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Sample records for c60oh24 protects mice

  1. Biodistribution and tumor uptake of C60(OH)x in mice

    International Nuclear Information System (INIS)

    Ji Zhiqiang; Sun Hongfang; Wang Haifang; Xie Qunying; Liu Yuangfang; Wang Zheng

    2006-01-01

    Radiolabeling of fullerol, 125 I-C 60 (OH) x , was performed by the traditional chloramine-T method. The C-I covalent bond in I-C 60 (OH) x was characterized by X-ray photoelectron spectroscopy (XPS) that was sufficiently stable for in vivo study. Laser light scattering spectroscopy clearly showed that C 60 (OH) x aggregated to large nanoparticle clumps with a wide range of distribution. The clumps formed were also visualized by transmission electron microscope (TEM). We examined the biodistribution and tumor uptake of C 60 (OH) x in five mouse bearing tumor models, including mouse H22 hepatocarcinoma, human lung giantcellcarcinoma PD, human colon cancer HCT-8, human gastric cancer MGC803, and human OS732 osteosarcoma. The accumulation ratios of 125 I-C 60 (OH) x in mouse H22 hepatocarcinoma to that in normal muscle tissue (T/N) and blood (T/B) at 1, 6, 24 and 72 h, reveal that 125 I-C 60 (OH) x gradually accumulates in H22 tumor, and retains for a quite long period (e.g., T/N 3.41, T/B 3.94 at 24 h). For the other four tumor models, the T/N ratio at 24 h ranges within 1.21-6.26, while the T/B ratio ranges between 1.23 and 4.73. The accumulation of C 60 (OH) x in tumor is mostly due to the enhanced permeability and retention effect (EPR) and the phagocytosis of mononuclear phagocytes. Hence, C 60 (OH) x might serve as a photosensitizer in the photodynamic therapy of some kinds of tumor

  2. Biodistribution and tumor uptake of C{sub 60}(OH){sub x} in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhiqiang, Ji; Sun Hongfang, E-mail: shf@pku.edu.cn; Haifang, Wang; Qunying, Xie; Yuangfang, Liu [Peking University, Department of Chemical Biology, College of Chemistry and Molecular Engineering (China); Zheng, Wang [Chinese Academy of Medical Sciences, Cancer Institute (China)

    2006-02-15

    Radiolabeling of fullerol, {sup 125}I-C{sub 60}(OH){sub x}, was performed by the traditional chloramine-T method. The C-I covalent bond in I-C{sub 60}(OH){sub x} was characterized by X-ray photoelectron spectroscopy (XPS) that was sufficiently stable for in vivo study. Laser light scattering spectroscopy clearly showed that C{sub 60}(OH){sub x} aggregated to large nanoparticle clumps with a wide range of distribution. The clumps formed were also visualized by transmission electron microscope (TEM). We examined the biodistribution and tumor uptake of C{sub 60}(OH){sub x} in five mouse bearing tumor models, including mouse H22 hepatocarcinoma, human lung giantcellcarcinoma PD, human colon cancer HCT-8, human gastric cancer MGC803, and human OS732 osteosarcoma. The accumulation ratios of {sup 125}I-C{sub 60}(OH){sub x} in mouse H22 hepatocarcinoma to that in normal muscle tissue (T/N) and blood (T/B) at 1, 6, 24 and 72 h, reveal that {sup 125}I-C{sub 60}(OH){sub x} gradually accumulates in H22 tumor, and retains for a quite long period (e.g., T/N 3.41, T/B 3.94 at 24 h). For the other four tumor models, the T/N ratio at 24 h ranges within 1.21-6.26, while the T/B ratio ranges between 1.23 and 4.73. The accumulation of C{sub 60}(OH){sub x} in tumor is mostly due to the enhanced permeability and retention effect (EPR) and the phagocytosis of mononuclear phagocytes. Hence, C{sub 60}(OH){sub x} might serve as a photosensitizer in the photodynamic therapy of some kinds of tumor.

  3. Bioapplication and activity of fullerenol C60(OH)24

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... represent a class of sphere-shaped molecules made entirely of .... 4942 Afr. J. Biotechnol. fullerenes. ... C60 and fullerenols C60(OH)x apparently employ different ... Alzheimer's and Parkinson's diseases, type-C hepatitis.

  4. Fullerenol C{sub 60}(OH){sub 24} nanoparticles decrease relaxing effects of dimethyl sulfoxide on rat uterus spontaneous contraction

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    Slavic, Marija, E-mail: marija17@ibiss.bg.ac.rs [University of Belgrade, Department for Physiology, Institute for Biological Research ' Sinisa Stankovic' (IBISS) (Serbia); Djordjevic, Aleksandar [University of Novi Sad, Department of Chemistry, Biochemistry and the Environment, Faculty of Sciences (Serbia); Radojicic, Ratko [University of Belgrade, Faculty of Biology (Serbia); Milovanovic, Slobodan [University of East Sarajevo, Department of Pharmacology, Faculty of Medicine at Foca (Bosnia and Herzegowina); Orescanin-Dusic, Zorana [University of Belgrade, Department for Physiology, Institute for Biological Research ' Sinisa Stankovic' (IBISS) (Serbia); Rakocevic, Zlatko [University of Belgrade, Institute for Nuclear Sciences ' Vinca' (Serbia); Spasic, Mihajlo B.; Blagojevic, Dusko [University of Belgrade, Department for Physiology, Institute for Biological Research ' Sinisa Stankovic' (IBISS) (Serbia)

    2013-05-15

    Dimethyl sulfoxide (DMSO) is a widely used solvent and cryoprotectant that can cause impaired blood flow, reduction in intracranial pressure, tissue edema, inflammatory reactions, inhibition of vascular smooth muscle cell migration and proliferation, processes which can lead to atherosclerosis of the coronary, peripheral and cerebral circulation. Although the adverse effects are rare when DMSO is administered in clinically established concentrations, there is no safe antagonist for an overdose. In this work, we treated isolated spontaneous and calcium-induced contractile active rat uteri (Wistar, virgo intacta), with DMSO and fullerenol C{sub 60}(OH){sub 24} nanoparticle (FNP) in DMSO. FNP is a water-soluble derivative of fullerene C{sub 60}. Its size is a 1.1 nm in diameter and is a very promising candidate for a drug carrier in nanomedicine. FNP also displays free radical scavenging activity. DMSO decreased both spontaneous and calcium-induced contractions. In contrast, FNP only decreased spontaneous contraction. FNP decreased copper-zinc superoxide dismutase activity and prevented the DMSO-induced increase in glutathione reductase activity. Atomic force microscopy detected that FNP aggregated with calcium ions. Our results indicate that FNP has properties that make it a good candidate to be a modulator of DMSO activity which could minimize side effects of the latter.

  5. Vaccination with recombinant heat shock protein 60 from Histoplasma capsulatum protects mice against pulmonary histoplasmosis.

    Science.gov (United States)

    Gomez, F J; Allendoerfer, R; Deepe, G S

    1995-07-01

    HIS-62 is a glycoprotein that has been isolated from the cell wall and cell membrane fraction of the pathogenic fungus Histoplasma capsulatum. It is a target of the cellular immune response to this fungus, and it protects mice against a lethal intravenous inoculum of H. capsulatum yeast cells. In this study, we cloned the gene encoding this antigen to reveal its biological nature and studied the immunological activity of recombinant antigen. The amino acid sequences of the NH2 terminus and internal peptides were obtained by Edman degradation. Degenerate oligonucleotides were used to isolate a gene fragment of HIS-62 by PCR. One 680-bp segment that corresponded to the known peptide sequence was amplified from H. capsulatum DNA. This DNA was used to screen a genomic library, and the full-length gene was isolated and sequenced. The deduced amino acid sequence of the gene demonstrated approximately 70 and approximately 50% identity to heat shock protein 60 (hsp 60) from Saccharomyces cerevisiae and hsp 60 from Escherichia coli, respectively. A cDNA was synthesized by reverse transcription PCR and was expressed in E. coli. Recombinant protein reacted with a monospecific polyclonal rabbit antiserum raised against native HIS-62, with monoclonal HIS-62-reactive T cells, and with splenocytes from mice immunized with viable yeast cells. Moreover, vaccination with the recombinant protein conferred protection in mice against a lethal intranasal inoculation with yeast cells. Thus, HIS-62 is a member of the hsp 60 family, and the recombinant hsp 60 is protective against pulmonary histoplasmosis in mice.

  6. Increased urine acylcarnitines in diabetic ApoE-/- mice: Hydroxytetradecadienoylcarnitine (C14:2-OH) reflects diabetic nephropathy in a context of hyperlipidemia

    International Nuclear Information System (INIS)

    Mirzoyan, Koryun; Klavins, Kristaps; Koal, Therese; Gillet, Marion; Marsal, Dimitri; Denis, Colette; Klein, Julie; Bascands, Jean-Loup; Schanstra, Joost P.; Saulnier-Blache, Jean-Sébastien

    2017-01-01

    Hyperlipidemia is a risk factor for initiation and progression of diabetic nephropathy but the metabolic pathways altered in the diabetic kidney in a context of hyperlipidemia remain incompletely described. Assuming that changes in urine composition reflect the alteration of renal metabolism and function, we analyzed the urine metabolite composition of diabetic (streptozotocin-treatment) and control (non diabetic) ApoE−/− mice fed a high cholesterol diet using targeted quantitative metabolomics. Urine metabolome was also compared to the plasma metabolome of the same animals. As previously shown, urine albuminuria/urine creatinine ratio (uACR) and glomerular area and plasma lipids (cholesterol, triglycerides) were more elevated in diabetic mice compared to control. After adjustment to urine creatinine, the abundance of 52 urine metabolites was significantly different in diabetic mice compared to control. Among them was a unique metabolite, C14:2-OH (3-hydroxytetradecadienoylcarnitine) that, in diabetic mice, was positively and significantly correlated with uACR, glomerular hypertrophy, blood glucose and plasma lipids. That metabolite was not detected in plasma. C14:2-OH is a long-chain acylcarnitine reminiscent of altered fatty acid beta oxidation. Other acylcarnitines, particularly the short chains C3-OH, C3-DC, C4:1, C5-DC, C5-M-DC, C5-OH that are reminiscent of altered oxidation of branched and aromatic amino acids were also exclusively detected in urine but were only correlated with plasma lipids. Finally, the renal gene expression of several enzymes involved in fatty acid and/or amino acid oxidation was significantly reduced in diabetic mice compared to control. This included the bifunctional enoyl-CoA hydratase/3-hydroxyacyl-CoA (Ehhadh) that might play a central role in C14:2-OH production. This study indicate that the development of diabetes in a context of hyperlipidemia is associated with a reduced capacity of kidney to oxidize fatty acids and amino

  7. Synthesis of C60(OH)18-20 in aqueous alkaline solution under O2-atmosphere

    International Nuclear Information System (INIS)

    Alves, Gustavo Catao; Ladeira, Luiz Orlando; Righi, Ariete; Krambrock, Klaus; Pinheiro, Mauricio Veloso B.; Calado, Hallen Daniel; Gil, Rossimiriam Pereira de Freitas

    2006-01-01

    In this work we report on an alternative synthesis of water-soluble fullerenes known as fullerols, aiming for biomedical applications. The synthesis is based on a process in which polyethylene glycol (PEG400) is used as phase-transfer catalyst between fullerene/benzene and aqueous NaOH solutions. The polyhydroxylation of the fullerenes occurs in the NaOH solution under a continuous flow of O 2 to enhance the reaction yield. The resulting compound was characterized with infrared spectroscopy, nuclear magnetic resonance, thermo-gravimetric analysis and optical absorption. The formation of C 60 (OH) 18-20 in high yields was confirmed. (author)

  8. Alpha-methyl-homocysteine thiolactone protects lung of BALB/c mice irradiated with 6 Gy

    International Nuclear Information System (INIS)

    Lubec, G.; Tichatschek, E.; Foltinova, J.; Leplawy, T.; Mallinger, R.; Getoff, N.

    1996-01-01

    The radiation protective activity of intaperitoneally administered alpha-methyl-homocysteine thiolactone (α-MHCTL); 100 mg/kg body weight) in female BALB/c mice and such treated with cysteine treated (100 mg/kg body weight), using unirradiated and placebo treated irradiated mice were tested as controls. 6Gy whole body irradiated was applied and after a period of three weeks the animals were sacrificed and lungs were taken for morphometry and the determination of o-tyrosine. Septal areas were highest in the irradiated, placebo treated mice (68.67 + 9.82% septal area to total area) and lowest in the α-MHCTL treated irradiated mice (55.67 + 11.29%), significant at the p < 0.05 level. Morphometric data were accompanied by highest levels of o-tyrosine, a reliable parameter for OH-attack, in the irradiated, placebo treated group with 1.87 + 0.40 μM/g lung tissue and 0.32 + 0.13 μM/g lung tissue in the αMHCTL treated group; the statistical difference was significant. Significant radiation protection in the mammalian system at the morphological and biochemical level were found. The potent effect could be explained by the influence of alpha-alkylation in homocysteine thiolactone (HCTL) which renders amino acids unmetabolizeable, nontoxic, increases lipophilicity and therefore improving permeability through membranes. The present report confirms morphological data on the radiation protective activity of this interesting thiol compound. (Author)

  9. Methamphetamine protects against MPTP neurotoxicity in C57BL mice.

    Science.gov (United States)

    Sziráki, I; Kardos, V; Patthy, M; Pátfalusi, M; Budai, G

    1994-01-14

    Methamphetamine (5 mg/kg) administered 30 min prior to each injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (3 x 30 mg/kg, at 24 h intervals) prevents the reduction of striatal levels of dopamine and its metabolites in C57BL mice. Methamphetamine and amphetamine inhibit the uptake of 1-methyl-4-phenylpyridinium (MPP+) by striatal synaptosomes of rats. A 30-min post-treatment with methamphetamine or amphetamine also prevents the MPTP-induced dopamine depletion, suggesting that their protective effect is related to the blockade of MPP+ uptake into dopaminergic neurons. Since amphetamine and methamphetamine are themselves neurotoxins at higher doses, this work demonstrated the protection against the actions of one neurotoxin by the administration of another.

  10. Synthesis of C{sub 60}(OH){sub 18-20} in aqueous alkaline solution under O{sub 2}-atmosphere

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    Alves, Gustavo Catao; Ladeira, Luiz Orlando; Righi, Ariete; Krambrock, Klaus; Pinheiro, Mauricio Veloso B. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Fisica; Calado, Hallen Daniel; Gil, Rossimiriam Pereira de Freitas [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Quimica]. E-mail: gustavo.catao@terra.com.br

    2006-09-15

    In this work we report on an alternative synthesis of water-soluble fullerenes known as fullerols, aiming for biomedical applications. The synthesis is based on a process in which polyethylene glycol (PEG400) is used as phase-transfer catalyst between fullerene/benzene and aqueous NaOH solutions. The polyhydroxylation of the fullerenes occurs in the NaOH solution under a continuous flow of O{sub 2} to enhance the reaction yield. The resulting compound was characterized with infrared spectroscopy, nuclear magnetic resonance, thermo-gravimetric analysis and optical absorption. The formation of C{sub 60}(OH){sub 18-20} in high yields was confirmed. (author)

  11. Translocation mechanism of C{sub 60} and C{sub 60} derivations across a cell membrane

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Lijun, E-mail: michael.lijunl@gmail.com [Hangzhou Dianzi University, College of Life Information Science and Instrument Engineering (China); Kang, Zhengzhong [Zhejiang University, Department of Chemistry (China); Shen, Jia-Wei, E-mail: shen.jiawei@hotmail.com [Hangzhou Normal University, School of Medicine (China)

    2016-11-15

    Carbon-based nanoparticles (NPs) such as fullerenes and nanotubes have been extensively studied for drug delivery in recent years. The permeation process of fullerene and its derivative molecules through membrane is essential to the utilization of fullerene-based drug delivery system, but the mechanism and the dynamics of permeation through cell membrane are still unclear. In this study, coarse-grained molecular dynamics simulations were performed to investigate the permeation process of functionalized fullerene molecules (ca. 0.72 nm) through the membrane. Our results show that single functionalized fullerene molecule in such nanoscale could permeate the lipid membrane in micro-second time scale. Pristine C{sub 60} molecules prefer to aggregate into several small clusters while C{sub 60}OH{sub 15} molecules could aggregate into one big cluster to permeate through the lipid membrane. After permeation of C{sub 60} or its derivatives into membrane, all C{sub 60} and C{sub 60}OH{sub 15} molecules disaggregated and monodispersed in the lipid membrane.

  12. Embryonic catalase protects against ethanol embryopathies in acatalasemic mice and transgenic human catalase-expressing mice in embryo culture.

    Science.gov (United States)

    Miller-Pinsler, Lutfiya; Wells, Peter G

    2015-09-15

    Reactive oxygen species (ROS) have been implicated in the mechanism of ethanol (EtOH) teratogenicity, but the protective role of the embryonic antioxidative enzyme catalase is unclear, as embryonic activity is only about 5% of maternal levels. We addressed this question in a whole embryo culture model. C57BL/6 mouse embryos expressing human catalase (hCat) or their wild-type (C57BL/6 WT) controls, and C3Ga.Cg-Cat(b)/J catalase-deficient, acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on gestational day (GD) 9 (plug=GD 1), exposed for 24h to 2 or 4mg/mL EtOH or vehicle, and evaluated for functional and morphological changes. hCat and C57BL/6 WT vehicle-exposed embryos developed normally, while EtOH was embryopathic in C57BL/6 WT embryos, evidenced by decreases in anterior neuropore closure, somites developed, turning and head length, whereas hCat embryos were protected (pcatalase (PEG-cat) 8h prior to embryo culture, which increases embryonic catalase activity, blocked all EtOH embryopathies (pcatalase is a determinant of risk for EtOH embryopathies. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Embryonic catalase protects against ethanol embryopathies in acatalasemic mice and transgenic human catalase-expressing mice in embryo culture

    International Nuclear Information System (INIS)

    Miller-Pinsler, Lutfiya; Wells, Peter G.

    2015-01-01

    Reactive oxygen species (ROS) have been implicated in the mechanism of ethanol (EtOH) teratogenicity, but the protective role of the embryonic antioxidative enzyme catalase is unclear, as embryonic activity is only about 5% of maternal levels. We addressed this question in a whole embryo culture model. C57BL/6 mouse embryos expressing human catalase (hCat) or their wild-type (C57BL/6 WT) controls, and C3Ga.Cg-Cat b /J catalase-deficient, acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on gestational day (GD) 9 (plug = GD 1), exposed for 24 h to 2 or 4 mg/mL EtOH or vehicle, and evaluated for functional and morphological changes. hCat and C57BL/6 WT vehicle-exposed embryos developed normally, while EtOH was embryopathic in C57BL/6 WT embryos, evidenced by decreases in anterior neuropore closure, somites developed, turning and head length, whereas hCat embryos were protected (p < 0.001). Maternal pretreatment of C57BL/6 WT dams with 50 kU/kg PEG-catalase (PEG-cat) 8 h prior to embryo culture, which increases embryonic catalase activity, blocked all EtOH embryopathies (p < 0.001). Vehicle-exposed aCat mouse embryos had lower yolk sac diameters compared to WT controls, suggesting that endogenous ROS are embryopathic. EtOH was more embryopathic in aCat embryos than WT controls, evidenced by reduced head length and somite development (p < 0.01), and trends for reduced anterior neuropore closure, turning and crown–rump length. Maternal pretreatment of aCat dams with PEG-Cat blocked all EtOH embryopathies (p < 0.05). These data suggest that embryonic catalase is a determinant of risk for EtOH embryopathies. - Highlights: • Ethanol (EtOH) exposure causes structural embryopathies in embryo culture. • Genetically enhanced catalase (hCat) protects against EtOH embryopathies. • Genetically deficient catalase (aCat) exacerbates EtOH embryopathies. • Embryonic catalase is developmentally important. • EtOH developmental

  14. Embryonic catalase protects against ethanol embryopathies in acatalasemic mice and transgenic human catalase-expressing mice in embryo culture

    Energy Technology Data Exchange (ETDEWEB)

    Miller-Pinsler, Lutfiya [Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Wells, Peter G., E-mail: pg.wells@utoronto.ca [Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario (Canada); Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada)

    2015-09-15

    Reactive oxygen species (ROS) have been implicated in the mechanism of ethanol (EtOH) teratogenicity, but the protective role of the embryonic antioxidative enzyme catalase is unclear, as embryonic activity is only about 5% of maternal levels. We addressed this question in a whole embryo culture model. C57BL/6 mouse embryos expressing human catalase (hCat) or their wild-type (C57BL/6 WT) controls, and C3Ga.Cg-Cat{sup b}/J catalase-deficient, acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on gestational day (GD) 9 (plug = GD 1), exposed for 24 h to 2 or 4 mg/mL EtOH or vehicle, and evaluated for functional and morphological changes. hCat and C57BL/6 WT vehicle-exposed embryos developed normally, while EtOH was embryopathic in C57BL/6 WT embryos, evidenced by decreases in anterior neuropore closure, somites developed, turning and head length, whereas hCat embryos were protected (p < 0.001). Maternal pretreatment of C57BL/6 WT dams with 50 kU/kg PEG-catalase (PEG-cat) 8 h prior to embryo culture, which increases embryonic catalase activity, blocked all EtOH embryopathies (p < 0.001). Vehicle-exposed aCat mouse embryos had lower yolk sac diameters compared to WT controls, suggesting that endogenous ROS are embryopathic. EtOH was more embryopathic in aCat embryos than WT controls, evidenced by reduced head length and somite development (p < 0.01), and trends for reduced anterior neuropore closure, turning and crown–rump length. Maternal pretreatment of aCat dams with PEG-Cat blocked all EtOH embryopathies (p < 0.05). These data suggest that embryonic catalase is a determinant of risk for EtOH embryopathies. - Highlights: • Ethanol (EtOH) exposure causes structural embryopathies in embryo culture. • Genetically enhanced catalase (hCat) protects against EtOH embryopathies. • Genetically deficient catalase (aCat) exacerbates EtOH embryopathies. • Embryonic catalase is developmentally important. • EtOH

  15. Modest vasomotor dysfunction induced by low doses of C60 fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Loft Steffen

    2009-02-01

    Full Text Available Abstract Background Exposure to small size particulate matter in urban air is regarded as a risk factor for cardiovascular effects, whereas there is little information about the impact on the cardiovascular system by exposure to pure carbonaceous materials in the nano-size range. C60 fullerenes are nano-sized particles that are expected to have a widespread use, including cosmetics and medicines. Methods We investigated the association between intraperitoneal injection of pristine C60 fullerenes and vasomotor dysfunction in the aorta of 11–13 and 40–42 weeks old apolipoprotein E knockout mice (apoE-/- with different degree of atherosclerosis. Results The aged apoE-/-mice had lower endothelium-dependent vasorelaxation elicited by acetylcholine in aorta segments mounted in myographs and the phenylephrine-dependent vasoconstriction response was increased. One hour after an intraperitoneal injection of 0.05 or 0.5 mg/kg of C60 fullerenes, the young apoE-/- mice had slightly reduced maximal endothelium-dependent vasorelaxation. A similar tendency was observed in the old apoE-/- mice. Hampered endothelium-independent vasorelaxation was also observed as slightly increased EC50 of sodium nitroprusside-induced vasorelaxation response in young apoE-/- mice. Conclusion Treatment with C60 fullerenes affected mainly the response to vasorelaxation in young apoE-/- mice, whereas the vasomotor dysfunction in old apoE-/- mice with more advanced atherosclerosis was less affected by acute C60 fullerene treatment. These findings represent an important step in the hazard characterization of C60 fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.

