYP2C6 and CYP2C11 in males, and CPY2C12 in females. CYP3A1/3A23 may also be involved in females. PMID:22807255

  3. Pacific island 'Awa (Kava) extracts, but not isolated kavalactones, promote proinflammatory responses in model mast cells.

    PubMed

    Shimoda, Lori M N; Park, Christy; Stokes, Alexander J; Gomes, Henry Halenani; Turner, Helen

    2012-12-01

    Kava ('Awa) is a traditional water-based beverage in Pacific island communities, prepared from the ground root and stems of Piper methysticum. Kava use is associated with an ichthyotic dermatitis and delayed type hypersensitivity reactions. In the current study we collated preparative methodologies from cultural practitioners and recreational kava users in various Pacific communities. We standardized culturally informed aqueous extraction methods and prepared extracts that were subjected to basic physicochemical analysis. Mast cells exposed to these extracts displayed robust intracellular free calcium responses, and concomitant release of proinflammatory mediators. In contrast, mast cells were refractory to single or combinatorial stimulation with kavalactones, including methysticin, dihydromethysticin and kavain. Moreover, we reproduced a traditional modification of the kava preparation methodology, pre-mixing with the mucilage of Hibiscus tiliaceus, and observed its potentiating effect on the activity of aqueous extracts in mast cells. Taken together, these data indicate that water extractable active ingredients may play a role in the physiological and pathophysiological effects of kava, and suggests that mast cell activation may be a mechanistic component of kava-related skin inflammations. PMID:22473598

  4. Determination of six kavalactones in dietary supplements and selected functional foods containing Piper methysticum by isocratic liquid chromatography with internal standard.

    PubMed

    Hu, Lihong; Jhoo, Jin-Woo; Ang, Catharina Y W; Dinovi, Michael; Mattia, Antonia

    2005-01-01

    Kava (Piper methysticum) dietary products have been sold worldwide for treatment of nervous anxiety, tension, and restlessness. Recent reports showed potential association of kava usage and liver injuries. This study was conducted to develop simple and reliable methodologies for the extraction and determination of 6 major kavalactones: (+)-methysticin, (+)-dihydromethysticin, (+)-kavain, (+)-dihydrokavain, yangonin, and desmethoxyyangonin. Ultrasonic extraction techniques and isocratic reversed-phase liquid chromatography (LC) were optimized for different types of samples, including capsules containing kava root extract or root powder, raw root material, tea bags, and snack bar. A suitable internal standard, 5,7-dihydroxyflavone, was used for LC calibration. Kavalactones were completely separated in 30 min using a Luna C18-2 column at 60 degrees C with an isocratic mobile phase consisting of 2-propanol-acetonitrile-water-acetic acid (16 + 16 + 68 + 0.1, v/v/v/v). Within-laboratory, intraday, and interday method variation (% relative standard deviation) for most samples extracted by methanol or methanol-water mixture were <5%. Lower levels of kavalactone contents and higher variations were observed for tea bags from water extraction or infusion as compared to methanol extraction. Labeling information of tea bags based on methanol extraction could be misleading to consumers. Analytical recoveries of snack bar fortified at 10 and 20 microg/g were >84% with RSD values <8%. Methods developed in this study offer a simple and reproducible means for analysis of kavalactones in various matrixes of dietary products. PMID:15759721

  5. Radiation Protection Using Carbon Nanotube Derivatives

    NASA Technical Reports Server (NTRS)

    Conyers, Jodie L., Jr.; Moore, Valerie C.; Casscells, S. Ward

    2010-01-01

    BHA and BHT are well-known food preservatives that are excellent radical scavengers. These compounds, attached to single-walled carbon nanotubes (SWNTs), could serve as excellent radical traps. The amino-BHT groups can be associated with SWNTs that have carbolyxic acid groups via acid-base association or via covalent association. The material can be used as a means of radiation protection or cellular stress mitigation via a sequence of quenching radical species using nano-engineered scaffolds of SWNTs and their derivatives. It works by reducing the number of free radicals within or nearby a cell, tissue, organ, or living organism. This reduces the risk of damage to DNA and other cellular components that can lead to chronic and/or acute pathologies, including (but not limited to) cancer, cardiovascular disease, immuno-suppression, and disorders of the central nervous system. These derivatives can show an unusually high scavenging ability, which could prove efficacious in protecting living systems from radical-induced decay. This technique could be used to protect healthy cells in a living biological system from the effects of radiation therapy. It could also be used as a prophylactic or antidote for radiation exposure due to accidental, terrorist, or wartime use of radiation- containing weapons; high-altitude or space travel (where radiation exposure is generally higher than desired); or in any scenario where exposure to radiation is expected or anticipated. This invention s ultimate use will be dependent on the utility in an overall biological system where many levels of toxicity have to be evaluated. This can only be assessed at a later stage. In vitro toxicity will first be assessed, followed by in vivo non-mammalian screening in zebra fish for toxicity and therapeutic efficacy.

  6. Pacific island ‘Awa (Kava) extracts, but not isolated kavalactones, promote pro-inflammatory responses in model mast cells

    PubMed Central

    Shimoda, Lori M.N.; Park, Christy; Stokes, Alexander J.; Gomes, Henry Halenani; Turner, Helen

    2013-01-01

    Kava (‘Awa) is a traditional water-based beverage in Pacific island communities, prepared from the ground root and stems of Piper methysticum. Kava use is associated with an ichthyotic dermatitis and delayed type hypersensitivity reactions. In the current study we collated preparative methodologies from cultural practitioners and recreational kava users in various Pacific communities. We standardized culturally-informed aqueous extraction methods and prepared extracts that were subjected to basic physicochemical analysis. Mast cells exposed to these extracts displayed robust intracellular free calcium responses, and concomitant release of pro-inflammatory mediators. In contrast, mast cells were refractory to single or combinatorial stimulation with kavalactones including methysticin, dihydromethysticin and kavain. Moreover, we reproduced a traditional modification of the kava preparation methodology, pre-mixing with the mucilage of Hibiscus taliaceus, and observed its potentiating effect on the activity of aqueous extracts in mast cells. Taken together, these data indicate that water extractable active ingredients may play a role in the physiological and pathophysiological effects of kava, and suggests that mast cell activation may be a mechanistic component of kava-related skin inflammations. PMID:22473598

  7. Halogenated coumarin derivatives as novel seed protectants.

    PubMed

    Brooker, N; Windorski, J; Bluml, E

    2008-01-01

    Development of new and improved antifungal compounds that are target-specific is backed by a strong Federal, public and commercial mandate. Many plant-derived chemicals have proven fungicidal properties, including the coumarins (1,2-Benzopyrone) found in a variety of plants such as clover, sweet woodruff and grasses. Preliminary research has shown the coumarins to be a highly active group of molecules with a wide range of antimicrobial activity against both fungi and bacteria. It is believed that these cyclic compounds behave as natural pesticidal defence molecules for plants and they represent a starting point for the exploration of new derivative compounds possessing a range of improved antifungal activity. Within this study, derivatives of coumarin that were modified with halogenated side groups were screened for their antifungal activity against a range of soil-borne plant pathogenic fungi. Fungi included in this in vitro screen included Macrophomina phaseolina (charcoal rot), Phytophthora spp. (damping off and seedling rot), Rhizoctonia spp. (damping off and root rot) and Pythium spp. (seedling blight), four phylogenetically diverse and economically important plant pathogens. Studies indicate that these halogenated coumarin derivatives work very effectively in vitro to inhibit fungal growth and some coumarin derivatives have higher antifungal activity and stability as compared to the original coumarin compound alone. The highly active coumarin derivatives are brominated, iodinated and chlorinated compounds and results suggest that besides being highly active, very small amounts can be used to achieve LD100 rates. In addition to the in vitro fungal inhibition assays, results of polymer seed coating compatibility and phytotoxicity testing using these compounds as seed treatments will also be reported. These results support additional research in this area of natural pesticide development. PMID:19226745

  8. A plant kavalactone desmethoxyyangonin prevents inflammation and fulminant hepatitis in mice.

    PubMed

    Chou, Tsui-Wei; Feng, Jia-Hua; Huang, Chi-Chang; Cheng, Ya-Wen; Chien, Shih-Chang; Wang, Sheng-Yang; Shyur, Lie-Fen

    2013-01-01

    Alpinia pricei Hayata is a Formosan plant which has been popularly used as nutraceutical or folk medicine for inflammation and various disorders. An active compound of the plant rhizomes, desmethoxyyangonin (DMY), was identified in this study for its novel effect against endotoxin lipopolysaccharide (LPS)-stimulated inflammation in murine macrophages and LPS/D-galactosamine (LPS/D-GalN)-induced fulminant hepatitis in mice. DMY was observed to significantly inhibit proliferation and activation of T cells ex vivo and the activity of several pro-inflammatory mediators in vitro. DMY also protected LPS/D-GalN-induced acute hepatic damages in mice through inhibiting aminotransferases activities and infiltrations of inflammatory macrophages, neutrophils and pathogenic T cells into the liver tissues. In addition, pretreatment with DMY significantly improved the survival rate of LPS/D-GalN-treated mice to 90% (9/10), compared to LPS/D-GalN-treated group (40%, 4/10). UPLC/MS platform-based comparative metabolomics approach was used to explore the serum metabolic profile in fulminant hepatic failure (FHF) mice with or without the DMY pretreatment. The results showed that LPS/D-GalN-induced hepatic damage is likely through perturbing amino acid metabolism, which leads to decreased pyruvate formation via catalysis of aminotransferases, and DMY treatment can prevent to a certain degree of these alterations in metabolic network in mouse caused by LPS/D-GalN. Mechanistic investigation demonstrated that DMY protects LPS or LPS/D-GalN-induced damages in cell or liver tissues mainly through de-regulating IKK/NFκB and Jak2/STAT3 signaling pathways. This report provides evidence-based knowledge to support the rationale for the use of A. pricei root extract in anti-inflammation and also its new function as hepatoprotetive agent against fulminant hepatitis. PMID:24143247

  9. Radiation Protection Using Single-Wall Carbon Nanotube Derivatives

    NASA Technical Reports Server (NTRS)

    Tour, James M.; Lu, Meng; Lucente-Schultz, Rebecca; Leonard, Ashley; Doyle, Condell Dewayne; Kosynkin, Dimitry V.; Price, Brandi Katherine

    2011-01-01

    This invention is a means of radiation protection, or cellular oxidative stress mitigation, via a sequence of quenching radical species using nano-engineered scaffolds, specifically single-wall carbon nanotubes (SWNTs) and their derivatives. The material can be used as a means of radiation protection by reducing the number of free radicals within, or nearby, organelles, cells, tissue, organs, or living organisms, thereby reducing the risk of damage to DNA and other cellular components (i.e., RNA, mitochondria, membranes, etc.) that can lead to chronic and/or acute pathologies, including but not limited to cancer, cardiovascular disease, immuno-suppression, and disorders of the central nervous system. In addition, this innovation could be used as a prophylactic or antidote for accidental radiation exposure, during high-altitude or space travel where exposure to radiation is anticipated, or to protect from exposure from deliberate terrorist or wartime use of radiation- containing weapons.

  10. Protective effects of some creatine derivatives in brain tissue anoxia.

    PubMed

    Perasso, Luisa; Lunardi, Gian Luigi; Risso, Federica; Pohvozcheva, Anna V; Leko, Maria V; Gandolfo, Carlo; Florio, Tullio; Cupello, Aroldo; Burov, Sergey V; Balestrino, Maurizio

    2008-05-01

    Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their protective effect in mouse hippocampal slices. We found that N-amidino-piperidine is harmful to brain tissue, and that phosphocreatine is ineffective. Creatine, creatine-Mg-complex (acetate) and phosphocreatine-Mg-complex (acetate) increased the latency to population spike disappearance during anoxia. Creatine and creatine-Mg-complex (acetate) also increased the latency of anoxic depolarization, while the delay induced by phosphocreatine-Mg-complex (acetate) was of borderline significance (P = 0.056). Phosphocreatine-Mg-complex (acetate) significantly reduced neuronal hyperexcitability during anoxia, an effect that no other compound (including creatine itself) showed. For all parameters except reduced hyperexcitability the effects statistically correlated with tissue levels of creatine or phosphocreatine. Summing up, exogenous phosphocreatine and N-amidino piperidine are not useful for brain protection, while chelates of both creatine and phosphocreatine do replicate some of the known protective effects of creatine. In addition, phosphocreatine-Mg-complex (acetate) also reduced neuronal hyperexcitability during anoxia. PMID:17940889

  11. Biologically-Derived Photonic Materials for Thermal Protection Systems

    NASA Technical Reports Server (NTRS)

    Johnson, Sylvia M.; Squire, Thomas H.; Lawson, John W.; Gusman, Michael; Lau, K.-H.; Sanjurjo, Angel

    2014-01-01

    Space vehicles entering a planetary atmosphere at high velocity can be subject to substantial radiative heating from the shock layer in addition to the convective heating caused by the flow of hot gas past the vehicle surface. The radiative component can be very high but of a short duration. Approaches to combat this effect include investigation of various materials to reflect the radiation. Photonic materials can be used to reflect radiation. The wavelengths reflected depend on the length scale of the ordered microstructure. Fabricating photonic structures, such as layers, can be time consuming and expensive. We have used a biologically-derived material as the template for forming a high temperature photonic material that could be incorporated into a heatshield thermal protection material.

  12. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    PubMed Central

    Wilson, S D; Horne, D W

    1983-01-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu gave rise to 5-formyl-H4PteGlu and 10-formyl-PteGlu. 5-Formyl-H4-PteGlu gave rise to a small amount of 10-formyl-PteGlu. 5-Methyl-H4PteGlu and PteGlu appeared stable to these conditions. These interconversions were not seen when solutions of these folate derivatives were kept at 0 degrees C in 1% ascorbate. These observations indicate that elevated temperatures are necessary for the interconversions of folates in ascorbate solutions. Assays of ascorbic acid solutions indicated the presence of formaldehyde (approximately equal to 6 mM). This was confirmed by the identification of 3,5-diacetyl-1,4-dihydrolutidine by UV, visible, and fluorescence spectroscopy and by thin-layer chromatography of chloroform extracts of the reaction mixture of ascorbic acid solutions, acetylacetone, and ammonium acetate. These results indicate that solutions of sodium ascorbate used at elevated temperatures are not suitable for extracting tissue for the subsequent assay of the individual folic acid derivatives. PMID:6415653

  13. Pericytes Derived from Adipose-Derived Stem Cells Protect against Retinal Vasculopathy

    PubMed Central

    Mendel, Thomas A.; Clabough, Erin B. D.; Kao, David S.; Demidova-Rice, Tatiana N.; Durham, Jennifer T.; Zotter, Brendan C.; Seaman, Scott A.; Cronk, Stephen M.; Rakoczy, Elizabeth P.; Katz, Adam J.; Herman, Ira M.; Peirce, Shayn M.; Yates, Paul A.

    2013-01-01

    Background Retinal vasculopathies, including diabetic retinopathy (DR), threaten the vision of over 100 million people. Retinal pericytes are critical for microvascular control, supporting retinal endothelial cells via direct contact and paracrine mechanisms. With pericyte death or loss, endothelial dysfunction ensues, resulting in hypoxic insult, pathologic angiogenesis, and ultimately blindness. Adipose-derived stem cells (ASCs) differentiate into pericytes, suggesting they may be useful as a protective and regenerative cellular therapy for retinal vascular disease. In this study, we examine the ability of ASCs to differentiate into pericytes that can stabilize retinal vessels in multiple pre-clinical models of retinal vasculopathy. Methodology/Principal Findings We found that ASCs express pericyte-specific markers in vitro. When injected intravitreally into the murine eye subjected to oxygen-induced retinopathy (OIR), ASCs were capable of migrating to and integrating with the retinal vasculature. Integrated ASCs maintained marker expression and pericyte-like morphology in vivo for at least 2 months. ASCs injected after OIR vessel destabilization and ablation enhanced vessel regrowth (16% reduction in avascular area). ASCs injected intravitreally before OIR vessel destabilization prevented retinal capillary dropout (53% reduction). Treatment of ASCs with transforming growth factor beta (TGF-β1) enhanced hASC pericyte function, in a manner similar to native retinal pericytes, with increased marker expression of smooth muscle actin, cellular contractility, endothelial stabilization, and microvascular protection in OIR. Finally, injected ASCs prevented capillary loss in the diabetic retinopathic Akimba mouse (79% reduction 2 months after injection). Conclusions/Significance ASC-derived pericytes can integrate with retinal vasculature, adopting both pericyte morphology and marker expression, and provide functional vascular protection in multiple murine models of

  14. Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

    PubMed Central

    Hauke, Sylvia

    2014-01-01

    Summary Cross metathesis of a lactate derived allylic alcohol and acrolein is the entry point to a de novo synthesis of 4-benzoate protected L-amicetose and a cinerulose derivative protected at C5 and C1. PMID:24991253

  15. PROCEDURES FOR DERIVING EQUILIBRIUM PARTITIONING SEDIMENT BENCHMARKS (ESBS) FOR THE PROTECTION OF BENTHIC ORGANISMS: DIELDRIN

    EPA Science Inventory

    This equilibrium partitioning sediment benchmark (ESB) document describes procedures to derive concentrations of the insecticide dieldrin in sediment which are protective of the presence of benthic organisms. The equilibrium partitioning (EqP) approach was chosen because it acco...

  16. PROCEDURES FOR DERIVING EQUILIBRIUM PARTITIONING BENCHMARKS (ESBS) FOR THE PROTECTION OF BENTHIC ORGANISM: PAH MIXTURES

    EPA Science Inventory

    This equilibrium partitioning sediment benchmark (ESB) document describes procedures to derive concentrations of PAH mixtures in sediment which are protective of the presence of benthic organisms. The equilibrium partitioning (EqP) approach was chosen because it accounts for t...

  17. Corrosion protection on copper by imidazole and its derivatives

    SciTech Connect

    Gasparac, R.; Stupnisek-Lisac, E.

    1999-11-01

    The efficiency of imidazole and its derivatives (4-methylimidazole, 4-methyl-5-hydroxymethylmidazone, 1 phenyl-4-methylimidazone, 1-[p-tolyl]-4-methylimidazone) for corrosion inhibition of copper in 0.5 M hydrochloric acid (HCl) was investigated. Corrosion inhibition was studied using impedance spectroscopy and potentiodynamic methods. Polarization resistances calculated from the alternating current (AC) impedance measurements were in good agreement with those obtained from direct current (DC) polarization measurements. Copper samples also were analyzed by scanning electron microscopy (SEM) and x-ray microanalysis. These studies showed that 1-(p-tolyl)-4 methylimidazone had the best inhibitory efficiency.

  18. Garlic-Derived Organic Polysulfides and Myocardial Protection.

    PubMed

    Bradley, Jessica M; Organ, Chelsea L; Lefer, David J

    2016-02-01

    For centuries, garlic has been shown to exert substantial medicinal effects and is considered to be one of the best disease-preventative foods. Diet is important in the maintenance of health and prevention of many diseases including cardiovascular disease (CVD). Preclinical and clinical evidence has shown that garlic reduces risks associated with CVD by lowering cholesterol, inhibiting platelet aggregation, and lowering blood pressure. In recent years, emerging evidence has shown that hydrogen sulfide (H2S) has cardioprotective and cytoprotective properties. The active metabolite in garlic, allicin, is readily degraded into organic diallyl polysulfides that are potent H2S donors in the presence of thiols. Preclinical studies have shown that enhancement of endogenous H2S has an impact on vascular reactivity. In CVD models, the administration of H2S prevents myocardial injury and dysfunction. It is hypothesized that these beneficial effects of garlic may be mediated by H2S-dependent mechanisms. This review evaluates the current knowledge concerning the cardioprotective effects of garlic-derived diallyl polysulfides. PMID:26764335

  19. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization

    PubMed Central

    Lv, Xue-man; Liu, Yan; Wu, Fei; Yuan, Yi; Luo, Min

    2016-01-01

    The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery. PMID:27212930

  20. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization.

    PubMed

    Lv, Xue-Man; Liu, Yan; Wu, Fei; Yuan, Yi; Luo, Min

    2016-04-01

    The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 10(6) human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery. PMID:27212930

  1. Fluoroform-Derived CuCF3 for Trifluoromethylation of Terminal and TMS-Protected Alkynes.

    PubMed

    He, Lisi; Tsui, Gavin Chit

    2016-06-17

    An efficient trifluoromethylation reaction of alkynes using a fluoroform-derived CuCF3 reagent is described. The CF3 source is the inexpensive industrial waste fluoroform (CF3H). The air-stable CuCF3 reagent can be prepared in large quantities and is convenient to use. Synthetically useful trifluoromethylated alkynes containing a wide range of functional groups were successfully synthesized under mild conditions. Both terminal and TMS-protected alkynes gave the products in one step. The beneficial effect of a diamine ligand tetramethylethylenediamine (TMEDA) with the fluoroform-derived CuCF3 reagent was also demonstrated. PMID:27258390

  2. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline

    PubMed Central

    Schwarz, Flavio; Springer, Stevan A.; Altheide, Tasha K.; Varki, Nissi M.; Gagneux, Pascal; Varki, Ajit

    2016-01-01

    The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer’s dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer’s disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin. PMID:26621708

  3. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline.

    PubMed

    Schwarz, Flavio; Springer, Stevan A; Altheide, Tasha K; Varki, Nissi M; Gagneux, Pascal; Varki, Ajit

    2016-01-01

    The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer's dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer's disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin. PMID:26621708

  4. Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach

    SciTech Connect

    MacNaughton, W.K.; Wallace, J.L. ); Cirino, G. )

    1989-01-01

    The role that nitric oxide, an endothelium-derived relaxing factor, may play in the regulation of gastric mucosal defense was investigated by assessing the potential protective actions of this factor against the damage caused by ethanol in an ex vivo chamber preparation of the rat stomach. Topical application of glyceryl trinitrate and sodium nitroprusside, which have been shown to release nitric oxide, markedly reduced the area of 70% ethanol-induced hemorrhagic damage. Topical application of a 0.01% solution of authentic nitric oxide also significantly reduced the severity of mucosal damage. Pretreatment with indomethacin precluded the involvement of endogenous prostaglandins in the protective effects of these agents. The protective effects of NO were transient, since a delay of 5 minutes between NO administration and ethanal administration resulted in a complete loss of the protective activity. The protection against ethanol afforded by 10 ug/ml nitroprusside could be completely reversed by intravenous infusion of either 1% methylene blue or 1 mM hemoglobin, both of which inhibit vasodilation induced by nitric oxide. Intravenous infusion of 1% methylene blue significantly increased the susceptibility of the mucosa to damage induced by topical 20% ethanol.

  5. Fluorinated amphiphilic amino acid derivatives as antioxidant carriers: a new class of protective agents.

    PubMed

    Ortial, Stéphanie; Durand, Grégory; Poeggeler, Burkhard; Polidori, Ange; Pappolla, Miguel A; Böker, Jutta; Hardeland, Rüdiger; Pucci, Bernard

    2006-05-01

    The use of classical antioxidants is limited by their low bioavailabilities, and therefore, high doses are usually required to display significant protective activity. In a recent article (J. Med. Chem. 2003, 46, 5230) we showed that the ability of the alpha-phenyl-N-tert-butylnitrone (PBN) to restore the viability of ATPase-deficient human skin fibroblasts was greatly enhanced by grafting it on a fluorinated amphiphilic carrier. With the aim of extending this concept to other antioxidants, we present here the design, the synthesis, and the physicochemical measurements of a new series of fluorinated amphiphilic antioxidant derivatives. The hydroxyl radical scavenging activity and the radical reducing potency of these newly designed compounds were respectively demonstrated in an ABTS competition and an ABTS(*+) reduction assay. We also showed that the protective effects of amphiphilic antioxidants derived from PBN, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) or lipoic acid (5-[1,2]-dithiolan-3-ylpentanoic acid) in primary cortical mixed cell cultures exposed to oxidotoxins are greatly improved compared to their parent compounds in the following rank-order: (1) PBN, (2) Trolox, and (3) lipoic acid. In contrast, the protective activity of indole-3-propionic acid was slightly decreased by grafting it on the amphiphilic carrier. Similar observations were made in in vivo experiments using aquatic invertebrate microorganisms, called rotifers, which were exposed to lethal concentrations of nonselective (H(2)O(2)) and mitochondria-selective (doxorubicin) oxidotoxins. The conclusion of these studies is that fluorinated amphiphilic PBN, Trolox, and lipoic acid derivatives exhibit very potent protective activities in in vitro and in vivo experiments. The findings demonstrated herein therefore strongly suggest that the amphiphilic character enhances the bioavailability of the antioxidants and allows for a selective targeting of mitochondria. PMID:16640342

  6. Pigment Epithelium Derived Factor Peptide Protects Murine Hepatocytes from Carbon Tetrachloride-Induced Injury

    PubMed Central

    Shih, Shou-Chuan; Ho, Tsung-Chuan; Chen, Show-Li; Tsao, Yeou-Ping

    2016-01-01

    Fibrogenesis is induced by repeated injury to the liver and reactive regeneration and leads eventually to liver cirrhosis. Pigment epithelium derived factor (PEDF) has been shown to prevent liver fibrosis induced by carbon tetrachloride (CCl4). A 44 amino acid domain of PEDF (44-mer) was found to have a protective effect against various insults to several cell types. In this study, we investigated the capability of synthetic 44-mer to protect against liver injury in mice and in primary cultured hepatocytes. Acute liver injury, induced by CCl4, was evident from histological changes, such as cell necrosis, inflammation and apoptosis, and a concomitant reduction of glutathione (GSH) and GSH redox enzyme activities in the liver. Intraperitoneal injection of the 44-mer into CCl4-treated mice abolished the induction of AST and ALT and markedly reduced histological signs of liver injury. The 44-mer treatment can reduce hepatic oxidative stress as evident from lower levels of lipid hydroperoxide, and higher levels of GSH. CCl4 caused a reduction of Bcl-xL, PEDF and PPARγ, which was markedly restored by the 44-mer treatment. Consequently, the 44-mer suppressed liver fibrosis induced by repeated CCl4 injury. Furthermore, our observations in primary culture of rat hepatocytes showed that PEDF and the 44-mer protected primary rat hepatocytes against apoptosis induced by serum deprivation and TGF-β1. PEDF/44-mer induced cell protective STAT3 phosphorylation. Pharmacological STAT3 inhibition prevented the antiapoptotic action of PEDF/44-mer. Among several PEDF receptor candidates that may be responsible for hepatocyte protection, we demonstrated that PNPLA2 was essential for PEDF/44-mer-mediated STAT3 phosphorylation and antiapoptotic activity by using siRNA to selectively knockdown PNPLA2. In conclusion, the PEDF 44-mer protects hepatocytes from single and repeated CCl4 injury. This protective effect may stem from strengthening the counter oxidative stress capacity and

  7. Quercetin protects against high glucose-induced damage in bone marrow-derived endothelial progenitor cells.

    PubMed

    Zhao, Li-Rong; Du, Yu-Jun; Chen, Lei; Liu, Zhi-Gang; Pan, Yue-Hai; Liu, Jian-Feng; Liu, Bin

    2014-10-01

    Endothelial progenitor cells (EPCs), a group of bone marrow-derived pro-angiogenic cells, contribute to vascular repair after damage. EPC dysfunction exists in diabetes and results in poor wound healing in diabetic patients with trauma or surgery. The aim of the present study was to determine the effect of quercetin, a natural flavonoid on high glucose‑induced damage in EPCs. Treatment with high glucose (40 mM) decreased cell viability and migration, and increased oxidant stress, as was evidenced by the elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase in bone marrow-derived EPCs. Moreover, high glucose reduced the levels of endothelial nitric oxide synthase (eNOS) phosphorylation, nitric oxide (NO) production and intracellular cyclic guanosine monophosphate (cGMP). Quercetin supplement protected against high glucose‑induced impairment in cell viability, migration, oxidant stress, eNOS phosphorylation, NO production and cGMP levels. Quercetin also increased Sirt1 expression in EPCs. Inhibition of Sirt1 by a chemical antagonist sirtinol abolished the protective effect of quercetin on eNOS phosphorylation, NO production and cGMP levels following high glucose stress. To the best of our knowledge, the results provide the first evidence that quercetin protects against high glucose‑induced damage by inducing Sirt1-dependent eNOS upregulation in EPCs, and suggest that quercetin is a promising therapeutic agent for diabetic patients undergoing surgery or other invasive procedures. PMID:25197782

  8. Ginger-derived nanoparticles protect against alcohol-induced liver damage.

    PubMed

    Zhuang, Xiaoying; Deng, Zhong-Bin; Mu, Jingyao; Zhang, Lifeng; Yan, Jun; Miller, Donald; Feng, Wenke; McClain, Craig J; Zhang, Huang-Ge

    2015-01-01

    Daily exposure of humans to nanoparticles from edible plants is inevitable, but significant advances are required to determine whether edible plant nanoparticles are beneficial to our health. Additionally, strategies are needed to elucidate the molecular mechanisms underlying any beneficial effects. Here, as a proof of concept, we used a mouse model to show that orally given nanoparticles isolated from ginger extracts using a sucrose gradient centrifugation procedure resulted in protecting mice against alcohol-induced liver damage. The ginger-derived nanoparticle (GDN)-mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the expression of a group of liver detoxifying/antioxidant genes and inhibited the production of reactive oxygen species, which partially contributes to the liver protection. Using lipid knock-out and knock-in strategies, we further identified that shogaol in the GDN plays a role in the induction of Nrf2 in a TLR4/TRIF-dependent manner. Given the critical role of Nrf2 in modulating numerous cellular processes, including hepatocyte homeostasis, drug metabolism, antioxidant defenses, and cell-cycle progression of liver, this finding not only opens up a new avenue for investigating GDN as a means to protect against the development of liver-related diseases such as alcohol-induced liver damage but sheds light on studying the cellular and molecular mechanisms underlying interspecies communication in the liver via edible plant-derived nanoparticles. PMID:26610593

  9. Ginger-derived nanoparticles protect against alcohol-induced liver damage

    PubMed Central

    Zhuang, Xiaoying; Deng, Zhong-Bin; Mu, Jingyao; Zhang, Lifeng; Yan, Jun; Miller, Donald; Feng, Wenke; McClain, Craig J.; Zhang, Huang-Ge

    2015-01-01

    Daily exposure of humans to nanoparticles from edible plants is inevitable, but significant advances are required to determine whether edible plant nanoparticles are beneficial to our health. Additionally, strategies are needed to elucidate the molecular mechanisms underlying any beneficial effects. Here, as a proof of concept, we used a mouse model to show that orally given nanoparticles isolated from ginger extracts using a sucrose gradient centrifugation procedure resulted in protecting mice against alcohol-induced liver damage. The ginger-derived nanoparticle (GDN)–mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the expression of a group of liver detoxifying/antioxidant genes and inhibited the production of reactive oxygen species, which partially contributes to the liver protection. Using lipid knock-out and knock-in strategies, we further identified that shogaol in the GDN plays a role in the induction of Nrf2 in a TLR4/TRIF-dependent manner. Given the critical role of Nrf2 in modulating numerous cellular processes, including hepatocyte homeostasis, drug metabolism, antioxidant defenses, and cell-cycle progression of liver, this finding not only opens up a new avenue for investigating GDN as a means to protect against the development of liver-related diseases such as alcohol-induced liver damage but sheds light on studying the cellular and molecular mechanisms underlying interspecies communication in the liver via edible plant–derived nanoparticles. PMID:26610593

  10. Exogenous Nitric Oxide Protects Human Embryonic Stem Cell-Derived Cardiomyocytes against Ischemia/Reperfusion Injury

    PubMed Central

    Pálóczi, János; Varga, Zoltán V.; Szebényi, Kornélia; Sarkadi, Balázs; Madonna, Rosalinda; De Caterina, Raffaele; Csont, Tamás; Eschenhagen, Thomas; Ferdinandy, Péter; Görbe, Anikó

    2016-01-01

    Background and Aims. Human embryonic stem cell- (hESC-) derived cardiomyocytes are one of the useful screening platforms of potential cardiocytoprotective molecules. However, little is known about the behavior of these cardiomyocytes in simulated ischemia/reperfusion conditions. In this study, we have tested the cytoprotective effect of an NO donor and the brain type natriuretic peptide (BNP) in a screening platform based first on differentiated embryonic bodies (EBs, 6 + 4 days) and then on more differentiated cardiomyocytes (6 + 24 days), both derived from hESCs. Methods. Both types of hESC-derived cells were exposed to 150 min simulated ischemia, followed by 120 min reperfusion. Cell viability was assessed by propidium iodide staining. The following treatments were applied during simulated ischemia in differentiated EBs: the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) (10−7, 10−6, and 10−5 M), BNP (10−9, 10−8, and 10−7 M), and the nonspecific NO synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10−5 M). Results. SNAP (10−6, 10−5 M) significantly attenuated cell death in differentiated EBs. However, simulated ischemia/reperfusion-induced cell death was not affected by BNP or by L-NNA. In separate experiments, SNAP (10−6 M) also protected hESC-derived cardiomyocytes. Conclusions. We conclude that SNAP, but not BNP, protects differentiated EBs or cardiomyocytes derived from hESCs against simulated ischemia/reperfusion injury. The present screening platform is a useful tool for discovery of cardiocytoprotective molecules and their cellular mechanisms. PMID:27403231

  11. Protective effects of macrophage-derived interferon against encephalomyocarditis virus-induced diabetes mellitus in mice.

    PubMed

    Hirasawa, K; Ogiso, Y; Takeda, M; Lee, M J; Itagaki, S; Doi, K

    1995-12-01

    The involvement of macrophages in protection against diabetes mellitus in mice of BALB/c (susceptible) and C57BL (resistant) strains infected with the B (non-diabetogenic) or D (highly diabetogenic) variant of encephalomyocarditis (EMC) virus was examined. Pretreatment with the B variant of EMC virus (EMC-B), avirulent interferon (IFN) inducer, or Corynebacterium parvum inhibited diabetes in BALB/c mice infected with the D variant of EMC virus (EMC-D). Treatment of C57BL mice with carrageenan to compromise macrophage function rendered C57BL mice susceptible to EMC-D-induced diabetes. In macrophage culture for BALB/c mice, EMC-B induced IFN at an earlier stage than did EMC-D. The C57BL mouse-derived macrophages produced more IFN than did BALB/c mouse-derived macrophages after stimulation with EMC-D. Moreover, C. parvum increased IFN production in macrophage cultures from BALB/c mice, whereas carrageenan inhibited that in macrophage cultures from C57BL mice. These results suggest that IFN derived from macrophages may have an important role in protecting mice against EMC virus infection. PMID:8746525

  12. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    SciTech Connect

    Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  13. PROCEDURES FOR THE DERIVATION OF EQUILIBRIUM PARTITIONING SEDIMENT BENCHMARKS (ESBS) FOR THE PROTECTION OF BENTHIC ORGANISMS: PAH MIXTURES

    EPA Science Inventory

    This equilibrium partitioning sediment benchmark (ESB) document describes procedures to derive concentrations of PAH mixtures in sediment which are protective of the presence of benthic organisms. The equilibrium partitioning (EqP) approach was chosen because it accounts for the ...

  14. Genipin Derivatives Protect RGC-5 from Sodium Nitroprusside-Induced Nitrosative Stress

    PubMed Central

    Wang, Rikang; Zhao, Jiaqiang; Zhang, Lei; Peng, Lizhi; Zhang, Xinyi; Zheng, Wenhua; Chen, Heru

    2016-01-01

    CHR20 and CHR21 are a pair of stable diastereoisomers derived from genipin. These stereoisomers are activators of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS). In the rat retinal ganglion (RGC-5) cell model these compounds are non-toxic. Treatment of RGC-5 with 750 μM of sodium nitroprusside (SNP) produces nitrosative stress. Both genipin derivatives, however, protect these cells against SNP-induced apoptic cell death, although CHR21 is significantly more potent than CHR20 in this regard. With Western blotting we showed that the observed neuroprotection is primarily due to the activation of protein kinase B (Akt)/eNOS and extracellular signal-regulated kinase (ERK1/2) signaling pathways. Therefore, LY294002 (a phosphatidylinositol 3-kinase (PI3K) inhibitor) or PD98059 (a MAPK-activating enzyme inhibitor) abrogated the protective effects of CHR20 and CHR21. Altogether, our results show that in our experimental setup neuroprotection by the diasteromeric pair is mediated through the PI3K/Akt/eNOS and ERK1/2 signaling pathways. Further studies are needed to establish the potential of these compounds to prevent ntric oxide (NO)-induced toxicity commonly seen in many neurodegenerative diseases. PMID:26797604

  15. A Food-Derived Flavonoid Luteolin Protects against Angiotensin II-Induced Cardiac Remodeling

    PubMed Central

    Nakao, Tomoko; Yamaguchi, Toshihiro; Sumida, Tomokazu; Ikeda, Yuichi; Kumagai, Hidetoshi; Motozawa, Yoshihiro; Takahashi, Tsukasa; Imaizumi, Atsushi; Hashimoto, Tadashi; Nagai, Ryozo; Komuro, Issei

    2015-01-01

    Oxidative stress has been implicated in cardiac remodeling (cardiac fibrosis and hypertrophy), which impairs cardiac function and metabolism; therefore, it is anticipated antioxidative compounds will have protective properties against cardiac remodeling. Luteolin (3’,4’,5,7-tetrahydroxyflavone), a widely distributed flavonoid found in many herbal extracts including celery, green pepper, perilla leaves and seeds, and chamomile, is a known to be a potent antioxidant and was previously demonstrated to exert an antifibrotic effect in the lungs and the liver. In this study, we clearly demonstrate that oral pretreatment with the higher-luteolin diet (0.035% (wt/wt)) protected against cardiac fibrosis and hypertrophy as well as a hyperoxidative state in Ang II-infused rats. In cardiac tissue, increased gene expression levels of TGFβ1, CTGF, Nox2, Nox4, ANP, and BNP induced by Ang II were restored by oral pretreatment of this high-luteolin diet. In cultured rat cardiac fibroblasts, H2O2-induced TGFβ1 expression and the phosphorylation of JNK were suppressed by luteolin pretreatment. In conclusion, food-derived luteolin has protective actions against Ang II-induced cardiac remodeling, which could be mediated through attenuation of oxidative stress. PMID:26327560

  16. A Food-Derived Flavonoid Luteolin Protects against Angiotensin II-Induced Cardiac Remodeling.

    PubMed

    Nakayama, Atsuko; Morita, Hiroyuki; Nakao, Tomoko; Yamaguchi, Toshihiro; Sumida, Tomokazu; Ikeda, Yuichi; Kumagai, Hidetoshi; Motozawa, Yoshihiro; Takahashi, Tsukasa; Imaizumi, Atsushi; Hashimoto, Tadashi; Nagai, Ryozo; Komuro, Issei

    2015-01-01

    Oxidative stress has been implicated in cardiac remodeling (cardiac fibrosis and hypertrophy), which impairs cardiac function and metabolism; therefore, it is anticipated antioxidative compounds will have protective properties against cardiac remodeling. Luteolin (3',4',5,7-tetrahydroxyflavone), a widely distributed flavonoid found in many herbal extracts including celery, green pepper, perilla leaves and seeds, and chamomile, is a known to be a potent antioxidant and was previously demonstrated to exert an antifibrotic effect in the lungs and the liver. In this study, we clearly demonstrate that oral pretreatment with the higher-luteolin diet (0.035% (wt/wt)) protected against cardiac fibrosis and hypertrophy as well as a hyperoxidative state in Ang II-infused rats. In cardiac tissue, increased gene expression levels of TGFβ1, CTGF, Nox2, Nox4, ANP, and BNP induced by Ang II were restored by oral pretreatment of this high-luteolin diet. In cultured rat cardiac fibroblasts, H2O2-induced TGFβ1 expression and the phosphorylation of JNK were suppressed by luteolin pretreatment. In conclusion, food-derived luteolin has protective actions against Ang II-induced cardiac remodeling, which could be mediated through attenuation of oxidative stress. PMID:26327560

  17. Cytoprotective dibenzoylmethane derivatives protect cells from oxidative stress-induced necrotic cell death.

    PubMed

    Hegedűs, Csaba; Lakatos, Petra; Kiss-Szikszai, Attila; Patonay, Tamás; Gergely, Szabolcs; Gregus, Andrea; Bai, Péter; Haskó, György; Szabó, Éva; Virág, László

    2013-06-01

    Screening of a small in-house library of 1863 compounds identified 29 compounds that protected Jurkat cells from hydrogen peroxide-induced cytotoxicity. From the cytoprotective compounds eleven proved to possess antioxidant activity (ABTS radical scavenger effect) and two were found to inhibit poly(ADP-ribosyl)ation (PARylation), a cytotoxic pathway operating in severely injured cells. Four cytoprotective dibenzoylmethane (DBM) derivatives were investigated in more detail as they did not scavenge hydrogen peroxide nor did they inhibit PARylation. These compounds protected cells from necrotic cell death while caspase activation, a parameter of apoptotic cell death was not affected. Hydrogen peroxide activated extracellular signal regulated kinase (ERK1/2) and p38 MAP kinases but not c-Jun N-terminal kinase (JNK). The cytoprotective DBMs suppressed the activation of Erk1/2 but not that of p38. Cytoprotection was confirmed in another cell type (A549 lung epithelial cells), indicating that the cytoprotective effect is not cell type specific. In conclusion we identified DBM analogs as a novel class of cytoprotective compounds inhibiting ERK1/2 kinase and protecting from necrotic cell death by a mechanism independent of poly(ADP-ribose) polymerase inhibition. PMID:23523665

  18. Natural Bizbenzoquinoline Derivatives Protect Zebrafish Lateral Line Sensory Hair Cells from Aminoglycoside Toxicity

    PubMed Central

    Kruger, Matthew; Boney, Robert; Ordoobadi, Alexander J.; Sommers, Thomas F.; Trapani, Josef G.; Coffin, Allison B.

    2016-01-01

    Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20–30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment. PMID:27065807

  19. Pantothenic acid and its derivatives protect Ehrlich ascites tumor cells against lipid peroxidation.

    PubMed

    Slyshenkov, V S; Rakowska, M; Moiseenok, A G; Wojtczak, L

    1995-12-01

    Preincubation of Ehrlich ascites tumor cells at 22 or 32 degrees C, but not at 0 degree C, with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine reduced lipid peroxidation (measured by production of thiobarbituric acid-reactive compounds) induced by the Fenton reaction (Fe2+ + H2O2) and partly protected the plasma membrane against the leakiness to cytoplasmic proteins produced by the same reagent. Pantothenic acid and its derivatives did not inhibit (Fe2+ + H2O2)-induced peroxidation of phospholipid multilamellar vesicles, thus indicating that their effect on the cells was not due to the scavenging mechanism. Homopantothenic acid and its 4'-phosphate ester (which are not precursors of CoA) neither protected Ehrlich ascites tumor cells against lipid peroxidation nor prevented plasma membrane leakiness under the same conditions. Incubation of the cells with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine significantly increased the amount of cellular CoA and potentiated incorporation of added palmitate into phospholipids and cholesterol esters. It is concluded that pantothenic acid and its related compounds protect the plasma membrane of Ehrlich ascites tumor cells against the damage by oxygen free radicals due to increasing cellular level of CoA. The latter compound may act by diminishing propagation of lipid peroxidation and promoting repair mechanisms, mainly the synthesis of phospholipids. PMID:8582649

  20. Natural Bizbenzoquinoline Derivatives Protect Zebrafish Lateral Line Sensory Hair Cells from Aminoglycoside Toxicity.

    PubMed

    Kruger, Matthew; Boney, Robert; Ordoobadi, Alexander J; Sommers, Thomas F; Trapani, Josef G; Coffin, Allison B

    2016-01-01

    Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20-30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment. PMID:27065807

  1. Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

    PubMed Central

    Coppola, Mariateresa; van den Eeden, Susan J. F.; Wilson, Louis; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.

    2015-01-01

    Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive, and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study investigated an SLP derived from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed by “dormant” M. tuberculosis and well recognized by T cells from latently M. tuberculosis-infected individuals. In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon-positive/tumor necrosis factor-positive (IFN-γ+/TNF+) and IFN-γ+ CD4+ T cells and Rv1733c-specific antibodies and led to a significant reduction in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was observed both in a pre- and in a post-M. tuberculosis challenge setting. Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy of BCG, demonstrating the potential of M. tuberculosis latency antigens to improve BCG efficacy. These data suggest a promising role for M. tuberculosis latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic and in a postinfection setting. PMID:26202436

  2. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain.

    PubMed

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation. PMID:26745377

  3. Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation

    PubMed Central

    Chu, Ling-Yun; Wang, Yi-Fu; Cheng, Huei-Hsuan; Kuo, Cheng-Chin; Wu, Kenneth K.

    2016-01-01

    The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5-MTP) as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier function. Conditioned medium of human umbilical vein endothelial cells (HUVECs) prevented endothelial hyperpermeability and VE-cadherin downregulation induced by VEGF, LPS and cytokines. We analyzed the metabolomic profile of HUVEC conditioned medium and detected 5-MTP but not melatonin, serotonin or their catabolites, which was confirmed by enzyme-linked immunosorbent assay. Addition of synthetic pure 5-MTP preserved VE-cadherin and maintained barrier function despite challenge with pro-inflammatory mediators. Tryptophan hydroxylase-1, an enzyme required for 5-MTP biosynthesis, was downregulated in HUVECs by pro-inflammatory mediators and it was accompanied by reduction of 5-MTP. 5-MTP protected VE-cadherin and prevented endothelial hyperpermeability by blocking p38 MAPK activation. A chemical inhibitor of p38 MAPK, SB202190, exhibited a similar protective effect as 5-MTP. To determine whether 5-MTP prevents vascular hyperpermeability in vivo, we evaluated the effect of 5-MTP administration on LPS-induced murine microvascular permeability with Evans blue. 5-MTP significantly prevented Evans blue dye leakage. Our findings indicate that 5-MTP is a new class of endothelium-derived molecules which protects endothelial barrier function by blocking p38 MAPK. PMID:27002329

  4. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain

    PubMed Central

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation. PMID:26745377

  5. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury.

    PubMed

    Masuzawa, Akihiro; Black, Kendra M; Pacak, Christina A; Ericsson, Maria; Barnett, Reanne J; Drumm, Ciara; Seth, Pankaj; Bloch, Donald B; Levitsky, Sidney; Cowan, Douglas B; McCully, James D

    2013-04-01

    Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 10(6)/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P < 0.05) creatine kinase MB, cardiac troponin-I, and apoptosis significantly in the RI zone. Infarct size following 4 wk of recovery was decreased significantly in RI-mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P < 0.05). Serial echocardiograms showed that RI-mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2-8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury. PMID:23355340

  6. Protective effect of pomegranate-derived products on UVB-mediated damage in human reconstituted skin.

    PubMed

    Afaq, Farrukh; Zaid, Mohammad Abu; Khan, Naghma; Dreher, Mark; Mukhtar, Hasan

    2009-06-01

    Solar ultraviolet (UV) radiation, particularly its UVB (290-320 nm) component, is the primary cause of many adverse biological effects including photoageing and skin cancer. UVB radiation causes DNA damage, protein oxidation and induces matrix metalloproteinases (MMPs). Photochemoprevention via the use of botanical antioxidants in affording protection to human skin against UVB damage is receiving increasing attention. Pomegranate, from the tree Punica granatum, contains anthocyanins and hydrolysable tannins and possesses strong antioxidant and anti-tumor-promoting properties. In this study, we determined the effect of pomegranate-derived products--POMx juice, POMx extract and pomegranate oil (POMo)--against UVB-mediated damage using reconstituted human skin (EpiDerm(TM) FT-200). EpiDerm was treated with POMx juice (1-2 microl/0.1 ml/well), POMx extract (5-10 microg/0.1 ml/well) and POMo (1-2 microl/0.1 ml/well) for 1 h prior to UVB (60 mJ/cm(2)) irradiation and was harvested 12 h post-UVB to assess protein oxidation, markers of DNA damage and photoageing by Western blot analysis and immunohistochemistry. Pretreatment of Epiderm with pomegranate-derived products resulted in inhibition of UVB-induced (i) cyclobutane pyrimidine dimers (CPD), (ii) 8-dihydro-2'-deoxyguanosine (8-OHdG), (iii) protein oxidation and (iv) proliferating cell nuclear antigen (PCNA) protein expression. We also found that pretreatment of Epiderm with pomegranate-derived products resulted in inhibition of UVB-induced (i) collagenase (MMP-1), (ii) gelatinase (MMP-2, MMP-9), (iii) stromelysin (MMP-3), (iv) marilysin (MMP-7), (v) elastase (MMP-12) and (vi) tropoelastin. Gelatin zymography revealed that pomegranate-derived products inhibited UVB-induced MMP-2 and MMP-9 activities. Pomegranate-derived products also caused a decrease in UVB-induced protein expression of c-Fos and phosphorylation of c-Jun. Collectively, these results suggest that all three pomegranate-derived products may be useful

  7. Protective role of small pigment epithelium-derived factor (PEDF) peptide in diabetic renal injury.

    PubMed

    Awad, Alaa S; Gao, Ting; Gvritishvili, Anzor; You, Hanning; Liu, Yanling; Cooper, Timothy K; Reeves, W Brian; Tombran-Tink, Joyce

    2013-09-15

    Pigment epithelium-derived factor (PEDF) is a multifunctional protein with antiangiogenic, antioxidative, and anti-inflammatory properties. PEDF is involved in the pathogenesis of diabetic retinopathy, but its direct role in the kidneys remains unclear. We hypothesize that a PEDF fragment (P78-PEDF) confers kidney protection in diabetic nephropathy (DN). The localization of the full-length PEDF protein were determined in DBA mice following multiple low doses of streptozotocin. Using immunohistochemistry, PEDF was localized in the kidney vasculature, interstitial space, glomeruli, tubules, and renal medulla. Kidney PEDF protein and mRNA expression were significantly reduced in diabetic mice. Continuous infusion of P78-PEDF for 6 wk resulted in protection from diabetic neuropathy as indicated by reduced albuminuria and blood urea nitrogen, increased nephrin expression, decreased kidney macrophage recruitment and inflammatory cytokines, and reduced histological changes compared with vehicle-treated diabetic mice. In vitro, P78-PEDF blocked the increase in podocyte permeability to albumin and disruption of the actin cytoskeleton induced by puromycin aminonucleoside treatment. These findings highlight the importance of P78-PEDF peptide as a potential therapeutic modality in early phase diabetic renal injury. PMID:23884140

  8. Bioefficacy of some plant derivatives that protect grain against the pulse beetle, Callosobruchus maculatus

    PubMed Central

    Rahman, A.; Talukder, F. A.

    2006-01-01

    Experiments were conducted to study the bioefficacies of different plant/weed derivatives that affect the development of the pulse beetle, Callosobruchus maculates F. (Coleoptera: Bruchidae) fed on black gram, Vigna mungo, seeds. Plant extracts, powder, ash and oil from nishinda (Vitex negundo L.), eucalyptus (Eucalyptus globules Labill.), bankalmi (Ipomoea sepiaria K.), neem (Azadirachta indica L.), safflower (Carthamus tinctorius L.), sesame (Sesamum indicum L.) and bablah (Acacia arabica L.) were evaluated for their oviposition inhibition, surface protectant, residual toxicity and direct toxicity effects on C. maculates. The results showed that plant oils were effective in checking insect infestation. The least number of F1 adults emerged from black gram seeds treated with neem oil. The nishinda oil extract was the most toxic of three extracts tested (nishinda, eucalyptus and bankalmi). Bablah ash was the most effective compared to the powdered leaves of nishinda, eucalyptus and bankalmi. The powdered leaves and extracts of nishinda, eucalyptus and bankalmi, at a 3% mixture, provided good protection for black gram seeds by reducing insect oviposition, F1 adult emergence, and grain infestation rates. The oil treatment did not show adverse effects on germination capability of seeds, even after three months of treatment. PMID:19537990

  9. Protective effects of five allium derived organosulfur compounds against mutation and oxidation.

    PubMed

    Chiu, Chih-Kwang; Chen, Tai-Yuan; Lin, Jou-Hsing; Wang, Chen-Ya; Wang, Bor-Sen

    2016-04-15

    In this study, we examined the ability of five allium-derived organosulfur compounds to protect cells against mutation and oxidation. The compounds tested were 1-propylmercaptan (PM), dimethyl disulfide (DMDS), diallyl disulfide (DADS), propyl disulfide (PDS), and 2,5-dimethylthiophene (DMT). Our results showed that when used at concentrations of 100-400 μmol/l, the five compounds inhibited the mutagenicity of 4-nitroquinoline-N-oxide, a direct mutagen, and benzo[a]pyrene, an indirect mutagen, toward Salmonella typhimurium TA 98 and TA 100. Furthermore, at these concentrations, all five of the compounds protected HepG2 cells against tert-butyl hydroperoxide-induced oxidative cytotoxicity. The compounds likely enhanced cell viability by suppressing the formation of reactive oxygen species and the depletion of glutathione depletion in cells. DMT and PM inhibited mutation and oxidation to a greater extent than DMDS, DADS, and PDS. These results demonstrate for the first time that DMT and PM can contribute to the antimutagenic and the antioxidative property of Allium vegetables. PMID:26617023

  10. Bioefficacy of some plant derivatives that protect grain against the pulse beetle, Callosobruchus maculatus.

    PubMed

    Rahman, A; Talukder, F A

    2006-01-01

    Experiments were conducted to study the bioefficacies of different plant/weed derivatives that affect the development of the pulse beetle, Callosobruchus maculates F. (Coleoptera: Bruchidae) fed on black gram, Vigna mungo, seeds. Plant extracts, powder, ash and oil from nishinda (Vitex negundo L.), eucalyptus (Eucalyptus globules Labill.), bankalmi (Ipomoea sepiaria K.), neem (Azadirachta indica L.), safflower (Carthamus tinctorius L.), sesame (Sesamum indicum L.) and bablah (Acacia arabica L.) were evaluated for their oviposition inhibition, surface protectant, residual toxicity and direct toxicity effects on C. maculates. The results showed that plant oils were effective in checking insect infestation. The least number of F(1) adults emerged from black gram seeds treated with neem oil. The nishinda oil extract was the most toxic of three extracts tested (nishinda, eucalyptus and bankalmi). Bablah ash was the most effective compared to the powdered leaves of nishinda, eucalyptus and bankalmi. The powdered leaves and extracts of nishinda, eucalyptus and bankalmi, at a 3% mixture, provided good protection for black gram seeds by reducing insect oviposition, F(1) adult emergence, and grain infestation rates. The oil treatment did not show adverse effects on germination capability of seeds, even after three months of treatment. PMID:19537990

  11. Melatonin Protects Human Adipose-Derived Stem Cells from Oxidative Stress and Cell Death

    PubMed Central

    Han, Xiaolian; Sivakumaran, Priyadharshini; Lim, Shiang Y.; Morrison, Wayne A.

    2016-01-01

    Background Adipose-derived stem cells (ASCs) have applications in regenerative medicine based on their therapeutic potential to repair and regenerate diseased and damaged tissue. They are commonly subject to oxidative stress during harvest and transplantation, which has detrimental effects on their subsequent viability. By functioning as an antioxidant against free radicals, melatonin may exert cytoprotective effects on ASCs. Methods We cultured human ASCs in the presence of varying dosages of hydrogen peroxide and/or melatonin for a period of 3 hours. Cell viability and apoptosis were determined with propidium iodide and Hoechst 33342 staining under fluorescence microscopy. Results Hydrogen peroxide (1–2.5 mM) treatment resulted in an incremental increase in cell death. 2 mM hydrogen peroxide was thereafter selected as the dose for co-treatment with melatonin. Melatonin alone had no adverse effects on ASCs. Co-treatment of ASCs with melatonin in the presence of hydrogen peroxide protected ASCs from cell death in a dose-dependent manner, and afforded maximal protection at 100 µM (n=4, one-way analysis of variance P<0.001). Melatonin co-treated ASCs displayed significantly fewer apoptotic cells, as demonstrated by condensed and fragmented nuclei under fluorescence microscopy. Conclusions Melatonin possesses cytoprotective properties against oxidative stress in human ASCs and might be a useful adjunct in fat grafting and cell-assisted lipotransfer. PMID:27218020

  12. Protection against canine parvovirus type 2 infection in puppies by colostrum-derived antibodies.

    PubMed

    Mila, Hanna; Grellet, Aurélien; Desario, Costantina; Feugier, Alexandre; Decaro, Nicola; Buonavoglia, Canio; Chastant-Maillard, Sylvie

    2014-01-01

    During the first weeks of life puppies remain protected against canine parvovirus type 2 (CPV2) infection thanks to maternally derived antibodies (MDA) absorbed with colostrum after birth. The objective of the present study was to present the variability in CPV2-specific passive immune transfer and its consequences in puppies naturally exposed to the parvovirus. Seventy-nine puppies from one breeding kennel were included in the study at birth and followed until 56 d of age. Once per week the MDA titre for CPV2 specific antibodies was determined in blood. Viral excretion was also evaluated on a rectal swab by CPV2 PCR assay and puppies were weighed to determine growth rate. At 2 d of age, thirty-four out of seventy-nine puppies (43 %) had MDA ≤1:160 (designed group A) and forty-five puppies (57 %) had greater MDA titres (designed group B). The level of absorbed maternal antibodies was shown to be associated with breed size and growth rate during the first 48 h of life. The MDA level declined with age in all cases; however, the proportion of puppies with the antibody level considered as protective against CPV2 infection was significantly higher in group B compared with A from day 2 until 42. Among all puppies surviving until 56 d of age, sixty-seven out of seventy (95·7 %) underwent CPV2 infection. However, puppies from group A excreted CPV2 significantly earlier than puppies from group B. The present study demonstrates the link between passive immune transfer, in terms of level of specific MDA absorbed, and length of the protection period against parvovirus infection in weaning puppies. PMID:26101622

  13. Protective role of macrophage-derived ceruloplasmin in inflammatory bowel disease

    PubMed Central

    Bakhautdin, Bakytzhan; Febbraio, Maria; Goksoy, Esen; de la Motte, Carol A; Gulen, Muhammet F; Childers, Erin Patricia; Hazen, Stanley L; Li, Xiaoxia; Fox, Paul L

    2013-01-01

    Objective Intestinal microflora and inflammatory cell infiltrates play critical roles in the pathogenesis of acute colitis. Ceruloplasmin is an acute-phase plasma protein produced by hepatocytes and activated macrophages, and has ferroxidase with bactericidal activities. The goal is to understand the role of ceruloplasmin in colitis progression in a genetically modified murine model. Design Experimental colitis was induced in ceruloplasmin null (Cp−/−) and wild-type (WT) mice by dextran sulphate sodium administration. The role of ceruloplasmin was further evaluated by transplantation of WT macrophages into Cp−/− mice. Results Cp−/− mice rapidly lost weight and were moribund by day 14, while WT mice survived at least 30 days. Colon culture supernatants from Cp−/− mice exhibited elevated levels of TNFα, KC and MCP-1, indicative of increased inflammation and neutrophil and macrophage infiltration. Elevated leucocytes and severe histopathology were observed in Cp−/− mice. Elevated protein carbonyl content was detected in colons from Cp−/− mice suggesting ceruloplasmin antioxidant activity might contribute to its protective function. Unexpectedly, intraperitoneal administration of human ceruloplasmin into Cp−/− mice did not afford protection. Bone marrow transplantation from WT mice or injection of isolated peripheral blood monocytes markedly reduced severity of colitis and morbidity in Cp−/− mice. Conclusion Macrophage-derived ceruloplasmin contributes importantly to protection against inflammation and tissue injury in acute and chronic experimental colitis. The findings suggest that defects in ceruloplasmin expression or processing may influence the onset or progression of inflammatory bowel disease in patients. PMID:22345661

  14. Design and Synthesis of Novel Xyloketal Derivatives and Their Protective Activities against H2O2-Induced HUVEC Injury

    PubMed Central

    Liu, Shixin; Luo, Rong; Xiang, Qi; Xu, Xianfang; Qiu, Liqin; Pang, Jiyan

    2015-01-01

    In this work, we designed and synthesized a series of amide derivatives (1–13), benzoxazine derivatives (16–28) and amino derivatives (29–30) from xyloketal B. All 28 new derivatives and seven known compounds (14, 15, 31–35) were evaluated for their protection against H2O2-induced HUVEC injury. 23 and 24 exhibited more potential protective activities than other derivatives; and the EC50 values of them and the leading compound 31 (xyloketal B) were 5.10, 3.59 and 15.97 μM, respectively. Meanwhile, a comparative molecular similarity indices analysis (CoMSIA) was constructed to explain the structural activity relationship of these xyloketal derivatives. This 3D QSAR model from CoMSIA suggested that the derived model exhibited good predictive ability in the external test-set validation. Derivative 24 fit well with the COMSIA map, therefore it possessed the highest activity of all compounds. Compounds 23, 24 and 31 (xyloketal B) were further to examine in the JC-1 mitochondrial membrane potential (MMP) assay of HUVECs using flow cytometry (FCM). The result indicated that 23 and 24 significantly inhibited H2O2-induced decrease of the cell mitochondrial membrane potential (ΔΨm) at 25 μM. Collectively, the protective effects of xyloketals on H2O2-induced endothelial cells may be generated from oxidation action by restraining ROS and reducing the MMP. PMID:25686273

  15. Protective effect of bile acid derivatives in phalloidin-induced rat liver toxicity.

    PubMed

    Herraez, Elisa; Macias, Rocio I R; Vazquez-Tato, Jose; Hierro, Carlos; Monte, Maria J; Marin, Jose J G

    2009-08-15

    Phalloidin causes severe liver damage characterized by marked cholestasis, which is due in part to irreversible polymerization of actin filaments. Liver uptake of this toxin through the transporter OATP1B1 is inhibited by the bile acid derivative BALU-1, which does not inhibit the sodium-dependent bile acid transporter NTCP. The aim of the present study was to investigate whether BALU-1 prevents liver uptake of phalloidin without impairing endogenous bile acid handling and hence may have protective effects against the hepatotoxicity induced by this toxin. In anaesthetized rats, i.v. administration of BALU-1 increased bile flow more than taurocholic acid (TCA). Phalloidin administration decreased basal (-60%) and TCA-stimulated bile flow (-55%) without impairing bile acid output. Phalloidin-induced cholestasis was accompanied by liver necrosis, nephrotoxicity and haematuria. In BALU-1-treated animals, phalloidin-induced cholestasis was partially prevented. Moreover haematuria was not observed, which was consistent with histological evidences of BALU-1-prevented injury of liver and kidney tissue. HPLC-MS/MS analysis revealed that BALU-1 was secreted in bile mainly in non-conjugated form, although a small proportion (<5%) of tauro-BALU-1 was detected. BALU-1 did not inhibit the biliary secretion of endogenous bile acids. When highly choleretic bile acids, - ursodeoxycholic (UDCA) and dehydrocholic acid (DHCA) - were administered, they were found less efficient than BALU-1 in preventing phalloidin-induced cholestasis. Biliary phalloidin elimination was low but it was increased by BALU-1>TCA>DHCA>UDCA. In conclusion, BALU-1 is able to protect against phalloidin-induced hepatotoxicity, probably due to an inhibition of the liver uptake and an enhanced biliary secretion of this toxin. PMID:19409403

  16. Protective effect of bile acid derivatives in phalloidin-induced rat liver toxicity

    SciTech Connect

    Herraez, Elisa; Macias, Rocio I.R.; Vazquez-Tato, Jose; Hierro, Carlos; Monte, Maria J.; Marin, Jose J.G.