  16. Differential neurotoxic effects of in utero and lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) on spontaneous locomotor activity and motor coordination in young adult male mice.

    Science.gov (United States)

    Haijima, Asahi; Lesmana, Ronny; Shimokawa, Noriaki; Amano, Izuki; Takatsuru, Yusuke; Koibuchi, Noriyuki

    2017-01-01

    We investigated whether in utero or lactational exposure to 4-hydroxy-2',3,3',4',5'-pentachlorobiphenyl (OH-PCB 106) affects spontaneous locomotor activity and motor coordination in young adult male mice. For in utero exposure, pregnant C57BL/6J mice received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from gestational day 10 to 18. For lactational exposure, the different groups of dams received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from postpartum day 3 to 13. At 6-7 weeks of age, the spontaneous locomotor activities of male offspring were evaluated for a 24-hr continuous session in a home cage and in an open field for 30-min. Motor coordination function on an accelerating rotarod was also measured. Mice exposed prenatally to OH-PCB 106 showed increased spontaneous locomotor activities during the dark phase in the home cage and during the first 10-min in the open field compared with control mice. Mice exposed lactationally to OH-PCB 106, however, did not show a time-dependent decrease in locomotor activity in the open field. Instead, their locomotor activity increased significantly during the second 10-min block. In addition, mice exposed lactationally to OH-PCB 106 displayed impairments in motor coordination in the rotarod test. These results suggest that perinatal exposure to OH-PCB 106 affects motor behaviors in young adult male mice. Depending on the period of exposure, OH-PCB 106 may have different effects on neurobehavioral development.

  17. Genistein Protects Against Biomarkers of Delayed Lung Sequelae in Mice Surviving High-Dose Total Body Irradiation

    Science.gov (United States)

    DAY, Regina M.; BARSHISHAT-KUPPER, Michal; MOG, Steven R.; MCCART, Elizabeth A.; PRASANNA, P. G. S.; DAVIS, Thomas A.; LANDAUER, Michael R.

    2008-01-01

    The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60Co, 0.6 Gy/min). Experimental groups were: No treatment + Sham (NC), Vehicle + Sham (VC), Genistein + Sham (GC), Radiation only (NR), Vehicle + Radiation (VR), Genistein + Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13–28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. PMID:18434686

  18. Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation

    International Nuclear Information System (INIS)

    Day, R.M.; Barshishat-Kupper, M.; Mog, S.R.; Mccart, E.A.; Prasanna, P.G.S.; Landauer, M.R.; Davis, T.A.

    2008-01-01

    The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60 Co, 0.6 Gy/min). Experimental groups were: No treatment+Sham (NC), Vehicle+Sham (VC), Genistein+Sham (GC), Radiation only (NR), Vehicle+Radiation (VR), Genistein+Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13-28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. (author)

  19. Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

    Science.gov (United States)

    Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

    2016-10-01

    Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

  20. Protective effects of vitamin C against gamma-ray induced wholly damage and genetic damage

    International Nuclear Information System (INIS)

    Fu Chunling; Jiang Weiwei; Zhang Ping; Chen Xiang; Zhu Shengtao

    2000-01-01

    Objective: Protective effects of supplemental vitamin C against 60 Co-gamma-ray induced wholly damage and genetic damage was investigated in mice. Method: Mice were divided into normal control group, irradiation control group and vitamin C experimental group 1,2,3 (which were orally given vitamin C 15, 30, 45 mg/kg.bw for 10 successive days respectively prior to gamma-ray irradiation). Micronuclei in the bone marrow polychromatophilic erythrocytes in each group of mice were examined and the 30 day survival rate of mice following whole-body 5.0 Gy γ irradiation were also determined. Results: Supplemental vitamin C prior to gamma-rays irradiation can significantly decrease bone marrow PECMN rate of mice and increase 30 day survival rate and prolong average survival time. The protection factor is 2.09. Conclusion: Vitamin C has potent protective effects against gamma irradiation induced damage in mice. In certain dose range, vitamin C can absolutely suppress the gamma-rays induced genetic damage in vivo

  1. Kinetic analysis of human CYP24A1 metabolism of vitamin D via the C24-oxidation pathway.

    Science.gov (United States)

    Tieu, Elaine W; Tang, Edith K Y; Tuckey, Robert C

    2014-07-01

    CYP24A1 is the multicatalytic cytochrome P450 responsible for the catabolism of vitamin D via the C23- and C24-oxidation pathways. We successfully expressed the labile human enzyme in Escherichia coli and partially purified it in an active state that permitted detailed characterization of its metabolism of 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] and the intermediates of the C24-oxidation pathway in a phospholipid-vesicle reconstituted system. The C24-oxidation pathway intermediates, 1,24,25-trihydroxyvitamin D3, 24-oxo-1,25-dihydroxyvitamin D3, 24-oxo-1,23,25-trihydroxyvitamin D3 and tetranor-1,23-dihydroxyvitamin D3, were enzymatically produced from 1,25(OH)2 D3 using rat CYP24A1. Both 1,25(OH)2 D3 and 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3 were found to partition strongly into the phospholipid bilayer when in aqueous medium. Changes to the phospholipid concentration did not affect the kinetic parameters for the metabolism of 1,25(OH)2 D3 by CYP24A1, indicating that it is the concentration of substrates in the membrane phase (mol substrate·mol phospholipid(-1) ) that determines their rate of metabolism. CYP24A1 exhibited Km values for the different C24-intermediates ranging from 0.34 to 15 mmol·mol phospholipid(-1) , with 24-oxo-1,23,25-trihydroxyvitamin D3 [24-oxo-1,23,25(OH)3 D3] displaying the lowest and 1,24,25-trihydroxyvitamin D3 [1,24,25(OH)3 D3] displaying the highest. The kcat values varied by up to 3.8-fold, with 1,24,25(OH)3 D3 displaying the highest kcat (34 min(-1) ) and 24-oxo-1,23,25(OH)3 D3 the lowest. The data show that the cleavage of the side chain of 24-oxo-1,23,25(OH)3 D3 occurs with the highest catalytic efficiency (kcat /Km ) and produces 1-hydroxy-23-oxo-24,25,26,27-tetranorvitamin D3 and not 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3, as the primary product. These kinetic analyses also show that intermediates of the C24-oxidation pathway effectively compete with precursor substrates for binding to the active site of the

  2. 40 CFR 60.32c - Designated facilities.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Designated facilities. 60.32c Section 60.32c Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Solid Waste Landfills § 60.32c Designated facilities. (a) The designated facility to which the...

  3. Carbon fullerenes (C60s) can induce inflammatory responses in the lung of mice

    International Nuclear Information System (INIS)

    Park, Eun-Jung; Kim, Hero; Kim, Younghun; Yi, Jongheop; Choi, Kyunghee; Park, Kwangsik

    2010-01-01

    Fullerenes (C60s) occur in the environment due to natural and anthropogenic sources such as volcanic eruptions, forest fires, and the combustion of carbon-based materials. Recently, production and application of engineered C60s have also rapidly increased in diverse industrial fields and biomedicine due to C60' unique physico-chemical properties, so toxicity assessment on environmental and human health is being evaluated as a valuable work. However, data related to the toxicity of C60s have not been abundant up to now. In this study, we studied the immunotoxic mechanism and change of gene expression caused by the instillation of C60s. As a result, C60s induced an increase in sub G1 and G1 arrest in BAL cells, an increase in pro-inflammatory cytokines such as IL-1, TNF-α, and IL-6, and an increase of Th1 cytokines such as IL-12 and IFN-r in BAL fluid. In addition, IgE reached the maximum at 1 day after treatment in both BAL fluid and the blood, and decreased in a time-dependent manner. Gene expression of the MHC class II (H2-Eb1) molecule was stronger than that of the MHC class I (H2-T23), and an increase in T cell distribution was also observed during the experiment period. Furthermore, cell infiltration and expression of tissue damage related genes in lung tissue were constantly observed during the experiment period. Based on this, C60s may induce inflammatory responses in the lung of mice.

  4. Oral lactoferrin protects against experimental candidiasis in mice.

    Science.gov (United States)

    Velliyagounder, K; Alsaedi, W; Alabdulmohsen, W; Markowitz, K; Fine, D H

    2015-01-01

    To determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO(-/-)) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO(-/-) mice. Antibiotic-treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO(-/-) I mice showed a 2 log (P = 0·001) higher CFUs of C. albicans in the oral cavity compared to the WT mice infected with C. albicans (WTI). LFKO(-/-) I mice given hLF had a 3 log (P = 0·001) reduction in CFUs in the oral cavity compared to untreated LFKO(-/-) I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO(-/-) I mice showed more white patches compared to WTI and LFKO(-/-) I + hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO(-/-) I mice when compared to WTI or LFKO(-/-) I + hLF mice. Human LF is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Human LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans. © 2014 The Society for Applied Microbiology.

  5. A lower dose threshold for the in vivo protective adaptive response to radiation. Tumorigenesis in chronically exposed normal and Trp53 heterozygous C57BL/6 mice

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Burchart, P.; Wyatt, H.

    2008-01-01

    Low doses of ionizing radiation to cells and animals may induce adaptive responses that reduce the risk of cancer. However, there are upper dose thresholds above which these protective adaptive responses do not occur. We have now tested the hypothesis that there are similar lower dose thresholds that must be exceeded in order to induce protective effects in vivo. We examined the effects of low dose/low dose rate fractionated exposures on cancer formation in Trp53 normal or cancer-prone Trp53 heterozygous female C57BL/6 mice. Beginning at 6 weeks of age, mice were exposed 5 days/week to single daily doses (0.33 mGy, 0.7 mGy/h) totaling 48, 97 or 146 mGy over 30, 60 or 90 weeks. The exposures for shorter times (up to 60 weeks) appeared to be below the level necessary to induce overall protective adaptive responses in Trp53 normal mice, and detrimental effects (shortened lifespan, increased frequency) evident for only specific tumor types (B- and T-cell lymphomas), were produced. Only when the exposures were continued for 90 weeks did the dose become sufficient to induce protective adaptive responses, balancing the detrimental effects for these specific cancers, and reducing the risk level back to that of the unexposed animals. Detrimental effects were not seen for other tumor types, and a protective effect was seen for sarcomas after 60 weeks of exposure, which was then lost when the exposure continued for 90 weeks. As previously shown for the upper dose threshold for protection by low doses, the lower dose boundary between protection and harm was influenced by Trp53 functionality. Neither protection nor harm was observed in exposed Trp53 heterozygous mice, indicating that reduced Trp53 function raises the lower dose/dose rate threshold for both detrimental and protective tumorigenic effects. (author)

  6. Improved Screening Test for Idiopathic Infantile Hypercalcemia Confirms Residual Levels of Serum 24,25-(OH)2 D3 in Affected Patients.

    Science.gov (United States)

    Kaufmann, Martin; Morse, Nicole; Molloy, Billy Joe; Cooper, Donald P; Schlingmann, Karl Peter; Molin, Arnaud; Kottler, Marie Laure; Gallagher, J Christopher; Armas, Laura; Jones, Glenville

    2017-07-01

    CYP24A1 mutations are now accepted as a cause of idiopathic infantile hypercalcemia (IIH). A rapid liquid-chromatography tandem mass spectrometry (LC-MS/MS)-based blood test enabling measurement of the 25-OH-D 3 :24,25-(OH) 2 D 3 ratio (R) can identify IIH patients on the basis of reduced C24-hydroxylation of 25-OH-D 3 by CYP24A1 in vivo. Although values of this ratio are significantly elevated in IIH, somewhat surprisingly, serum 24,25-(OH) 2 D 3 remains detectable. The current study explores possible explanations for this including: residual CYP24A1 enzyme activity in individuals with certain CYP24A1 genotypes, expression of alternative C24-hydroxylases, and the possibility of isobaric contamination of the 24,25-(OH) 2 D 3 peak on LC-MS/MS. We employed an extended 20-min run time on LC-MS/MS to study serum vitamin D metabolites in patients with IIH due to mutations of CYP24A1 or SLC34A1; in unaffected heterozygotes and dialysis patients; in patients with vitamin D deficiency; as well as in normal subjects exhibiting a broad range of 25-OH-D levels. We identified 25,26-(OH) 2 D 3 as a contaminant of the 24,25-(OH) 2 D 3 peak. In normals, the concentration of 24,25-(OH) 2 D 3 greatly exceeds 25,26-(OH) 2 D 3 ; however, 25,26-(OH) 2 D 3 becomes more significant in IIH with CYP24A1 mutations and in dialysis patients, where 24,25-(OH) 2 D 3 levels are low when CYP24A1 function is compromised. Mean R in 30 IIH-CYP24A1 patients was 700 (range, 166 to 2168; cutoff = 140) as compared with 31 in 163 controls. Furthermore, patients possessing CYP24A1 L409S alleles exhibited higher 24,25-(OH) 2 D 3 levels and lower R (mean R = 268; n = 8) than patients with other mutations. We conclude that a chromatographic approach which resolves 24,25-(OH) 2 D 3 from 25,26-(OH) 2 D 3 produces a more accurate R that can be used to differentiate pathological states where CYP24A1 activity is altered. The origin of the residual serum 24,25-(OH) 2 D 3 in IIH patients appears to be

  7. Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non-Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60 Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells

    DEFF Research Database (Denmark)

    Nordentoft, Iver Kristiansen; Jeppesen, Per Bendix; Nielsen, Anders Lade

    2007-01-01

    In the present study we investigate the expression levels of cytosolic phospholipase A2 alpha (cPLA2alpha) interacting histone acetyl transferase proteins TIP60alpha and TIP60beta in non-diabetic C57BL wild-type mice and obese type 2 diabetic KKAy model mice. The aim was to test our hypothesis...

  8. Protection efficacy of the Brucella abortus ghost vaccine candidate lysed by the N-terminal 24-amino acid fragment (GI24) of the 36-amino acid peptide PMAP-36 (porcine myeloid antimicrobial peptide 36) in murine models.

    Science.gov (United States)

    Kwon, Ae Jeong; Moon, Ja Young; Kim, Won Kyong; Kim, Suk; Hur, Jin

    2016-11-01

    Brucella abortus cells were lysed by the N-terminal 24-amino acid fragment (GI24) of the 36-amino acid peptide PMAP-36 (porcine myeloid antimicrobial peptide 36). Next, the protection efficacy of the lysed fragment as a vaccine candidate was evaluated. Group A mice were immunized with sterile PBS, group B mice were intraperitoneally (ip) immunized with 3 × 10 8 colony-forming units (CFUs) of B. abortus strain RB51, group C mice were immunized ip with 3 × 10 8 cells of the B. abortus vaccine candidate, and group D mice were orally immunized with 3 × 10 9 cells of the B. abortus vaccine candidate. Brucella lipopolysaccharide (LPS)-specific serum IgG titers were considerably higher in groups C and D than in group A. The levels of interleukin (IL)-4, IL-10, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) were significantly higher in groups B-D than in group A. After an ip challenge with B. abortus 544, only group C mice showed a significant level of protection as compared to group A. Overall, these results show that ip immunization with a vaccine candidate lysed by GI24 can effectively protect mice from systemic infection with virulent B. abortus.

  9. Protective effect of WR-2823 in irradiated mice

    International Nuclear Information System (INIS)

    Milovanovicj, A.; Tanasijevicj, D.; Cvetkovicj, M.; Cjosicj, M.; Chizmicj, Z.

    1987-01-01

    A chemical compound named WR-2823 has been synthetised. The acute toxicity after IP application has been investigated and LD 50 estimated. The protective ability of the radioprotector has been investigated in mice with gamma rays of 60 Co, or at the origin of 252 Cf. High protective potency in mice, treated with lethal doses of gamma rays and neutrons have been estimated. (author) 8 refs.; 1 tab

  10. Andrographolide protects against radiation-induced lung injury in mice

    International Nuclear Information System (INIS)

    Kang Yahui; Wang Jinfeng; Zhang Qu; Huang Guanhong; Ma Jianxin; Yang Baixia; He Xiangfeng; Wang Zhongming

    2014-01-01

    Objective: To investigate the protective effect of andrographolide against radiation-induced lung injury (RILI) in C57BL/6 mice. Methods: Eighty C57BL mice were randomly divided into four groups: un-irradiated and normal saline-treated group (n = 20, control group), un-irradiated and andrographolide-treated group (n = 20, drug group), radiation plus normal saline-treated group (n = 20, radiation group) and radiation plus andrographolide-treated group (n = 20, treatment group). Before radiation, the mice in drug group and treatment group were administered daily via gavage with andrographolide (20 mg·kg -1 ·d -1 )) for 30 d, while the same volume of normal saline solution was given daily in the control and radiation groups. The model of RILI in C57BL mice was established by irradiating whole mouse chest with a single dose of 15 Gy of 6 MV X-rays. The pathological changes of the lung stained with HE/Masson were observed with a light microscope. The transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) in serum were examined by enzyme-linked immunosorbent assay. The activities of malondialdehyde (MDA) and superoxide dismutase (SOD) and the content of hydroxyproline in lung tissues were examined by corresponding kits. Results: Compared with radiation group, there was an obvious amelioration in pathological injury of lung tissue in the treatment group. The lung coefficient, the activities of lung tissue MDA, the content of Hyp, the serum content of hydroxide free radical, and the serum levels of TGF-β1 and TNF-α in the treatment group were significantly lower than those in radiation group at 24 th week, (t lung coefficient = 1.60, t MDA = 7.06, t Hyp = 17.44, t TGF-β1 = 16.67, t TNF-α = 14.03, P < 0.05), while slightly higher than those in control group. The activity of SOD was significantly higher in the treatment group than that in radiation group (t = 60.81, P < 0.05), while lower than those in control group and drug group. There were no

  11. γ-irradiation-induced mortality: protective effect of protease inhibitors in chickens and mice

    International Nuclear Information System (INIS)

    Palladino, M.A.; Galton, J.E.; Troll, W.; Thorbecke, G.J.

    1982-01-01

    Chickens (Gallus domesticus) were protected from the acute γ-irradiation-induced mortality (within 24 hours) by the proteolytic enzyme inhibitors, soy-bean trypsin inhibitor (SBTI), lima bean inhibitor (LBTI), antipain, α-N-benzoyl-L-arginine ethyl ester HCl (BAEE), trasylol, and leupeptin. Several other enzyme inhibitors, p-tosyl-L-arginine methyl ester HCl (TAME), α-tosyl-lysyl-chloromethyl ketone HCl (TLCK) and epsilon-amino caproic acid (EACA), did not protect. EACA even increased the mortality caused by γ-irradiation. The pattern of protective enzyme inhibitors suggests involvement of a kallikrein-like enzyme. SBTI and antipain also protected against low range lethal γ-irradiation exposures, 690 R in BALB/c and 880 R in SJL/J mice. It is suggested that enhanced vascular permeability, which in chickens is known to be the cause of the irradiation mortality during the first 24 hours, may also contribute to the mortality in mice during the first week after irradiation. (author)

  12. [Chinese medicinal monomer and compound for 60Co-gamma-induced spermatogenic disturbance in mice].

    Science.gov (United States)

    Zhang, Wei-xing; Wang, Hua-li; Wang, Rui; Li, Rui; He, Wei; Zhang, Tian-biao

    2010-05-01

    To explore the effects of the monomer and compound of the Chinese herbal drugs resveratrol, lycium barbarum polysaccharide (LBP) and icariin on 60Co-gamma-induced spermatogenic disturbance in mice based on the theory of modern Chinese medicine. A total of 105 male Kunming mice were randomly divided into seven groups, with 15 in each. Group A were normally raised and Groups B, C, D, E, F and G irradiated by 60Co-gamma 6 Gy followed by 60Co-gamma 4 Gy at the interval of 7 days. A week later, Groups C, D, E, F and G received intragastrically the suspension of resveratrol, resveratrol + LBP, resveratrol + icariin, resveratrol + LBP + icariin and resveratrol + LBP + icariin + L-carnitine, respectively, at the dose of 80 mg/(kg x d) for 60 days. The general condition, physical signs and body weight changes of the mice were recorded, and 24 hours after the intragastric medication, their testes were harvested to obtain the testicular weight and indexes, the levels of FSH, LH, T and E2 determined by ELISA, the T/E2 ratio calculated, and the histology of the testis tissues observed under the microscope. The testicular indexes of the mice were decreased by radiation-induced damage, but restored to some extent after intragastric medication, especially in Groups E, F and G. The levels of FSH, LH and T were obviously improved by LBP. The T level and testis weight were increased by Icariin. The level of T/E2 was elevated in Groups E, F and G. The best results were achieved in Group F, which exhibited almost complete recovery from reproductive endocrine disorder and spermatogenic damage. The Chinese medicinal monomer is effective for 60Co-gamma-induced spermatogenic disturbance in mice, and the compound suspension of resveratrol + LBP + icariin produces the best result.