    2009-08-15

    Phalloidin causes severe liver damage characterized by marked cholestasis, which is due in part to irreversible polymerization of actin filaments. Liver uptake of this toxin through the transporter OATP1B1 is inhibited by the bile acid derivative BALU-1, which does not inhibit the sodium-dependent bile acid transporter NTCP. The aim of the present study was to investigate whether BALU-1 prevents liver uptake of phalloidin without impairing endogenous bile acid handling and hence may have protective effects against the hepatotoxicity induced by this toxin. In anaesthetized rats, i.v. administration of BALU-1 increased bile flow more than taurocholic acid (TCA). Phalloidin administration decreased basal (- 60%) and TCA-stimulated bile flow (- 55%) without impairing bile acid output. Phalloidin-induced cholestasis was accompanied by liver necrosis, nephrotoxicity and haematuria. In BALU-1-treated animals, phalloidin-induced cholestasis was partially prevented. Moreover haematuria was not observed, which was consistent with histological evidences of BALU-1-prevented injury of liver and kidney tissue. HPLC-MS/MS analysis revealed that BALU-1 was secreted in bile mainly in non-conjugated form, although a small proportion (< 5%) of tauro-BALU-1 was detected. BALU-1 did not inhibit the biliary secretion of endogenous bile acids. When highly choleretic bile acids, - ursodeoxycholic (UDCA) and dehydrocholic acid (DHCA) - were administered, they were found less efficient than BALU-1 in preventing phalloidin-induced cholestasis. Biliary phalloidin elimination was low but it was increased by BALU-1 > TCA > DHCA > UDCA. In conclusion, BALU-1 is able to protect against phalloidin-induced hepatotoxicity, probably due to an inhibition of the liver uptake and an enhanced biliary secretion of this toxin.

  17. Intervention With an Erythropoietin-Derived Peptide Protects Against Neuroglial and Vascular Degeneration During Diabetic Retinopathy

    PubMed Central

    McVicar, Carmel M.; Hamilton, Ross; Colhoun, Liza M.; Gardiner, Tom A.; Brines, Michael; Cerami, Anthony; Stitt, Alan W.

    2011-01-01

    OBJECTIVE Erythropoietin (EPO) may be protective for early stage diabetic retinopathy, although there are concerns that it could exacerbate retinal angiogenesis and thrombosis. A peptide based on the EPO helix-B domain (helix B-surface peptide [pHBSP]) is nonerythrogenic but retains tissue-protective properties, and this study evaluates its therapeutic potential in diabetic retinopathy. RESEARCH DESIGN AND METHODS After 6 months of streptozotocin-induced diabetes, rats (n = 12) and age-matched nondiabetic controls (n = 12) were evenly split into pHBSP and scrambled peptide groups and injected daily (10 μg/kg per day) for 1 month. The retina was investigated for glial dysfunction, microglial activation, and neuronal DNA damage. The vasculature was dual stained with isolectin and collagen IV. Retinal cytokine expression was quantified using real-time RT-PCR. In parallel, oxygen-induced retinopathy (OIR) was used to evaluate the effects of pHBSP on retinal ischemia and neovascularization (1–30 μg/kg pHBSP or control peptide). RESULTS pHBSP or scrambled peptide treatment did not alter hematocrit. In the diabetic retina, Müller glial expression of glial fibrillary acidic protein was increased when compared with nondiabetic controls, but pHBSP significantly reduced this stress-related response (P < 0.001). CD11b+ microglia and proinflammatory cytokines were elevated in diabetic retina responses, and some of these responses were attenuated by pHBSP (P < 0.01–0.001). pHBSP significantly reduced diabetes-linked DNA damage as determined by 8-hydroxydeoxyguanosine and transferase-mediated dUTP nick-end labeling positivity and also prevented acellular capillary formation (P < 0.05). In OIR, pHBSP had no effect on preretinal neovascularization at any dose. CONCLUSIONS Treatment with an EPO-derived peptide after diabetes is fully established can significantly protect against neuroglial and vascular degenerative pathology without altering hematocrit or exacerbating

  18. Macrophage-derived reactive oxygen species protects against autoimmune priming with a defined polymeric adjuvant.

    PubMed

    Shakya, Akhilesh Kumar; Kumar, Ashok; Holmdahl, Rikard; Nandakumar, Kutty Selva

    2016-01-01

    Understanding the nature of adjuvants and the immune priming events in autoimmune diseases, such as rheumatoid arthritis, is a key challenge to identify their aetiology. Adjuvants are, however, complex structures with inflammatory and immune priming properties. Synthetic polymers provide a possibility to separate these functions and allow studies of the priming mechanisms in vivo. A well-balanced polymer, poly-N-isopropyl acrylamide (PNiPAAm) mixed with collagen type II (CII) induced relatively stronger autoimmunity and arthritis compared with more hydrophilic (polyacrylamide) or hydrophobic (poly-N-isopropylacrylamide-co-poly-N-tertbutylacrylamide and poly-N-tertbutylacrylamide) polymers. Clearly, all the synthesized polymers except the more hydrophobic poly-N-tertbutylacrylamide induced arthritis, especially in Ncf1-deficient mice, which are deficient in reactive oxygen species (ROS) production. We identified macrophages as the major infiltrating cells present at PNiPAAm-CII injection sites and demonstrate that ROS produced by the macrophages attenuated the immune response and the development of arthritis. Our results reveal that thermo-responsive polymers with high immune priming capacity could trigger an autoimmune response to CII and the subsequent arthritis development, in particular in the absence of NOX2 derived ROS. Importantly, ROS from macrophages protected against the autoimmune priming, demonstrating a critical regulatory role of macrophages in immune priming events. PMID:26455429

  19. Protective efficacy of a peptide derived from a potential adhesin of Pseudomonas aeruginosa against corneal infection.

    PubMed

    Yuan, Qing; Wu, Yuting; Wang, Yiqiang; Chen, Lin; Qu, Mingli; Duan, Kangmin; Zhao, Ge

    2016-02-01

    Dissecting the interactions between Pseudomonas aeruginosa and corneal cells is important to identify a novel target for prevention and treatment of Pseudomonas keratitis. The current study began with a peptide identified by phage display, and was to investigate the protective efficacy against P. aeruginosa infection in cornea. The original peptide Pc-E, with high homology to a hypothetical membrane protein (HmpA) in P. aeruginosa, and the derived peptide Pc-EP, with the same sequence as a region in HmpA, were synthesized. Peptide Pc-EP could directly bind to HCEC, stronger than Pc-E, and specifically activate toll-like receptor 5, and thereby significantly induce the production of pro-inflammatory factors, such as IL-1β, IL-6, IFN-γ and IL-17. Moreover, Pc-EP could act as an antagonist to inhibit the adhesion of wild-type P. aeruginosa to HCEC and mouse corneas. No inhibitory effect was observed on the adhesion of the strain loss of HmpA. When compared to the wild-type strain, the adhesion of the hmpA mutant to corneal cells was significantly decreased. Treatment of infected mouse corneas with Pc-EP before infection significantly decreased the bacterial load in the cornea and attenuated the corneal pathology. These results indicate that Pc-EP can be a useful prophylactic agent for P. aeruginosa keratitis. PMID:26500187

  20. Protective effects of a dimeric derivative of ferulic acid in animal models of Alzheimer's disease.

    PubMed

    Jung, Jun-Sub; Yan, Ji-Jing; Li, Hong-Mei; Sultan, Md Tipu; Yu, Jaehoon; Lee, Hee-Sul; Shin, Kye-Jung; Song, Dong-Keun

    2016-07-01

    Ferulic acid is a compound with potent anti-oxidant and anti-inflammatory activities. We previously reported the protective effects of ferulic acid administration against two animal models of Alzheimer's disease (AD): intracerebroventricular (i.c.v.) injection of Aß1-42 in mice and APP/PS1 mutant transgenic mice. In this study using the same AD animal models, we examined the effect of KMS4001, one of dimeric derivatives of ferulic acid. Intragastric pretreatment of mice with KMS4001 (30mg/kg/day) for 5 days significantly attenuated the Aß1-42 (i.c.v.)-induced memory impairment both in passive avoidance test and in Y-maze test. APP/PS1 mutant transgenic mice at KMS4001 doses of 3 and 30mg/kg/day via drinking water showed the significantly enhanced novel-object recognition memory at both 1.5 and 3 months after the start of KMS4001 treatment. Treatment of APP/PS1 mutant transgenic mice with KMS4001 for 3 months at the doses of 3 and 30mg/kg/day markedly decreased Aβ1-40 and Aβ1-42 levels in the frontal cortex. The KMS4001 dose-response relationships for Aβ decrease and for improvement in novel-object recognition test corresponded to each other. Taken together, these results suggest that KMS4001 could be an effective drug candidate against AD. PMID:27118174

  1. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria

    PubMed Central

    Jonker, Johan W.; Buitelaar, Marije; Wagenaar, Els; van der Valk, Martin A.; Scheffer, George L.; Scheper, Rik J.; Plösch, Torsten; Kuipers, Folkert; Elferink, Ronald P. J. Oude; Rosing, Hilde; Beijnen, Jos H.; Schinkel, Alfred H.

    2002-01-01

    The breast cancer resistance protein (BCRP/ABCG2) is a member of the ATP-binding cassette family of drug transporters and confers resistance to various anticancer drugs. We show here that mice lacking Bcrp1/Abcg2 become extremely sensitive to the dietary chlorophyll-breakdown product pheophorbide a, resulting in severe, sometimes lethal phototoxic lesions on light-exposed skin. Pheophorbide a occurs in various plant-derived foods and food supplements. Bcrp1 transports pheophorbide a and is highly efficient in limiting its uptake from ingested food. Bcrp1−/− mice also displayed a previously unknown type of protoporphyria. Erythrocyte levels of the heme precursor and phototoxin protoporphyrin IX, which is structurally related to pheophorbide a, were increased 10-fold. Transplantation with wild-type bone marrow cured the protoporphyria and reduced the phototoxin sensitivity of Bcrp1−/− mice. These results indicate that humans or animals with low or absent BCRP activity may be at increased risk for developing protoporphyria and diet-dependent phototoxicity and provide a striking illustration of the importance of drug transporters in protection from toxicity of normal food constituents. PMID:12429862

  2. Deriving protection thresholds for threatened and endangered species potentially exposed to pesticides

    EPA Science Inventory

    The Endangered Species Act requires specific and stringent protection to threatened and endangered species and their critical habitat. Therefore, protective methods for risk assessment for such species are needed. Species sensitivity distributions (SSDs) are a common tool used fo...

  3. Protection against Marek's disease-derived tumor transplants by the nononcogenic SB-1 strain of Marek's disease virus.

    PubMed Central

    Schat, K A; Calnek, B W

    1978-01-01

    A series of experiments was conducted to study the in vivo protection against Marek's disease-derived tumor transplants by the nononcogenic SB-1 strain of Marek's disease virus. Intact, embryonally bursectomized (Bx), thymectomized (Tx), or cyclophosphamide (Cy)-treated chickens of four genetic lines were vaccinated with live or inactivated SB-1. JMV, a non-virus-producing transplant, and GA/Tr-1 and MDT-198, two virus-producing transplants were used for challenge. Optimal protection against JMV was present 7 days postvaccination, but there was significant protection even when SB-1 and JMV were administered together. Protection was abolished by an increase in the number of tumor cells used for challenge or by combined Tx and Cy treatment. Inactivated SB-1-infected cells were unable to induce protection against JMV challenge. Protection was also present against challenge with GA/Tr-1, but not against MDT-198, except in vaccinated, Bx chickens. It was concluded that protection against JMV was T-cell dependent and required the induction of neo-antigens not present in an inactivated SB-1 cellular preparation. The absence of protection in intact chickens against MDT-198 could not be explained. PMID:215543

  4. Derivation of human health-based ambient water quality criteria: a consideration of conservatism and protectiveness goals.

    PubMed

    Tatum, Vickie; Wiegand, Paul; Stratton, Steve; Louch, Jeffrey; Ebert, Ellen; Anderson, Paul

    2015-04-01

    Under the terms of the Clean Water Act, criteria for the protection of human health (Human Health Ambient Water Quality Criteria [HHWQC]) are traditionally derived using equations recommended by the US Environmental Protection Agency (USEPA) that include parameters for exposure assessment. To derive "adequately protective" HHWQC, USEPA proposes the use of default values for these parameters that are a combination of medians, means, and percentile estimates targeting the high end (90th percentile) of the general population. However, in practice, in nearly all cases, USEPA's recommended default assumptions represent upper percentiles. This article considers the adequacy of the exposure assessment component of USEPA-recommended equations to yield criteria that are consistent with corresponding health protection targets established in USEPA recommendations or state policies, and concludes that conservative selections for exposure parameters can result in criteria that are substantially more protective than the health protection goals for HHWQC recommended by USEPA, due in large part to the compounding effect that occurs when multiple conservative factors are combined. This situation may be mitigated by thoughtful selection of exposure parameter values when using a deterministic approach, or by using a probabilistic approach based on data distributions for many of these parameters. PMID:25345861

  5. Derivation of guideline values for gold (III) ion toxicity limits to protect aquatic ecosystems.

    PubMed

    Nam, Sun-Hwa; Lee, Woo-Mi; Shin, Yu-Jin; Yoon, Sung-Ji; Kim, Shin Woong; Kwak, Jin Il; An, Youn-Joo

    2014-01-01

    This study focused on estimating the toxicity values of various aquatic organisms exposed to gold (III) ion (Au(3+)), and to propose maximum guideline values for Au(3+) toxicity that protect the aquatic ecosystem. A comparative assessment of methods developed in Australia and New Zealand versus the European Community (EC) was conducted. The test species used in this study included two bacteria (Escherichia coli and Bacillus subtilis), one alga (Pseudokirchneriella subcapitata), one euglena (Euglena gracilis), three cladocerans (Daphnia magna, Moina macrocopa, and Simocephalus mixtus), and two fish (Danio rerio and Oryzias latipes). Au(3+) induced growth inhibition, mortality, immobilization, and/or developmental malformations in all test species, with responses being concentration-dependent. According to the moderate reliability method of Australia and New Zealand, 0.006 and 0.075 mg/L of guideline values for Au(3+) were obtained by dividing 0.33 and 4.46 mg/L of HC5 and HC50 species sensitivity distributions (SSD) with an FACR (Final Acute to Chronic Ratio) of 59.09. In contrast, the EC method uses an assessment factor (AF), with the 0.0006 mg/L guideline value for Au(3+) being divided with the 48-h EC50 value for 0.60 mg/L (the lowest toxicity value obtained from short term results) by an AF of 1000. The Au(3+) guideline value derived using an AF was more stringent than the SSD. We recommend that more toxicity data using various bioassays are required to develop more accurate ecological risk assessments. More chronic/long-term exposure studies on sensitive endpoints using additional fish species and invertebrates not included in the current dataset will be needed to use other derivation methods (e.g., US EPA and Canadian Type A) or the "High Reliability Method" from Australia/New Zealand. Such research would facilitate the establishment of guideline values for various pollutants that reflect the universal effects of various pollutants in aquatic ecosystems. To

  6. Autophagy Protects Against Aminochrome-Induced Cell Death in Substantia Nigra-Derived Cell Line

    PubMed Central

    Paris, Irmgard; Muñoz, Patricia; Huenchuguala, Sandro; Couve, Eduardo; Sanders, Laurie H.; Greenamyre, John Timothy; Caviedes, Pablo; Segura-Aguilar, Juan

    2011-01-01

    Aminochrome, the precursor of neuromelanin, has been proposed to be involved in the neurodegeneration neuromelanin-containing dopaminergic neurons in Parkinson’s disease. We aimed to study the mechanism of aminochrome-dependent cell death in a cell line derived from rat substantia nigra. We found that aminochrome (50μM), in the presence of NAD(P)H-quinone oxidoreductase, EC 1.6.99.2 (DT)-diaphorase inhibitor dicoumarol (DIC) (100μM), induces significant cell death (62 ± 3%; p < 0.01), increase in caspase-3 activation (p < 0.001), release of cytochrome C, disruption of mitochondrial membrane potential (p < 0.01), damage of mitochondrial DNA, damage of mitochondria determined with transmission electron microscopy, a dramatic morphological change characterized as cell shrinkage, and significant increase in number of autophagic vacuoles. To determine the role of autophagy on aminochrome-induced cell death, we incubated the cells in the presence of vinblastine and rapamycin. Interestingly, 10μM vinblastine induces a 5.9-fold (p < 0.001) and twofold (p < 0.01) significant increase in cell death when the cells were incubated with 30μM aminochrome in the absence and presence of DIC, respectively, whereas 10μM rapamycin preincubated 24 h before addition of 50μM aminochrome in the absence and the presence of 100μM DIC induces a significant decrease (p < 0.001) in cell death. In conclusion, autophagy seems to be an important protective mechanism against two different aminochrome-induced cell deaths that initially showed apoptotic features. The cell death induced by aminochrome when DT-diaphorase is inhibited requires activation of mitochondrial pathway, whereas the cell death induced by aminochrome alone requires inhibition of autophagy-dependent degrading of damaged organelles and recycling through lysosomes. PMID:21427056

  7. Isoflurane Preconditioning Elicits Competent Endogenous Mechanisms of Protection from Oxidative Stress in Cardiomyocytes Derived from Human Embryonic Stem Cells

    PubMed Central

    Sepac, Ana; Sedlic, Filip; Si-Tayeb, Karim; Lough, John; Duncan, Stephen A.; Bienengraeber, Martin; Park, Frank; Kim, Jinhee; Bosnjak, Zeljko J.

    2010-01-01

    Background Human embryonic stem cell (hESC)-derived cardiomyocytes potentially represent a powerful experimental model complementary to myocardium obtained from patients, relatively inaccessible for research purposes. We tested whether anesthetic-induced preconditioning (APC) with isoflurane elicits competent protective mechanisms in hESC-derived cardiomyocytes against oxidative stress to be used as a model of human cardiomyocytes for studying preconditioning. Methods H1 hESC cell line was differentiated into cardiomyocytes using growth factors activin A and bone morphogenetic protein-4. Living ventricular hESC-derived cardiomyocytes were identified using lentiviral vector expressing a reporter gene (enhanced green fluorescent protein) driven by a cardiac-specific human myosin light chain 2v promoter. Mitochondrial membrane potential, reactive oxygen species production, opening of mitochondrial permeability transition pore, and survival of hESC-derived cardiomyocytes were assessed using confocal microscopy. Oxygen consumption was measured in contracting cell clusters. Results Differentiation yielded a high percentage (∼85%) of cardiomyocytes in beating clusters that were positive for cardiac-specific markers and exhibited action potentials resembling mature cardiomyocytes. Isoflurane depolarized mitochondria, attenuated oxygen consumption, and stimulated generation of reactive oxygen species. APC protected these cells from oxidative stress-induced death and delayed mitochondrial permeability transition pore opening. Conclusions APC elicits competent protective mechanisms against oxidative stress in hESC-derived cardiomyocytes, suggesting the feasibility to use these cells as a model of human cardiomyocytes for studying APC and potentially other treatments/diseases. Our differentiation protocol is very efficient and yields a high percentage of cardiomyocytes. These results also suggest a promising ability of APC to protect and improve engraftment of hESC-derived

  8. Conducting a battery of bioassays for gold nanoparticles to derive guideline value for the protection of aquatic ecosystems.

    PubMed

    Nam, Sun-Hwa; Shin, Yu-Jin; Lee, Woo-Mi; Kim, Shin Woong; Kwak, Jin Il; Yoon, Sung-Ji; An, Youn-Joo

    2015-05-01

    Gold nanoparticles (Au-NPs) are used in many applications, including the manufacture of products like cosmetics, paints, and electrochemical immunosensors, and in the detection, diagnosis, and treatment of tumors. However, there are no legal or recommended guidelines for protecting aquatic ecosystems from Au-NPs. In this study, we conducted a battery of bioassays and present toxicity values for two bacteria, one alga, one euglena, three cladoceran, and two fish species that were exposed to Au-NPs. Guideline values for protecting aquatic ecosystems from Au-NPs were derived using methods that are generally used to derive water-quality guidelines and are used in Australia, New Zealand, Canada, the European Community (EC), and the USA. Au-NPs had adverse effects on all test species, including growth inhibition of both bacteria, the alga, and the euglena; mortality and immobilization in the three cladocerans; and developmental malformations in the embryos and larvae of the two fish. Guideline values of 0.15 and 0.04 × 10(10) particles/mL were derived for Au-NPs using a species sensitivity distribution (SSD) and assessment factor. The guideline value derived for Au-NPs using an assessment factor was more stringent than that derived using SSD. This is the first study to derive guideline values for nanoparticles in water environments. PMID:24983899

  9. Fmoc-Sec(Xan)-OH: synthesis and utility of Fmoc selenocysteine SPPS derivatives with acid-labile sidechain protection.

    PubMed

    Flemer, Stevenson

    2015-01-01

    We report here the synthesis of the first selenocysteine SPPS derivatives which bear TFA-labile sidechain protecting groups. New compounds Fmoc-Sec(Xan)-OH and Fmoc-Sec(Trt)-OH are presented as useful and practical alternatives to the traditional Fmoc-Sec-OH derivatives currently available to the peptide chemist. From a bis Fmoc-protected selenocystine precursor, multiple avenues of diselenide reduction were attempted to determine the most effective method for subsequent attachment of the protecting group electrophiles. Our previously reported one-pot reduction methodology was ultimately chosen as the optimal approach toward the synthesis of these novel building blocks, and both were easily obtained in high yield and purity. Fmoc-Sec(Xan)-OH was discovered to be bench-stable for extended timeframes while the corresponding Fmoc-Sec(Trt)-OH derivative appeared to detritylate slowly when not stored at -20 °C. Both Sec derivatives were incorporated into single- and multiple-Sec-containing test peptides in order to ascertain the peptides' deprotection behavior and final form upon TFA cleavage. Single-Sec-containing test peptides were always isolated as their corresponding diselenide dimers, while dual-Sec-containing peptide sequences were afforded exclusively as their intramolecular diselenides. PMID:25504629

  10. N-Octanoyl Dopamine, a Non-Hemodyanic Dopamine Derivative, for Cell Protection during Hypothermic Organ Preservation

    PubMed Central

    Beck, Grietje; Schnuelle, Peter; Höger, Simone; Wehling, Martin; Yard, Benito A.

    2010-01-01

    Background Although donor dopamine treatment reduces the requirement for post transplantation dialysis in renal transplant recipients, implementation of dopamine in donor management is hampered by its hemodynamic side-effects. Therefore novel dopamine derivatives lacking any hemodynamic actions and yet are more efficacious in protecting tissue from cold preservation injury are warranted. We hypothesized that variation of the molecular structure would yield more efficacious compounds avoid of any hemodynamic effects. Methodology/Principal Findings To this end, we assessed protection against cold preservation injury in HUVEC by the attenuation of lactate dehydrogenase (LDH) release. Modification of dopamine by an alkanoyl group increased cellular uptake and significantly improved efficacy of protection. Further variation revealed that only compounds bearing two hydroxy groups in ortho or para position at the benzene nucleus, i.e. strong reductants, were protective. However, other reducing agents like N-acetyl cysteine and ascorbate, or NADPH oxidase inhibition did not prevent cellular injury following cold storage. Unlike dopamine, a prototypic novel compound caused no hemodynamic side-effects. Conclusions/Significance In conclusion, we demonstrate that protection against cold preservation injury by catecholamines is exclusively governed by strong reducing capacity and sufficient lipophilicity. The novel dopamine derivatives might be of clinical relevance in donor pre-conditioning as they are completely devoid of hemodynamic action, their increased cellular uptake would reduce time of treatment and therefore also may have a potential use for non-heart beating donors. PMID:20300525

  11. Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection

    PubMed Central

    Reed, Matthew D.; Wilder, Julie A.; Mega, William M.; Hutt, Julie A.; Kuehl, Philip J.; Valderas, Michelle W.; Chew, Lawrence L.; Liang, Bertrand C.; Squires, Charles H.

    2015-01-01

    Protective antigen (PA), one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax). Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively) supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions. Mutant derivatives of the protective antigen that will not form the anthrax toxins have been described. We have cloned and expressed both mutant (PA SNKE167-ΔFF-315-E308D) and native PA molecules recombinantly and purified them. In this study, both the mutant and native PA molecules, formulated with alum (Alhydrogel), elicited high titers of anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both mutant and native PA vaccine preparations protected rabbits from lethal, aerosolized, B. anthracis spore challenge subsequent to two immunizations at doses of less than 1 μg. PMID:26207820

  12. Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection.

    PubMed

    Reed, Matthew D; Wilder, Julie A; Mega, William M; Hutt, Julie A; Kuehl, Philip J; Valderas, Michelle W; Chew, Lawrence L; Liang, Bertrand C; Squires, Charles H

    2015-01-01

    Protective antigen (PA), one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax). Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively) supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions. Mutant derivatives of the protective antigen that will not form the anthrax toxins have been described. We have cloned and expressed both mutant (PA SNKE167-ΔFF-315-E308D) and native PA molecules recombinantly and purified them. In this study, both the mutant and native PA molecules, formulated with alum (Alhydrogel), elicited high titers of anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both mutant and native PA vaccine preparations protected rabbits from lethal, aerosolized, B. anthracis spore challenge subsequent to two immunizations at doses of less than 1 μg. PMID:26207820

  13. Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity.

    PubMed

    Lee, Won-Hee; Choi, Hyun-Il; Hong, Sung-Wook; Kim, Kwang-Sun; Gho, Yong Song; Jeon, Seong Gyu

    2015-01-01

    The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria-induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co-stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections. PMID:26358222

  14. Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity

    PubMed Central

    Lee, Won-Hee; Choi, Hyun-Il; Hong, Sung-Wook; Kim, Kwang-sun; Gho, Yong Song; Jeon, Seong Gyu

    2015-01-01

    The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria-induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co-stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections. PMID:26358222

  15. Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques

    PubMed Central

    Rosenberg, Yvonne J.; Montefiori, David C.; LaBranche, Celia C.; Lewis, Mark G.; Sack, Markus; Lees, Jonathan P.; Jiang, Xiaoming

    2016-01-01

    Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown promise for prevention and treatment of HIV infection. However, multiple IV administrations in geographic locations with poor accessibility to medical care have practical limitations. We have assessed the efficacy of plant-derived PGT121 delivered subcutaneously (SC) against pre-and post-intravaginal challenge using a rigorous SHIV-SF162P3 macaque protection model. SC administered PGT121 exhibited a longer serum half-life than IV administration and was more consistent than intramuscular delivery. A dose of 3.5mg/kg PGT121 prevented infection at a minimum ID50 neutralization titer of 1:295 while 5mg/kg protected five of six macaques when delivered immediately post-challenge. These results suggest the utility of plant-derived bnAbs delivered SC for HIV prevention. PMID:27031108

  16. Synthesis and membrane-protective activity of novel derivatives of α-mangostin at the C-4 position.

    PubMed

    Buravlev, Evgeny V; Shevchenko, Oksana G; Kutchin, Aleksandr V

    2015-02-15

    A series of new C-4-derivatives of α-mangostin has been synthesized with the use of Mannich reaction and alkylation with 4-bromomethyl-2,6-dialkylphenols. It has been shown on a model of H2O2-induced erythrocyte hemolysis that the Mannich bases containing morpholinomethyl and piperidinomethyl fragments differ from parent α-mangostin by their high antioxidant and membrane-protective activity. PMID:25592715

  17. Sol-gel derived C-SiC composites and protective coatings for sustained durability in the space environment

    NASA Astrophysics Data System (ADS)

    Haruvy, Yair; Liedtke, Volker

    2003-09-01

    Composites and coatings were produced via the fast sol-gel process of a mixture of alkoxysilane precursors. The composites were comprised of carbon fibers, fabrics, or their precursors as reinforcement, and sol-gel-derived silicon carbide as matrix, aiming at high-temperature stable ceramics that can be utilized for re-entry structures. The protective coatings were comprised of fluorine-rich sol-gel derived resins, which exhibit high flexibility and coherence to provide sustained ATOX protection necessary for LEO space-exposed elements. For producing the composites, the sol-gel-derived resin is cast onto the reinforcement fibers/fabrics mat (carbon or its precursors) to produce a 'green' composite that is being cured. The 'green' composite is converted into a C-SiC composite via a gradual heat-pressure process under inert atmosphere, during which the organic substituents on the silicon atoms undergo internal oxidative pyrolysis via the schematic reaction: (SiRO3/2)n -> SiC + CO2 + H2O. The composition of the resultant silicon-oxi-carbide is tailorable via modifying the composition of the sol-gel reactants. The reinforcement, when made of carbon precursors, is converted into carbon during the heat-and-pressure processing as well. The C-SiC composites thus derived exhibit superior thermal stability and comparable thermal conductivity, combined with good mechanical strength features and failure resistance, which render them greatly applicable for re-entry shielding, heat-exchange pipes, and the like. Fluorine rich sol-gel derived coatings were developed as well, via the use of HF rich sol-gel process. These coatings provide oxidation-protection via the silica formation process, together with flexibility that allows 18,000 repetitive folding of the coating without cracking.

  18. Process for the preparation of protected 3-amino-1,2-dihydroxypropane acetal and derivatives thereof

    DOEpatents

    Hollingsworth, Rawle I.; Wang, Guijun

    2000-01-01

    A process for producing protected 3-amino-1,2-dihydroxypropane acetal, particularly in chiral forms, for use as an intermediate in the preparation of various 3-carbon compounds which are chiral. In particular, the present invention relates to the process for preparation of 3-amino-1,2-dihydroxypropane isopropylidene acetal. The protected 3-amino-1,2-dihydroxypropane acetal is a key intermediate to the preparation of chiral 3-carbon compounds which in turn are intermediates to various pharmaceuticals.

  19. Process for the preparation of protected dihydroxypropyl trialkylammonium salts and derivatives thereof

    DOEpatents

    Hollingsworth, Rawle I.; Wang, Guijun

    2000-01-01

    A process for the preparation of protected dihydroxypropyl trialkylammonium salts, particularly in chiral form is described. In particular, a process for the preparation of (2,2-dimethyl-1,3-dioxolan-4-ylmethyl)trialkylammonium salts, particularly in chiral form is described. Furthermore, a process is described wherein the (2,2-dimethyl-1,3-dioxolan-4ylmethyl)trialkylammonium salts is a 2,2-dimethyl-1,3-dioxolan-4-ylmethyl trimethylammonium salt, preferably in chiral form. The protected dihydroxypropyl trialkylammonium salts lead to L-carnitine (9) when in chiral form (5).

  20. Food-Derived Bioactives Can Protect the Anti-Inflammatory Activity of Cortisol with Antioxidant-Dependent and -Independent Mechanisms

    PubMed Central

    Ruijters, Erik J. B.; Haenen, Guido R. M. M.; Willemsen, Mathijs; Weseler, Antje R.; Bast, Aalt

    2016-01-01

    In chronic inflammatory diseases the anti-inflammatory effect of glucocorticoids (GCs) is often decreased, leading to GC resistance. Inflammation is related with increased levels of reactive oxygen species (ROS), leading to oxidative stress which is thought to contribute to the development of GC resistance. Plant-derived compounds such as flavonoids are known for their ability to protect against ROS. In this exploratory study we screened a broad range of food-derived bioactives for their antioxidant and anti-inflammatory effects in order to investigate whether their antioxidant effects are associated with the ability to preserve the anti-inflammatory effects of cortisol. The anti-inflammatory potency of the tested compounds was assessed by measuring the oxidative stress–induced GC resistance in human macrophage-like cells. Cells were pre-treated with H2O2 (800 µM) with and without bioactives and then exposed to lipopolysaccharides (LPS) (10 ng/mL) and cortisol (100 nM). The level of inflammation was deducted from the concentration of interleukin-8 (IL-8) in the medium. Intracellular oxidative stress was measured using the fluorescent probe 2′,7′-dichlorofluorescein (DCFH). We found that most of the dietary bioactives display antioxidant and anti-inflammatory action through the protection of the cortisol response. All compounds, except for quercetin, revealing antioxidant activity also protect the cortisol response. This indicates that the antioxidant activity of compounds plays an important role in the protection of the GC response. However, next to the antioxidant activity of the bioactives, other mechanisms also seem to be involved in this protective, anti-inflammatory effect. PMID:26891295

  1. Food-Derived Bioactives Can Protect the Anti-Inflammatory Activity of Cortisol with Antioxidant-Dependent and -Independent Mechanisms.

    PubMed

    Ruijters, Erik J B; Haenen, Guido R M M; Willemsen, Mathijs; Weseler, Antje R; Bast, Aalt

    2016-01-01

    In chronic inflammatory diseases the anti-inflammatory effect of glucocorticoids (GCs) is often decreased, leading to GC resistance. Inflammation is related with increased levels of reactive oxygen species (ROS), leading to oxidative stress which is thought to contribute to the development of GC resistance. Plant-derived compounds such as flavonoids are known for their ability to protect against ROS. In this exploratory study we screened a broad range of food-derived bioactives for their antioxidant and anti-inflammatory effects in order to investigate whether their antioxidant effects are associated with the ability to preserve the anti-inflammatory effects of cortisol. The anti-inflammatory potency of the tested compounds was assessed by measuring the oxidative stress-induced GC resistance in human macrophage-like cells. Cells were pre-treated with H₂O₂ (800 µM) with and without bioactives and then exposed to lipopolysaccharides (LPS) (10 ng/mL) and cortisol (100 nM). The level of inflammation was deducted from the concentration of interleukin-8 (IL-8) in the medium. Intracellular oxidative stress was measured using the fluorescent probe 2',7'-dichlorofluorescein (DCFH). We found that most of the dietary bioactives display antioxidant and anti-inflammatory action through the protection of the cortisol response. All compounds, except for quercetin, revealing antioxidant activity also protect the cortisol response. This indicates that the antioxidant activity of compounds plays an important role in the protection of the GC response. However, next to the antioxidant activity of the bioactives, other mechanisms also seem to be involved in this protective, anti-inflammatory effect. PMID:26891295

  2. Oxidation of cholesterol and O-protected derivatives by the environmental pollutant NO2˙.

    PubMed

    Zalewski, A N; Nathanael, J G; White, J M; Wille, U

    2016-03-01

    Exposure of O-protected and free cholesterol to NO2˙ under exclusion of water leads to nitroimine nitrates through a non-radical mechanism, which reveals the high susceptibility of the π system to oxidative damage. In the presence of moisture the reaction leads to 6-nitrocholesterols , which result from hydrolysis and oxidation of . PMID:26892038

  3. Protective effects of onion-derived quercetin on glutamate-mediated hippocampal neuronal cell death

    PubMed Central

    Yang, Eun-Ju; Kim, Geum-Soog; Kim, Jeong Ah; Song, Kyung-Sik

    2013-01-01

    Background: Neurodegenerative diseases are characterized by progressive neuron degeneration in specific functional systems of the central or peripheral nervous system. This study investigated the protective effects of quercetin isolated from onion on neuronal cells and its protective mechanisms against glutamate-induced apoptosis in HT22 cells. Materials and Methods: HT22 cells were cultured to study the neuroprotective mechanism of quercetin against glutamate-mediated oxidative stress. The intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (ΔΨm) were measured. The protein expression of calpain, spectrin, Bcl-2, Bax, Bid, cytochrome c, and mitogen-activated protein kinases (MAPKs) was evaluated by Western blotting. Results: Quercetin had a protective effect by reducing both intracellular ROS overproduction and glutamate-mediated Ca2+ influx. These effects were due to the downregulation of several apoptosis-related biochemical markers. Calpain expression was reduced and spectrin cleavage was inhibited by quercetin in glutamate-exposed HT22 cells. Disruption of the mitochondrial membrane potential (ΔΨm), activation of the pro-apoptotic proteins Bid and Bax, and cytochrome c release in response to glutamate-induced oxidative stress were reduced. Quercetin also suppressed phosphorylation of MAPKs. Conclusion: This is the first report on the detailed mechanisms of the protective effect of quercetin on HT22 cells. Onion extract and quercetin may be useful for preventing or treating neurodegenerative disorders. PMID:24124281

  4. Maternal Immunization with Pneumococcal Surface Protein A Protects against Pneumococcal Infections among Derived Offspring

    PubMed Central

    Hollingshead, Susan K.; Briles, David E.; Yamanaka, Noboru

    2011-01-01

    Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA). Mother mice were intranasally immunized with recombinant PspA (rPspA) and cholera toxin B subunit (CTB) prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood. (191 words) PMID:22073127

  5. Maternal immunization with pneumococcal surface protein A protects against pneumococcal infections among derived offspring.

    PubMed

    Kono, Masamitsu; Hotomi, Muneki; Hollingshead, Susan K; Briles, David E; Yamanaka, Noboru

    2011-01-01

    Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA). Mother mice were intranasally immunized with recombinant PspA (rPspA) and cholera toxin B subunit (CTB) prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood. PMID:22073127

  6. Decreased outer membrane permeability protects mycobacteria from killing by ubiquitin-derived peptides.

    PubMed

    Purdy, Georgiana E; Niederweis, Michael; Russell, David G

    2009-09-01

    Ubiquitin-derived peptides are bactericidal in vitro and contribute to the mycobactericidal activity of the lysosome. To further define interactions of ubiquitin-derived peptides with mycobacteria, we screened for mutants with increased resistance to the bactericidal activity of the synthetic ubiquitin-derived peptide Ub2. The four Ub2-resistant Mycobacterium smegmatis mutants were also resistant to the bactericidal action of other antimicrobial peptides and macrophages. Two mutants were in the mspA gene encoding the main M. smegmatis porin. Using a translocation-deficient MspA point mutant, we showed that susceptibility of M. smegmatis to Ub2 was independent of MspA channel activity. Instead, the M. smegmatis Ub2-resistant mutants shared a common phenotype of decreased cell wall permeability compared with wild-type bacteria. Expression of mspA rendered Mycobacterium tuberculosis CDC1551 more susceptible both to ubiquitin-derived peptides in vitro and to lysosomal killing in macrophages. Finally, biochemical assays designed to assess membrane integrity indicated that Ub2 treatment impairs membrane function of M. smegmatis and M. tuberculosis cells. The M. smegmatis Ub2-resistant mutants were more resistant than wild-type M. smegmatis to this damage. We conclude that Ub2 targets mycobacterial membranes and that reduced membrane permeability provides mycobacteria intrinsic resistance against antimicrobial compounds including bactericidal ubiquitin-derived peptides. PMID:19682257

  7. Studies on Emblica officinalis Derived Tannins for Their Immunostimulatory and Protective Activities against Coccidiosis in Industrial Broiler Chickens

    PubMed Central

    Kaleem, Qari Muhammad; Akhtar, Masood; Awais, Mian Muhammad; Saleem, Muhammad; Zafar, Muddassar; Iqbal, Zafar; Muhammad, Faqir

    2014-01-01

    The present study reports the effect of Emblica officinalis (EO) derived tannins on humoral immune responses and their protective efficacy against Eimeria infection in chickens. Tannins were extracted from EO and characterized by HPLC. EO derived tannins (EOT) and commercial tannins (CT) were orally administered in broiler chicks in graded doses for three consecutive days, that is, 5th-7th days of age. On day 14 after administration of tannins, humoral immune response was detected against sheep red blood cells (SRBCs) by haemagglutination assay. Protective efficacy of tannins was measured against coccidial infection, induced by Eimeria species. Results revealed higher geomean titers against SRBCs in chickens administered with EOT as compared to those administered with CT and control group. Mean oocysts per gram of droppings were significantly lower (P < 0.05) in EOT administered chickens as compared to control group. Lesion scoring also showed the lowest caecal and intestinal lesion score of mild to moderate intensity in chickens administered with EOT. Further, significantly higher (P < 0.05) daily body weight gains and antibody titers were detected in EOT administered chickens as compared to those of CT administered and control groups. EOT showed the immunostimulatory properties in broilers and their administration in chickens boost the protective immunity against coccidiosis. PMID:24578631

  8. Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

    SciTech Connect

    Watson, A.P.

    2003-07-24

    Percutaneous vapor toxicity guidelines are provided for assessment and selection of chemical protective ensembles (CPEs) to be used by civilian and military first responders operating in a chemical warfare agent vapor environment. The agents evaluated include the G-series and VX nerve agents, the vesicant sulfur mustard (agent HD) and, to a lesser extent, the vesicant Lewisite (agent L). The focus of this evaluation is percutaneous vapor permeation of CPEs and the resulting skin absorption, as inhalation and ocular exposures are assumed to be largely eliminated through use of SCBA and full-face protective masks. Selection of appropriately protective CPE designs and materials incorporates a variety of test parameters to ensure operability, practicality, and adequacy. One aspect of adequacy assessment should be based on systems tests, which focus on effective protection of the most vulnerable body regions (e.g., the groin area), as identified in this analysis. The toxicity range of agent-specific cumulative exposures (Cts) derived in this analysis can be used as decision guidelines for CPE acceptance, in conjunction with weighting consideration towards more susceptible body regions. This toxicity range is bounded by the percutaneous vapor estimated minimal effect (EME{sub pv}) Ct (as the lower end) and the 1% population threshold effect (ECt{sub 01}) estimate. Assumptions of exposure duration used in CPE certification should consider that each agent-specific percutaneous vapor cumulative exposure Ct for a given endpoint is a constant for exposure durations between 30 min and 2 hours.

  9. Oxic microshield and local pH enhancement protects Zostera muelleri from sediment derived hydrogen sulphide.

    PubMed

    Brodersen, Kasper Elgetti; Nielsen, Daniel Aagren; Ralph, Peter J; Kühl, Michael

    2015-02-01

    Seagrass is constantly challenged with transporting sufficient O₂ from above- to belowground tissue via aerenchyma in order to maintain aerobic metabolism and provide protection against phytotoxins. Electrochemical microsensors were used in combination with a custom-made experimental chamber to analyse the belowground biogeochemical microenvironment of Zostera muelleri under changing environmental conditions. Measurements revealed high radial O₂ release of up to 500 nmol O2 cm(-2) h(-1) from the base of the leaf sheath, maintaining a c. 300-μm-wide plant-mediated oxic microzone and thus protecting the vital meristematic regions of the rhizome from reduced phytotoxic metabolites such as hydrogen sulphide (H₂S). H₂S intrusion was prevented through passive diffusion of O₂ to belowground tissue from leaf photosynthesis in light, as well as from the surrounding water column into the flow-exposed plant parts during darkness. Under water column hypoxia, high belowground H₂S concentrations at the tissue surface correlated with the inability to sustain the protecting oxic microshield around the meristematic regions of the rhizome. We also found increased pH levels in the immediate rhizosphere of Z. muelleri, which may contribute to further detoxification of H₂S through shifts in the chemical speciation of sulphide. Zostera muelleri can modify the geochemical conditions in its immediate rhizosphere, thereby reducing its exposure to H₂S. PMID:25367685

  10. Liver-protective activities of aucubin derived from traditional oriental medicine.

    PubMed

    Chang, I M

    1998-11-01

    The iridoid glycosides including aucubin (AU), catalpol (CA), swertimarin (SW), and gardenoside (GA) are frequently found as natural constituents of many traditional oriental medicinal plants including Chinese herbs. Among these iridoid glycosides, AU was systematically studied for its potent liver-protective activities using experimental systems of hepatic damage. AU showed high liver-protective activity against carbon tetrachloride-induced hepatic damage in mice. Also AU showed significant protective activity against alpha-amanitin-induced hepatic damage in mice, and it prevented a depression of liver RNA biosynthesis caused by alpha-amanitin administration. Potent antidotal effects on mushroom poisoning in beagle dogs ingested with aqueous extract of Amanita virosa was observed; beagle dogs completely survived, even when AU administration was withheld for half an hour after mushroom poisoning. In addition, AU was found to suppress hepatitis B viral DNA replication in vitro. Conversion of AU to its aglycone form appeared to be a prerequisite step for an exhibition of such antiviral activity. PMID:10100510

  11. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis.

    PubMed

    Kang, Chil-Sung; Ban, Mingi; Choi, Eun-Jeong; Moon, Hyung-Geun; Jeon, Jun-Sung; Kim, Dae-Kyum; Park, Soo-Kyung; Jeon, Seong Gyu; Roh, Tae-Young; Myung, Seung-Jae; Gho, Yong Song; Kim, Jae Gyu; Kim, Yoon-Keun

    2013-01-01

    Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis. PMID:24204633

  12. A novel pyrazole derivative protects from ovariectomy-induced osteoporosis through the inhibition of NADPH oxidase

    PubMed Central

    Joo, Jung Hee; Huh, Jeong-Eun; Lee, Jee Hyun; Park, Doo Ri; Lee, Yoonji; Lee, Seul Gee; Choi, Sun; Lee, Hwa Jeong; Song, Seong-Won; Jeong, Yongmi; Goo, Ja-Il; Choi, Yongseok; Baek, Hye Kyung; Yi, Sun Shin; Park, Soo Jin; Lee, Ji Eun; Ku, Sae Kwang; Lee, Won Jae; Lee, Kee-In; Lee, Soo Young; Bae, Yun Soo

    2016-01-01

    Osteoclast cells (OCs) are differentiated from bone marrow-derived macrophages (BMMs) by activation of receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). Activation of NADPH oxidase (Nox) isozymes is involved in RANKL-dependent OC differentiation, implicating Nox isozymes as therapeutic targets for treatment of osteoporosis. Here, we show that a novel pyrazole derivative, Ewha-18278 has high inhibitory potency on Nox isozymes. Blocking the activity of Nox with Ewha-18278 inhibited the responses of BMMs to RANKL, including reactive oxygen species (ROS) generation, activation of mitogen-activated protein (MAP) kinases and NF-κB, and OC differentiation. To evaluate the anti-osteoporotic function of Ewha-18278, the derivative was applied to estrogen-deficient ovariectomized (OVX) ddY mice. Oral administration of Ewha-18278 (10 mg/kg/daily, 4 weeks) into the mice recovered bone mineral density, trabecular bone volume, trabecular bone length, number and thickness, compared to control OVX ddY mice. Moreover, treatment of OVX ddY mice with Ewha-18278 increased bone strength by increasing cortical bone thickness. We provide that Ewha-18278 displayed Nox inhibition and blocked the RANKL-dependent cell signaling cascade leading to reduced differentiation of OCs. Our results implicate Ewha-18278 as a novel therapeutic agent for the treatment of osteoporosis. PMID:26975635

  13. Detoxified pneumolysin derivative Plym2 directly protects against pneumococcal infection via induction of inflammatory cytokines.

    PubMed

    Lu, Jingcai; Sun, Tianxu; Hou, Hongjia; Xu, Man; Gu, Tiejun; Dong, Yunliang; Wang, Dandan; Chen, Pinxu; Wu, Chunlai; Liang, Chunshu; Sun, Shiyang; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2014-01-01

    Streptococcus pneumoniae is a major cause of infectious disease and complications worldwide, such as pneumonia, otitis media, bacteremia and meningitis. New generation protein-based pneumococcal vaccines are recognized as alternative vaccine candidates. Pneumolysin (Ply) is a cholesterol-dependent cytolysin produced by all clinical isolates of S. pneumoniae. Our research group previously developed a highly detoxified Ply mutant designated Plym2 by replacement of two animo acids (C428G and W433F). Exhibiting undetectable levels of cytotoxicity, Plym2 could still elicit high titer neutralizing antibodies against the native toxin. However, evaluation of the active immunoprotective effects of Plym2 by subcutaneous immunization and lethal challenge with S. pneumoniae in mice did not yield favorable results. In the present work, we confirmed the previous observations by using passive immunization and systemic challenge. Results of the passive immunization were consistent with those of active immunization. Further experiments were conducted to explain the inability of high titer neutralizing antibodies against Ply to protect mice from S. pneumoniae challenge. Pneumococcal Ply is known to be the major factor responsible for the induction of inflammation that benefits the host. Proinflammatory cytokines facilitate the clearance of invaders by the recruitment and activation of leukocytes at the early infection stage. We demonstrated that Plym2 could induce proinflammatory cytokines similarly to wild-type Ply. A systemic infection model was used to clarify that Plym2 lacking cytolytic activity could protect mice from intraperitoneal challenge directly, while antibodies to the mutant had no effect. Therefore, the protective function of Plym2 may be due to its induction of proinflammatory cytokines. When used in the systemic infection model, Plym2 antibodies may block the induction of proinflammatory cytokines by Ply. These findings demonstrate that a Ply-based vaccine would

  14. [Stress-protective properties of lithium nicotinate--a new derivative of nicotinic acid].

    PubMed

    Kresiun, V I

    1984-03-01

    Experiments were made to study stress-protective properties of a new psychotropic agent lithium nicotinate developed on the basis of natural metabolites. Prophylactic treatment of the drug given in courses entails an increase in the physical endurance and work fitness, improvement of animals' orientation under stress, facilitating the avoidance behavior. These effects were particularly demonstrable in highly emotional animals. In these animals, stress produced a paralyzing action. According to the electro- and ballisto-cardiography, the drug prevented the stress-induced disorders of cardiovascular function. PMID:6538449

  15. PROCEDURES FOR DERIVING EQUILIBRIUM PARTITIONING SEDIMENT BENCHMARKS (ESBS) FOR THE PROTECTION OF BENTHIC ORGANISMS: METALS MIXTURES (CADMIUM, COPPER, LEAD, NICKEL, SILVER, AND ZINC)

    EPA Science Inventory

    This equilibrium partitioning sediment benchmark (ESB) document describes procedures to derive concentrations of metal mixtures in sediment which are protective of the presence of benthic organisms. The equilibrium partitioning (EqP) approach was chosen because it accounts for t...

  16. PROCEDURES FOR THE DERIVATION OF EQUILIBRIUM PARTITIONING SEDIMENT BENCHMARKS (ESBS) FOR THE PROTECTION OF BENTHIC ORGANISMS: COMPENDIUM OF TIER 2 VALUES FOR NONIONIC ORGANICS

    EPA Science Inventory

    This equilibrium partitioning sediment benchmark (ESB) document describes procedures to derive concentrations for 32 nonionic organic chemicals in sediment which are protective of the presence of freshwater and marine benthic organisms. The equilibrium partitioning (EqP) approach...

  17. Bone Marrow-Derived, Neural-Like Cells Have the Characteristics of Neurons to Protect the Peripheral Nerve in Microenvironment

    PubMed Central

    Guo, Shi-lei; Zhang, Zhi-ying; Zhi, Yun-xia; Han, Chang-jie; Zhou, Yu-hao; Liu, Fang; Lin, Hai-yan; Zhang, Chuan-sen

    2015-01-01

    Effective repair of peripheral nerve defects is difficult because of the slow growth of new axonal growth. We propose that “neural-like cells” may be useful for the protection of peripheral nerve destructions. Such cells should prolong the time for the disintegration of spinal nerves, reduce lesions, and improve recovery. But the mechanism of neural-like cells in the peripheral nerve is still unclear. In this study, bone marrow-derived neural-like cells were used as seed cells. The cells were injected into the distal end of severed rabbit peripheral nerves that were no longer integrated with the central nervous system. Electromyography (EMG), immunohistochemistry, and transmission electron microscopy (TEM) were employed to analyze the development of the cells in the peripheral nerve environment. The CMAP amplitude appeared during the 5th week following surgery, at which time morphological characteristics of myelinated nerve fiber formation were observed. Bone marrow-derived neural-like cells could protect the disintegration and destruction of the injured peripheral nerve. PMID:25861281

  18. Bone marrow-derived, neural-like cells have the characteristics of neurons to protect the peripheral nerve in microenvironment.

    PubMed

    Guo, Shi-Lei; Zhang, Zhi-Ying; Xu, Yan; Zhi, Yun-Xia; Han, Chang-Jie; Zhou, Yu-Hao; Liu, Fang; Lin, Hai-Yan; Zhang, Chuan-Sen

    2015-01-01

    Effective repair of peripheral nerve defects is difficult because of the slow growth of new axonal growth. We propose that "neural-like cells" may be useful for the protection of peripheral nerve destructions. Such cells should prolong the time for the disintegration of spinal nerves, reduce lesions, and improve recovery. But the mechanism of neural-like cells in the peripheral nerve is still unclear. In this study, bone marrow-derived neural-like cells were used as seed cells. The cells were injected into the distal end of severed rabbit peripheral nerves that were no longer integrated with the central nervous system. Electromyography (EMG), immunohistochemistry, and transmission electron microscopy (TEM) were employed to analyze the development of the cells in the peripheral nerve environment. The CMAP amplitude appeared during the 5th week following surgery, at which time morphological characteristics of myelinated nerve fiber formation were observed. Bone marrow-derived neural-like cells could protect the disintegration and destruction of the injured peripheral nerve. PMID:25861281

  19. Macrophage-derived Lipocalin-2 contributes to ischemic resistance mechanisms by protecting from renal injury

    PubMed Central

    Jung, Michaela; Brüne, Bernhard; Hotter, Georgina; Sola, Anna

    2016-01-01

    Renal ischemia-reperfusion injury triggers an inflammatory response associated to infiltrating macrophages which determines the further outcome of disease. Brown Norway rats are known to show endogenous resistance to ischemia-induced renal damage. By contrast, Sprague Dawley rats exhibit a higher susceptibility to ischemic injury. In order to ascertain cytoprotective mechanisms, we focused on the implication of lipocalin-2 protein in main resistance mechanisms in renal ischemia/reperfusion injury by using adoptive macrophage administration, genetically modified ex vivo either to overexpress or to knockdown lipocalin-2. In vitro experiments with bone marrow-derived macrophages both from Brown Norway rats and from Sprague Dawley rats under hypoxic conditions showed endogenous differences regarding cytokine and lipocalin-2 expression profile in the two strains. Most interestingly, we observed that macrophages of the resistant strain express significantly more lipocalin-2. In vivo studies showed that tubular epithelial cell apoptosis and renal injury significantly increased and reparative markers decreased in Brown Norway rats after injection of lipocalin-2-knockdown macrophages, while the administration of lipocalin-2-overexpressing cells significantly decreased Sprague Dawley susceptibility. These data point to a crucial role of macrophage-derived lipocalin-2 in endogenous cytoprotective mechanisms. We conclude that expression of lipocalin-2 in tissue-infiltrating macrophages is pivotal for kidney-intrinsic cytoprotective pathways during ischemia reperfusion injury. PMID:26911537

  20. Monocyte-derived extracellular Nampt-dependent biosynthesis of NAD(+) protects the heart against pressure overload.

    PubMed

    Yano, Masamichi; Akazawa, Hiroshi; Oka, Toru; Yabumoto, Chizuru; Kudo-Sakamoto, Yoko; Kamo, Takehiro; Shimizu, Yu; Yagi, Hiroki; Naito, Atsuhiko T; Lee, Jong-Kook; Suzuki, Jun-ichi; Sakata, Yasushi; Komuro, Issei

    2015-01-01

    Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in the salvage pathway for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, and thereby regulates the deacetylase activity of sirtuins. Here we show accommodative regulation of myocardial NAD(+) by monocyte-derived extracellular Nampt (eNampt), which is essential for hemodynamic compensation to pressure overload. Although intracellular Nampt (iNampt) expression was decreased in pressure-overloaded hearts, myocardial NAD(+) concentration and Sirt1 activity were preserved. In contrast, iNampt was up-regulated in spleen and monocytes, and circulating eNampt protein and nicotinamide mononucleotide (NMN), a key precursor of NAD(+), were significantly increased. Pharmacological inhibition of Nampt by FK866 or depletion of monocytes/macrophages by clodronate liposomes disrupted the homeostatic mechanism of myocardial NAD(+) levels and NAD(+)-dependent Sirt1 activity, leading to susceptibility to cardiomyocyte apoptosis and cardiac decompensation in pressure-overloaded mice. These biochemical and hemodynamic defects were prevented by systemic administration of NMN. Our studies uncover a crucial role of monocyte-derived eNampt in myocardial adaptation to pressure overload, and highlight a potential intervention controlling myocardial NAD(+) against heart failure. PMID:26522369

  1. Memory T Cell-Derived interferon-γ Instructs Potent Innate Cell Activation For Protective Immunity

    PubMed Central

    Soudja, Saidi M’Homa; Chandrabos, Ceena; Yakob, Ernest; Veenstra, Mike; Palliser, Deborah; Lauvau, Grégoire

    2014-01-01

    SUMMARY Cells of the innate immune system are essential for host defenses against primary microbial pathogen infections, yet their involvement in effective memory responses of vaccinated individuals has been poorly investigated. Here we show that memory T cells instruct innate cells to become potent effector cells in a systemic and a mucosal model of infection. Memory T cells controlled phagocyte, dendritic cell and NK or NK T cell mobilization and induction of a strong program of differentiation, which included their expression of effector cytokines and microbicidal pathways, all of which were delayed in non-vaccinated hosts. Disruption of IFN-γ-signaling in Ly6C+ monocytes, dendritic cells and macrophages impaired these processes and the control of pathogen growth. These results reveal how memory T cells, through rapid secretion of IFN-γ, orchestrate extensive modifications of host innate immune responses that are essential for effective protection of vaccinated hosts. PMID:24931122

  2. A Critical Protection Level Derived from Dengue Infection Mathematical Model Considering Asymptomatic and Symptomatic Classes

    NASA Astrophysics Data System (ADS)

    Anggriani, N.; Supriatna, A. K.; Soewono, E.

    2013-04-01

    In this paper we formulate a model of dengue fever transmission by considering the presence of asymptomatic and symptomatic compartments. The model takes the form as a system of differential equations representing a host-vector SIR (Susceptible - Infective -Recovered) disease transmission. It is assumed that both host and vector populations are constant. It is also assumed that reinfection of recovered hosts by the disease is possible due to a wanning immunity in human body. We analyze the model to determine the qualitative behavior of the model solution and use the concept of effective basic reproduction number (fraktur Rp) as a control criteria of the disease transmission. The effect of mosquito biting protection (e.g. by using insect repellent) is also considered. We compute the long-term ratio of the asymptomatic and symptomatic classes and show a condition for which the iceberg phenomenon could appear.

  3. The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction

    PubMed Central

    Sreekumar, Parameswaran G.; Ishikawa, Keijiro; Spee, Chris; Mehta, Hemal H.; Wan, Junxiang; Yen, Kelvin; Cohen, Pinchas; Kannan, Ram; Hinton, David R.

    2016-01-01

    Purpose To investigate the expression of humanin (HN) in human retinal pigment epithelial (hRPE) cells and its effect on oxidative stress–induced cell death, mitochondrial bioenergetics, and senescence. Methods Humanin localization in RPE cells and polarized RPE monolayers was assessed by confocal microscopy. Human RPE cells were treated with 150 μM tert-Butyl hydroperoxide (tBH) in the absence/presence of HN (0.5–10 μg/mL) for 24 hours. Mitochondrial respiration was measured by XF96 analyzer. Retinal pigment epithelial cell death and caspase-3 activation, mitochondrial biogenesis and senescence were analyzed by TUNEL, immunoblot analysis, mitochondrial DNA copy number, SA-β-Gal staining, and p16INK4a expression and HN levels by ELISA. Oxidative stress–induced changes in transepithelial resistance were studied in RPE monolayers with and without HN cotreatment. Results A prominent localization of HN was found in the cytoplasmic and mitochondrial compartments of hRPE. Humanin cotreatment inhibited tBH-induced reactive oxygen species formation and significantly restored mitochondrial bioenergetics in hRPE cells. Exogenous HN was taken up by RPE and colocalized with mitochondria. The oxidative stress–induced decrease in mitochondrial bioenergetics was prevented by HN cotreatment. Humanin treatment increased mitochondrial DNA copy number and upregulated mitochondrial transcription factor A, a key biogenesis regulator protein. Humanin protected RPE cells from oxidative stress–induced cell death by STAT3 phosphorylation and inhibiting caspase-3 activation. Humanin treatment inhibited oxidant-induced senescence. Polarized RPE demonstrated elevated cellular HN and increased resistance to cell death. Conclusions Humanin protected RPE cells against oxidative stress–induced cell death and restored mitochondrial function. Our data suggest a potential role for HN therapy in the prevention of retinal degeneration, including AMD. PMID:26990160

  4. Evaluation of a 7-Methoxycoumarin-3-carboxylic Acid Ester Derivative as a Fluorescent, Cell-Cleavable, Phosphonate Protecting Group.

    PubMed

    Wiemer, Andrew J; Shippy, Rebekah R; Kilcollins, Ashley M; Li, Jin; Hsiao, Chia-Hung Christine; Barney, Rocky J; Geng, M Lei; Wiemer, David F

    2016-01-01

    Cell-cleavable protecting groups often enhance cellular delivery of species that are charged at physiological pH. Although several phosphonate protecting groups have achieved clinical success, it remains difficult to use these prodrugs in live cells to clarify biological mechanisms. Here, we present a strategy that uses a 7-methoxycoumarin-3-carboxylic acid ester as a fluorescent protecting group. This strategy was applied to synthesis of an (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) analogue to assess cellular uptake and human Vγ9Vδ2 T cell activation. The fluorescent ester displayed low cellular toxicity (IC50 >100 μm) and strong T cell activation (EC50 =0.018 μm) relative to the unprotected anion (EC50 =23 μm). The coumarin-derived analogue allowed no-wash analysis of biological deprotection, which revealed rapid internalization of the prodrug. These results demonstrate that fluorescent groups can be applied both as functional drug delivery tools and useful biological probes of drug uptake. PMID:26503489

  5. Protection against experimental visceral leishmaniasis by immunostimulation with herbal drugs derived from Withania somnifera and Asparagus racemosus.

    PubMed

    Kaur, Sukhbir; Chauhan, Kalpana; Sachdeva, Heena

    2014-10-01

    Visceral leishmaniasis (VL) is a vector-borne parasitic disease targeting tissue macrophages. It is among the most neglected infectious diseases. As available therapeutics for treatment of this disease have many side effects, there is a need for safer alternatives. One of the immunopathological consequences of active visceral leishmaniasis is suppression of protective T-helper (Th)-1 cells and induction of disease-promoting Th-2 cells, and thus the treatment of VL relies on immunomodulation. In the current study, herbal drugs derived as whole-plant extracts of Asparagus racemosus and Withania somnifera were used to treat Leishmania donovani-infected BALB/c mice. Keeping the scenario of immunosuppression during VL in mind, the potential of these drugs in the restoration of murine Th-1-type protective immune responses was evaluated. To investigate the propensity of these drugs to treat VL, liver parasite load, delayed-type hypersensitivity responses and parasite-specific immunoglobulin levels were studied. Various biochemical and haematological tests were also carried out. A positive-control group used the standard drug treatment of sodium stibogluconate. Treatment of infected mice with A. racemosus and W. somnifera in combination at the higher dose of 200 mg (kg body weight)(-1) not only resulted in a successful reduction in parasite load but also generated protective Th1-type immune responses with normalization of biochemical and haematological parameters, suggesting their potential as potent anti-leishmanial agents. PMID:25082945

  6. Protective Effects of Nicotine Against Aminochrome-Induced Toxicity in Substantia Nigra Derived Cells: Implications for Parkinson’s Disease

    PubMed Central

    Muñoz, Patricia; Huenchuguala, Sandro; Paris, Irmgard; Cuevas, Carlos; Villa, Monica; Caviedes, Pablo; Segura-Aguilar, Juan

    2013-01-01

    Parkinson’s disease is a debilitating progressive neurodegenerative disorder that results from the loss of or damage to dopaminergic cells containing neuromelanin in the substantia nigra (SN). The underlying neurodegenerative mechanism(s), however, remain elusive. Aminochrome, the precursor of neuromelanin is an endogenous substance capable of inducing selective neurotoxicity to dopaminergic neurons in SN. Nicotine, on the other hand, may offer protective effects against dopaminergic cell damage induced by various neurotoxins including MPTP and salsolinol. In this study, we sought to determine whether nicotine may also protect against aminochrome-induced toxicity in SN derived RCSN-3 cells. Exposure of RCSN-3 cells to a combination of aminochrome (50 μM) and dicoumarol (50 μM) for 48 h induced approximately 70 % cell death. Pretreatment with nicotine, dose-dependently blocked this toxicity. The effects of nicotine in turn were dose-dependently blocked by mecamylamine, a non-selective nicotinic receptor antagonist. These results suggest involvement of nicotinic receptors in protective effects of nicotine against aminochrome-induced toxicity and provide further evidence for possible therapeutic effects of nicotine or nicotinic agonists in Parkinson’s disease. PMID:22528249

  7. Protective effect of some amino acids synthesized derivatives and their chelates on Escherichia coli under X-ray irradiation.

    PubMed

    Kirakosyan, G; Torgomyan, H; Malakyan, M; Bajinyan, S; Trchounian, A

    2013-08-01

    The protective effects of novel synthesized derivatives of some amino acids--nicotinyl-L-tyrosinate and nicotinyl-L-tryptophanate schiff bases and their Cu(II) and Mn(II) chelates on growth, survival and membrane-associated ATPase activity of E. coli under X-ray irradiation were investigated. The specific growth rate and survival of E. coli were decreased at 10, 20 and 30 Gy doses. However, as 30 Gy was found to be the most effective irradiation dose, it was chosen for studying the radio-protective properties of different compounds. These compounds could increase the bacterial cell protection against X-ray irradiation in concentration-dependent manner. They had a role in stimulation of synthesis or regulation of activity of metal-dependent enzymes, required for reversing the X-ray irradiation damage. The study may prove useful for further estimation of the effectiveness of different compounds as radio-protectors on bacteria and other cells, especially mammalian cells under X-ray irradiation. PMID:24772948

  8. Protective effect of reduced glutathione C60 derivative against hydrogen peroxide-induced apoptosis in HEK 293T cells.

    PubMed

    Huang, Jin; Zhou, Chi; He, Jun; Hu, Zheng; Guan, Wen-Chao; Liu, Sheng-Hong

    2016-06-01

    Hydrogen peroxide (H2O2) and free radicals cause oxidative stress, which induces cellular injuries, metabolic dysfunction, and even cell death in various clinical abnormalities. Fullerene (C60) is critical for scavenging oxygen free radicals originated from cell metabolism, and reduced glutathione (GSH) is another important endogenous antioxidant. In this study, a novel water-soluble reduced glutathione fullerene derivative (C60-GSH) was successfully synthesized, and its beneficial roles in protecting against H2O2-induced oxidative stress and apoptosis in cultured HEK 293T cells were investigated. Fourier Transform infrared spectroscopy and (1)H nuclear magnetic resonance were used to confirm the chemical structure of C60-GSH. Our results demonstrated that C60-GSH prevented the reactive oxygen species (ROS)-mediated cell damage. Additionally, C60-GSH pretreatment significantly attenuated H2O2-induced superoxide dismutase (SOD) consumption and malondialdehyde (MDA) elevation. Furthermore, C60-GSH inhibited intracellular calcium mobilization, and subsequent cell apoptosis via bcl-2/bax-caspase-3 signaling pathway induced by H2O2 stimulation in HEK 293T cells. Importantly, these protective effects of C60-GSH were superior to those of GSH. In conclusion, these results suggested that C60-GSH has potential to protect against H2O2-induced cell apoptosis by scavenging free radicals and maintaining intracellular calcium homeostasis without evident toxicity. PMID:27376803

  9. A Curcumin Derivative That Inhibits Vinyl Carbamate-Induced Lung Carcinogenesis via Activation of the Nrf2 Protective Response

    PubMed Central

    Shen, Tao; Jiang, Tao; Long, Min; Chen, Jun; Ren, Dong-Mei; Wong, Pak Kin

    2015-01-01

    Abstract Aims: Lung cancer has a high worldwide morbidity and mortality. The employment of chemopreventive agents is effective to reduce lung cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) mitigates insults from both exogenous and endogenous sources and thus has been verified as a target for chemoprevention. Curcumin has long been recognized as a chemopreventive agent, but poor bioavailability and weak Nrf2 induction have prohibited clinical application. Thus, we have developed new curcumin derivatives and tested their Nrf2 induction. Results: Based on curcumin, we synthesized curcumin analogs with five carbon linkages and established a structure–activity relationship for Nrf2 induction. Among these derivatives, bis[2-hydroxybenzylidene]acetone (BHBA) was one of the most potent Nrf2 inducers with minimal toxicity and improved pharmacological properties and was thus selected for further investigation. BHBA activated the Nrf2 pathway in the canonical Keap1-Cys151-dependent manner. Furthermore, BHBA was able to protect human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. More importantly, in an in vivo vinyl carbamate-induced lung cancer model in A/J mice, preadministration of BHBA significantly reduced lung adenocarcinoma, while curcumin failed to show any effects even at high doses. Innovation: The curcumin derivative, BHBA, is a potent inducer of Nrf2. It was demonstrated to protect against As(III) toxicity in lung epithelial cells in an Nrf2-dependent manner. Furthermore, compared with curcumin, BHBA displayed improved chemopreventive activities in a carcinogen-induced lung cancer model. Conclusion: Taken together, our results demonstrate that BHBA, a curcumin analog with improved Nrf2-activating and chemopreventive activities both in vitro and in vivo, could be developed into a chemoprotective pharmacological agent. Antioxid. Redox Signal. 23, 651–664. PMID:25891177

  10. Expert-derived monitoring thresholds for impacts of megaherbivores on vegetation cover in a protected area.

    PubMed

    Smit, Izak P J; Landman, Marietjie; Cowling, Richard M; Gaylard, Angela

    2016-07-15

    Monitoring is meant to inform conservation authorities, yet managers often don't know when to respond to monitoring results. One of the reasons is that management often lacks consensus on monitoring thresholds for intervention. This results in aimless monitoring without a clear directive on when monitoring indicates a trajectory towards an unacceptable state or impending change, which possibly necessitates intervention. Although experts rarely provide simple, measureable and quantifiable monitoring thresholds as required by management, they are often more comfortable expressing opinions on whether a specific area is desirable or not. This allows thresholds to be reverse engineered: by getting experts to identify sites as desirable and undesirable, field variables can subsequently be measured to derive the boundary between subjectively identified desirable and undesirable states. Such a boundary provides a defendable point for management to assess and consider intervention. Here we describe the identification of monitoring thresholds by defining the limits of desirable canopy cover, derived from expert stakeholder preferences, in the Sundays Spekboom Thicket vegetation of the Addo Elephant National Park, South Africa. The park has experienced variable utilization intensity by large herbivores, especially elephant. For years managers have grappled with the question of what percentage shrub canopy cover is desirable as a management target, but science has failed to provide this. Using experts to assess pre-selected sites as desirable or undesirable across a range of canopy covers, we showed that a canopy cover of ∼65% (±15%) would be desirable for expert stakeholders. We then used satellite imagery to map canopy cover, providing managers for the first time with a large-scale map of canopy cover, indicating desirability status. This approach was useful for facilitating joint-decision making between conservation agencies and stakeholders on tangible indicators of

  11. The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites.

    PubMed

    Kaiko, Gerard E; Ryu, Stacy H; Koues, Olivia I; Collins, Patrick L; Solnica-Krezel, Lilianna; Pearce, Edward J; Pearce, Erika L; Oltz, Eugene M; Stappenbeck, Thaddeus S

    2016-06-16

    In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem/progenitor cells at their base. The mammalian intestine also harbors a diverse array of microbial metabolite compounds that potentially modulate stem/progenitor cell activity. Unbiased screening identified butyrate, a prominent bacterial metabolite, as a potent inhibitor of intestinal stem/progenitor proliferation at physiologic concentrations. During homeostasis, differentiated colonocytes metabolized butyrate likely preventing it from reaching proliferating epithelial stem/progenitor cells within the crypt. Exposure of stem/progenitor cells in vivo to butyrate through either mucosal injury or application to a naturally crypt-less host organism led to inhibition of proliferation and delayed wound repair. The mechanism of butyrate action depended on the transcription factor Foxo3. Our findings indicate that mammalian crypt architecture protects stem/progenitor cell proliferation in part through a metabolic barrier formed by differentiated colonocytes that consume butyrate and stimulate future studies on the interplay of host anatomy and microbiome metabolism. PMID:27264604

  12. Protective effects of adipose-derived stem cells secretome on human dermal fibroblasts from ageing damages

    PubMed Central

    Wang, Ting; Guo, Shu; Liu, Xuehui; Xv, Nan; Zhang, Shuangyi

    2015-01-01

    Background: Combined effects of intrinsic and extrinsic ageing factors on skin tissue and the therapies have been rarely studied before. ADSCs have gained popularity in anti-ageing field, which may provide promising methods to fight against skin ageing. Objective: To find out the fate of HDFs exposed to intrinsic or extrinsic ageing factors or both of them and further examine the impacts of ADSC-CM on the damaged HDFs. Methods: We irradiated HDFs with UVB at different senescent levels, and then treated them with ADSC-CM. After 48 h, we detected cellular proliferative activity, morphology, SA-β-Gal expression, apoptosis, mRNA expression of collagen I, collagen III and elastin. Results: Intrinsic ageing factors inhibited cellular proliferation, increased senescent ratio and reduced mRNA expression of collagen I, collagen III and elastin, so did UVB, except for its induction of elastin mRNA expression. Furthermore, ADSC-CM treatment can slightly or significantly improve cellular proliferative activity and restore functions both in irradiated and non-irradiated HDFs. Besides, ADSC-CM treatment decreased cellular apoptosis and senescence induced by UVB but had no obvious effect on cellular senescence induced by intrinsic ageing factors. The results were similar in three generations of HDFs, yet in different degrees. Conclusions: The results suggest that ADSCs secretome protect HDFs from ageing damages but with some limitations. PMID:26884843

  13. Immunization with a Neural-Derived Peptide Protects the Spinal Cord from Apoptosis after Traumatic Injury

    PubMed Central

    Rodríguez-Barrera, Roxana; Fernández-Presas, Ana M.; García, Elisa; Flores-Romero, Adrian; Martiñón, Susana; González-Puertos, Viridiana Yazmín; Mestre, Humberto; Flores-Dominguez, Carmina; Rodriguez-Mata, Verónica; Königsberg, Mina; Solano, Sandra; Ibarra, Antonio

    2013-01-01

    Apoptosis is one of the most destructive mechanisms that develop after spinal cord (SC) injury. Immunization with neural-derived peptides (INDPs) such as A91 has shown to reduce the deleterious proinflammatory response and the amount of harmful compounds produced after SC injury. With the notion that the aforementioned elements are apoptotic inducers, we hypothesized that INDPs would reduce apoptosis after SC injury. In order to test this assumption, adult rats were subjected to SC contusion and immunized either with A91 or phosphate buffered saline (PBS; control group). Seven days after injury, animals were euthanized to evaluate the number of apoptotic cells at the injury site. Apoptosis was evaluated using DAPI and TUNEL techniques; caspase-3 activity was also evaluated. To further elucidate the mechanisms through which A91 exerts this antiapoptotic effects we quantified tumor necrosis factor-alpha (TNF-α). To also demonstrate that the decrease in apoptotic cells correlated with a functional improvement, locomotor recovery was evaluated. Immunization with A91 significantly reduced the number of apoptotic cells and decreased caspase-3 activity and TNF-α concentration. Immunization with A91 also improved the functional recovery of injured rats. The present study shows the beneficial effect of INDPs on preventing apoptosis and provides more evidence on the neuroprotective mechanisms exerted by this strategy. PMID:24236295

  14. Squamosamide derivative FLZ protects dopaminergic neurons against inflammation-mediated neurodegeneration through the inhibition of NADPH oxidase activity

    PubMed Central

    Zhang, Dan; Hu, Xiaoming; Wei, Sung-Jen; Liu, Jie; Gao, Huiming; Qian, Li; Wilson, Belinda; Liu, Gengtao; Hong, Jau-Shyong

    2008-01-01

    Background Inflammation plays an important role in the pathogenesis of Parkinson's disease (PD) through over-activation of microglia, which consequently causes the excessive production of proinflammatory and neurotoxic factors, and impacts surrounding neurons and eventually induces neurodegeneration. Hence, prevention of microglial over-activation has been shown to be a prime target for the development of therapeutic agents for inflammation-mediated neurodegenerative diseases. Methods For in vitro studies, mesencephalic neuron-glia cultures and reconstituted cultures were used to investigate the molecular mechanism by which FLZ, a squamosamide derivative, mediates anti-inflammatory and neuroprotective effects in both lipopolysaccharide-(LPS)- and 1-methyl-4-phenylpyridinium-(MPP+)-mediated models of PD. For in vivo studies, a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-(MPTP-) induced PD mouse model was used. Results FLZ showed potent efficacy in protecting dopaminergic (DA) neurons against LPS-induced neurotoxicity, as shown in rat and mouse primary mesencephalic neuronal-glial cultures by DA uptake and tyrosine hydroxylase (TH) immunohistochemical results. The neuroprotective effect of FLZ was attributed to a reduction in LPS-induced microglial production of proinflammatory factors such as superoxide, tumor necrosis factor-α (TNF-α), nitric oxide (NO) and prostaglandin E2 (PGE2). Mechanistic studies revealed that the anti-inflammatory properties of FLZ were mediated through inhibition of NADPH oxidase (PHOX), the key microglial superoxide-producing enzyme. A critical role for PHOX in FLZ-elicited neuroprotection was further supported by the findings that 1) FLZ's protective effect was reduced in cultures from PHOX-/- mice, and 2) FLZ inhibited LPS-induced translocation of the cytosolic subunit of p47PHOX to the membrane and thus inhibited the activation of PHOX. The neuroprotective effect of FLZ demonstrated in primary neuronal-glial cultures was further

  15. Derivation of freshwater quality criteria for zinc using interspecies correlation estimation models to protect aquatic life in China.

    PubMed

    Feng, C L; Wu, F C; Dyer, S D; Chang, H; Zhao, X L

    2013-01-01

    Species sensitivity distributions (SSDs) are usually used in the development of water quality criteria and require a large number of toxicity values to define a hazard level to protect the majority of species. However, some toxicity data for certain chemicals are limited, especially for endangered and threatened species. Thus, it is important to predict the unknown species toxicity data using available toxicity data. To address this need, interspecies correlation estimation (ICE) models were developed by US EPA to predict acute toxicity of chemicals to diverse species based on a more limited data set of surrogate species toxicity data. Use of SSDs generated from ICE models allows for the prediction of protective water quality criteria, such as the HC5 (hazard concentration, 5th percentile). In the present study, we tested this concept using toxicity data collected for zinc. ICE-based-SSDs were generated using three surrogate species (common carp (Cyprinus carpio), rainbow trout (Oncorhynchus mykiss), and Daphnia magna) and compared with the measured-based SSD and corresponding HC5. The results showed that no significant differences were observed between the ICE- and the measured-based SSDs and HC5s. Furthermore, the examination of species placements within the SSDs indicated that the most sensitive species to zinc were invertebrates, especially crustaceans. Given the similarity of SSD and HC5s for zinc, the use of ICE to derive potential water quality criteria for diverse chemicals in China is proposed. Further, a combination of measured and ICE-derived data will prove useful for assessing water quality and chemical risks in the near future. PMID:23058200

  16. Bone marrow-derived microglia-based neurturin delivery protects against dopaminergic neurodegeneration in a mouse model of Parkinson's disease.

    PubMed

    Biju, K C; Santacruz, Rene A; Chen, Cang; Zhou, Qing; Yao, Jiemin; Rohrabaugh, Sara L; Clark, Robert A; Roberts, James L; Phillips, Kimberley A; Imam, Syed Z; Li, Senlin

    2013-02-22

    Although neurotrophic factors have long been recognized as potent agents for protecting against neuronal degeneration, clinical success in treating Parkinson's disease and other neurodegenerative disorders has been hindered by difficulties in delivery of trophic factors across the blood brain barrier (BBB). Bone marrow hematopoietic stem cell-based gene therapy is emerging as a promising tool for overcoming drug delivery problems, as myeloid cells can cross the BBB and are recruited in large numbers to sites of neurodegeneration, where they become activated microglia that can secrete trophic factors. We tested the efficacy of bone marrow-derived microglial delivery of neurturin (NTN) in protecting dopaminergic neurons against neurotoxin-induced death in mice. Bone marrow cells were transduced ex vivo with lentivirus expressing the NTN gene driven by a synthetic macrophage-specific promoter. Infected bone marrow cells were then collected and transplanted into recipient animals. Eight weeks after transplantation, the mice were injected with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropuridine (MPTP) for seven days to induce dopaminergic neurodegeneration. Microglia-mediated NTN delivery dramatically ameliorated MPTP-induced degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and their terminals in the striatum. Microglia-mediated NTN delivery also induced significant recovery of synaptic marker staining in the striatum of MPTP-treated animals. Functionally, NTN treatment restored MPTP-induced decline in general activity, rearing behavior, and food intake. Thus, bone marrow-derived microglia can serve as cellular vehicles for sustained delivery of neurotrophic factors capable of mitigating dopaminergic injury. PMID:23295906

  17. A new synthesis of lysophosphatidylcholines and related derivatives. Use of p-toluenesulfonate for hydroxyl group protection.

    PubMed

    Rosseto, Renato; Bibak, Niloufar; DeOcampo, Rosemarie; Shah, Trishul; Gabrielian, Ara; Hajdu, Joseph

    2007-03-01

    A new stereoselective synthesis of lysophosphatidylcholines is reported. The synthesis is based upon (1) the use of 3-p-toluenesulfonyl-sn-glycerol to provide the stereocenter for construction of the optically active lysophospholipid molecule, (2) tetrahydropyranylation of the secondary alcohol function to achieve orthogonal protection of the sn-2- and sn-3-glycerol positions, and (3) elaboration of the phosphodiester headgroup using a 2-chloro-1,3,2-dioxaphospholane/trimethylamine sequence. In the course of developing the synthesis it has been discovered that methoxyacetate displacement of the sn-3-p-toluenesulfonate yields a reactive methoxyacetyl ester, which in turn can be selectively cleaved with methanol/tert-butylamine, while the ester group at the sn-1-position remains unaffected. The sequence has been shown to be suitable for preparation of spectroscopically labeled lysophosphatidylcholines. One of these compounds was readily converted to a double-labeled mixed-chain phosphatidylcholine applicable for real-time fluorescence resonance energy transfer (FRET) assay of lipolytic enzymes. In addition, the work led to new synthetic strategies based on chemoselective manipulation of the tosyl group in the presence of other base-labile groups such as FMOC derivatives that are often used for the protection of amino and hydroxyl groups in syntheses. PMID:17284078

  18. Protective effects of andrographolide derivative AL-1 on high glucose-induced oxidative stress in RIN-m cells.

    PubMed

    Yan, Hui; Li, Yongmei; Yang, Yali; Zhang, Zaijun; Zhang, Gaoxiao; Sun, Yewei; Yu, Pei; Wang, Yuqiang; Xu, Lipeng

    2016-01-01

    AL-1 is a novel andrographolide derivative synthesized by conjugating andrographolide and alpha lipoic acid. AL-1 has been found to increase insulin secretion, decrease blood glucose level and protect β-cell mass and function in alloxan-induced diabetic mouse model. However, the protective mechanism of AL-1 on high glucose-induced pancreatic β-cell injury is still not clear. In the present study, we found that AL-1 reduced reactive oxygen species (ROS) and nitric oxide (NO) generation induced by high glucose in RIN-m cells, and which elevated the activities of superoxide dismutase (SOD) and catalase (CAT). In addition, AL-1 increased the expression of NF-E2-related factor 2 (Nrf2), thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO- 1) proteins in RIN-m cells. These results suggest that AL-1 prevented RIN-m cells from high glucose-induced oxidative damage via upregulation of Nrf2 signaling pathway. PMID:26391852

  19. Derivation of Ecological Protective Concentration using the Probabilistic Ecological Risk Assessment applicable for Korean Water Environment: (I) Cadmium

    PubMed Central

    Nam, Sun-Hwa; Lee, Woo-Mi

    2012-01-01

    Probabilistic ecological risk assessment (PERA) for deriving ecological protective concentration (EPC) was previously suggested in USA, Australia, New Zealand, Canada, and Netherland. This study suggested the EPC of cadmium (Cd) based on the PERA to be suitable to Korean aquatic ecosystem. First, we collected reliable ecotoxicity data from reliable data without restriction and reliable data with restrictions. Next, we sorted the ecotoxicity data based on the site-specific locations, exposure duration, and water hardness. To correct toxicity by the water hardness, EU’s hardness corrected algorithm was used with slope factor 0.89 and a benchmark of water hardness 100. EPC was calculated according to statistical extrapolation method (SEM), statistical extrapolation methodAcute to chronic ratio (SEMACR), and assessment factor method (AFM). As a result, aquatic toxicity data of Cd were collected from 43 acute toxicity data (4 Actinopterygill, 29 Branchiopoda, 1 Polychaeta, 2 Bryozoa, 6 Chlorophyceae, 1 Chanophyceae) and 40 chronic toxicity data (2 Actinopterygill, 23 Branchiopoda, 9 Chlorophyceae, 6 Macrophytes). Because toxicity data of Cd belongs to 4 classes in taxonomical classification, acute and chronic EPC (11.07 μg/l and 0.034 μg/l, respectively) was calculated according to SEM technique. These values were included in the range of international EPCs. This study would be useful to establish the ecological standard for the protection of aquatic ecosystem in Korea. PMID:24278601

  20. Adipose Tissue-Derived Stem Cell Secreted IGF-1 Protects Myoblasts from the Negative Effect of Myostatin

    PubMed Central

    Gehmert, Sebastian; Nerlich, Michael; Gosau, Martin; Klein, Silvan; Schreml, Stephan; Prantl, Lukas

    2014-01-01

    Myostatin, a TGF-β family member, is associated with inhibition of muscle growth and differentiation and might interact with the IGF-1 signaling pathway. Since IGF-1 is secreted at a bioactive level by adipose tissue-derived mesenchymal stem cells (ASCs), these cells (ASCs) provide a therapeutic option for Duchenne Muscular Dystrophy (DMD). But the protective effect of stem cell secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the present study murine myoblasts were exposed to myostatin under presence of ASCs conditioned medium and investigated for proliferation and apoptosis. The protective effect of IGF-1 was further examined by using IGF-1 neutralizing and receptor antibodies as well as gene silencing RNAi technology. MyoD expression was detected to identify impact of IGF-1 on myoblasts differentiation when exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore, IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside fusion and transdifferentiation the beneficial effect of ASCs is mediated by paracrine secreted cytokines, particularly IGF-1. The present study underlines the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and other dystrophic muscle diseases. PMID:24575400

  1. Naringin protects human adipose-derived mesenchymal stem cells against hydrogen peroxide-induced inhibition of osteogenic differentiation.

    PubMed

    Wang, Lei; Zhang, Yu-Ge; Wang, Xiu-Mei; Ma, Long-Fei; Zhang, Yuan-Min

    2015-12-01

    Extensive evidence indicates that oxidative stress plays a pivotal role in the development of osteoporosis. We show that naringin, a natural antioxidant and anti-inflammatory compound, effectively protects human adipose-derived mesenchymal stem cells (hADMSCs) against hydrogen peroxide (H2O2)-induced inhibition of osteogenic differentiation. Naringin increased viability of hAMDSCs and attenuated H2O2-induced cytotoxicity. Naringin also reversed H2O2-induced oxidative stress. Oxidative stress induced by H2O2 inhibits osteogenic differentiation by decreasing alkaline phosphatase (ALP) activity, calcium content and mRNA expression levels of osteogenesis marker genes RUNX2 and OSX in hADMSCs. However, addition of naringin leads to a significant recovery, suggesting the protective effects of naringin against H2O2-induced inhibition of osteogenic differentiation. Furthermore, the H2O2-induced decrease of protein expressions of β-catenin and clyclin D1, two important transcriptional regulators of Wnt-signaling, was successfully rescued by naringin treatment. Also, in the presence of Wnt inhibitor DKK-1, naringin is no longer effective in stimulating ALP activity, increasing calcium content and mRNA expression levels of RUNX2 and OSX in H2O2-exposed hADMSCs. These data clearly demonstrates that naringin protects hADMSCs against oxidative stress-induced inhibition of osteogenic differentiation, which may involve Wnt signaling pathway. Our work suggests that naringin may be a useful addition to the treatment armamentarium for osteoporosis and activation of Wnt signaling may represent attractive therapeutic strategy for the treatment of degenerative disease of bone tissue. PMID:26482937

  2. Chimeric Newcastle Disease Virus Protects Chickens against Avian Influenza in the Presence of Maternally Derived NDV Immunity

    PubMed Central

    Steglich, Constanze; Grund, Christian; Ramp, Kristina; Breithaupt, Angele; Höper, Dirk; Keil, Günther; Veits, Jutta; Ziller, Mario; Granzow, Harald; Mettenleiter, Thomas C.; Römer-Oberdörfer, Angela

    2013-01-01

    Newcastle disease virus (NDV), an avian paramyxovirus type 1, is a promising vector for expression of heterologous proteins from a variety of unrelated viruses including highly pathogenic avian influenza virus (HPAIV). However, pre-existing NDV antibodies may impair vector virus replication, resulting in an inefficient immune response against the foreign antigen. A chimeric NDV-based vector with functional surface glycoproteins unrelated to NDV could overcome this problem. Therefore, an NDV vector was constructed which carries the fusion (F) and hemagglutinin-neuraminidase (HN) proteins of avian paramyxovirus type 8 (APMV-8) instead of the corresponding NDV proteins in an NDV backbone derived from the lentogenic NDV Clone 30 and a gene expressing HPAIV H5 inserted between the F and HN genes. After successful virus rescue by reverse genetics, the resulting chNDVFHN PMV8H5 was characterized in vitro and in vivo. Expression and virion incorporation of the heterologous proteins was verified by Western blot and electron microscopy. Replication of the newly generated recombinant virus was comparable to parental NDV in embryonated chicken eggs. Immunization with chNDVFHN PMV8H5 stimulated full protection against lethal HPAIV infection in chickens without as well as with maternally derived NDV antibodies. Thus, tailored NDV vector vaccines can be provided for use in the presence or absence of routine NDV vaccination. PMID:24023747

  3. Adipose-Derived Stromal Cells Protect Intervertebral Disc Cells in Compression: Implications for Stem Cell Regenerative Disc Therapy

    PubMed Central

    Sun, Zhen; Luo, Beier; Liu, Zhi-Heng; Samartzis, Dino; Liu, Zhongyang; Gao, Bo; Huang, Liangliang; Luo, Zhuo-Jing

    2015-01-01

    Introduction: Abnormal biomechanics plays a role in intervertebral disc degeneration. Adipose-derived stromal cells (ADSCs) have been implicated in disc integrity; however, their role in the setting of mechanical stimuli upon the disc's nucleus pulposus (NP) remains unknown. As such, the present study aimed to evaluate the influence of ADSCs upon NP cells in compressive load culture. Methods: Human NP cells were cultured in compressive load at 3.0MPa for 48 hours with or without ADSCs co-culture (the ratio was 50:50). We used flow cytometry, live/dead staining and scanning electron microscopy (SEM) to evaluate cell death, and determined the expression of specific apoptotic pathways by characterizing the expression of activated caspases-3, -8 and -9. We further used real-time (RT-) PCR and immunostaining to determine the expression of the extracellular matrix (ECM), mediators of matrix degradation (e.g. MMPs, TIMPs and ADAMTSs), pro-inflammatory factors and NP cell phenotype markers. Results: ADSCs inhibited human NP cell apoptosis via suppression of activated caspase-9 and caspase-3. Furthermore, ADSCs protected NP cells from the degradative effects of compressive load by significantly up-regulating the expression of ECM genes (SOX9, COL2A1 and ACAN), tissue inhibitors of metalloproteinases (TIMPs) genes (TIMP-1 and TIMP-2) and cytokeratin 8 (CK8) protein expression. Alternatively, ADSCs showed protective effect by inhibiting compressive load mediated increase of matrix metalloproteinases (MMPs; MMP-3 and MMP-13), disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs; ADAMTS-1 and 5), and pro-inflammatory factors (IL-1beta, IL-6, TGF-beta1 and TNF-alpha). Conclusions: Our study is the first in vitro study assessing the impact of ADSCs on NP cells in an un-physiological mechanical stimulation culture environment. Our study noted that ADSCs protect compressive load induced NP cell death and degradation by inhibition of activated caspase-9 and -3

  4. Brain-Derived Neurotrophic Factor Regulates TRPC3/6 Channels and Protects Against Myocardial Infarction in Rodents

    PubMed Central

    Hang, Pengzhou; Zhao, Jing; Cai, Benzhi; Tian, Shanshan; Huang, Wei; Guo, Jing; Sun, Chuan; Li, Yue; Du, Zhimin

    2015-01-01

    Background: Brain-derived neurotrophic factor (BDNF) is associated with coronary artery diseases. However, its role and mechanism in myocardial infarction (MI) is not fully understood. Methods: Wistar rat and Kunming mouse model of MI were induced by the ligation of left coronary artery. Blood samples were collected from MI rats and patients. Plasma BDNF level, protein expression of BDNF, tropomyosin-related kinase B (TrkB) and its downstream transient receptor potential canonical (TRPC)3/6 channels were examined by enzyme-linked immunosorbent assay and Western blot. Infarct size, cardiac function and cardiomyocyte apoptosis were measured after intra-myocardium injection with recombinant human BDNF. Protective role of BDNF against cardiomyocyte apoptosis was confirmed by BDNF scavenger TrkB-Fc. The regulation of TRPC3/6 channels by BDNF was validated by pretreating with TRPC blocker (2-Aminoethyl diphenylborinate, 2-APB) and TRPC3/6 siRNAs. Results: Circulating BDNF was significantly enhanced in MI rats and patients. Protein expression of BDNF, TrkB and TRPC3/6 channels were upregulated in MI. 3 days post-MI, BDNF treatment markedly reduced the infarct size and serum lactate dehydrogenase activity. Meanwhile, echocardiography indicated that BDNF significantly improved cardiac function of MI mice. Furthermore, BDNF markedly inhibited cardiomyocyte apoptosis by upregulating Bcl-2 expression and downregulating caspase-3 expression and activity in ischemic myocardium. In neonatal rat ventricular myocytes, cell viability was dramatically increased by BDNF in hypoxia, which was restored by TrkB-Fc. Furthermore, protective role of BDNF against hypoxia-induced apoptosis was reversed by 2-APB and TRPC3/6 siRNAs. Conclusion: BDNF/TrkB alleviated cardiac ischemic injury and inhibited cardiomyocytes apoptosis by regulating TRPC3/6 channels, which provides a novel potential therapeutic candidate for MI. PMID:25892961

  5. Suppression of coronary atherosclerosis by helix B surface Peptide, a nonerythropoietic, tissue-protective compound derived from erythropoietin.

    PubMed

    Ueba, Hiroto; Shiomi, Masashi; Brines, Michael; Yamin, Michael; Kobayashi, Tsutomu; Ako, Junya; Momomura, Shin-Ichi; Cerami, Anthony; Kawakami, Masanobu

    2013-01-01

    Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (≈70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-α and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-α expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-α production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease. PMID:23648638

  6. A novel snake venom-derived GPIb antagonist, anfibatide, protects mice from acute experimental ischaemic stroke and reperfusion injury

    PubMed Central

    Li, Ting-Ting; Fan, Man-Li; Hou, Shi-Xiang; Li, Xiao-Yi; Barry, Devin M; Jin, Hui; Luo, Sheng-Yong; Kong, Feng; Lau, Lit-Fui; Dai, Xiang-Rong; Zhang, Guo-Hui; Zhou, Lan-Lan

    2015-01-01

    Background and Purpose Ischaemic stroke is a serious disease with limited therapy options. Glycoprotein (GP)Ib binding to von Willebrand factor (vWF) exposed at vascular injury initiates platelet adhesion and contributes to platelet aggregation. GPIb has been suggested as an effective target for antithrombotic therapy in stroke. Anfibatide is a GPIb antagonist derived from snake venom and we investigated its protective effect on experimental brain ischaemia in mice. Experimental Approach Focal cerebral ischaemia was induced by 90 min of transient middle cerebral artery occlusion (MCAO). These mice were then treated with anfibatide (4, 2, 1 μg·kg−1), injected i.v., after 90 min of MCAO, followed by 1 h of reperfusion. Tirofiban, a GPIIb/IIIα antagonist, was used as a positive control. Key Results Twenty-four hours after MCAO, anfibatide-treated mice showed significantly improved ischaemic lesions in a dose-dependent manner. The mice had smaller infarct volumes, less severe neurological deficits and histopathology of cerebrum tissues compared with the untreated MCAO mice. Moreover, anfibatide decreased the amount of GPIbα, vWF and accumulation of fibrin(ogen) in the vasculature of the ischaemic hemisphere. Tirofiban had similar effects on infarct size and fibrin(ogen) deposition compared with the MCAO group. Importantly, the anfibatide-treated mice showed a lower incidence of intracerebral haemorrhage and shorter tail bleeding time compared with the tirofiban-treated mice. Conclusions and Implications Our data indicate anfibatide is a safe GPIb antagonist that exerts a protective effect on cerebral ischaemia and reperfusion injury. Anfibatide is a promising candidate that could be beneficial for the treatment of ischaemic stroke. PMID:25917571

  7. Cystathionine-γ lyase-derived hydrogen sulfide mediates the cardiovascular protective effects of moxonidine in diabetic rats.

    PubMed

    El-Sayed, Shaimaa S; Zakaria, Mohamed N M; Abdel-Ghany, Rasha H; Abdel-Rahman, Abdel A

    2016-07-15

    Blunted cystathionine-γ lyase (CSE) activity (reduced endogenous H2S-level) is implicated in hypertension and myocardial dysfunction in diabetes. Here, we tested the hypothesis that CSE derived H2S mediates the cardiovascular protection conferred by the imidazoline I1 receptor agonist moxonidine in a diabetic rat model. We utilized streptozotocin (STZ; 55mg/kg i.p) to induce diabetes in male Wistar rats. Four weeks later, STZ-treated rats received vehicle, moxonidine (2 or 6mg/kg; gavage), CSE inhibitor DL-propargylglycine, (37.5mg/kg i.p) or DL-propargylglycine with moxonidine (6mg/kg) for 3 weeks. Moxonidine improved the glycemic state, and reversed myocardial hypertrophy, hypertension and baroreflex dysfunction in STZ-treated rats. Ex vivo studies revealed that STZ caused reductions in CSE expression/activity, H2S and nitric oxide (NO) levels and serum adiponectin and elevations in myocardial imidazoline I1 receptor expression, p38 and extracellular signal-regulated kinase, ERK1/2, phosphorylation and lipid peroxidation (expressed as malondialdehyde). Moxonidine reversed these biochemical responses, and suppressed the expression of death associated protein kinase-3. Finally, pharmacologic CSE inhibition (DL-propargylglycine) abrogated the favorable cardiovascular, glycemic and biochemical responses elicited by moxonidine. These findings present the first evidence for a mechanistic role for CSE derived H2S in the glycemic control and in the favorable cardiovascular effects conferred by imidazoline I1 receptor activation (moxonidine) in a diabetic rat model. PMID:27138707

  8. Protective Effect of Tempol on Buthionine Sulfoximine-Induced Mitochondrial Impairment in Hippocampal Derived HT22 Cells

    PubMed Central

    Salvi, Ankita; Patki, Gaurav; Khan, Eisha; Asghar, Mohammad; Salim, Samina

    2016-01-01

    Using a simulated oxidative stress model of hippocampus-derived immortalized cell line (HT22), we report that prooxidant buthionine sulfoximine (BSO, 1 mM, 14 h), without adversely affecting cell viability or morphology, induced oxidative stress by inhibiting glutathione synthesis. BSO treatment also significantly reduced superoxide dismutase (SOD) activity (p < 0.05) and significantly lowered total antioxidant capacity (p < 0.001) in HT22 cells when compared to vehicle treated control cells. Antioxidant tempol, a piperidine nitroxide considered a SOD mimetic, reversed BSO-induced decline in SOD activity (p < 0.01) and also increased BSO-induced decline in total antioxidant capacity (p < 0.05). Interestingly, BSO treatment significantly reduced mitochondrial oxygen consumption (p < 0.05), decreased mitochondrial membrane potential (p < 0.05), and lowered ATP production (p < 0.05) when compared to vehicle treated control cells, collectively indicative of mitochondrial impairment. Antioxidant tempol treatment mitigated all three indicators of mitochondrial impairment. We postulate that BSO-induced oxidative stress in HT22 cells caused mitochondrial impairment, and tempol by increasing SOD activity and improving antioxidant capacity presumably protected the cells from BSO-induced mitochondrial impairment. In conclusion, present study provides an interesting simulation of oxidative stress in hippocampal cells, which will serve as an excellent model to study mitochondrial functions. PMID:27069531

  9. Protective effects of a new phloretin derivative against UVB-induced damage in skin cell model and human volunteers.

    PubMed

    Shin, Seoungwoo; Kum, Hyunwoo; Ryu, Dehun; Kim, Minkyung; Jung, Eunsun; Park, Deokhoon

    2014-01-01

    The phenolic compound phloretin is a prominent member of the chemical class of dihydrochalcones. Phloretin is specifically found in apple and apple juice and known for its biological properties. We were particularly interested in its potential dermo-cosmetic applications. However, practical limitations of phloretin do exist due to its poor water-solubility. Phloretin was sulfonated with sulfuric acid (98%, wt) and mixed with saturated salt water to produce phloretin 3',3-disulfonate in order to increase its water-solubility. Here we reported the photoprotective effect of phloretin 3',3-disulfonate (PS), a new semi-synthetic derivative of phloretin. Results showed that PS attenuated cyclobutane pyrimidine dimer (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by ultraviolet B (UVB). The photoprotective effect of PS is tightly correlated to the enhancement of nucleotide excision repair (NER) gene expression. Furthemore, PS had inhibitory effects on UVB-induced release of the inflammatory mediators, such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of PS on human skin. Overall, the results demonstrated significant benefits of PS on the protection of keratinocytes against UVB-induced injuries and suggested its potential use in skin photoprotection. PMID:25334063

  10. Protective Effects of a New Phloretin Derivative against UVB-Induced Damage in Skin Cell Model and Human Volunteers

    PubMed Central

    Shin, Seoungwoo; Kum, Hyunwoo; Ryu, Dehun; Kim, Minkyung; Jung, Eunsun; Park, Deokhoon

    2014-01-01

    The phenolic compound phloretin is a prominent member of the chemical class of dihydrochalcones. Phloretin is specifically found in apple and apple juice and known for its biological properties. We were particularly interested in its potential dermo-cosmetic applications. However, practical limitations of phloretin do exist due to its poor water-solubility. Phloretin was sulfonated with sulfuric acid (98%, wt) and mixed with saturated salt water to produce phloretin 3',3-disulfonate in order to increase its water-solubility. Here we reported the photoprotective effect of phloretin 3',3-disulfonate (PS), a new semi-synthetic derivative of phloretin. Results showed that PS attenuated cyclobutane pyrimidine dimer (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by ultraviolet B (UVB). The photoprotective effect of PS is tightly correlated to the enhancement of nucleotide excision repair (NER) gene expression. Furthemore, PS had inhibitory effects on UVB-induced release of the inflammatory mediators, such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of PS on human skin. Overall, the results demonstrated significant benefits of PS on the protection of keratinocytes against UVB-induced injuries and suggested its potential use in skin photoprotection. PMID:25334063

  11. Suppression of Dendritic Cell-Derived IL-12 by Endogenous Glucocorticoids Is Protective in LPS-Induced Sepsis

    PubMed Central

    Mittelstadt, Paul R.; Castro, Ehydel; Ashwell, Jonathan D.

    2015-01-01

    Sepsis, an exaggerated systemic inflammatory response, remains a major medical challenge. Both hyperinflammation and immunosuppression are implicated as causes of morbidity and mortality. Dendritic cell (DC) loss has been observed in septic patients and in experimental sepsis models, but the role of DCs in sepsis, and the mechanisms and significance of DC loss, are poorly understood. Here, we report that mice with selective deletion of the glucocorticoid receptor (GR) in DCs (GRCD11c-cre) were highly susceptible to LPS-induced septic shock, evidenced by elevated inflammatory cytokine production, hypothermia, and mortality. Neutralizing anti-IL-12 antibodies prevented hypothermia and death, demonstrating that endogenous GC-mediated suppression of IL-12 is protective. In LPS-challenged GRCD11c-cre mice, CD8+ DCs were identified as the major source of prolonged IL-12 production, which correlated with elevations of NK cell-derived IFN-γ. In addition, the loss of GR in CD11c+ cells rescued LPS-induced loss of CD8+ DCs but not other DC subsets. Unlike wild-type animals, exposure of GRCD11c-cre mice to low-dose LPS did not induce CD8+ DC loss or tolerance to subsequent challenge with high dose, but neutralization of IL-12 restored the ability of low-dose LPS to tolerize. Therefore, endogenous glucocorticoids blunt LPS-induced inflammation and promote tolerance by suppressing DC IL-12 production. PMID:26440998

  12. Comparative study of Zn deficiency in L. sativa and B. oleracea plants: NH4(+) assimilation and nitrogen derived protective compounds.

    PubMed

    Navarro-León, Eloy; Barrameda-Medina, Yurena; Lentini, Marco; Esposito, Sergio; Ruiz, Juan M; Blasco, Begoña

    2016-07-01

    Zinc (Zn) deficiency is a major problem in agricultural crops of many world regions. N metabolism plays an essential role in plants and changes in their availability and their metabolism could seriously affect crop productivity. The main objective of the present work was to perform a comparative analysis of different strategies against Zn deficiency between two plant species of great agronomic interest such as Lactuca sativa cv. Phillipus and Brassica oleracea cv. Bronco. For this, both species were grown in hydroponic culture with different Zn doses: 10μM Zn as control and 0.01μM Zn as deficiency treatment. Zn deficiency treatment decreased foliar Zn concentration, although in greater extent in B. oleracea plants, and caused similar biomass reduction in both species. Zn deficiency negatively affected NO3(-) reduction and NH4(+) assimilation and enhanced photorespiration in both species. Pro and GB concentrations were reduced in L. sativa but they were increased in B. oleracea. Finally, the AAs profile changed in both species, highlighting a great increase in glycine (Gly) concentration in L. sativa plants. We conclude that L. sativa would be more suitable than B. oleracea for growing in soils with low availability of Zn since it is able to accumulate a higher Zn concentration in leaves with similar biomass reduction. However, B. oleracea is able to accumulate N derived protective compounds to cope with Zn deficiency stress. PMID:27181942

  13. Bone marrow-derived mesenchymal stem cells in three-dimensional culture promote neuronal regeneration by neurotrophic protection and immunomodulation.

    PubMed

    Han, Sufang; Wang, Bin; Li, Xing; Xiao, Zhifeng; Han, Jin; Zhao, Yannan; Fang, Yongxiang; Yin, Yanyun; Chen, Bing; Dai, Jianwu

    2016-07-01

    Accumulating evidence has revealed three-dimensional (3D) culture could better mimic the stem cell niche in vivo in comparison with conventional two-dimensional (2D) culture. In this study, we found that bone marrow derived mesenchymal stem cells (BMSCs) cultured in 3D collagen scaffold (3D BMSCs) exhibited distinctive features including significantly enhancing neurotrophic factor secretions and reducing macrophage activations challenged by lipopolysaccharide (LPS) in vitro. To further evaluate 3D BMSCs' potential benefits to the regeneration of spinal cord injury (SCI), the 3D and 2D BMSCs were respectively implanted in rat hemisected SCI. Compared with 2D cohort, 3D BMSCs transplantation significantly reduced the expressions of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 at 5 days after transplantation, markedly enhanced axonal regeneration, and promoted motor functional recovery during 8 weeks of observation. When Nocodazole was used to depolymerize the cytoskeleton of 3D BMSCs, the changed expressions of neurotrophic factors and inflammatory cytokines were blunted, at least partially. Thus synergistic effects of neuronal protection and immunomodulation of 3D BMSCs may lead to a better functional recovery of SCI and the underlying mechanism may involve the alteration of their cellular morphology because of 3D culture. This study contributes to a better understanding of the cellular characteristics of 3D BMSCs and provides a novel strategy to promote the repair of the injured spinal cord. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1759-1769, 2016. PMID:26990583

  14. Protecting Neural Structures and Cognitive Function During Prolonged Space Flight by Targeting the Brain Derived Neurotrophic Factor Molecular Network

    NASA Technical Reports Server (NTRS)

    Schmidt, M. A.; Goodwin, T. J.

    2014-01-01

    Brain derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophin in the human nervous system. BDNF is implicated in production of new neurons from dentate gyrus stem cells (hippocampal neurogenesis), synapse formation, sprouting of new axons, growth of new axons, sprouting of new dendrites, and neuron survival. Alterations in the amount or activity of BDNF can produce significant detrimental changes to cortical function and synaptic transmission in the human brain. This can result in glial and neuronal dysfunction, which may contribute to a range of clinical conditions, spanning a number of learning, behavioral, and neurological disorders. There is an extensive body of work surrounding the BDNF molecular network, including BDNF gene polymorphisms, methylated BDNF gene promoters, multiple gene transcripts, varied BDNF functional proteins, and different BDNF receptors (whose activation differentially drive the neuron to neurogenesis or apoptosis). BDNF is also closely linked to mitochondrial biogenesis through PGC-1alpha, which can influence brain and muscle metabolic efficiency. BDNF AS A HUMAN SPACE FLIGHT COUNTERMEASURE TARGET Earth-based studies reveal that BDNF is negatively impacted by many of the conditions encountered in the space environment, including oxidative stress, radiation, psychological stressors, sleep deprivation, and many others. A growing body of work suggests that the BDNF network is responsive to a range of diet, nutrition, exercise, drug, and other types of influences. This section explores the BDNF network in the context of 1) protecting the brain and nervous system in the space environment, 2) optimizing neurobehavioral performance in space, and 3) reducing the residual effects of space flight on the nervous system on return to Earth

  15. Protective effect of polydatin on learning and memory impairments in neonatal rats with hypoxic‑ischemic brain injury by up‑regulating brain‑derived neurotrophic factor.

    PubMed

    Sun, Jin; Qu, Yunxia; He, Huiming; Fan, Xiaolei; Qin, Yuanhua; Mao, Weifeng; Xu, Lixin

    2014-12-01

    Polydatin is a key component of Polygonum cuspidatum, a herb with medical and nutritional value. The present study investigated the protective effect of polydatin against learning and memory impairment in neonatal rats with hypoxic‑ischemic brain injury (HIBI). The unilateral common carotid artery ligation method was used to generate neonatal HIBI rats. Y‑maze testing revealed that rats with HIBI exhibited memory impairment, while rats with HIBI treated with polydatin displayed enhanced long‑term learning and memory. Of note, polydatin was found to upregulate the expression of hippocampal brain‑derived neurotrophic factor (BDNF) in rats with HIBI. BDNF has a role in protecting HIBI‑induced brain tissue injury and alleviating memory impairment. These findings showed that polydatin had a protective effect against learning and memory impairment in neonatal rats with HIBI and that the protective effect may be mediated through the upregulation of BDNF. PMID:25241777

  16. Defining the mechanism(s) of protection by cytolytic CD8 T cells against a cryptic epitope derived from a retroviral alternative reading frame

    PubMed Central

    Rutkowski, Melanie R.; Ho, On; Green, William R.

    2009-01-01

    The biological significance of protective CD8 T-cell-mediated responses against non-traditional alternative reading frame epitopes remains relatively unknown. Cytolytic CD8 T cells (CTL) specific for a non-traditional cryptic MHC class I epitope, SYNTGRFPPL, are critically involved in the protection of mice during infection with the LP-BM5 murine retrovirus. The goal of this study was to determine the functional properties of the protective SYNTGRFPPL-specific CTL during LP-BM5 infection of susceptible BALB/c CD8−/− mice. Direct infection experiments and adoptive transfer of CD8 T cells derived from perforin (pfp)−/−, IFNγ−/−, FasL−/− and, as a positive control, wild-type BALB/c mice, were utilized to assess the effector mechanisms responsible for protection. Our results indicate that SYNTGRFPPL-specific effector CTL preferentially utilize perforin-mediated cytolysis to provide protection against LP-BM5-induced pathogenesis, whereas CTL production of IFNγ is not required. Our results also suggest a minimal contribution of FasL/Fas-mediated lysis during the effector response. Collectively, these results provide insight into effector mechanisms utilized by protective CTL directed against non-traditional cryptic epitopes during disease protection. PMID:19539970

  17. Seasonal shift in the sensitivity of a natural benthic microalgal community to a herbicide mixture: impact on the protective level of thresholds derived from species sensitivity distributions.

    PubMed

    Larras, Floriane; Montuelle, Bernard; Rimet, Frédéric; Chèvre, Nathalie; Bouchez, Agnès

    2014-08-01

    Seasonal changes in the structure and composition of a benthic microalgal community may lead to different responses to herbicide contamination during different seasons. Consequently, the thresholds derived from risk assessment tools such as species sensitivity distributions (SSDs) must allow for these changes. We built a single-substance SSD for each of four herbicides (atrazine, terbutryn, diuron and isoproturon), which was specific to the sensitivity of the benthic diatoms found in Lake Geneva, in order to derive protective thresholds for a mixture of these four herbicides using the concentration addition model. We then investigated (1) the structural parameters of a Lake Geneva benthic microalgal community during two contrasting seasons (summer 2012 and winter 2013), (2) the response of these communities to a herbicide mixture, and (3) the protective levels of the thresholds derived. The winter community was characterized by having greater biomass, diatom species richness, and diversity metrics, and lower non-diatom species richness than the summer community. The differences in the diatom communities composition in these seasons appeared to be primarily driven by the environmental nitrate concentrations and the temperature. Moreover, the species in the winter community were more resistant to herbicides than those found in the summer community. Consequently, the protective threshold for this herbicide mixture obtained in this study was in fact protective for the winter community, but not for the summer community based on their structural parameters. Thus, the protective level against herbicides of the threshold for the benthic microalgal community should take into account changes in the environmental physico-chemical conditions that strongly influence the structure and composition of the community. The fact that the succession of species over time (i.e., over the seasons) is difficult to predict introduces uncertainties into the estimation of protective

  18. Protective immunity against Eimeria tenella infection in chickens induced by immunization with a recombinant C-terminal derivative of EtIMP1.

    PubMed

    Yin, Guangwen; Lin, Qian; Wei, Wenjun; Qin, Mei; Liu, Xianyong; Suo, Xun; Huang, Zhijian

    2014-12-15

    Immune mapped protein-1 (IMP1) is a new protective protein in apicomplexan parasites, and exits in Eimeria tenella. Cloning and sequence analysis has predicted the antigen to be a novel membrane protein of apicomplexan parasites. In order to assess the immunogenicity of EtIMP1, a C-terminal derivative of EtIMP1 was expressed in a bacterial host system and was used to immunize chickens. The protective efficacy against a homologous challenge was evaluated by body weight gains, lesion scores and fecal oocyst shedding. The results showed that the subunit vaccine can improve weight gains, reduced cecal pathology and lower oocyst fecal shedding compared with non immunized controls. The results suggested that the C-terminal derivative of EtIMP1 might be considered as a candidate in the development of subunit vaccines against Eimeria infection. PMID:25464823

  19. MOF derived composites for cathode protection: coatings of LiCoO2 from UiO-66 and MIL-53 as ultra-stable cathodes.

    PubMed

    Qi, Pengfei; Han, Yuzhen; Zhou, Junwen; Fu, Xiaotao; Li, Siwu; Zhao, Jingshu; Wang, Lu; Fan, Xinxin; Feng, Xiao; Wang, Bo

    2015-08-11

    A mechanochemical synthetic method of preparing LiCoO2 coated by MOF-derived metal oxide composites is introduced. Mono-dispersed ZrO2 and Al2O3 are applied as protection layers. These composites show 148 mA h g(-1) at a current density of 2325 mA g(-1) and excellent thermal stability (55 °C). PMID:26140444

  20. Protection of gerbils from amebic liver abscess by immunization with a recombinant protein derived from the 170-kilodalton surface adhesin of Entamoeba histolytica.

    PubMed Central

    Zhang, T; Stanley, S L

    1994-01-01

    The protozoan parasite Entamoeba histolytica causes extensive morbidity and mortality worldwide through intestinal infection and amebic liver abscess. Here we show that vaccination of gerbils, a standard model for amebic liver abscess, with recombinant proteins derived from the 170-kDa galactose-binding adhesin of E. histolytica and the serine-rich E. histolytica protein or a combination of the two recombinant antigens provides excellent protection against subsequent hepatic challenge with virulent E. histolytica trophozoites. PMID:8188384

  1. Human adipose derived stromal/stem cells (hASCs) protect against STZ-induced hyperglycemia; analysis of hASC-derived paracrine effectors

    PubMed Central

    Kono, Tatsuyoshi M.; Sims, Emily K.; Moss, Dan R.; Yamamoto, Wataru; Ahn, Geonyoung; Diamond, Julie; Tong, Xin; Day, Kathleen H.; Territo, Paul R.; Hanenberg, Helmut; Traktuev, Dmitry O.; March, Keith L.; Evans-Molina, Carmella

    2014-01-01

    Adipose-derived stromal/stem cells (ASCs) ameliorate hyperglycemia in rodent models of islet transplantation and autoimmune diabetes, yet the precise human ASC (hASC)-derived factors responsible for these effects remain largely unexplored. Here, we show that systemic administration of hASCs improved glucose tolerance, preserved β cell mass, and increased β cell proliferation in STZ-treated NOD-SCID mice. Co-culture experiments combining mouse or human islets with hASCs demonstrated that islet viability and function were improved by hASCs following prolonged culture or treatment with pro-inflammatory cytokines. Analysis of hASC-derived factors revealed VEGF and TIMP-1 to be highly abundant factors secreted by hASCs. Notably, TIMP-1 secretion increased in the presence of islet stress from cytokine treatment, while TIMP-1 blockade was able to abrogate in vitro pro-survival effects of hASCs. Following systemic administration by tail vein injection, hASCs were detected in the pancreas and human TIMP-1 was increased in the serum of injected mice, while recombinant TIMP-1 increased viability in INS-1 cells treated with IL-1β, IFN-γ and TNF-α. In aggregate, our data support a model whereby factors secreted by hASCs, such as TIMP-1, are able to mitigate against β cell death in rodent and in vitro models of Type 1 diabetes through a combination of local paracrine as well as systemic effects. PMID:24519994

  2. PROCEDURES FOR THE DERIVATION OF EQUILIBRIUM PARTITIONING SEDIMENT BENCHMARKS (ESBS) FOR THE PROTECTION OF BENTHIC ORGANISMS: ENDRIN

    EPA Science Inventory

    Under the Clean Water Act, EPA and the States develop programs for protecting the chemical, physical, and biological integrity of the nation's waters. To support these programs, efforts are conducted to develop and publish equilibrium partitioning sediment benchmarks (ESBs) for ...

  3. Protective Effects and Mechanisms of Salvianolic Acid B Against H₂O₂-Induced Injury in Induced Pluripotent Stem Cell-Derived Neural Stem Cells.

    PubMed

    Shu, Tao; Pang, Mao; Rong, Limin; Liu, Chang; Wang, Juan; Zhou, Wei; Wang, Xuan; Liu, Bin

    2015-06-01

    Induced pluripotent stem cells (iPSCs) have the potential to differentiate into neural lineages. Salvianolic acid B (Sal B) is a commonly used, traditional Chinese medicine for enhancing neuroprotective effects, and has antioxidant, anti-inflammatory, and antiapoptotic properties. Here, we explore the potential mechanism of Sal B in protecting iPSC-derived neural stem cells (NSCs) against H2O2-induced injury. iPSCs were induced into NSCs, iPSC-derived NSCs were treated with 50 μM Sal B for 24.5 h and 500 μM H2O2 for 24 h. The resulting effects were examined by flow cytometry analysis, quantitative reverse-transcription polymerase chain reaction, and western blotting. Upon H2O2 exposure, Sal B significantly promoted cell viability and stabilization of the mitochondrial membrane potential. Sal B also visibly decreased the cell apoptotic ratio. In addition, Sal B markedly reduced expression of matrix metalloproteinase (MMP)-2 and -9, and phosphospecific signal transducer and activator of transcription 3 (p-STAT3), and increased the level of tissue inhibitor of metalloproteinase (TIMP)-2 in iPSC-derived NSCs induced by H2O2. These results suggest that Sal B protects iPSC-derived NSCs against H2O2-induced oxidative stress. The mechanisms of this stress tolerance may be attributed to modulation of the MMP/TIMP system and inhibition of the STAT3 signaling pathway. PMID:25855584

  4. Proper Timing of Foot-and-Mouth Disease Vaccination of Piglets with Maternally Derived Antibodies Will Maximize Expected Protection Levels.

    PubMed

    Dekker, Aldo; Chénard, Gilles; Stockhofe, Norbert; Eblé, Phaedra L

    2016-01-01

    We investigated to what extent maternally derived antibodies interfere with foot-and-mouth disease (FMD) vaccination in order to determine the factors that influence the correct vaccination for piglets. Groups of piglets with maternally derived antibodies were vaccinated at different time points following birth, and the antibody titers to FMD virus (FMDV) were measured using virus neutralization tests (VNT). We used 50 piglets from 5 sows that had been vaccinated 3 times intramuscularly in the neck during pregnancy with FMD vaccine containing strains of FMDV serotypes O, A, and Asia-1. Four groups of 10 piglets were vaccinated intramuscularly in the neck at 3, 5, 7, or 9 weeks of age using a monovalent Cedivac-FMD vaccine (serotype A TUR/14/98). One group of 10 piglets with maternally derived antibodies was not vaccinated, and another group of 10 piglets without maternally derived antibodies was vaccinated at 3 weeks of age and served as a control group. Sera samples were collected, and antibody titers were determined using VNT. In our study, the antibody responses of piglets with maternally derived antibodies vaccinated at 7 or 9 weeks of age were similar to the responses of piglets without maternally derived antibodies vaccinated at 3 weeks of age. The maternally derived antibody levels in piglets depended very strongly on the antibody titer in the sow, so the optimal time for vaccination of piglets will depend on the vaccination scheme and quality of vaccine used in the sows and should, therefore, be monitored and reviewed on regular basis in countries that use FMD prophylactic vaccination. PMID:27446940

  5. Proper Timing of Foot-and-Mouth Disease Vaccination of Piglets with Maternally Derived Antibodies Will Maximize Expected Protection Levels

    PubMed Central

    Dekker, Aldo; Chénard, Gilles; Stockhofe, Norbert; Eblé, Phaedra L.

    2016-01-01

    We investigated to what extent maternally derived antibodies interfere with foot-and-mouth disease (FMD) vaccination in order to determine the factors that influence the correct vaccination for piglets. Groups of piglets with maternally derived antibodies were vaccinated at different time points following birth, and the antibody titers to FMD virus (FMDV) were measured using virus neutralization tests (VNT). We used 50 piglets from 5 sows that had been vaccinated 3 times intramuscularly in the neck during pregnancy with FMD vaccine containing strains of FMDV serotypes O, A, and Asia-1. Four groups of 10 piglets were vaccinated intramuscularly in the neck at 3, 5, 7, or 9 weeks of age using a monovalent Cedivac-FMD vaccine (serotype A TUR/14/98). One group of 10 piglets with maternally derived antibodies was not vaccinated, and another group of 10 piglets without maternally derived antibodies was vaccinated at 3 weeks of age and served as a control group. Sera samples were collected, and antibody titers were determined using VNT. In our study, the antibody responses of piglets with maternally derived antibodies vaccinated at 7 or 9 weeks of age were similar to the responses of piglets without maternally derived antibodies vaccinated at 3 weeks of age. The maternally derived antibody levels in piglets depended very strongly on the antibody titer in the sow, so the optimal time for vaccination of piglets will depend on the vaccination scheme and quality of vaccine used in the sows and should, therefore, be monitored and reviewed on regular basis in countries that use FMD prophylactic vaccination. PMID:27446940

  6. The Flaxseed-Derived Lignan Phenolic Secoisolariciresinol Diglucoside (SDG) Protects Non-Malignant Lung Cells from Radiation Damage

    PubMed Central

    Velalopoulou, Anastasia; Tyagi, Sonia; Pietrofesa, Ralph A.; Arguiri, Evguenia; Christofidou-Solomidou, Melpo

    2015-01-01

    Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS) has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed’s protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG). SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR)-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1. Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure. PMID:26703588

  7. Deriving Sediment Interstitial Water Remediation Goals (IWRGs) at Superfund Sites for the Protection of Benthic Organisms from Direct Toxicity

    EPA Science Inventory

    This document contains a methodology for developing interstitial water remediation goals (IWRGs) for nonionic organic pollutants (toxicants) in sediments for the protection of benthic organisms. The document provides the basis for using the final chronic values (FCVs) from EPA’s...

  8. Role of silicone derivative plus onion extract gel in presternal hypertrophic scar protection: a prospective randomized, double blinded, controlled trial.

    PubMed

    Jenwitheesuk, Kamonwan; Surakunprapha, Palakorn; Jenwitheesuk, Kriangsak; Kuptarnond, Chusak; Prathanee, Sompop; Intanoo, Worawit

    2012-08-01

    Use of silicone derivative and onion extract had been reported in the prevention of hypertrophic scarring. Our experience showed the preventive use of silicone derivative plus onion extract gel on hypertrophic scars after median sternotomy. In a randomized, double blinded, placebo-controlled study, 60 patients after median sternotomy incisions were separated into two groups. All patients were treated either with silicone derivative plus onion extract gel (Cybele(®) scagel) or placebo gel twice daily for a total treatment period of 12 weeks. During each visit, pain and itching scores were graded by the patients and scar characteristics were observed by surgeons using the Vancouver scar scale. Pain and itch score values from patients' who applied silicone derivative plus onion extract gel was less than another group (P < 0·05). Pigmentation was significantly different between two groups (P < 0·05) and the reduction of scores on vascularity, pliability, height in treated group was not superior to the untreated group. No adverse events were reported by any of the patients. A silicone derivative plus onion extract gel is safe and effective for the preventing the hypertrophic scarring after median sternotomy. PMID:22168750

  9. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    PubMed

    Mann, Alex J; Noulin, Nicolas; Catchpole, Andrew; Stittelaar, Koert J; de Waal, Leon; Veldhuis Kroeze, Edwin J B; Hinchcliffe, Michael; Smith, Alan; Montomoli, Emanuele; Piccirella, Simona; Osterhaus, Albert D M E; Knight, Alastair; Oxford, John S; Lapini, Giulia; Cox, Rebecca; Lambkin-Williams, Rob

    2014-01-01

    We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and

  10. Cannabinoid receptors are involved in the protective effect of a novel curcumin derivative C66 against CCl4-induced liver fibrosis.