  13. Immunogenicity is unrelated to protective immunity when induced by soluble and particulate antigens from Nocardia brasiliensis in BALB/c mice.

    Science.gov (United States)

    Salinas-Carmona, Mario C; Ramos, Alma I; Pérez-Rivera, Isabel

    2006-08-01

    Cell-mediated immunity plays a major role in protection against intracellular microbes. Nocardia brasiliensis is a facultative intracellular pathogen that causes chronic actinomycetoma. In this work, we injected BALB/c mice with soluble P24 and particulate antigens from N. brasiliensis. A higher antibody titer and lymphocyte proliferation was induced by the particulate antigen than by the soluble antigen. However, five months after antigen injection, antibody concentration and lymphocyte proliferation were similar. An increase in CD45R and CD4 T cells was unrelated to protective immunity. Active immunization with soluble or particulate antigens induced complete protection during the primary immune response. This protective response was IgM mediated. The higher immunogenicity was not related to protective immunity since the particulate antigen induced protection similar to the soluble antigen. Using particulate antigens for vaccination guarantees a stronger immune response, local and systemic side effects, but not necessarily protection.

  14. Effects of carbon nanomaterials fullerene C60 and fullerol C60(OH)18–22 on gills of fish Cyprinus carpio (Cyprinidae) exposed to ultraviolet radiation

    International Nuclear Information System (INIS)

    Socoowski Britto, Roberta; Longaray Garcia, Márcia; Martins da Rocha, Alessandra; Artigas Flores, Juliana; Pinheiro, Maurício V. Brant; Monserrat, José María; Ribas Ferreira, Josencler L.

    2012-01-01

    In consequence of their growing use and demand, the inevitable environmental presence of nanomaterials (NMs) has raised concerns about their potential deleterious effects to aquatic environments. The carbon NM fullerene (C 60 ), which forms colloidal aggregates in water, and its water-soluble derivative fullerol (C 60 (OH) 18–22 ), which possesses antioxidant properties, are known to be photo-excited by ultraviolet (UV) or visible light. To investigate their potential hazards to aquatic organisms upon exposure to UV sunlight, this study analyzed (a) the in vitro behavior of fullerene and fullerol against peroxyl radicals (ROO·) under UV-A radiation and (b) the effects of these photo-excited NMs on oxidative stress parameters in functional gills extracted from the fish Cyprinus carpio (Cyprinidae). The variables measured were the total antioxidant capacity, lipid peroxidation (TBARS), the activities of the antioxidant enzymes glutathione reductase (GR) and glutamate cysteine ligase (GCL), and the levels of the non-enzymatic antioxidant glutathione (GSH). The obtained results revealed the following: (1) both NMs behaved in vitro as antioxidants against ROO· in the dark and as pro-oxidants in presence of UV-A, the latter effect being reversed by the addition of sodium azide, which is a singlet oxygen ( 1 O 2 ) quencher; (2) fullerene induced toxicity with or without UV-A incidence, with a significant (p 1 O 2 generation; and (3) fullerol also decreased GCL activity and GSH formation (p 1 O 2 formation.

  15. Comparison of Protective Effect of Green Tea and Vitamin C Against Cypermethrin Induce Nephrotoxicity in Mice

    International Nuclear Information System (INIS)

    Manzoor, S.; Mehboob, K.; Naveed, A. K.

    2016-01-01

    Background: Insecticide toxicity is the problem of every person in under developed countries. It is necessary to counteract its effect by natural and cheap remedies like green tea and vitamin C. In this manner common man can also enjoy blessings of life. The current research was performed to compare the protective function of green tea and vitamin C on experimental cypermethrin provoked nephrotoxicity Method: Forty healthy Balb/C mice purchased from National Institute of Health, Islamabad, Pakistan and divided in to four groups (10 each). Group a was control which received only normal diet. Group B, group C and group D were experimental groups which were given Cypermethrin, Cypermethrin with green tea and Cypermethrin with vitamin C respectively. These groups were also given normal diet. After 1 month blood was drawn by intra-cardiac method to assess renal parameters. Results: One month research showed increase in serum urea to 6.8±.48 m.mol/l (n=3.9±.44) while green tea and vitamin C normalize them to 4.0±.83 m.mol/l and 3.4±.33 m.mol/l respectively. Serum creatinine increased to 42.90±3.28 m.mol/l (n=29.50±3.95) while green tea and vitamin C normalize them to 28.80±4.58 m.mol/l and 22.60±2.06 m.mol/l correspondingly. Conclusion The results showed that green tea and vitamin C neutralized toxicity induced by Cypermethrin in mice and their effect is comparable. (author)

  16. Protection of C57BL/10 mice by vaccination with association of purified proteins from Leishmania (Leishmania amazonensis

    Directory of Open Access Journals (Sweden)

    MORA Ana Mariela

    1999-01-01

    Full Text Available In the past few years, induction of protective immunity to cutaneous leishmaniasis has been attempted by many researchers using a variety of antigenic preparations, such as living promastigotes or promastigote extracts, partially purified, or defined proteins. In this study, eleven proteins from Leishmania (Leishmania amazonensis (LLa with estimated molecular mass ranging from 97 to 13.5kDa were isolated by polyacrylamide gel electrophoresis and electro-elution. The proteins were associated as vaccine in different preparations with gp63 and BCG (Bacilli Calmette-Guérin. The antigenicity of these vaccines was measured by their ability to induce the production of IFN-g by lymphocyte from subjects vaccinated with Leishvacinâ . The immunogenicity was evaluated in vaccinated mice. C57BL/10 mice were vaccinated with three doses of each vaccine consisting of 30 mg of each protein at 15 days interval. One hundred mg of live BCG was only used in the first dose. Seven days after the last dose, they received a first challenge infection with 105 infective promastigotes and four months later, a second challenge was done. Two months after the second challenge, 42.86% of protection was obtained in the group of mice vaccinated with association of proteins of gp63+46+22kDa, gp63+13.5+25+42kDa, gp63+46+42kDa, gp63+66kDa, and gp63+97kDa; 57.14% of protection was demonstrated with gp63+46+97+13.5kDa, gp63+46+97kDa, gp63+46+33kDa, and 71.43% protection for gp63 plus all proteins. The vaccine of gp63+46+40kDa that did not protect the mice, despite the good specific stimulation of lymphocytes (LSI = 7.60 and 10.77UI/ml of IFN-g production. When crude extract of L. (L. amazonensis was used with BCG a 57.14% of protection was found after the first challenge and 28.57% after the second, the same result was observed for gp63. The data obtained with the vaccines can suggest that the future vaccine probably have to contain, except the 40kDa, a cocktail of proteins that

  17. Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice

    Directory of Open Access Journals (Sweden)

    Yao Xin-Sheng

    2011-10-01

    Full Text Available Abstract Background Lutein is an important eye-protective nutrient. This study investigates the protective effects and mechanisms of lutein on lipopolysaccharides (LPS-induced uveitis in mice. Methods Lutein, suspended in drinking water at a final concentration of 12.5 and 25 mg/mL, was administered to mice at 0.1 mL/10 g body weight for five consecutive days. Control and model group received drinking water only. Uveitis was induced by injecting LPS (100 mg per mouse into the footpad in the model and lutein groups on day 5 after the last drug administration. Eyes of the mice were collected 24 hours after the LPS injection for the detection of indicators using commercial kits and reverse transcription-polymerase chain reaction. Results LPS-induced uveitis was confirmed by significant pathological damage and increased the nitric oxide level in eye tissue of BALB/C mice 24 hours after the footpad injection. The elevated nitric oxide level was significantly reduced by oral administration of lutein (125 and 500 mg/kg/d for five days before LPS injection. Moreover, lutein decreased the malondialdehyde content, increased the oxygen radical absorbance capacity level, glutathione, the vitamin C contents and total superoxide dismutase (SOD and glutathione peroxidase (GPx activities. Lutein further increased expressions of copper-zinc SOD, manganese SOD and GPx mRNA. Conclusion The antioxidant properties of lutein contribute to the protection against LPS-induced uveitis, partially through the intervention of inflammation process.

  18. Mutant Brucella abortus membrane fusogenic protein induces protection against challenge infection in mice.

    Science.gov (United States)

    de Souza Filho, Job Alves; de Paulo Martins, Vicente; Campos, Priscila Carneiro; Alves-Silva, Juliana; Santos, Nathalia V; de Oliveira, Fernanda Souza; Menezes, Gustavo B; Azevedo, Vasco; Cravero, Silvio Lorenzo; Oliveira, Sergio Costa

    2015-04-01

    Brucella species can cause brucellosis, a zoonotic disease that causes serious livestock economic losses and represents a public health threat. The mechanism of virulence of Brucella spp. is not yet fully understood. Therefore, it is crucial to identify new molecules that serve as virulence factors to better understand this host-pathogen interplay. Here, we evaluated the role of the Brucella membrane fusogenic protein (Mfp) and outer membrane protein 19 (Omp19) in bacterial pathogenesis. In this study, we showed that B. abortus Δmfp::kan and Δomp19::kan deletion mutant strains have reduced persistence in vivo in C57BL/6 and interferon regulatory factor 1 (IRF-1) knockout (KO) mice. Additionally, 24 h after macrophage infection with a Δmfp::kan or Δomp19::kan strain expressing green fluorescent protein (GFP) approximately 80% or 65% of Brucella-containing vacuoles (BCVs) retained the late endosomal/lysosomal marker LAMP-1, respectively, whereas around 60% of BCVs containing wild-type S2308 were found in LAMP-1-negative compartments. B. abortus Δomp19::kan was attenuated in vivo but had a residual virulence in C57BL/6 and IRF-1 KO mice, whereas the Δmfp::kan strain had a lower virulence in these same mouse models. Furthermore, Δmfp::kan and Δomp19::kan strains were used as live vaccines. Challenge experiments revealed that in C57BL/6 and IRF-1 KO mice, the Δmfp::kan strain induced greater protection than the vaccine RB51 and protection similar that of vaccine S19. However, a Δomp19::kan strain induced protection similar to that of RB51. Thus, these results demonstrate that Brucella Mfp and Omp19 are critical for full bacterial virulence and that the Δmfp::kan mutant may serve as a potential vaccine candidate in future studies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Myricetin protects against diet-induced obesity and ameliorates oxidative stress in C57BL/6 mice.

    Science.gov (United States)

    Su, Hong-Ming; Feng, Li-Na; Zheng, Xiao-Dong; Chen, Wei

    2016-06-01

    Myricetin is a naturally occurring antioxidant commonly found in various plants. However, little information is available with respect to its direct anti-obesity effects. This study was undertaken to investigate the effect of myricetin on high-fat diet (HFD)-induced obesity in C57BL/6 mice. Administration of myricetin dramatically reduced the body weight of diet-induced obese mice compared with solely HFD-induced mice. Several parameters related to obesity including serum glucose, triglyceride, and cholesterol were significantly decreased in myricetin-treated mice. Moreover, obesity-associated oxidative stress (glutathione peroxidase (GPX) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA)) and inflammation (tumor necrosis factor-α (TNF-α)) were ameliorated in myricetin-treated mice. Further investigation revealed that the protective effect of myricetin against HFD-induced obesity in mice appeared to be partially mediated through the down-regulation of mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP-1c). Consumption of myricetin may help to prevent obesity and obesity-related metabolic complications.

  20. 40 CFR 60.57c - Monitoring requirements.

    Science.gov (United States)

    2010-07-01

    ... 60.57c Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... defined in § 60.50c(a)(3) and (4) that uses selective noncatalytic reduction technology shall install... date, time, and duration. (d) The owner or operator of an affected facility using an air pollution...

  1. 40 CFR 60.55c - Waste management plan.

    Science.gov (United States)

    2010-07-01

    ... management plan shall identify both the feasibility and the approach to separate certain components of solid... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Waste management plan. 60.55c Section 60.55c Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED...

  2. Melatonin and sesamol protects spleenocytes against 60Co γ-irradiation induced damages in male C57BL/6 mice

    International Nuclear Information System (INIS)

    Khan, Shahanshah; Rizvi, Moshahid; Kumar, Arun; Kalra, Nmita; Adhikari, Jawahar; Chaudhury, Nabo; Khan, Shahanshah

    2013-01-01

    Natural antioxidants have strong potential for development of radioprotectors. In earlier studies we have shown radioprotective efficacy of melatonin/sesamol (100 mg/kg body weight) in recovery of whole-body γ-irradiated (7.5 Gy) induced damages in gastrointestinal tract and germ cells. In the present study, we report detailed studies on spleenocytes. Therefore, the first objectives of these studies, to determine the antioxidant capacity of spleen induced by melatonin/sesamol. Second, to investigate the radioprotective effect of melatonin/sesamol in spleenocytes of whole-body γ-irradiated male C57BL/6 mice. Animals (8-9 week-old) were divided into six groups e.g., control, melatonin/sesamol (100 mg/kg body weight through intra-peritoneal), radiation (7.5 Gy, 1 Gy/minute, whole-body using 60 Co Tele-therapy unit), melatonin/sesamol+radiation (100 mg/kg body weight 30 minute prior to 7.5 Gy). Mice were sacrificed at 30 minutes and their spleen homogenates (10% w/v in PBS) were used for ABTS and DPPH assays.Those mice sacrificed on 4th, 7th, 15th, 21st and 30th day post-irradiation were used for immunological investigations (Annexin-V, CD4/CD8, Cell Cycle) by flow cytometry. Relative spleen mass was determined by dividing spleen mass(mg) with body mass(gm). ABTS and DPPH assays in spleen showed higher level of antioxidant capacity in melatonin/sesamol treated groups (p<0.009) from control group at 30 minute. Melatonin/sesamol+radiation treated groups significantly reduce apoptosis (p<0.026) and recover CD4+ and CD8+ T cells populations (p<0.022) as well as their ratio onwards 4th day post-irradiation in spleen as compared to radiation group. Melatonin/sesamol+radiation treated groups also showed recovery in radiation induced cell cycle perturbation and relative spleen mass from 7th day post-irradiation as compared to radiation group. Therefore, it is concluded that a single dose of 100 mg/kg body weight of melatonin/sesamol prior to 30 minute increase the capacity

  3. Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice.

    Science.gov (United States)

    McCullough, Rebecca L; McMullen, Megan R; Das, Dola; Roychowdhury, Sanjoy; Strainic, Michael G; Medof, M Edward; Nagy, Laura E

    2016-07-01

    Complement is implicated in the development of alcoholic liver disease. C3 and C5 contribute to ethanol-induced liver injury; however, the role of C5a receptor (C5aR) on myeloid and non-myeloid cells to progression of injury is not known. C57BL/6 (WT), global C5aR-/-, myeloid-specific C5aR-/-, and non-myeloid-specific C5aR-/- mice were fed a Lieber-DeCarli diet (32%kcal EtOH) for 25 days. Cultured hepatocytes were challenged with ethanol, TNFα, and C5a. Chronic ethanol feeding increased expression of pro-inflammatory mediators in livers of WT mice; this response was completely blunted in C5aR-/- mice. However, C5aR-/- mice were not protected from other measures of hepatocellular damage, including ethanol-induced increases in hepatic triglycerides, plasma alanine aminotransferase and hepatocyte apoptosis. CYP2E1 and 4-hydroxynonenal protein adducts were induced in WT and C5aR-/- mice. Myeloid-specific C5aR-/- mice were protected from ethanol-induced increases in hepatic TNFα, whereas non-myeloid-specific C5aR-/- displayed increased hepatocyte apoptosis and inflammation after chronic ethanol feeding. In cultured hepatocytes, cytotoxicity induced by challenge with ethanol and TNFα was completely eliminated by treatment with C5a in cells from WT, but not C5aR-/- mice. Further, treatment with C5a enhanced activation of pro-survival signal AKT in hepatocytes challenged with ethanol and TNFα. Taken together, these data reveal a differential role for C5aR during ethanol-induced liver inflammation and injury, with C5aR on myeloid cells contributing to ethanol-induced inflammatory cytokine expression, while non-myeloid C5aR protects hepatocytes from death after chronic ethanol feeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody protects mice from morbidity without interfering with the development of protective immunity to subsequent homologous challenge.

    Science.gov (United States)

    Wilson, Jason R; Belser, Jessica A; DaSilva, Juliana; Guo, Zhu; Sun, Xiangjie; Gansebom, Shane; Bai, Yaohui; Stark, Thomas J; Chang, Jessie; Carney, Paul; Levine, Min Z; Barnes, John; Stevens, James; Maines, Taronna R; Tumpey, Terrence M; York, Ian A

    2017-11-01

    The emergence of A(H7N9) virus strains with resistance to neuraminidase (NA) inhibitors highlights a critical need to discover new countermeasures for treatment of A(H7N9) virus-infected patients. We previously described an anti-NA mAb (3c10-3) that has prophylactic and therapeutic efficacy in mice lethally challenged with A(H7N9) virus when delivered intraperitoneally (i.p.). Here we show that intrananasal (i.n.) administration of 3c10-3 protects 100% of mice from mortality when treated 24h post-challenge and further characterize the protective efficacy of 3c10-3 using a nonlethal A(H7N9) challenge model. Administration of 3c10-3 i.p. 24h prior to challenge resulted in a significant decrease in viral lung titers and deep sequencing analysis indicated that treatment did not consistently select for viral variants in NA. Furthermore, prophylactic administration of 3c10-3 did not inhibit the development of protective immunity to subsequent homologous virus re-challenge. Taken together, 3c10-3 highlights the potential use of anti-NA mAb to mitigate influenza virus infection. Published by Elsevier Inc.

  5. Asymmetric fission and evaporation of C60r+ (r = 2-4) fullerene ions in ion-C60 collisions: I. Proton results

    International Nuclear Information System (INIS)

    Rentenier, A; Bordenave-Montesquieu, A; Moretto-Capelle, P; Bordenave-Montesquieu, D

    2004-01-01

    A quantitative description of the asymmetric fission (AF) of C 60 r+ fullerene ions (r = 2-4), using a multistop coincidence technique between both fragment ions, is presented. Charged light fragment (LF) and heavy fragment (HF) size distributions are discussed together with the corresponding averaged sizes. Complete AF distributions are reported for the first time for C 60 2+ ions. Simple dependences of the more probable channels and averaged fragment sizes on the partner size are found and discussed. The LF ones are not very sensitive to the parent fullerene ion charge r and vary linearly with the HF size at least for the largest ones. On the other hand the HF ones present an oscillating dependence against the LF size, the odd-numbered LFs being correlated to a smaller HF size, and depend on r. In the comparison of branching ratios between AF and the competing pure neutral evaporation channel, some emphasis is given to the behaviour of the unimolecular processes with r which are compared with the evolution of the activation energies and fission barriers. From a close examination of the individual HF distributions the production mechanisms of odd-n fragments are discussed, and the most probable dissociation channels of even-numbered C n + excited carbon clusters identified. Finally, an analysis of the neutral channels is also presented for the first time, the total neutral mass N (in carbon units) being deduced from the mass conservation law. Surprising similarities between the charged LF- and N-distributions are found. AF processes are also identified where light neutrals and ions play a symmetrical role. These findings lead us to suggest that a concerted emission of ions and heavy neutrals is probably a fission mechanism to be considered to understand the AF process of the C 60 molecule in addition to the often assumed multistep fragmentation cascade scheme

  6. Immunization of C57BL/6 Mice with GRA2 Combined with MPL Conferred Partial Immune Protection against Toxoplasma gondii

    Science.gov (United States)

    Babaie, Jalal; Amiri, Samira; Homayoun, Robab; Azimi, Ebrahim; Mohabati, Reyhaneh; Berizi, Mahboobe; Sadaie, M. Reza; Golkar, Majid

    2018-01-01

    We have previously reported that immunization with GRA2 antigen of Toxoplasma gondii induces protective immunity in CBA/J (H2k) and BALB/c mice (H2d). We aimed to examine whether immunization of a distinct strain of rodent with recombinant dense granule antigens (GRA2) combined with monophosphorryl lipid A (MPL) adjuvant elicits protective immune response against T. gondii. C57BL/6 (H2b haplotype) mice were immunized with GRA2, formulated in MPL adjuvant. Strong humoral response, predominantly of IgG1 subclass and cellular response, IFN-γ, was detected at three weeks post immunization. Mice immunized with GRA2 had significantly (p < 0.01) fewer brain cysts than those in the adjuvant group, upon challenge infection. Despite the production of a strong antibody response, IFN-γ production and brain cyst reduction were not significant when the immunized mice were infected four months after the immunization. We can conclude that GRA2 immunization partially protects against T. gondii infection in C57BL/6 mice, though the potency and longevity of this antigen as a standalone vaccine may vary in distinct genetic backgrounds. This observation further emphasizes the utility of GRA2 for incorporation into a multi-antigenic vaccine against T. gondii.

  7. Adverse Effects of Caffeine on Development of Femur of BALB/c Mice and Protective Role of Vitamin D/sub 3/

    International Nuclear Information System (INIS)

    Khan, M.; Butt, S. A.