    PubMed

    Huang, Si-Si; Chen, Da-Zhi; Wu, He; Chen, Rui-Cong; Du, Shan-Jie; Dong, Jia-Jia; Liang, Guang; Xu, Lan-Man; Wang, Xiao-Dong; Yang, Yong-Ping; Yu, Zhen-Ping; Feng, Wen-Ke; Chen, Yong-Ping

    2016-05-15

    Liver fibrosis is one of the major causes of morbidity and mortality worldwide and lacks efficient therapy. Recent studies suggest the curcumin protects liver from fibrosis. However, curcumin itself is in low bioavailable concentration when administered orally, and the protective mechanism remains poorly understood. The current study aimed to investigate whether a more stable derivative of curcumin, C66, protects against CCl4-inudced liver fibrosis and examine the underlying mechanism involving cannabinoid receptor (CB receptor). At a dose lower than curcumin itself, C66 displayed a superior anti-fibrotic effect. C66 significantly reduced collagen deposition, pro-inflammatory cytokine expression, and liver enzyme activities. Mechanistic study revealed that C66 treatment decreased CCl4-induced cannabinoid receptor 1 (CB1 receptor) expression and increased cannabinoid receptor 2 (CB2 receptor) expression, along with an inhibition of JNK/NF-κB-mediated inflammatory signaling. In conclusion, this curcumin derivative attenuates liver fibrosis likely involving a CB/JNK/NF-κB-mediated pathway. PMID:26945822

  11. Overexpression of mitochondrial Hsp75 protects neural stem cells against microglia-derived soluble factor-induced neurotoxicity by regulating mitochondrial permeability transition pore opening in vitro.

    PubMed

    Wang, Yan; Lin, Jizong; Chen, Qing-Zhuang; Zhu, Ning; Jiang, De-Qi; Li, Ming-Xing; Wang, Yong

    2015-12-01

    Microglia (MG)-induced neurotoxicity, a major determinant of Alzheimer's disease, is closely related to the survival of neural stem cells (NSCs). Heat shock protein 75 (Hsp75) has been reported to exert protective effects against environmental stresses; however, whether or not it protects NSCs against MG-derived soluble factor-induced neurotoxicity remains unclear. In the present study, we constructed NSCs that overexpressed human Hsp75 protein and established a co-culture system in order to elucidate the role of Hsp75 in NSC-MG interactions. The results obtained indicated that Hsp75 expression increased after 12 h of soluble factor induction and continued to increase for up to 36 h of treatment. The overexpression of Hsp75 decreased NSC apoptosis and preserved mitochondrial membrane potential. Further experiments revealed that the overexpression of Hsp75 inhibited the formation of cyclophilin D (CypD)-dependent mitochondrial permeability transition pore (mPTP) involvement in neurotoxicity-mediated mitochondrial dysfunction and suppressed the activation of the mitochondrial apoptotic cascade, as demonstrated by the inhibition of the release of cytochrome c (Cytc) and the activation of caspase-3. The findings of this study demonstrate that Hsp75 overexpression prevents the impairment of NSCs induced by MG-derived soluble factors by regulating the opening of mPTP. Thus, Hsp75 warrants further investigation as a potential candidate for protection against neurotoxicity. PMID:26500047

  12. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington's disease.

    PubMed

    Zeng, Yixuan; Guo, Wenyuan; Xu, Guangqing; Wang, Qinmei; Feng, Luyang; Long, Simei; Liang, Fengyin; Huang, Yi; Lu, Xilin; Li, Shichang; Zhou, Jiebin; Burgunder, Jean-Marc; Pang, Jiyan; Pei, Zhong

    2016-01-01

    Huntington's disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt). Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington's disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson's and Alzheimer's diseases. To identify potential neuroprotective molecules for Huntington's disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington's disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a stable trimeric complex that can prevent the formation of mutant Htt aggregates. Taken together, we conclude that xyloketal derivatives could be novel drug candidates for treating Huntington's disease. Molecular target analysis is a good method to simulate the interaction between proteins and drug compounds. Further, protective candidate drugs could be designed in future using the guidance of molecular docking results. PMID:27110099

  13. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    PubMed Central

    Zeng, Yixuan; Guo, Wenyuan; Xu, Guangqing; Wang, Qinmei; Feng, Luyang; Long, Simei; Liang, Fengyin; Huang, Yi; Lu, Xilin; Li, Shichang; Zhou, Jiebin; Burgunder, Jean-Marc; Pang, Jiyan; Pei, Zhong

    2016-01-01

    Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt). Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a stable trimeric complex that can prevent the formation of mutant Htt aggregates. Taken together, we conclude that xyloketal derivatives could be novel drug candidates for treating Huntington’s disease. Molecular target analysis is a good method to simulate the interaction between proteins and drug compounds. Further, protective candidate drugs could be designed in future using the guidance of molecular docking results. PMID:27110099

  14. Divergent, stereoselective access to heterocyclic α,α-quaternary- and β(2,3,3)-amino acid derivatives from a N-Pmp-protected Orn-derived β-lactam.

    PubMed

    Núñez-Villanueva, Diego; García-López, M Teresa; Martín-Martínez, Mercedes; González-Muñiz, Rosario

    2015-05-14

    A suitably protected Orn-derived (3S,4S)-β-lactam was used as common intermediate in the synthesis of conformationally constrained (3S,4S)-2-oxoazepane α,α- and (2S,3S)-2-oxopiperidine-β(2,3,3)-amino acid derivatives. Compared to alternative procedures using an N-p-methoxybenzyl group at the 2-azetidinone, the incorporation of a p-methoxyphenyl moiety is crucial for the excellent stereochemical outcomes in the preparation of these heterocyclic amino acids. Chemoselective 7- or 6-exo-trig cyclization was achieved through alternative sequences of Pmp-deprotection/Boc-activation, followed by inter- and intramolecular β-lactam ring opening, respectively. PMID:25849279

  15. Induction of protective immunity against Eimeria tenella, Eimeria maxima, and Eimeria acervulina infections using DC-derived exosomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study describes a novel immunization strategy against avian coccidiosis using exosomes derived from Eimeria parasite antigen (Ag)-loaded dendritic cells (DCs) in the absence of soluble Ag. Chicken intestinal DCs were isolated and pulsed in vitro with a mixture of sporozoite-extracted Ags from E...

  16. The need for empirically derived permeation data for personal protective equipment: the death of Dr. Karen E. Wetterhahn.

    PubMed

    Blayney, M B

    2001-02-01

    Personal protective equipment (PPE) is an essential component in any occupational health and safety program. The appropriate selection and use of PPE can help prevent or limit exposure to hazardous materials. The inappropriate selection or use of PPE can lead to unnecessary exposure or --with extremely hazardous materials--serious harm including death. In 1997, Dr. Karen E. Wetterhahn died from mercury poisoning resulting from a single exposure to dimethylmercury almost a year before. Her death raised numerous questions as to how this tragedy occurred and what could be done to protect against a chemical as dangerous as dimethylmercury. This article provides a brief review of the case and discusses the glove permeation testing done during the course of the accident investigation. Using this case as an example, the author argues that all recommendations for PPE be based on empirical testing using accepted methods and that this information be readily available. PMID:11217716

  17. A Vibrio cholerae ghost-based subunit vaccine induces cross-protective chlamydial immunity that is enhanced by CTA2B, the nontoxic derivative of cholera toxin

    PubMed Central

    Ekong, Eno E.; Okenu, Daniel N.; Mania-Pramanik, Jayanti; He, Qing; Igietseme, Joseph U.; Ananaba, Godwin A.; Lyn, Deborah; Black, Carolyn; Eko, Francis O.

    2011-01-01

    The Vibrio cholerae ghost (rVCG) platform is an effective carrier and delivery system for designing efficacious Chlamydia vaccines. We investigated whether CTA2B, the nontoxic derivative of cholera toxin, can augment protective immunity conferred by an rVCG-based chlamydial vaccine and enhance cross-protection against heterologous chlamydial strains. An rVCG vaccine coexpressing chlamydial major outer membrane protein and CTA2B was genetically constructed and antigens were targeted to the inner membrane of V. cholerae before ghost production by gene E-mediated lysis. Effective immunomodulation by CTA2B was demonstrated by the ability of the vaccine construct to enhance the activation and maturation of dendritic cells in vitro. Also, C57BL/6 mice immunized via mucosal and systemic routes showed increased specific mucosal and systemic antibody and T-helper type-1 (Th1) responses, irrespective of the route. The enhanced production of IFN-γ, but not IL-4 by genital mucosal and splenic T cells, indicated a predominantly Th1 response. Clearance of the Chlamydia muridarum vaginal infection was significantly enhanced by codelivery of the vaccine with CTA2B, with the intravaginal route showing a moderate advantage. These results indicate that the rVCG-based vaccine is capable of inducing cross-protection against heterologous chlamydial serovars and that incorporation of mucosal adjuvants, such as CTA2B in the rVCG delivery platform, may enhance protective immunity. PMID:19040663

  18. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.

    PubMed

    Mwangi, Simon Musyoka; Peng, Sophia; Nezami, Behtash Ghazi; Thorn, Natalie; Farris, Alton B; Jain, Sanjay; Laroui, Hamed; Merlin, Didier; Anania, Frank; Srinivasan, Shanthi

    2016-01-15

    Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease. PMID:26564715

  19. Piglets with maternally derived antibodies from sows immunized with rAdV-SFV-E2 were completely protected against lethal CSFV challenge.

    PubMed

    Xia, Shui-Li; Du, Mingliang; Lei, Jian-Lin; Liu, Yan; Wang, Yimin; Ji, Shengwei; Xiang, Guang-Tao; Li, Lian-Feng; Cong, Xin; Luo, Yuzi; Shao, Lina; Qiu, Hua-Ji; Sun, Yuan

    2016-07-15

    Classical swine fever (CSF) is an economically important infectious disease of pigs caused by Classical swine fever virus (CSFV). To facilitate the eradication of CSF in endemic areas, a marker vaccine enabling differentiation of infected from vaccinated animals (DIVA) is urgently needed. Previously, we have demonstrated that the DIVA vaccine rAdV-SFV-E2, an adenovirus-vectored Semliki Forest virus replicon expressing the E2 glycoprotein of CSFV, induces complete protection from lethal CSFV challenge. The aim of this study was to investigate whether maternally derived antibodies (MDAs) from sows immunized with rAdV-SFV-E2 can effectively protect piglets against lethal CSFV challenge. Three groups of five-week-old piglets (n=4), with or without MDAs, were challenged with the highly virulent CSFV Shimen strain. Clinical signs, CSFV-specific antibodies, viremia and pathological and histopathological changes were monitored. The results showed that the piglets with MDAs from the sow immunized with rAdV-SFV-E2 were protected clinically, virologically and pathologically, while the piglets with undetectable MDAs from the rAdV-SFV-E2-immunized sow were partially protected (2/4 survival), in contrast with the piglets from the non-vaccinated sow, which displayed CSF-typical clinical signs, viremia, deaths (4/4) and pathological/histopathological lesions. These results indicate that MDAs from the sow immunized with rAdV-SFV-E2 are able to confer full passive immunity to newborn piglets. PMID:27283854

  20. Antioxidative Peptides Derived from Enzyme Hydrolysis of Bone Collagen after Microwave Assisted Acid Pre-Treatment and Nitrogen Protection

    PubMed Central

    Lin, Yun-Jian; Le, Guo-Wei; Wang, Jie-Yun; Li, Ya-Xin; Shi, Yong-Hui; Sun, Jin

    2010-01-01

    This study focused on the preparation method of antioxidant peptides by enzymatic hydrolysis of bone collagen after microwave assisted acid pre-treatment and nitrogen protection. Phosphoric acid showed the highest ability of hydrolysis among the four other acids tested (hydrochloric acid, sulfuric acid and/or citric acid). The highest degree of hydrolysis (DH) was 9.5% using 4 mol/L phosphoric acid with a ratio of 1:6 under a microwave intensity of 510 W for 240 s. Neutral proteinase gave higher DH among the four protease tested (Acid protease, neutral protease, Alcalase and papain), with an optimum condition of: (1) ratio of enzyme and substrate, 4760 U/g; (2) concentration of substrate, 4%; (3) reaction temperature, 55 °C and (4) pH 7.0. At 4 h, DH increased significantly (P < 0.01) under nitrogen protection compared with normal microwave assisted acid pre-treatment hydrolysis conditions. The antioxidant ability of the hydrolysate increased and reached its maximum value at 3 h; however DH decreased dramatically after 3 h. Microwave assisted acid pre-treatment and nitrogen protection could be a quick preparatory method for hydrolyzing bone collagen. PMID:21151439

  1. Deriving site-specific soil clean-up values for metals and metalloids: Rationale for including protection of soil microbial processes

    PubMed Central

    Kuperman, Roman G; Siciliano, Steven D; Römbke, Jörg; Oorts, Koen

    2014-01-01

    Although it is widely recognized that microorganisms are essential for sustaining soil fertility, structure, nutrient cycling, groundwater purification, and other soil functions, soil microbial toxicity data were excluded from the derivation of Ecological Soil Screening Levels (Eco-SSL) in the United States. Among the reasons for such exclusion were claims that microbial toxicity tests were too difficult to interpret because of the high variability of microbial responses, uncertainty regarding the relevance of the various endpoints, and functional redundancy. Since the release of the first draft of the Eco-SSL Guidance document by the US Environmental Protection Agency in 2003, soil microbial toxicity testing and its use in ecological risk assessments have substantially improved. A wide range of standardized and nonstandardized methods became available for testing chemical toxicity to microbial functions in soil. Regulatory frameworks in the European Union and Australia have successfully incorporated microbial toxicity data into the derivation of soil threshold concentrations for ecological risk assessments. This article provides the 3-part rationale for including soil microbial processes in the development of soil clean-up values (SCVs): 1) presenting a brief overview of relevant test methods for assessing microbial functions in soil, 2) examining data sets for Cu, Ni, Zn, and Mo that incorporated soil microbial toxicity data into regulatory frameworks, and 3) offering recommendations on how to integrate the best available science into the method development for deriving site-specific SCVs that account for bioavailability of metals and metalloids in soil. Although the primary focus of this article is on the development of the approach for deriving SCVs for metals and metalloids in the United States, the recommendations provided in this article may also be applicable in other jurisdictions that aim at developing ecological soil threshold values for protection of

  2. Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter

    SciTech Connect

    Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun; Lovelace, Gregory L.; Smith, Charles D.; Lemasters, John J.

    2013-11-15

    Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs–Ringer–HEPES buffer at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca{sup 2+} uptake was measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca{sup 2+} uptake and suppressed the Ca{sup 2+}-induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca{sup 2+} uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. - Highlights: • Minocycline and doxycycline are the only cytoprotective tetracyclines of those tested • Cytoprotective tetracyclines inhibit the MPT and mitochondrial calcium and iron uptake. • Cytoprotective

  3. Endothelium-derived intermedin/adrenomedullin-2 protects human ventricular cardiomyocytes from ischaemia-reoxygenation injury predominantly via the AM₁ receptor.

    PubMed

    Bell, David; Campbell, Malcolm; McAleer, Stephen F; Ferguson, Matthew; Donaghy, Liz; Harbinson, Mark T

    2016-02-01

    Application of intermedin/adrenomedullin-2 (IMD/AM-2) protects cultured human cardiac vascular cells and fibroblasts from oxidative stress and simulated ischaemia-reoxygenation injury (I-R), predominantly via adrenomedullin AM1 receptor involvement; similar protection had not been investigated previously in human cardiomyocytes (HCM). Expression of IMD, AM and their receptor components was studied in HCM. Receptor subtype involvement in protection by exogenous IMD against injury by simulated I-R was investigated using receptor component-specific siRNAs. Direct protection by endogenous IMD against HCM injury, both as an autocrine factor produced in HCM themselves and as a paracrine factor released from HCMEC co-cultured with HCM, was investigated using peptide-specific siRNA for IMD. IMD, AM and their receptor components (CLR, RAMPs1-3) were expressed in HCM. IMD 1nmol L(-1), applied either throughout ischaemia (3h) and re-oxygenation (1h) or during re-oxygenation (1h) alone, attenuated HCM injury (P<0.05); cell viabilities were 59% and 61% respectively vs. 39% in absence of IMD. Cytoskeletal disruption, protein carbonyl formation and caspase activity followed similar patterns. Pre-treatment (4 days) of HCM with CLR and RAMP2 siRNAs attenuated (P<0.05) protection by exogenous IMD. Pre-treatment of HCMEC with IMD (and AM) siRNA augmented (P<0.05) I-R injury: cell viabilities were 22% (and 32%) vs. 39% untreated HCMEC. Pre-treatment of HCM with IMD (and AM) siRNA did not augment HCM injury: cell viabilities were 37% (and 39%) vs. 39% untreated HCM. Co-culture with HCMEC conferred protection from injury on HCM; such protection was attenuated when HCMEC were pre-treated with IMD (but not AM) siRNA before co-culture. Although IMD is present in HCM, IMD derived from HCMEC and acting in a paracrine manner, predominantly via AM1 receptors, makes a marked contribution to cardiomyocyte protection by the endogenous peptide against acute I-R injury. PMID:26743504

  4. Protective effects of chitosan and its water-soluble derivatives against lead-induced oxidative stress in mice.

    PubMed

    Wang, Zhihua; Yan, Yongbin; Yu, Xiaohua; Li, Wei; Li, Bojie; Qin, Caiqin

    2016-02-01

    Lead-induced oxidative stress was generated in mice under lead exposure, and the antioxidant activity of chitosan (CS) and its water-soluble derivatives was compared in vivo. The results indicated that there was significant difference (P<0.05) for the biochemical variables of lead-treated groups. After lead exposure, the contents of reduced glutathione (GSH) and total thiols (T-SH) in blood and tissues decreased, and the contents of protein oxidation, oxidized glutathione (GSSG), malondialdehyde (MDA) and reactive oxygen species (ROS) increased compared with the control group. Administration of CS and its derivatives made for the removal of lead from blood and tissues, especially for hydroxypropyl chitosan (HPCS) and quaternary ammonium salt of chitosan (HACC). And the changed biochemical variables showed recovery with different degrees, which indicated that CS and its derivatives were helpful for alleviating lead-induced oxidation damage in vivo. But the antioxidant activity for different CS was different, followed by HPCS>HACC>carboxymethyl chitosan (CMCS)>CS, which was in close with the introduction of different substituent groups. In particular, for the dietary of HPCS, there was significant recovery for the changed biochemical variables (P<0.05) in mice after lead exposure, except GSSG in kidney and MDA in brain. PMID:26454108

  5. Preparation, stability, and photoreactivity of thiolato ruthenium polypyridyl complexes: Can cysteine derivatives protect ruthenium-based anticancer complexes?

    PubMed

    van Rixel, Vincent H S; Busemann, Anja; Göttle, Adrien J; Bonnet, Sylvestre

    2015-09-01

    Ruthenium polypyridyl complexes may act as light-activatable anticancer prodrugs provided that they are protected by well-coordinated ligands that i) prevent coordination of other biomolecules to the metal center in the dark and ii) can be removed by visible light irradiation. In this paper, the use of monodentate thiol ligands RSH as light-cleavable protecting groups for the ruthenium complex [Ru(tpy)(bpy)(OH2)](PF6)2 ([1](PF6)2; tpy=2,2';6',2″-terpyridine, bpy=2,2'-bypyridine), is investigated. The reaction of [1](2+) with RSH=H2Cys (L-cysteine), H2Acys (N-acetyl-L-cysteine), and HAcysMe (N-acetyl-L-cysteine methyl ester), is studied by UV-visible spectroscopy, NMR spectroscopy, and mass spectrometry. Coordination of the monodentate thiol ligands to the ruthenium complex takes place upon heating to 353 K, but full conversion to the protected complex [Ru(tpy)(bpy)(SR)]PF6 is only possible when a large excess of ligand is used. Isolation and characterization of the two new thiolato complexes [Ru(tpy)(bpy)(κS-HCys)]PF6 ([2]PF6) and [Ru(tpy)(bpy)(κS-HAcys)]PF6 ([3]PF6) is reported. [3]PF6 shows a metal-to-ligand charge-transfer absorption band that is red shifted (λmax=492 nm in water) compared to its methionine analogue [Ru(tpy)(bpy)(κS-HAmet)](Cl)2 ([5](Cl)2, λmax=452 nm; HAmet=N-acetyl-methionine). In the dark the thiolate ligand coordinated to ruthenium is oxidized even by traces of oxygen, which first leads to the sulfenato, sulfinato, and disulfide ruthenium complexes, and finally to the formation of the aqua complex [1](2+). [3]PF6 showed slow photosubstitution of the thiolate ligand by water under blue light irradiation, together with faster photooxidation of the thiolate ligand compared to dark conditions. The use of thiol vs. thioether monodentate ligands is discussed for the protection of anticancer ruthenium-based prodrugs. PMID:26187140

  6. A sericin-derived peptide protects sf9 insect cells from death caused by acute serum deprivation.

    PubMed

    Takahashi, Masakazu; Tsujimoto, Kazuhisa; Kato, Youichi; Yamada, Hideyuki; Takagi, Hiroshi; Nakamori, Shigeru

    2005-07-01

    Sericin is the silk protein enveloping fibroin fibers in cocoons. Sericin hydrolysate protects cultured Sf9 insect cells from death caused by serum deprivation; the activity depends on the repeats of 38 amino acids. A partial peptide from the 38 residues, SGGSSTYGYS, inhibited serum-deprivation death as well. Cell viabilities in the presence of 10% (v/v) foetal calf serum, no additives and 1 mM: SGGSSTYGYS were 96, 12 and 31% on the third day after inoculation, respectively. Aromatic residues seemed to be important because SGGSSTWGWS had the same activity as SGGSSTYGYS but SGGSSTAGAS had no activity. PMID:16091882

  7. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window.

    PubMed

    Yrjänheikki, J; Tikka, T; Keinänen, R; Goldsteins, G; Chan, P H; Koistinaho, J

    1999-11-01

    The only treatment of patients with acute ischemic stroke is thrombolytic therapy, which benefits only a fraction of stroke patients. Both human and experimental studies indicate that ischemic stroke involves secondary inflammation that significantly contributes to the outcome after ischemic insult. Minocycline is a semisynthetic second-generation tetracycline that exerts antiinflammatory effects that are completely separate from its antimicrobial action. Because tetracycline treatment is clinically well tolerated, we investigated whether minocycline protects against focal brain ischemia with a wide therapeutic window. Using a rat model of transient middle cerebral artery occlusion, we show that daily treatment with minocycline reduces cortical infarction volume by 76 +/- 22% when the treatment is started 12 h before ischemia and by 63 +/- 35% when started even 4 h after the onset of ischemia. The treatment inhibits morphological activation of microglia in the area adjacent to the infarction, inhibits induction of IL-1beta-converting enzyme, and reduces cyclooxygenase-2 expression and prostaglandin E(2) production. Minocycline had no effect on astrogliosis or spreading depression, a wave of ionic transients thought to contribute to enlargement of cortical infarction. Treatment with minocycline may act directly on brain cells, because cultured primary neurons were also salvaged from glutamate toxicity. Minocycline may represent a prototype of an antiinflammatory compound that provides protection against ischemic stroke and has a clinically relevant therapeutic window. PMID:10557349

  8. Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques

    PubMed Central

    Olinger, Gene Garrard; Pettitt, James; Kim, Do; Working, Cara; Bohorov, Ognian; Bratcher, Barry; Hiatt, Ernie; Hume, Steven D.; Johnson, Ashley K.; Morton, Josh; Pauly, Michael; Whaley, Kevin J.; Lear, Calli M.; Biggins, Julia E.; Scully, Corinne; Hensley, Lisa; Zeitlin, Larry

    2012-01-01

    Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure. PMID:23071322

  9. Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations.

    PubMed

    Safar, Marwa M; Arab, Hany H; Rizk, Sherine M; El-Maraghy, Shohda A

    2016-04-01

    Vascular endothelial dysfunction plays a key role in the pathogenesis of Alzheimer's disease (AD). Patients with AD have displayed decreased circulating endothelial progenitor cells (EPCs) which repair and maintain the endothelial function. Transplantation of EPCs has emerged as a promising approach for the management of cerebrovascular diseases including ischemic stroke, however, its impact on AD has been poorly described. Thus, the current study aimed at investigating the effects of bone marrow-derived (BM) EPCs transplantation in repeated scopolamine-induced cognitive impairment, an experimental model that replicates biomarkers of AD. Intravenously transplanted BM-EPCs migrated into the brain of rats and improved the learning and memory deficits. Meanwhile, they mitigated the deposition of amyloid plaques and associated histopathological alterations. At the molecular levels, BM-EPCs blunted the increase of hippocampal amyloid beta protein (Aβ), amyloid precursor protein (APP) and reinstated the Aβ-degrading neprilysin together with downregulation of p-tau and its upstream glycogen synthase kinase-3β (GSK-3β). They also corrected the perturbations of neurotransmitter levels including restoration of acetylcholine and associated esterase along with dopamine, GABA, and the neuroexitatory glutamate. Furthermore, BM-EPCs induced behavioral recovery via boosting of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and its upstream cAMP response element binding (CREB), suppression of the proinflammatory tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and upregulation of interleukin-10 (IL-10). BM-EPCs also augmented Nrf2 and seladin-1. Generally, these actions were analogous to those exerted by adipose tissue-derived mesenchymal stem cells (AT-MSCs) and the reference anti-Alzheimer donepezil. For the first time, these findings highlight the beneficial actions of BM-EPCs against the memory

  10. Deriving Freshwater Quality Criteria for Iron, Lead, Nickel, and Zinc for Protection of Aquatic Life in Malaysia

    PubMed Central

    Shuhaimi-Othman, M.; Nadzifah, Y.; Nur-Amalina, R.; Umirah, N. S.

    2012-01-01

    Freshwater quality criteria for iron (Fe), lead (Pb), nickel (Ni), and zinc (Zn) were developed with particular reference to aquatic biota in Malaysia, and based on USEPA's guidelines. Acute toxicity tests were performed on eight different freshwater domestic species in Malaysia which were Macrobrachium lanchesteri (prawn), two fish: Poecilia reticulata and Rasbora sumatrana, Melanoides tuberculata (snail), Stenocypris major (ostracod), Chironomus javanus (midge larvae), Nais elinguis (annelid), and Duttaphrynus melanostictus (tadpole) to determine 96 h LC50 values for Fe, Pb, Ni, and Zn. The final acute value (FAV) for Fe, Pb, Ni, and Zn were 74.5, 17.0, 165, and 304.9 μg L−1, respectively. Using an estimated acute-to-chronic ratio (ACR) of 8.3, the value for final chronic value (FCV) was derived. Based on FAV and FCV, a criterion maximum concentration (CMC) and a criterion continuous concentration (CCC) for Fe, Pb, Ni, and Zn that are 37.2, 8.5, 82.5, and 152.4 μg L−1 and 9.0, 2.0, 19.9, and 36.7 μg L−1, respectively, were derived. The results of this study provide useful data for deriving national or local water quality criteria for Fe, Pb, Ni, and Zn based on aquatic biota in Malaysia. Based on LC50 values, this study indicated that N. elinguis, M. lanchesteri, N. elinguis, and R. sumatrana were the most sensitive to Fe, Pb, Ni, and Zn, respectively. PMID:22919358

  11. Deriving freshwater quality criteria for iron, lead, nickel, and zinc for protection of aquatic life in Malaysia.

    PubMed

    Shuhaimi-Othman, M; Nadzifah, Y; Nur-Amalina, R; Umirah, N S

    2012-01-01

    Freshwater quality criteria for iron (Fe), lead (Pb), nickel (Ni), and zinc (Zn) were developed with particular reference to aquatic biota in Malaysia, and based on USEPA's guidelines. Acute toxicity tests were performed on eight different freshwater domestic species in Malaysia which were Macrobrachium lanchesteri (prawn), two fish: Poecilia reticulata and Rasbora sumatrana, Melanoides tuberculata (snail), Stenocypris major (ostracod), Chironomus javanus (midge larvae), Nais elinguis (annelid), and Duttaphrynus melanostictus (tadpole) to determine 96 h LC(50) values for Fe, Pb, Ni, and Zn. The final acute value (FAV) for Fe, Pb, Ni, and Zn were 74.5, 17.0, 165, and 304.9 μg L(-1), respectively. Using an estimated acute-to-chronic ratio (ACR) of 8.3, the value for final chronic value (FCV) was derived. Based on FAV and FCV, a criterion maximum concentration (CMC) and a criterion continuous concentration (CCC) for Fe, Pb, Ni, and Zn that are 37.2, 8.5, 82.5, and 152.4 μg L(-1) and 9.0, 2.0, 19.9, and 36.7 μg L(-1), respectively, were derived. The results of this study provide useful data for deriving national or local water quality criteria for Fe, Pb, Ni, and Zn based on aquatic biota in Malaysia. Based on LC(50) values, this study indicated that N. elinguis, M. lanchesteri, N. elinguis, and R. sumatrana were the most sensitive to Fe, Pb, Ni, and Zn, respectively. PMID:22919358

  12. Multispecies toxicity test for silver nanoparticles to derive hazardous concentration based on species sensitivity distribution for the protection of aquatic ecosystems.

    PubMed

    Kwak, Jin Il; Cui, Rongxue; Nam, Sun-Hwa; Kim, Shin Woong; Chae, Yooeun; An, Youn-Joo

    2016-06-01

    With increasing concerns about the release of silver nanoparticles (AgNPs) into the environment and the risks they pose to ecological and human health, a number of studies of AgNP toxicity to aquatic organisms have been conducted. USEPA and EU JRC have published risk assessment reports for AgNPs. However, most previous studies have focused on the adverse effects of AgNPs on individual species. Hazardous concentration (HC) of AgNPs for protection of aquatic ecosystems that are based on species sensitivity distributions (SSDs) have not yet been derived because sufficient data have not been available. In this study, we conducted multispecies toxicity tests, including acute assays using eight species from five different taxonomic groups (bacteria, algae, flagellates, crustaceans and fish) and chronic assays using six species from four different taxonomic groups (algae, flagellates, crustaceans and fish). Using the results of these assays, we used a SSD approach to derive an AgNP aquatic HC5 (Hazard concentrations at the 5% species) of 0.614 μg/L. To our knowledge, this is the first report of a proposed HC of AgNPs for the protection of aquatic ecosystems that is based on SSDs and uses chronic toxicity data. PMID:26634622

  13. A facile approach to derive binder protective film on high voltage spinel cathode materials against high temperature degradation

    NASA Astrophysics Data System (ADS)

    Chou, Wei-Yu; Jin, Yi-Chun; Duh, Jenq-Gong; Lu, Cheng-Zhang; Liao, Shih-Chieh

    2015-11-01

    The electrochemical performance of spinel LiNi0.5Mn1.5O4 cathode combined with different binders at elevated temperature is firstly investigated. The water soluble binder, such as sodium carboxymethyl cellulose (CMC) and sodium alginate (SA), is compared with the polyvinylidene difluoride (PVdF) binder used in non-aqueous process. The aqueous process can meet the need of Li-ion battery industry due to environmental-friendly and cost effectiveness by replacing toxic organic solvent, such as N-methyl-pyrrolidone (NMP). In this study, a significantly improved high temperature cycling performance is successfully obtained as compared to the traditional PVdF binder. The aqueous binder can serve as a protective film which inhibits the serious Ni and Mn dissolution especially at elevated temperature. Our result demonstrates a facile approach to solve the problem of capacity fading for high voltage spinel cathodes.

  14. Spirituality and positive psychology go hand in hand: an investigation of multiple empirically derived profiles and related protective benefits.

    PubMed

    Barton, Yakov A; Miller, Lisa

    2015-06-01

    We investigate the relationship between personal spirituality and positive psychology traits as potentially presented in multiple profiles, rather than monolithically across a full sample. A sample of 3966 adolescents and emerging adults (aged 18-25, mean = 20.19, SD = 2.08) and 2014 older adults (aged 26-82, mean = 38.41, SD = 11.26) completed a survey assessing daily spiritual experiences (relationship with a Higher Power and sense of a sacred world), forgiveness, gratitude, optimism, grit, and meaning. To assess the relative protective benefits of potential profiles, we also assessed the level of depressive symptoms and frequency of substance use (tobacco, marijuana, alcohol, and heavy alcohol use). Latent class analysis (LCA) was used to examine common subgroupings of study participants across report on personal spirituality and positive psychology scales in each age cohort, with potential difference between latent classes then tested in level of depressive symptoms and degree of substance use. LCA determined a four-class and a three-class best-fitting models for the younger and older cohorts, respectively. Level of personal spirituality and level of positive psychology traits were found to coincide in 83 % of adolescents and emerging adults and in 71 % of older adults, suggesting personal spirituality and positive psychology traits go hand in hand. A minority subgroup of "virtuous humanists" showed high levels of positive psychology traits but low levels of personal spirituality, across both age cohorts. Whereas level of depression was found to be inversely associated with positive psychology traits and personal spirituality, uniquely personal spirituality was protective against degree of substance use across both age cohorts. Overall interpretation of the study findings suggests that personal spirituality may be foundational to positive psychology traits in the majority of people. PMID:25862339

  15. Engrafted Human Induced Pluripotent Stem Cell-Derived Anterior Specified Neural Progenitors Protect the Rat Crushed Optic Nerve

    PubMed Central

    Satarian, Leila; Javan, Mohammad; Kiani, Sahar; Hajikaram, Maryam; Mirnajafi-Zadeh, Javad; Baharvand, Hossein

    2013-01-01

    Background Degeneration of retinal ganglion cells (RGCs) is a common occurrence in several eye diseases. This study examined the functional improvement and protection of host RGCs in addition to the survival, integration and neuronal differentiation capabilities of anterior specified neural progenitors (NPs) following intravitreal transplantation. Methodology/Principal Findings NPs were produced under defined conditions from human induced pluripotent stem cells (hiPSCs) and transplanted into rats whose optic nerves have been crushed (ONC). hiPSCs were induced to differentiate into anterior specified NPs by the use of Noggin and retinoic acid. The hiPSC-NPs were labeled by green fluorescent protein or a fluorescent tracer 1,1′ -dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) and injected two days after induction of ONC in hooded rats. Functional analysis according to visual evoked potential recordings showed significant amplitude recovery in animals transplanted with hiPSC-NPs. Retrograde labeling by an intra-collicular DiI injection showed significantly higher numbers of RGCs and spared axons in ONC rats treated with hiPSC-NPs or their conditioned medium (CM). The analysis of CM of hiPSC-NPs showed the secretion of ciliary neurotrophic factor, basic fibroblast growth factor, and insulin-like growth factor. Optic nerve of cell transplanted groups also had increased GAP43 immunoreactivity and myelin staining by FluoroMyelin™ which imply for protection of axons and myelin. At 60 days post-transplantation hiPSC-NPs were integrated into the ganglion cell layer of the retina and expressed neuronal markers. Conclusions/Significance The transplantation of anterior specified NPs may improve optic nerve injury through neuroprotection and differentiation into neuronal lineages. These NPs possibly provide a promising new therapeutic approach for traumatic optic nerve injuries and loss of RGCs caused by other diseases. PMID:23977164

  16. 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. PMID:26953144

  17. 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

  18. Downregulation of Bim by brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from paclitaxel but not etoposide or cisplatin-induced cell death.

    PubMed

    Li, Z; Zhang, J; Liu, Z; Woo, C-W; Thiele, C J

    2007-02-01

    Chemoresistance and increased expression of TrkB and brain-derived neurotrophic factor (BDNF) are biomarkers of poor prognosis in tumors from patients with neuroblastoma (NB). Previously, we found BDNF activation of TrkB through PI3K/Akt protects NB from etoposide/cisplatin-induced cell death. In this study, the role of Bim, a proapoptotic protein, was investigated. Bim was involved in paclitaxel but not etoposide or cisplatin-induced cell death in NB cells. Pharmacological and genetic studies showed that BDNF-induced decreases in Bim were regulated by MAPK and not PI3K/Akt pathway. Both MAPK and PI3K pathways were involved in BDNF protection of NB cells from paclitaxel-induced cell death, while PI3K predominantly mediated BDNF protection of NB cells from etoposide or cisplatin-induced cell death. These data indicate that different chemotherapeutic drugs induce distinct death pathways and growth factors utilize different signal transduction pathways to modulate the effects of chemotherapy on cells. PMID:16778834

  19. Full protection against African horsesickness (AHS) in horses induced by baculovirus-derived AHS virus serotype 4 VP2, VP5 and VP7.

    PubMed

    Martínez-Torrecuadrada, J L; Díaz-Laviada, M; Roy, P; Sánchez, C; Vela, C; Sánchez-Vizcaíno, J M; Casal, J I

    1996-06-01

    African horsesickness virus serotype 4 (AHSV-4) outer capsid protein VP2, or VP2 and VP5 plus inner capsid protein VP7, derived from single or dual recombinant baculovirus expression vectors were used in different combinations to immunize horses. When the proteins were purified by affinity chromatography, the combination of all three proteins induced low levels of neutralizing antibodies and conferred protection against virulent virus challenge. However, purified VP2 or VP2 and VP5 in the absence of VP7 failed to induce neutralizing antibodies and protection. Immunization with non-purified proteins enhanced the titres of neutralizing antibodies. Again, the combination of the three proteins was able to confer total protection to immunized horses, which showed absence of viraemia. The antigenicity of recombinant VP2 was analysed with a collection of 30 MAbs. Both purified and unpurified recombinant VP2 proteins showed different antigenic patterns in comparison to that of VP2 on virions. An immunization experiment with four more horses confirmed these results. The vaccine described here would not only prevent the disease, but would drastically reduce the propagation of the virus by vectors. PMID:8683209

  20. A new strategy for the synthesis of taurine derivatives using the 'safety-catch' principle for the protection of sulfonic acids.

    PubMed

    Seeberger, Sonja; Griffin, Roger J; Hardcastle, Ian R; Golding, Bernard T

    2007-01-01

    The safety-catch principle has been applied for the development of a new method for protecting sulfonic acids. 2,2-Dimethylsuccinic acid was reduced to 2,2-dimethylbutane-1,4-diol, which was selectively silylated to give 4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutan-1-ol. Reaction of the latter compound with 2-chloroethanesulfonyl chloride in the presence of triethylamine afforded 4-(tert-butyldiphenylsilyloxy)-2,2-dimethylbutyl ethenesulfonate directly. The ethenesulfonate underwent Michael-type addition with secondary amines to give protected derivatives of taurine (2-aminoethanesulfonic acid). Deprotection was achieved on treatment with tetrabutylammonium fluoride, whereby cleavage of the silicon-oxygen bond led to an intermediate alkoxide that immediately cyclised to 2,2-dimethyltetrahydrofuran with liberation of a sulfonate. Pure sulfonic acids were obtained from the crude product by ion exchange chromatography on a strongly basic resin, which was eluted with aqueous acetic acid. The method developed should be generally applicable to the protection of sulfonic acids and is amenable to a multiparallel format. PMID:17164917

  1. Intranasal Vaccination With Salmonella-Derived Serodominant Secreted Effector Protein B Associated With Gas-Filled Microbubbles Partially Protects Against Gut Infection in Mice.

    PubMed

    Pigny, Fiona; Lassus, Anne; Terrettaz, Jacques; Tranquart, François; Corthésy, Blaise; Bioley, Gilles

    2016-08-01

    Salmonella infection is an increasingly important public health problem owing to the emergence of multidrug resistance and the lack of broadly efficient vaccines. Novel strategies of vaccination are required to induce protective immune responses at mucosal surfaces and in the circulation, to limit bacteria entry and dissemination. To this aim, intranasal anti-Salmonella vaccination with an innovative formulation composed of gas-filled microbubbles and the pathogen-derived protective protein serodominant secreted effector protein B (SseB-MB) was evaluated in a mouse infection model. Intranasal application of SseB-MB induced gut and systemic immunoglobulin A, T-helper type 17 cell (Th17), and Th1 responses, all of which are associated with natural immunity against Salmonella In vaccinated mice, a significant reduction in bacterial load was observed in intestinal tissues and the spleen after an otherwise lethal oral infection. Therefore, MB serve as an efficient carrier for nasal delivery of a Salmonella antigen that results in protection upon activation of the common mucosal immune system. PMID:27122591

  2. Immunogenicity and Protective Efficacy of a Vero Cell Culture-Derived Whole-Virus H7N9 Vaccine in Mice and Guinea Pigs

    PubMed Central

    Wodal, Walter; Schwendinger, Michael G.; Savidis-Dacho, Helga; Crowe, Brian A.; Hohenadl, Christine; Fritz, Richard; Brühl, Peter; Portsmouth, Daniel; Karner-Pichl, Anita; Balta, Dalida; Grillberger, Leopold; Kistner, Otfried; Barrett, P. Noel; Howard, M. Keith

    2015-01-01

    Background A novel avian H7N9 virus with a high case fatality rate in humans emerged in China in 2013. We evaluated the immunogenicity and protective efficacy of a candidate Vero cell culture-derived whole-virus H7N9 vaccine in small animal models. Methods Antibody responses induced in immunized DBA/2J mice and guinea pigs were evaluated by hemagglutination inhibition (HI), microneutralization (MN), and neuraminidase inhibition (NAi) assays. T-helper cell responses and IgG subclass responses in mice were analyzed by ELISPOT and ELISA, respectively. Vaccine efficacy against lethal challenge with wild-type H7N9 virus was evaluated in immunized mice. H7N9-specific antibody responses induced in mice and guinea pigs were compared to those induced by a licensed whole-virus pandemic H1N1 (H1N1pdm09) vaccine. Results The whole-virus H7N9 vaccine induced dose-dependent H7N9-specific HI, MN and NAi antibodies in mice and guinea pigs. Evaluation of T-helper cell responses and IgG subclasses indicated the induction of a balanced Th1/Th2 response. Immunized mice were protected against lethal H7N9 challenge in a dose-dependent manner. H7N9 and H1N1pdm09 vaccines were similarly immunogenic. Conclusions The induction of H7N9-specific antibody and T cell responses and protection against lethal challenge suggest that the Vero cell culture-derived whole-virus vaccine would provide an effective intervention against the H7N9 virus. PMID:25719901

  3. Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Eldridge, Sandy; Guo, Liang; Mussio, Jodie; Furniss, Mike; Hamre, John; Davis, Myrtle

    2014-10-01

    Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as an in vitro model system in cardiac biology and in drug discovery (e.g., cardiotoxicity testing). Qualification of these cells for use in mechanistic investigations will require detailed evaluations of cardiomyocyte signaling pathways and cellular responses. ErbB signaling and the ligand neuregulin play critical roles in survival and functional integrity of cardiac myocytes. As such, we sought to characterize the expression and activity of the ErbB family of receptors. Antibody microarray analysis performed on cell lysates derived from maturing hiPSC-CMs detected expression of ∼570 signaling proteins. EGFR/ErbB1, HER2/ErbB2, and ErbB4, but not ErbB3 receptors, of the epidermal growth factor receptor family were confirmed by Western blot. Activation of ErbB signaling by neuregulin-1β (NRG, a natural ligand for ErbB4) and its modulation by trastuzumab (a monoclonal anti-ErbB2 antibody) and lapatinib (a small molecule ErbB2 tyrosine kinase inhibitor) were evaluated through assessing phosphorylation of AKT and Erk1/2, two major downstream kinases of ErbB signaling, using nanofluidic proteomic immunoassay. Downregulation of ErbB2 expression by siRNA silencing attenuated NRG-induced AKT and Erk1/2 phosphorylation. Activation of ErbB signaling with NRG, or inhibition with trastuzumab, alleviated or aggravated doxorubicin-induced cardiomyocyte damage, respectively, as assessed by a real-time cellular impedance analysis and ATP measurement. Collectively, these results support the expanded use of hiPSC-CMs to examine mechanisms of cardiotoxicity and support the value of using these cells in early assessments of cardiotoxicity or efficacy. PMID:25055963

  4. Examining the Protective Role of ErbB2 Modulation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

    PubMed Central

    Eldridge, Sandy; Mussio, Jodie; Furniss, Mike; Hamre, John; Davis, Myrtle

    2014-01-01

    Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as an in vitro model system in cardiac biology and in drug discovery (e.g., cardiotoxicity testing). Qualification of these cells for use in mechanistic investigations will require detailed evaluations of cardiomyocyte signaling pathways and cellular responses. ErbB signaling and the ligand neuregulin play critical roles in survival and functional integrity of cardiac myocytes. As such, we sought to characterize the expression and activity of the ErbB family of receptors. Antibody microarray analysis performed on cell lysates derived from maturing hiPSC-CMs detected expression of ∼570 signaling proteins. EGFR/ErbB1, HER2/ErbB2, and ErbB4, but not ErbB3 receptors, of the epidermal growth factor receptor family were confirmed by Western blot. Activation of ErbB signaling by neuregulin-1β (NRG, a natural ligand for ErbB4) and its modulation by trastuzumab (a monoclonal anti-ErbB2 antibody) and lapatinib (a small molecule ErbB2 tyrosine kinase inhibitor) were evaluated through assessing phosphorylation of AKT and Erk1/2, two major downstream kinases of ErbB signaling, using nanofluidic proteomic immunoassay. Downregulation of ErbB2 expression by siRNA silencing attenuated NRG-induced AKT and Erk1/2 phosphorylation. Activation of ErbB signaling with NRG, or inhibition with trastuzumab, alleviated or aggravated doxorubicin-induced cardiomyocyte damage, respectively, as assessed by a real-time cellular impedance analysis and ATP measurement. Collectively, these results support the expanded use of hiPSC-CMs to examine mechanisms of cardiotoxicity and support the value of using these cells in early assessments of cardiotoxicity or efficacy. PMID:25055963

  5. Zinc protects against diabetes-induced pathogenic changes in the aorta: roles of metallothionein and nuclear factor (erythroid-derived 2)-like 2

    PubMed Central

    2013-01-01

    Background Cardiovascular diseases remain a leading cause of the mortality world-wide, which is related to several risks, including the life style change and the increased diabetes prevalence. The present study was to explore the preventive effect of zinc on the pathogenic changes in the aorta. Methods A genetic type 1 diabetic OVE26 mouse model was used with/without zinc supplementation for 3 months. To determine gender difference either for pathogenic changes in the aorta of diabetic mice or for zinc protective effects on diabetes-induced pathogenic changes, both males and females were investigated in parallel by histopathological and immunohistochemical examinations, in combination of real-time PCR assay. Results Diabetes induced significant increases in aortic oxidative damage, inflammation, and remodeling (increased fibrosis and wall thickness) without significant difference between genders. Zinc treatment of these diabetic mice for three months completely prevented the above pathogenic changes in the aorta, and also significantly up-regulated the expression and function of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a pivotal regulator of anti-oxidative mechanism, and the expression of metallothionein (MT), a potent antioxidant. There was gender difference for the protective effect of zinc against diabetes-induced pathogenic changes and the up-regulated levels of Nrf2 and MT in the aorta. Conclusions These results suggest that zinc supplementation provides a significant protection against diabetes-induced pathogenic changes in the aorta without gender difference in the type 1 diabetic mouse model. The aortic protection by zinc against diabetes-induced pathogenic changes is associated with the up-regulation of both MT and Nrf2 expression. PMID:23536959

  6. Thermally stable derivatives or propylenepolyamines as protective additives for lubricating oils used in compressors handling hydrogen sulfide-containing gas

    SciTech Connect

    Trofimov, V.A.; Panidi, I.S.; Spirkin, V.G.

    1995-09-01

    In the transmission of natural, associated, and petroleum gases containing hydrogen sulfide, carbon dioxide, water, and other corrosive impurities, problems are created by the saturation of the compressor lubricating oil with these impurities and failure of components of the lubricating and sealing system. Hydrogen sulfide is distinguished by the greatest affinity for oil and the highest corrosivity. Its solubility in oils may be as high as 10 g/liter under standard conditions. In the work reported here, we investigated the protective properties of salts and amides based on higher aliphatic, alkylaromatic, and unsaturated carboxylic acids with certain substituted propylenepolyamines. In synthesizing the additives, we used the following: a commercial C{sub 17} - C{sub 20} fraction of synthetic fatty acids (SFA): C{sub 25+} still bottoms; technical alkyl (C{sub 16} - C {sub 18}) salicylic acids; and oleic acid. From these materials, we obtained salts and amides of N,N-dimethylpropanediamine, N-benzylpropanediamine, N-cyanoethylpropanediamine, N,N,N`,N`-tetramethyldipropylenetriamine, and N,N-dimethyldipropylenetriamine.

  7. Improved performance by plasma-treated silicate phosphor particles with a sol-gel derived protective coating of indium oxide

    NASA Astrophysics Data System (ADS)

    Kim, Hyeon; Yun, Changhun; Jeon, Sie Wook; Lee, June Key; Kim, Jae Pil

    2016-03-01

    The optical properties and reliability of silicate phosphor was fairly improved by an amorphous In2O3 protective coating on plasma-treated phosphor particles. The In2O3 layers were coated using a conventional sol-gel method with alkoxide precursor in N2 gas. The surface morphology of silicate particles was smoother after Ar-plasma surface modification. When plasma surface treatment of the phosphor was applied before sol-gel coating, the In2O3 coating was almost 3-times thicker, and the surface of the phosphor particles was smoother, than could be obtained when sol-gel coating was not preceded by plasma treatment. This was because the treatment caused the surface to become hydrophilic. The light absorption rate and quantum efficiency were increased from 75.3% and 93.8%, to 79.2% and 95.7%, after plasma-treated In2O3 coating. Bare silicate phosphor used in 450-nm vertical-type LEDs, displayed 10% decreased optical output, whereas In2O3-coated phosphor showed just 3% decreased optical output after 1000 h of input current at 350 mA; under conditions of high humidity and high temperature.

  8. Pigment Epithelium-Derived Factor (PEDF) Protects Osteoblastic Cell Line from Glucocorticoid-Induced Apoptosis via PEDF-R.

    PubMed

    Yao, Shengcheng; Zhang, Yingnan; Wang, Xiaoyu; Zhao, Fengchao; Sun, Maji; Zheng, Xin; Dong, Hongyan; Guo, Kaijin

    2016-01-01

    Pigment epithelial-derived factor (PEDF) is known as a widely expressed multifunctional secreted glycoprotein whose biological actions are cell-type dependent. Recent studies demonstrated that PEDF displays cytoprotective activity in several cell types. However, it remains unknown whether PEDF is involved in glucocorticoid-induced osteoblast death. The aim of this study was to examine the role of PEDF in osteoblast survival in response to dexamethasone, an active glucocorticoid analogue, and explore the underlying mechanism. In the present study, dexamethasone (DEX) was used to induce MC3T3-E1 pre-osteoblast apoptosis. PEDF mRNA and protein levels and cell apoptosis were determined respectively. Then PEDF receptor (PEDF-R)- and lysophosphatidic acid (LPA)-related signal transductions were assessed. Here we show that DEX down-regulates PEDF expression, which contributes to osteoblast apoptosis. As a result, exogenous recombinant PEDF (rPEDF) inhibited DEX-induced cell apoptosis. We confirmed that PEDF-R was expressed on MC3T3-E1 pre-osteoblast membrane and could bind to PEDF which increased the level of LPA and activated the phosphorylation of Akt. Our results suggest that PEDF attenuated DEX-induced apoptosis in MC3T3-E1 pre-osteoblasts through LPA-dependent Akt activation via PEDF-R. PMID:27187377

  9. Derivation of soil screening thresholds to protect chisel-toothed kangaroo rat from uranium mine waste in northern Arizona

    USGS Publications Warehouse

    Hinck, Jo E.; Linder, Greg L.; Otton, James K.; Finger, Susan E.; Little, Edward E.; Tillitt, Donald E.

    2013-01-01

    Chemical data from soil and weathered waste material samples collected from five uranium mines north of the Grand Canyon (three reclaimed, one mined but not reclaimed, and one never mined) were used in a screening-level risk analysis for the Arizona chisel-toothed kangaroo rat (Dipodomys microps leucotis); risks from radiation exposure were not evaluated. Dietary toxicity reference values were used to estimate soil-screening thresholds presenting risk to kangaroo rats. Sensitivity analyses indicated that body weight critically affected outcomes of exposed-dose calculations; juvenile kangaroo rats were more sensitive to the inorganic constituent toxicities than adult kangaroo rats. Species-specific soil-screening thresholds were derived for arsenic (137 mg/kg), cadmium (16 mg/kg), copper (1,461 mg/kg), lead (1,143 mg/kg), nickel (771 mg/kg), thallium (1.3 mg/kg), uranium (1,513 mg/kg), and zinc (731 mg/kg) using toxicity reference values that incorporate expected chronic field exposures. Inorganic contaminants in soils within and near the mine areas generally posed minimal risk to kangaroo rats. Most exceedances of soil thresholds were for arsenic and thallium and were associated with weathered mine wastes.

  10. DNA Microarray Highlights Nrf2-Mediated Neuron Protection Targeted by Wasabi-Derived Isothiocyanates in IMR-32 Cells.

    PubMed

    Trio, Phoebe Zapanta; Fujisaki, Satoru; Tanigawa, Shunsuke; Hisanaga, Ayami; Sakao, Kozue; Hou, De-Xing

    2016-01-01

    6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC), 6-(methylthio)hexyl isothiocyanate (6-MTITC), and 4-(methylsulfinyl)butyl isothiocyanate (4-MSITC) are isothiocyanate (ITC) bioactive compounds from Japanese Wasabi. Previous in vivo studies highlighted the neuroprotective potential of ITCs since ITCs enhance the production of antioxidant-related enzymes. Thus, in this present study, a genome-wide DNA microarray analysis was designed to profile gene expression changes in a neuron cell line, IMR-32, stimulated by these ITCs. Among these ITCs, 6-MSITC caused the expression changes of most genes (263), of which 100 genes were upregulated and 163 genes were downregulated. Gene categorization showed that most of the differentially expressed genes are involved in oxidative stress response, and pathway analysis further revealed that Nrf2-mediated oxidative stress pathway is the top of the ITC-modulated signaling pathway. Finally, real-time polymerase chain reaction (PCR) and Western blotting confirmed the gene expression and protein products of the major targets by ITCs. Taken together, Wasabi-derived ITCs might target the Nrf2-mediated oxidative stress pathway to exert neuroprotective effects. PMID:27547033

  11. Pigment Epithelium-Derived Factor (PEDF) Protects Osteoblastic Cell Line from Glucocorticoid-Induced Apoptosis via PEDF-R

    PubMed Central

    Yao, Shengcheng; Zhang, Yingnan; Wang, Xiaoyu; Zhao, Fengchao; Sun, Maji; Zheng, Xin; Dong, Hongyan; Guo, Kaijin

    2016-01-01

    Pigment epithelial-derived factor (PEDF) is known as a widely expressed multifunctional secreted glycoprotein whose biological actions are cell-type dependent. Recent studies demonstrated that PEDF displays cytoprotective activity in several cell types. However, it remains unknown whether PEDF is involved in glucocorticoid-induced osteoblast death. The aim of this study was to examine the role of PEDF in osteoblast survival in response to dexamethasone, an active glucocorticoid analogue, and explore the underlying mechanism. In the present study, dexamethasone (DEX) was used to induce MC3T3-E1 pre-osteoblast apoptosis. PEDF mRNA and protein levels and cell apoptosis were determined respectively. Then PEDF receptor (PEDF-R)- and lysophosphatidic acid (LPA)-related signal transductions were assessed. Here we show that DEX down-regulates PEDF expression, which contributes to osteoblast apoptosis. As a result, exogenous recombinant PEDF (rPEDF) inhibited DEX-induced cell apoptosis. We confirmed that PEDF-R was expressed on MC3T3-E1 pre-osteoblast membrane and could bind to PEDF which increased the level of LPA and activated the phosphorylation of Akt. Our results suggest that PEDF attenuated DEX-induced apoptosis in MC3T3-E1 pre-osteoblasts through LPA-dependent Akt activation via PEDF-R. PMID:27187377

  12. DNA Microarray Highlights Nrf2-Mediated Neuron Protection Targeted by Wasabi-Derived Isothiocyanates in IMR-32 Cells

    PubMed Central

    Trio, Phoebe Zapanta; Fujisaki, Satoru; Tanigawa, Shunsuke; Hisanaga, Ayami; Sakao, Kozue; Hou, De-Xing

    2016-01-01

    6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC), 6-(methylthio)hexyl isothiocyanate (6-MTITC), and 4-(methylsulfinyl)butyl isothiocyanate (4-MSITC) are isothiocyanate (ITC) bioactive compounds from Japanese Wasabi. Previous in vivo studies highlighted the neuroprotective potential of ITCs since ITCs enhance the production of antioxidant-related enzymes. Thus, in this present study, a genome-wide DNA microarray analysis was designed to profile gene expression changes in a neuron cell line, IMR-32, stimulated by these ITCs. Among these ITCs, 6-MSITC caused the expression changes of most genes (263), of which 100 genes were upregulated and 163 genes were downregulated. Gene categorization showed that most of the differentially expressed genes are involved in oxidative stress response, and pathway analysis further revealed that Nrf2-mediated oxidative stress pathway is the top of the ITC-modulated signaling pathway. Finally, real-time polymerase chain reaction (PCR) and Western blotting confirmed the gene expression and protein products of the major targets by ITCs. Taken together, Wasabi-derived ITCs might target the Nrf2-mediated oxidative stress pathway to exert neuroprotective effects. PMID:27547033

  13. Fatigue is a Brain-Derived Emotion that Regulates the Exercise Behavior to Ensure the Protection of Whole Body Homeostasis

    PubMed Central

    Noakes, Timothy David

    2012-01-01

    An influential book written by A. Mosso in the late nineteenth century proposed that fatigue that “at first sight might appear an imperfection of our body, is on the contrary one of its most marvelous perfections. The fatigue increasing more rapidly than the amount of work done saves us from the injury which lesser sensibility would involve for the organism” so that “muscular fatigue also is at bottom an exhaustion of the nervous system.” It has taken more than a century to confirm Mosso’s idea that both the brain and the muscles alter their function during exercise and that fatigue is predominantly an emotion, part of a complex regulation, the goal of which is to protect the body from harm. Mosso’s ideas were supplanted in the English literature by those of A. V. Hill who believed that fatigue was the result of biochemical changes in the exercising limb muscles – “peripheral fatigue” – to which the central nervous system makes no contribution. The past decade has witnessed the growing realization that this brainless model cannot explain exercise performance. This article traces the evolution of our modern understanding of how the CNS regulates exercise specifically to insure that each exercise bout terminates whilst homeostasis is retained in all bodily systems. The brain uses the symptoms of fatigue as key regulators to insure that the exercise is completed before harm develops. These sensations of fatigue are unique to each individual and are illusionary since their generation is largely independent of the real biological state of the athlete at the time they develop. The model predicts that attempts to understand fatigue and to explain superior human athletic performance purely on the basis of the body’s known physiological and metabolic responses to exercise must fail since subconscious and conscious mental decisions made by winners and losers, in both training and competition, are the ultimate determinants of both fatigue and athletic

  14. Pelleted Bone Marrow Derived Mesenchymal Stem Cells Are Better Protected from the Deleterious Effects of Arthroscopic Heat Shock

    PubMed Central

    Kalamegam, Gauthaman; Abbas, Mohammed; Gari, Mamdooh; Alsehli, Haneen; Kadam, Roaa; Alkaff, Mohammed; Chaudhary, Adeel; Al-Qahtani, Mohammed; Abuzenadah, Adel; Kafienah, Wael; Mobasheri, Ali

    2016-01-01

    Introduction: The impact of arthroscopic temperature on joint tissues is poorly understood and it is not known how mesenchymal stem cells (MSCs) respond to the effects of heat generated by the device during the process of arthroscopy assisted experimental cell-based therapy. In the present study, we isolated and phenotypically characterized human bone marrow mesenchymal stem cells (hBMMSCs) from osteoarthritis (OA) patients, and evaluated the effect of arthroscopic heat on cells in suspension and pellet cultures. Methods: Primary cultures of hBMMSCs were isolated from bone marrow aspirates of OA patients and cultured using DMEM supplemented with 10% FBS and characterized for their stemness. hBMMSCs (1 × 106 cells) cultured as single cell suspensions or cell pellets were exposed to an illuminated arthroscope for 10, 20, or 30 min. This was followed by analysis of cellular proliferation and heat shock related gene expression. Results: hBMMSCs were viable and exhibited population doubling, short spindle morphology, MSC related CD surface markers expression and tri-lineage differentiation into adipocytes, chondrocytes and osteoblasts. Chondrogenic and osteogenic differentiation increased collagen production and alkaline phosphatase activity. Exposure of hBMMSCs to an illuminated arthroscope for 10, 20, or 30 min for 72 h decreased metabolic activity of the cells in suspensions (63.27% at 30 min) and increased metabolic activity in cell pellets (62.86% at 10 min and 68.57% at 20 min). hBMMSCs exposed to 37, 45, and 55°C for 120 s demonstrated significant upregulation of BAX, P53, Cyclin A2, Cyclin E1, TNF-α, and HSP70 in cell suspensions compared to cell pellets. Conclusions: hBMMSC cell pellets are better protected from temperature alterations compared to cell suspensions. Transplantation of hBMMSCs as pellets rather than as cell suspensions to the cartilage defect site would therefore support their viability and may aid enhanced cartilage regeneration. PMID

  15. Plant-derived H7 VLP vaccine elicits protective immune response against H7N9 influenza virus in mice and ferrets.

    PubMed

    Pillet, S; Racine, T; Nfon, C; Di Lenardo, T Z; Babiuk, S; Ward, B J; Kobinger, G P; Landry, N

    2015-11-17

    In March 2013, the Chinese Centre for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A H7N9 virus. Infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. The risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. Here, we describe the rapid (19 days) development of a plant-derived VLP vaccine based on the hemagglutinin sequence of influenza H7N9 A/Hangzhou/1/2013. The immunogenicity of the H7 VLP vaccine was assessed in mice and ferrets after one or two intramuscular dose(s) with and without adjuvant (alum or GLA-SE™). In ferrets, we also measured H7-specific cell-mediated immunity. The mice and ferrets were then challenged with H7N9 A/Anhui/1/2013 influenza virus. A single immunization with the adjuvanted vaccine elicited a strong humoral response and protected mice against an otherwise lethal challenge. Two doses of unadjuvanted vaccine significantly increased humoral response and resulted in 100% protection with significant reduction of clinical signs leading to nearly asymptomatic infections. In ferrets, a single immunization with the alum-adjuvanted H7 VLP vaccine induced strong humoral and CMI responses with antigen-specific activation of CD3(+) T cells. Compared to animals injected with placebo, ferrets vaccinated with alum-adjuvanted vaccine displayed no weight loss during the challenge. Moreover, the vaccination significantly reduced the viral load in lungs and nasal washes 3 days after the infection. This candidate plant-made H7 vaccine therefore induced protective responses after either one adjuvanted or two unadjuvanted doses. Studies are currently ongoing to better characterize the immune response elicited by the plant-derived VLP vaccines. Regardless, these data are very promising for the rapid production of an immunogenic and protective vaccine against

  16. Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter.

    PubMed

    Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun; Lovelace, Gregory L; Smith, Charles D; Lemasters, John J

    2013-11-15

    Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50μM of each tetracycline-derived compound 20 min prior to exposure to 500μM iodoacetic acid plus 1mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs-Ringer-HEPES buffer at pH6.2 for 4h prior to reoxygenation at pH7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca(2+) uptake was measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca(2+) uptake and suppressed the Ca(2+)-induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca(2+) uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. PMID:24012766

  17. Minocycline and Doxycycline, but not Other Tetracycline-Derived Compounds, Protect Liver Cells from Chemical Hypoxia and Ischemia/Reperfusion Injury by Inhibition of the Mitochondrial Calcium Uniporter

    PubMed Central

    Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun; Lovelace, Gregory L.; Smith, Charles D.; Lemasters, John J.