    2017-01-01

    Objective: To determine the effects of caffeine ingestion on the development of femur and role of vitamin D3 in preventing these effects in BALB/c mice. Study Design: Experimental study. Place and Duration of Study: Department of Anatomy, Army Medical College, Rawalpindi, in cooperation with NIH(National Institute of Health), Islamabad, from October 2014 to October 2015. Methodology: Thirty (100%) BALB/c mice, 50% male and female each, three weeks old, weighing 12-14 grams were taken and divided equally and randomly into three groups, each having 10 (33.3%) mice; 5 (16.6%) male and female. G1 (control group) was given normal diet with water ad libitum. G2 and G3 (experimental groups) were given 10 mg of caffeine per 100g body weight, three days a week, through oral gavage for 60 days on alternate days. However, experimental group G3 was additionally provided 0.1 micro g vitamin D3 daily, through oral gavage for 60 days. Experimental groups were compared with control group and data was analyzed statistically. Results: The mean weight of mice femur of G1(control group) was 0.387+-0.019 g; while mean weights of right femur of G2 and G3 (experimental groups) were 0.316+-0.020 g and 0.345+-0.020 g, respectively. Similarly, mean right femur length of group G1 was 20.70 +- 0.609 mm; while for groups G2 and G3, it was 24.382 +- 1.087 mm and 22.966 +- 0.822 mm, respectively. In comparison with group G1 for groups G2 and G3, femur weight decreased, however femur length increased. Conclusion: Caffeine intake caused femur length to increase and weight to decrease, but treatment with vitamin D3 ameliorated these effects of caffeine. (author)

  8. Protective effect of melatonin on thrombocytopoiesis in irratiated mice

    International Nuclear Information System (INIS)

    Liu Aiguo; Hu Qun; Yang Mo; Li Zhiguang; Huang Weizhe; Pang Yaxuan; Li Guixia; Wu Baixiang; Huo Taihui

    2005-01-01

    Objective: To study the protective effect of melatonin on thrombocytopoiesis (T) and its mechanism in total-bodily irradiated mice. Methods: Altogether 18 female BALB/c mice were randomly divided into three experimental groups (6 each): Group 1(normal control, N) received neither irradiation nor melatonin; Group 2 (model control, C); received total body-irradiation for 4 Gy gamma-rays and Group 3 (melatonin, M), received melatonin after irradiation at the dosage of 10 mg·kg -1 ·d -1 via i. p. injection in consecutive 21 days. In Group C normal saline instead of melatonin was administered in the same way as above. Peripheral blood platelets and white blood cells (WBC) were analyzed for the three groups on day 0, day 7, day 14, and day 21. All the mice were sacrificed to collect bone marrow cells for the assays of colony-forming unit-megakaryocyte (CFU-MK) and of colony-forming unit-fibroblast (CFU-F). The effects of melatonin of different concentrations (0-500 nmol/L) on CFU-MK formation were observed in vitro. Results: The results showed that melatonin enhanced the recovery of T. Moreover, melatonin also promoted the increase of CFU-F (28 ± 10.4 vs 14.6 ± 2.8) and CFU-MK (19.63 ± 3.28 vs 11 ± 2.24) in vivo. The amount of CFU-MK in vitro was dependent on the concentration of melatonin. Compared with the control group, the size of CFU-MK in Group M was much larger and MK cells were more mature, especially when the melatonin concentration was 200 nmol/L. Conclusion: Melatonin provides protective effect on T in irradiated mice. It enhances T in vivo and promotes the growth of bone marrow stromal cells as well as megakaryocytes in vitro. Therefore, we speculate that the T-protective activity of melatonin may be mediated via promoting growth of the progenitors of platelet, megakaryocytes, and bone marrow stromal cells. (authors)

  9. Protective effect of gingerol on leucocyte and bone marrow DNA of 60Co γ-rays irradiated mice

    International Nuclear Information System (INIS)

    Xie Zhenfei; Zhou Yu; Geng Yanyan; Zeng Xianyin

    2012-01-01

    In this article, the effect of gingerol on peripheral leucocyte and bone marrow DNA of 60 Co γ-rays irradiated mice was developed., Twenty-four healthy healthy female Kunming mice were randomly divided into 4 groups: control, gingerol, irradiation and gingerol + irradiation group. Gingerol group and gingerol + irradiation group were given gingerol intragastrically once a day for five days. Irradiation group and gingerol + irradiation group were suffered from 5 Gy 60 Co γ-rays irradiation at the rate of 1.2 Gy/min on the 6 th day. Blood samples, spleens, livers and thigh bones were collected to be measured after 48 h. The results showed that, compared with irradiation group, gingerol + irradiation group had significantly higher spleen index (p 60 Co γ-rays irradiated mice. (authors)

  10. Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice.

    Science.gov (United States)

    Bocco, B M; Fernandes, G W; Lorena, F B; Cysneiros, R M; Christoffolete, M A; Grecco, S S; Lancellotti, C L; Romoff, P; Lago, J H G; Bianco, A C; Ribeiro, M O

    2016-03-01

    Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

  11. Histopathological studies show protective efficacy of Hippophae leaf extract against damage to jejunum in whole body 60Co-a-irradiated mice

    International Nuclear Information System (INIS)

    Gupta, Manish; Prasad, Jagdish; Madhu Bala

    2012-01-01

    Background: Ionizing radiation affect living tissue by causing majority of in vivo damage by free radical production. Earlier we reported that our preparation from Hippophae leaf offered survival benefit to >90% mice population which was whole body irradiated ( 60 Co-a-rays, 10 Gy). Objective: This study was planned to examine the protective effects of our drug (from Hippophae leaf) on ( 60 Co-a-ray induced oxidative damage and histopathological changes in jejunum. Methods: Around 2 months old adult male Strain 'A' mice were irradiated (10 Gy). Drug was administered intraperitoneally (-30 mm.). Histological parameters were studied after staining the sections with hematoxylin and eosin. Malondialdehyde formation (index of lipid peroxidation), alkaline phosphatase activity, and total thiol content were determined by biochemical techniques. The data was obtained at different time interval upto 30 days. Results: Biochemical studies showed that in comparison to the untreated controls, in the irradiated (10 Gy) mice, there was significant increase in the alkaline phosphatase activity and level of malondialdehyde whereas decrease in total thiol content within 2 days. Histological studies showed that whole body irradiation (10 Gy), damaged the jejunam crypt cells and decreased the villi height within 2 days. Intra-peritoneal administration of drug, 30 mm prior to irradiation, protected the crypt cells and villi height, countered the radiation induced increase in alkaline phosphatase activity and lipid peroxidation and values were comparable to the level of control in 30 days. Conclusions: These biochemical and histopathological studies suggested that our drug can offer effective radioprotection against the oxidative damage to jejunum in vivo. (author)

  12. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

    Directory of Open Access Journals (Sweden)

    Barbara D Boyan

    Full Text Available Osteoarthritis (OA in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OHD3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH2D3] accumulates in articular cartilage following injection of [3H]-25(OHD3. Previously, we showed that 24R,25(OH2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH2D3 or 1α,25(OH2D3. 24R,25(OH2D3 but not 1α,25(OH2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH2D3 or vehicle (t = 0, 7, 14, 21 days. Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis.

  13. Highly Stable [C60AuC60]+/- Dumbbells.

    Science.gov (United States)

    Goulart, Marcelo; Kuhn, Martin; Martini, Paul; Chen, Lei; Hagelberg, Frank; Kaiser, Alexander; Scheier, Paul; Ellis, Andrew M

    2018-05-17

    Ionic complexes between gold and C 60 have been observed for the first time. Cations and anions of the type [Au(C 60 ) 2 ] +/- are shown to have particular stability. Calculations suggest that these ions adopt a C 60 -Au-C 60 sandwich-like (dumbbell) structure, which is reminiscent of [XAuX] +/- ions previously observed for much smaller ligands. The [Au(C 60 ) 2 ] +/- ions can be regarded as Au(I) complexes, regardless of whether the net charge is positive or negative, but in both cases, the charge transfer between the Au and C 60 is incomplete, most likely because of a covalent contribution to the Au-C 60 binding. The C 60 -Au-C 60 dumbbell structure represents a new architecture in fullerene chemistry that might be replicable in synthetic nanostructures.

  14. Humoral immunity through immunoglobulin M protects mice from an experimental actinomycetoma infection by Nocardia brasiliensis.

    Science.gov (United States)

    Salinas-Carmona, Mario C; Pérez-Rivera, Isabel

    2004-10-01

    An experimental model of infection with Nocardia brasiliensis, used as an example of a facultative intracellular pathogen, was tested. N. brasiliensis was injected into the rear foot pads of BALB/c mice to establish an infection. Within 30 days, infected animals developed a chronic actinomycetoma infection. Batch cultures of N. brasiliensis were used to purify P61, P38, and P24 antigens; P61 is a catalase, and P38 is a protease with strong caseinolytic activity. Active and passive immunizations of BALB/c mice with these three purified soluble antigens were studied. Protection was demonstrated for actively immunized mice. However, immunity lasted only 30 days. Other groups of immunized mice were bled at different times, and their sera were passively transferred to naive recipients that were then infected with N. brasiliensis. Sera collected 5, 6, and 7 days after donor immunization conferred complete, long-lasting protection. The protective effect of passive immunity decreased when sera were collected 2 weeks after donor immunization. However, neither the early sera (1-, 2-, and 3-day sera) nor the later sera (30- or 45-day sera) prevented the infection. Hyperimmune sera with the highest levels of immunoglobulin G (IgG) to N. brasiliensis antigens did not protect at all. The antigens tested induced two IgM peaks. The first peak was present 3 days after immunization but was not antigen specific and did not transfer protection. The second peak was evident 7 days after immunization, was an IgM response, was antigen specific, and conferred protection. This results clearly demonstrate that IgM antibodies protect the host against a facultative intracellular bacterium.

  15. Protective effects of lemongrass (Cymbopogon citratus STAPF) essential oil on DNA damage and carcinogenesis in female Balb/C mice.

    Science.gov (United States)

    Bidinotto, Lucas T; Costa, Celso A R A; Salvadori, Daisy M F; Costa, Mirtes; Rodrigues, Maria A M; Barbisan, Luís F

    2011-08-01

    This study investigated the protective effect of oral treatment with lemongrass (Cymbopogon citratus STAPF) essential oil (LGEO) on leukocyte DNA damage induced by N-methyl-N-nitrosurea (MNU). Also, the anticarcinogenic activity of LGEO was investigated in a multi-organ carcinogenesis bioassay induced by 7,12-dimethylbenz(a)antracene, 1,2-dimethylhydrazine and N-butyl-N-(4-hydroxibuthyl)nitrosamine in Balb/C female Balb/c mice (DDB-initiated mice). In the short-term study, the animals were allocated into three groups: vehicle group (negative control), MNU group (positive control) and LGEO 500 mg kg⁻¹ (five times per week for 5 weeks) plus MNU group (test group). Blood samples were collected to analyze leukocyte DNA damage by comet assay 4 h after each MNU application at the end of weeks 3 and 5. The LGEO 500 mg kg⁻¹ treated group showed significantly lower (P lemongrass essential oil provided protective action against MNU-induced DNA damage and a potential anticarcinogenic activity against mammary carcinogenesis in DDB-initiated female Balb/C mice. Copyright © 2010 John Wiley & Sons, Ltd.

  16. Humoral and cellular immune responses in BALB/c and C57BL/6 mice immunized with cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens, in acute experimental Trypanosoma cruzi infection.

    Science.gov (United States)

    Pereira, Valéria R A; Lorena, Virginia M B; Nakazawa, Mineo; Luna, Carlos F; Silva, Edimilson D; Ferreira, Antonio G P; Krieger, Marco Aurélio; Goldenberg, Samuel; Soares, Milena B P; Coutinho, Eridan M; Correa-Oliveira, Rodrigo; Gomes, Yara M

    2005-06-01

    In previous studies, cytoplasmic repetitive antigen (CRA) and flagellar repetitive antigen (FRA) proteins induced specific humoral and cellular immune responses in susceptible and resistant mice in the absence of Trypanosoma cruzi infection with a significant induction of the Interferon-gamma (IFN-gamma) production in those animals. In this follow-up paper, the immunostimulatory and protective effects of these proteins were evaluated by immunizing with CRA or FRA antigens, BALB/c and C57BL/6 mice and challenging with a T. cruzi (Y strain). Both proteins induced humoral response with high levels of IgG isotypes as well as cellular immunity with high levels of IFN-gamma when compared to controls. However, the lymphocyte proliferative response was minimal. The survival rate at 30 days post-infection was significant in CRA (60%) or FRA (50%)--immunized BALB/c mice and CRA (83.3%)--immunized C57BL/6 mice. Taken as a whole these findings indicate that CRA and FRA are immunogenic and potentially important for protective immunity.

  17. Vaccination evokes gender-dependent protection against tularemia infection in C57BL/6Tac mice.

    Science.gov (United States)

    Sunagar, Raju; Kumar, Sudeep; Franz, Brian J; Gosselin, Edmund J

    2016-06-17

    Francisella tularensis (Ft) is a Category A biothreat agent for which there currently is no FDA-approved vaccine. Thus, there is a substantial effort underway to develop an effective tularemia vaccine. While it is well established that gender can significantly impact susceptibility to primary infection, the impact of gender on vaccine efficacy is not well established. Thus, development of a successful vaccine against tularemia will require an understanding of the impact gender has on vaccine-induced protection against this organism. In this study, a role for gender in vaccine-induced protection following Ft challenge is identified for the first time. In the present study, mucosal vaccination with inactivated Ft (iFt) LVS elicited gender-based protection in C57BL/6Tac mice against respiratory challenge with Ft LVS. Specifically, vaccinated male mice were more susceptible to subsequent Ft LVS challenge. This increased susceptibility in male mice correlated with increased bacterial burden, increased tissue inflammation, and increased proinflammatory cytokine production late in post-challenge infection. In contrast, improved survival of iFt-vaccinated female mice correlated with reduced bacterial burden and enhanced levels of Ft-specific Abs in serum and broncho-alveolar lavage (BAL) fluid post-challenge. Furthermore, vaccination with a live attenuated vaccine consisting of an Ft LVS superoxide dismutase (SodB) mutant, which has proven efficacious against the highly virulent Ft SchuS4 strain, demonstrated similar gender bias in protection post-Ft SchuS4 challenge. Of particular significance is the fact that these are the first studies to demonstrate that gender differences impact disease outcome in the case of lethal respiratory tularemia following mucosal vaccination. In addition, these studies further emphasize the fact that gender differences must be a serious consideration in any future tularemia vaccine development studies. Copyright © 2016 Elsevier Ltd. All

  18. DNA vaccine expressing herpes simplex virus 1 glycoprotein C and D protects mice against herpes simplex keratitis

    Directory of Open Access Journals (Sweden)

    Li-Li Dong

    2017-11-01

    Full Text Available AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1 (HSV-1 glycoprotein C (gC and glycoprotein D (gD will achieve better protective effect against herpes simplex keratitis (HSK than DNA vaccine encoding gD alone. METHODS: DNA vaccine expressing gD or gC combined gD (gD.gC were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS: Fusion protein gD.gC could be expressed successfully in cultured 293T cells. And, pRSC-gC.gD-IL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and sIgA production, enhanced cytotoxicities of splenocytes and nature killer cells (NK, when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION: gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future.

  19. DNA vaccine expressing herpes simplex virus 1 glycoprotein C and D protects mice against herpes simplex keratitis

    Science.gov (United States)

    Dong, Li-Li; Tang, Ru; Zhai, Yu-Jia; Malla, Tejsu; Hu, Kai

    2017-01-01

    AIM To investigate whether DNA vaccine encoding herpes simplex virus 1 (HSV-1) glycoprotein C (gC) and glycoprotein D (gD) will achieve better protective effect against herpes simplex keratitis (HSK) than DNA vaccine encoding gD alone. METHODS DNA vaccine expressing gD or gC combined gD (gD.gC) were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS Fusion protein gD.gC could be expressed successfully in cultured 293T cells. And, pRSC-gC.gD-IL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and sIgA production, enhanced cytotoxicities of splenocytes and nature killer cells (NK), when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future. PMID:29181304

  20. Protective role of Hippopahe leaves against kidney damage in total body 60Co-gamma-irradiated mice

    International Nuclear Information System (INIS)

    Saini, Manu; Prasad, Jagdish; Bala, Madhu

    2012-01-01

    Hippophae rhamnoides has diverse therapeutic applications in Indian, Chinese and Tibetan medicine. Our earlier studies have shown that pretreatment with Hippophae leaf extract rendered >90% survival in mice population. The objective of this study was to investigate the role of our herbal preparation from Hippophae leaf against radiation induced kidney damage. The study was conducted with Strain 'A' male mice weighing approximately 28 ±2 g. The mice were administered Hippophae leaf extract, 30 minutes prior to 60 cobalt-gamma irradiation. The weight of kidneys and histological changes in kidney tissues at the light microscopic level were examined at 2, 5, 7, 10 and 15 days after treatment. The results showed that no significant change was observed in kidney weight after 60 cobalt-gamma irradiation. The glomerular damage in the form of glomerular sclerosis and percentage of damaged glomeruli; tubular damage in form of tubular dilations; apoptosis, and interstitial hemorrhages in renal cortex was also observed after radiation treatment. The pretreatment with Hippophae leaf extract countered most of the histological alterations induced by radiation. In comparison to radiation alone group, there was a significant decrease (p 60 cobalt gamma radiation induced damage. (author)

  1. The protective effects of resveratral on acute radiation injury in mice

    International Nuclear Information System (INIS)

    Yan Hao; Wang Hui; Zhang Heng

    2014-01-01

    Objective: To study the protective function of resveratrol on radiation-induced small intestine injury and lethal effect in mice. Methods: Mice were randomly divided into three groups: irradiation (IR) control, IR only, and IR+ resveratrol. 15 mice each group were irradiated on abdomen with 7.2 Gy γ-rays for cell lethal assay and 8 mice each group were irradiated with 6.5 Gy for small intestine injury assay. For the IR+ resveratrol group, the mouse was given resveratrol by intragastric administration 24 h before irradiation and then was fed with resveratrol daily for 5 days. The control and IR alone groups were fed with placebo. After 30 days of IR, mouse survival rate was detected. For small intestine injury experiments, 24 h after IR, the mice were terminated and the small intestines were treated with HE and immunohistochemical staining. Results: Compared with the irradiation group, resveratrol increased mouse survival by 33.3%, decreased apoptosis in intestinal crypt cells (t = 17.35, P < 0.05), and increased Ki67 expression (t = 13.62, P < 0.05). Conclusion: Resveratrol could protect small intestine injury from ionizing irradiation. (authors)

  2. Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3

    International Nuclear Information System (INIS)

    Yamato, H.; Matsumoto, T.; Fukumoto, S.; Ikeda, K.; Ishizuka, S.; Ogata, E.

    1989-01-01

    Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected [1 beta-3H]1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of [3H]24,25-(OH)2D3 to [3H]1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level

  3. Synthesis and enhanced neuroprotective activity of C60-based ebselen derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Liu, X.-F. [Huazhong Univ. of Science and Technology, Dept. of Chemistry, Wuhan (China); Hubei Univ., Ministry of Education Key Lab. for the Synthesis and Application of Organic Functional Molecules, Wuhan (China); Guan, W.-C. [Huazhong Univ. of Science and Technology, Dept. of Chemistry, Wuhan (China)], E-mail: wcguan04@yahoo.com.cn; Ke, W.-S. [Hubei Univ., College of Life Science, Wuhan (China)

    2007-03-15

    A C{sub 60}-based ebselen derivative 4 was synthesized through the cycloaddition of C{sub 60} with the azide (3) containing the ebselen component. It was obtained in a four-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol in 53% yield (based on consumed C{sub 60}). Its structure was characterized by {sup 1}H NMR, {sup 13}C NMR, IR, UV, and FAB-MS. To verify that the C{sub 60}-based ebselen derivative 4 had enhanced antioxidative and neuroprotective activity, the C{sub 60} derivative 5 and the ebselen derivative 6 were selected to treat cortical neuronal cells using the same procedures as with the C{sub 60}-based ebselen derivative 4. The cellular viability of different derivative treatment groups was estimated by LDH leakage assay and MTT assay. At the same final concentration (30 {mu}mol/L), the results showed that the antioxidative and protective potencies of the C{sub 60}-based ebselen derivative 4 (MTT (OD) 0.340 {+-} 0.035, LDH release (UL{sup -1}) 4.80 {+-} 0.16) against H{sub 2}O{sub 2}-mediated neuronal injury have an advantage over those of C{sub 60} derivative 5 (MTT (OD) 0.297 {+-} 0.036, LDH release (UL{sup -1}) 5.37 {+-} 0.31) and ebselen derivative 6 (MTT (OD) 0.267 {+-} 0.027, LDH release (UL{sup -1}) 5.85 {+-} 0.26). Correspondingly, the GPX activity of 4 (1.62 U/{mu}mol) was higher than that of 5 (0.77 U/{mu}mol) and 6 (1.24 U/{mu}mol). These findings demonstrate that the incorporation of two components with similar biological activity (C{sub 60} component and ebselen component) may be a desirable way of obtaining a new and more biologically effective C{sub 60}-based compound. (author)

  4. Synthesis and enhanced neuroprotective activity of C60-based ebselen derivatives

    International Nuclear Information System (INIS)

    Liu, X.-F.; Guan, W.-C.; Ke, W.-S.

    2007-01-01

    A C 60 -based ebselen derivative 4 was synthesized through the cycloaddition of C 60 with the azide (3) containing the ebselen component. It was obtained in a four-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol in 53% yield (based on consumed C 60 ). Its structure was characterized by 1 H NMR, 13 C NMR, IR, UV, and FAB-MS. To verify that the C 60 -based ebselen derivative 4 had enhanced antioxidative and neuroprotective activity, the C 60 derivative 5 and the ebselen derivative 6 were selected to treat cortical neuronal cells using the same procedures as with the C 60 -based ebselen derivative 4. The cellular viability of different derivative treatment groups was estimated by LDH leakage assay and MTT assay. At the same final concentration (30 μmol/L), the results showed that the antioxidative and protective potencies of the C 60 -based ebselen derivative 4 (MTT (OD) 0.340 ± 0.035, LDH release (UL -1 ) 4.80 ± 0.16) against H 2 O 2 -mediated neuronal injury have an advantage over those of C 60 derivative 5 (MTT (OD) 0.297 ± 0.036, LDH release (UL -1 ) 5.37 ± 0.31) and ebselen derivative 6 (MTT (OD) 0.267 ± 0.027, LDH release (UL -1 ) 5.85 ± 0.26). Correspondingly, the GPX activity of 4 (1.62 U/μmol) was higher than that of 5 (0.77 U/μmol) and 6 (1.24 U/μmol). These findings demonstrate that the incorporation of two components with similar biological activity (C 60 component and ebselen component) may be a desirable way of obtaining a new and more biologically effective C 60 -based compound. (author)

  5. Interleukin-12 induces a Th1-like response to Burkholderia mallei and limited protection in BALB/c mice.

    Science.gov (United States)

    Amemiya, Kei; Meyers, Jennifer L; Trevino, Sylvia R; Chanh, Tran C; Norris, Sarah L; Waag, David M

    2006-02-27

    We evaluated the effect of interleukin (IL)-12 on the immune response to Burkholderia mallei in BALB/c mice. Mice were vaccinated with non-viable B. mallei cells with or without IL-12. There was a seven- to nine-fold increase in IgG2a levels, and a significant increase in the proliferative response and interferon (IFN)-gamma production by splenocytes from mice that received B. mallei and IL-12. We saw an increase in survivors in the groups of mice that received B. mallei and IL-12 when challenged, compared to mice that received only B. mallei or IL-12. The results suggest that IL-12 can enhance the Th1-like immune response to B. mallei and mediate limited protection from a lethal challenge.

  6. Chronic free-choice drinking in crossed high alcohol preferring mice leads to sustained blood ethanol levels and metabolic tolerance without evidence of liver damage.

    Science.gov (United States)

    Matson, Liana; Liangpunsakul, Suthat; Crabb, David; Buckingham, Amy; Ross, Ruth Ann; Halcomb, Meredith; Grahame, Nicholas

    2013-02-01

    Crossed high alcohol preferring (cHAP) mice were selectively bred from a cross of the HAP1 × HAP2 replicate lines, and we demonstrate blood ethanol concentrations (BECs) during free-choice drinking that are reminiscent of those observed in alcohol-dependent humans. Therefore, this line may provide an unprecedented opportunity to learn about the consequences of excessive voluntary ethanol (EtOH) consumption, including metabolic tolerance and liver pathology. Cytochrome p450 2E1 (CYP2E1) induction plays a prominent role in driving both metabolic tolerance and EtOH-induced liver injury. In this report, we sought to characterize cHAP drinking by assessing whether pharmacologically relevant BEC levels are sustained throughout the active portion of the light-dark cycle. Given that cHAP intakes and BECs are similar to those observed in mice given an EtOH liquid diet, we assessed whether free-choice exposure results in metabolic tolerance, hepatic enzyme induction, and hepatic steatosis. In experiment 1, blood samples were taken across the dark portion of a 12:12 light-dark cycle to examine the pattern of EtOH accumulation in these mice. In experiments 1 and 2, mice were injected with EtOH following 3 to 4 weeks of access to water or 10% EtOH and water, and blood samples were taken to assess metabolic tolerance. In experiment 3, 24 mice had 4 weeks of access to 10% EtOH and water or water alone, followed by necropsy and hepatological assessment. In experiment 1, cHAP mice mean BEC values exceeded 80 mg/dl at all sampling points and approached 200 mg/dl during the middle of the dark cycle. In experiments 1 and 2, EtOH-exposed mice metabolized EtOH faster than EtOH-naïve mice, demonstrating metabolic tolerance (p alcohol dehydrogenase and aldehyde dehydrogenase. These results demonstrate that excessive intake by cHAP mice results in sustained BECs throughout the active period, leading to the development of metabolic tolerance and evidence of CYP2E1 induction

  7. DNA vaccine expressing herpes simplex virus 1 glycoprotein C and D protects mice against herpes simplex keratitis

    OpenAIRE

    Li-Li Dong; Ru Tang; Yu-Jia Zhai; Tejsu Malla; Kai Hu

    2017-01-01

    AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1 (HSV-1) glycoprotein C (gC) and glycoprotein D (gD) will achieve better protective effect against herpes simplex keratitis (HSK) than DNA vaccine encoding gD alone. METHODS: DNA vaccine expressing gD or gC combined gD (gD.gC) were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293T cells by Western-blot. For immunization, mice w...

  8. An enhanced postnatal autoimmune profile in 24 week-old C57BL/6 mice developmentally exposed to TCDD

    International Nuclear Information System (INIS)

    Mustafa, A.; Holladay, S.D.; Goff, M.; Witonsky, S.G.; Kerr, R.; Reilly, C.M.; Sponenberg, D.P.; Gogal, R.M.

    2008-01-01

    Developmental exposure of mice to the environmental contaminant and AhR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), causes persistent postnatal suppression of T cell-mediated immune responses. The extent to which prenatal TCDD may induce or exacerbate postnatal autoimmune disease remains unknown. In the present study, time-pregnant high affinity AhR C57BL/6 mice received a single oral administration of 0, 2.5, or 5 μg/kg TCDD on gestation day (gd) 12. Offspring of these mice (n = 5/gender/treatment) were evaluated at 24 weeks-of-age and showed considerable immune dysregulation that was often gender-specific. Decreased thymic weight and percentages of CD4 + CD8 + thymocytes, and increased CD4 + CD8 - thymocytes, were present in the female but not male offspring. Males but not females showed decreased CD4 - CD8 + T cells, and increased Vβ3 + and Vβ17a + T cells, in the spleen. Males but not females also showed increased percentages of bone marrow CD24 - B220 + B cell progenitors. Antibody titers to dsDNA, ssDNA and cardiolipin displayed increasing trends in both male and female mice, reaching significance for anti-dsDNA in both genders and for ssDNA in males at 5 μg/kg TCDD. Immunofluorescent staining of IgG and C3 deposition in kidney glomeruli increased in both genders of prenatal TCDD-exposed mice, suggestive of early stages of autoimmune glomerulonephritis. Collectively, these results show that exposure to TCDD during immune system development causes persistent humoral immune dysregulation as well as altered cell-mediated responses, and induces an adult profile of changes suggestive of increased risk for autoimmune disease

  9. Characterization of vitamin D-deficient klotho(-/-) mice: do increased levels of serum 1,25(OH)2D3 cause disturbed calcium and phosphate homeostasis in klotho(-/-) mice?

    NARCIS (Netherlands)

    Woudenberg-Vrenken, T.E.; van der Eerden, B.C.; van der Kemp, A.W.; Leeuwen, J.P. van; Bindels, R.J.M.; Hoenderop, J.G.J.

    2012-01-01

    BACKGROUND: Klotho(-/-) mice display disturbed Ca(2+) and vitamin D homeostasis. Renal cytochrome p450 27b1 (Cyp27b1), the enzyme that catalyzes the hydrolysis to 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), is increased in klotho(-/-) mice, and a 1,25(OH)(2)D(3)-deficient diet partially normalized

  10. Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.

    Science.gov (United States)

    Joo, Jin Deok; Kim, Mihwa; D'Agati, Vivette D; Lee, H Thomas

    2006-11-01

    Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.

  11. Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice.

    Science.gov (United States)

    Kim, Hyunseong; Keum, Dong June; Kwak, Jung won; Chung, Hwan-Suck; Bae, Hyunsu

    2014-01-01

    The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2) from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg) in mice. Acetaminophen (APAP) is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10-/-) mice were injected with PLA2 once a day for five days and sacrificed 24 h (h) after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO) compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10-/- mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

  12. Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice.

    Directory of Open Access Journals (Sweden)

    Hyunseong Kim

    Full Text Available The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2 from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg in mice. Acetaminophen (APAP is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10-/- mice were injected with PLA2 once a day for five days and sacrificed 24 h (h after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST and alanine aminotransferase (ALT. PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10-/- mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

  13. Protective effects of hydroxysaffor yellow A on brain injury in mice irradiated by 300 MeV/n 12C6+ ions

    International Nuclear Information System (INIS)

    Gan Lu; Wang Zhenhua; Zhang Hong; Ma Chengjun; Li Guang

    2012-01-01

    Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction, to which no ideal prevention method is available until now. Hydroxysaffor yellow A (HSYA) is the main active ingredient of the traditional Chinese medicine safflower, with protective effects against cerebral ischemic injury. In this work, we investigated the protective effects of HSYA on brain injury in mice irradiated by 300 MeV/u 12 C 6+ ion beam. The whole head of male Kunming mouse was irradiated to 4.0 Gy after receiving daily intra-peritoneal injection HSYA for 3 d. One month later, the Morris water maze test was used to detect the spatial memory in mice. The Evans blue was used as the tracer to evaluate the permeability of blood-brain barrier. The SOD activity and MDA content in brain tissue were assayed by test kits. The results showed that the 12 C 6+ irradiation significantly impaired the spatial learning and memory in mice, increased the permeability of blood-brain barrier and the MDA content in brain tissue, whereas decreased the SOD activity in brain tissue. The pretreatment with HSYA could improve the spatial memory deficits and inhibit the changes of the blood-brain barrier, the SOD activity and the MDA content in brain tissue in mice. All these demonstrate that HSYA possesses the protective effect against brain injury induced by 12 C 6+ particle therapy. (authors)

  14. Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice.

    Science.gov (United States)

    Yadav, Umesh C S; Shoeb, Mohammed; Srivastava, Satish K; Ramana, Kota V

    2011-10-17

    To investigate the effect of aldose reductase (AR) deficiency in protecting the chronic experimental autoimmune (EAU) and acute endotoxin-induced uveitis (EIU) in c57BL/6 mice. The WT and AR-null (ARKO) mice were immunized with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20), to induce EAU, or were injected subcutaneously with lipopolysaccharide (LPS; 100 μg) to induce EIU. The mice were killed on day 21 for EAU and at 24 hours for EIU, when the disease was at its peak, and the eyes were immediately enucleated for histologic and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen-specific immune response in vitro and in vivo. In WT-EAU mice, severe damage to the retinal wall, especially to the photoreceptor layer was observed, corresponding to a pathologic score of ∼2, which was significantly prevented in the ARKO or AR inhibitor-treated mice. The levels of cytokines and chemokines increased markedly in the whole-eye homogenates of WT-EAU mice, but not in ARKO-EAU mice. Further, expression of inflammatory marker proteins such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule (VCAM)-1 was increased in the WT-EIU mouse eyes but not in the ARKO-EIU eyes. The T cells proliferated vigorously when exposed to the hIRPB antigen in vitro and secreted various cytokines and chemokines, which were significantly inhibited in the T cells isolated from the ARKO mice. These findings suggest that AR-deficiency/inhibition protects against acute as well as chronic forms of ocular inflammatory complications such as uveitis.

  15. In vivo evaluation of the 3-carboranyl thymidine analogue (3-CTA), N5-2OH, for neutron capture therapy

    International Nuclear Information System (INIS)

    Barth, Rolf F.; Yang, Weilian; Wu, Gong; Byun, Youngjoo; Tjarks, Werner; Eriksson, Staffan; Binns, Peter J.; Riley, Kent J.

    2006-01-01

    The purpose of the present study was to evaluate a 3 CTA, designated N5-2OH, as a boron delivery agent for NCT. Target validation was established using the thymidine kinase 1 (+) wild type L929 cell line and its TK1(-) counterpart, which were implanted subcutaneously into NIH nu/nu mice. 10 B-enriched N5-2OH, solubilized in DMSO (50μg 10 B in 15μl), was administered by 2 intratumoral (i.t.) injections at 2 h intervals. Two hours later the animals were irradiated at the MITR-II Research Reactor, following which tumor volumes were determined over a period of 30 days. Mice bearing TK1(+) wild type tumors, which had received N5-2OH, had a 15 fold inhibition in tumor growth compared to TK1(-) controls (247 versus 3,603 mm 3 ). Based on these data, biodistribution and therapy studies were initiated in F98 glioma bearing rats. Animals received 500μg of N5-2OH, administered intracerebrally (i.c.) by convection enhanced delivery (CED) using ALZET pumps (8μl/h for 24 h). The tumor boron concentration was 17.3μg/g compared to undetectable amounts in normal brain and blood. BNCT was carried out 14 d following i.c. implantation of 10 3 F98 glioma cells and 24 h following CED of N5-2OH (500μg/200μl). The mean survival time (MST) of these animals was 38 d compared to 31 d and 25 d, respectively, for irradiated and untreated controls. Studies are planned to optimize the delivery and formulation of N5-2OH and additional therapy studies will be carried out using N5-2OH in combination with BPA and BSH. (author)

  16. Effects of carbon nanomaterials fullerene C{sub 60} and fullerol C{sub 60}(OH){sub 18-22} on gills of fish Cyprinus carpio (Cyprinidae) exposed to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Socoowski Britto, Roberta; Longaray Garcia, Marcia; Martins da Rocha, Alessandra [Universidade Federal do Rio Grande - FURG, Instituto de Ciencias Biologicas, Campus Carreiros, Av. Italia km 8 s/n, Rio Grande, RS (Brazil); Programa de Pos Graduacao em Fisiologia Animal Comparada - Fisiologia Animal Comparada, FURG (Brazil); Artigas Flores, Juliana [Universidade Federal do Rio Grande - FURG, Instituto de Ciencias Biologicas, Campus Carreiros, Av. Italia km 8 s/n, Rio Grande, RS (Brazil); Pinheiro, Mauricio V. Brant [Departamento de Fisica, ICEx, Universidade Federal de Minas Gerais, MG (Brazil); Monserrat, Jose Maria [Universidade Federal do Rio Grande - FURG, Instituto de Ciencias Biologicas, Campus Carreiros, Av. Italia km 8 s/n, Rio Grande, RS (Brazil); Programa de Pos Graduacao em Fisiologia Animal Comparada - Fisiologia Animal Comparada, FURG (Brazil); Ribas Ferreira, Josencler L., E-mail: josenclerf@gmail.com [Universidade Federal do Rio Grande - FURG, Instituto de Ciencias Biologicas, Campus Carreiros, Av. Italia km 8 s/n, Rio Grande, RS (Brazil); Programa de Pos Graduacao em Fisiologia Animal Comparada - Fisiologia Animal Comparada, FURG (Brazil)

    2012-06-15

    In consequence of their growing use and demand, the inevitable environmental presence of nanomaterials (NMs) has raised concerns about their potential deleterious effects to aquatic environments. The carbon NM fullerene (C{sub 60}), which forms colloidal aggregates in water, and its water-soluble derivative fullerol (C{sub 60}(OH){sub 18-22}), which possesses antioxidant properties, are known to be photo-excited by ultraviolet (UV) or visible light. To investigate their potential hazards to aquatic organisms upon exposure to UV sunlight, this study analyzed (a) the in vitro behavior of fullerene and fullerol against peroxyl radicals (ROO{center_dot}) under UV-A radiation and (b) the effects of these photo-excited NMs on oxidative stress parameters in functional gills extracted from the fish Cyprinus carpio (Cyprinidae). The variables measured were the total antioxidant capacity, lipid peroxidation (TBARS), the activities of the antioxidant enzymes glutathione reductase (GR) and glutamate cysteine ligase (GCL), and the levels of the non-enzymatic antioxidant glutathione (GSH). The obtained results revealed the following: (1) both NMs behaved in vitro as antioxidants against ROO{center_dot} in the dark and as pro-oxidants in presence of UV-A, the latter effect being reversed by the addition of sodium azide, which is a singlet oxygen ({sup 1}O{sub 2}) quencher; (2) fullerene induced toxicity with or without UV-A incidence, with a significant (p < 0.05) increase in lipid peroxidation (with greater damage under illumination), a decrease in GCL activity, and the depletion of GSH stocks (under illumination), all of which were attributed to {sup 1}O{sub 2} generation; and (3) fullerol also decreased GCL activity and GSH formation (p < 0.05) but without lipid damage. The overall results show that fullerene can be toxic with or without light incidence, whereas UV radiation seems to play a key role in the environmental toxicity of carbon NMs through {sup 1}O{sub 2} formation.

  17. Monoclonal antibodies passively protect BALB/c mice against Burkholderia mallei aerosol challenge.

    Science.gov (United States)

    Treviño, Sylvia R; Permenter, Amy R; England, Marilyn J; Parthasarathy, Narayanan; Gibbs, Paul H; Waag, David M; Chanh, Tran C

    2006-03-01

    Glanders is a debilitating disease with no vaccine available. Murine monoclonal antibodies were produced against Burkholderia mallei, the etiologic agent of glanders, and were shown to be effective in passively protecting mice against a lethal aerosol challenge. The antibodies appeared to target lipopolysaccharide. Humoral antibodies may be important for immune protection against B. mallei infection.

  18. 10 CFR 60.9 - Employee protection.

    Science.gov (United States)

    2010-01-01

    ... occurs because the employee has engaged in protected activities. An employee's engagement in protected... 10 Energy 2 2010-01-01 2010-01-01 false Employee protection. 60.9 Section 60.9 Energy NUCLEAR... Provisions § 60.9 Employee protection. (a) Discrimination by a Commission licensee, an applicant for a...

  19. 40 CFR 60.33c - Emission guidelines for municipal solid waste landfill emissions.

    Science.gov (United States)

    2010-07-01

    ... waste landfill emissions. 60.33c Section 60.33c Protection of Environment ENVIRONMENTAL PROTECTION... Guidelines and Compliance Times for Municipal Solid Waste Landfills § 60.33c Emission guidelines for municipal solid waste landfill emissions. (a) For approval, a State plan shall include control of MSW...

  20. Asymmetric fission and evaporation of C{sub 60}{sup r+} (r = 2-4) fullerene ions in ion-C{sub 60} collisions: I. Proton results

    Energy Technology Data Exchange (ETDEWEB)

    Rentenier, A; Bordenave-Montesquieu, A; Moretto-Capelle, P; Bordenave-Montesquieu, D [LCAR-IRSAMC, UMR 5589 Universite Paul Sabatier-CNRS, 118 rte de Narbonne, 31062 Toulouse Cedex (France)

    2004-06-28

    A quantitative description of the asymmetric fission (AF) of C{sub 60}{sup r+} fullerene ions (r = 2-4), using a multistop coincidence technique between both fragment ions, is presented. Charged light fragment (LF) and heavy fragment (HF) size distributions are discussed together with the corresponding averaged sizes. Complete AF distributions are reported for the first time for C{sub 60}{sup 2+} ions. Simple dependences of the more probable channels and averaged fragment sizes on the partner size are found and discussed. The LF ones are not very sensitive to the parent fullerene ion charge r and vary linearly with the HF size at least for the largest ones. On the other hand the HF ones present an oscillating dependence against the LF size, the odd-numbered LFs being correlated to a smaller HF size, and depend on r. In the comparison of branching ratios between AF and the competing pure neutral evaporation channel, some emphasis is given to the behaviour of the unimolecular processes with r which are compared with the evolution of the activation energies and fission barriers. From a close examination of the individual HF distributions the production mechanisms of odd-n fragments are discussed, and the most probable dissociation channels of even-numbered C{sub n}{sup +} excited carbon clusters identified. Finally, an analysis of the neutral channels is also presented for the first time, the total neutral mass N (in carbon units) being deduced from the mass conservation law. Surprising similarities between the charged LF- and N-distributions are found. AF processes are also identified where light neutrals and ions play a symmetrical role. These findings lead us to suggest that a concerted emission of ions and heavy neutrals is probably a fission mechanism to be considered to understand the AF process of the C{sub 60} molecule in addition to the often assumed multistep fragmentation cascade scheme.

  1. Survival of bone marrow-engrafted mice subsequent to protection from lethal radiation by WR 2721

    International Nuclear Information System (INIS)

    Kinnamon, K.E.; Ketterling, L.L.; Ledney, G.D.; Lorenz, G.B.; Mioduszewski, R.J.; Stampfli, H.F.

    1980-01-01

    For the first time data are presented for animals treated with bone marrow cells after lethal radiation exposure while protected with WR 2721 (the single radioprotective chemical compound with the highest known dose reduction factor). The LD 50 30 (lethal dose to 50% in 30 days) for mice exposed to whole-body 60 Co radiation was elevated from 824 +- 8 rad in unprotected and untreated mice to (a) 1181 +- 33 rad in animals which received syngeneic bone marrow cells after exposure; (b) 1342 +- 27 rad in animals which received WR 2721 before radiation exposure; and (c) 1608 +- 33 rad in animals receiving both the radioprotective agent before exposure and bone marrow engraftment after exposure

  2. Immune Response Induced by an Immunodominant 60 kDa Glycoprotein of the Cell Wall of Sporothrix schenckii in Two Mice Strains with Experimental Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Carlos A. Alba-Fierro

    2016-01-01

    Full Text Available Cell wall (CW components of fungus Sporothrix schenckii are the major inductors antigens of immune responses. The immunodominant 60 kDa glycoprotein (gp60 has been shown to be associated with the virulence of this fungus but its role in experimental sporotrichosis is unknown. In this work, the immunological effects of CW-purified gp60 were investigated in a model of experimental subcutaneous sporotrichosis in normal and gp60-preimmunized C57BL/6 and BALB/c mice strains which were then infected with S. schenckii conidia. Results showed that both mice strains use different cytokine profiles in order to fight S. schenckii infection; C57BL/6 mice seem to use a Th17 response while BALB/c mice tend to depend on a Th1 profile. Preimmunization with gp60 showed a downregulatory effect on the immune response since cytokines levels were diminished in both strains. There were no significant differences in the magnitude of dorsoplantar inflammation between gp60-preimmunized and nonimmunized mice of both strains. However, skin lesions due to the infection in gp60-preimmunized mice were more severe in BALB/c than in C57BL/6 mice, suggesting that the antigen exerts a higher downregulatory effect on the Th1 response.

  3. Immune Response Induced by an Immunodominant 60 kDa Glycoprotein of the Cell Wall of Sporothrix schenckii in Two Mice Strains with Experimental Sporotrichosis.