    2015-01-01

    Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs-Ringer-Hepes buffer (KRH) at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca2+ uptake was measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometery was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca2+ uptake and suppressed the Ca2+-induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca2+ uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. PMID:24012766

  18. Protective effects of exercise in metabolic disorders are mediated by inhibition of mitochondrial-derived sterile inflammation.

    PubMed

    Peeri, Maghsoud; Amiri, Shayan

    2015-12-01

    While beneficial properties of physical activity and exercise on human health have been extensively reported in literature, the exact mechanism(s) underpinning impacts of exercise are not well understood. Focusing on metabolic disorders, as the main causes of social and economic burden in current century, exercise exhibited promising effects in prevention, alleviation and retardation of these disorders including, type 2 diabetes (T2D), Alzheimer's disease (AD), major depressive disorder (MDD) and obesity. Recent evidence has unmasked the role of mitochondrial dysfunction and chronic inflammation in pathophysiology of these disorders. Despite of the wealth of research on the etiology of metabolic disorders, intimate connections between these diseases, complex pathophysiology and their comorbidity still remains a challenging dilemma. In addition, although physical activity has improving effects on human health, it is not clear that how exercise is able to exert its modulatory effects on outcomes of metabolic disorders. Among several mechanisms, we assumed the hypothesis that exercise mitigates the production of mitochondrial-induced reactive oxygen species (ROS) and danger associated molecular patterns (DAMPs) as the main triggering factors for inflammasome formation. Since inflammasomes are of highly deleterious molecules relevant to pathogenesis of metabolic disorders, we hypothesized that beneficial effects of exercise may be associated with its ability to enhance the mitochondrial biogenesis and glucose transportation through generation of brain derived neurotrophic factor (BDNF). Also, we proposed that boosting impact of exercise on autophagy process accelerates the elimination of damaged mitochondria and thus, results in considerable decrease in production of ROS and DAMPs and consequently sterile inflammation. PMID:26527493

  19. A novel polysaccharide compound derived from algae extracts protects retinal pigment epithelial cells from high glucose-induced oxidative damage in vitro.

    PubMed

    Xie, Peiyu; Fujii, Isao; Zhao, Ji'en; Shinohara, Makoto; Matsukura, Makoto

    2012-01-01

    Diabetic retinopathy is a common complication of diabetes mellitus (DM). The oxidative damage inflicted on retinal pigment epithelial (RPE) cells by high glucose closely approximates the molecular basis for the loss of vision associated with this disease. We investigate a novel algae-derived polysaccharide compound for its role in protecting ARPE-19 cells from high glucose-induced oxidative damage. ARPE-19 cells were cultured for 4 d with normal concentration of D-glucose, and exposed to either normal or high concentrations of D-glucose in the presence or absence of the polysaccharide compound at variety of concentrations for another 48 h. Taurine was used as a positive control. Activity of super oxide dismutase (SOD) and concentration of glutathione (GSH) were measured as well as cytotoxicity of high glucose and the polysaccharide compound. To analyse cellular damage by high glucose, activation of Annexin V and p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) were examined. Our results showed that a significant cellular damage on ARPE-19 cells after 48 h treatment with high glucose, accompanied by a decrease in SOD activity and GSH concentration; high glucose also caused ARPE-19 cell apoptosis and activation of p38MAPK and ERK. As the non-toxic polysaccharide compound protected ARPE-19 cells from high glucose-induced cellular damage, the compound recovered SOD activity and concentration of GSH in the cells. The compound also abrogated the cell apoptosis and activation of p38MAPK and ERK. Therefore, the polysaccharide compound derived from algae extracts could be unique candidate for a new class of anti-DM and anti-oxidative damage. PMID:22975494

  20. Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice

    PubMed Central

    2010-01-01

    Antibodies generated against West Nile virus (WNV) during infection are essential for controlling dissemination. Recent studies have demonstrated that epitopes in all three domains of the flavivirus envelope protein (E) are targets for neutralizing antibodies, with determinants in domain III (DIII) eliciting antibodies with strong inhibitory properties. In order to increase the magnitude and quality of the antibody response against the WNV E protein, DNA vaccines with derivatives of the WNV E gene (full length E, truncated E, or DIII region, some in the context of the pre-membrane [prM] gene) were conjugated to the molecular adjuvant P28. The P28 region of the complement protein C3d is the minimum CR2-binding domain necessary for the adjuvant activity of C3d. Delivery of DNA-based vaccines by gene gun and intramuscular routes stimulated production of IgG antibodies against the WNV DIII region of the E protein. With the exception of the vaccine expressing prM/E given intramuscularly, only mice that received DNA vaccines by gene gun produced protective neutralizing antibody titers (FRNT80 titer >1/40). Correspondingly, mice vaccinated by the gene gun route were protected to a greater level from lethal WNV challenge. In general, mice vaccinated with P28-adjuvated vaccines produced higher IgG titers than mice vaccinated with non-adjuvanted vaccines. PMID:20462412

  1. Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice.

    PubMed

    Dunn, Matthew D; Rossi, Shannan L; Carter, Donald M; Vogt, Matthew R; Mehlhop, Erin; Diamond, Michael S; Ross, Ted M

    2010-01-01

    Antibodies generated against West Nile virus (WNV) during infection are essential for controlling dissemination. Recent studies have demonstrated that epitopes in all three domains of the flavivirus envelope protein (E) are targets for neutralizing antibodies, with determinants in domain III (DIII) eliciting antibodies with strong inhibitory properties. In order to increase the magnitude and quality of the antibody response against the WNV E protein, DNA vaccines with derivatives of the WNV E gene (full length E, truncated E, or DIII region, some in the context of the pre-membrane [prM] gene) were conjugated to the molecular adjuvant P28. The P28 region of the complement protein C3d is the minimum CR2-binding domain necessary for the adjuvant activity of C3d. Delivery of DNA-based vaccines by gene gun and intramuscular routes stimulated production of IgG antibodies against the WNV DIII region of the E protein. With the exception of the vaccine expressing prM/E given intramuscularly, only mice that received DNA vaccines by gene gun produced protective neutralizing antibody titers (FRNT80 titer >1/40). Correspondingly, mice vaccinated by the gene gun route were protected to a greater level from lethal WNV challenge. In general, mice vaccinated with P28-adjuvated vaccines produced higher IgG titers than mice vaccinated with non-adjuvanted vaccines. PMID:20462412

  2. Squamosamide derivative FLZ protects retinal pigment epithelium cells from oxidative stress through activation of epidermal growth factor receptor (EGFR)-AKT signaling.

    PubMed

    Cheng, Li-Bo; Chen, Chun-Ming; Zhong, Hong; Zhu, Li-Juan

    2014-01-01

    Reactive oxygen species (ROS)-mediated retinal pigment epithelium (RPE) cell apoptosis is attributed to age-related macular degeneration (AMD) pathogenesis. FLZ, a novel synthetic squamosamide derivative from a Chinese herb, Annona glabra, has displayed significant cyto-protective activity. In the current study, we explored the pro-survival effect of FLZ in oxidative stressed-RPE cells and studied the underlying signaling mechanisms. Our results showed that FLZ attenuated hydrogen peroxide (H2O2)-induced viability decrease and apoptosis in the RPE cell line (ARPE-19 cells) and in primary mouse RPE cells. Western blotting results showed that FLZ activated AKT signaling in RPE cells. The AKT-specific inhibitor, MK-2206, the phosphoinositide 3-kinase (PI3K)/AKT pan inhibitor, wortmannin, and AKT1-shRNA (short hairpin RNA) depletion almost abolished FLZ-mediated pro-survival/anti-apoptosis activity. We discovered that epidermal growth factor receptor (EGFR) trans-activation mediated FLZ-induced AKT activation and the pro-survival effect in RPE cells, and the anti-apoptosis effect of FLZ against H2O2 was inhibited by the EGFR inhibitor, PD153035, or by EGFR shRNA-knockdown. In conclusion, FLZ protects RPE cells from oxidative stress through activation of EGFR-AKT signaling, and our results suggest that FLZ might have therapeutic values for AMD. PMID:25329617

  3. Protections of SMND-309, a novel derivate of salvianolic acid B, on brain mitochondria contribute to injury amelioration in cerebral ischemia rats.

    PubMed

    Tian, Jingwei; Fu, Fenghua; Li, Guisheng; Gao, Yubai; Zhang, Yunjuan; Meng, Qingsheng; Li, Changlu; Liu, Fu

    2009-08-01

    SMND-309, a novel compound named (2E)-2-{6-[(E)-2-carboxylvinyl]-2,3-dihydroxyphenyl}-3-(3,4-dihydroxyphenyl) propenoic acid, is a new derivate of salvianolic acid B. The present study was conducted to investigate whether SMND-309 has a protective effect on brain injury after focal cerebral ischemia, and if it did so, to investigate its effects on brain mitochondria. Adult male SD rats were subjected to middle cerebral artery occlusion (MCAO) by bipolar electro-coagulation. Behavioral tests and brain patho-physiological tests were used to evaluate the damage to central nervous system. Origin targets including mitochondria production of reactive oxygen species, antioxidant potentia, membrane potential, energy metabolism, mitochondrial respiratory enzymes activities and mitochondria swelling degree were evaluated. The results showed that SMND-309 decreased neurological deficit scores, reduced the number of dead hippocampal neuronal cells in accordance with its depression on mitochondria swelling degree, reactive oxygen species production, improvements on mitochondria swelling, energy metabolism, membrane potential level and mitochondrial respiratory chain complex activities. All of these findings indicate that SMND-309 exerted potent neuroprotective effects in the model of permanent cerebral ischemia, contributed to its protections on brain mitochondrial structure and function. PMID:19481432

  4. Protective effect of 17β-estradiol on serum deprivation-induced apoptosis and oxidative stress in bone marrow-derived mesenchymal stem cells.

    PubMed

    Mirzamohammadi, S; Mehrabani, M; Tekiyehmaroof, N; Sharifi, A M

    2016-03-01

    Stem cell transplantation has indicated great promise for cell therapy in a wide range of diseases, but poor and insufficient viability of cells within damaged tissues has limited its potential therapeutic effects. 17 β-Estradiol (E2) is a steroid hormone that plays an important role in expression of many genes and regulating proliferation, viability, and intracellular redox status in different cell types. In this study, we aimed to assess the effect of E2 on bone marrow-derived mesenchymal stem cells (BM-MSCs). Apoptosis was induced by serum deprivation (SD), and cells were exposed to E2 in the presence or absence of serum for varying periods of time, after which cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Expression of proapoptotic and antiapoptotic proteins after exposure to E2 was examined by Western blotting. The ability of E2 to prevent reactive oxygen species (ROS) production was also measured. The results indicated that E2 significantly enhanced the viability of the cells and protected BM-MSCs against SD-induced overproduction of ROS. It could reduce lipid peroxidation, total antioxidant power, and also Bax/Bcl-2 ratio as well as expression of caspase-3. Taken together, our data support that E2 treatment protects BM-MSCs against SD-induced damage by regulating ROS production and upregulation of antiapoptotic/proapoptotic proteins ratio. PMID:25964380

  5. Protective effects of NSP-116, a novel imidazolyl aniline derivative, against light-induced retinal damage in vitro and in vivo.

    PubMed

    Izawa, Hiroshi; Shimazawa, Masamitsu; Inoue, Yuki; Uchida, Seiichi; Moroe, Hiroko; Tsuruma, Kazuhiro; Hara, Hideaki

    2016-07-01

    In this study, we investigated the protective effects of NSP-116 [4-(4-acetylpiperazin-1-yl)-2-(1H-imidazol-1-yl) aniline], a novel imidazolyl aniline derivative, against light-induced photoreceptor cell damage. In an in vitro experiment, murine photoreceptor (661W) cells were damaged by exposure to light for 24h. Viability of 661W cells after light exposure was assessed by Hoechst 33342/Propidium iodide nuclear staining and a tetrazolium salt (WST-8) assay. Intracellular radical production in 661W cells was evaluated using the reactive oxygen species (ROS) sensitive probe 5-(and 6)-chloromethyl-2, 7-dichlorodihydrofluorescein diacetate acetyl ester (CM-H2DCFDA). NSP-116 significantly suppressed light-induced cell death and ROS production in 661W cells. In an in vivo mouse experiment, retinal damage was induced by exposure to white light at 8000lx for 3h after dark adaptation. Retinal damage was evaluated by recording the electroretinogram and measuring the outer nuclear layer (ONL) thickness at 5 days after light exposure. Single oral administration of NSP-116 before light exposure protected retinal function and ONL thinning after light exposure. Furthermore, the effect of NSP-116 on lipid peroxidation was evaluated using thiobarbituric acid reactive substance (TBARS) assay in porcine retina, and was found to decrease the production of TBARS. Electron spin resonance (ESR) measurements showed that NSP-116 exhibited radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide anion radical (∙O2(-)), and hydroxyl radical (∙OH). These findings suggest that NSP-116 has protective effects against light-induced photoreceptor degeneration in vitro and in vivo as a free radical scavenger, and it may be a novel therapeutic agent for retinal degenerative disorders, such as dry age-related macular degeneration (AMD). PMID:27151507

  6. The transplantation of Akt-overexpressing amniotic fluid-derived mesenchymal stem cells protects the heart against ischemia-reperfusion injury in rabbits.

    PubMed

    Wang, Yan; Li, Yigang; Song, Lei; Li, Yanyan; Jiang, Shan; Zhang, Song

    2016-07-01

    Amniotic fluid-derived mesenchymal stem cells (AFMSCs) are an attractive cell source for applications in regenerative medicine, due to characteristics such as proliferative capacity and multipotency. In addition, Akt, a serine‑threonine kinase, maintains stem cells by promoting viability and proliferation. Whether the transplantation of Akt-overexpressing AFMSCs protects the heart against ischemia‑reperfusion (I/R) injury has yet to be elucidated. Accordingly, the Akt gene was overexpressed in AFMSCs using lentiviral transduction, and Akt‑AFMSCs were transplanted into the ischemic myocardium of rabbits prior to reperfusion. Any protective effects resulting from this procedure were subsequently sought after three weeks later. A histological examination revealed that there was a decrease in intramyocardial inflammation and ultrastructural damage, and an increase in capillary density and in the levels of GATA binding protein 4, connexin 43 and cardiac troponin T in the Akt‑AFMSC group compared with the control group. A significant decrease in cardiomyocyte apoptosis, accompanying an increase in phosphorylated Akt and B‑cell lymphoma 2 (Bcl-2) and a decrease in caspase‑3, was also observed. Furthermore, the left ventricular function was markedly augmented in the Akt‑AFMSC group compared with the control group. These observations suggested that the protective effect of AFMSCs may be due to the delivery of secreted cytokines, promotion of neoangiogenesis, prevention of cardiomyocyte apoptosis, transdifferentiation into cardiomyocytes and promotion of the viability of AFMSCs, which are assisted by Akt gene modification. Taken together, the results of the present study have indicated that transplantation of Akt-AFMSCs is able to alleviate myocardial I/R injury and improve cardiac function. PMID:27151366

  7. The transplantation of Akt-overexpressing amniotic fluid-derived mesenchymal stem cells protects the heart against ischemia-reperfusion injury in rabbits

    PubMed Central

    WANG, YAN; LI, YIGANG; SONG, LEI; LI, YANYAN; JIANG, SHAN; ZHANG, SONG

    2016-01-01

    Amniotic fluid-derived mesenchymal stem cells (AFMSCs) are an attractive cell source for applications in regenerative medicine, due to characteristics such as proliferative capacity and multipotency. In addition, Akt, a serine-threonine kinase, maintains stem cells by promoting viability and proliferation. Whether the transplantation of Akt-overexpressing AFMSCs protects the heart against ischemia-reperfusion (I/R) injury has yet to be elucidated. Accordingly, the Akt gene was overexpressed in AFMSCs using lentiviral transduction, and Akt-AFMSCs were transplanted into the ischemic myocardium of rabbits prior to reperfusion. Any protective effects resulting from this procedure were subsequently sought after three weeks later. A histological examination revealed that there was a decrease in intramyocardial inflammation and ultrastructural damage, and an increase in capillary density and in the levels of GATA binding protein 4, connexin 43 and cardiac troponin T in the Akt-AFMSC group compared with the control group. A significant decrease in cardiomyocyte apoptosis, accompanying an increase in phosphorylated Akt and B-cell lymphoma 2 (Bcl-2) and a decrease in caspase-3, was also observed. Furthermore, the left ventricular function was markedly augmented in the Akt-AFMSC group compared with the control group. These observations suggested that the protective effect of AFMSCs may be due to the delivery of secreted cytokines, promotion of neoangiogenesis, prevention of cardiomyocyte apoptosis, transdifferentiation into cardiomyocytes and promotion of the viability of AFMSCs, which are assisted by Akt gene modification. Taken together, the results of the present study have indicated that transplantation of Akt-AFMSCs is able to alleviate myocardial I/R injury and improve cardiac function. PMID:27151366

  8. Protective efficacy of baculovirus-derived influenza virus-like particles bearing H5 HA alone or in combination with M1 in chickens.

    PubMed

    Choi, Jun-Gu; Kim, Min-Chul; Kang, Hyun-Mi; Kim, Kwang-Il; Lee, Kyu-Jun; Park, Choi-Kyu; Kwon, Jun-Hun; Kim, Jae-Hong; Lee, Youn-Jeong

    2013-03-23

    Since 2003, the highly pathogenic avian influenza (HPAI) H5N1 has become a serious problem in animals and an increasing threat to public health. To develop effective vaccines for H5 HPAI in chickens, virus-like particles (VLP) were produced using a baculovirus expression system. The particles comprised hemagglutinin (HA) alone (HA-VLP) or HA in combination with a matrix protein (M1; HAM-VLP) derived from a recent clade 2.3.2.1 H5N1 HPAI virus. To compare the immunogenicity and protective efficacy of these VLPs, 10 μg HAM-VLP, the equivalent amounts of HA incorporated HA-VLP or whole inactivated virus (WIV), were emulsified with mineral oil and used to immunize chickens. The serum hemagglutination inhibition antibody levels induced by HA-VLP and HAM-VLP were comparable to WIV. Antibodies to nucleoprotein were detected only in the WIV group. Immunized chickens in each group survived and were protected against a lethal homologous virus challenge, showing no clinical signs of infection. The challenge virus was detected intermittently in some oropharyngeal swabs, but not in cloacal swabs or various organs, which means that VLPs and WIV provide protection against systemic but not local virus replication in chickens. After the challenge, the HA-VLP group showed significantly increased serum antibody levels compared to the HAM-VLP and WIV groups, and some chickens in the HA-VLP group seroconverted with respect to nucleoprotein. Taken together, these results suggest that VLPs may be an effective method for controlling HPAI in chickens. They could be applied to a differentiating infected from vaccinated animals (DIVA) strategy. In addition, it is likely that HAM-VLP is more efficacious than HA-VLP in chickens. PMID:23265240

  9. A method to derive the relationship between the annual and short-term air quality limits--analysis using the WHO Air Quality Guidelines for health protection.

    PubMed

    Lai, Hak-Kan; Hedley, Anthony J; Thach, Thuan-Quoc; Wong, Chit-Ming

    2013-09-01

    The World Health Organization (WHO) Air Quality Guidelines (AQG) were launched in 2006, but gaps remain in evidence on health impacts and relationships between short-term and annual AQG needed for health protection. We tested whether relationships between WHO short-term and annual AQG for particulates (PM10 and PM2.5) and nitrogen dioxide (NO2) are concordant worldwide and derived the annual limits for sulfur dioxide (SO2) and ozone (O3) based on the short-term AQG. We obtained air pollutant data over seven years (2004-2010) in seven cities from Asia-Pacific, North America and Europe. Based on probability distribution concept using maximum as the short-term limit and arithmetic mean as the annual limit, we developed a new method to derive limit value one from another in each paired limits for each pollutant with capability to account for allowable exceedances. We averaged the limit derived each year for each city, then used meta-analysis to pool the limit values in all cities. Pooled mean short-term limit for NO2 (140.5μg/m(3) [130.6-150.4]) was significantly lower than the WHO AQG of 200μg/m(3) while for PM10 (46.4μg/m(3) [95CI:42.1-50.7]) and PM2.5 (28.6μg/m(3) [24.5-32.6]) were not significantly different from the WHO AQG of 50 and 25μg/m(3) respectively. Pooled mean annual limits for SO2 and O3 were 4.6μg/m(3) [3.7-5.5] and 27.0μg/m(3) [21.7-32.2] respectively. Results were robust in various sensitivity analyses. The distribution relationships between the current WHO short-term and annual AQG are supported by empirical data from seven cities for PM10 and PM2.5, but not for NO2. The short-term AQG for NO2 should be lowered for concordance with the selected annual AQG for health protection. PMID:23792417

  10. Autophagy Plays a Protective Role in Tumor Necrosis Factor-α-Induced Apoptosis of Bone Marrow-Derived Mesenchymal Stem Cells.

    PubMed

    Yang, Rui; Ouyang, Yi; Li, Weiping; Wang, Peng; Deng, Haiquan; Song, Bin; Hou, Jingyi; Chen, Zhong; Xie, Zhongyu; Liu, Zhenhua; Li, Jinteng; Cen, Shuizhong; Wu, Yanfeng; Shen, Huiyong

    2016-05-15

    Bone marrow-derived mesenchymal stem cells (BMSCs) are being broadly investigated for treating numerous inflammatory diseases. However, the low survival rate of BMSCs during the transplantation process has limited their application. Autophagy can maintain cellular homeostasis and protect cells against environmental stresses. Tumor necrosis factor-α (TNF-α) is an important inflammatory cytokine that can induce both autophagy and apoptosis of BMSCs. However, the actual role of autophagy in TNF-α-induced apoptosis of BMSCs remains poorly understood. In the current study, BMSCs were treated with TNF-α/cycloheximide (CHX), and cell death was examined by the Cell Counting Kit-8, Hoechst 33342 staining, and flow cytometric analysis as well as by the level of caspase-3 and caspase-8. Meanwhile, autophagic flux was examined by analyzing the level of microtubule-associated protein light chain 3 B (LC3B)-II and SQSTEM1/p62 and by examining the amount of green fluorescent protein-LC3B by fluorescence microscopy. Then, the cell death and autophagic flux of BMSCs were examined after pretreatment and cotreatment with 3-methyladenine (3-MA, autophagy inhibitor) or rapamycin (Rap, autophagy activator) together with TNF-α/CHX. Moreover, BMSCs pretreated with lentiviruses encoding short hairpin RNA of beclin-1 (BECN1) were treated with TNF-α/CHX, and then cell death and autophagic flux were detected. We showed that BMSCs treated with TNF-α/CHX presented dramatically elevated autophagic flux and cell death. Furthermore, we showed that 3-MA and shBECN1 treatment accelerated TNF-α/CHX-induced apoptosis, but that Rap treatment ameliorated cell death. Our results demonstrate that autophagy protects BMSCs against TNF-α-induced apoptosis. Enhancing the autophagy of BMSCs may elevate cellular survival in an inflammatory microenvironment. PMID:26985709

  11. Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge

    PubMed Central

    Herbert, Andrew S; Heffron, Lynn; Sundick, Roy; Roberts, Paul C

    2009-01-01

    Background Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine. Results We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4) fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. In vivo efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th1/Th2 humoral immune response, similar to live virus infections. Conclusion We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective. PMID:19393093

  12. Intranasal vaccination with a plant-derived H5 HA vaccine protects mice and ferrets against highly pathogenic avian influenza virus challenge.

    PubMed

    Major, Diane; Chichester, Jessica A; Pathirana, Rishi D; Guilfoyle, Kate; Shoji, Yoko; Guzman, Carlos A; Yusibov, Vidadi; Cox, Rebecca J

    2015-01-01

    Highly pathogenic avian influenza H5N1 infection remains a public health threat and vaccination is the best measure of limiting the impact of a potential pandemic. Mucosal vaccines have the advantage of eliciting immune responses at the site of viral entry, thereby preventing infection as well as further viral transmission. In this study, we assessed the protective efficacy of hemagglutinin (HA) from the A/Indonesia/05/05 (H5N1) strain of influenza virus that was produced by transient expression in plants. The plant-derived vaccine, in combination with the mucosal adjuvant (3',5')-cyclic dimeric guanylic acid (c-di-GMP) was used for intranasal immunization of mice and ferrets, before challenge with a lethal dose of the A/Indonesia/05/05 (H5N1) virus. Mice vaccinated with 15 μg or 5 μg of adjuvanted HA survived the viral challenge, while all control mice died within 10 d of challenge. Vaccinated animals elicited serum hemagglutination inhibition, IgG and IgA antibody titers. In the ferret challenge study, all animals vaccinated with the adjuvanted plant vaccine survived the lethal viral challenge, while 50% of the control animals died. In both the mouse and ferret models, the vaccinated animals were better protected from weight loss and body temperature changes associated with H5N1 infection compared with the non-vaccinated controls. Furthermore, the systemic spread of the virus was lower in the vaccinated animals compared with the controls. Results presented here suggest that the plant-produced HA-based influenza vaccine adjuvanted with c-di-GMP is a promising vaccine/adjuvant combination for the development of new mucosal influenza vaccines. PMID:25714901

  13. Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene Expression Profiles and Histopathology.

    PubMed

    Sung, Dong Kyung; Chang, Yun Sil; Ahn, So Yoon; Sung, Se In; Yoo, Hye Soo; Choi, Soo Jin; Kim, Soo Yoon; Park, Won Soon

    2015-01-01

    The aim of this study was to determine the optimal route of mesenchymal stem cell (MSC) transplantation. To this end, gene expression profiling was performed to compare the effects of intratracheal (i.t.) versus intravenous (i.v.) MSC administration. Furthermore, the therapeutic efficacy of each route to protect against neonatal hyperoxic lung injury was also determined. Newborn Sprague-Dawley rats were exposed to hyperoxia (90% oxygen) from birth for 14 days. Human umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through either the i.t. (5×10(5)) or i.v. (2×10(6)) route at postnatal day (P) 5. At P14, lungs were harvested for histological, biochemical and microarray analyses. Hyperoxic conditions induced an increase in the mean linear intercept and mean alveolar volume (MAV), indicative of impaired alveolarization. The number of ED-1 positive cells was significantly decreased by both i.t. and i.v. transplantations. However, i.t. administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to i.v. administration. Moreover, the number of TUNEL-positive cells was significantly decreased in the i.t. group, but not in the i.v. group. Although the i.t. group received only one fourth of the number of MSCs that the i.v. group did, a significantly higher number of donor cell-derived red PKH 26 positivity were recovered in the i.t. group. Hyperoxic conditions induced the up regulation of genes associated with the inflammatory response, such as macrophage inflammatory protein-1 α, tumor necrosis factor-α and inter leukin-6; genes associated with cell death, such as p53 and caspases; and genes associated with fibrosis, such as connective tissue growth factor. In contrast, hyperoxic conditions induced the dwon-regulation of vascular endothelial growth factor and hepatocyte growth factor. These hyperoxia-induced changes in gene expression were decreased in the i.t. group, but not in the i.v. group. Thus, local i.t. MSC

  14. Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene Expression Profiles and Histopathology

    PubMed Central

    Ahn, So Yoon; Sung, Se In; Yoo, Hye Soo; Choi, Soo Jin; Kim, Soo Yoon; Park, Won Soon

    2015-01-01

    The aim of this study was to determine the optimal route of mesenchymal stem cell (MSC) transplantation. To this end, gene expression profiling was performed to compare the effects of intratracheal (IT) versus intravenous (IV) MSC administration. Furthermore, the therapeutic efficacy of each route to protect against neonatal hyperoxic lung injury was also determined. Newborn Sprague-Dawley rats were exposed to hyperoxia (90% oxygen) from birth for 14 days. Human umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through either the IT (5×105) or IV (2×106) route at postnatal day (P) 5. At P14, lungs were harvested for histological, biochemical and microarray analyses. Hyperoxic conditions induced an increase in the mean linear intercept and mean alveolar volume (MAV), indicative of impaired alveolarization. The number of ED-1 positive cells was significantly decreased by both IT and IV transplantations. However, IT administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to IV administration. Moreover, the number of TUNEL-positive cells was significantly decreased in the IT group, but not in the IV group. Although the IT group received only one fourth of the number of MSCs that the IV group did, a significantly higher number of donor cell-derived red PKH 26 positivity were recovered in the IT group. Hyperoxic conditions induced the up regulation of genes associated with the inflammatory response, such as macrophage inflammatory protein-1 α, tumor necrosis factor-α and inter leukin-6; genes associated with cell death, such as p53 and caspases; and genes associated with fibrosis, such as connective tissue growth factor. In contrast, hyperoxic conditions induced the dwon-regulation of vascular endothelial growth factor and hepatocyte growth factor. These hyperoxia-induced changes in gene expression were decreased in the IT group, but not in the IV group. Thus, local IT MSC transplantation was more effective

  15. Protection of atherogenesis in thromboxane A2 receptor-deficient mice is not associated with thromboxane A2 receptor in bone marrow-derived cells

    SciTech Connect

    Zhuge Xin; Arai, Hidenori . E-mail: harai@kuhp.kyoto-u.ac.jp; Xu, Yang; Murayama, Toshinori; Kobayashi, Takuya; Narumiya, Shuh; Kita, Toru; Yokode, Masayuki

    2006-12-29

    In the previous study, we generated mice lacking thromboxane A2 receptor (TP) and apolipoprotein E, apoE{sup -/-}TP{sup -/-} mice, and reported that the double knockout mice developed markedly smaller atherosclerotic lesions than those in apoE{sup -/-} mice. To investigate the mechanism responsible for reduced atherosclerosis in apoE{sup -/-}TP{sup -/-} mice, we examined the role of TP in bone marrow (BM)-derived cells in the development of the atherosclerotic lesions. When we compared the function of macrophages in apoE{sup -/-} and in apoE{sup -/-}TP{sup -/-} mouse in vitro, there was no difference in the expression levels of cytokines and chemokines after stimulation with lipopolysaccharide. We then transplanted the BM from either apoE{sup -/-} or apoE{sup -/-}TP{sup -/-} mice to either apoE{sup -/-} or apoE{sup -/-}TP{sup -/-} mice after sublethal irradiation. After 12 weeks with high fat diet, we analyzed the atherosclerotic lesion of aortic sinus. When the BM from apoE{sup -/-} or apoE{sup -/-}TP{sup -/-} mice was transplanted to apoE{sup -/-} mice, the lesion size was almost the same as that of apoE{sup -/-} mice without BM transplantation. In contrast, when the BM from apoE{sup -/-} or apoE{sup -/-}TP{sup -/-} mice was transplanted to apoE{sup -/-}TP{sup -/-} mice, the lesion size was markedly reduced. These results indicate that the protection of atherogenesis in TP{sup -/-} mice is not associated with TP in BM-derived cells.

  16. Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, protects the pancreas from apoptosis and proliferation via oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Park, Chan Hum; Lee, Joo Young; Kim, Min Yeong; Shin, Sung Ho; Roh, Seong-Soo; Choi, Jae Sue; Chung, Hae Young; Song, Yeong-Ok; Shin, Yu Su; Yokozawa, Takako

    2016-07-13

    We have identified the effects of oligonol, a low-molecular polyphenol derived from lychee fruit, on diabetes-induced pancreatic damage via oxidative stress. Oligonol was orally administered at 10 or 20 mg (kg d)(-1) for 10 days to streptozotocin (STZ)-induced diabetic rats, and we assessed the changes in the serum glucose and insulin levels, as well as those of body weight and food and water consumption. In addition, analyses of the weight, insulin content, reactive oxygen species (ROS) level, and western blots of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4 (Nox-4), p22(phox), p47(phox), phosphor-c-Jun N-terminal kinase (p-JNK), Bax, cytochrome c, caspase 3, pancreatic-duodenal homeobox (PDX-1) and cyclin E were also performed in the pancreas. However, these unfavorable outcomes under diabetes were reversed by oligonol administration. Oligonol treatment led to significantly attenuated histological damage in the pancreas. In conclusion, this study suggests that oligonol protects the pancreas from Bax and PDX-1 via oxidative stress for the prevention or delaying of diabetes mellitus. PMID:27248500

  17. Protection against HPV-16-Associated Tumors Requires the Activation of CD8+ Effector Memory T Cells and the Control of Myeloid-Derived Suppressor Cells.

    PubMed

    Diniz, Mariana O; Sales, Natiely S; Silva, Jamile R; Ferreira, Luís Carlos S

    2016-08-01

    Active anticancer immunotherapeutic approaches have been shown to induce cellular or humoral immune responses in patients, but, thus far, the observed outcomes did not ensure their recommendation for clinical use. The induction of tumor-specific CD8(+) T cells, although required for the clearance of most solid tumors, was shown to be insufficient for the development of a successful immunotherapeutic approach. The suppressive immune environment triggered by tumors, including the expansion of myeloid-derived suppressor cells (MDSC), is detrimental to the development of antitumor immune responses and precludes the generation of more promising clinical outcomes. In this work, we characterized the CD8(+) T-cell population specifically involved in the control of tumor growth and the role of MDSCs after administration of an antitumor therapeutic DNA vaccine targeting human papillomavirus type 16 (HPV-16)-associated tumors. Activation of cytotoxic high-avidity CD8(+) T cells with an effector memory phenotype was found in mice grafted with tumor cells expressing the HPV-16 oncoproteins. In addition, MDSC antibody depletion further enhanced the immunotherapeutic effects of the vaccine, resulting in the complete eradication of tumor cells. Collectively, the current results indicate that the simultaneous control of MDSCs and activation of high-avidity tumor-specific effector memory CD8(+) T cells are key features for tumor protection by immunotherapeutic approaches and deserve further testing under clinical conditions. Mol Cancer Ther; 15(8); 1920-30. ©2016 AACR. PMID:27222537

  18. A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats

    PubMed Central

    Li, Guoling; Tian, Yufei; Zhang, Yuzhong; Hong, Ying; Hao, Yingzhi; Chen, Chunxiao; Wang, Penglong; Lei, Haimin

    2015-01-01

    Broad-spectrum drugs appear to be more promising for the treatment of acute ischemic stroke. In our previous work, a new ligustrazine derivative (3,5,6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoate (T-VA) showed neuroprotective effect on injured PC12 cells (EC50 = 4.249 µM). In the current study, we show that this beneficial effect was due to the modulation of nuclear transcription factor-κB/p65 (NF-κB/p65) and cyclooxygenase-2 (COX-2) expressions. We also show that T-VA exhibited neuroprotective effect in a rat model of ischemic stroke with concomitant improvement of motor functions. We propose that the protective effect observed in vivo is owing to increased vascular endothelial growth factor (VEGF) expression, decreased oxidative stress, and up-regulation of Ca2+–Mg2+ ATP enzyme activity. Altogether, our results warrant further studies on the utility of T-VA for the potential treatment of ischemic brain injuries, such as stroke. PMID:26370988

  19. Human Amnion-Derived Mesenchymal Stem Cells Protect Human Bone Marrow Mesenchymal Stem Cells against Oxidative Stress-Mediated Dysfunction via ERK1/2 MAPK Signaling

    PubMed Central

    Wang, Yuli; Ma, Junchi; Du, Yifei; Miao, Jing; Chen, Ning

    2016-01-01

    Epidemiological evidence suggests that bone is especially sensitive to oxidative stress, causing bone loss in the elderly. Previous studies indicated that human amnion-derived mesenchymal stem cells (HAMSCs), obtained from human amniotic membranes, exerted osteoprotective effects in vivo. However, the potential of HAMSCs as seed cells against oxidative stress-mediated dysfunction is unknown. In this study, we systemically investigated their antioxidative and osteogenic effects in vitro. Here, we demonstrated that HAMSCs signi cantly promoted the proliferation and osteoblastic differentiation of H2O2-induced human bone marrow mesenchymal stem cells (HBMSCs), and down-regulated the reactive oxygen species (ROS) level. Further, our results suggest that activation of the ERK1/2 MAPK signal transduction pathway is essential for both HAMSCs-mediated osteogenic and protective effects against oxidative stress-induced dysfunction in HBMSCs. U0126, a highly selective inhibitor of extracellular ERK1/2 MAPK signaling, significantly suppressed the antioxidative and osteogenic effects in HAMSCs. In conclusion, by modulating HBMSCs, HAMSCs show a strong potential in treating oxidative stress- mediated bone deficiency. PMID:26743906

  20. Linoleic acid derivative DCP-LA protects neurons from oxidative stress-induced apoptosis by inhibiting caspase-3/-9 activation.

    PubMed

    Yaguchi, Takahiro; Fujikawa, Hirokazu; Nishizaki, Tomoyuki

    2010-05-01

    The present study aimed at understanding the effect of the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) on oxidative stress-induced neuronal death. Sodium nitroprusside (SNP; 1 mM) reduced viability of cultured rat cerebral cortical neurons to 50% of basal levels, but DCP-LA significantly prevented the SNP effect in a concentration (1-100 nM)-dependent manner. In addition, DCP-LA (100 nM) rescued neurons from SNP-induced degradation. SNP (1 mM) activated caspase-3 and -9 in cultured rat cerebral cortical neurons, but DCP-LA (100 nM) abolished the caspase activation. For a mouse model of middle cerebral artery occlusion, oral administration with DCP-LA (1 mg/kg) significantly diminished degraded area due to cerebral infarction. The results of the present study, thus, demonstrate that DCP-LA protects neurons at least in part from oxidative stress-induced apoptosis by inhibiting activation of caspase-3/-9. PMID:20099079

  1. Protection of stromal cell-derived factor 2 by heat shock protein 72 prevents oxaliplatin-induced cell death in oxaliplatin-resistant human gastric cancer cells.

    PubMed

    Takahashi, Katsuyuki; Tanaka, Masako; Yashiro, Masakazu; Matsumoto, Masaki; Ohtsuka, Asuka; Nakayama, Keiichi I; Izumi, Yasukatsu; Nagayama, Katsuya; Miura, Katsuyuki; Iwao, Hiroshi; Shiota, Masayuki

    2016-08-01

    Heat shock protein 72 (Hsp72) is a molecular chaperone that assists in the folding of nascent polypeptides and in the refolding of denatured proteins. In many cancers, Hsp72 is constitutively expressed at elevated levels, which can result in enhanced stress tolerance. Similarly, following treatment with anticancer drugs, Hsp72 binds to denatured proteins that may be essential for survival. We therefore hypothesized that Hsp72 client proteins may play a crucial role in drug resistance. Here, we aimed to identify proteins that are critical for oxaliplatin (OXA) resistance by analyzing human gastric cancer cell lines, as well as OXA-resistant cells via a mass spectrometry-based proteomic approach combined with affinity purification using anti-Hsp72 antibodies. Stromal cell-derived factor 2 (SDF-2) was identified as an Hsp72 client protein unique to OCUM-2M/OXA cells. SDF-2 was overexpressed in OXA-resistant cells and SDF-2 silencing promoted the apoptotic effects of OXA. Furthermore, Hsp72 prevented SDF-2 degradation in a chaperone activity-dependent manner. Together, our data demonstrate that Hsp72 protected SDF-2 to avoid OXA-induced cell death. We propose that inhibition of SDF-2 may comprise a novel therapeutic strategy to counteract OXA-resistant cancers. PMID:27157913

  2. Protection of dopamine neurons by vibration training and up-regulation of brain-derived neurotrophic factor in a MPTP mouse model of Parkinson's disease.

    PubMed

    Zhao, L; He, L X; Huang, S N; Gong, L J; Li, L; Lv, Y Y; Qian, Z M

    2014-01-01

    It is unknown whether the longer duration of vibration training (VT) has a beneficial effect on Parkinson's disease (PD). And also, the mechanisms underlying the reported sensorimotor-improvement in PD induced by short-duration of VT has not been determined. Here, we investigated the effects of longer duration (4 weeks) of low amplitude vibration (LAV) training on the numbers of dopaminergic neurons in the substantia nigra by immunostaining and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) in the striatum by HPLC and ELISA in the chronic MPTP lesion mouse. We demonstrated for the first time that the longer duration of VT could significantly increase the numbers of nigrostriatal DA neurons and the contents of striatal DA and BDNF in the MPTP mice. Our findings implied that longer duration of VT could protect dopaminergic neurons from the MPTP-induced damage probably by upregulating BDNF and also provided evidence for the beneficial effect of longer duration of VT on PD at the cellular and molecular level. PMID:24908088

  3. Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

    PubMed Central

    Rahavi, Hossein; Hashemi, Seyed Mahmoud; Soleimani, Masoud; Mohammadi, Jamal; Tajik, Nader

    2015-01-01

    Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) might be applied for type 1 diabetes mellitus (T1DM) treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs) immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ-) induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate) and nonspecific (PHA) triggers in a dose-dependent manner (P < 0.05). Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P < 0.05). Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P < 0.05). In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future. PMID:25893202

  4. PBN (Phenyl-N-Tert-Butylnitrone)-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage

    PubMed Central

    Stiles, Megan; Moiseyev, Gennadiy P.; Budda, Madeline L.; Linens, Annette; Brush, Richard S.; Qi, Hui; White, Gary L.; Wolf, Roman F.; Ma, Jian-xing; Floyd, Robert; Anderson, Robert E.; Mandal, Nawajes A.

    2015-01-01

    A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardt’s disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75–80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina

  5. Long Term Study of Protective Mechanisms of Human Adipose Derived Mesenchymal Stem Cells on Cisplatin Induced Kidney injury in Sprague-Dawley Rats

    PubMed Central

    Elhusseini, Fatma M; Saad, Mohamed-Ahdy A.A; Anber, Nahla; Elghannam, Doaa; Sobh, Mohamed-Ahmed; Alsayed, Aziza; El-dusoky, Sara; Sheashaa, Hussein; Abdel-Ghaffar, Hassan; Sobh, Mohamed

    2016-01-01

    Background/Aims: Long-term evaluation of cisplatin induced nephrotoxicity and the probable renal protective activities of stem cells are lacking up until now. We evaluated the early and long-term role of human adipose derived mesenchymal stem cells (ADMSCs) in prevention or amelioration of cisplatin induced acute kidney injury (AKI) in Sprague-Dawley rats. For this, we determined the kidney tissue level of oxidative stress markers in conjugation with a renal histopathological scoring system of both acute and chronic renal changes. Methods: This study used eighty Sprague-Dawley (SD) rats weighing 250-300g. They were assigned into four equal groups (each group n=20): (I) Negative control group, rats injected with single dose of 1 ml normal saline. (II) Positive control cisplatin, rats injected with a single dose of 5 mg/kg I.P in 1 ml saline. (III) Cisplatin and culture media group, rats injected with 0.5 ml of culture media single dose into the tail vein and (IV) Cisplatin and ADMSCs group, rats injected with a single dose of 0.5 ml of culture media containing 5 x106ADMSCs into the tail vein one day after cisplatin administration. Each main group was further divided according to the timing of sacrifice into four subgroups (each subgroup n=5). Rats in the subgroup A were sacrificed after 4 days; subgroup B were sacrificed after 7 days; subgroup C were sacrificed after 11 days; and subgroup D were sacrificed after 30 days. Before sacrifice, 24 hrs.-urine was collected using a metabolic cage. Renal function was evaluated through blood urea nitrogen (BUN), serum creatinine and creatinine clearance. Kidney tissue homogenate oxidative stress parameters, Malondialdehyde (MDA), Superoxide dismutase (SOD) and Glutathione (GSH) were determined. In addition, histopathological analysis for active injury, regenerative and chronic changes was performed. Results: ADMSCs were characterized and their capability of differentiation was proved. Cisplatin induced a significant increase

  6. Evaluation of adjuvant activity of fractions derived from Agaricus blazei, when in association with the recombinant LiHyp1 protein, to protect against visceral leishmaniasis.

    PubMed

    de Jesus Pereira, Nathália Cristina; Régis, Wiliam César Bento; Costa, Lourena Emanuele; de Oliveira, Jamil Silvano; da Silva, Alanna Gomes; Martins, Vivian Tamietti; Duarte, Mariana Costa; de Souza, José Roberto Rodrigues; Lage, Paula Sousa; Schneider, Mônica Santos; Melo, Maria Norma; Soto, Manuel; Soares, Sandra Aguiar; Tavares, Carlos Alberto Pereira; Chávez-Fumagalli, Miguel Angel; Coelho, Eduardo Antonio Ferraz

    2015-06-01

    The development of effective prophylactic strategies to prevent leishmaniasis has become a high priority. No less important than the choice of an antigen, the association of an appropriate adjuvant is necessary to achieve a successful vaccination, as the majority of the tested antigens contain limited immunogenic properties, and need to be supplemented with immune response adjuvants in order to boost their immunogenicity. However, few effective adjuvants that can be used against leishmaniasis exist on the market today; therefore, it is possible to speculate that the research aiming to identify new adjuvants could be considered relevant. Recently, Agaricus blazei extracts have proved to be useful in enhancing the immune response to DNA vaccines against some diseases. This was based on the Th1 adjuvant activity of the polysaccharide-rich fractions from this mushroom. In this context, the present study evaluated purified fractions derived from Agaricus blazei as Th1 adjuvants through in vitro assays of their immune stimulation of spleen cells derived from naive BALB/c mice. Two of the tested six fractions (namely F2 and F4) were characterized as polysaccharide-rich fractions, and were able to induce high levels of IFN-γ, and low levels of IL-4 and IL-10 in the spleen cells. The efficacy of adjuvant action against L. infantum was evaluated in BALB/c mice, with these fractions being administered together with a recombinant antigen, LiHyp1, which was previously evaluated as a vaccine candidate, associated with saponin, against visceral leishmaniasis (VL). The associations between LiHyp1/F2 and LiHyp1/F4 were able to induce an in vivo Th1 response, which was primed by high levels of IFN-γ, IL-12, and GM-CSF, by low levels of IL-4 and IL-10; as well as by a predominance of IgG2a antibodies in the vaccinated animals. After infection, the immune profile was maintained, and the vaccines proved to be effective against L. infantum. The immune stimulatory effects in the

  7. Deriving site-specific clean-up criteria to protect ecological receptors (plants and soil invertebrates) exposed to metal or metalloid soil contaminants via the direct contact exposure pathway

    PubMed Central

    Checkai, Ron; Van Genderen, Eric; Sousa, José Paulo; Stephenson, Gladys; Smolders, Erik

    2014-01-01

    Soil contaminant concentration limits for the protection of terrestrial plants and soil invertebrates are commonly based on thresholds derived using data from laboratory ecotoxicity tests. A comprehensive assessment has been made for the derivation of ecological soil screening levels (Eco-SSL) in the United States; however, these limits are conservative because of their focus on high bioavailability scenarios. Here, we explain and evaluate approaches to soil limit derivation taken by 4 jurisdictions, 2 of which allow for correction of data for factors affecting bioavailability among soils, and between spiked and field-contaminated soils (Registration Evaluation Authorisation and Restriction of Chemicals [REACH] Regulation, European Union [EU], and the National Environment Protection Council [NEPC], Australia). Scientifically advanced features from these methods have been integrated into a newly developed method for deriving soil clean-up values (SCVs) within the context of site-specific baseline ecological risk assessment. Resulting site-specific SCVs that account for bioavailability may permit a greater residual concentration in soil when compared to generic screening limit concentrations (e.g., Eco-SSL), while still affording acceptable protection. Two choices for selecting the level of protection are compared (i.e., allowing higher effect levels per species, or allowing a higher percentile of species that are potentially unprotected). Implementation of this new method is presented for the jurisdiction of the United States, with a focus on metal and metalloid contaminants; however, the new method can be used in any jurisdiction. A case study for molybdate shows the large effect of bioavailability corrections and smaller effects of protection level choices when deriving SCVs. Integr Environ Assess Manag 2014;10:346–357. PMID:24470189

  8. Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity

    PubMed Central

    Mesquita, Fernanda C. P.; Brasil, Guilherme V.; Rocha, Nazareth N.; Takiya, Christina M.; Lima, Ana Paula C. A.; Campos de Carvalho, Antonio C.; Goldenberg, Regina S.; Carvalho, Adriana B.

    2015-01-01

    Background Chagas disease, caused by the protozoan Trypanosoma cruzi (T.cruzi), is a complex disease endemic in Central and South America. It has been gathering interest due to increases in non-vectorial forms of transmission, especially in developed countries. The objective of this work was to investigate if adipose tissue-derived mesenchymal stromal cells (ASC) can alter the course of the disease and attenuate pathology in a mouse model of chagasic cardiomyopathy. Methodology/Principal Findings ASC were injected intraperitoneally at 3 days post-infection (dpi). Tracking by bioluminescence showed that cells remained in the abdominal cavity for up to 9 days after injection and most of them migrated to the abdominal or subcutaneous fat, an early parasite reservoir. ASC injection resulted in a significant reduction in blood parasitemia, which was followed by a decrease in cardiac tissue inflammation, parasitism and fibrosis at 30 dpi. At the same time point, analyses of cytokine release in cells isolated from the heart and exposed to T. cruzi antigens indicated an anti-inflammatory response in ASC-treated animals. In parallel, splenocytes exposed to the same antigens produced a pro-inflammatory response, which is important for the control of parasite replication, in placebo and ASC-treated groups. However, splenocytes from the ASC group released higher levels of IL-10. At 60 dpi, magnetic resonance imaging revealed that right ventricular (RV) dilation was prevented in ASC-treated mice. Conclusions/Significance In conclusion, the injection of ASC early after T. cruzi infection prevents RV remodeling through the modulation of immune responses. Lymphoid organ response to the parasite promoted the control of parasite burden, while the heart, a target organ of Chagas disease, was protected from damage due to an improved control of inflammation in ASC-treated mice. PMID:26248209

  9. Trichinella spiralis: intranasal immunization with attenuated Salmonella enterica carrying a gp43 antigen-derived 30mer epitope elicits protection in BALB/c mice.

    PubMed

    Pompa-Mera, E N; Yépez-Mulia, L; Ocaña-Mondragón, A; García-Zepeda, E A; Ortega-Pierres, G; González-Bonilla, C R

    2011-12-01

    Trichinellosis is a public health problem and is considered an emergent/re-emergent disease in various countries. The etiological agent of trichinellosis is the nematode Trichinella, which infects domestic animals such as pigs and horses, as well as wild animals and humans. A veterinary vaccine could be an option to control the disease in domestic animals. Although several vaccine candidates have shown promising results, a vaccine against trichinellosis remains unavailable to date. Attenuated Salmonella strains are especially attractive live vectors because they elicit mucosal immunity, which is known to be important for the control of Trichinella spiralis infection at the intestinal level and can be administered by oral or intranasal routes. In this study, the autotransporter ShdA was used to display, on the surface of the Salmonella enterica serovar Typhimurium SL3261, the 210-239 amino acid epitope, (designated as Ag30) derived from the 43 kDa glycoprotein of T. spiralis muscle larvae. The fusion protein elicited antibodies in BALB/c mice that were able to recognize the native epitope on the surface of T. spiralis muscle larvae. Mice immunized by intranasal route with the recombinant Salmonella induced a protective immune response against the T. spiralis challenge, reducing by 61.83% the adult burden at day eight postinfection. This immune response was characterized by the induction of antigen-specific IgG1 and of IL-5 production. This study demonstrates the usefulness of Salmonella as a carrier of nematode epitopes providing a surface display system for intestinal parasite vaccine applications. PMID:21907709

  10. Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis-Derived Protein Antigens and Contribute to Protection Against Infection.

    PubMed

    Shang, Shaobin; Siddiqui, Sarah; Bian, Yao; Zhao, Jie; Wang, Chyung-Ru

    2016-06-01

    MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or β2m (β2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly β2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules. PMID:27272249

  11. Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early-stage breast cancer

    PubMed Central

    Ng, Terence; Teo, Shu Mei; Yeo, Hui Ling; Shwe, Maung; Gan, Yan Xiang; Cheung, Yin Ting; Foo, Koon Mian; Cham, Mooi Tai; Lee, Jung Ah; Tan, Yee Pin; Fan, Gilbert; Yong, Wei Sean; Preetha, Madhukumar; Loh, Wei-Jen Kiley; Koo, Si-Lin; Jain, Amit; Lee, Guek Eng; Wong, Mabel; Dent, Rebecca; Yap, Yoon Sim; Ng, Raymond; Khor, Chiea Chuen; Ho, Han Kiat; Chan, Alexandre

    2016-01-01

    Background Brain-derived neurotrophic factor (BDNF), a neurotrophin that regulates neuronal function and development, is implicated in several neurodegenerative conditions. Preliminary data suggest that a reduction of BDNF concentrations may lead to postchemotherapy cognitive impairment. We hypothesized that a single nucleotide polymorphism (rs6265) of the BDNF gene may predispose patients to cognitive impairment. This study aimed to evaluate the effect of BDNF gene polymorphism on chemotherapy-associated cognitive impairment. Methods Overall, 145 patients receiving chemotherapy for early-stage breast cancer (mean age: 50.8 ± 8.8 y; 82.1% Chinese) were recruited. Patients' cognitive functions were assessed longitudinally using the validated Functional Assessment of Cancer Therapy–Cognitive Function (v.3) and an objective computerized tool, Headminder. Genotyping was performed using Sanger sequencing. Logistic regression was used to evaluate the association between BDNF Val66Met polymorphism and cognition after adjusting for ethnicity and clinically important covariates. Results Of the 145 patients, 54 (37%) reported cognitive impairment postchemotherapy. The Met/Met genotype was associated with statistically significant lower odds of developing cognitive impairment (odds ratio [OR] = 0.26; 95% CI: 0.08–0.92; P = .036). The Met carriers were less likely to experience impairment in the domains of verbal fluency (OR = 0.34; 95% CI: 0.12–0.90; P = .031) and multitasking ability (OR = 0.37; 95% CI: 0.15–0.91; P = .030) compared with the Val/Val homozygote. No associations were observed between Headminder and the BDNF Val66Met polymorphism. Conclusions This is the first study to provide evidence that carriers of the BDNF Met allele are protected against chemotherapy-associated cognitive impairment. Further studies are required to validate the findings. PMID:26289590

  12. Extracellular membrane vesicles from umbilical cord blood-derived MSC protect against ischemic acute kidney injury, a feature that is lost after inflammatory conditioning

    PubMed Central

    Kilpinen, Lotta; Impola, Ulla; Sankkila, Lotta; Ritamo, Ilja; Aatonen, Maria; Kilpinen, Sami; Tuimala, Jarno; Valmu, Leena; Levijoki, Jouko; Finckenberg, Piet; Siljander, Pia; Kankuri, Esko; Mervaala, Eero; Laitinen, Saara

    2013-01-01

    Background Mesenchymal stromal cells (MSC) are shown to have a great therapeutic potential in many immunological disorders. Currently the therapeutic effect of MSCs is considered to be mediated via paracrine interactions with immune cells. Umbilical cord blood is an attractive but still less studied source of MSCs. We investigated the production of extracellular membrane vesicles (MVs) from human umbilical cord blood derived MSCs (hUCBMSC) in the presence (MVstim) or absence (MVctrl) of inflammatory stimulus. Methods hUCBMSCs were cultured in serum free media with or without IFN-γ and MVs were collected from conditioned media by ultracentrifugation. The protein content of MVs were analyzed by mass spectrometry. Hypoxia induced acute kidney injury rat model was used to analyze the in vivo therapeutic potential of MVs and T-cell proliferation and induction of regulatory T cells were analyzed by co-culture assays. Results Both MVstim and MVctrl showed similar T-cell modulation activity in vitro, but only MVctrls were able to protect rat kidneys from reperfusion injury in vivo. To clarify this difference in functionality we made a comparative mass spectrometric analysis of the MV protein contents. The IFN-γ stimulation induced dramatic changes in the protein content of the MVs. Complement factors (C3, C4A, C5) and lipid binding proteins (i.e apolipoproteins) were only found in the MVctrls, whereas the MVstim contained tetraspanins (CD9, CD63, CD81) and more complete proteasome complex accompanied with MHCI. We further discovered that differently produced MV pools contained specific Rab proteins suggesting that same cells, depending on external signals, produce vesicles originating from different intracellular locations. Conclusions We demonstrate by both in vitro and in vivo models accompanied with a detailed analysis of molecular characteristics that inflammatory conditioning of MSCs influence on the protein content and functional properties of MVs revealing the

  13. Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis-Derived Protein Antigens and Contribute to Protection Against Infection

    PubMed Central

    Shang, Shaobin; Siddiqui, Sarah; Bian, Yao; Zhao, Jie; Wang, Chyung-Ru

    2016-01-01

    MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or β2m (β2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly β2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules. PMID:27272249

  14. Adenoviral-Mediated Glial Cell Line–Derived Neurotrophic Factor Gene Transfer Has a Protective Effect on Sciatic Nerve Following Constriction-Induced Spinal Cord Injury

    PubMed Central

    Chou, An-Kuo; Yang, Ming-Chang; Tsai, Hung-Pei; Chai, Chee-Yin; Tai, Ming-Hong; Kwan, Aij-Li; Hong, Yi-Ren

    2014-01-01

    Neuropathic pain due to peripheral nerve injury may be associated with abnormal central nerve activity. Glial cell-line-derived neurotrophic factor (GDNF) can help attenuate neuropathic pain in different animal models of nerve injury. However, whether GDNF can ameliorate neuropathic pain in the spinal cord dorsal horn (SCDH) in constriction-induced peripheral nerve injury remains unknown. We investigated the therapeutic effects of adenoviral-mediated GDNF on neuropathic pain behaviors, microglial activation, pro-inflammatory cytokine expression and programmed cell death in a chronic constriction injury (CCI) nerve injury animal model. In this study, neuropathic pain was produced by CCI on the ipsilateral SCDH. Mechanical allodynia was examined with von Frey filaments and thermal sensitivity was tested using a plantar test apparatus post-operatively. Target proteins GDNF-1, GDNFRa-1, MMP2, MMP9, p38, phospho-p38, ED1, IL6, IL1β, AIF, caspase-9, cleaved caspase-9, caspase-3, cleaved caspase-3, PARP, cleaved PARP, SPECTRIN, cleaved SPECTRIN, Beclin-1, PKCσ, PKCγ, iNOS, eNOS and nNOS were detected. Microglial activity was measured by observing changes in immunoreactivity with OX-42. NeuN and TUNEL staining were used to reveal whether apoptosis was attenuated by GDNF. Results showed that administrating GDNF began to attenuate both allodynia and thermal hyperalgesia at day 7. CCI-rats were found to have lower GDNF and GDNFRa-1 expression compared to controls, and GDNF re-activated their expression. Also, GDNF significantly down-regulated CCI-induced protein expression except for MMP2, eNOS and nNOS, indicating that the protective action of GDNF might be associated with anti-inflammation and prohibition of microglia activation. Immunocytochemistry staining showed that GDNF reduced CCI-induced neuronal apoptosis. In sum, GDNF enhanced the neurotrophic effect by inhibiting microglia activation and cytokine production via p38 and PKC signaling. GDNF could be a good

  15. Well-Dispersed ZIF-Derived Co,N-Co-doped Carbon Nanoframes through Mesoporous-Silica-Protected Calcination as Efficient Oxygen Reduction Electrocatalysts.

    PubMed

    Shang, Lu; Yu, Huijun; Huang, Xing; Bian, Tong; Shi, Run; Zhao, Yufei; Waterhouse, Geoffrey I N; Wu, Li-Zhu; Tung, Chen-Ho; Zhang, Tierui

    2016-02-24

    A well-dispersed Co,N co-doped carbon nanoframework (Co,N-CNF) with hierarchically porous structure is successfully synthesized from zeolitic imidazolate framework (ZIF) precursors via a mesoporous-silica-protected calcination strategy. By preventing the irreversible fusion and aggregation during the high-temperature pyrolysis step with this protection strategy, the Co,N-CNF exhibits comparable oxygen reduction reaction (ORR) catalytic activity to that of commercial Pt catalysts with the same loading. PMID:26677131

  16. Immunogenic dialyzable factor derived from a ribosomal fraction of Salmonella typhimurium. I. Preparation of the protective dialyzable factor from the ribosomal fraction by the freeze-thaw procedure.

    PubMed

    Kita, E; Matsuura, H; Masuda, S; Tomihata, S; Kashiba, S

    1983-01-01

    The preparation, properties, and immunogenicity of the dialyzable factor from a ribosomal fraction of Salmonella typhimurium are described. The ribosomal fraction was purified to eliminate O-antigenic components, by affinity chromatography (Sepharose-anti-O antibody conjugates used as immunoadsorbent). The dialyzable factor was obtained in the concentrated dialysate of the purified ribosomal fraction which was alternately frozen in dry-ice acetone and thawed in an 80 C water bath, for a total of five or six cycles. When this preparation was tested for its ability to protect mice against challenge with 1,000 LD50 of the homologous bacteria, it afforded 100% protection at a dose equivalent to 5.0 micrograms of RNA. The protection conferred by this factor was mainly cell mediated but immune serum enhanced this immunity despite the fact that no antibodies were detected in it. The protective activity of this factor was sensitive to RNase digestion but resistant to proteolytic enzymes. Ion exchange chromatography of this factor with DEAE-Sephadex A-25 (in 7 M Urea-0.02 M Tris-HCl buffer, pH 7.5) resulted in a single A260 peak which was found to be immunogenic. Chemical analysis of this peak after it was concentrated and desalted revealed that this immunogenic fraction was composed mainly of mixed nucleotides. The data indicate that protective immunity conferred by a ribosomal vaccine is associated with RNA but may not require the intact RNA molecule. PMID:6346023

  17. Identification of 1,2,3-triazole derivatives that protect pancreatic β cells against endoplasmic reticulum stress-mediated dysfunction and death through the inhibition of C/EBP-homologous protein expression.

    PubMed

    Duan, Hongliang; Arora, Daleep; Li, Yu; Setiadi, Hendra; Xu, Depeng; Lim, Hui-Ying; Wang, Weidong

    2016-06-15

    The C/EBP-homologous protein (CHOP) acts as a mediator of endoplasmic reticulum (ER) stress-induced pancreatic insulin-producing β cell death, a key element in the pathogenesis of diabetes. Chemicals that inhibit the expression of CHOP might therefore protect β cells from ER stress-induced apoptosis and prevent or ameliorate diabetes. Here, we used high-throughput screening to identify a series of 1,2,3-triazole amide derivatives that inhibit ER stress-induced CHOP-luciferase reporter activity. Our SAR studies indicate that compounds with an N,1-diphenyl-5-methyl-1H-1,2,3-triazole-4-carboxamide backbone potently protect β cell against ER stress. Several representative compounds inhibit ER stress-induced up-regulation of CHOP mRNA and protein, without affecting the basal level of CHOP expression. We further show that a 1,2,3-triazole derivative 4e protects β cell function and survival against ER stress in a CHOP-dependent fashion, as it is inactive in CHOP-deficient β cells. Finally, we show that 4e significantly lowers blood glucose levels and increases concomitant β cell survival and number in a streptozotocin-induced diabetic mouse model. Identification of small molecule inhibitors of CHOP expression that prevent ER stress-induced β cell dysfunction and death may provide a new modality for the treatment of diabetes. PMID:27157393

  18. Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells

    PubMed Central

    Lee, Boon Kiat; Tang, Jiansong; Wu, Xilin; Cheung, Ka-Wai; Lok Lo, Nathan Tin; Man, Kwan; Liu, Li; Chen, Zhiwei

    2015-01-01

    A key focus in cancer immunotherapy is to investigate the mechanism of efficacious vaccine responses. Using HIV-1 GAG-p24 in a model PD1-based DNA vaccine, we recently reported that vaccine-elicited CD8+ T cells conferred complete prevention and therapeutic cure of AB1-GAG malignant mesothelioma in immunocompetent BALB/c mice. Here, we further investigated the efficacy and correlation of protection on the model vaccine-mediated antigen spreading against wild-type AB1 (WT-AB1) mesothelioma. We found that this vaccine was able to protect mice completely from three consecutive lethal challenges of AB1-GAG mesothelioma. Through antigen spreading these animals also developed tumor-specific cytotoxic CD8+ T cells, but neither CD4+ T cells nor antibodies, rejecting WT-AB1 mesothelioma. A majority of these protected mice (90%) were also completely protected against the lethal WT-AB1 challenge. Adoptive cell transfer experiments further demonstrated that antigen spreading-induced CD8+ T cells conferred efficacious therapeutic effects against established WT-AB1 mesothelioma and prevented the increase of exhausted PD-1+ and Tim-3+ CD8+ T cells. A significant inverse correlation was found between the frequency of functional PD1−Tim3− CD8+ T cells and that of MDSCs or tumor mass in vivo. Mechanistically, we found that WT-AB1 mesothelioma induced predominantly polymorphonuclear (PMN) MDSCs in vivo. In co-cultures with efficacious CD8+ T cells, a significant number of PMN-MDSCs underwent apoptosis in a dose-dependent way. Our findings indicate that efficacious CD8+ T cells capable of eliminating both tumor cells and MDSCs are likely necessary for fighting wild-type malignant mesothelioma. PMID:26431275

  19. MHC class II derived recombinant T cell receptor ligands protect DBA/1LacJ mice from collagen-induced arthritis.

    PubMed

    Huan, Jianya; Kaler, Laurie J; Mooney, Jeffery L; Subramanian, Sandhya; Hopke, Corwyn; Vandenbark, Arthur A; Rosloniec, Edward F; Burrows, Gregory G; Offner, Halina

    2008-01-15

    We previously demonstrated the therapeutic effects of MHC class II derived recombinant T cell receptor ligands (RTL), single-chain two domain complexes of the alpha1 and beta1 domains of MHC class II molecules genetically linked with an immunodominant peptide, in experimental autoimmune encephalomyelitis. In the current study, we produced a monomeric murine I-Aq-derived RTL construct covalently linked with bovine collagen type II peptide (bCII257-270) suitable for use in DBA/1LacJ mice that develop collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis, after immunization with bCII protein in CFA. In this study, we demonstrate that the I-Aq-derived RTLs reduced the incidence of the disease, suppressed the clinical and histological signs of CIA and induced long-term modulation of T cells specific for arthritogenic Ags. Our results showed that the I-Aq/bCII257-270 molecule could systemically reduce proinflammatory IL-17 and IFN-gamma production and significantly increase anti-inflammatory IL-10, IL-13, and FoxP3 gene expression in splenocytes. Moreover, I-Aq/bCII257-270 molecule could also selectively inhibit IL-1beta, IL-6, and IL-23 expression in local joint tissue. This is the first report demonstrating effective prevention of joint inflammation and clinical signs of CIA with an I-Aq-derived RTL, thus supporting the possible clinical use of this approach for treating rheumatoid arthritis in humans. PMID:18178865

  20. MHC Class II Derived Recombinant T Cell Receptor Ligands Protect DBA/1LacJ Mice from Collagen-Induced Arthritis1

    PubMed Central

    Huan, Jianya; Kaler, Laurie J.; Mooney, Jeffery L.; Subramanian, Sandhya; Hopke, Corwyn; Vandenbark, Arthur A.; Rosloniec, Edward F.; Burrows, Gregory G.; Offner, Halina

    2012-01-01

    We previously demonstrated the therapeutic effects of MHC class II derived recombinant T cell receptor ligands (RTL), single-chain two domain complexes of the α1 and β1 domains of MHC class II molecules genetically linked with an immunodominant peptide, in experimental autoimmune encephalomyelitis. In the current study, we produced a monomeric murine I-Aq-derived RTL construct covalently linked with bovine collagen type II peptide (bCII257–270) suitable for use in DBA/1LacJ mice that develop collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis, after immunization with bCII protein in CFA. In this study, we demonstrate that the I-Aq-derived RTLs reduced the incidence of the disease, suppressed the clinical and histological signs of CIA and induced long-term modulation of T cells specific for arthritogenic Ags. Our results showed that the I-Aq/bCII257–270 molecule could systemically reduce proinflammatory IL-17 and IFN-γ production and significantly increase anti-inflammatory IL-10, IL-13, and FoxP3 gene expression in splenocytes. Moreover, I-Aq/bCII257–270 molecule could also selectively inhibit IL-1β, IL-6, and IL-23 expression in local joint tissue. This is the first report demonstrating effective prevention of joint inflammation and clinical signs of CIA with an I-Aq-derived RTL, thus supporting the possible clinical use of this approach for treating rheumatoid arthritis in humans. PMID:18178865

  1. NCX-1015, a nitric-oxide derivative of prednisolone, enhances regulatory T cells in the lamina propria and protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice

    PubMed Central

    Fiorucci, Stefano; Antonelli, Elisabetta; Distrutti, Eleonora; Del Soldato, Piero; Flower, Roderick J.; Clark, Mark J. Paul; Morelli, Antonio; Perretti, Mauro; Ignarro, Louis J.

    2002-01-01

    NCX-1015 is a nitric oxide (NO)-releasing derivative of prednisolone. In this study we show NCX-1015 protects mice against the S. A. development and induces healing of T helper cell type 1-mediated experimental colitis induced by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The beneficial effect of NCX-1015 was reflected in increased survival rates, improvement of macroscopic and histologic scores, a decrease in the mucosal content of T helper cell type 1 cytokines (protein and mRNA), and diminished myeloperoxidase activity in the colon. In contrast to its NO derivative, only very high doses of prednisolone were effective in reproducing these beneficial effects. NCX-1015 was 10- to 20-fold more potent than the parent compound in inhibiting IFN-γ secretion by lamina propria mononuclear cells. Protection against developing colitis correlated with inhibition of nuclear translocation of p65/Rel A in these cells. In vivo treatment with NCX-1015 potently stimulated IL-10 production, suggesting that the NO steroid induces a regulatory subset of T cells that negatively modulates intestinal inflammation. PMID:12427966

  2. Induction of cytotoxic T-cell activity by the protective antigen of Schistosoma mansoni Sm28GST or its derived C-terminal lipopeptide.

    PubMed

    Pancré, V; Gras-Masse, H; Delanoye, A; Herno, J; Capron, A; Auriault, C

    1996-11-01

    In a previous work the authors demonstrated that immunization with Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST) was able to reduce hepatic damage in infected mice and that the adoptive transfer of Sm28GST-specific T cells reproduced the protective effect obtained with the recombinant molecule. In the present paper, the authors show that Sm28GST is also able to stimulate an antigen-specific, cytotoxic T-cell response against Sm28GST-pulsed P815 target cells in normal mice and that effector cells induced in vivo were classical Class I MHC-restricted CD8+ lymphocytes. The authors found no spontaneous CTL activity against Sm28GST-pulsed target cells during the course of the infection by S. mansoni although Sm28GST is expressed at different developmental stages of the parasite. It was observed, however, that immunization with Sm28GST is sufficient to elicit a significant level of CTL response for 6 weeks in infected mice. The role of these Class I MHC-restricted CD8+ lymphocytes in the protection observed precisely at the same period in immunized mice remains to be elucidated. The authors also observe that immunization with the lipopeptide form of the C-terminal peptide of the molecule (190-211 peptide) led to a CTL activation comparable to that observed after immunization with the whole molecule demonstrating the feasibility of using a synthetic lipopeptide as immunogen for a CTL response against Sm28GST epitopes. Moreover, like Sm28GST-specific CTLs, 190-211 lipopeptide-specific cells were also Class I MHC-restricted lymphocytes. PMID:8947600

  3. Protective effect of chronic caffeine intake on gene expression of brain derived neurotrophic factor signaling and the immunoreactivity of glial fibrillary acidic protein and Ki-67 in Alzheimer’s disease

    PubMed Central

    Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Abo El-khair, Salwa M; Helaly, Ahmed MN; Mahmoud, El-Hassanin M; Elshafey, Saad H

    2015-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive degeneration of the hippocampal and cortical neurons. This study was designed to demonstrate the protective effect of caffeine on gene expression of brain derived neurotrophic factor (BDNF) and its receptor neural receptor protein-tyrosine kinase-β (TrkB) as well as glial fibrillary acidic protein (GFAP) and Ki-67 immunoreactivity in Aluminum chloride (AlCl3) induced animal model of AD. Fifty adult rats included in this study were classified into 5 group (10 rats each); negative and positive control groups (I&II), AD model group (III), group treated with caffeine from the start of AD induction (IV) and group treated with caffeine two weeks before AD induction (V). Hippocampal tissue BDNF and its receptor (TrkB) gene expression by real time RT-PCR in addition to immunohistochemical study of GFAP and Ki67 immunoreactivity were performed for all rats in the study. The results of this study revealed that caffeine has protective effect through improving the histological and immunohistochemical findings induced by AlCl3 as well as BDNF and its receptor gene expression. It could be concluded from the current study, that chronic caffeine consumption in a dose of 1.5 mg/kg body weight daily has a potentially good protective effect against AD. PMID:26339337

  4. Protective Effects of Human iPS-Derived Retinal Pigmented Epithelial Cells in Comparison with Human Mesenchymal Stromal Cells and Human Neural Stem Cells on the Degenerating Retina in rd1 mice.

    PubMed

    Sun, Jianan; Mandai, Michiko; Kamao, Hiroyuki; Hashiguchi, Tomoyo; Shikamura, Masayuki; Kawamata, Shin; Sugita, Sunao; Takahashi, Masayo

    2015-05-01

    Retinitis pigmentosa (RP) is a group of visual impairments characterized by progressive rod photoreceptor cell loss due to a genetic background. Pigment epithelium-derived factor (PEDF) predominantly secreted by the retinal pigmented epithelium (RPE) has been reported to protect photoreceptors in retinal degeneration models, including rd1. In addition, clinical trials are currently underway outside Japan using human mesenchymal stromal cells and human neural stem cells to protect photoreceptors in RP and dry age-related macular degeneration, respectively. Thus, this study aimed to investigate the rescue effects of induced pluripotent stem (iPS)-RPE cells in comparison with those types of cells used in clinical trials on photoreceptor degeneration in rd1 mice. Cells were injected into the subretinal space of immune-suppressed 2-week-old rd1 mice. The results demonstrated that human iPS-RPE cells significantly attenuated photoreceptor degeneration on postoperative days (PODs) 14 and 21 and survived longer up to at least 12 weeks after operation than the other two types of graft cells with less immune responses and apoptosis. The mean PEDF concentration in the intraocular fluid in RPE-transplanted eyes was more than 1 µg/ml at PODs 14 and 21, and this may have contributed to the protective effect of RPE transplantation. Our findings suggest that iPS-RPE cells serve as a competent source to delay photoreceptor degeneration through stable survival in degenerating ocular environment and by releasing neuroprotective factors such as PEDF. PMID:25728228

  5. Cobalt Protoporphyrin Pretreatment Protects Human Embryonic Stem Cell-Derived Cardiomyocytes From Hypoxia/Reoxygenation Injury In Vitro and Increases Graft Size and Vascularization In Vivo

    PubMed Central

    Luo, Jun; Weaver, Matthew S.; Cao, Baohong; Dennis, James E.; Van Biber, Benjamin; Laflamme, Michael A.

    2014-01-01

    Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) can regenerate infarcted myocardium. However, when implanted into acutely infarcted hearts, few cells survive the first week postimplant. To improve early graft survival, hESC-CMs were pretreated with cobalt protoporphyrin (CoPP), a transcriptional activator of cytoprotective heme oxygenase-1 (HO-1). When hESC-CMs were challenged with an in vitro hypoxia/reoxygenation injury, mimicking cell transplantation into an ischemic site, survival was significantly greater among cells pretreated with CoPP versus phosphate-buffered saline (PBS)-pretreated controls. Compared with PBS-pretreated cells, CoPP-pretreated hESC-CM preparations exhibited higher levels of HO-1 expression, Akt phosphorylation, and vascular endothelial growth factor production, with reduced apoptosis, and a 30% decrease in intracellular reactive oxygen species. For in vivo translation, 1 × 107 hESC-CMs were pretreated ex vivo with CoPP or PBS and then injected intramyocardially into rat hearts immediately following acute infarction (permanent coronary ligation). At 1 week, hESC-CM content, assessed by quantitative polymerase chain reaction for human Alu sequences, was 17-fold higher in hearts receiving CoPP- than PBS-pretreated cells. On histomorphometry, cardiomyocyte graft size was 2.6-fold larger in hearts receiving CoPP- than PBS-pretreated cells, occupying up to 12% of the ventricular area. Vascular density of host-perfused human-derived capillaries was significantly greater in grafts composed of CoPP- than PBS-pretreated cells. Taken together, these experiments demonstrate that ex vivo pretreatment of hESC-CMs with a single dose of CoPP before intramyocardial implantation more than doubled resulting graft size and improved early graft vascularization in acutely infarcted hearts. These findings open the door for delivery of these, or other, stem cells during acute interventional therapy following myocardial infarction or ischemia. PMID

  6. Ion-induced secondary electron emission behavior of sol-gel-derived MgO thin films used for protective layers in alternating current plasma display panels

    NASA Astrophysics Data System (ADS)

    Jung, Hyun Suk; Lee, Jung-Kun; Hong, Kug Sun; Youn, Hyuk-Joon

    2002-09-01

    MgO thin films were prepared using two sols (hydrolyzed sol and stabilized sol) and the ion-induced secondary electron emission behavior of the resultant thin films was investigated. A severe fluctuation in the secondary electron emission current was found in MgO films from hydrolyzed sol. The instability of the ion-induced current was due to the nanosized pores, which were formed during the topotactic reaction of Mg(OH)2 to MgO. Nonhydrolyzed MgO films, however, showed a stable ion-induced current. The ion-induced secondary electron emission coefficients (gammai) of the MgO films had a maximum of 0.95plus-or-minus0.02 when the films were heat treated at 550 degC in O2. The change in gammai of nonhydrolyzed films was discussed from the viewpoint of crystallinity, residual organics, and surface roughness. The high gammai and low processing temperature of nonhydrolyzed MgO films revealed that the sol-gel process is suitable to prepare MgO films for use as a protective layer in ac plasma display panel cells.

  7. Omega-3 fatty acids protect renal functions by increasing docosahexaenoic acid-derived metabolite levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

    PubMed

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Al Mamun, Abdullah; Tanabe, Yoko; Iwamoto, Ryo; Arita, Makoto; Tsuchikura, Satoru; Shido, Osamu

    2014-01-01

    The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) protect against diabetic nephropathy by inhibiting inflammation. The aim of this study was to assess the effects of highly purified DHA and EPA or EPA only administration on renal function and renal eicosanoid and docosanoid levels in an animal model of metabolic syndrome, SHR.Cg-Lepr(cp)/NDmcr (SHRcp) rats. Male SHRcp rats were divided into 3 groups. Control (5% arabic gum), TAK-085 (300 mg/kg/day, containing 467 mg/g EPA and 365 mg/g DHA), or EPA (300 mg/kg/day) was orally administered for 20 weeks. The urinary albumin to creatinine ratio in the TAK-085-administered group was significantly lower than that in other groups. The glomerular sclerosis score in the TAK-085-administered group was significantly lower than that in the other groups. Although DHA levels were increased in total kidney fatty acids, the levels of nonesterified DHA were not significantly different among the 3 groups, whereas the levels of protectin D1, resolvin D1, and resolvin D2 were significantly increased in the TAK-085-administered group. The results show that the use of combination therapy with DHA and EPA in SHRcp rats improved or prevented renal failure associate with metabolic syndrome with decreasing triglyceride levels and increasing ω-3 PUFA lipid mediators. PMID:24642910

  8. Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

    PubMed Central

    Kistner, Otfried; Howard, Keith; Spruth, Martin; Wodal, Walter; Brühl, Peter; Gerencer, Marijan; Crowe, Brian A.; Savidis-Dacho, Helga; Livey, Ian; Reiter, Manfred; Mayerhofer, Ines; Tauer, Christa; Grillberger, Leopold; Mundt, Wolfgang; Falkner, Falko G.; Barrett, P. Noel

    2007-01-01

    The rapid spread and the transmission to humans of avian influenza virus (H5N1) has induced world-wide fears of a new pandemic and raised concerns over the ability of standard influenza vaccine production methods to rapidly supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains were developed and demonstrated to be highly immunogenic in animal models. The vaccines induce cross-neutralising antibodies, highly cross-reactive T-cell responses and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from another clade. These data indicate that cell culture-grown, whole virus vaccines, based on the wild-type virus, allow the rapid high yield production of a candidate pandemic vaccine. PMID:17614165

  9. Derivation of soil-screening thresholds to protect the chisel-toothed kangaroo rat from uranium mine waste in northern Arizona.

    PubMed

    Hinck, Jo Ellen; Linder, Greg; Otton, James K; Finger, Susan E; Little, Edward; Tillitt, Donald E

    2013-08-01

    Chemical data from soil and weathered waste material samples collected from five uranium mines north of the Grand Canyon (three reclaimed, one mined but not reclaimed, and one never mined) were used in a screening-level risk analysis for the Arizona chisel-toothed kangaroo rat (Dipodomys microps leucotis); risks from radiation exposure were not evaluated. Dietary toxicity reference values were used to estimate soil-screening thresholds presenting risk to kangaroo rats. Sensitivity analyses indicated that body weight critically affected outcomes of exposed-dose calculations; juvenile kangaroo rats were more sensitive to the inorganic constituent toxicities than adult kangaroo rats. Species-specific soil-screening thresholds were derived for arsenic (137 mg/kg), cadmium (16 mg/kg), copper (1,461 mg/kg), lead (1,143 mg/kg), nickel (771 mg/kg), thallium (1.3 mg/kg), uranium (1,513 mg/kg), and zinc (731 mg/kg) using toxicity reference values that incorporate expected chronic field exposures. Inorganic contaminants in soils within and near the mine areas generally posed minimal risk to kangaroo rats. Most exceedances of soil thresholds were for arsenic and thallium and were associated with weathered mine wastes. PMID:23604138

  10. The azetidine derivative, KHG26792 protects against ATP-induced activation of NFAT and MAPK pathways through P2X7 receptor in microglia.

    PubMed

    Kim, Eun-A; Cho, Chang Hun; Kim, Jiae; Hahn, Hoh-Gyu; Choi, Soo Young; Yang, Seung-Ju; Cho, Sung-Woo

    2015-12-01

    Azetidine derivatives are of interest for drug development because they may be useful therapeutic agents. However, their mechanisms of action remain to be completely elucidated. Here, we have investigated the effects of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) on ATP-induced activation of NFAT and MAPK through P2X7 receptor in the BV-2 mouse microglial cell line. KHG26792 decreased ATP-induced TNF-α release from BV-2 microglia by suppressing, at least partly, P2X7 receptor stimulation. KHG26792 also inhibited the ATP-induced increase in IL-6, PGE2, NO, ROS, CXCL2, and CCL3. ATP induced NFAT activation through P2X7 receptor, with KHG26792 reducing the ATP-induced NFAT activation. KHG26792 inhibited an ATP-induced increase in iNOS protein and ERK phosphorylation. KHG26792 prevented an ATP-induced increase in MMP-9 activity through the P2X7 receptor as a result of degradation of TIMP-1 by cathepsin B. Our data provide mechanistic insights into the role of KHG26792 in the inhibition of TNF-α produced via P2X7 receptor-mediated activation of NFAT and MAPK pathways in ATP-treated BV-2 cells. This study highlights the potential use of KHG26792 as a therapeutic agent for the many diseases of the CNS related to activated microglia. PMID:26522449

  11. A hot water extract of Aralia cordata activates bone marrow-derived macrophages via a myeloid differentiation protein 88-dependent pathway and protects mice from bacterial infection.

    PubMed

    Seo, Dong-Won; Cho, Yong-Il; Gu, Suna; Kim, Da-Hee; Park, Jung-Hee; Yi, Young-Joo; Lee, Sang-Myeong

    2016-05-01

    In traditional Asian medicine, Aralia cordata (AC) is a known as a pain reliever and anti-inflammatory drug. Although several of its biological activities have been reported, the immunomodulatory effects of a hot water extract of AC (HAC) have not yet been described. The aim of this study was to investigate whether HAC modulates the activation of macrophages, which play important roles in innate immune responses against microbial pathogens, and if so, to determine the molecular mechanisms by which HAC mediates this process. It was found that HAC activates bone marrow-derived macrophages (BMDM) and increases amounts of nitric oxide and proinflammatory cytokines in a dose-dependent manner. In addition, HAC was found to induce phosphorylation of NF-κB and mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinases, extracellular signal-regulated kinases and p38. Interestingly, these effects were absent in BMDM prepared from myeloid differentiation protein 88-knockout mice. Polysaccharides from HAC exerted stronger immunostimulatory effects than HAC itself. Furthermore, orally administered HAC clearly enhanced clearance of the intracellular pathogen Listeria monocytogenes by boosting innate immune responses. These results demonstrate that HAC exerts immunostimulatory effects through the TLR/MyD88 and NF-κB/MAPK signal transduction pathways. PMID:26989992

  12. Epigallocatechin-3-gallate Protects against Hydrogen Peroxide-Induced Inhibition of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

    PubMed Central

    Wang, Dawei; Wang, Yonghui; Xu, Shihong; Wang, Fu; Wang, Bomin; Han, Ke; Sun, Daqing; Li, Lianxin

    2016-01-01

    Oxidative stress induces bone loss and osteoporosis, and epigallocatechin-3-gallate (EGCG) may be used to combat these diseases due to its antioxidative property. Herein, oxidative stress in human bone marrow-derived mesenchymal stem cells (BM-MSCs) was induced by H2O2, resulting in an adverse effect on their osteogenic differentiation. However, this H2O2-induced adverse effect was nullified when the cells were treated with EGCG. In addition, treatment of BM-MSCs with EGCG alone also resulted in the enhancement of osteogenic differentiation of BM-MSCs. After EGCG treatment, expressions of β-catenin and cyclin D1 were upregulated, suggesting that the Wnt pathway was involved in the effects of EGCG on the osteogenic differentiation of BM-MSCs. This was also confirmed by the fact that the Wnt pathway inhibitor, Dickkopf-1 (DKK-1), can nullify the EGCG-induced enhancement effect on BM-MSC's osteogenic differentiation. Hence, our results suggested that EGCG can reduce the effects of oxidative stress on Wnt pathway in osteogenic cells, which supported a potentially promising therapy of bone disorders induced by oxidative stress. Considering its positive effects on BM-MSCs, EGCG may also be beneficial for stem cell-based bone repair. PMID:26977159

  13. Antagonist Targeting microRNA-155 Protects against Lithium-Pilocarpine-Induced Status Epilepticus in C57BL/6 Mice by Activating Brain-Derived Neurotrophic Factor

    PubMed Central

    Cai, Zhengxu; Li, Song; Li, Sheng; Song, Fan; Zhang, Zhen; Qi, Guanhua; Li, Tianbai; Qiu, Juanjuan; Wan, Jiajia; Sui, Hua; Guo, Huishu

    2016-01-01

    Epilepsy is a severe brain disorder affecting numerous patients. Recently, it is inferred that modulation of microRNA-155 (miR-155) could serve as a promising treatment of mesial temporal lobe epilepsy. In the current study, the therapeutic potential of miR-155 antagonist against temporal lobe epilepsy (TLE) was evaluated and the underlying mechanism involved in this regulation was explored. TLE model was induced by lithium-pilocarpine method. The effect of miR-155 antagonist on epilepticus symptoms of TLE mice was assessed using Racine classification and electroencephalogram (EEG) recordings. The expression of brain-derived neurotrophic factor (BDNF) and its association with miR-155 were also assessed with a series of experiments. Our results showed that level of miR-155 was significantly up-regulated after induction of TLE model. Based on the results of EEG and behavior analyses, seizures in mice were alleviated by miR-155 antagonist. Moreover, administration of miR-155 antagonist also significantly increased the level of BDNF. The results of dual luciferase assay and Western blotting showed that miR-155 antagonist exerted its action on status epilepticus by directly regulating the activity of BDNF. Taken all the information together, our results demonstrated that miR-155 antagonist might firstly induce the expression of BDNF, which then contributed to the alleviation of epilepsy in the current study. PMID:27303295

  14. Use of autologous blood-derived endothelial progenitor cells at point-of-care to protect against implant thrombosis in a large animal model

    PubMed Central

    Jantzen, Alexandra E.; Lane, Whitney O.; Gage, Shawn M.; Jamiolkowski, Ryan M.; Haseltine, Justin M.; Galinat, Lauren J.; Lin, Fu-Hsiung; Lawson, Jeffrey H.; Truskey, George A.; Achneck, Hardean E.

    2011-01-01

    Titanium (Ti) is commonly utilized in many cardiovascular devices, e.g. as a component of Nitinol stents, intra- and extracorporeal mechanical circulatory assist devices, but is associated with the risk of thromboemboli formation. We propose to solve this problem by lining the Ti blood-contacting surfaces with autologous peripheral blood-derived late outgrowth endothelial progenitor cells (EPCs) after having previously demonstrated that these EPCs adhere to and grow on Ti under physiological shear stresses and functionally adapt to their environment under flow conditions ex vivo. Autologous fluorescently-labeled porcine EPCs were seeded at the point-of-care in the operating room onto Ti tubes for 30 minutes and implanted into the pro-thrombotic environment of the inferior vena cava of swine (n = 8). After 3 days, Ti tubes were explanted, disassembled, and the blood-contacting surface was imaged. A blinded analysis found all 4 cell-seeded implants to be free of clot, whereas 4 controls without EPCs were either entirely occluded or partially thrombosed. Pre-labeled EPCs had spread and were present on all 4 cell-seeded implants while no endothelial cells were observed on control implants. These results suggest that late outgrowth autologous EPCs represent a promising source of lining Ti implants to reduce thrombosis in vivo. PMID:21840592

  15. Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress.

    PubMed

    Ali, Mohammed Ragab Abdel-Aziz; Abo-Youssef, Amira Morad Hussein; Messiha, Basim Anwar Shehata; Khattab, Mahmoud Mohamed

    2016-06-01

    We aim to evaluate the protective role of the central angiotensin-converting enzyme (ACE) inhibitor perindopril, compared with the standard reactive oxygen species (ROS) scavenger tempol, against lipopolysaccharide (LPS)-induced cognition impairment and amyloidogenesis in a simulation to Alzheimer's disease (AD). Mice were allocated into a control group, an LPS control group (0.8 mg/kg, i.p., once), a tempol (100 mg/kg/day, p.o., 7 days) treatment group, and two perindopril (0.5 and 1 mg/kg/day, p.o., 7 days) treatment groups. A behavioral study was conducted to evaluate spatial and nonspatial memory in mice, followed by a biochemical study involving assessment of brain levels of Aβ and BDNF as Alzheimer and neuroplasticity markers; tumor necrosis factor-alpha (TNF-α), nitric oxide end-products (NOx), neuronal nitric oxide synthase (nNOS), and inducible nitric oxide synthase (iNOS) as inflammatory markers; and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using both routine and special staining. Tempol and perindopril improved spatial and nonspatial memory in mice without affecting locomotor activity; decreased brain Aβ deposition and BDNF depletion; decreased brain TNF-α, NOx, nNOS, iNOS, MDA, and NT levels; and increased brain SOD and GSH contents, parallel to confirmatory histopathological findings. Tempol and perindopril may be promising agents against AD progression via suppression of Aβ deposition and BDNF decline, suppression of TNF-α production, support of brain antioxidant status, and amelioration of oxido-nitrosative stress and NT production. PMID:27026404

  16. PrP{sup C} displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrP{sup C} knockout mice

    SciTech Connect

    Bertuchi, Fernanda R.; Bourgeon, Dominique M.G.; Landemberger, Michele C.; Martins, Vilma R.; Cerchiaro, Giselle

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer PrP{sup C} in solution acts as a radical scavenger. Black-Right-Pointing-Pointer PrP{sup C} reduces hydrogen peroxide toxicity in astrocytes. Black-Right-Pointing-Pointer Increase in ROS disrupted the cell cycle in the PrP{sup C}-knockout astrocytes. Black-Right-Pointing-Pointer PrP{sup C} prevents the cell death independently of an SOD-like activity. -- Abstract: The PrP{sup C} protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrP{sup C} in solution and its participation as a cell protector in astrocytes that were subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrP{sup C} decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu{sup 2+}/ascorbate/H{sub 2}O{sub 2}), which was demonstrated by approximately 70% less DMPO/OH{sup {center_dot}}. In cultured PrP{sup C}-knockout astrocytes from mice, the absence of PrP{sup C} caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3 h of H{sub 2}O{sub 2} treatment. This rapid increase in ROS disrupted the cell cycle in the PrP{sup C}-knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrP{sup C} in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia.

  17. Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase–derived PGD2 biosynthesis

    PubMed Central

    Tokudome, Satori; Sano, Motoaki; Shinmura, Ken; Matsuhashi, Tomohiro; Morizane, Shintaro; Moriyama, Hidenori; Tamaki, Kayoko; Hayashida, Kentaro; Nakanishi, Hiroki; Yoshikawa, Noritada; Shimizu, Noriaki; Endo, Jin; Katayama, Takaharu; Murata, Mitsushige; Yuasa, Shinsuke; Kaneda, Ruri; Tomita, Kengo; Eguchi, Naomi; Urade, Yoshihiro; Asano, Koichiro; Utsunomiya, Yasunori; Suzuki, Takeshi; Taguchi, Ryo; Tanaka, Hirotoshi; Fukuda, Keiichi

    2009-01-01

    Lipocalin-type prostaglandin D synthase (L-PGDS), which was originally identified as an enzyme responsible for PGD2 biosynthesis in the brain, is highly expressed in the myocardium, including in cardiomyocytes. However, the factors that control expression of the gene encoding L-PGDS and the pathophysiologic role of L-PGDS in cardiomyocytes are poorly understood. In the present study, we demonstrate that glucocorticoids, which act as repressors of prostaglandin biosynthesis in most cell types, upregulated the expression of L-PGDS together with cytosolic calcium-dependent phospholipase A2 and COX2 via the glucocorticoid receptor (GR) in rat cardiomyocytes. Accordingly, PGD2 was the most prominently induced prostaglandin in vivo in mouse hearts and in vitro in cultured rat cardiomyocytes after exposure to GR-selective agonists. In isolated Langendorff-perfused mouse hearts, dexamethasone alleviated ischemia/reperfusion injury. This cardioprotective effect was completely abrogated by either pharmacologic inhibition of COX2 or disruption of the gene encoding L-PGDS. In in vivo ischemia/reperfusion experiments, dexamethasone reduced infarct size in wild-type mice. This cardioprotective effect of dexamethasone was markedly reduced in L-PGDS–deficient mice. In cultured rat cardiomyocytes, PGD2 protected against cell death induced by anoxia/reoxygenation via the D-type prostanoid receptor and the ERK1/2-mediated pathway. Taken together, these results suggest what we believe to be a novel interaction between glucocorticoid-GR signaling and the cardiomyocyte survival pathway mediated by the arachidonic acid cascade. PMID:19451694

  18. Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis

    PubMed Central

    Fan, Heng; Tang, Qing; Shou, Zhe-Xing; Zuo, Dong-Mei; Zou, Zhou; Xu, Meng; Chen, Qian-Yun; Peng, Ying; Deng, Shuang-Jiao; Liu, Yu-Jin

    2015-01-01

    The administration of bone mesenchymal stem cells (BMSCs) could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs derived extracellular vesicles (BMSC-EVs), including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI) and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65), tumor necrosis factor-alpha (TNF-α), induciblenitric oxidesynthase (iNOS) and cyclooxygenase-2 (COX-2) in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1β (IL-1β) and an increase in interleukin-10 (IL-10) expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO) and Malondialdehyde (MDA), as well as an increase in superoxide dismutase (SOD) and glutathione (GSH). BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis. PMID:26469068

  19. Attenuation of high-glucose-induced inflammatory response by a novel curcumin derivative B06 contributes to its protection from diabetic pathogenic changes in rat kidney and heart.

    PubMed

    Pan, Yong; Zhu, Guanghui; Wang, Yi; Cai, Lu; Cai, Yuepiao; Hu, Jie; Li, Yilan; Yan, Yongbo; Wang, Zengshou; Li, Xiaokun; Wei, Tiemin; Liang, Guang

    2013-01-01

    There is increasing evidence indicating that inflammatory processes are involved in the development and progression of diabetic complications. However, effective anti-inflammatory treatments for patients who have diabetic complications have yet been practically identified. Curcumin is a main component of Curcuma longa with numerous pharmacological activities. Previously, we synthesized a novel curcumin analogue (B06) that exhibited an improved pharmacokinetic and enhanced anti-inflammatory activity compared to curcumin. The present study aimed to test the hypothesis that B06 may reduce high-glucose-induced inflammation and inflammation-mediated diabetic complications. In vitro, pretreatment with B06 at a concentration of 5 μM significantly reduced the high-glucose-induced overexpression of inflammatory cytokines in macrophages. This anti-inflammatory activity of B06 is associated with its inhibition of c-Jun N-terminal kinase/nuclear factor κB activation. In vivo, despite that B06 administration at 0.2 mg · kg(-1) · d(-1) for 6 weeks did not affect the blood glucose profile of diabetic rats, the B06-treated animals displayed significant decreases in inflammatory mediators in the serum, kidney, and heart and renal macrophage infiltration. This was accompanied with an attenuation of diabetes-induced structural and functional abnormalities in the kidney and heart. Taken together, these data suggest that the novel derivative B06 might be a potential therapeutic agent for diabetic complications via an anti-inflammatory mechanism and support the potential application in diabetic complication therapy via anti-inflammatory strategy. PMID:22819547

  20. Protective effect of melatonin-supported adipose-derived mesenchymal stem cells against small bowel ischemia-reperfusion injury in rat.

    PubMed

    Chang, Chia-Lo; Sung, Pei-Hsun; Sun, Cheuk-Kwan; Chen, Chih-Hung; Chiang, Hsin-Ju; Huang, Tien-Hung; Chen, Yi-Ling; Zhen, Yen-Yi; Chai, Han-Tan; Chung, Sheng-Ying; Tong, Meng-Shen; Chang, Hsueh-Wen; Chen, Hong-Hwa; Yip, Hon-Kan

    2015-09-01

    We tested the hypothesis that combined melatonin and autologous adipose-derived mesenchymal stem cells (ADMSC) was superior to either alone against small bowel ischemia-reperfusion (SBIR) injury induced by superior mesenteric artery clamping for 30 min followed by reperfusion for 72 hr. Male adult Sprague Dawley rats (n = 50) were equally categorized into sham-operated controls SC, SBIR, SBIR-ADMSC (1.0 × 10(6) intravenous and 1.0 × 10(6) intrajejunal injection), SBIR-melatonin (intraperitoneal 20 mg/kg at 30 min after SI ischemia and 50 mg/kg at 6 and 18 hr after SI reperfusion), and SBIR-ADMSC-melatonin groups. The results demonstrated that the circulating levels of TNF-α, MPO, LyG6+ cells, CD68+ cells, WBC count, and gut permeability were highest in SBIR and lowest in SC, significantly higher in SBIR-ADMSC group and further increased in SBIR-melatonin group than in the combined therapy group (all P < 0.001). The ischemic mucosal damage score, the protein expressions of inflammation (TNF-α, NF-κB, MMP-9, MPO, and iNOS), oxidative stress (NOX-1, NOX-2, and oxidized protein), apoptosis (APAF-1, mitochondrial Bax, cleaved caspase-3 and PARP), mitochondrial damage (cytosolic cytochrome C) and DNA damage (γ-H2AX) markers, as well as cellular expressions of proliferation (PCNA), apoptosis (caspase-3, TUNEL assay), and DNA damage (γ-H2AX) showed an identical pattern, whereas mitochondrial cytochrome C exhibited an opposite pattern compared to that of inflammation among all groups (all P < 0.001). Besides, antioxidant expressions at protein (NQO-1, GR, and GPx) and cellular (HO-1) levels progressively increased from SC to the combined treatment group (all P < 0.001). In conclusion, combined melatonin-ADMSC treatment offered additive beneficial effect against SBIR injury. PMID:26013733

  1. Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin

    PubMed Central

    Dorri, Somaye Ardebili; Hosseinzadeh, Hossein; Abnous, Khalil; Hasani, Faezeh Vahdati; Robati, Rezvan Yazdian; Razavi, Bibi Marjan

    2015-01-01

    Objective(s): In this study the effect of crocin, a carotenoid isolated from saffron, on malathion (an organophosphate insecticide) induced depressive- like behavior in subacute exposure was investigated. Moreover the molecular mechanism of malathion induced depressive- like behavior and its decreasing effect on the level of brain derived neurotrophic factor (BDNF) in rat hippocampus and cerebral cortex were evaluated. Materials and Methods: Male Wistar rats were exposed to malathion (50 mg/kg/day, IP) alone or in combination with crocin (10, 20 and 40 mg/kg/day, IP), imipramine (20 mg/kg/day, IP) and vitamin E (200 mg/kg, three times a week, IP) respectively for 14 days. The forced swimming test (FST) was performed on days 1st, 7th and 14st. The level of malondealdehyde (MDA) and reduced glutathione (GSH) were measured in cerebral cortex and hippocampus of rats. The protein level of BDNF was evaluated using Western blot analysis. Results: Malathion (50 mg/kg, IP) increased immobility time in the FST, without affecting total locomotor activity in open-field test. Malathion increased the malondealdehyde (MDA) and decreased the glutathione (GSH), whereas these effects were reversed by crocin and vitamin E. Malathion decreased plasma acetylcholinesterase activity, however this effect was not reversed by crocin or vitamin E. Malathion reduced the protein level of BDNF in rat hippocampus. Imipramine and crocin prevented the decreasing effect of malathion on BDNF. Conclusion: These results showed that crocin attenuates some neurochemical and behavioral effects induced by malathion. This neuroprotective effect of crocin may be in part due to its effect on BDNF. PMID:26730329

  2. Downregulation of importin-9 protects MCF-7 cells against apoptosis induced by the combination of garlic-derived alliin and paclitaxel.

    PubMed

    Izdebska, Magdalena; Grzanka, Dariusz; Gagat, Maciej; Hałas-Wiśniewska, Marta; Grzanka, Alina

    2016-05-01

    Numerous studies on the biological mechanism of breast cancer have identified a number of potential therapeutic molecular targets. In this context, one type of potential candidates appears to be agents that target the actin cytoskeleton of cancer cells or regulate actin cytoskeleton dynamics. The aim of the present study was to study the impact of altered actin transport between the cytoplasm and nucleus by the downregulation of importin-9 (IPO9) in breast adenocarcinoma MCF-7 cells exposed to an apoptosis-inducing combination of garlic-derived S-allyl-L-cysteine sulfoxide (alliin) and paclitaxel (PTX). The expression of IPO9 was downregulated by the transfection of non-aggressive breast cancer MCF-7 cells with siRNA against IPO9. The altered expression of IPO9 and cofilin-1 (CFL1) was examined using western blotting. Moreover, the effect of the downregulation of IPO9 on cell death induced by the combination of PTX and alliin was also investigated. The alterations of IPO9 and CFL1 levels were also related with F-actin organizational changes and F-actin fluorescence intensity in the nuclear/perinuclear area of the cells. The results presented here indicate that alliin and PTX act synergistically to promote and potentiate apoptosis in MCF-7 cells. Furthermore, using RNA interference technique, we showed that downregulation of IPO9 expression was correlated with a significant reduction in the apoptotic cell population as well as with a decrease in F-actin content in whole cells, and in the cortical and nuclear/perinuclear areas of the cells. Simultaneously, the downregulation of IPO9 was also accompanied by the increased post-translational expression of CFL1. Furthermore, the data obtained in the present study allow us to conclude that CFL1 itself does not translocate actin into the cell nucleus but this transport requires the functional expression of IPO9. PMID:26934847

  3. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

    PubMed Central

    Castillo-Melendez, Margie; Yawno, Tamara; Jenkin, Graham; Miller, Suzanne L.

    2013-01-01

    In the research, clinical, and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however, this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical, and logistical considerations, together with the propensity for native cells to form teratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs), or umbilical cord blood (UCB) stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  4. Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives

    PubMed Central

    2015-01-01

    Methods have recently been developed for the phosphine-catalyzed asymmetric γ-addition of nucleophiles to readily available allenoates and alkynoates to generate useful α,β-unsaturated carbonyl compounds that bear a stereogenic center in either the γ or the δ position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at both termini of the new bond could be controlled effectively. In this report, we describe the achievement of this objective, specifically, that a chiral phosphepine can catalyze the stereoconvergent γ-addition of a racemic nucleophile to a racemic electrophile; through the choice of an appropriate heterocycle as the nucleophilic partner, this new method enables the synthesis of protected α,α-disubstituted α-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity. PMID:26192217

  5. Immunization of Saimiri sciureus Monkeys with a Recombinant Hybrid Protein Derived from the Plasmodium falciparum Antigen Glutamate-Rich Protein and Merozoite Surface Protein 3 Can Induce Partial Protection with Freund and Montanide ISA720 Adjuvants

    PubMed Central

    Carvalho, Leonardo J. M.; Alves, Francisco A.; Bianco, Cesare; Oliveira, Salma G.; Zanini, Graziela M.; Soe, Soe; Druilhe, Pierre; Theisen, Michael; Muniz, José A. P. C.; Daniel-Ribeiro, Cláudio T.

    2005-01-01

    The immunogenicity and efficacy of a hybrid recombinant protein derived from the N-terminal end of the glutamate-rich protein (GLURP) and the C-terminal portion of the merozoite surface protein 3 (MSP3) of Plasmodium falciparum was evaluated in Saimiri sciureus monkeys. The GLURP/MSP3 hybrid protein, expressed in Lactococcus lactis, was administered in association with alum, Montanide ISA720, or complete or incomplete Freund adjuvant (CFA/IFA) in groups of five animals each. The three formulations were shown to be immunogenic, but the one with alum was shown to be weak compared to the other two, particularly CFA/IFA, which provided very high antibody titers (enzyme-linked immunosorbent assay titers of >3,000,000 and immunofluorescence antibody test titers of 6,400). After a challenge infection with P. falciparum FUP strain, all five monkeys from the GLURP/MSP3-alum group showed a rapid increase in parasitemia, reaching 10% and were treated early. The two monkeys with the highest antibody titers in group GLURP/MSP3-Montanide ISA720 had a delay in the course of parasitemia and were treated late due to a low hematocrit. In the GLURP/MSP3-CFA/IFA group, parasitemia remained below this threshold in four of the five animals and, after it reached a peak, parasitemia started to decrease and monkeys were treated late. When all animals were grouped according to the outcome, a statistically significant association between high antibody titers and partial protection was observed. The challenge infection boosted the antibody titers, and the importance of this event for vaccine efficacy in areas where this parasite is endemic is discussed. In conclusion, these data suggest that GLURP and MSP3 can induce protection against malaria infection if antibodies are induced at properly high titers. PMID:15699417

  6. Comparative Analysis of the Magnitude, Quality, Phenotype and Protective Capacity of SIV Gag-Specific CD8+ T Cells Following Human-, Simian- and Chimpanzee-Derived Recombinant Adenoviral Vector Immunisation

    PubMed Central

    Quinn, Kylie M.; Costa, Andreia Da; Yamamoto, Ayako; Berry, Dana; Lindsay, Ross W.B.; Darrah, Patricia A.; Wang, Lingshu; Cheng, Cheng; Kong, Wing-Pui; Gall, Jason G.D.; Nicosia, Alfredo; Folgori, Antonella; Colloca, Stefano; Cortese, Riccardo; Gostick, Emma; Price, David A.; Gomez, Carmen E.; Esteban, Mariano; Wyatt, Linda S.; Moss, Bernard; Morgan, Cecilia; Roederer, Mario; Bailer, Robert T.; Nabel, Gary J.; Koup, Richard A.; Seder, Robert A.

    2013-01-01

    Recombinant adenoviral vectors (rAds) are the most potent recombinant vaccines for eliciting CD8+ T cell-mediated immunity in humans; however, prior exposure from natural adenoviral infection can decrease such responses. Here we show low seroreactivity in humans against simian- (sAd11, sAd16), or chimpanzee-derived (chAd3, chAd63) compared to human-derived (rAd5, rAd28, rAd35) vectors across multiple geographic regions. We then compared the magnitude, quality, phenotype and protective capacity of CD8+ T cell responses in mice vaccinated with rAds encoding SIV Gag. Using a dose range (1 × 107 to 109 PU), we defined a hierarchy among rAd vectors based on the magnitude and protective capacity of CD8+ T cell responses, from most to least as: rAd5 and chAd3, rAd28 and sAd11, chAd63, sAd16, and rAd35. Selection of rAd vector or dose could modulate the proportion and/or frequency of IFNγ+TNFα+IL-2+ and KLRG1+CD127- CD8+ T cells, but strikingly ~30–80% of memory CD8+ T cells co-expressed CD127 and KLRG1. To further optimise CD8+ T cell responses, we assessed rAds as part of prime-boost regimens. Mice primed with rAds and boosted with NYVAC generated Gag-specific responses that approached ~60% of total CD8+ T cells at peak. Alternatively, priming with DNA or rAd28 and boosting with rAd5 or chAd3 induced robust and equivalent CD8+ T cell responses compared to prime or boost alone. Collectively, these data provide the immunologic basis for using specific rAd vectors alone or as part of prime-boost regimens to induce CD8+ T cells for rapid effector function or robust long-term memory, respectively. PMID:23390298

  7. Sun protection

    MedlinePlus

    ... age spots are caused by exposure to the sun. The two types of sun rays that can injure the skin are ultraviolet ... changes is to protect your skin from the sun. This includes using sunscreen and other protective measures. ...

  8. Rat adipose-derived stem cells express low level of α-Gal and are dependent on CD59 for protection from human xenoantibody and complement-mediated lysis

    PubMed Central

    Jia, Yu; Zhao, Yue; Wang, Lu; Xiang, Ying; Chen, Song; Ming, Chang-Sheng; Wang, Cong-Yi; Chen, Gang

    2016-01-01

    Since increasing evidence has indicated that adipose-derived stem cells (ASCs) can function across the species barrier, the use of xenogeneic ASCs may be a practical alternative to the autotransplantation and allotransplantation. Before animal ASCs can be used clinically, evidence needs to be provided to indicate whether they will survive in a human host. In the present study, we investigated whether rat ASCs (rASCs) could resist human xenoantibody and complement-mediated lysis as well as investigated the possible mechanisms involved. We found that rASCs could significantly resist human natural antibody and complement-mediated cytotoxicity when incubated with 20% or 50% normal human serum (NHS) in vitro, as compared with rat lymphocytes (rLCs). Mechanistically, rASCs expressed lower level of xenoantigen Galα1-3Galβ1-4GlcNAc (α-Gal), which was correlated with decreased binding of human xenoreactive IgG and IgM and reduced deposition of complement C3c and C4c. More interestingly, rASCs had minimal deposition of human membrane attack complex (C5b-9). When the expression of CD55 and CD59 was analyzed by flow cytometry, we found that rASCs expressed very weak CD55 but expressed much higher level of CD59 than rLCs. Moreover, the knockdown of CD59 expression by siRNA largely reversed the resistance of rASCs to the human serum-mediated lysis. Taken together, these data have demonstrated for the first time that rat ASCs are capable to protect themselves from human xenoantibody and complement-mediated lysis, which is dependent on CD59 and is correlated with low expression of α-Gal. Xenogenic ASCs may have the potential to treat patients in the future. PMID:27347314

  9. Insider protection

    SciTech Connect

    Waddoups, I.G.

    1993-07-01

    The government community is broadly addressing the insider threat. The first section of this paper defines protection approaches and the latter sections present various applicable technology developments. The bulk of the paper discusses technology developments applied to (1) personnel and material tracking and inventory, (2) classified document protection, and (3) protecting security systems. The personnel and material tracking system uses a PC based-host to (1) collect information from proximity tags and material movement sensors, (2) apply rules to this input to assure that the ongoing activity meets the site selectable rules and, (3) forward the results to either an automated inventory system or an alarm system. The document protection system uses a PC network to efficiently and securely control classified material which is stored on write-once-read-mostly optical media. The protection of sensor to multiplexer communications in a security system is emphasized in the discussion of protecting security systems.

  10. The protective effect of astrocyte-derived 14,15-EET on H2O2-induced cell injury in Astrocyte-dopaminergic neuronal cell line co-culture

    PubMed Central

    Terashvili, Maia; Sarkar, Pallabi; Van Nostrand, Meg; Falck, John R.; Harder, David R.

    2014-01-01

    Astrocytes perform several functions that are essential for normal neuronal activity. They play a critical role in neuronal survival during ischemia and other degenerative injuries and also modulate neuronal recovery by influencing neurite outgrowth. In this study, we investigated the neuroprotective effects of astrocyte-derived 14,15-epoxyeicosatrienoic acid (14,15-EET), metabolite of arachidonic acid by Cytochrome P450 epoxygenases (CYP), against oxidative stress induced by hydrogen peroxide (H2O2). We found that dopaminergic neuronal cells (N27 cell line) stimulated with two different doses of H2O2 (0.1 and 1 mM) for 1h showed decreased cell viability compared to the control group, while astrocytes co-cultured with dopaminergic neuronal cell lines prevented cell during after stimulation with the same doses of H2O2 for 1h. Dopaminergic neuronal cells (N27 cell line) pretreated with different doses of 14, 15-EET (0.1–30 μM, 30 min) before H2O2 stimulation also showed increased cell viability. Furthermore, pre-treatment of the co-cultured cells with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), an inhibitor of the EET metabolizing enzyme, soluble epoxide hydrolase (sEH), before H2O2 stimulation (1 mM, for 1h) increased cell viability. It also increased the endogenous level of 14,15-EET in the media compared to control group. However, pretreatment with the CYP epoxygenase inhibitor miconazole (1–20 μM, 1h) before H2O2 (1 mM, 1h) stimulation showed decreased cell viability. Our data suggest that 14,15-EET which is released from astrocytes, enhances cell viability against oxidant induced injury. Further understanding of the mechanism of 14,15-EET-mediated protection in dopaminergic neurons is imperative, as it could lead to novel therapeutic approaches for treating CNS neuropathologies, such as Parkinson’s disease. PMID:22863680

  11. Exendin-4 protects bone marrow-derived mesenchymal stem cells against oxygen/glucose and serum deprivation-induced apoptosis through the activation of the cAMP/PKA signaling pathway and the attenuation of ER stress

    PubMed Central

    HE, JIEQIONG; WANG, CHAO; SUN, YUNPENG; LU, BO; CUI, JINJIN; DONG, NANA; ZHANG, MAOMAO; LIU, YOUBING; YU, BO

    2016-01-01

    Exendin-4 (ex-4) is a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist which exerts beneficial effects on glycemic control and promotes cell viability. In the present study, we investigated the anti-apoptotic effects of ex-4, as well as the potential mechanisms responsible for these effects in rat bone marrow-derived mesenchymal stem cells (BM-MSCs) under conditions of oxygen, glucose and serum deprivation (OGD). The apoptosis of the MSCs was induced by subjecting the cells to OGD conditions for 4 h and was detected by Annexin V/PI and Hoechst 33258 staining. The MSCs were pre-conditioned with ex-4 for 12 h prior to being subjected to OGD conditions, and the expression levels of an apoptotic marker (cleaved caspase-3), endoplasmic reticulum (ER) stress markers [phosphorylated (p-)protein kinase RNA-like endoplasmic reticulum kinase (PERK), PERK, binding immunoglobulin protein (BIP), activating transcription factor 4 (ATF-4) and C/EBP homologous protein (CHOP)], as well as those of a survival marker (Bcl-2) were measured by western blot analysis. Furthermore, the mRNA levels of ATF-4 and CHOP were determined by RT-qPCR. ELISA was used to examine the activity of intracellular cAMP. Moreover, the GLP-1R antagonist, exendin9-39 (ex9-39), the protein kinase A (PKA) inhibitor, H89, and small interfering RNA (siRNA) targeting rat ATF-4 and CHOP were co-incubated with the MSCs. The apoptotic rate was markedly diminished following pre-conditioning with ex-4 in a dose-dependent manner (P<0.05). The ER stress markers, p-PERK, BIP, ATF-4 and CHOP, were upregulated in the cells subjected to OGD conditions. Ex-4 pre-conditioning significantly decreased the mRNA and protein levels of ATF-4 and CHOP (P<0.05), and increased the activity of intracellular cAMP (P<0.05). Furthermore, the anti-apoptotic effects of ex-4 were almost reversed by treatment with either H89 or ex9-39 (P<0.05); transfection with siRNA-CHOP significantly reduced the apoptotic rate of the MSCs and

  12. 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. PMID:23292546

  13. Memory protection

    NASA Technical Reports Server (NTRS)

    Denning, Peter J.

    1988-01-01

    Accidental overwriting of files or of memory regions belonging to other programs, browsing of personal files by superusers, Trojan horses, and viruses are examples of breakdowns in workstations and personal computers that would be significantly reduced by memory protection. Memory protection is the capability of an operating system and supporting hardware to delimit segments of memory, to control whether segments can be read from or written into, and to confine accesses of a program to its segments alone. The absence of memory protection in many operating systems today is the result of a bias toward a narrow definition of performance as maximum instruction-execution rate. A broader definition, including the time to get the job done, makes clear that cost of recovery from memory interference errors reduces expected performance. The mechanisms of memory protection are well understood, powerful, efficient, and elegant. They add to performance in the broad sense without reducing instruction execution rate.

  14. Protective Eyewear

    MedlinePlus

    ... Whether you’re on the basketball court, in chemistry class, or sitting by the pool, wearing protective ... remember to wear safety goggles. Using chemicals in chemistry class? Look like a real scientist by wearing ...

  15. Corrosion protection

    DOEpatents

    Brown, Donald W.; Wagh, Arun S.

    2003-05-27

    There has been invented a chemically bonded phosphate corrosion protection material and process for application of the corrosion protection material for corrosion prevention. A slurry of iron oxide and phosphoric acid is used to contact a warm surface of iron, steel or other metal to be treated. In the presence of ferrous ions from the iron, steel or other metal, the slurry reacts to form iron phosphates which form grains chemically bonded onto the surface of the steel.

  16. 40 CFR 721.1820 - Bisphenol derivative.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Bisphenol derivative. 721.1820 Section... Substances § 721.1820 Bisphenol derivative. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisphenol derivative (PMN No. P-92-509)...

  17. 40 CFR 721.1820 - Bisphenol derivative.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Bisphenol derivative. 721.1820 Section... Substances § 721.1820 Bisphenol derivative. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisphenol derivative (PMN No. P-92-509)...

  18. 40 CFR 721.1820 - Bisphenol derivative.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Bisphenol derivative. 721.1820 Section... Substances § 721.1820 Bisphenol derivative. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisphenol derivative (PMN No. P-92-509)...

  19. 40 CFR 721.1820 - Bisphenol derivative.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Bisphenol derivative. 721.1820 Section... Substances § 721.1820 Bisphenol derivative. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisphenol derivative (PMN No. P-92-509)...

  20. 40 CFR 721.646 - Aminofluoran derivative (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Aminofluoran derivative (generic name). 721.646 Section 721.646 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.646 Aminofluoran derivative (generic name). (a) Chemical substance and significant new...

  1. 40 CFR 721.646 - Aminofluoran derivative (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Aminofluoran derivative (generic name). 721.646 Section 721.646 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.646 Aminofluoran derivative (generic name). (a) Chemical substance and significant new...

  2. 40 CFR 721.646 - Aminofluoran derivative (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Aminofluoran derivative (generic name). 721.646 Section 721.646 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.646 Aminofluoran derivative (generic name). (a) Chemical substance and significant new...

  3. 40 CFR 721.646 - Aminofluoran derivative (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Aminofluoran derivative (generic name). 721.646 Section 721.646 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.646 Aminofluoran derivative (generic name). (a) Chemical substance and significant new...

  4. 40 CFR 721.646 - Aminofluoran derivative (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Aminofluoran derivative (generic name). 721.646 Section 721.646 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.646 Aminofluoran derivative (generic name). (a) Chemical substance and significant new...

  5. Complex derivatives

    NASA Astrophysics Data System (ADS)

    Battiston, Stefano; Caldarelli, Guido; Georg, Co-Pierre; May, Robert; Stiglitz, Joseph

    2013-03-01

    The intrinsic complexity of the financial derivatives market has emerged as both an incentive to engage in it, and a key source of its inherent instability. Regulators now faced with the challenge of taming this beast may find inspiration in the budding science of complex systems.

  6. 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

  7. Lightning Protection

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Kit-built airplanes are more affordable because they are assembled by the owner and do not require Federal Aviation Administration (FAA) certification. The Glasair III, is an advanced technology homebuilt, constructed of a fiberglass and graphite fiber composite material, and equipped with digital instruments. Both technologies make the airplane more susceptible to lightning effects. When Glasair manufacturer, Stoddard-Hamilton, decided that lightning protection would enable more extensive instrument flight and make the plane more marketable, they proposed a joint development program to NASA Langley Research Center (LAR). Under a Small Business Innovation Research (SBIR) contract, Langley contractors designed and tested a lightning protection system, and the Glasair III-LP became the first kit-built composite aircraft to be lightning tested and protection-verified under FAA guidelines for general aviation aircraft.

  8. Lightning Protection

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Lightning Technologies, Inc., Pittsfield, MA, - a spinoff company founded by president J. Anderson Plumer, a former NASA contractor employee who developed his expertise with General Electric Company's High Voltage Laboratory - was a key player in Langley Research Center's Storm Hazards Research Program. Lightning Technologies used its NASA acquired experience to develop protective measures for electronic systems and composite structures on aircraft, both of which are particularly susceptible to lightning damage. The company also provides protection design and verification testing services for complete aircraft systems or individual components. Most aircraft component manufacturers are among Lightning Technologies' clients.

  9. Noise Protection

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Environmental Health Systems puts forth an increasing effort in the U.S. to develop ways of controlling noise, particularly in industrial environments due to Federal and State laws, labor union insistence and new findings relative to noise pollution impact on human health. NASA's Apollo guidance control system aided in the development of a noise protection product, SMART. The basis of all SMART products is SMART compound a liquid plastic mixture with exceptional energy/sound absorbing qualities. The basic compound was later refined for noise protection use.

  10. Protective Clothing

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Beta Glass material, originating from the Apollo program is supplied to Fyrepel by Owens-Corning and incorporated into Fyrepel's Fyretex and Beta-Mex aluminized fabrics. Fabrics are used in fire entry suits, several other types of protective suits for wear in hot industrial environments and such accessory items as heat-reflecting curtains for industrial applications.

  11. Protect thyself

    SciTech Connect

    Sullivan, A.M.

    1982-06-01

    The article considers items of personal protection for miners: Self-rescuers, respirators, hard hats and cap lamps. A table provides a comparison between five types of self-contained self-rescuer. Details are also given of hard hat cap lamp and respirator manufacturers.

  12. Protecting Privacy.

    ERIC Educational Resources Information Center

    Coyle, Karen

    2001-01-01

    Discusses privacy issues related to use of the Internet. Topics include data gathering functions that are built into applications of the World Wide Web; cookies that identify Web site visitors; personal identity information; libraries and privacy, including the need for privacy policies; protecting your privacy; and developing privacy literacy.…

  13. Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor γ and Glucagon-Like Peptide-1.

    PubMed

    den Besten, Gijs; Gerding, Albert; van Dijk, Theo H; Ciapaite, Jolita; Bleeker, Aycha; van Eunen, Karen; Havinga, Rick; Groen, Albert K; Reijngoud, Dirk-Jan; Bakker, Barbara M

    2015-01-01

    The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs), have been suggested to play an important role. Recently, we showed that SCFAs protect against the metabolic syndrome via a signaling cascade that involves peroxisome proliferator-activated receptor (PPAR) γ repression and AMP-activated protein kinase (AMPK) activation. In this study we investigated the molecular mechanism via which the dietary fiber guar gum protects against the metabolic syndrome. C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber guar gum for 12 weeks and effects on lipid and glucose metabolism were studied. We demonstrate that, like SCFAs, also guar gum protects against high-fat diet-induced metabolic abnormalities by PPARγ repression, subsequently increasing mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the activation of AMPK and culminating in enhanced oxidative metabolism in both liver and adipose tissue. Moreover, guar gum markedly increased peripheral glucose clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like peptide-1. Overall, this study provides novel molecular insights into the beneficial effects of guar gum on the metabolic syndrome and strengthens the potential role of guar gum as a dietary-fiber intervention. PMID:26292284

  14. ASSESSING BIOACCUMULATION FOR DERIVING NATIONAL HUMAN HEALTH WATER QUALITY CRITERIA

    EPA Science Inventory

    The United States Environmental Protection Agency is revising its methodology for deriving national ambient water quality criteria (AWQC) to protect human health. A component of this guidance involves assessing the potential for chemical bioaccumulation in commonly consumed fish ...

  15. Protective Coating

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Inorganic Coatings, Inc.'s K-Zinc 531 protective coating is water-based non-toxic, non-flammable and has no organic emissions. High ratio silicate formula bonds to steel, and in 30 minutes, creates a very hard ceramic finish with superior adhesion and abrasion resistance. Improved technology allows application over a minimal commercial sandblast, fast drying in high humidity conditions and compatibility with both solvent and water-based topcoats. Coating is easy to apply and provides long term protection with a single application. Zinc rich coating with water-based potassium silicate binder offers cost advantages in materials, labor hours per application, and fewer applications over a given time span.

  16. Protective Coatings

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Ameron International Protective Coatings Group developed a special coating for NASA that would withstand the high temperatures generated by the Space Shuttle rocket engines. The coating remains intact for at least 10 minutes, and insulates the launch pad so that it does not exceed 150 degrees and buckle. The NASA formulation was from Ameron's Engineered Siloxane (PSX) chemistry, which employs an inorganic silicon-oxygen structure which the company states is stronger and more reliable than organic polymers. Some of Ameron's PSX product line is based on the NASA technology, used for everything from industrial equipment to bridges.

  17. Protecting Antarctica

    NASA Astrophysics Data System (ADS)

    Carlowicz, Michael

    House Science Committee Chairman Robert Walker (R-Pa.) has introduced a bill into Congress to give the United States the legislative authority to implement the 1991 Environmental Protocol to the Antarctic Treaty. That protocol established rules and principles to shield the Antarctic environment from human spoilage—placing limits on the discharge of pollutants, protecting plant and animal life, and requiring environmental impact assessments before new activities and programs are launched. The protocol also forbids prospecting or developing of mineral resources except for scientific research.

  18. Lifecourse Models for Ensuring Children's Health Protection

    EPA Science Inventory

    New knowledge about environmental risks to human reproduction and development directly relevant to children’s health protection derives from the fields of developmental and reproductive toxicology, exposure science, epidemiology, risk assessment, and public health. Together, thi...