    Science.gov (United States)

    Alba-Fierro, Carlos A; Pérez-Torres, Armando; Toriello, Conchita; Pulido-Camarillo, Evelyn; López-Romero, Everardo; Romo-Lozano, Yolanda; Gutiérrez-Sánchez, Gerardo; Ruiz-Baca, Estela

    2016-01-01

    Cell wall (CW) components of fungus Sporothrix schenckii are the major inductors antigens of immune responses. The immunodominant 60 kDa glycoprotein (gp60) has been shown to be associated with the virulence of this fungus but its role in experimental sporotrichosis is unknown. In this work, the immunological effects of CW-purified gp60 were investigated in a model of experimental subcutaneous sporotrichosis in normal and gp60-preimmunized C57BL/6 and BALB/c mice strains which were then infected with S. schenckii conidia. Results showed that both mice strains use different cytokine profiles in order to fight S. schenckii infection; C57BL/6 mice seem to use a Th17 response while BALB/c mice tend to depend on a Th1 profile. Preimmunization with gp60 showed a downregulatory effect on the immune response since cytokines levels were diminished in both strains. There were no significant differences in the magnitude of dorsoplantar inflammation between gp60-preimmunized and nonimmunized mice of both strains. However, skin lesions due to the infection in gp60-preimmunized mice were more severe in BALB/c than in C57BL/6 mice, suggesting that the antigen exerts a higher downregulatory effect on the Th1 response.

  4. Protective effect of urinary trypsin inhibitor on the development of radiation-induced lung fibrosis in mice

    International Nuclear Information System (INIS)

    Katoh, Hiroyuki; Ishikawa, Hitoshi; Suzuki, Yoshiyuki; Ohno, Tatsuya; Takahashi, Takeo; Nakano, Takashi; Hasegawa, Masatoshi; Yoshida, Yukari

    2010-01-01

    This study aimed to analyze whether Ulinastatin, a urinary trypsin inhibitor (UTI), inhibits the transforming growth factor (TGF)-β signaling pathway and lung fibrosis induced by thoracic irradiation in a lung injury mouse model. The thoraces of 9-week-old female fibrosis-sensitive C57BL/6 mice were irradiated with a single X-ray dose of 12 Gy or 24 Gy. UTI was administrated intraperitoneally at a dose of 200,000 units/kg concurrently with radiation (concurrent UTI) or daily during the post-irradiation period for 8-14 days (post-RT UTI). Mice were sacrificed at 16 weeks after irradiation to assess the histological grade of lung fibrosis and immunohistochemical TGF-β expression. Survival rates of mice given 24 Gy to the whole lung ±UTI were also compared. Post-RT UTI reduced the score of lung fibrosis in mice, but concurrent UTI had no beneficial effects in irradiated mice. The fibrosis score in post-RT UTI mice was 3.2±1.0, which was significantly smaller than that of irradiated mice without UTI treatment (RT alone; 6.0±1.3; p 2 =0.26, p<0.01). The survival rate at 30 weeks for post-RT UTI mice was significantly better than that of RT alone mice (33% vs. 10%, p<0.05). The administration of post-RT UTI suppressed TGF-β expression and radiation-induced lung fibrosis, which resulted in significant survival prolongation of the irradiated mice. (author)

  5. HUMORAL IMMUNE-RESPONSE TO 2,4-DINITROPHENYL KEYHOLE LIMPET HEMOCYANIN IN ANTIGEN-FREE, GERM-FREE AND CONVENTIONAL BALB/C MICE

    NARCIS (Netherlands)

    BOS, NA; PLOPLIS, VA

    The B cell immune response to 2,4-dinitrophenyl (DNP) keyhole limpet hemocyanin was compared in antigen-free, germ-free and conventional BALB/c mice. The numbers of total and of DNP-specific IgM-, IgG- and IgA-secreting cells in the spleen were determined by enzyme-linked immunosorbent plaque assays

  6. Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.

    Science.gov (United States)

    Sun, Qian; Zhang, Wenliang; Zhong, Wei; Sun, Xinguo; Zhou, Zhanxiang

    2016-10-01

    Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP. This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD. Copyright © 2016 by the Research Society on Alcoholism.

  7. Murine polyomavirus virus-like particles carrying full-length human PSA protect BALB/c mice from outgrowth of a PSA expressing tumor.

    Directory of Open Access Journals (Sweden)

    Mathilda Eriksson

    Full Text Available Virus-like particles (VLPs consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV VLPs carrying the entire human Prostate Specific Antigen (PSA (PSA-MPyVLPs for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs. Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4(+ and CD8(+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4(+ and CD8(+ cells with a low induction of anti-VLP antibodies.

  8. Murine Polyomavirus Virus-Like Particles Carrying Full-Length Human PSA Protect BALB/c Mice from Outgrowth of a PSA Expressing Tumor

    Science.gov (United States)

    Eriksson, Mathilda; Andreasson, Kalle; Weidmann, Joachim; Lundberg, Kajsa; Tegerstedt, Karin

    2011-01-01

    Virus-like particles (VLPs) consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV) VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs). Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4+ and CD8+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4+ and CD8+ cells with a low induction of anti-VLP antibodies. PMID:21858228

  9. Temporal characteristics of stress-induced decrease in benzodiazepine reception in C57BL/6 and BALB/c mice.

    Science.gov (United States)

    Yarkova, M A; Seredenin, S B

    2014-10-01

    We studied the duration of the drop of specific (3)H-flunitrazepam binding by synaptosomal membranes from the brain of C57Bl/6 and BALB/c mice after open-field and "contact with predator" tests. It was found that reduced benzodiazepine reception in BALB/c mice after open-field test persisted for 1.5 h, but no changes of this parameter were found in C57Bl/6 mice. After contact with predator, the binding capacity of the benzodiazepine site of GABAA receptor was reduced for 8 h in BALB/c mice and for 24 h in C57Bl/6 mice.

  10. Dietary oligofructose and inulin protect mice from enteric and systemic pathogens and tumor inducers.

    Science.gov (United States)

    Buddington, Karyl K; Donahoo, Jillian B; Buddington, Randal K

    2002-03-01

    Prebiotics induce changes in the population and metabolic characteristics of the gastrointestinal bacteria, modulate enteric and systemic immune functions, and provide laboratory rodents with resistance to carcinogens that promote colorectal cancer. There is less known about protection from other challenges. Therefore, mice of the B6C3F1 strain were fed for 6 wk a control diet with 100 g/kg cellulose or one of two experimental diets with the cellulose replaced entirely by the nondigestible oligosaccharides (NDO) oligofructose and inulin. From each diet, 25 mice were challenged by a promoter of colorectal cancer (1,2-dimethylhydrazine), B16F10 tumor cells, the enteric pathogen Candida albicans (enterically), or were infected systemically with Listeria monocytogenes or Salmonella typhimurium. The incidences of aberrant crypt foci in the distal colon after exposure to dimethylhdrazine for mice fed inulin (53%) and oligofructose (54%) were lower than in control mice (76%; P 80% for control mice), but fewer of the mice fed inulin died (60%; P dietary NDO was not elucidated, but the findings are consistent with enhanced immune functions in response to changes in the composition and metabolic characteristics of the bacteria resident in the gastrointestinal tract.

  11. Protection against ultraviolet-B radiation-induced local and systemic suppression of contact hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols

    International Nuclear Information System (INIS)

    Katiyar, S.K.; Elmets, C.A.; Agarwal, Rajesh; Mukhtar, Hasan

    1995-01-01

    Exposure of skin to UV radiation can cause diverse biological effects, including induction of inflammation, alteration in cutaneous immune cells and impairment of contact hypersensitivity (CHS) responses. Our laboratory has demonstrated that oral feeding as well as topical application of a polyphenolic fraction isolated from green tea (GTP) affords protection against the carcinogenic effects of UVB (280-320 nm) radiation. In this study, we investigated whether GTP could protect against UVB-induced immunosuppression and cutaneous inflammatory responses in C3H mice. Immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UVB-irradiated skin (local suppression) or to a distant site (systemic suppression), while double skin-fold swelling was used as the measure of UVB-induced inflammation. (author)

  12. IgM but not IgG monoclonal anti-Nocardia brasiliensis antibodies confer protection against experimental actinomycetoma in BALB/c mice.

    Science.gov (United States)

    Gonzalez-Suarez, Maria L; Salinas-Carmona, Mario C; Pérez-Rivera, Isabel

    2009-10-01

    Nocardia brasiliensis is a facultative intracellular microorganism that produces a human chronic infection known as actinomycetoma. Human and mouse anti-N. brasiliensis antibody response identify P24, P26 and P61 immunodominant antigens. In this work, we generated immunoglobulin M (IgM) and IgG monoclonal antibodies (mAbs) specific to immunodominant P61 antigen. The monoclonal IgM (NbM1) and IgG2a (NbG1) antibodies were assessed for their in vitro bactericidal activity, in vivo protective effect and ability to block catalase activity. These mAbs specifically recognized P61, but they did not inhibit its enzyme activity. The in vitro bactericidal effect of NbG1 was higher than the killing ability of the IgM mAb. In vivo experiments with a murine model of experimental infection with N. brasiliensis injected into rear footpads was used to test the effect of NbM1 and NbG1. The negative untreated group developed a chronic actinomycetoma within 4 weeks. IgM mAbs conferred protection to BALB/c mice infected with N. brasiliensis. IgG mAb lacked this protective effect. IgM mAb showed a dose-response correlation between antibody concentration and lesion size. These results demonstrate that humoral immune response mediated by antigen-specific IgM antibody protects against an intracellular bacterial infection.

  13. Rotational dynamics of C60 in Na2RbC60

    International Nuclear Information System (INIS)

    Christides, C.; Prassides, K.; Neumann, D.A.; Copley, J.R.D.; Mizuki, J.; Tanigaki, K.; Hirosawa, I.; Ebbesen, T.W.

    1993-01-01

    We have measured the low-energy neutron inelastic-scattering (NIS) spectra of superconducting Na 2 RbC 60 in the temperature range 50-350 K. Well-defined librational peaks are observed at 50 K at 2.83(17) meV (FWHM = 1.7(5) meV). They soften and broaden with increasing temperature. Their behaviour mimics that found in solid C 60 and differs markedly from K 3 C 60 . The rotational barrier for C 60 reorientations in Na 2 RbC 60 is somewhat higher than in pristine C 60 and approximately half as large as in K 3 C 60 . An order-disorder transition is anticipated at a temperature higher than that found in C 60 . (orig.)

  14. Protective effect of melatonin on radiation damage of splenocytes in mice

    International Nuclear Information System (INIS)

    Zhang Xuan; Gong Shouliang; Zhang Ming; Liu Shuzheng

    2005-01-01

    This paper is to explore the effect of melatonin (MLT) on the damage of mouse splenocytes induced by whole-body irradiation (WBI) and its mechanism. MLT was administered to Kunming mice by peritoneal injection 60 min before WBI with 1.0-4.0 Gy X-rays. For consecutive administration of MLT, changes in splenocyte number were observed 24 h after WBI; for single administration of MLT, apoptotic body percentage (ABP) and cell percentages of cell cycle phases in splenocytes were determined with flow cytometry, and DNA fragmentation rate (DFR) was assayed by fluorescence spectrophotometry. The number of splenocytes increased significantly after daily consecutive administration of MLT for 1 week, in 0.1 mg·kg -1 (BW) group (p -1 ·d -1 ) for 1 week before WBI (p 0 /G 1 and G 2 + M phase splenocytes increased significantly (p 1 and G 2 arrests. When MLT was administered once before irradiation, ABP and DLR of splenocytes decreased significantly (p 1 arrest was attenuated while G 2 arrest became more serious. The administration of MLT to mice before WBI has protective effect on immunity as evidenced by decreased damage of splenocytes after WBI. (authors)

  15. Effect of lead acetate on follicular count of mice ovary and the protective role of garlic extract

    International Nuclear Information System (INIS)

    Waseem, N.; Hamid, S.; Butt, S.A.

    2014-01-01

    Objective: The study was conducted to evaluate the effects of lead acetate and protective role of garlic extract on the histomorphology of the ovarian follicles in an animal model. Study Design: Laboratory based randomized control trial Place and Duration of Study: Department of Anatomy, Army Medical College in collaboration with National Institute of Health from April-June 2013 Material and Methods: Thirty female BALBc mice were selected. Mice were randomly divided into three groups. 10 animals were placed in each group. Group A being the control was given normal diet. Group B was given lead acetate at a dose of 30 mg/kg/day. Group C was given lead acetate 30mg/kg/day and garlic extract 500 mg/kg/day through oral lavage tube for 60 days. Animals were sacrificed and dissected at the end of 60th day. Length and width of the ovary were measured, right ovary was processed, embedded and stained for histological study. Primary, secondary and graafian follicles were counted and noted. Results: There was reduction in the number of primary and graafian follicles in group B when compared to group A. In group C there was relatively increase in number of follicles, when compared to group B. Number of secondary follicles was almost same in all the groups. The length of ovary was higher in group A as compared to group B. In group C results were same as group A regarding length of the ovary. Width of ovary was same between the respective groups. Conclusion: The follicular count was markedly affected in lead acetate treated group which improved when co treated with garlic extract in experimental group C. Hence, garlic had a protective role against lead induced changes in mice ovary. (author)

  16. Altered methanol embryopathies in embryo culture with mutant catalase-deficient mice and transgenic mice expressing human catalase

    International Nuclear Information System (INIS)

    Miller, Lutfiya; Wells, Peter G.

    2011-01-01

    The mechanisms underlying the teratogenicity of methanol (MeOH) in rodents, unlike its acute toxicity in humans, are unclear, but may involve reactive oxygen species (ROS). Embryonic catalase, although expressed at about 5% of maternal activity, may protect the embryo by detoxifying ROS. This hypothesis was investigated in whole embryo culture to remove confounding maternal factors, including metabolism of MeOH by maternal catalase. C57BL/6 (C57) mouse embryos expressing human catalase (hCat) or their wild-type (C57 WT) controls, and C3Ga.Cg-Catb/J acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on gestational day (GD) 9 (plug = GD 1), exposed for 24 h to 4 mg/ml MeOH or vehicle, and evaluated for functional and morphological changes. hCat and C57 WT vehicle-exposed embryos developed normally. MeOH was embryopathic in C57 WT embryos, evidenced by decreases in anterior neuropore closure, somites developed and turning, whereas hCat embryos were protected. Vehicle-exposed aCat mouse embryos had lower yolk sac diameters compared to C3H WT controls, suggesting that endogenous ROS are embryopathic. MeOH was more embryopathic in aCat embryos than WT controls, with reduced anterior neuropore closure and head length only in catalase-deficient embryos. These data suggest that ROS may be involved in the embryopathic mechanism of methanol, and that embryonic catalase activity may be a determinant of teratological risk.

  17. Water-soluble C60 fullerenes reduce manifestations of acute cholangitis in rats

    Science.gov (United States)

    Kuznietsova, H. M.; Lynchak, O. V.; Dziubenko, N. V.; Osetskyi, V. L.; Ogloblya, O. V.; Prylutskyy, Yu I.; Rybalchenko, V. K.; Ritter, U.; Scharff, P.

    2018-03-01

    Sclerosing cholangitis is the liver disease of uncertain etiology, extremely unfavorable prognosis and lack of effective medication therapy. Therefore, the effect of water-soluble biocompatible C60 fullerenes (C60FAS) on the liver functional state on rat acute-cholangitis model was aimed to be discovered. Acute cholangitis was simulated by single α-naphthyl isothiocyanate (ANIT, 100 mg/kg) per os administration; C60FAS (0.5 mg/kg) was administered either per os or intraperitoneally in 24 and 48 h after ANIT ingestion, and in 72 h the animals were sacrificed. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), the total and direct bilirubin, creatinine and urea in the blood serum were determined, and the liver morphological state was assessed. In animals experienced ANIT-induced acute cholangitis, the total and direct bilirubin, creatinine, ALT, AST, ALP and LDH 1.5-4-fold increase were observed, indicating cytolysis of hepatocytes, cholestasis, and renal dysfunction. The features of periductal fibrosis, biliary epithelium atrophy, and portal-portal linking septa formation were detected, confirming the sclerosing cholangitis development. C60FAS promoted to the normalization of direct and total bilirubin levels, the ALT activity and diminution of fibrotic features. In addition, C60FAS intraperitoneal administration also normalized the ALP activity, indicating the attenuation of disease symptoms. However, the AST activity and creatinine level remained unchanged, and the LDH activity even increased, manifesting the partial persistence of cholestasis and renal dysfunction. Thus, the therapeutic application of C60FAS promotes a partial protection of liver against cholangitis.

  18. Antitumor properties of (5E,7E) analogs of vitamin D3.

    Science.gov (United States)

    Filip, B; Milczarek, M; Wietrzyk, J; Chodyński, M; Kutner, A

    2010-07-01

    Geometric isomers (5E,7E) of major active metabolites of vitamin D3 [1alpha,25(OH)2D3 and (24R)-1,24(OH)2D3] were synthesized by a new convenient procedure. Vitamin D triene system of the metabolites was first derivatized as a Diels-Alder adduct. Removal of the triene protecting group, in a key synthetic step, yielded the title compounds PRI-2208 and PRI-2209, respectively. The analogs were examined for their antiproliferative activity in vitro against human breast cancer cells (MCF-7) and promyelocytic leukemia (HL-60) cells. The activity was compared with one of the parent compounds. Both analogs examined revealed similar or higher antiproliferative activity compared to 1alpha,25(OH)2D3 or to (24R)-1,24(OH)2D3. The studies of calcemic activity in vivo showed that analogs PRI-2208 and PRI-2209 did not influence the serum calcium level in doses, in which 1alpha,25(OH)2D3 or (24R)-1,24(OH)2D3 significantly increased this level. The antitumor activity of these analogs in the LLC mice tumor model was studied. Analog PRI-2208 was found to be more active in inhibiting LLC tumor growth than 1alpha,25(OH)2D3, as well as than PRI-2191 and PRI-2209. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  19. 24 CFR 3800.60 - Settlements.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Settlements. 3800.60 Section 3800... DEVELOPMENT INVESTIGATIONS IN CONSUMER REGULATORY PROGRAMS § 3800.60 Settlements. (a) At any time during an investigation, the Department and the parties subject to an investigation may conduct settlement negotiations...

  20. Immunogenicity and protective effect of recombinant Brucella abortus Ndk (rNdk) against a virulent strain B. abortus 544 infection in BALB/c mice.

    Science.gov (United States)

    Hop, Huynh Tan; Simborio, Hannah Leah; Reyes, Alisha Wehdnesday Bernardo; Arayan, Lauren Togonon; Min, WonGi; Lee, Hu Jang; Kim, Dong Hee; Chang, Hong Hee; Kim, Suk

    2015-02-01

    In this study, we particularly evaluated the protective effect of recombinant protein encoded by Brucella abortus 544 ndk (nucleoside diphosphate kinase) gene against B. abortus infection in the BALB/c mice. Cloning and expression of B. abortus Ndk was accomplished by PCR amplification into a pMAL expression system, and purification of a recombinant Ndk (rNdk). As for the determination of IgG responses, rNdk induced vigorous IgG production, especially higher in IgG2a compared to IgG1 with titers of 5.2 and 4.8, respectively, whereas titers of these in mice immunized with MBP were 2.4 of IgG2a and 2.6 of IgG1. The analysis of cytokine has revealed that rNdk can strongly induce production of IFN-γ as well as proinflammatory cytokines (TNF, MCP1 and IL-6) but not much IL-10, suggesting rNdk elicited predominantly cell-mediated immune responses. Furthermore, the spleen proliferation and bacterial burden in the spleen of rNdk immunized mice were significantly lower than those of MBP-immunized mice against virulent B. abortus challenge (P abortus might be a useful candidate for subunit vaccine for brucellosis in animals. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Impaired bone healing at tooth extraction sites in CD24-deficient mice: A pilot study.

    Science.gov (United States)

    Avivi-Arber, Limor; Avivi, Doran; Perez, Marilena; Arber, Nadir; Shapira, Shiran

    2018-01-01

    To use a micro-computed tomography (micro-CT) to quantify bone healing at maxillary first molar extraction sites, and test the hypothesis that bone healing is impaired in CD24-knockout mice as compared with wild-type C57BL/6J mice. Under ketamine-xylazine general anaesthesia, mice had either extraction of the right maxillary first molar tooth or sham operation. Mice were sacrificed 1 (n = 12/group), 2 (n = 6/group) or 4 (n = 6/group) weeks postoperatively. The right maxillae was disected. Micro-CT was used to quantify differences in bone microstructural features at extrction sites, between CD24-knockout mice and wild-type mice. CD24-Knockout mice displayed impaired bone healing at extraction sites that was manifested as decreased trabecular bone density, and decreased number and thickness of trabeculae. This pilot study suggests that CD24 plays an important role in extraction socket bone healing and may be used as a novel biomarker of bone quality and potential therapeutic target to improve bone healing and density following alveolar bone injury.

  2. A recombinant bivalent fusion protein rVE confers active and passive protection against Yersinia enterocolitica infection in mice.

    Science.gov (United States)

    Singh, Amit Kumar; Kingston, Joseph Jeyabalaji; Murali, Harishchandra Sripathy; Batra, Harsh Vardhan

    2014-03-05

    In the present study, a bivalent chimeric protein rVE comprising immunologically active domains of Yersinia pestis LcrV and YopE was assessed for its prophylactic abilities against Yersinia enterocolitica O:8 infection in murine model. Mice immunized with rVE elicited significantly higher antibody titers with substantial contribution from the rV component (3:1 ratio). Robust and significant resistance to Y. enterocolitica infection with 100% survival (Penterocolitica O:8 against the 75%, 60% and 75% survival seen in mice immunized with rV, rE, rV+rE, respectively. Macrophage monolayer supplemented with anti-rVE polysera illustrated efficient protection (89.41% survival) against challenge of Y. enterocolitica O:8. In contrast to sera from sham-immunized mice, immunization with anti-rVE polysera provided complete protection to BALB/c mice against I.P. challenge with 10(8)CFU of Y. enterocolitica O:8 and developed no conspicuous signs of infection in necropsy. The histopathological analysis of microtome sections confirmed significantly reduced lesion size or no lesion in liver and intestine upon infection in anti-rVE immunized mice. The findings from this study demonstrated the fusion protein rVE as a potential candidate subunit vaccine and showed the functional role of antibodies in protection against Y. enterocolitica infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. PET imaging of brain with the β-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease

    International Nuclear Information System (INIS)

    Toyama, Hiroshi; Ye, Daniel; Cohen, Robert M.; Ichise, Masanori; Liow, Jeih-San; Cai, Lisheng; Musachio, John L.; Hong, Jinsoo; Crescenzo, Mathew; Tipre, Dnyanesh; Lu, Jian-Qiang; Zoghbi, Sami; Vines, Douglass C.; Pike, Victor W.; Innis, Robert B.; Jacobowitz, David; Seidel, Jurgen; Green, Michael V.; Katada, Kazuhiro

    2005-01-01

    The purpose of this study was to evaluate the capacity of [ 11 C]6-OH-BTA-1 and positron emission tomography (PET) to quantify β-amyloid (Aβ) plaques in the Tg2576 mouse model of Alzheimer's disease (AD). PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0±1.8 months; 23.6±2.6 g) overexpressing a mutated form of human β-amyloid precursor protein (APP) known to result in the production of Aβ plaques, and in six elderly wild-type litter mates (age 21.8±1.6 months; 29.5±4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13-46 MBq of [ 11 C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time-activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S. TACs for [ 11 C]6-OH-BTA-1 in all ROIs peaked early (at 30-55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12-30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06±0.04 vs 0.98±0.07, p=0.04; 1.06±0.09 vs 0.93±0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread Aβ plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild-type mice. Marked reductions in brain uptake of this

  4. Ovarian protection in cyclophosphamide-treated mice by fennel

    Directory of Open Access Journals (Sweden)

    Azam Hassanpour

    Full Text Available Evaluation of protective effect of fennel on mouse ovary against the destructive effects of cyclophosphamide (CP was the aim of this study. Adult female NMARI mice were randomly divided into six groups (n = 8: (A negative control, (B CP200 mg/kg, (C fennel 400 mg/kg/day, (E, F, and D that received fennel 200, 400 and 100 mg/kg/day respectively + CP200 mg/kg. Their ovary weight, volume, and diameter (WVD were measured. Five micron sections were stained using the H&E method. The serum levels of oestrogen and progesterone were measured using ELISA kit. The results showed that WVD significantly reduced in the CP-treated groups in comparison with the A and C, but WVD increased after treatment of the mice with fennel extract, in comparison with B group. A significant decrease of serum in terms of oestrogen and progesterone levels among CP-treated groups in comparison with the A group was observed. In the CP-treated groups a reduction in the number of different ovarian follicles in comparison with the A and C groups was observed. However, in the treated animals with fennel extract, these parameters significantly increased in comparison with the B group. Finally, it is concluded that fennel can protect ovary from cyclophosphamide side effects. Keywords: Cyclophosphamide, Fennel, Mice, Ovary

  5. Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α4/δ GABAA Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice

    Science.gov (United States)

    Sanna, Enrico; Talani, Giuseppe; Obili, Nicola; Mascia, Maria Paola; Mostallino, Maria Cristina; Secci, Pietro Paolo; Pisu, Maria Giuseppina; Biggio, Francesca; Utzeri, Cinzia; Olla, Pierluigi; Biggio, Giovanni; Follesa, Paolo

    2011-01-01

    Post-weaning social isolation (SI) is a model of prolonged mild stress characterized by behavioral and neurochemical alterations. We used SI in C57BL/6J mice to investigate the effects of ethanol (EtOH) in the free-choice drinking paradigm on gene expression and function of γ-aminobutyric acid type A receptors (GABAARs) and the role of neuroactive steroids in the actions of EtOH in the hippocampus. SI stress induced a marked reduction in hippocampal 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) and was associated with molecular and functional changes of the GABAAR. The gene expression of the α4 and δ subunits was increased in the hippocampus of SI C57BL/6J mice; the expression of the γ2 subunit was decreased whereas that of the α1 did not change. Patch-clamp recordings in dentate gyrus (DG) granule cells obtained from SI C57BL/6J mice revealed a greater enhancement of tonic currents induced by α-(4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridin-3-ol (THIP) compared to that in control C57BL/6J mice. These neurochemical, molecular and functional changes observed in SI C57BL/6J mice were associated with an increased EtOH intake and EtOH preference. Nevertheless, the increase in EtOH consumption did not restore the reduction in hippocampal 3α,5α-TH PROG induced by SI. EtOH self-administration blocked the changes in gene expression of the α4 subunit but not those of the δ and γ2 subunits induced by SI. In addition, EtOH self-administration did not block the SI-induced changes in GABAAR-mediated tonic inhibition in hippocampal granule cells but increased the frequency of basal GABAergic sIPSCs in DG granule cells. We conclude that self-administration of EtOH selectively abolishes the increase of α4 subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress. PMID:21347217

  6. Protective effect of vitamins C and E on Gamma radiation induced Genetic injuries in male mice germ cells

    International Nuclear Information System (INIS)

    Anwar, W.A.; El-Daway, H.A.E.; Tawfik, S.S.M.

    1999-01-01

    The effects of vitamins C and E on meiotic chromosomal metaphase-8 at diakinesis of the mouse to 3 Gy of whole body gamma- irradiation were studied. These vitamins were injected intraperitoneally as acute doses 2 hr before irradiation. Both vitamins significantly reduced the frequencies of chromosomal aberration in spermatic germ cells. The protective effect of vitamin E was greater than that afforded by vitamin C. A combined treatment of both vitamins resulted in additional protection over that offered by each vitamine alone. In all animal groups the most frequent aberration found was translocation in the from of either ring four (R IV) or chain four (C IV). The percentage of each or them was significantly increased in male mice sacrificed after 15 days post-irradiation. Other types of aberrations as autosomal univalent, X-Gamma univalent and polyploidy were rarely present

  7. Electrodeposition of Ni(OH)2 reinforced polyaniline coating for corrosion protection of 304 stainless steel

    Science.gov (United States)

    Jiang, Li; Syed, Junaid Ali; Gao, Yangzhi; Lu, Hongbin; Meng, Xiangkang

    2018-05-01

    In the present paper, polyaniline (PANI) coating was electropolymerized in the presence of phosphoric acid with subsequent deposition of Ni(OH)2 particles. The Ni(OH)2 reinforced PANI coating significantly enhances the corrosion resistance of 304 stainless steel (304SS) in comparison with the pristine PANI coating. The galvanostatically deposited Ni(OH)2 particles fill the pores of the pristine PANI coating and improves the coatings hydrophobicity which decreases the diffusion of aggressive media. Importantly, the Rp values of Ni(OH)2 reinforced PANI coating is much higher than that of pristine PANI coating and the Ni(OH)2 reinforced PANI coating presents a long-term anti-corrosive ability (360 h) in 3.5 wt% NaCl solution. The prolonged corrosion protection of Ni(OH)2 reinforced PANI coating is attributed to the improved physical barrier as well as the facile formation of passive oxide film that sustain the anodic protection of the coating.

  8. Biochemical aspects of the immunomodular action in irradiated survival mice with 60C gama irradiation

    International Nuclear Information System (INIS)

    Garcia Agudo, N.L. del M. de.

    1983-01-01

    The radioprotective action of Calmetti-Guerin bacillus (BCG), Corynebacterium parvum, Escherichia coli Lipopolysccharides (LPS) and peptone proteose was evaluated. A single injection of the macrophage activiting agents prior to 60 Co whole-body irradiation increased the survival rate of mice in the lethal dose range. (L.M.J.) [pt

  9. Vibrational spectra of 1-hydroxy- and 1,4-dihydroxyanthraquinones and their magnesium chelate complexes. I. Isotopic effects of OH/OD and 24Mg/26Mg substitutions

    International Nuclear Information System (INIS)

    Kirszenbaum, Marek

    1977-01-01

    The vibrational spectra of 1-hydroxy- and 1,4-dihydroxyanthraquinones, their deuterated derivatives and their 24 Mg/ 26 Mg chelate complexes are examined in the spectral region 1700-250cm -1 . The study of deuteroxyanthraquinones allow an assignment of the OH/OD group vibrations and show the multiple coupling of the delta OH vibrations with the vCC and delta CH quinonic vibrations. These results lead to a modification of some spectral assignments of magnesium chelate complexe of 1-OH-AQ. The isotopic 24 Mg/ 26 Mg substitution enables the chelate ring vibrations which depend on the motions of the magnesium atom to be observed. The vC=O and vC-O vibrations frequencies of magnesium chelate complexe [Mg(1,4-O 2 -AQ)]sub(n) show an important difference of the chelate ring electronic state in comparison of those of 1,4-(OH) 2 -AQ. The discussion of the infrared and Raman spectra in the Mg-O vibrations region lead to the conclusion that the configuration of oxygens arround the magnesium is tetrahedral [fr

  10. Hepatoprotective standardized EtOH-water extract from the seeds of Fraxinus rhynchophylla Hance.

    Science.gov (United States)

    Guo, Sen; Guo, Tiantian; Cheng, Ni; Liu, Qingchao; Zhang, Yunting; Bai, Lu; Zhang, Li; Cao, Wei; Ho, Chi-Tang; Bai, Naisheng

    2017-04-01

    Fraxinus rhynchophylla Hance (Oleaceae), its stem barks are known as Cortex fraxini ( qín pí) listed in Chinese Pharmacopoeia. Phytochemical study has indicated that methanol extracts from Qinpi has protective effect on acute liver injury. The present study investigates the hepatoprotective activity of EtOH-water extract from the seeds of F. rhynchophylla Hance against carbon tetrachloride-induced liver injury in mice. The EtOH-water extract significantly alleviated liver damage as indicated by the decreased levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the malondialdehyde (MDA) content, and increased the levels of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px), and reduced the pathological tissue injury induced by CCl 4 . Quantitative analysis of seven major constituents ( 1-7 ) in EtOH-water extract (EWE) was developed by high performance liquid chromatography-diode-array detector (HPLC-DAD). The current research indicates that the EWE from the seeds of F. rhynchophylla Hance decreased liver index, inhibited the increase of serum aminotransferase induced by CCl 4 , and decreased hepatic MDA content, SOD and GSH-Px activities. These results suggested that the pretreatment with EWE protected mice against CCl 4 -induced liver injuries. Based on the results, the EtOH-water extract from the seeds of F. rhynchophylla Hance is efficacious for prevention and treatment of CCl 4 -induced hepatic injury in mice. Secoiridoid and tyrosol glucosides might be the active ingredients responsible for the biological and pharmacological activities of hepatoprotection.

  11. Protection effect of ginkgo albumin extract on γ-ray irradiated mice

    International Nuclear Information System (INIS)

    Deng Qianchun; Duan Huike; Wang Lan; Xie Bijun; Chen Chunyan

    2005-01-01

    Water soluble ginkgo albumin extract (GAE), which was extracted for the first time from seeds of Ginkgo bilbo L in our laboratory has good antioxidant and anti-aging activity. In this paper, protective effect of GAE on γ-rays irradiated mice was studied. The results showed that the mice irradiated to 8.5 Gy were zero, whereas survival rate of the high dosage GAE group was 20 percent. Blood picture of the 8.5 Gy irradiated mice suffered damages of different degrees, while blood picture index of the GAE group decreased slower and recovered faster significantly than the irradiation control group. GAE and Vitamin C could significantly enhance serum SOD activity in serum and increase DNA content in bone marrow cells, and also promote recovery of damaged immunology function of the irradiated mice. These suggest that GAE may protect mice from the radiation damages by enhancement of antioxidant activity, hemopoiesis function and immunologic function of mice. (authors)

  12. Radioprotective effect of both vitamins E and / or C on some blood components of male mice

    International Nuclear Information System (INIS)

    Anwar, W.A.; El-Daway, H.A.E.; Tawfik, S.S.M.; Soliman, S.M.

    1999-01-01

    The protective effects of vitamin C and/or vitamin E on some blood components and serum level of thiobarbituric reactive substances (as indicator to level of lipid peroxidation) of irradiated male mice at dose 3 Gy sacrificed after 15,24 and 46 days of irradiation have been assessed in comparison with control and non-irradiated-treated with vitamin C and/or vitamin E groups. Vit. C, vit. E or in combination decreased the effect of irradiation on blood components and the level of thiobarbituric reactive substances, but average haemoglobin level RBC count, total WBC count, neutrophil count and lymphocyte count did not reach to the original average level even after 36 days of irradiation. Vit. E had a more protective effect than vit. C in case of total white blood cells, while vit. C was more protective in case of lymphocyte count. The combination of vitamins C and E had more protective effect than either of both vitamins alone. The decrease in lipid peroxidation products due to administration of vit. E and vit. C as antioxidants supported the theory that lipid peroxidation increased due to free radicals induced by irradiation

  13. Synthetic bovine proline-rich-polypeptides generate hydroxyl radicals and fail to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in mice.

    Science.gov (United States)

    Knaryan, Varduhi H; Samantaray, Supriti; Varghese, Merina; Srinivasan, Ambika; Galoyan, Armen A; Mohanakumar, Kochupurackal P

    2006-08-01

    Proline-rich-polypeptides (PRPs) isolated from bovine hypothalamus have been shown to render protection against neuronal injury of the brain and spinal cord. We examined two PRPs containing 15 and 10 amino acid residues (PRP-1 and PRP-4 synthetic polypeptide) for their effect, if any, on dopaminergic neuronal damage caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Effects of these PRPs on hydroxyl radical ((*)OH) generation in a Fenton-like reaction as well as from isolated mitochondria were monitored, employing a sensitive salicylate hydroxylation procedure. Balb/c mice treated (i.p., twice, 16 h apart) with MPTP (30 mg/kg) or PRP-1 (1.6 mg/kg), but not PRP-4 (1.6 mg/kg) showed significant loss of striatal dopamine and norepinephrine as assayed by an HPLC-electrochemical procedure. Pretreatment with the PRPs, 30 min prior to the neurotoxin administration failed to attenuate MPTP-induced striatal dopamine or norepinephrine depletion, but significantly attenuated the MPTP-induced decrease in dopamine turnover. A significant increase in the generation of (*)OH by the PRPs in a Fenton-like reaction or from isolated mitochondria suggests their pro-oxidant action, and explains their failure to protect against MPTP-induced parkinsonism in mice.

  14. Lecithin-cholesterol acyltransferase in brain: Does oxidative stress influence the 24-hydroxycholesterol esterification?

    Science.gov (United States)

    La Marca, Valeria; Maresca, Bernardetta; Spagnuolo, Maria Stefania; Cigliano, Luisa; Dal Piaz, Fabrizio; Di Iorio, Giuseppe; Abrescia, Paolo

    2016-04-01

    24-Hydroxycholesterol (24OH-C) is esterified by the enzyme lecithin-cholesterol acyltransferase (LCAT) in the cerebrospinal fluid (CSF). We report here that the level of 24OH-C esters was lower in CSF of patients with amyotrophic lateral sclerosis than in healthy subjects (54% vs 68% of total 24OH-C, p=0.0005; n=8). Similarly, the level of 24OH-C esters in plasma was lower in patients than in controls (62% vs 77% of total 24OH-C; p=0.0076). The enzyme amount in CSF, as measured by densitometry of the protein band revealed by immunoblotting, was about 4-fold higher in patients than in controls (p=0.0085). As differences in the concentration of the LCAT stimulator Apolipoprotein E were not found, we hypothesized that the reduced 24OH-C esterification in CSF of patients might depend on oxidative stress. We actually found that oxidative stress reduced LCAT activity in vitro, and 24OH-C effectively stimulated the enzyme secretion from astrocytoma cells in culture. Enhanced LCAT secretion from astrocytes might represent an adaptive response to the increase of non-esterified 24OH-C percentage, aimed to avoid the accumulation of this neurotoxic compound. The low degree of 24OH-C esterification in CSF or plasma might reflect reduced activity of LCAT during neurodegeneration. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  15. Lahar inundated, modified, and preserved 1.88 Ma early hominin (OH24 and OH56) Olduvai DK site.

    Science.gov (United States)

    Stanistreet, I G; Stollhofen, H; Njau, J K; Farrugia, P; Pante, M C; Masao, F T; Albert, R M; Bamford, M K

    2018-03-01

    Archaeological excavations at the DK site in the eastern Olduvai Basin, Tanzania, age-bracketed between ∼1.88 Ma (Bed I Basalt) and ∼1.85 Ma (Tuff IB), record the oldest lahar inundation, modification, and preservation of a hominin "occupation" site yet identified. Our landscape approach reconstructs environments and processes at high resolution to explain the distribution and final preservation of archaeological materials at the DK site, where an early hominin (likely Homo habilis) assemblage of stone tools and bones, found close to hominin specimens OH24 and OH56, developed on an uneven heterogeneous surface that was rapidly inundated by a lahar and buried to a depth of 0.4-1.2 m (originally ∼1.0-2.4 m pre-compaction). The incoming intermediate to high viscosity mudflow selectively modified the original accumulation of "occupation debris," so that it is no longer confined to the original surface. A dispersive debris "halo" was identified within the lahar deposit: debris is densest immediately above the site, but tails off until not present >150 m laterally. Voorhies indices and metrics derived from limb bones are used to define this dispersive halo spatially and might indicate a possible second assemblage to the east that is now eroded away. Based upon our new data and prior descriptions, two possibilities for the OH24 skull are suggested: it was either entrained by the mudflow from the DK surface and floated due to lower density toward its top, or it was deposited upon the solid top surface after its consolidation. Matrix adhering to material found in association with the parietals indicates that OH56 at least was relocated by the mudflow. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Protective Effect of Vitamin D3 and Gp63 Conjugated with Tetanus Toxoid on Outcome of Cutaneous Leishmaniasis Lesions in Balb/C Mice

    Directory of Open Access Journals (Sweden)

    S Soudi

    2006-01-01

    Full Text Available Introduction: GP63 is a major surface protease of Leishmania promastigotes that plays an important role in its virulance. As GP63 on its own can not develop an effective protection against leishmaniasis, the goal of this study was to evaluate the protective effect of GP63 conjugated with tetanus toxoid (TT and Vitamin D3 in susceptible BALB/c mice against cutaneous leishmaniasis. Methods: This study was a basic-applied experimental study performed in Tarbiat Modarres University from September 2002 to April 2005. Cloned virulant Leishmania (L. major [MRHO / IR / 75 / ER] strain was cultured and 5109 cells were harvested. GP63 Molecule was purified and conjugated with TT and conjugated molecule was used for immunization of 8 groups of female BALB/c mice. Results: Results showed that the group of mice receiving conjugated molecule with Vitamin D3 had significant differences from other groups regarding lesion progression (P0.05. The culture of spleen cells showed that the disease did not become systemic in this group. Conclusion: Conjugation of GP63 with TT strengthens cell immunity and its use along with vitamin D3 provokes macrophages activity. This basis can be used for production of an appropriate preparation for protection against Leishmaniasis.

  17. Protective effect of yeast β-glucan on immune system of mice irradiated by carbon ions

    International Nuclear Information System (INIS)

    Wang Ying; Lu Dong; Wei Wei; Jing Xigang; Wang Jufang; Li Wenjian

    2012-01-01

    Abstract. To detect Yeast β-glucan's protective effect on mice's immune system after C ion beam radiation, mice were used as the test model. We observed the weight, hair color and behavior of mice everyday within a 7 d period of time after irradiation. Meanwhile, the content of white blood cell, on the 2nd and 7th day after irradiation was detected. We detected the thymus and spleen SOD, GSH-PX activity and MDA content of the mice on the 8th day. The results showed that yeast β-glucan could reduce the rapid weight loss of mice, increase white blood cell content, increase thymus and spleen SOD, GSH-PX activity, decrease MDA content of thymus and spleen. These results indicate that yeast 13-glucan can protect mice's immune system against C ion beam radiation damage. (authors)

  18. Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

    Science.gov (United States)

    Greenberg, G D; Huang, L C; Spence, S E; Schlumbohm, J P; Metten, P; Ozburn, A R; Crabbe, J C

    2016-04-01

    Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice. Published by Elsevier B.V.

  19. Preparative-scale separation of C60 and C70 on polystyrene gel

    International Nuclear Information System (INIS)

    Guegel, A.; Becker, M.; Hammel, D.; Mindach, L.; Raeder, J.; Simon, T.; Wagner, M.; Muellen, K.

    1992-01-01

    Five grams of a mixture of C 60 /C 70 can be separated in 24 hours by gel permeation chromatography on polystyrene gel. The mobile phase can be completely recovered, and the method can be scaled up by a simple increase in the inner diameter of the column. (orig.) [de

  20. Experimental transmission of M. leprae into the testes of mice born from 60Co-irradiated pregnant mice

    International Nuclear Information System (INIS)

    Sushida, Kiyo; Tanemura, Mutsuko

    1979-01-01

    R 1 -mice, which were born from pregnant mice (R-P) irradiated with 60 CO 300 R were inoculated with leprosy bacilli into the testis. Recently, the author reported that the skin homograft survival duration in 60 CO-irradiated mice (R-P) was shown to be longer than the duration in the R 1 -F mice. The acid-fast bacilli, the so-called globi, were often found at the inoculated site of R-P mice, but not in the R 1 -F mice. The R 1 -F females bred with normal males and the R 2 -F females bred with normal males were both irradiated with 60 CO 300 R, and the R 2 -F male offspring from this R 1 -F and the R 3 -F male offspring from this R 2 -F showed the same increase in sensitivity to leprosy bacilli as the R-P generation. Acid-fast bacilli (globi, +G) were also found in the testes of the R 2 -F and R 3 -F males. IR-F mice which had received 131 I-Na 100 μci injections and also 60 CO 300 R irradiations during their fetus-term, showed few increase in sensitivity to infection of leprosy bacilli. (author)

  1. Comparison of potential protection conferred by three immunization strategies (protein/protein, DNA/DNA, and DNA/protein) against Brucella infection using Omp2b in BALB/c Mice.