  19. An MDCK Cell Culture-Derived Formalin-Inactivated Influenza Virus Whole-Virion Vaccine from an Influenza Virus Library Confers Cross-Protective Immunity by Intranasal Administration in Mice

    PubMed Central

    Haredy, Ahmad M.; Takenaka, Nobuyuki; Yamada, Hiroshi; Sakoda, Yoshihiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Omasa, Takeshi; Ohtake, Hisao; Mori, Yasuko; Kida, Hiroshi; Yamanishi, Koichi

    2013-01-01

    It is currently impossible to predict the next pandemic influenza virus strain. We have thus established a library of influenza viruses of all hemagglutinin and neuraminidase subtypes and their genes. In this article, we examine the applicability of a rapid production model for the preparation of vaccines against emerging pandemic influenza viruses. This procedure utilizes the influenza virus library, cell culture-based vaccine production, and intranasal administration to induce a cross-protective immune response. First, an influenza virus reassortant from the library, A/duck/Hokkaido/Vac-3/2007 (H5N1), was passaged 22 times (P22) in Madin-Darby canine kidney (MDCK) cells. The P22 virus had a titer of >2 ×108 PFU/ml, which was 40 times that of the original strain, with 4 point mutations, which altered amino acids in the deduced protein sequences encoded by the PB2 and PA genes. We then produced a formalin-inactivated whole-virion vaccine from the MDCK cell-cultured A/duck/Hokkaido/Vac-3/2007 (H5N1) P22 virus. Intranasal immunization of mice with this vaccine protected them against challenges with lethal influenza viruses of homologous and heterologous subtypes. We further demonstrated that intranasal immunization with the vaccine induced cross-reactive neutralizing antibody responses against the homotypic H5N1 influenza virus and its antigenic variants and cross-reactive cell-mediated immune responses to the homologous virus, its variants within a subtype, and even an influenza virus of a different subtype. These results indicate that a rapid model for emergency vaccine production may be effective for producing the next generation of pandemic influenza virus vaccines. PMID:23637045

  20. In Vitro and In Vivo Studies for Assessing the Immune Response and Protection-Inducing Ability Conferred by Fasciola hepatica-Derived Synthetic Peptides Containing B- and T-Cell Epitopes

    PubMed Central

    Rojas-Caraballo, Jose; López-Abán, Julio; Pérez del Villar, Luis; Vizcaíno, Carolina; Vicente, Belén; Fernández-Soto, Pedro; del Olmo, Esther; Patarroyo, Manuel Alfonso; Muro, Antonio

    2014-01-01

    Fasciolosis is considered the most widespread trematode disease affecting grazing animals around the world; it is currently recognised by the World Health Organisation as an emergent human pathogen. Triclabendazole is still the most effective drug against this disease; however, resistant strains have appeared and developing an effective vaccine against this disease has increasingly become a priority. Several bioinformatics tools were here used for predicting B- and T-cell epitopes according to the available data for Fasciola hepatica protein amino acid sequences. BALB/c mice were immunised with the synthetic peptides by using the ADAD vaccination system and several immune response parameters were measured (antibody titres, cytokine levels, T-cell populations) to evaluate their ability to elicit an immune response. Based on the immunogenicity results so obtained, seven peptides were selected to assess their protection-inducing ability against experimental infection with F. hepatica metacercariae. Twenty-four B- or T-epitope-containing peptides were predicted and chemically synthesised. Immunisation of mice with peptides so-called B1, B2, B5, B6, T14, T15 and T16 induced high levels of total IgG, IgG1 and IgG2a (p<0.05) and a mixed Th1/Th2/Th17/Treg immune response, according to IFN-γ, IL-4, IL-17 and IL-10 levels, accompanied by increased CD62L+ T-cell populations. A high level of protection was obtained in mice vaccinated with peptides B2, B5, B6 and T15 formulated in the ADAD vaccination system with the AA0029 immunomodulator. The bioinformatics approach used in the present study led to the identification of seven peptides as vaccine candidates against the infection caused by Fasciola hepatica (a liver-fluke trematode). However, vaccine efficacy must be evaluated in other host species, including those having veterinary importance. PMID:25122166

  1. Characterization of the l-alanine exporter AlaE of Escherichia coli and its potential role in protecting cells from a toxic-level accumulation of l-alanine and its derivatives

    PubMed Central

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Hori, Hatsuhiro; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2015-01-01

    We previously reported that the alaE gene of Escherichia coli encodes the l-alanine exporter AlaE. The objective of this study was to elucidate the mechanism of the AlaE exporter. The minimum inhibitory concentration of l-alanine and l-alanyl-l-alanine in alaE-deficient l-alanine-nonmetabolizing cells MLA301ΔalaE was 4- and >4000-fold lower, respectively, than in the alaE-positive parent cells MLA301, suggesting that AlaE functions as an efflux pump to avoid a toxic-level accumulation of intracellular l-alanine and its derivatives. Furthermore, the growth of the alaE-deficient mutant derived from the l-alanine-metabolizing strain was strongly inhibited in the presence of a physiological level of l-alanyl-l-alanine. Intact MLA301ΔalaE and MLA301ΔalaE/pAlaE cells producing plasmid-borne AlaE, accumulated approximately 200% and 50%, respectively, of the [3H]l-alanine detected in MLA301 cells, suggesting that AlaE exports l-alanine. When 200 mmol/L l-alanine-loaded inverted membrane vesicles prepared from MLA301ΔalaE/pAlaE were placed in a solution containing 200 mmol/L or 0.34 μmol/L l-alanine, energy-dependent [3H]l-alanine accumulation occurred under either condition. This energy-dependent uphill accumulation of [3H]l-alanine was strongly inhibited in the presence of carbonyl cyanide m-chlorophenylhydrazone but not by dicyclohexylcarbodiimide, suggesting that the AlaE-mediated l-alanine extrusion was driven by proton motive force. Based on these results, physiological roles of the l-alanine exporter are discussed. PMID:26073055

  2. Characterization of the l-alanine exporter AlaE of Escherichia coli and its potential role in protecting cells from a toxic-level accumulation of l-alanine and its derivatives.

    PubMed

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Hori, Hatsuhiro; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2015-08-01

    We previously reported that the alaE gene of Escherichia coli encodes the l-alanine exporter AlaE. The objective of this study was to elucidate the mechanism of the AlaE exporter. The minimum inhibitory concentration of l-alanine and l-alanyl-l-alanine in alaE-deficient l-alanine-nonmetabolizing cells MLA301ΔalaE was 4- and >4000-fold lower, respectively, than in the alaE-positive parent cells MLA301, suggesting that AlaE functions as an efflux pump to avoid a toxic-level accumulation of intracellular l-alanine and its derivatives. Furthermore, the growth of the alaE-deficient mutant derived from the l-alanine-metabolizing strain was strongly inhibited in the presence of a physiological level of l-alanyl-l-alanine. Intact MLA301ΔalaE and MLA301ΔalaE/pAlaE cells producing plasmid-borne AlaE, accumulated approximately 200% and 50%, respectively, of the [(3) H]l-alanine detected in MLA301 cells, suggesting that AlaE exports l-alanine. When 200 mmol/L l-alanine-loaded inverted membrane vesicles prepared from MLA301ΔalaE/pAlaE were placed in a solution containing 200 mmol/L or 0.34 μmol/L l-alanine, energy-dependent [(3) H]l-alanine accumulation occurred under either condition. This energy-dependent uphill accumulation of [(3) H]l-alanine was strongly inhibited in the presence of carbonyl cyanide m-chlorophenylhydrazone but not by dicyclohexylcarbodiimide, suggesting that the AlaE-mediated l-alanine extrusion was driven by proton motive force. Based on these results, physiological roles of the l-alanine exporter are discussed. PMID:26073055

  3. Protective effect of pyrroloquinoline quinine on ultraviolet A irradiation-induced human dermal fibroblast senescence in vitro proceeds via the anti-apoptotic sirtuin 1/nuclear factor-derived erythroid 2-related factor 2/heme oxygenase 1 pathway.

    PubMed

    Zhang, Chunli; Wen, Chuanjun; Lin, Jinde; Shen, Gan

    2015-09-01

    The aim of the present study was to determine whether pyrroloquinoline quinine (PQQ) exerts a protective effect on ultraviolet A (UVA) irradiation‑induced senescence in human dermal fibroblasts (HDFs) and to elucidate its mechanism of action in vitro. A senescence model was constructed as follows: HDFs (1x10(4)‑1x10(6)) were cultured in a six‑well plate in vitro and then exposed to UVA irradiation at a dosage of 9 J/cm2. Various concentrations of PQQ (50, 100 and 200 ng/ml) were added to the culture medium 24 h prior to UVA exposure. Following 72 h of irradiation, senescence‑associated β‑galactosidase staining was performed in order to evaluate the senescence state. Furthermore, mRNA expression of the senescence marker genes matrix‑metalloprotease (MMP)1 and MMP3 was determined using reverse transcription quantitative polymerase chain reaction. Protein expression of sirtuin (SIRT)1, SIRT6, nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase 1 (HO‑1) were detected using western blot analysis. The results showed that the percentage of cells stained by X‑gal following 9 J/cm2 UVA irradiation was markedly increased compared with that of the control group (53 and 8%, respectively), while 50 ng/ml PQQ attenuated the ratio of positive staining compared with that of the UVA‑only cells (29 vs. 53%, respectively). Expression of fibroblast senescence marker genes MMP1 and MMP3 was decreased in cells treated with UVA and 50 ng/ml PQQ compared with that of cells in the UVA‑only group. Western blot analysis revealed significant effects of PQQ on SIRT1 and SIRT6. Nrf2 and HO‑1 exbibited mild changes with the same trend when treated with or without UVA and PQQ. In conclusion, the results of the present study showed that pyrroloquinoline quinine may have a protective effect on UVA irradiation‑induced HDF aging, which may be associated with the anti‑apoptotic SIRT1/Nrf2/HO‑1 pathway as well as SIRT6 signaling. PMID:26126510

  4. Protective Coatings

    NASA Technical Reports Server (NTRS)

    1980-01-01

    General Magnaplate Corporation's pharmaceutical machine is used in the industry for high speed pressing of pills and capsules. Machine is automatic system for molding glycerine suppositories. These machines are typical of many types of drug production and packaging equipment whose metal parts are treated with space spinoff coatings that promote general machine efficiency and contribute to compliance with stringent federal sanitation codes for pharmaceutical manufacture. Collectively known as "synergistic" coatings, these dry lubricants are bonded to a variety of metals to form an extremely hard slippery surface with long lasting self lubrication. The coatings offer multiple advantages; they cannot chip, peel or be rubbed off. They protect machine parts from corrosion and wear longer, lowering maintenance cost and reduce undesired heat caused by power-robbing friction.

  5. The new β amyloid-derived peptide Aβ1-6A2V-TAT(D) prevents Aβ oligomer formation and protects transgenic C. elegans from Aβ toxicity.

    PubMed

    Diomede, Luisa; Romeo, Margherita; Cagnotto, Alfredo; Rossi, Alessandro; Beeg, Marten; Stravalaci, Matteo; Tagliavini, Fabrizio; Di Fede, Giuseppe; Gobbi, Marco; Salmona, Mario

    2016-04-01

    One attractive pharmacological strategy for Alzheimer's disease (AD) is to design small peptides to interact with amyloid-β (Aβ) protein reducing its aggregation and toxicity. Starting from clinical observations indicating that patients coding a mutated Aβ variant (AβA2V) in the heterozygous state do not develop AD, we developed AβA2V synthetic peptides, as well as a small peptide homologous to residues 1-6. These hindered the amyloidogenesis of Aβ and its neurotoxicity in vitro, suggesting a basis for the design of a new small peptide in D-isomeric form, linked to the arginine-rich TAT sequence [Aβ1-6A2V-TAT(D)], to allow translocation across biological membranes and the blood-brain barrier. Aβ1-6A2V-TAT(D) was resistant to protease degradation, stable in serum and specifically able to interfere with Aβ aggregation in vitro, reducing the appearance of toxic soluble species and protecting transgenic C. elegans from toxicity related to the muscular expression of human Aβ. These observations offer a proof of concept for future pharmacological studies in mouse models of AD, providing a foundation for the design of AβA2V-based peptidomimetic molecules for therapeutic purposes. PMID:26792398

  6. Some Active Derivatives of Penicillin

    PubMed Central

    Brown, Loman D.; Zygmunt, Walter A.; Stavely, Homer E.

    1969-01-01

    The antibacterial activities of a number of amide derivatives of penicillin against both penicillin-sensitive and penicillin-resistant cultures were determined. Several of them were found to possess significant inhibitory activity against certain gram-positive bacteria. The amides, although resistant to the destructive action of β-lactamase, did not protect G in competitive experiments. One derivative, the O-benzylhydroxamide of penicillin G, was active against six or eight penicillin-resistant strains of Staphylococcus aureus (minimal inhibitory concentration, 0.2 μg/ml or less), but was found to have only a minimal in vivo activity against mouse Streptococcus infections. PMID:5780394

  7. Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25-35 peptide-injected mice, a nontransgenic Alzheimer's disease model.

    PubMed

    Lahmy, Valentine; Long, Romain; Morin, Didier; Villard, Vanessa; Maurice, Tangui

    2014-01-01

    Alzheimer's disease (AD), the most prevalent dementia in the elderly, is characterized by progressive synaptic and neuronal loss. Mitochondrial dysfunctions have been consistently reported as an early event in AD and appear before Aβ deposition and memory decline. In order to define a new neuroprotectant strategy in AD targeting mitochondrial alterations, we develop tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine (ANAVEX2-73, AE37), a mixed muscarinic receptor ligand and a sigma-1 receptor (σ1R) agonist. We previously reported that ANAVEX2-73 shows anti-amnesic and neuroprotective activities in mice injected intracerebroventricular (ICV) with oligomeric amyloid-β25-35 peptide (Aβ25-35). The σ1R is present at mitochondria-associated endoplasmic reticulum (ER) membranes, where it acts as a sensor/modulator of ER stress responses and local Ca(2+) exchanges with the mitochondria. We therefore evaluated the effect of ANAVEX2-73 and PRE-084, a reference σ1R agonist, on preservation of mitochondrial integrity in Aβ25-35-injected mice. In isolated mitochondria from hippocampus preparations of Aβ25-35 injected animals, we measured respiration rates, complex activities, lipid peroxidation, Bax/Bcl-2 ratios and cytochrome c release into the cytosol. Five days after Aβ25-35 injection, mitochondrial respiration in mouse hippocampus was altered. ANAVEX2-73 (0.01-1 mg/kg IP) restored normal respiration and PRE-084 (0.5-1 mg/kg IP) increased respiration rates. Both compounds prevented Aβ25-35-induced increases in lipid peroxidation levels, Bax/Bcl-2 ratio and cytochrome c release into the cytosol, all indicators of increased toxicity. ANAVEX2-73 and PRE-084 efficiently prevented the mitochondrial respiratory dysfunction and resulting oxidative stress and apoptosis. The σ1R, targeted selectively or non-selectively, therefore appears as a valuable target for protection against mitochondrial damages in AD. PMID:25653589

  8. High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells.

    PubMed

    Wang, Xu; Yang, Chunhui; Ihsan, Awais; Luo, Xun; Guo, Pu; Cheng, Guyue; Dai, Menghong; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

    2016-02-01

    Quinoxaline 1,4-dioxide derivatives (QdNOs) with a wide range of biological activities are used in animal husbandry worldwide. It was found that QdNOs significantly inhibited the gene expression of CYP11B1 and CYP11B2, the key aldosterone synthases, and thus reduced aldosterone levels. However, whether the metabolites of QdNOs have potential adrenal toxicity and the role of oxidative stress in the adrenal toxicity of QdNOs remains unclear. The relatively new QdNOs, cyadox (CYA), mequindox (MEQ), quinocetone (QCT) and their metabolites, were selected for elucidation of their toxic mechanisms in H295R cells. Interestingly, the results showed that the main toxic metabolites of QCT, MEQ, and CYA were their N1-desoxy metabolites, which were more harmful than other metabolites and evoked dose and time-dependent cell damage on adrenal cells and inhibited aldosterone production. Gene and protein expression of CYP11B1 and CYP11B2 and mRNA expression of transcription factors, such as NURR1, NGFIB, CREB, SF-1, and ATF-1, were down regulated by N1-desoxy QdNOs. The natural inhibitors of oxidant stress, oligomeric proanthocyanidins (OPC), could upregulate the expression of diverse transcription factors, including CYP11B1 and CYP11B2, and elevated aldosterone levels to reduce adrenal toxicity. This study demonstrated for the first time that N1-desoxy QdNOs have the potential to be the major toxic metabolites in adrenal toxicity, which may shed new light on the adrenal toxicity of these fascinating compounds and help to provide a basic foundation for the formulation of safety controls for animal products and the design of new QdNOs with less harmful effects. PMID:26802905

  9. Intravenous Transplants of Human Adipose-Derived Stem Cell Protect the Brain from Traumatic Brain Injury-Induced Neurodegeneration and Motor and Cognitive Impairments: Cell Graft Biodistribution and Soluble Factors in Young and Aged Rats

    PubMed Central

    Tajiri, Naoki; Acosta, Sandra A.; Shahaduzzaman, Md; Ishikawa, Hiroto; Shinozuka, Kazutaka; Pabon, Mibel; Hernandez-Ontiveros, Diana; Kim, Dae Won; Metcalf, Christopher; Staples, Meaghan; Dailey, Travis; Vasconcellos, Julie; Franyuti, Giorgio; Gould, Lisa; Patel, Niketa

    2014-01-01

    Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 months) and aged (20 months) F344 rats. Animals were transplanted intravenously with 4 × 106 hADSCs (Tx), conditioned media (CM), or vehicle (unconditioned media) at 3 h after TBI. Significant amelioration of motor and cognitive functions was revealed in young, but not aged, Tx and CM groups. Fluorescent imaging in vivo and ex vivo revealed 1,1′ dioactadecyl-3-3-3′,3′-tetramethylindotricarbocyanine iodide-labeled hADSCs in peripheral organs and brain after TBI. Spatiotemporal deposition of hADSCs differed between young and aged rats, most notably reduced migration to the aged spleen. Significant reduction in cortical damage and hippocampal cell loss was observed in both Tx and CM groups in young rats, whereas less neuroprotection was detected in the aged rats and mainly in the Tx group but not the CM group. CM harvested from hADSCs with silencing of either NEAT1 (nuclear enriched abundant transcript 1) or MALAT1 (metastasis associated lung adenocarcinoma transcript 1), long noncoding RNAs (lncRNAs) known to play a role in gene expression, lost the efficacy in our model. Altogether, hADSCs are promising therapeutic cells for TBI, and lncRNAs in the secretome is an important mechanism of cell therapy. Furthermore, hADSCs showed reduced efficacy in aged rats, which may in part result from decreased homing of the cells to the spleen. PMID:24381292

  10. Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25–35 peptide-injected mice, a nontransgenic Alzheimer’s disease model

    PubMed Central

    Lahmy, Valentine; Long, Romain; Morin, Didier; Villard, Vanessa; Maurice, Tangui

    2015-01-01

    Alzheimer’s disease (AD), the most prevalent dementia in the elderly, is characterized by progressive synaptic and neuronal loss. Mitochondrial dysfunctions have been consistently reported as an early event in AD and appear before Aβ deposition and memory decline. In order to define a new neuroprotectant strategy in AD targeting mitochondrial alterations, we develop tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine (ANAVEX2-73, AE37), a mixed muscarinic receptor ligand and a sigma-1 receptor (σ1R) agonist. We previously reported that ANAVEX2-73 shows anti-amnesic and neuroprotective activities in mice injected intracerebroventricular (ICV) with oligomeric amyloid-β25–35 peptide (Aβ25–35). The σ1R is present at mitochondria-associated endoplasmic reticulum (ER) membranes, where it acts as a sensor/modulator of ER stress responses and local Ca2+ exchanges with the mitochondria. We therefore evaluated the effect of ANAVEX2-73 and PRE-084, a reference σ1R agonist, on preservation of mitochondrial integrity in Aβ25–35-injected mice. In isolated mitochondria from hippocampus preparations of Aβ25–35 injected animals, we measured respiration rates, complex activities, lipid peroxidation, Bax/Bcl-2 ratios and cytochrome c release into the cytosol. Five days after Aβ25–35 injection, mitochondrial respiration in mouse hippocampus was altered. ANAVEX2-73 (0.01–1 mg/kg IP) restored normal respiration and PRE-084 (0.5–1 mg/kg IP) increased respiration rates. Both compounds prevented Aβ25–35-induced increases in lipid peroxidation levels, Bax/Bcl-2 ratio and cytochrome c release into the cytosol, all indicators of increased toxicity. ANAVEX2-73 and PRE-084 efficiently prevented the mitochondrial respiratory dysfunction and resulting oxidative stress and apoptosis. The σ1R, targeted selectively or non-selectively, therefore appears as a valuable target for protection against mitochondrial damages in AD. PMID:25653589

  11. Research in biomechanics of occupant protection.

    PubMed

    King, A I; Yang, K H

    1995-04-01

    This paper discusses the biomechanical bases for occupant protection against frontal and side impact. Newton's Laws of Motion are used to illustrate the effect of a crash on restrained and unrestrained occupants, and the concept of ride down is discussed. Occupant protection through the use of energy absorbing materials is described, and the mechanism of injury of some of the more common injuries is explained. The role of the three-point belt and the airbag in frontal protection is discussed along with the potential injuries that can result from the use of these restraint systems. Side impact protection is more difficult to attain but some protection can be derived from the use of padding or a side impact airbag. It is concluded that the front seat occupants are adequately protected against frontal impact if belts are worn in an airbag equipped vehicle. Side impact protection may not be uniform in all vehicles. PMID:7723097

  12. A new amphiphilic derivative, N-{[4-(lactobionamido)methyl]benzylidene}-1,1-dimethyl-2-(octylsulfanyl)ethylamine N-oxide, has a protective effect against copper-induced fulminant hepatitis in Long-Evans Cinnamon rats at an extremely low concentration compared with its original form alpha-phenyl-N-(tert-butyl) nitrone.

    PubMed

    Asanuma, Taketoshi; Yasui, Hironobu; Inanami, Osamu; Waki, Kenji; Takahashi, Momoko; Iizuka, Daisuke; Uemura, Taketo; Durand, Grégory; Polidori, Ange; Kon, Yasuhiro; Pucci, Bernard; Kuwabara, Mikinori

    2007-09-01

    An amphiphilic alpha-phenyl-N-(tert-butyl) nitrone (PBN) derivative, N-{[4-(lactobionamido)methyl]benzylidene}-1,1-dimethyl-2-(octylsulfanyl)ethylamine N-oxide (LPBNSH), newly synthesized from its original form PBN in hopes of clinical use, was intraperitoneally administered to Long-Evans Cinnamon (LEC) rats every 2 days at the concentrations of 0.1, 0.5, 1.0, and 2.0 mg/kg. We found that LPBNSH protected against copper-induced hepatitis with jaundice in LEC rats at concentrations of 0.1 and 0.5 mg/kg, which were extremely low compared with that of PBN. It also effectively prevented the loss of body weight, reduced the death rate, and suppressed the increase in serum aspartate aminotransferase and alanine aminotransferase values arising from fulminant hepatitis with jaundice at the same concentrations. Similar results were observed when PBN was administered at the concentration of 150 mg/kg. Immunohistochemical analysis of 8-hydroxy-2'-deoxyguanosine and measurement of thiobarbituric acid-reactive substances in the liver showed that LPBNSH largely suppressed the formation of these oxidative products at same concentrations. No difference in the abnormal accumulation of copper in the liver between the LPBNSH administered and control groups was observed. From these results, it was concluded that LPBNSH exhibited liver-protective effects against fulminant hepatitis with jaundice at ca. 1/1000, 500 the molar concentration of PBN and, therefore, was clinically promising. PMID:17886845

  13. On the protection of "protected areas".

    PubMed

    Joppa, Lucas N; Loarie, Scott R; Pimm, Stuart L

    2008-05-01

    Tropical moist forests contain the majority of terrestrial species. Human actions destroy between 1 and 2 million km(2) of such forests per decade, with concomitant carbon release into the atmosphere. Within these forests, protected areas are the principle defense against forest loss and species extinctions. Four regions-the Amazon, Congo, South American Atlantic Coast, and West Africa-once constituted about half the world's tropical moist forest. We measure forest cover at progressively larger distances inside and outside of protected areas within these four regions, using datasets on protected areas and land-cover. We find important geographical differences. In the Amazon and Congo, protected areas are generally large and retain high levels of forest cover, as do their surroundings. These areas are protected de facto by being inaccessible and will likely remain protected if they continue to be so. Deciding whether they are also protected de jure-that is, whether effective laws also protect them-is statistically difficult, for there are few controls. In contrast, protected areas in the Atlantic Coast forest and West Africa show sharp boundaries in forest cover at their edges. This effective protection of forest cover is partially offset by their very small size: little area is deep inside protected area boundaries. Lands outside protected areas in the Atlantic Coast forest are unusually fragmented. Finally, we ask whether global databases on protected areas are biased toward highly protected areas and ignore "paper parks." Analysis of a Brazilian database does not support this presumption. PMID:18451028

  14. Cats protecting birds revisited.

    PubMed

    Fan, Meng; Kuang, Yang; Feng, Zhilan

    2005-09-01

    In this paper, we revisit the dynamical interaction among prey (bird), mesopredator (rat), and superpredator (cat) discussed in [Courchamp, F., Langlais, M., Sugihara, G., 1999. Cats protecting birds: modelling the mesopredator release effect. Journal of Animal Ecology 68, 282-292]. First, we develop a prey-mesopredator-superpredator (i.e., bird-rat-cat, briefly, BRC) model, where the predator's functional responses are derived based on the classical Holling's time budget arguments. Our BRC model overcomes several model construction problems in Courchamp et al. (1999), and admits richer, reasonable and realistic dynamics. We explore the possible control strategies to save or restore the bird by controlling or eliminating the rat or the cat when the bird is endangered. We establish the existence of two types of mesopredator release phenomena: severe mesopredator release, where once superpredators are suppressed, a burst of mesopredators follows which leads their shared prey to extinction; and mild mesopredator release, where the mesopredator release could assert more negative impact on the endemic prey but does not lead the endemic prey to extinction. A sharp sufficient criterion is established for the occurrence of severe mesopredator release. We also show that, in a prey-mesopredator-superpredator trophic food web, eradication of introduced superpredators such as feral domestic cats in the BRC model, is not always the best solution to protect endemic insular prey. The presence of a superpredator may have a beneficial effect in such systems. PMID:15998496

  15. Occupant Protection Project

    NASA Technical Reports Server (NTRS)

    Bopp, Genie; Somers, Jeff; Granderson, Brad; Gernhardt, Mike; Currie, Nancy; Lawrence, Chuck

    2010-01-01

    Topics include occupant protection overview with a focus on crew protection during dynamic phases of flight; occupant protection collaboration; modeling occupant protection; occupant protection considerations; project approach encompassing analysis tools, injury criteria, and testing program development; injury criteria update methodology, unique effects of pressure suits and other factors; and a summary.

  16. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  17. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  18. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  19. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  20. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  1. 40 CFR 721.10330 - Pyrazolone derivative (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Pyrazolone derivative (generic). 721... Substances § 721.10330 Pyrazolone derivative (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as pyrazolone derivative (PMN...

  2. 40 CFR 721.10330 - Pyrazolone derivative (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Pyrazolone derivative (generic). 721... Substances § 721.10330 Pyrazolone derivative (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as pyrazolone derivative (PMN...

  3. 40 CFR 721.10330 - Pyrazolone derivative (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Pyrazolone derivative (generic). 721... Substances § 721.10330 Pyrazolone derivative (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as pyrazolone derivative (PMN...

  4. 40 CFR 721.10317 - Alkyl phosphate derivative (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl phosphate derivative (generic... Specific Chemical Substances § 721.10317 Alkyl phosphate derivative (generic). (a) Chemical substance and... phosphate derivative (PMN P-02-1040) is subject to reporting under this section for the significant new...

  5. 40 CFR 721.10317 - Alkyl phosphate derivative (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl phosphate derivative (generic... Specific Chemical Substances § 721.10317 Alkyl phosphate derivative (generic). (a) Chemical substance and... phosphate derivative (PMN P-02-1040) is subject to reporting under this section for the significant new...

  6. 40 CFR 721.10317 - Alkyl phosphate derivative (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl phosphate derivative (generic... Specific Chemical Substances § 721.10317 Alkyl phosphate derivative (generic). (a) Chemical substance and... phosphate derivative (PMN P-02-1040) is subject to reporting under this section for the significant new...

  7. COMMUNITY BASED ENVIRONMENTAL PROTECTION

    EPA Science Inventory

    Community Based Environmental Protection intends to make environmental protection spring from the needs and values of the community of interest. Real community involvement in protecting the environment requires a process in which the environmental needs of communities and ecosyst...

  8. Neutrophil-derived cathelicidin protects from neointimal hyperplasia

    PubMed Central

    Soehnlein, Oliver; Wantha, Sarawuth; Simsekyilmaz, Sakine; Döring, Yvonne; Megens, Remco T. A.; Mause, Sebastian F.; Drechsler, Maik; Smeets, Ralf; Weinandy, Stefan; Schreiber, Fabian; Gries, Thomas; Jockenhoevel, Stefan; Möller, Martin; Vijayan, Santosh; van Zandvoort, Marc A. M. J.; Agerberth, Birgitta; Pham, Christine T.; Gallo, Richard L.; Hackeng, Tilman M.; Liehn, Elisa A.; Zernecke, Alma; Klee, Doris; Weber, Christian

    2011-01-01

    Percutaneous transluminal angioplasty with stent implantation is used to dilate of arteries narrowed by atherosclerotic plaques and to revascularize coronary arteries occluded by atherothrombosis in myocardial infarction. Commonly applied drug-eluting stents release anti-proliferative or anti-inflammatory agents to reduce the incidence of in-stent stenosis. However, these stents may lead to in-stent stenosis and increase the rate late stent thrombosis, an obstacle to optimal revascularization possibly related to endothelial recovery. Here we examined the contribution of neutrophils and neutrophilic granule proteins to arterial healing after injury. We found that neutrophil-born cathelicidin (mouse CRAMP, human LL-37) promoted re-endothelization and thereby limited neointima formation after stent implantation. We then translated these findings, generating a neutrophil-instructing biofunctionalized miniaturized Nitinol stent coated with LL-37. This stent reduced in-stent stenosis in a mouse model of atherosclerosis, suggesting that LL-37 may promote vascular healing after interventional therapy. PMID:21974936

  9. 40 CFR 721.3560 - Derivative of tetra-chloro-ethy-lene.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Derivative of tetra-chloro-ethy-lene. 721.3560 Section 721.3560 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3560 Derivative...

  10. 40 CFR 721.3560 - Derivative of tetra-chloro-ethy-lene.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Derivative of tetra-chloro-ethy-lene. 721.3560 Section 721.3560 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3560 Derivative...

  11. Capacity of surface warship's protective bulkhead subjected to blast loading

    NASA Astrophysics Data System (ADS)

    Peng, Xing-Ning; Nie, Wu; Yan, Bo

    2009-03-01

    The protective bulkhead of the large surface warship need to be designed working in the membrane mode. In this paper, a formula is derived for calculating the plastic deformation of the protective bulkhead subjected to blast loading by the energy method, and the ultimate capability of the protective bulkhead can be calculated. The design demand of the protective bulkhead is discussed. The calculation is compared with external experiments, which indicates that the formula is of great application value.

  12. 76 FR 4751 - Position Limits for Derivatives

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-26

    ...Title VII of the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010 (``Dodd-Frank Act'') requires the Commodity Futures Trading Commission (``Commission'' or ``CFTC'') to establish position limits for certain physical commodity derivatives. The Commission is proposing to simultaneously establish position limits and limit formulas for certain physical commodity futures and option......

  13. Sol-Gel Derived Hafnia Coatings

    NASA Technical Reports Server (NTRS)

    Feldman, Jay D.; Stackpoole, Mairead; Blum, Yigal; Sacks, Michael; Ellerby, Don; Johnson, Sylvia M.; Venkatapathy, Ethiras (Technical Monitor)

    2002-01-01

    Sol-gel derived hafnia coatings are being developed to provide an oxidation protection layer on ultra-high temperature ceramics for potential use in turbine engines (ultra-efficient engine technology being developed by NASA). Coatings using hafnia sol hafnia filler particles will be discussed along with sol synthesis and characterization.

  14. Synthetic Bioluminescent Coelenterazine Derivatives.

    PubMed

    Nishihara, Ryo; Citterio, Daniel; Suzuki, Koji

    2016-01-01

    The development of coelenterazine (CTZ) derivatives resulting in superior optical characteristics is an efficient method to extend the range of its possible applications. Here, we describe the synthesis of three C-6 substituted CTZ derivatives retaining the recognition by Renilla luciferase (RLuc) and its derivatives. The novel derivatives are useful as bright blue-shifted CTZ derivatives, which can be used as an alternative to hitherto reported compound DeepBlueC™. PMID:27424892

  15. Integrating weather derivatives for managing risks

    SciTech Connect

    Bilski, B.

    1999-11-01

    As deregulation and customer choice loom on the horizon, many energy utilities and other energy suppliers are scrambling to find new services that add value for consumers. Many are also seeking opportunities for increasing efficiency to ensure that costs remain competitive. Integrating weather derivatives with marketing programs and financial management can produce attractive new services and increase efficiency. Weather derivatives can be used to create innovative consumer services, such as a guaranteed annual energy bill which is unaffected by weather and energy price changes. They can also be used to protect the earnings of energy suppliers from one of their most significant financial risks, unpredictable weather. There are three basic types of weather derivatives available today. Option or insurance based derivatives (options), swaps or hedge based derivatives (swaps) and packages where other services are combined with one or both of the above.

  16. Transgenic plants protected from insect attack

    NASA Astrophysics Data System (ADS)

    Vaeck, Mark; Reynaerts, Arlette; Höfte, Herman; Jansens, Stefan; de Beuckeleer, Marc; Dean, Caroline; Zabeau, Marc; Montagu, Marc Van; Leemans, Jan

    1987-07-01

    The Gram-positive bacterium Bacillus thuringiensis produces proteins which are specifically toxic to a variety of insect species. Modified genes have been derived from bt2, a toxin gene cloned from one Bacillus strain. Transgenic tobacco plants expressing these genes synthesize insecticidal proteins which protect them from feeding damage by larvae of the tobacco hornworm.

  17. Personal protective equipment

    MedlinePlus

    ... protective equipment. Available at: www.cdc.gov/niosh/ppe . Accessed October 27, 2015. Holland MG, Cawthon D. Personal protective equipment and decontamination of adults and children. Emerg Med Clin N ...

  18. MSFC Respiratory Protection Services

    NASA Technical Reports Server (NTRS)

    CoVan, James P.

    1999-01-01

    An overview of the Marshall Space Flight Center Respiratory Protection program is provided in this poster display. Respiratory protection personnel, building, facilities, equipment, customers, maintenance and operational activities, and Dynatech fit testing details are described and illustrated.

  19. Medicare Rights and Protections

    MedlinePlus

    CENTERS for MEDICARE & MEDICAID SERVICES Medicare Rights & Protections This official government booklet has important information about: Your rights & protections in: ■ ■ Original Medicare ■ ■ Medicare Advantage Plan or other Medicare health ...

  20. Protecting Children's Online Privacy.

    ERIC Educational Resources Information Center

    Kresses, Mamie

    2001-01-01

    Discuss provisions of new federal Children's Online Privacy Protection Act that principals should know to protect student privacy on the Internet. Also discusses relevant provisions of the Family Educational Rights and Privacy Act. (PKP)

  1. Corium protection assembly

    DOEpatents

    Gou, Perng-Fei; Townsend, Harold E.; Barbanti, Giancarlo

    1994-01-01

    A corium protection assembly includes a perforated base grid disposed below a pressure vessel containing a nuclear reactor core and spaced vertically above a containment vessel floor to define a sump therebetween. A plurality of layers of protective blocks are disposed on the grid for protecting the containment vessel floor from the corium.

  2. Careers in Environmental Protection.

    ERIC Educational Resources Information Center

    Millard, Reed

    The book presents concerns of our society in protecting our environment and the challenges involved in meaningful careers in environmental protection and management. "Estimates by the Environmental Protection Agency indicate that, compared with their numbers in the mid-'70's, the need for environmental professionals will triple by 1980.'" In a…

  3. Fire Protection Program Manual

    SciTech Connect

    Sharry, J A

    2012-05-18

    This manual documents the Lawrence Livermore National Laboratory (LLNL) Fire Protection Program. Department of Energy (DOE) Orders 420.1B, Facility Safety, requires LLNL to have a comprehensive and effective fire protection program that protects LLNL personnel and property, the public and the environment. The manual provides LLNL and its facilities with general information and guidance for meeting DOE 420.1B requirements. The recommended readers for this manual are: fire protection officers, fire protection engineers, fire fighters, facility managers, directorage assurance managers, facility coordinators, and ES and H team members.

  4. Occupant Protection at NASA

    NASA Technical Reports Server (NTRS)

    Somers, Jeffrey; Granderson, Brad; Scheuring, Rick

    2010-01-01

    This slide presentation reviews NASA's efforts to arrive at protection of occupants of the ORION space craft on landing. An Abbreviated Injury Scale (AIS) has been developed, it is an anatomically-based, consensus-derived, global severity scoring system that classifies each injury by body region according to its relative importance on a 6-point ordinal scale. It reviews an Operationmally Relevant Injury Scale (ORIS), a classification methodology, and shows charts that detail the results of applying this ORIS to the injury databases. One chart uses NASCAR injury classification. It discusses providing a context for the level of risk inherent in the Orion landings in terms that people understand and have a sense for. For example is the risk of injury during an Orion landing roughly the same, better or worse than: An aircraft carrier landing, a NASCAR crash, or a helicopter crash, etc? The data for NASCAR and Indy Racing league (IRL) racing crash and injury data was reviewed. The risk from the Air Force, Navy, and Army injury data was also reviewed. Past NASA and the Soyuz programs injury risks are also reviewed. The work is an attempt to formulate a recommendation to the Orion Project for an acceptable level of injury risk associated with Nominal and Off-Nominal landing cases. The presentation also discusses the data mining and use of the data to Validate NASA Operationally-Relevant Injury Scale (NORIS) / Military Operationally-Relevant Injury Scale (MORIS), developing injury risk criteria, the types of data that are required, NASCAR modeling techniques and crash data, and comparison with the Brinkley model. The development of injury risk curves for each biodynamic response parameter is discussed. One of the main outcomes of this work is to establish an accurate Automated Test Dummy (ATD) that can be used to measure human tolerances.

  5. Direct Density Derivative Estimation.

    PubMed

    Sasaki, Hiroaki; Noh, Yung-Kyun; Niu, Gang; Sugiyama, Masashi

    2016-06-01

    Estimating the derivatives of probability density functions is an essential step in statistical data analysis. A naive approach to estimate the derivatives is to first perform density estimation and then compute its derivatives. However, this approach can be unreliable because a good density estimator does not necessarily mean a good density derivative estimator. To cope with this problem, in this letter, we propose a novel method that directly estimates density derivatives without going through density estimation. The proposed method provides computationally efficient estimation for the derivatives of any order on multidimensional data with a hyperparameter tuning method and achieves the optimal parametric convergence rate. We further discuss an extension of the proposed method by applying regularized multitask learning and a general framework for density derivative estimation based on Bregman divergences. Applications of the proposed method to nonparametric Kullback-Leibler divergence approximation and bandwidth matrix selection in kernel density estimation are also explored. PMID:27140943

  6. 40 CFR 721.2025 - Substituted phenylimino carbamate derivative.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted phenylimino carbamate... Specific Chemical Substances § 721.2025 Substituted phenylimino carbamate derivative. (a) Chemical... as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject to reporting under...

  7. 40 CFR 721.2025 - Substituted phenylimino carbamate derivative.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted phenylimino carbamate... Specific Chemical Substances § 721.2025 Substituted phenylimino carbamate derivative. (a) Chemical... as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject to reporting under...

  8. 40 CFR 721.2025 - Substituted phenylimino carbamate derivative.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted phenylimino carbamate... Specific Chemical Substances § 721.2025 Substituted phenylimino carbamate derivative. (a) Chemical... as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject to reporting under...

  9. 40 CFR 721.2025 - Substituted phenylimino carbamate derivative.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted phenylimino carbamate... Specific Chemical Substances § 721.2025 Substituted phenylimino carbamate derivative. (a) Chemical... as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject to reporting under...

  10. 40 CFR 721.2025 - Substituted phenylimino carbamate derivative.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted phenylimino carbamate... Specific Chemical Substances § 721.2025 Substituted phenylimino carbamate derivative. (a) Chemical... as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject to reporting under...

  11. 40 CFR 721.10328 - Salt of polyalkylenepolyamine derivative (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Salt of polyalkylenepolyamine... Specific Chemical Substances § 721.10328 Salt of polyalkylenepolyamine derivative (generic). (a) Chemical... as salt of polyalkylenepolyamine derivative (PMN P-03-530) is subject to reporting under this...

  12. 40 CFR 721.10328 - Salt of polyalkylenepolyamine derivative (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Salt of polyalkylenepolyamine... Specific Chemical Substances § 721.10328 Salt of polyalkylenepolyamine derivative (generic). (a) Chemical... as salt of polyalkylenepolyamine derivative (PMN P-03-530) is subject to reporting under this...

  13. 40 CFR 721.10328 - Salt of polyalkylenepolyamine derivative (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Salt of polyalkylenepolyamine... Specific Chemical Substances § 721.10328 Salt of polyalkylenepolyamine derivative (generic). (a) Chemical... as salt of polyalkylenepolyamine derivative (PMN P-03-530) is subject to reporting under this...

  14. State protection under collective damping and diffusion

    SciTech Connect

    Ponte, M. A. de; Mizrahi, S. S.; Moussa, M. H. Y.

    2011-07-15

    In this paper we provide a recipe for state protection in a network of oscillators under collective damping and diffusion. Our strategy is to manipulate the network topology, i.e., the way the oscillators are coupled together, the strength of their couplings, and their natural frequencies, in order to create a relaxation-diffusion-free channel. This protected channel defines a decoherence-free subspace (DFS) for nonzero-temperature reservoirs. Our development also furnishes an alternative approach to build up DFSs that offers two advantages over the conventional method: it enables the derivation of all the network-protected states at once, and also reveals, through the network normal modes, the mechanism behind the emergence of these protected domains.

  15. Office for Human Research Protections

    MedlinePlus

    ... Office for Human Research Protections The Office for Human Research Protections (OHRP) provides leadership in the protection of the rights, welfare, and wellbeing of human subjects involved in ...

  16. Resilience from coastal protection.

    PubMed

    Ewing, Lesley C

    2015-10-28

    Coastal areas are important residential, commercial and industrial areas; but coastal hazards can pose significant threats to these areas. Shoreline/coastal protection elements, both built structures such as breakwaters, seawalls and revetments, as well as natural features such as beaches, reefs and wetlands, are regular features of a coastal community and are important for community safety and development. These protection structures provide a range of resilience to coastal communities. During and after disasters, they help to minimize damages and support recovery; during non-disaster times, the values from shoreline elements shift from the narrow focus on protection. Most coastal communities have limited land and resources and few can dedicate scarce resources solely for protection. Values from shore protection can and should expand to include environmental, economic and social/cultural values. This paper discusses the key aspects of shoreline protection that influence effective community resilience and protection from disasters. This paper also presents ways that the economic, environmental and social/cultural values of shore protection can be evaluated and quantified. It presents the Coastal Community Hazard Protection Resilience (CCHPR) Index for evaluating the resilience capacity to coastal communities from various protection schemes and demonstrates the use of this Index for an urban beach in San Francisco, CA, USA. PMID:26392613

  17. 40 CFR 721.1300 - [(Dinitrophenyl)azo]-[2,4-dia-mino-5-methoxybenzene] derivatives.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false - derivatives. 721.1300 Section 721.1300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1300 - derivatives. (a) Chemical...

  18. 40 CFR 721.1300 - [(Dinitrophenyl)azo]-[2,4-dia-mino-5-methoxybenzene] derivatives.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false - derivatives. 721.1300 Section 721.1300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1300 - derivatives. (a) Chemical...

  19. 40 CFR 721.1300 - [(Dinitrophenyl)azo]-[2,4-dia-mino-5-methoxybenzene] derivatives.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false - derivatives. 721.1300 Section 721.1300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1300 - derivatives. (a) Chemical...

  20. 40 CFR 721.1300 - [(Dinitrophenyl)azo]-[2,4-dia-mino-5-methoxybenzene] derivatives.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false - derivatives. 721.1300 Section 721.1300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1300 - derivatives. (a) Chemical...

  1. 40 CFR 721.1300 - [(Dinitrophenyl)azo]-[2,4-dia-mino-5-methoxybenzene] derivatives.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false - derivatives. 721.1300 Section 721.1300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1300 - derivatives. (a) Chemical...

  2. Multiwall thermal protection system

    NASA Technical Reports Server (NTRS)

    Jackson, L. R. (Inventor)

    1982-01-01

    Multiwall insulating sandwich panels are provided for thermal protection of hypervelocity vehicles and other enclosures. In one embodiment, the multiwall panels are formed of alternate layers of dimpled and flat metal (titanium alloy) foil sheets and beaded scarfed edge seals to provide enclosure thermal protection up to 1000 F. An additional embodiment employs an intermediate fibrous insulation for the sandwich panel to provide thermal protection up to 2000 F. A third embodiment employs a silicide coated columbium waffle as the outer panel skin and fibrous layered intermediate protection for thermal environment protection up to 2500 F. The use of multiple panels on an enclosure facilitate repair and refurbishment of the thermal protection system due to the simple support provided by the tab and clip attachment for the panels.

  3. Emergency Protection from Aerosols

    SciTech Connect

    Cristy, G.A.

    2001-11-13

    Expedient methods were developed that could be used by an average person, using only materials readily available, to protect himself and his family from injury by toxic (e.g., radioactive) aerosols. The most effective means of protection was the use of a household vacuum cleaner to maintain a small positive pressure on a closed house during passage of the aerosol cloud. Protection factors of 800 and above were achieved.

  4. NASA Fire Protection

    NASA Technical Reports Server (NTRS)

    Clark, Theodore

    2001-01-01

    This viewgraph presentation provides information on fire protection operations and administration at Stennis Space Center (SSC). The presentation also lists innovative practices and recent improvements.

  5. Protection - Principles and practice.

    NASA Technical Reports Server (NTRS)

    Graham, G. S.; Denning, P. J.

    1972-01-01

    The protection mechanisms of computer systems control the access to objects, especially information objects. The principles of protection system design are formalized as a model (theory) of protection. Each process has a unique identification number which is attached by the system to each access attempted by the process. Details of system implementation are discussed, taking into account the storing of the access matrix, aspects of efficiency, and the selection of subjects and objects. Two systems which have protection features incorporating all the elements of the model are described.

  6. Endohedral Metallofullerene Derivatives

    NASA Technical Reports Server (NTRS)

    Dorn, Harry C. (Inventor); Iezzi, Erick B. (Inventor); Duchamp, James (Inventor)

    2008-01-01

    Trimetallic nitride endohedral metallofullerene derivatives and their preparation are described. The trimetallic nitride endohedral metallofullerene derivatives have the general formula A(sub 3-n)X(sub n)@C(sub m)(R) where n ranges from 0 to 3, A and X may be trivalent metals and may be either rare earth metal or group IIIB metals, m is between about 60 and about 200, and R is preferably an organic group. Derivatives where the R group forms cyclized derivatives with the fullerene cage are also described.

  7. Protective area of laser eye protectors

    NASA Astrophysics Data System (ADS)

    Sutter, E.; Schirmacher, A.

    2001-06-01

    An objective definition of the protective area of laser eye protectors is discussed. First an appropriate test method is described, which is based on the current eye protection standard EN 168. For a variety of already CE type approved laser eye protectors, i.e. for different goggle and spectacle types, results of corresponding measurements are shown. From these results the requirements on the vertical and horizontal angle ranges are derived, which have to be covered by laser eye protectors. This proposal will be implemented in the currently processed amendments of the laser safety standards EN 207 and EN 208.

  8. Irregularities in Imperfective Derivation

    ERIC Educational Resources Information Center

    Levin, Maurice I.

    1977-01-01

    This article discusses presentation of Russian conjugation via the one-stem system advocated by Lipson and Townsend, and attempts a more unified and complete presentation of irregularities in imperfect derivation. Two major irregularities are occurrence of an unexpected suffix and unpredictable alternation in the root of the derived imperfective.…

  9. The Dangers of Derivatives.

    ERIC Educational Resources Information Center

    Blumenstyk, Goldie

    1994-01-01

    Heavy investment in derivatives, whose value derives from the price movement of some underlying security, has meant heavy losses for some colleges and universities despite the fact that institutional investors are required to assure that they understand the risks of such investment. (MSE)

  10. DERIVE in Slovenian Schools.

    ERIC Educational Resources Information Center

    Lokar, Matija

    This paper describes several projects concerning the use of the DERIVE programming language for symbolic computation in Slovenia. The main topics discussed include preparing books and materials using DERIVE in Slovenian language, and a survey on the use of programs for symbolic computation by mathematics teachers in Slovenian secondary schools.…

  11. Protecting the Crown Jewels.

    ERIC Educational Resources Information Center

    Andrus, Cecil

    1979-01-01

    The National Park Service seeks to set the standard for environmental protection in the federally-owned lands which it administers. Often pollution from sources outside park boundaries creates adverse impacts within the parks. Innovative approaches and cooperative efforts are then required to protect the parks. (RE)

  12. A Duty to Protect

    ERIC Educational Resources Information Center

    Lee, James

    2009-01-01

    Asylum is a value. At its most basic, it is about the importance of protecting someone's life from persecution. The 1951 Refugee Convention seeks to achieve this--by ensuring that those people with a well-founded fear of persecution should be able to find protection within a state that has signed up to the Convention. The UK's commitments under…

  13. Environmental protection Implementation Plan

    SciTech Connect

    R. C. Holland

    1999-12-01

    This ``Environmental Protection Implementation Plan'' is intended to ensure that the environmental program objectives of Department of Energy Order 5400.1 are achieved at SNL/California. This document states SNL/California's commitment to conduct its operations in an environmentally safe and responsible manner. The ``Environmental Protection Implementation Plan'' helps management and staff comply with applicable environmental responsibilities.

  14. Protective Garment Ensemble

    NASA Technical Reports Server (NTRS)

    Wakefield, M. E.

    1982-01-01

    Protective garment ensemble with internally-mounted environmental- control unit contains its own air supply. Alternatively, a remote-environmental control unit or an air line is attached at the umbilical quick disconnect. Unit uses liquid air that is vaporized to provide both breathing air and cooling. Totally enclosed garment protects against toxic substances.

  15. Electroplating offers embrittlement protection

    NASA Technical Reports Server (NTRS)

    Daniels, C. M., Jr.

    1970-01-01

    Thin copper electrodeposited layer protects metal parts in environments with which they may be incompatible. Originally developed for main engine of Space Shuttle where high strength nickle alloy bellows must operate in high-pressure hydrogen, technique protects nickel and is unaffected by forming process or subsequent heat treatment and preinstallation processing.

  16. Protection of multimaterial assemblies

    NASA Astrophysics Data System (ADS)

    Mikhail, L. Zheludkevich; Silvar, Kallip; Maria, Serdechnova

    2016-01-01

    The light-weight design calls for broader utilization of multimaterial mixes (M3) in different engineering structures, especially in the transportation area. Together with joining technologies for hybrid structures, the optimization of the life cycle of such systems is an issue of prime importance. Multimaterial structures are often prone to faster degradation under service conditions because of galvanically forced electrochemical corrosion. The protection technologies traditionally used for single-material structures are not always applicable for multimaterial design because of compatibility issues and a stronger thermodynamic driving force for degradation. In this chapter different strategies for protection of multimaterials structures are briefly overviewed. The main focus is on new alternative protection systems based on combination of synergistic inhibiting mixtures introduced into protective coatings. A road map which can be followed in order to create an efficient active protection coating for hybrid structures is suggested.

  17. Evolution of Military Combat Eye Protection.

    PubMed

    Auvil, James R

    2016-01-01

    Appreciation for combat eye protection steadily increased following World War II. Products derived from experiences in World War I, World War II, Korea, Vietnam, and the Iran/Iraq war drove technical improvements throughout the 1980s and 1990s. Dismal wear compliance prior to 2004 indicates Soldiers and their leaders did not appreciate these improvements and found little value in the bulky, ugly, and uncomfortable products. In 2003, the 10th Mountain Division requested enhanced eye protection. Program Executive Office Soldier, the optometry consultant to the Army Surgeon General, members of the Tri-Service Vision Conservation and Readiness Program, and other subject matter experts selected and tested commercial off-the-shelf eye protection against military ballistic impact standards. Optical devices that met ballistic standards formed the first Authorized Protective Eyewear List and were fielded beginning in 2004. Wear compliance rose dramatically for the stylish protective eyewear, reaching 85% to 95% and eye injuries decreased across the Department of Defense even as the incidence of attacks in Iraq increased. Researchers continue to evaluate new materials and designs to increase the capabilities, features and level of protection of future ballistic eyewear. PMID:27215881

  18. 40 CFR 721.5255 - 2-Naphthalenol, mono and dioctyl derivs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 2-Naphthalenol, mono and dioctyl derivs. 721.5255 Section 721.5255 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.5255...

  19. 40 CFR 721.5255 - 2-Naphthalenol, mono and dioctyl derivs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 2-Naphthalenol, mono and dioctyl derivs. 721.5255 Section 721.5255 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.5255...

  20. 40 CFR 721.3560 - Derivative of tetra-chloro-ethy-lene.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Health Administration regulations and set forth at 29 CFR 1910.134, and 30 CFR part 11, respectively, and... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Derivative of tetra-chloro-ethy-lene. 721.3560 Section 721.3560 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)...

  1. 40 CFR 721.3560 - Derivative of tetra-chloro-ethy-lene.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Health Administration regulations and set forth at 29 CFR 1910.134, and 30 CFR part 11, respectively, and... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Derivative of tetra-chloro-ethy-lene. 721.3560 Section 721.3560 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)...

  2. 40 CFR 721.3560 - Derivative of tetra-chloro-ethy-lene.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Health Administration regulations and set forth at 29 CFR 1910.134, and 30 CFR part 11, respectively, and... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Derivative of tetra-chloro-ethy-lene. 721.3560 Section 721.3560 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)...

  3. Wake Shield Target Protection

    SciTech Connect

    Valmianski, Emanuil I.; Petzoldt, Ronald W.; Alexander, Neil B.

    2003-05-15

    The heat flux from both gas convection and chamber radiation on a direct drive target must be limited to avoid target damage from excessive D-T temperature increase. One of the possibilities of protecting the target is a wake shield flying in front of the target. A shield will also reduce drag force on the target, thereby facilitating target tracking and position prediction. A Direct Simulation Monte Carlo (DSMC) code was used to calculate convection heat loads as boundary conditions input into ANSYS thermal calculations. These were used for studying the quality of target protection depending on various shapes of shields, target-shield distance, and protective properties of the shield moving relative to the target. The results show that the shield can reduce the convective heat flux by a factor of 2 to 5 depending on pressure, temperature, and velocity. The protective effect of a shield moving relative to the target is greater than the protective properties of a fixed shield. However, the protective effect of a shield moving under the drag force is not sufficient for bringing the heat load on the target down to the necessary limit. Some other ways of diminishing heat flux using a protective shield are discussed.

  4. Radiation protection standards in space.

    PubMed

    Sinclair, W K

    1986-01-01

    Radiation protection standards for the individual exposed to ionizing radiation in his/her daily work have evolved over more than 50 years since the first recommendations on limits by the NCRP and the ICRP. Initial standards were based on the absence of observable harm, notably skin erythema, but have since been modified as other concerns, such as leukemia and genetic effects, became more important. More recently, the general carcinogenic effect of radiation has become the principal concern at low doses. Genetic effects are also of concern in the younger individual. Modern radiation protection practices take both of these risks into account. Quantification of these risks improves as new information emerges. The study of the Japanese survivors of the atomic bombs continues to yield new information and the recent revisions in the dosimetry are about to be completed. The special circumstances of space travel suggest approaches to limits not unlike those for radiation workers on the ground. One approach is to derive a career limit based on the risks of accident faced by many nonradiation workers in a lifetime. The career limit can be apportioned according to the type of mission. The NCRP is considering this and other approaches to the specification of radiation standards in space. PMID:11537242

  5. Radiation protection standards in space

    NASA Astrophysics Data System (ADS)

    Sinclair, Warren K.

    Radiation protection standards for the individual exposed to ionizing radiation in his/her daily work have evolved over more than 50 years since the first recommendations on limits by the NCRP and the ICRP. Initial standards were based on the absence of observable harm, notably skin erythema, but have since been modified as other concerns, such as leukemia and genetic effects, became more important. More recently, the general carcinogenic effect of radiation has become the principal concern at low doses. Genetic effects are also of concern in the younger individual. Modern radiation protection practices take both of these risks into account. Quantification of these risks improves as new information emerges. The study of the Japanese survivors of the atomic bombs continues to yield new information and the recent revisions in the dosimetry are about to be completed. The special circumstances of space travel suggest approaches to limits not unlike those for radiation workers on the ground. One approach is to derive a career limit based on the risks of accident faced by many nonradiation workers in a lifetime. The career limit can be apportioned according to the type of mission. The NCRP is considering this and other approaches to the specification of radiation standards in space.

  6. Radiation protection in space.

    PubMed

    Reitz, G; Facius, R; Sandler, H

    1995-01-01

    Radiation environment, basic concepts of radiation protection, and specific aspects of the space radiation field are reviewed. The discussion of physico-chemical and subcellular radiation effects includes mechanisms of radiation action and cellular consequences. The discussion of radiobiological effects includes unique aspects of HZE particle effects, space flight findings, terrestrial findings, analysis of somatic radiation effects and effects on critical organs, and early and delayed effects. Other topics include the impact of the space flight environment, measurement of radiation exposure, establishing radiation protection limits, limitations in establishing space-based radiation exposure limits, radiation protection measures, and recommendations. PMID:11541474

  7. Optimization of radiation protection

    SciTech Connect

    Lochard, J.

    1981-07-01

    The practical and theoretical problems raised by the optimization of radiological protection merit a review of decision-making methods, their relevance, and the way in which they are used in order to better determine what role they should play in the decision-making process. Following a brief summary of the theoretical background of the cost-benefit analysis, we examine the methodological choices implicit in the model presented in the International Commission on Radiological Protection Publication No. 26 and, particularly, the consequences of the theory that the level of radiation protection, the benefits, and the production costs of an activity can be treated separately.

  8. Protected areas and poverty

    PubMed Central

    Brockington, Daniel; Wilkie, David

    2015-01-01

    Protected areas are controversial because they are so important for conservation and because they distribute fortune and misfortune unevenly. The nature of that distribution, as well as the terrain of protected areas themselves, have been vigorously contested. In particular, the relationship between protected areas and poverty is a long-running debate in academic and policy circles. We review the origins of this debate and chart its key moments. We then outline the continuing flashpoints and ways in which further evaluation studies could improve the evidence base for policy-making and conservation practice. PMID:26460124

  9. Fire protection design criteria

    SciTech Connect

    1997-03-01

    This Standard provides supplemental fire protection guidance applicable to the design and construction of DOE facilities and site features (such as water distribution systems) that are also provided for fire protection. It is intended to be used in conjunction with the applicable building code, national Fire Protection Association Codes and Standards, and any other applicable DOE construction criteria. This Standard, along with other delineated criteria, constitutes the basic criteria for satisfying DOE fire and life safety objectives for the design and construction or renovation of DOE facilities.

  10. A quantum protective mechanism in photosynthesis

    NASA Astrophysics Data System (ADS)

    Marais, Adriana; Sinayskiy, Ilya; Petruccione, Francesco; van Grondelle, Rienk

    2015-03-01

    Since the emergence of oxygenic photosynthesis, living systems have developed protective mechanisms against reactive oxygen species. During charge separation in photosynthetic reaction centres, triplet states can react with molecular oxygen generating destructive singlet oxygen. The triplet product yield in bacteria is observed to be reduced by weak magnetic fields. Reaction centres from plants' photosystem II share many features with bacterial reaction centres, including a high-spin iron whose function has remained obscure. To explain observations that the magnetic field effect is reduced by the iron, we propose that its fast-relaxing spin plays a protective role in photosynthesis by generating an effective magnetic field. We consider a simple model of the system, derive an analytical expression for the effective magnetic field and analyse the resulting triplet yield reduction. The protective mechanism is robust for realistic parameter ranges, constituting a clear example of a quantum effect playing a macroscopic role vital for life.

  11. A quantum protective mechanism in photosynthesis

    PubMed Central

    Marais, Adriana; Sinayskiy, Ilya; Petruccione, Francesco; van Grondelle, Rienk

    2015-01-01

    Since the emergence of oxygenic photosynthesis, living systems have developed protective mechanisms against reactive oxygen species. During charge separation in photosynthetic reaction centres, triplet states can react with molecular oxygen generating destructive singlet oxygen. The triplet product yield in bacteria is observed to be reduced by weak magnetic fields. Reaction centres from plants' photosystem II share many features with bacterial reaction centres, including a high-spin iron whose function has remained obscure. To explain observations that the magnetic field effect is reduced by the iron, we propose that its fast-relaxing spin plays a protective role in photosynthesis by generating an effective magnetic field. We consider a simple model of the system, derive an analytical expression for the effective magnetic field and analyse the resulting triplet yield reduction. The protective mechanism is robust for realistic parameter ranges, constituting a clear example of a quantum effect playing a macroscopic role vital for life. PMID:25732807

  12. The azobenzene derivatives

    NASA Astrophysics Data System (ADS)

    Ionita, Ionica; Radulescu, Cristiana; Poinescu, Aurora Anca; Anghelina, Florina Violeta; Bunghez, Raluca; Ion, Rodica-Mariana

    2015-02-01

    Azobenzene derivatives constitute a group of dyes which have photochromic properties and have been investigated as promising systems for diverse applications in the unconventional optic area, their properties can be moulded with help of light.

  13. Synthesis of phenoxatellurine derivatives

    SciTech Connect

    Maksimenko, A.A.; Rivkin, B.B.; Sadekov, I.D.; Minkin, V.I.

    1985-12-01

    The reaction of dimedon enol acetate with tellurium tetrachloride gives derivatives of octahydrophenoxatellurine. The reaction of cyclohexanone enol acetate and methyl ethyl ketone with tellurium tetrachloride or aryltellurium trichloride gives the respective organotellurium trichloride and diorganotellurium dichloride.

  14. Protect Your Fertility

    MedlinePlus

    ... lead to infertility. To protect your chances of conceiving, maintain a healthy weight through proper nutrition and ... decreased sperm production. To improve your chances of conceiving in the future, avoid drugs now. For more ...

  15. Health protection well inventory

    SciTech Connect

    Janssen, J.

    1989-03-01

    This report is an inventory of the wells contained in Health Protection (HP) documents since the startup of the Savannah River Plan (SRP) and includes wells monitored by special request and SRL research wells.

  16. Protective relaying performance reporting

    SciTech Connect

    Taylor, R.P.; Ingelson, J.W.; Arnold, P.F.; Babcock, G.; Burzese, A.A.; Cornelison, J.R.; Drum, P.R.; Hasenwinkle, I.; Johnson, R.; Marsh, W. J. Jr.

    1992-10-01

    This paper reports on the performance of protective relaying systems which is an issue within the electric power industry which has received inadequate attention. The wide variations in relaying types and styles and applications, as well as differences in company structures and industry terminology, have hindered the adoption of a standardized system for the evaluation of protective relaying system performance. Such a system, if adopted by a significant portion of the industry, would provide suppliers and users better information with which to improve the product and its application and operation. The Protective Relaying Performance Criteria Working Group of the IEEE Power System Relaying Committee has generated this paper for the purpose of defining a standardized protective relaying performance reporting system.

  17. Fire Protection Materials

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Avco has drawn upon its heat shield experience to develop a number of widely-accepted commercial fire protection materials. Originating from NASA's space shuttle thermal protection system, one such material is Chartek 59 fireproofing, an intumescent epoxy coating specifically designed for outdoor use by industrial facilities dealing with highly flammable products such as oil refineries and chemical plants. The coating is applied usually by spray gun to exterior structural steel conduits, pipes and valves, offshore platforms and liquefied petroleum gas tanks. Fireproofing provides two types of protection: ablation or dissipation of heat by burn-off and "intumescence" or swelling; the coating swells to about five times its original size, forming a protective blanket of char which retards transfer of heat to the metal structure preventing loss of structural strength and possible collapse which would compound the fire fighting problem.

  18. Protect Yourself: Respirators

    MedlinePlus

    ... worn whenever you are working in a hazardous atmosphere. The appropriate respi- rator will depend on the ... must not be used to protect from hazardous atmospheres. However, they may be useful in providing comfort ...

  19. Radiation Protection Handbook

    NASA Technical Reports Server (NTRS)

    1972-01-01

    A handbook which sets forth the Kennedy Space Center radiation protection policy is presented. The book also covers administrative direction and guidance on organizational and procedural requirements of the program. Only ionizing radiation is covered.

  20. Protective Face Mask

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Mask to protect the physically impaired from injuries to the face and head has been developed by Langley Research Center. It is made of composite materials, usually graphite or boron fibers woven into a matrix. Weighs less than three ounces.

  1. Wired for Protection.

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2002-01-01

    Describes how growing acceptance of security measures such as access-control cards, video surveillance, and biometric devices is allowing colleges to protect students and their belongings more effectively. (EV)

  2. Tomboy as protective identity.

    PubMed

    Craig, Traci; Lacroix, Jessica

    2011-01-01

    The tomboy in contemporary U.S. culture is a complex identity, providing meaning to many girls and women. In this article, we argue tomboy as a gendered social identity also provides temporary "protections" to girls and women in three main ways. First, tomboy identity can excuse masculine-typed behavior in girls and women and, in doing so, protect women from presumptions about sexual reputation and sexual orientation. Second, tomboy identities can provide some protection for lesbian girls and women who prefer to not divulge their sexual orientation. And, third, tomboy identity can gain women limited privilege to spaces for which masculinity is an unspoken requirement. The temporary nature of the protections provided to tomboys undermines the ability of tomboys to truly transcend the binary gender system. PMID:21973066

  3. Advanced worker protection system

    SciTech Connect

    Caldwell, B.; Duncan, P.; Myers, J.

    1995-12-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D&D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D&D costs while providing appropriate protection to DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D&D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project will result in the development of an Advanced Worker Protection System (AWPS). The AWPS will be built around a life support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack will be combined with advanced protective garments, advanced liquid cooling garment, respirator, communications, and support equipment to provide improved worker protection, simplified system maintenance, and dramatically improve worker productivity through longer duration work cycles. Phase I of the project has resulted in a full scale prototype Advanced Worker Protection Ensemble (AWPE, everything the worker will wear), with sub-scale support equipment, suitable for integrated testing and preliminary evaluation. Phase II will culminate in a full scale, certified, pre-production AWPS and a site demonstration.

  4. Lightweight Protective Garments

    NASA Technical Reports Server (NTRS)

    Du Fresne, E. R.

    1986-01-01

    Proposed garment material protects wearer from poisonous chemicals, bacteria, and radioactive particulates. Garment allows heat, moisture, and carbon dioxide to pass from inside to outside so wearer remains comfortable. Garment made of cotton fabric on which thin layer of polyacrylate rubber is deposited by calendering or spraying. Lighter and cooler than existing protective garments. Polyacrylate rubber selected for garment material because it transmits water vapor and carbon dioxide at high rates.

  5. Maintaining radiation protection records

    SciTech Connect

    Not Available

    1992-11-30

    This Report is part of a series prepared under the auspices of Scientific Committee 46 on Operational Radiation Safety. It provides guidance on maintaining radiation protection records. Record keeping is an essential element of every radiation protection program. This Report describes the elements that should enter into the design of a program for the maintenance of operational radiation safety records. The problems of the length of time for retention of records for operational, regulatory, epidemiologic and legal uses are discussed in detail.

  6. REDUCED PROTECTIVE CLOTHING DETERMINATIONS

    SciTech Connect

    BROWN, R.L.

    2003-06-13

    This technical basis document defines conditions where reduced protective clothing can be allowed, defines reduced protective clothing, and documents the regulatory review that determines the process is compliant with the Tank Farm Radiological Control Manual (TFRCM) and Title 10, Part 835, of the Code of Federal Regulations (10CFR835). The criteria, standards, and requirements contained in this document apply only to Tank Farm Contractor (TFC) facilities.

  7. Advanced worker protection system

    SciTech Connect

    Caldwell, B.; Duncan, P.; Myers, J.

    1995-10-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D&D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D&D costs while providing appropriate protection to DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D&D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project describes the development of an Advanced Worker Protection System (AWPS) which will include a life-support backpack with liquid air for cooling and as a supply of breathing gas, protective clothing, respirators, communications, and support equipment.

  8. 40 CFR 721.558 - Salt of a fatty alkylamine derivative (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Salt of a fatty alkylamine derivative... Specific Chemical Substances § 721.558 Salt of a fatty alkylamine derivative (generic). (a) Chemical... as a salt of a fatty alkylamine derivative (PMN P-96-1426) is subject to reporting under this...

  9. 40 CFR 721.558 - Salt of a fatty alkylamine derivative (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Salt of a fatty alkylamine derivative... Specific Chemical Substances § 721.558 Salt of a fatty alkylamine derivative (generic). (a) Chemical... as a salt of a fatty alkylamine derivative (PMN P-96-1426) is subject to reporting under this...

  10. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this...

  11. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this...

  12. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this...

  13. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this...

  14. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this...

  15. 40 CFR 721.558 - Salt of a fatty alkylamine derivative (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Salt of a fatty alkylamine derivative... Specific Chemical Substances § 721.558 Salt of a fatty alkylamine derivative (generic). (a) Chemical... as a salt of a fatty alkylamine derivative (PMN P-96-1426) is subject to reporting under this...

  16. 40 CFR 721.558 - Salt of a fatty alkylamine derivative (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Salt of a fatty alkylamine derivative... Specific Chemical Substances § 721.558 Salt of a fatty alkylamine derivative (generic). (a) Chemical... as a salt of a fatty alkylamine derivative (PMN P-96-1426) is subject to reporting under this...

  17. 40 CFR 454.60 - Applicability; description of manufacture of rosin-based derivatives subcategory.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... manufacture of rosin-based derivatives subcategory. 454.60 Section 454.60 Protection of Environment... manufacture of rosin-based derivatives subcategory. The provisions of this subpart are applicable to discharges resulting from the manufacture of rosin-based derivatives....

  18. 40 CFR 454.60 - Applicability; description of manufacture of rosin-based derivatives subcategory.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... manufacture of rosin-based derivatives subcategory. 454.60 Section 454.60 Protection of Environment... manufacture of rosin-based derivatives subcategory. The provisions of this subpart are applicable to discharges resulting from the manufacture of rosin-based derivatives....

  19. 40 CFR 454.60 - Applicability; description of manufacture of rosin-based derivatives subcategory.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... manufacture of rosin-based derivatives subcategory. 454.60 Section 454.60 Protection of Environment... manufacture of rosin-based derivatives subcategory. The provisions of this subpart are applicable to discharges resulting from the manufacture of rosin-based derivatives....

  20. 40 CFR 454.60 - Applicability; description of manufacture of rosin-based derivatives subcategory.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... manufacture of rosin-based derivatives subcategory. 454.60 Section 454.60 Protection of Environment... manufacture of rosin-based derivatives subcategory. The provisions of this subpart are applicable to discharges resulting from the manufacture of rosin-based derivatives....

  1. 40 CFR 454.60 - Applicability; description of manufacture of rosin-based derivatives subcategory.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... manufacture of rosin-based derivatives subcategory. 454.60 Section 454.60 Protection of Environment... manufacture of rosin-based derivatives subcategory. The provisions of this subpart are applicable to discharges resulting from the manufacture of rosin-based derivatives....

  2. NASA Manned Launch Vehicle Lightning Protection Development

    NASA Technical Reports Server (NTRS)

    McCollum, Matthew B.; Jones, Steven R.; Mack, Jonathan D.

    2009-01-01

    Historically, the National Aeronautics and Space Administration (NASA) relied heavily on lightning avoidance to protect launch vehicles and crew from lightning effects. As NASA transitions from the Space Shuttle to the new Constellation family of launch vehicles and spacecraft, NASA engineers are imposing design and construction standards on the spacecraft and launch vehicles to withstand both the direct and indirect effects of lightning. A review of current Space Shuttle lightning constraints and protection methodology will be presented, as well as a historical review of Space Shuttle lightning requirements and design. The Space Shuttle lightning requirements document, NSTS 07636, Lightning Protection, Test and Analysis Requirements, (originally published as document number JSC 07636, Lightning Protection Criteria Document) was developed in response to the Apollo 12 lightning event and other experiences with NASA and the Department of Defense launch vehicles. This document defined the lightning environment, vehicle protection requirements, and design guidelines for meeting the requirements. The criteria developed in JSC 07636 were a precursor to the Society of Automotive Engineers (SAE) lightning standards. These SAE standards, along with Radio Technical Commission for Aeronautics (RTCA) DO-160, Environmental Conditions and Test Procedures for Airborne Equipment, are the basis for the current Constellation lightning design requirements. The development and derivation of these requirements will be presented. As budget and schedule constraints hampered lightning protection design and verification efforts, the Space Shuttle elements waived the design requirements and relied on lightning avoidance in the form of launch commit criteria (LCC) constraints and a catenary wire system for lightning protection at the launch pads. A better understanding of the lightning environment has highlighted the vulnerability of the protection schemes and associated risk to the vehicle

  3. Semisynthetic Derivatives of Epothilones

    NASA Astrophysics Data System (ADS)

    Altmann, Karl-Heinz

    Semisynthetic derivatives of natural products traditionally occupy a prominent space in natural-product-based drug discovery (1, 2). As many biologically active natural products exhibit a high degree of structural complexity (3), the chemical derivatization of material isolated from natural sources often represents the only feasible means (or at least the only economically viable approach) to explore structure-activity-relationships (SAR) and to produce analogs with more favorable pharmacokinetic and pharmacological properties than the natural product lead. Examples of clinically important drugs that are semisynthetic derivatives of natural products exist in virtually all disease areas (1, 2); in the treatment of cancer this includes compounds such as etoposide or teniposide (derived from podophyllotoxin) (4-6), irinotecan and topotecan (derived from camptothecin) (7-9), or docetaxel (derived from 10-deacetylbaccatin III) (10, 11). Even for taxol (11), which is a natural product (12), the sustained supply of sufficient quantities of material for widespread clinical use could only be secured through the development of a semisynthetic production process from another natural product, namely, 10-deacetylbaccatin III (13). In light of these facts, it is not surprising that semisynthesis approaches have also featured prominently in the elucidation of the SAR for epothilones and in the discovery of a number of clinical development candidates.

  4. Ferroelectricity in corundum derivatives

    NASA Astrophysics Data System (ADS)

    Ye, Meng; Vanderbilt, David

    The search for new ferroelectric (FE) materials holds promise for broadening our understanding of FE mechanisms and extending the range of application of FE materials. The known FE materials LiNbO3 can be regarded as derived from the A2O3 corundum structure with cation ordering. Here we consider more general binary (AB O3) and ternary (A2 BB' O6) corundum derivatives as an extended class of potential FE materials, motivated by the fact that some members of this class have recently been synthesized. There are four structure types for these corundum derivatives, and the number of cation combinations is enormous, but in many cases the energy barriers for polarization reversal may be too large to allow FE behavior. Here we present a first-principles study of the polar structure, coherent FE barrier, and domain-wall switching barrier for a representative set of polar corundum derivatives, allowing us to identify several potentially new FE materials. We also discuss the conditions under which ferroelectricity is compatible with magnetic ordering. Finally, we identify several empirical measures that can provide a rule of thumb for estimating the barrier energies. Our results should assist in the experimental search for new FE materials in the corundum derivative family. This work is supported by ONR Grant No. N-00014-12-1-1035.

  5. Protecting the Moon

    NASA Astrophysics Data System (ADS)

    Rummel, John

    Historically speaking, the Earth's Moon has been subject to a wide variety of protections and cautions associated with space exploration. Early lunar missions (cf., the Ranger series) were initially subjected to sterilization procedures to protect the Moon from biological contamination, and though these were relaxed in later periods (e.g., Surveyor, Apollo), those measures were never entirely abandoned until the mid-1980s. More recent lunar missions (e.g., Clementine, Lunar Prospector, SMART-1) have only been inadvertently concerned with protection of the Moon—Clementine in the attempt to have it leave the vicinity of the Earth entirely, Lunar Prospector in it end-of-mission crash into the lunar south pole (with a resultant outcry by the Navajo population in the US), and SMART-1 because of the keen attention paid by the astronomical community to its end-of-mission location. While operations on the Moon are not constrained by current COSPAR planetary protection restrictions, an increasing interest in the Moon suggests that additional protections should be imposed in the future. For example, if lunar ices exist as a repository of past impact volatiles, then the contamination of lunar ices with non-organically-clean spacecraft and tools presents an initial concern for the potentially lost science, as well as future resource contamination concerns if such ices are found and can be used to as part of a comprehensive life-support strategy for human outposts. Requirements for the protection of this aspect of the lunar environment, as well as others, has been initiated both within COSPAR and by NASA, which (in NPR 8715.6) now requires orbital debris protection for spacecraft in lunar orbit, and prior approval of any future landing (or crashing) sites on the Moon, requiring those to "be chosen (or precluded) with due regard to the planned usage of those sites in future exploration or scientific study and the interests of other spacefaring nations."

  6. Child protection: a 50-year perspective.

    PubMed

    Skellern, Catherine Yvette

    2015-01-01

    It has been 50 years since Kempe et al. published 'The Battered Child Syndrome', describing harm from inflicted injury mechanisms derived from parents and care givers. Since then, there has emerged a rapidly expanding literature on paediatric forensic medicine and child protection, which has offered new insights into injury mechanisms, informed us of the sequelae of abuse and neglect, aided diagnosis and guided clinical practice in the treatment and management of children who become involved in the child protection system. Through the scrutiny of government inquiries and at times uncomfortable media exposure, there have been improvements in child protection and forensic practices resulting in recognition of need for specialised forensic training, improved funding, development of resources and development of professional standards that support accountable, objective, safe and robust practice. From the perspective of an Australian child protection paediatrician, this paper chronicles some of the most significant and at times controversial research in the last 50 years in child protection that have played a key role in shaping our current understanding of child abuse and neglect. PMID:25534472

  7. Vectored vaccines to protect against PRRSV.

    PubMed

    Cruz, Jazmina L G; Zúñiga, Sonia; Bécares, Martina; Sola, Isabel; Ceriani, Juan E; Juanola, Sandra; Plana, Juan; Enjuanes, Luis

    2010-12-01

    PRRSV is the causative agent of the most important infectious disease affecting swine herds worldwide, producing great economic losses. Commercially available vaccines are only partially effective in protection against PRRSV. Moreover, modified live vaccines may allow virus shedding, and could revert generating virulent phenotypes. Therefore, new efficient vaccines are required. Vaccines based on recombinant virus genomes (virus vectored vaccines) against PRRSV could represent a safe alternative for the generation of modified live vaccines. In this paper, current vectored vaccines to protect against PRRSV are revised, including those based on pseudorabies virus, poxvirus, adenovirus, and virus replicons. Special attention has been provided to the use of transmissible gastroenteritis virus (TGEV) as vector for the expression of PRRSV antigens. This vector has the capability of expressing high levels of heterologous genes, is a potent interferon-α inducer, and presents antigens in mucosal surfaces, eliciting both secretory and systemic immunity. A TGEV derived vector (rTGEV) was generated, expressing PRRSV wild type or modified GP5 and M proteins, described as the main inducers of neutralizing antibodies and cellular immune response, respectively. Protection experiments showed that vaccinated animals developed a faster and stronger humoral immune response than the non-vaccinated ones. Partial protection in challenged animals was observed, as vaccinated pigs showed decreased lung damage when compared with the non-vaccinated ones. Nevertheless, the level of neutralizing antibodies was low, what may explain the limited protection observed. Several strategies are proposed to improve current rTGEV vectors expressing PRRSV antigens. PMID:20600388

  8. Rack Protection Monitor

    SciTech Connect

    Orr, Stanley G.

    1998-10-21

    A hardwired, fail-safe rack protection monitor utilizes electromechanical relays to respond to the detection by condition sensors of abnormal or alarm conditions (such as smoke, temperature, wind or water) that might adversely affect or damage equipment being protected. When the monitor is reset, the monitor is in a detection mode with first and second alarm relay coils energized. If one of the condition sensors detects an abnormal condition, the first alarm relay coil will be de-energized, but the second alarm relay coil will remain energized. This results in both a visual and an audible alarm being activated. If a second alarm condition is detected by another one of the condition sensors while the first condition sensor is still detecting the first alarm condition, both the first alarm relay coil and the second alarm relay coil will be de-energized. With both the first and second alarm relay coils de-energized, both a visual and an audible alarm will be activated. In addition, power to the protected equipment will be terminated and an alarm signal will be transmitted to an alarm central control. The monitor can be housed in a separate enclosure so as to provide an interface between a power supply for the protected equipment and the protected equipment.

  9. Sports eyewear protective standards.

    PubMed

    Dain, Stephen J

    2016-01-01

    Eye injuries sustained during sport comprise up to 20 per cent of all injuries to the eye serious enough for medical attention to be sought. The prevalence of eye injuries in sport is not easily assessed due to lack of authoritative participation rates, so most studies report total numbers in a time period. The evidence on the proportion of all ocular injuries that are from sport is reviewed. The relative frequencies in different sports are compared in a qualitative manner and the sports with greater numbers of ocular injuries are detailed. In common with occupational injuries to the eye, most sports eye injuries are considered preventable. The hierarchy of action for occupational risk is detailed and adapted to use in a sports scenario. All the available international, regional and national standards on sports eye protection are detailed and their provisions compared. The major function of the standards is to provide adequate protection against the hazard of the sport concerned. These are detailed and compared as a function of energy transfer. Eye protection must not introduce additional or secondary hazards (for instance, fracturing into sharp fragments on impact) and not introduce features that would deter the wearing of eye protection (for instance, restricting field of view to impede playing the sport). The provisions of the standards intended to limit secondary hazards are detailed and compared. The need for future work in standards writing and the activities of the International Standardization Organization in sports eye protection are detailed. PMID:26875849

  10. Rack protection monitor

    DOEpatents

    Orr, Stanley G.

    2000-01-01

    A hardwired, fail-safe rack protection monitor utilizes electromechanical relays to respond to the detection by condition sensors of abnormal or alarm conditions (such as smoke, temperature, wind or water) that might adversely affect or damage equipment being protected. When the monitor is reset, the monitor is in a detection mode with first and second alarm relay coils energized. If one of the condition sensors detects an abnormal condition, the first alarm relay coil will be de-energized, but the second alarm relay coil will remain energized. This results in both a visual and an audible alarm being activated. If a second alarm condition is detected by another one of the condition sensors while the first condition sensor is still detecting the first alarm condition, both the first alarm relay coil and the second alarm relay coil will be de-energized. With both the first and second alarm relay coils de-energized, both a visual and an audible alarm will be activated. In addition, power to the protected equipment will be terminated and an alarm signal will be transmitted to an alarm central control. The monitor can be housed in a separate enclosure so as to provide an interface between a power supply for the protected equipment and the protected equipment.

  11. Myeloid derived suppressor cells

    PubMed Central

    Waldron, Todd J.; Quatromoni, Jon G.; Karakasheva, Tatiana A.; Singhal, Sunil; Rustgi, Anil K.

    2013-01-01

    The goal of achieving measurable response with cancer immunotherapy requires counteracting the immunosuppressive characteristics of tumors. One of the mechanisms that tumors utilize to escape immunosurveillance is the activation of myeloid derived suppressor cells (MDSCs). Upon activation by tumor-derived signals, MDSCs inhibit the ability of the host to mount an anti-tumor immune response via their capacity to suppress both the innate and adaptive immune systems. Despite their relatively recent discovery and characterization, anti-MDSC agents have been identified, which may improve immunotherapy efficacy. PMID:23734336

  12. Data protection, privacy.

    PubMed

    La Monaca, G; Schiralli, I

    2010-01-01

    The topic of data protection is referred closely to the concept of privacy--characterized by the American political philosophy in order to indicate a sphere recognized as personal, and therefore private or intimate, of the person, which exclude other individuals or society--whose protection has deep roots in the international right. The technological progress in the field of telecommunication has increased the facility of acquisition and spreading of information, the exchange of data, and the possibility of access to confidential information by other people. This made it made necessary the regulation of the management and the transfer of these information in order to protect individual rights and, on the other hand, an easy circulation of data for legitimate and useful goals. PMID:20499037

  13. Microscope collision protection apparatus

    DOEpatents

    DeNure, Charles R.

    2001-10-23

    A microscope collision protection apparatus for a remote control microscope which protects the optical and associated components from damage in the event of an uncontrolled collision with a specimen, regardless of the specimen size or shape. In a preferred embodiment, the apparatus includes a counterbalanced slide for mounting the microscope's optical components. This slide replaces the rigid mounts on conventional upright microscopes with a precision ball bearing slide. As the specimen contacts an optical component, the contacting force will move the slide and the optical components mounted thereon. This movement will protect the optical and associated components from damage as the movement causes a limit switch to be actuated, thereby stopping all motors responsible for the collision.

  14. Advanced Worker Protection System

    SciTech Connect

    1996-04-01

    The Advanced Worker Protection System (AWPS) is a liquid-air-based, self-contained breathing and cooling system with a duration of 2 hrs. AWPS employs a patented system developed by Oceaneering Space Systems (OSS), and was demonstrated at their facility in Houston, TX as well as at Kansas State University, Manhattan. The heart of the system is the life-support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack is combined with advanced protective garments, an advanced liquid cooling garment (LCG), a respirator, and communications and support equipment. The prototype unit development and testing under Phase 1 has demonstrated that AWPS has the ability to meet performance criteria. These criteria were developed with an understanding of both the AWPS capabilities and the DOE decontamination and decommissioning (D and D) activities protection needs.

  15. Effects of sulfate chitosan derivatives on nonalcoholic fatty liver disease

    NASA Astrophysics Data System (ADS)

    Yu, Mingming; Wang, Yuanhong; Jiang, Tingfu; Lv, Zhihua

    2014-06-01

    Sulfate chitosan derivatives have good solubility and therapeutic effect on the cell model of NAFLD. The aim of this study was to examine the therapeutic effect of sulfate chitosan derivatives on NAFLD. The male Wistar rats were orally fed high fat emulsion and received sulfate chitosan derivatives for 5 weeks to determine the pre-treatment effect of sulfate chitosan derivatives on NAFLD. To evaluate the therapeutic effect of sulfate chitosan derivatives on NAFLD, the rats were orally fed with high concentration emulsion for 5 weeks, followed by sulfate chitosan derivatives for 3 weeks. Histological analysis and biomedical assays showed that sulfate chitosan derivatives can dramatically prevent the development of hepatic steatosis in hepatocyte cells. In animal studies, pre-treatment and treatment with sulfate chitosan derivatives significantly protected against hepatic steatohepatitis induced by high fat diet according to histological analysis. Furthermore, increased TC, ALT, MDA, and LEP in NAFLD were significantly ameliorated by pre-treatment and treatment with sulfate chitosan derivatives. Furthermore, increased TG, AST, and TNF-α in NAFLD were significantly ameliorated by treatment with sulfate chitosan derivatives. Sulfate chitosan derivatives have good pre-treatment and therapeutic effect on NAFLD.

  16. Spacecraft ceramic protective shield

    NASA Technical Reports Server (NTRS)

    Larriva, Rene F. (Inventor); Nelson, Anne (M.); Czechanski, James G. (Inventor); Poff, Ray E. (Inventor)

    1995-01-01

    A low areal density protective shield apparatus, and method for making same, for protecting spacecraft structures from impact with hypervelocity objects, including a bumper member comprising a bumper ceramic layer, a bumper shock attenuator layer, and a bumper confining layer. The bumper ceramic layer can be SiC or B.sub.4 C; the bumper shock attenuator layer can be zirconia felt; and the bumper confining layer can be aluminum. A base armor member can be spaced from the bumper member and a ceramic fiber-based curtain can be positioned between the bumper and base armor members.

  17. Material for radioactive protection

    DOEpatents

    Taylor, R.S.; Boyer, N.W.

    A boron containing burn resistant, low-level radiation protection material useful, for example, as a liner for radioactive waste disposal and storage, a component for neutron absorber, and a shield for a neutron source is described. The material is basically composed of borax in the range of 25 to 50%, coal tar in the range of 25 to 37.5%, with the remainder being an epoxy resin mix. A preferred composition is 50% borax, 25% coal tar and 25% epoxy resin. The material is not susceptible to burning and is about 1/5 the cost of existing radiation protection material utilized in similar applications.

  18. Radiation protection in space

    SciTech Connect

    Blakely, E.A.; Fry, R.J.M.

    1995-02-01

    The challenge for planning radiation protection in space is to estimate the risk of events of low probability after low levels of irradiation. This work has revealed many gaps in the present state of knowledge that require further study. Despite investigations of several irradiated populations, the atomic-bomb survivors remain the primary basis for estimating the risk of ionizing radiation. Compared to previous estimates, two new independent evaluations of available information indicate a significantly greater risk of stochastic effects of radiation (cancer and genetic effects) by about a factor of three for radiation workers. This paper presents a brief historical perspective of the international effort to assure radiation protection in space.

  19. Coral reef protection

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    The National Oceanic and Atmospheric Administration announced the establishment on 13 November of the first U.S. zone to protect a sensitive coral reef area from potential damage by ships.The Florida Keys' Particularly Sensitive Sea Area, just one of a handful of such areas globally, has been designated by the International Maritime Organization, a specialized agency of the United Nations. The area protects a zone of more than 3,000 square nautical miles stretching from the Biscayne National Park to the Dry Tortugas.

  20. Protection of Marine Mammals.

    PubMed

    Knoll, Michaela; Ciaccia, Ettore; Dekeling, René; Kvadsheim, Petter; Liddell, Kate; Gunnarsson, Stig-Lennart; Ludwig, Stefan; Nissen, Ivor; Lorenzen, Dirk; Kreimeyer, Roman; Pavan, Gianni; Meneghetti, Nello; Nordlund, Nina; Benders, Frank; van der Zwan, Timo; van Zon, Tim; Fraser, Leanne; Johansson, Torbjörn; Garmelius, Martin

    2016-01-01

    Within the European Defense Agency (EDA), the Protection of Marine Mammals (PoMM) project, a comprehensive common marine mammal database essential for risk mitigation tools, was established. The database, built on an extensive dataset collection with the focus on areas of operational interest for European navies, consists of annual and seasonal distribution and density maps, random and systematic sightings, an encyclopedia providing knowledge on the characteristics of 126 marine mammal species, data on marine mammal protection areas, and audio information including numerous examples of various vocalizations. Special investigations on marine mammal acoustics were carried out to improve the detection and classification capabilities. PMID:26611003

  1. Protective overcoating of films

    NASA Technical Reports Server (NTRS)

    Maas, K. A.

    1972-01-01

    Kodak Film Type SO-212 was emulsion overcoated with gelatin and lacquer to evaluate the feasibility of application of the coatings, any image degradation, and the relative protection offered against abrasion. Evaluated were: Eastman motion picture film lacquer Type 485, water solutions of Eastman purified Calfskin gelatin, and experimental Eastman gelatin stripping film of 4 and 6 microns. Conclusions reached were: (1) All coatings can be applied with relative ease with the only limitation being that of equipment. (2) None of the coatings degrade the processed image. (3) All of the coatings provide protection to the emulsion. These conclusions apply to any film which may be considered for overcoating.

  2. Protection from space radiation

    SciTech Connect

    Tripathi, R.K.; Wilson, J.W.; Shinn, J.L.

    2000-07-01

    The exposures anticipated for astronauts in the anticipated human exploration and development of space will be significantly higher (both annual and carrier) than for any other occupational group. In addition, the exposures in deep space result largely from galactic cosmic rays for which there is as yet little experience. Some evidence exists indicating that conventional linear energy transfer defined protection quantities (quality factors) may not be appropriate. The authors evaluate their current understanding of radiation protection with laboratory and flight experimental data and discuss recent improvements in interaction models and transport methods.

  3. Pesticide personal protective clothing.

    PubMed

    Branson, D H; Sweeney, M

    1991-01-01

    A fairly large established data base provides information on clothing worn by U.S. and Canadian farmers to work with pesticides, their attitudes and beliefs about pesticide risk, and clothing as a dermal barrier. Very limited similar data are available for farmers in less developed countries. Clearly, farmers perceive the benefits of pesticides to far exceed any risks. While few report poisoning symptoms, most believe that their usual work clothing offers a sufficient pesticide barrier, and few wear special-purpose protective clothing. Gloves of various materials, including cotton and leather, appear to be the major protective clothing item. Although farmers feel that their usual work clothing provides excellent protection, fabric penetration research does not support this. Shirting-weight fabrics offer some limited protection against light spray of field-strenght pesticides. Heavier-weight fabrics, such as denim and twill, are better barriers. With a heavier spray or a spill, usual work clothing does not give sufficient protection. Greater protection can usually be achieved with the use of a fluorocarbon finished fabric, such as Scotchgard or Zepel. Scotchgard can readily be applied at home. A durable-press finish does not appear to improve fabric's pesticide-barrier resistance and some data suggest that it may decrease barrier properties. A second alternative for increased protection is the use of a special-purpose fabric, such as a coated nonwoven or possibly Gore-Tex. Numerous other new "waterproof breathable" fabrics have recently come to the market. Many of these are finished or coated fabrics and one would expect them to be at least somewhat resistant to pesticides. However, they have not been tested. Wearing an additional layer also appears to be another clothing strategy to minimize exposure. Fabric penetration research also shows that pesticide formulation, volume or spray regime, concentration, and active ingredients influence the barrier properties of

  4. Thermal Protection Materials Development

    NASA Technical Reports Server (NTRS)

    Selvaduray, Guna; Cox, Michael

    1998-01-01

    The main portion of this contract year was spent on the development of materials for high temperature applications. In particular, thermal protection materials were constantly tested and evaluated for thermal shock resistance, high-temperature dimensional stability, and tolerance to hostile environmental effects. The analytical laboratory at the Thermal Protection Materials Branch (TPMB), NASA-Ames played an integral part in the process of materials development of high temperature aerospace applications. The materials development focused mainly on the determination of physical and chemical characteristics of specimens from the various research programs.

  5. Protection from Space Radiation

    NASA Technical Reports Server (NTRS)

    Tripathi, R. K.; Wilson, J. W.; Shinn, J. L.; Singleterry, R. C.; Clowdsley, M. S.; Cucinotta, F. A.; Badhwar, G. D.; Kim, M. Y.; Badavi, F. F.; Heinbockel, J. H.

    2000-01-01

    The exposures anticipated for our astronauts in the anticipated Human Exploration and Development of Space (HEDS) will be significantly higher (both annual and carrier) than any other occupational group. In addition, the exposures in deep space result largely from the Galactic Cosmic Rays (GCR) for which there is as yet little experience. Some evidence exists indicating that conventional linear energy transfer (LET) defined protection quantities (quality factors) may not be appropriate [1,2]. The purpose of this presentation is to evaluate our current understanding of radiation protection with laboratory and flight experimental data and to discuss recent improvements in interaction models and transport methods.

  6. Fire Protection Jacket

    NASA Technical Reports Server (NTRS)

    1991-01-01

    NERAC, Inc., Tolland, CT, aided Paul Monroe Engineering, Orange, CA, in the development of their PC1200 Series Fire Protection Jacket that protects the oil conduit system on an offshore drilling platform from the intense hydrocarbon fires that cause buckling and could cause structural failure of the platform. The flame-proof jacketing, which can withstand temperatures of 2000 degrees Fahrenheit for four hours or more, was developed from a combination of ceramic cloth (similar to the ceramic in Space Shuttle tiles), and laminates used in space suits.

  7. Oxygenated Derivatives of Hydrocarbons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For the book entitled “Insect Hydrocarbons: Biology, Biochemistry and Chemical Ecology”, this chapter presents a comprehensive review of the occurrence, structure and function of oxygenated derivatives of hydrocarbons. The book chapter focuses on the occurrence, structural identification and functi...

  8. 78 FR 32191 - Derivatives

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-29

    ... alternatives. \\5\\ 71 FR 5155 (February 2, 2012). C. 1998 IRPS This proposed rule is consistent with a 1998... promulgation of this proposed rule. \\7\\ 76 FR 37030 (June 24, 2011). First, the Board asked if it should... derivatives transactions independently. \\9\\ 77 FR 5416 (Feb. 3, 2012). Question One. The Board asked if...

  9. Biotechnology and derived products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Microorganisms able to infect and kill insect pests, metabolites from plants and microorganisms, and transgenic crops are biotechnologically derived products that are being promoted for use to control insect pests in lieu of chemical insecticides. Products based on these technologies effectively co...

  10. Ferroelectricity in corundum derivatives

    NASA Astrophysics Data System (ADS)

    Ye, Meng; Vanderbilt, David

    2016-04-01

    The search for new ferroelectric (FE) materials holds promise for broadening our understanding of FE mechanisms and extending the range of application of FE materials. Here we investigate a class of A B O3 and A2B B'O6 materials that can be derived from the X2O3 corundum structure by mixing two or three ordered cations on the X site. Most such corundum derivatives have a polar structure, but it is unclear whether the polarization is reversible, which is a requirement for a FE material. In this paper, we propose a method to study the FE reversal path of materials in the corundum derivative family. We first categorize the corundum derivatives into four classes and show that only two of these allow for the possibility of FE reversal. We then calculate the energy profile and energy barrier of the FE reversal path using first-principles density functional methods with a structural constraint. Furthermore, we identify several empirical measures that can provide a rule of thumb for estimating the energy barriers. Finally, the conditions under which the magnetic ordering is compatible with ferroelectricity are determined. These results lead us to predict several potentially new FE materials.

  11. Passive Protection Against Coccidiosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The protective effect of chicken egg antibody (IgY) powder which were prepared from hens hyperimmunized with a purified recombinant protein from Eimeria acervulina merozoites (3-E) was evaluated in a chicken challenge model with 2 different Eimeria species, E. acervulina and E. tenella. The chickens...

  12. Advanced extravehicular protective systems

    NASA Technical Reports Server (NTRS)

    Sutton, J. G.; Heimlich, P. F.; Tepper, E. H.

    1972-01-01

    New technologies are identified and recommended for developing a regenerative portable life support system that provides protection for extravehicular human activities during long duration missions on orbiting space stations, potential lunar bases, and possible Mars landings. Parametric subsystems analyses consider: thermal control, carbon dioxide control, oxygen supply, power supply, contaminant control, humidity control, prime movers, and automatic temperature control.

  13. Protective coatings for concrete

    SciTech Connect

    NAGY, KATHRYN L.; CYGAN, RANDALL T.; BRINKER, C. JEFFREY; SELLINGER, ALAN

    2000-05-01

    The new two-layer protective coating developed for monuments constructed of limestone or marble was applied to highway cement and to tobermorite, a component of cement, and tested in batch dissolution tests. The goal was to determine the suitability of the protective coating in retarding the weathering rate of concrete construction. The two-layer coating consists of an inner layer of aminoethylaminopropylsilane (AEAPS) applied as a 25% solution in methanol and an outer layer of A2** sol-gel. In previous work, this product when applied to calcite powders, had resulted in a lowering of the rate of dissolution by a factor of ten and was shown through molecular modeling to bind strongly to the calcite surface, but not too strongly so as to accelerate dissolution. Batch dissolution tests at 22 C of coated and uncoated tobermorite (1.1 nm phase) and powdered cement from Gibson Blvd. in Albuquerque indicated that the coating exhibits some protective behavior, at least on short time scales. However, the data suggest that the outer layer of sol-gel dissolves in the high-pH environment of the closed system of cement plus water. Calculated binding configuration and energy of AEAPS to the tobermorite surface suggests that AEAPS is well-suited as the inner layer binder for protecting tobermorite.

  14. Armored garment for protecting

    DOEpatents

    Purvis, James W.; Jones, II, Jack F.; Whinery, Larry D.; Brazfield, Richard; Lawrie, Catherine; Lawrie, David; Preece, Dale S.

    2009-08-11

    A lightweight, armored protective garment for protecting an arm or leg from blast superheated gases, blast overpressure shock, shrapnel, and spall from a explosive device, such as a Rocket Propelled Grenade (RPG) or a roadside Improvised Explosive Device (IED). The garment has a ballistic sleeve made of a ballistic fabric, such as an aramid fiber (e.g., KEVLAR.RTM.) cloth, that prevents thermal burns from the blast superheated gases, while providing some protection from fragments. Additionally, the garment has two or more rigid armor inserts that cover the upper and lower arm and protect against high-velocity projectiles, shrapnel and spall. The rigid inserts can be made of multiple plies of a carbon/epoxy composite laminate. The combination of 6 layers of KEVLAR.RTM. fabric and 28 plies of carbon/epoxy laminate inserts (with the inserts being sandwiched in-between the KEVLAR.RTM. layers), can meet the level IIIA fragmentation minimum V.sub.50 requirements for the US Interceptor Outer Tactical Vest.

  15. Partners in Environmental Protection

    ERIC Educational Resources Information Center

    Morehouse, Karen

    1975-01-01

    The Environmental Protection Agency's (EPA) and the Comprehensive Employment and Training Act's (CETA) cooperative relationship regarding the development of environmental manpower programs on a State and local level is discussed. Environmental programs resulting from CETA aid are described and EPA statistics given, stating that such programs are…

  16. Protecting against Disaster

    ERIC Educational Resources Information Center

    Howell, Kevin R.

    2006-01-01

    This article features an assistant professor of technology who shares his story of near disaster and offers advice for others about protecting their data. The author presents steps that can be taken to prevent unexpected events from destroying data. The author strongly recommends using backup files as a way of securing computer files and data.…

  17. Lightning protection of aircraft

    NASA Technical Reports Server (NTRS)

    Fisher, F. A.; Plumer, J. A.

    1977-01-01

    The current knowledge concerning potential lightning effects on aircraft and the means that are available to designers and operators to protect against these effects are summarized. The increased use of nonmetallic materials in the structure of aircraft and the constant trend toward using electronic equipment to handle flight-critical control and navigation functions have served as impetus for this study.

  18. Protectiveness, Persecution, and Powerlessness

    ERIC Educational Resources Information Center

    Weeks, Kathleen G.

    1977-01-01

    This paper is an investigation of family pathology from a transactional viewpoint. The thesis proposed is that family pathology is a means of protecting the family and ensuring its survival. The father, mother, and child assume and exchange the roles of the Karpman drama triangle; namely, Persecutor, Victim, and Rescuer. (Author)

  19. Thermal protection apparatus

    DOEpatents

    Bennett, Gloria A.; Elder, Michael G.; Kemme, Joseph E.

    1985-01-01

    An apparatus which thermally protects sensitive components in tools used in a geothermal borehole. The apparatus comprises a Dewar within a housing. The Dewar contains heat pipes such as brass heat pipes for thermally conducting heat from heat sensitive components to a heat sink such as ice.

  20. ECOLOGICAL PROTECTION AND RESTORATION

    EPA Science Inventory

    To carry out this mission, GLNPO established its Ecological Protection and Restoration Team (the E Team), consisting of a staff plus extended team members from EPA Regions 2, 3, and 5, other federal and state agencies, and non-governmental organizations. GLNPO expect...

  1. Protection of Intellectual Property.

    ERIC Educational Resources Information Center

    Hoffman, Gary M.; McGrath, William T.

    1990-01-01

    The first of two articles discusses the extent to which piracy of intellectual property hurts the U.S. economy, the role of developing nations in piracy, and who benefits from the protection of intellectual property. The second explores the implications of a Supreme Court ruling on copyrighting of computer programs created by independent…

  2. Global protected area impacts

    PubMed Central

    Joppa, Lucas N.; Pfaff, Alexander

    2011-01-01

    Protected areas (PAs) dominate conservation efforts. They will probably play a role in future climate policies too, as global payments may reward local reductions of loss of natural land cover. We estimate the impact of PAs on natural land cover within each of 147 countries by comparing outcomes inside PAs with outcomes outside. We use ‘matching’ (or ‘apples to apples’) for land characteristics to control for the fact that PAs very often are non-randomly distributed across their national landscapes. Protection tends towards land that, if unprotected, is less likely than average to be cleared. For 75 per cent of countries, we find protection does reduce conversion of natural land cover. However, for approximately 80 per cent of countries, our global results also confirm (following smaller-scale studies) that controlling for land characteristics reduces estimated impact by half or more. This shows the importance of controlling for at least a few key land characteristics. Further, we show that impacts vary considerably within a country (i.e. across a landscape): protection achieves less on lands far from roads, far from cities and on steeper slopes. Thus, while planners are, of course, constrained by other conservation priorities and costs, they could target higher impacts to earn more global payments for reduced deforestation. PMID:21084351

  3. Protective Policy Laws.

    ERIC Educational Resources Information Center

    Gehrin, Donald D.

    1994-01-01

    Offers ways to help student affairs administrators understand protective policy laws and regulations. Looks at how such federal guidelines affect campus policies, practices, and procedures. Examines the Buckley Amendment, student consumer information, student right-to-know, campus security, and the Drug Free Schools and Communities Act. (Includes…

  4. Thermal protection apparatus

    DOEpatents

    Bennett, G.A.; Elder, M.G.; Kemme, J.E.

    1984-03-20

    The disclosure is directed to an apparatus for thermally protecting sensitive components in tools used in a geothermal borehole. The apparatus comprises a Dewar within a housing. The Dewar contains heat pipes such as brass heat pipes for thermally conducting heat from heat sensitive components such as electronics to a heat sink such as ice.

  5. Protecting Gas Chromatographic Syringes

    NASA Astrophysics Data System (ADS)

    Ruekberg, Ben

    1995-12-01

    This article describes the construction of a device which protects gas chromatographic syringes. The device lessens the likelihood of syringes rolling off tables and breaking. If the syringe is dropped, the glass barrel is less apt to be struck and shattered.

  6. The TLWP cathodic protection system

    SciTech Connect

    Evans, S. )

    1992-08-01

    This paper details the subsea corrosion protection system of the tension leg well platform (TLWP), which comprises coatings and cathodic protection (CP). Postinstallation surveys reveal potentials of at least 150 mV more protective than the minimum potential required for protection. The TLWP protection system weighs 434,000 lbm less than the conventional CP design, with 286,000 lbm less on the floating portion of the TLWP.

  7. Derived enriched uranium market

    SciTech Connect

    Rutkowski, E.

    1996-12-01

    The potential impact on the uranium market of highly enriched uranium from nuclear weapons dismantling in the Russian Federation and the USA is analyzed. Uranium supply, conversion, and enrichment factors are outlined for each country; inventories are also listed. The enrichment component and conversion components are expected to cause little disruption to uranium markets. The uranium component of Russian derived enriched uranium hexafluoride is unresolved; US legislation places constraints on its introduction into the US market.

  8. 40 CFR 721.1825 - Bisphenol A, epichloro-hy-drin, polyalkylenepolyol and poly-iso-cyanato derivative.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Bisphenol A, epichloro-hy-drin, polyalkylenepolyol and poly-iso-cyanato derivative. 721.1825 Section 721.1825 Protection of Environment ENVIRONMENTAL..., polyalkylenepolyol and poly-iso-cyanato derivative. (a) Chemical substance and significant new uses subject...

  9. 40 CFR 721.1825 - Bisphenol A, epichloro-hy-drin, polyalkylenepolyol and poly-iso-cyanato derivative.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Bisphenol A, epichloro-hy-drin, polyalkylenepolyol and poly-iso-cyanato derivative. 721.1825 Section 721.1825 Protection of Environment ENVIRONMENTAL..., polyalkylenepolyol and poly-iso-cyanato derivative. (a) Chemical substance and significant new uses subject...

  10. Future Interoperability of Camp Protection Systems (FICAPS)

    NASA Astrophysics Data System (ADS)

    Caron, Sylvie; Gündisch, Rainer; Marchand, Alain; Stahl, Karl-Hermann

    2013-05-01

    The FICAPS Project has been established as a Project of the European Defence Agency based on an initiative of Germany and France. Goal of this Project was to derive Guidelines, which by a proper implementation in future developments improve Camp Protection Systems (CPS) by enabling and improving interoperability between Camp Protection Systems and its Equipments of different Nations involved in multinational missions. These Guidelines shall allow for: • Real-time information exchange between equipments and systems of different suppliers and nations (even via SatCom), • Quick and easy replacement of equipments (even of different Nations) at run-time in the field by means of plug and play capability, thus lowering the operational and logistic costs and making the system highly available, • Enhancement of system capabilities (open and modular systems) by adding new equipment with new capabilities (just plug-in, automatic adjustment of the HMI Human Machine Interface) without costly and time consuming validation and test on system level (validation and test can be done on Equipment level), Four scenarios have been identified to summarize the interoperability requirements from an operational viewpoint. To prove the definitions given in the Guideline Document, a French and a German Demonstration System, based on existing national assets, were realized. Demonstrations, showing the capabilities given by the defined interoperability requirements with respect to the operational scenarios, were performed. Demonstrations included remote control of a CPS by another CPS, remote sensor control (Electro-Optic/InfraRed EO/IR) and remote effector control. This capability can be applied to extend the protection area or to protect distant infrastructural assets Demonstrations have been performed. The required interoperability functionality was shown successfully. Even if the focus of the FICAPS project was on camp protection, the solution found is also appropriate for other

  11. Protecting our patients by protecting ourselves

    PubMed Central

    Ziegler, Blake; Alsabbagh, Wasem; Houle, Sherilyn; Wenger, Lisa; Church, Dana; Waite, Nancy

    2016-01-01

    Background: With recent expansions to scope of practice that have allowed Canadian pharmacists to play a larger role in administering influenza vaccinations to the public, it is important that pharmacists themselves meet Canadian guidelines recommending that 80% of health care professionals and 100% of vaccinators receive an annual influenza vaccination. Unvaccinated health care professionals pose an infection risk to patients they serve and are at an increased risk of infection themselves. Methods: An online, anonymous survey was sent to Ontario community pharmacists to determine whether they had received the influenza vaccination during the 2013–2014 influenza season. All significant univariate chi-square analysis respondent characteristics were included in a multivariate regression analysis model to determine predictors of vaccination status. Results: A total of 780 pharmacists completed the survey (18.1% response rate), which showed that 7 in 10 Ontario community pharmacists received the influenza vaccine. Those certified to immunize were nearly 3 times more likely to have received the influenza vaccine than those not certified (81.6% versus 61.2%, respectively). Discussion: Having 70% of Ontario community pharmacists vaccinated against influenza is both an accomplishment and an opportunity to improve vaccination rates. While similar to the influenza immunization rates of other health care professions, Ontario community pharmacists did not meet Public Health Canada’s recommendations. Comprehensive worksite programs, including promotion, education and convenient access to influenza vaccination at no cost, could increase community pharmacist influenza vaccination rates. Conclusion: The authors issue a call to arms to encourage all pharmacists to receive the influenza vaccine to protect the public and themselves. PMID:27540407

  12. Using Derivatives to Hedge Interest Rate Risk: A Student Exercise

    ERIC Educational Resources Information Center

    Donaldson, Jeff; Flagg, Donald

    2014-01-01

    In a world of fluctuating asset prices, many firms find the need to hedge in order to avoid or reduce losses. From a gold miner selling gold derivatives to airlines buying oil futures to protect against rising fuel costs, hedging is common practice across many different industries. In this paper, we provide students with a simplified example of a…

  13. 75 FR 63113 - Financial Resources Requirements for Derivatives Clearing Organizations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-14

    ... number of small entities. \\17\\ 5 U.S.C. 601 et seq. \\18\\ 47 FR 18618 (Apr. 30, 1982). \\19\\ See 66 FR... COMMISSION 17 CFR Parts 39 and 140 RIN 3038-AC98, 3038-AD02 Financial Resources Requirements for Derivatives... Protection Act (Dodd-Frank Act). The proposed regulations establish financial resources requirements...

  14. 76 FR 3697 - Risk Management Requirements for Derivatives Clearing Organizations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ...The Commodity Futures Trading Commission (Commission) is proposing regulations to implement Title VII and Title VIII of the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act). Proposed regulations would establish the regulatory standards for compliance with derivatives clearing organization (DCO) Core Principles C (Participant and Product Eligibility), D (Risk......

  15. Multifunction protective relay

    NASA Astrophysics Data System (ADS)

    Harlow, J.; Yalla, M.; Kantor, J.

    1991-11-01

    Since the enactment of the National Energy Act of 1979, many private energy producers have been planning and building small generation and cogeneration facilities in order to sell power to the local utility. Many of the non-utility generators built after 1979 are connected directly to the closest utility distribution circuit. Aware of the problems associated with connecting generators in this manner, electric utilities across the country developed specifications and standards to allow safe and reliable interconnection. The report describes a malfunction protective relay which uses state-of-the-art digital signal processing procedures to accomplish the objective of providing most of the relay requirements of utility electrical interconnections. The relay has been demonstrated to be suitable for this critical application through extensive laboratory and in-service field testing. The relay, incorporating thirteen distinct protection functions affords the user the savings of the initial capital cost plus simplicity of installation and use.

  16. Radiation protection in space.

    PubMed

    Blakely, E A; Fry, R J

    1995-08-01

    The challenge for planning radiation protection in space is to estimate the risk of events of low probability after low levels of irradiation. This work has revealed many gaps in our knowledge that require further study. Despite investigations of several irradiated populations, the atomic-bomb survivors remain the primary basis for estimating the risk of ionizing radiation. Compared with previous estimates, two new independent evaluations of available information indicate a significantly greater risk of stochastic effects of radiation (cancer and genetic effects) by about a factor of three for radiation workers, including space travelers. This paper presents a brief historical perspective of the international effort to assure radiation protection in space. PMID:7480625

  17. Force protection: today's reality.

    PubMed

    Torgerson, Ron

    2004-11-11

    Most US infrastructure and major chemical manufacturing facilities as well as their supporting utility systems are inherently vulnerable to a terrorist attack. Force protection is a military and civilian term used to protect personnel and critical facilities and assets against would-be aggressors or terrorists. The war on terrorism is a 200-300-year war. Terrorist attacks on US soil could become as common-place as in the State of Israel. It is very easy to penetrate infrastructure or plants as evidenced by vulnerability assessments performed for states, cities, plants, and military facilities by Versar and others around the country. Chemical, biological, radiological, nuclear, and explosive weapons can be readily used to attack facilities in the US. This paper will explain some of those vulnerabilities, outline the current DoD standard as it relates to vulnerability assessments, and explain how this may be used in commercial applications to deter potential aggressors. PMID:15573418

  18. Protected Flux Pairing Qubit

    NASA Astrophysics Data System (ADS)

    Bell, Matthew; Zhang, Wenyuan; Ioffe, Lev; Gershenson, Michael

    2014-03-01

    We have studied the coherent flux tunneling in a qubit containing two submicron Josephson junctions shunted by a superinductor (a dissipationless inductor with an impedance much greater than the resistance quantum). The two low energy quantum states of this device, 0 and 1, are represented by even and odd number of fluxes in the loop, respectively. This device is dual to the charge pairing Josephson rhombi qubit. The spectrum of the device, studied by microwave spectroscopy, reflects the interference between coherent quantum phase slips in the two junctions (the Aharonov-Casher effect). The time domain measurements demonstrate the suppression of the qubit's energy relaxation in the protected regime, which illustrates the potential of this flux pairing device as a protected quantum circuit. Templeton Foundation, NSF, and ARO.

  19. Protective orders: questions and conundrums.

    PubMed

    Logan, T K; Shannon, Lisa; Walker, Robert; Faragher, Teri Marie

    2006-07-01

    Current media portrayal of protective orders is often negative, focusing on weaknesses in how protective orders are obtained and enforced. This review of research findings on protective orders examines issues and suggests areas in need of future research to clarify and improve public policy. More specifically, this review has five main objectives: (a) to provide background information about partner violence and the need for protective orders; (b) to describe what protective orders are, how many women obtain them, and the advantages and disadvantages of obtaining protective orders; (c) to examine characteristics of women who seek protective orders; (d) to explore research on whether protective orders actually increase women's safety; and (e) to highlight opportunities and gaps in the practice and research literature regarding the use of protective orders for women with violent partners or ex-partners. PMID:16785286

  20. Protective garment ventilation system

    NASA Technical Reports Server (NTRS)

    Lang, R. (Inventor)

    1970-01-01

    A method and apparatus for ventilating a protective garment, space suit system, and/or pressure suits to maintain a comfortable and nontoxic atmosphere within is described. The direction of flow of a ventilating and purging gas in portions of the garment may be reversed in order to compensate for changes in environment and activity of the wearer. The entire flow of the ventilating gas can also be directed first to the helmet associated with the garment.

  1. Protecting beans from ozone

    SciTech Connect

    Pierce, R.

    1983-03-01

    A chemical treatment to protect navy beans from ozone damage increased yields by an average of more than 20% in 3 years of tests. An experimental antioxidant chemical, EDU, made by the DuPont company was tested as soil applications and sprays on several varieties and under a variety of soil and planting conditions. The average yield increases were between 16 and 24%. Chemical treatment also increased snap bean pod production by 12%.

  2. [History of sun protection].

    PubMed

    Couteau, Céline; Coiffard, Laurence

    2010-07-01

    Human behavior towards the sun has changed over the years along with trends. Tan succeeded the white complexion. The sunscreens appeared recently in history. It is lining up with the discovery of bad effects due to prolonged exposure to ultraviolet at the end of the 19th century. Initially, those products had no signs of efficacy on their packaging, then the solar protection factors increased gradually, up to a limit value of 50+ more recently. PMID:21032925

  3. Nitrite in organ protection

    PubMed Central

    Rassaf, Tienush; Ferdinandy, Peter; Schulz, Rainer

    2014-01-01

    In the last decade, the nitrate-nitrite-nitric oxide pathway has emerged to therapeutical importance. Modulation of endogenous nitrate and nitrite levels with the subsequent S-nitros(yl)ation of the downstream signalling cascade open the way for novel cytoprotective strategies. In the following, we summarize the actual literature and give a short overview on the potential of nitrite in organ protection. PMID:23826831

  4. Protective immunity against plague.

    PubMed

    Cornelius, Claire; Quenee, Lauriane; Anderson, Deborah; Schneewind, Olaf

    2007-01-01

    Plague, an infectious disease that reached catastrophic proportions during three pandemics, continues to be a legitimate public health concern worldwide. Although antibiotic therapy for the causative agent Yersinia pestis is available, pharmaceutical supply limitations, multi-drug resistance from natural selection as well as malicious bioengineering are a reality. Consequently, plague vaccinology is a priority for biodefense research. Development of a multi-subunit vaccine with Fraction 1 and LcrV as protective antigens seems to be receiving the most attention. However, LcrV has been shown to cause immune suppression and Y. pestis mutants lacking F1 expression are thought to be fully virulent in nature and in animal experiments. The LcrV variant, rV10, retains the well documented protective antigenic properties of LcrV but with diminished inhibitory effects on the immune system. More research is required to examine the molecular mechanisms of vaccine protection afforded by surface protein antigens and to decipher the host mechanisms responsible for vaccine success. PMID:17966437

  5. Thermal Protection and Control

    NASA Technical Reports Server (NTRS)

    Greene, Effie E.

    2013-01-01

    During all phases of a spacecraft's mission, a Thermal Protection System (TPS) is needed to protect the vehicle and structure from extreme temperatures and heating. When designing TPS, low weight and cost while ensuring the protection of the vehicle is highly desired. There are two main types of TPS, ablative and reusable. The Apollo missions needed ablators due to the high heat loads from lunar reentry. However, when the desire for a reusable space vehicle emerged, the resultant_ Space Shuttle program propelled a push for the development of reusable TPS. With the growth of reqsable TPS, the need for ablators declined, triggering a drop off of the ablator industry. As a result, the expertise was not heavily maintained within NASA or the industry. When the Orion Program initiated a few years back, a need. for an ablator reemerged. Yet, due to of the lack of industry capability, redeveloping the ablator material took several years and came at a high cost. As NASA looks towards the future with both the Orion and Commercial Crew Programs, a need to preserve reusable, ablative, and other TPS technologies is essential. Research of the different TPS materials alongside their properties, capabilities, and manufacturing process was performed, and the benefits of the materials were analyzed alongside the future of TPS. Knowledge of the different technologies has the ability to help us know what expertise to maintain and ensure a lack in the industry does not occur again.

  6. Lightning Protection for Explosive Facilities

    SciTech Connect

    Ong, M

    2001-12-01

    Lawrence Livermore National Laboratory funds construction of lightning protection systems to protect explosive processing and storage facilities. This paper provides an intuitive understanding of the lighting risks and types of lightning protection available. Managers can use this information to decide if limited funds should be spent constructing a lightning protection system for their own facilities. This paper answers the following questions: (1) Why do you need lightning protection systems? (2) How do lightning protection systems work? and (3) Why are there no documented cases of lightning problems at existing explosive facilities?

  7. 40 CFR 721.7270 - 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride. 721.7270 Section 721.7270 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

  8. 40 CFR 721.10056 - Benzenemethanaminium, N-(3-aminopropyl)-N,N-dimethyl-, N-soya acyl derivs., chlorides.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzenemethanaminium, N-(3-aminopropyl)-N,N-dimethyl-, N-soya acyl derivs., chlorides. 721.10056 Section 721.10056 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses...

  9. 40 CFR Appendix Vii to Part 266 - Health-Based Limits for Exclusion of Waste-Derived Residues*

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Health-Based Limits for Exclusion of Waste-Derived Residues* VII Appendix VII to Part 266 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES OF HAZARDOUS...

  10. Space Derived Air Monitor

    NASA Technical Reports Server (NTRS)

    1983-01-01

    COPAMS, Commonwealth of Pennsylvania Air Monitoring System, derives from technology involved in building unmanned spacecraft. The Nimbus spacecraft carried experimental sensors to measure temperature, pressure, ozone, and water vapor, and instruments for studying solar radiation and telemetry. The process which relayed these findings to Earth formed the basis for COPAMS. The COPAMS system consists of data acquisition units which measure and record pollution level, and sense wind speed and direction, etc. The findings are relayed to a central station where the information is computerized. The system is automatic and supplemented by PAQSS, PA Air Quality Surveillance System.

  11. 40 CFR 721.10148 - Acryloxy alkanoic alkane derivative with mixed metal oxides (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES... mixed metal oxides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as acryloxy alkanoic alkane derivative with mixed...

  12. In defense of derivations

    NASA Astrophysics Data System (ADS)

    Mungan, Carl E.

    2016-05-01

    At the 2015 AAPT Summer Meeting, I presented four derivations of the formula for motional emf. Such physics derivations involve the construction of explanatory frameworks involving diagrams and mathematical models. Although textbooks devote considerable space to such explanations, many teachers and students spend their time on worksheets, end-of-chapter problems, and the like. The book is reduced to a bank of solved (i.e., example) and unsolved (i.e., homework) questions, along with equations in colored boxes that presumably are to be used to answer those questions. Such an approach encourages fragmentation of knowledge, the view that there is only one right answer to a problem with the goal of physics being to find that answer (neatly boxed of course), and the inability to reason about even a slightly different (much less a novel) situation. If we are to develop scientific literacy, significant course time must be devoted to explaining the structure of and support for the models and equations we use.

  13. Coating protects magnesium-lithium alloys against corrosion

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Coating protects newly developed magnesium-lithium alloys against corrosion. The procedure includes heating the ingots in a salt bath and rolling them to the desired sheet thickness. The black coating, which is tough though thin and ductile, is derived mainly from chromium.

  14. Thermophysical Characteristics of the Protective Coating of the Soldering Rod

    NASA Astrophysics Data System (ADS)

    Shtennikov, V. N.

    2015-01-01

    An analytical dependence of the change in the soldering temperature on the material, thickness of the soldering rod protective coating, and the time of soldering is obtained. The relation derived allows one to ensure the needed temperature of contact soldering of electronic and electrical-engineering components and, consequently, their high quality.

  15. The Design of Lightning Protection

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Engineering study guides design and monitoring of lightning protection. Design studies for project are collected in 150-page report, containing wealth of information on design of lightning protection systems and on instrumentation for monitoring current waveforms of lightning strokes.

  16. Future Trends in Park Protection.

    ERIC Educational Resources Information Center

    Dwyer, William O.; Murrell, Dan S.

    1986-01-01

    The roles of ranger and park police in America's parks have shifted from visitor protection and resources management to visitor management and resources protection. Eight issues facing park police are discussed. (MT)

  17. ESA Missions Planetary Protection Status

    NASA Astrophysics Data System (ADS)

    Kminek, Gerhard

    2016-07-01

    This presentation will report the planetary protection status of ESA flight projects with planetary protection requirements. It will cover Rosetta, Mars Express, ExoMars 2016, ExoMars 2018, JUICE, Solar Orbiter, and Bepi Colombo.

  18. Chemical Protection Against Radiation Damage

    ERIC Educational Resources Information Center

    Campaigne, Ernest

    1969-01-01

    Discusses potential war time and medical uses for chemical compounds giving protection against radiation damage. Describes compounds known to protect, research aimed at discovering such compounds, and problems of toxicity. (EB)

  19. Acquiring Knowledge of Derived Nominals and Derived Adjectives in Context

    ERIC Educational Resources Information Center

    Marinellie, Sally A.; Kneile, Lynn A.

    2012-01-01

    Purpose: This research investigated children's ability to acquire semantic and syntactic knowledge of derived nominals and derived adjectives in the context of short passages. The study also investigated the relation of morphological awareness and the ability to acquire knowledge of derived words in context. Method: A total of 106 children in…

  20. Experts' Understanding of Partial Derivatives Using the Partial Derivative Machine

    ERIC Educational Resources Information Center

    Roundy, David; Weber, Eric; Dray, Tevian; Bajracharya, Rabindra R.; Dorko, Allison; Smith, Emily M.; Manogue, Corinne A.

    2015-01-01

    Partial derivatives are used in a variety of different ways within physics. Thermodynamics, in particular, uses partial derivatives in ways that students often find especially confusing. We are at the beginning of a study of the teaching of partial derivatives, with a goal of better aligning the teaching of multivariable calculus with the needs of…