    Science.gov (United States)

    Golshani, Maryam; Rafati, Sima; Nejati-Moheimani, Mehdi; Ghasemian, Melina; Bouzari, Saeid

    2016-12-25

    In the present study, immunogenicity and protective efficacy of the Brucella outer membrane protein 2b (Omp2b) was evaluated in BALB/c mice using Protein/Protein, DNA/DNA and DNA/Protein vaccine strategies. Immunization of mice with three vaccine regimens elicited a strong specific IgG response (higher IgG2a titers over IgG1 titers) and provided Th1-oriented immune response. Vaccination of BALB/c mice with the DNA/Pro regimen induced higher levels of IFN-γ/IL-2 and conferred more protection levels against B. melitenisis and B. abortus challenge than did the protein or DNA alone. In conclusion, Omp2b is able to stimulate specific immune responses and to confer cross protection against B. melitensis and B. abortus infection. Therefore, it could be introduced as a new potential candidate for the development of a subunit vaccine against Brucella infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. BLOCKADE OF PGE2, PGD2 RECEPTORS CONFERS PROTECTION AGAINST PREPATENT SCHISTOSOMIASIS MANSONI IN MICE.

    Science.gov (United States)

    Abdel-Ghany, Rasha; Rabia, Ibrahim; El-Ahwany, Eman; Saber, Sameh; Gamal, Rasha; Nagy, Faten; Mahmoud, Olaa; Hamad, Rabab Salem; Barakat, Walled

    2015-12-01

    Schistosomiasis is a chronic disease with considerable social impact. Despite the availability of affordable chemotherapy, drug treatment has not significantly reduced the overall number of disease cases. Among other mechanisms, the parasite produces PGE2 and PGD2 to evade host immune defenses. To investigate the role of PGE2 and PGD2 in schistosomiasis, we evaluated the effects of L-161,982, Ah6809 (PGE2 receptor antagonists alone of combined with each other) and MK-0524 (PGD2 receptor antagonist) during prepatent Schistosoma mansoni infection. Drugs were administered intraperitoneally an hour before and 24 hours after infection of C57BL/6 mice with 100 Schistosoma mansoni cercariae. L-161,982, Ah6809, their combination and MK-0524 caused partial protection against pre-patent S. mansoni infection which was mediated by biasing the immune response towards Th1 phenotype. These results showed that blockade of PGE2 and PGD2 receptors confers partial protection against pre-patent S. mansoni infection in mice and that they may be useful as adjunctive therapy to current anti-schistosomal drugs or vaccines.

  3. MF59- and Al(OH3-adjuvanted Staphylococcus aureus (4C-Staph vaccines induce sustained protective humoral and cellular immune responses, with a critical role for effector CD4 T cells at low antibody titers.

    Directory of Open Access Journals (Sweden)

    Elisabetta eMonaci

    2015-09-01

    Full Text Available Staphylococcus aureus (S. aureus is an important opportunistic pathogen that may cause invasive life-threatening infections like sepsis and pneumonia. Due to increasing antibiotic-resistance, the development of an effective vaccine against S. aureus is needed. Although a correlate of protection against staphylococcal diseases is not yet established, several findings suggest that both antibodies and CD4 T cells might contribute to optimal immunity. In this study, we show that adjuvanting a multivalent vaccine (4C-Staph with MF59, an oil-in-water emulsion licensed in human vaccines, further potentiated antigen-specific IgG titers and CD4 T cell responses compared to alum and conferred protection in the peritonitis model of S. aureus infection. Moreover, we showed that MF59- and alum-adjuvanted 4C-Staph vaccines induced persistent antigen-specific humoral and T cell responses, and protected mice from infection up to 4 months after immunization. Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune compartment is involved in vaccine-induced protection. Using CD4 T cell-depleted mice or B cell deficient mice, we demonstrated that both T and B cell responses contributed to 4C-Staph vaccine-mediated protective immunity. However, the role of CD4 T cells seemed more evident in the presence of low antibody responses. This study provides preclinical data further supporting the use of the adjuvanted 4C-Staph vaccines against S. aureus diseases, and provides critical insights on the correlates of protective immunity necessary to combat this pathogen.

  4. HeLa cell tumor response to 60Co, Cs-137, Cf-252 radiations and cisplatin chemotherapy in nude mice

    International Nuclear Information System (INIS)

    Maruyama, Y.; Feola, J.M.; Beach, J.L.

    1984-01-01

    HeLa cells were implanted into athymic nude mice from tissue culture and solid tumors established (HeLa cell tumor or HCT). Large cell numbers of 1 X 10 7 were required to obtain consistent and progressive growth, and tumor growth followed a Gompertzian mode. Irradiation studies were carried out using acute Cobalt-60 (60Co), low-dose-rate (LDR) Cs-137 and LDR Cf-252. Cf-252, a neutron-emitting radioisotope, produced an immediate tumor shrinkage and regression response after a dose of 279 cGy. Acute 60Co or LDR Cs-137 irradiation with 1000 cGy had little effect on the HCT. After a dose of 2000 cGy of 60Co radiation tumor shrinkage followed a latent period of approximately 5 days. Cisplatin had no effect on the HCT in nude mice in stationary or late exponential growth

  5. Protective Effects of Dihydromyricetin against •OH-Induced Mesenchymal Stem Cells Damage and Mechanistic Chemistry

    Directory of Open Access Journals (Sweden)

    Xican Li

    2016-05-01

    Full Text Available As a natural flavonoid in Ampelopsis grossedentata, dihydromyricetin (DHM, 2R,3R-3,5,7,3′,4′,5′-hexahydroxy-2,3-dihydroflavonol was observed to increase the viability of •OH-treated mesenchymal stem cells using a MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl] assay and flow cytometry analysis. This protective effect indicates DHM may be a beneficial agent for cell transplantation therapy. Mechanistic chemistry studies indicated that compared with myricetin, DHM was less effective at ABTS+• (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical scavenging and reducing Cu2+, and had higher •O2− and DPPH• (1,1-diphenyl-2-picrylhydrazyl radical scavenging activities. Additionally, DHM could also chelate Fe2+ to give an absorption maximum at 589 nm. Hence, such protective effect of DHM may arise from its antioxidant activities which are thought to occur via direct radical-scavenging and Fe2+-chelation. Direct radical-scavenging involves an electron transfer (ET pathway. The hydrogenation of the 2,3-double bond is hypothesized to reduce the ET process by blocking the formation of a larger π-π conjugative system. The glycosidation of the 3–OH in myricitrin is assumed to sterically hinder atom transfer in the •O2− and DPPH• radical-scavenging processes. In DHM, the Fe2+-chelating effect can actually be attributed to the 5,3′,4′,5′–OH and 4–C=O groups, and the 3–OH group itself can neither scavenge radicals nor chelate metal.

  6. Empirical study on protective effect of dendrobium candidum wall.ex lindl drop on acute radiation-injuried mice

    International Nuclear Information System (INIS)

    Sun Jingping; Zhang Guoqing

    2008-01-01

    Objective: To study the protective effect of Dendrobium candidum Wall.ex Lindl drop (DCWD) on acute radiation-injuried mice and the correlative mechanism. Methods: According to the body weight BALB/c mice were divided into the control group, radiation-injuried group and DCWD groups which were divided into two groups according to the dose of DCWD. Before whole-body irradiation with 4.0 Gy 6 MV X-rays, the BALB/c mice were supplied with DCWD every day. After being irradiated, these mice were continued to be given DCWD until they were killed. The DNA contents of bone marrow, the CD4 + /CD8 + ratios of peripheral blood and splenic cells, blastation of lymphocyte and the contents of IL-2 were observed. Results: DCWD hasincreased the DNA contents of bone marrow, the ability of blastation of lymphocyte and the IL-2 contents of irradiated mice. It has protected T leukomonocyte by accommodating the hyprotypes of T leukomonocyte. Conclusion: DCWD can protect the acute radiation-injuried mice which relates with protecting the hematopoiesis and the immune function etc. (authors)

  7. Fullerene C[sub 60

    Energy Technology Data Exchange (ETDEWEB)

    Koruga, D; Hameroff, S; Sundareshan, M [Univ. of Arizona, Tucson, AZ (United States); Withers, J; Loutfy, R [MER Corp., Tucson, AZ (United States)

    1993-01-01

    This book, one of the first to be published in the exciting field of fullerenes, includes a short history of scientific discovery, as well as one possible answer to the question: for what purposes can C[sub 60] be utilized. The book opens with a review of the life of Buckminster Fuller. Modern history of fivefold symmetry and the icosahedron began between 1984 and 1985, when Shechtman and his research team opened a new branch in crystallography (fivefold symmetry) and when the Kroto/Smalley research team discovered the C[sub 60] molecule (truncated icosahedron). Production of solid C[sub 60] by the Huffman/Kraeschner research team in 1990 provided a new stimulus for research by producing C[sub 60] in macroscopic amounts for use by the scientific and technological community. This achievement led to developments such as Koruga's August 1992 creation of the dimer C[sub 116] using scanning tunneling engineering and Loutfy's hydrogenation of C[sub 60] and construction of the first Ni/C[sub 60] rechargeable batteries in December 1992. New inventions based on C[sub 60] will continue to be forthcoming, particularly in the areas of superconductivity, quantum devices, and molecular electronic devices. Discovery of the C[sub 60] molecule (Kroto/Smalley), production of solid C[sub 60] (Huffman/Kraeschmer) and technological inventions such as C[sub 116] (Koruga) have been chance discoveries. A short history of these discoveries is detailed in the book along with the results of the authors' Fullerene research efforts, including atomic resolution images of Fullerene C[sub 60], Ni/C[sub 60] batteries, nanotechnology of C[sub 60], comparison of C[sub 60] with biological systems, and others. As Fullerene C[sub 60] will require control engineering, an overview of control systems, in particular, general and optimal control of the Schroedinger equation, is contained. Some experimental and theoretical work of other researchers are also presented. 140 figs., 4 tabs., 342 refs.

  8. Caffeine-11C, ephedrine-11C and methylephedrine-11C: synthesis and distribution in mice

    International Nuclear Information System (INIS)

    Saji, Hideo; Ido, Tatsuo; Iwata, Ren; Suzuki, Kazutoshi; Tamate, Kazuhiko

    1978-01-01

    Caffeine, ephedrine and methylephedrine were labeled with carbon-11 by the action of methyliodide- 11 C on theophylline, norephedrine and ephedrine, respectively. Caffeine- 11 C was prepared in 44 min. with a radiochemical yield of 40%, ephedrine- 11 C in 45 min. with a 11% radiochemical yield and methylephedrine- 11 C in 36 min. with a 43% radiochemical yield. When injected in mice intravenously, these products show a high uptake in the liver, the kidney and the blood for caffeine- 11 C and in the liver and the kidney for ephedrine- 11 C and methylephedrine- 11 C. The brain uptake for these products was found to be 2.4 to 3.9% of the injected dose per gram at 5 min. after injection. These studies in mice have demonstrated that these products are potentially useful agents for the dynamic studies of the brain. (auth.)

  9. Protective effect study of polysaccharides from tremella fuciformis on hematopoietic function in radiation-injured mice

    International Nuclear Information System (INIS)

    Xu Wenqing; Chinese Academy of Medical Sciences, Tianjin; Gao Wenyuan; Shen Xiu; Wang Yueying; Liu Peixun

    2006-01-01

    Objective: To study the protective effects of polysaccharides of Tremella fuciformis on hematopoietic function in radiation-injured mice. Methods; Colony-forming unit of spleen (CFU-S), number of nucleated cells in bone marrow (BMNC) and spleen index were used to investigated the effect of polysacharides from tremella fuciformis at 6 mg/kg, 12 mg/kg, 24 mg/kg on hematopoietic function of mice irradiated with 7.5 Gy 137 Cs γ-rays. Results: On the 9 the day after irradiation compared with the negative control group number of nucleated cells in bone marrow, colony-forming unit of spleen and spleen index of mice have treated with polysaccharides from Tremella fuciformis intraperitoneally for three days prior to irradiation increased markedly. Conclusion: Polysaccharides of tremella fuciformis have protective effect on hematopoietic function of radiation-injured mice. (authors)

  10. Influences of atom Ar on Ar at C60 + Ar at C60 collisions

    International Nuclear Information System (INIS)

    Zhao Qiang; Zhou Hongyu; Zhang Fengshou

    2007-01-01

    A semi-emperical molecular dynamics model was developed. The central collisions of C 60 + C 60 and Ar at C 60 + Ar at C 60 at the same incident energy were investigated within this model. The fullerene dimers could be formed by a self-assembly of C 60 fullerene, and the new fullerene structure like 'peanut' could be formed by a self-assembly of Ar at C 60 . It was found that atom Ar had a great effect on the collision of Ar at C 60 + Ar at C 60 . (authors)

  11. Vaccination of adult and newborn mice of a resistant strain (C57BL/6J) against challenge with leukemias induced by Moloney murine leukemia virus

    International Nuclear Information System (INIS)

    Reif, A.E.

    1985-01-01

    Adult or newborn C57BL/6J mice were immunized with isogenic Moloney strain MuLV-induced leukemia cells irradiated with 10,000 rads or treated with low concentrations of formalin. Groups of immunized and control mice were challenged with a range of doses of viable leukemia cells, and tumor deaths were recorded for 90 days after challenge. Then, the doses of challenge cells which produced 50% tumor deaths were calculated for immunized and control mice. The logarithm of their ratio quantified the degree of protection provided by immunization. For adult C57BL/6J mice, a single immunization with MuLV-induced leukemia cells was not effective; either cells plus Bacillus Calmette-Guerin or Corynebacterium parvum, or else two immunizations with irradiated leukemia cells were needed to produce statistically significant increases in the values of the doses of challenge cells which produced 50% tumor deaths. Cross-protection was obtained by immunization with other isogenic MuLV-induced leukemias, but not by immunization with isogenic carcinogen-induced tumors or with an isogenic spontaneous leukemia. For newborn mice, a single injection of irradiated leukemia cells provided 1.3 to 1.5 logs of protection, and admixture of B. Calmette-Guerin or C. parvum increased this protection to 2.4 to 2.7 logs. Since irradiated and frozen-thawed MuLV-induced leukemia cells contained viable MuLV, leukemia cells treated with 0.5 or 1.0% formalin were tested as an alternative. A single injection of formalin-treated isogenic leukemia cells admixed with C. parvum provided between 1.7 and 2.8 logs of protection. These results demonstrate that a single vaccination of newborn animals against a highly antigenic virally induced leukemia produces strong protection against a subsequent challenge with viable leukemia cells

  12. Modest vasomotor dysfunction induced by low doses of C60 fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

    DEFF Research Database (Denmark)

    Vesterdal, Lise K; Folkmann, Janne K; Jacobsen, Nicklas R

    2009-01-01

    ABSTRACT: BACKGROUND: Exposure to small size particulate matter in urban air is regarded as a risk factor for cardiovascular effects, whereas there is little information about the impact on the cardiovascular system by exposure to pure carbonaceous materials in the nano-size range. C60 fullerenes...... (apoE-/-) with different degree of atherosclerosis. RESULTS: The aged apoE-/-mice had lower endothelium-dependent vasorelaxation elicited by acetylcholine in aorta segments mounted in myographs and the phenylephrine-dependent vasoconstriction response was increased. One hour after an intraperitoneal...

  13. 24 CFR 236.60 - Excess Income.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Excess Income. 236.60 Section 236... § 236.60 Excess Income. (a) Definition. Excess Income consists of cash collected as rent from the... Rent. The unit-by-unit requirement necessitates that, if a unit has Excess Income, the Excess Income...

  14. 47 CFR 24.237 - Interference protection.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Interference protection. 24.237 Section 24.237... SERVICES Broadband PCS § 24.237 Interference protection. (a) All licensees are required to coordinate their... protection criterion shall be such that the interfering signal will not produce more than 1.0 dB degradation...

  15. Protective effects of a polysaccharide from Spirulina platensis on dopaminergic neurons in an MPTP-induced Parkinson′s disease model in C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    Fang Zhang

    2015-01-01

    Full Text Available The present study aimed to determine whether a polysaccharide obtained from Spirulina platensis shows protective effects on dopaminergic neurons. A Parkinson′s disease model was established through the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP in C57BL/6J mice. Prior to the MPTP injection, some mice were pretreated with intraperitoneal injections of a polysaccharide derived from Spirulina platensis once daily for 10 days. The results showed that the immunoreactive staining and mRNA expression of the dopamine transporter and tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, in the substantia nigra, were significantly increased in mice pretreated with 800 mg/kg of the polysaccharide compared with those in MPTP-treated mice. The activities of superoxide dismutase and glutathione peroxidase in the serum and midbrain were also increased significantly in mice injected with MPTP after pretreatment with the polysaccharide from Spirulina platensis. By contrast, the activity of monoamine oxidase B in serum and midbrain maintained unchanged. These experimental findings indicate that the polysaccharide obtained from Spirulina platensis plays a protective role against the MPTP-induced loss of dopaminergic neurons in C57BL/6J mice, and that the antioxidative properties of this polysaccharide likely underlie its neuroprotective effect.

  16. PET imaging of brain with the {beta}-amyloid probe, [{sup 11}C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Hiroshi [Fujita Health University, Department of Radiology, Aichi (Japan); National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ye, Daniel; Cohen, Robert M. [National Institutes of Health, Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ichise, Masanori; Liow, Jeih-San; Cai, Lisheng; Musachio, John L.; Hong, Jinsoo; Crescenzo, Mathew; Tipre, Dnyanesh; Lu, Jian-Qiang; Zoghbi, Sami; Vines, Douglass C.; Pike, Victor W.; Innis, Robert B. [National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Jacobowitz, David [USUHS, Department of Anatomy, Physiology, and Genetics, Bethesda, Maryland (United States); Seidel, Jurgen; Green, Michael V. [National Institutes of Health, Department of Nuclear Medicine, Warren Grant Magnuson Clinical Center, Bethesda, Maryland (United States); Katada, Kazuhiro [Fujita Health University, Department of Radiology, Aichi (Japan)

    2005-04-01

    The purpose of this study was to evaluate the capacity of [{sup 11}C]6-OH-BTA-1 and positron emission tomography (PET) to quantify {beta}-amyloid (A{beta}) plaques in the Tg2576 mouse model of Alzheimer's disease (AD). PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0{+-}1.8 months; 23.6{+-}2.6 g) overexpressing a mutated form of human {beta}-amyloid precursor protein (APP) known to result in the production of A{beta} plaques, and in six elderly wild-type litter mates (age 21.8{+-}1.6 months; 29.5{+-}4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13-46 MBq of [{sup 11}C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time-activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S. TACs for [{sup 11}C]6-OH-BTA-1 in all ROIs peaked early (at 30-55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12-30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06{+-}0.04 vs 0.98{+-}0.07, p=0.04; 1.06{+-}0.09 vs 0.93{+-}0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread A{beta} plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild

  17. 6 CFR 13.24 - Protective order.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Protective order. 13.24 Section 13.24 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.24 Protective order. (a) A party or a prospective witness or deponent may file a motion for a protective order...

  18. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Galisteo Junior, Andres [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; E-mail: galisteo@usp.br; Zorgi, Nahiara Esteves; Andrade Junior, Heitor Franco de [Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; Alves, Janaina Baptista; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Hiramoto, Roberto Mitsuyoshi [instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2007-07-01

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/{sup 60}Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 10{sup 7} RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral

  19. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    International Nuclear Information System (INIS)

    Jimenez Galisteo Junior, Andres

    2007-01-01

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/ 60 Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 10 7 RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral vaccines could

  20. Inactivated Eyedrop Influenza Vaccine Adjuvanted with Poly(I:C Is Safe and Effective for Inducing Protective Systemic and Mucosal Immunity.

    Directory of Open Access Journals (Sweden)

    Eun-Do Kim

    Full Text Available The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1 virus challenge. Additionally, ocular inoculation with poly(I:C plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity.

  1. Vaccination with recombinant heat shock protein 60 from Histoplasma capsulatum protects mice against pulmonary histoplasmosis.

    OpenAIRE

    Gomez, F J; Allendoerfer, R; Deepe, G S

    1995-01-01

    HIS-62 is a glycoprotein that has been isolated from the cell wall and cell membrane fraction of the pathogenic fungus Histoplasma capsulatum. It is a target of the cellular immune response to this fungus, and it protects mice against a lethal intravenous inoculum of H. capsulatum yeast cells. In this study, we cloned the gene encoding this antigen to reveal its biological nature and studied the immunological activity of recombinant antigen. The amino acid sequences of the NH2 terminus and in...

  2. Enhanced sensitivity to ethanol-induced inhibition of LTP in CA1 pyramidal neurons of socially isolated C57BL/6J mice: role of neurosteroids

    Directory of Open Access Journals (Sweden)

    Giuseppe eTalani

    2011-10-01

    Full Text Available Ethanol (EtOH–induced impairment of long-term potentiation (LTP in the rat hippocampus is prevented by the 5α-reductase inhibitor finasteride, suggesting that this effect of EtOH is dependent on the increased local release of neurosteroids such as 3α,5α-THP that promote GABA–mediated transmission. Given that social isolation (SI in rodents is associated with altered plasma and brain levels of such neurosteroids as well as with an enhanced neurosteroidogenic action of EtOH, we examined whether the inhibitory effect of EtOH on LTP at CA3-CA1 hippocampal excitatory synapses is altered in C57BL/6J mice subjected to SI for 6 weeks in comparison with group-housed (GH animals. Extracellular recording of fEPSPs as well as patch-clamp analysis were performed in hippocampal slices prepared from both SI and GH mice. Consistent with previous observations, recording of fEPSPs revealed that the extent of LTP induced in the CA1 region of SI mice was significantly reduced compared with that in GH animals. EtOH (40 mM inhibited LTP in slices from SI mice but not in those from GH mice, and this effect of EtOH was abolished by co-application of 1 µM finasteride. Current-clamp analysis of CA1 pyramidal neurons revealed a decrease in action potential frequency and an increase in the intensity of injected current required to evoke the first action potential in SI mice compared with GH mice, indicative of a decrease in neuronal excitability associated with SI. Together, our data suggest that SI results in reduced levels of neuronal excitability and synaptic plasticity in the hippocampus. Furthermore, the increased sensitivity to the neurosteroidogenic effect of EtOH associated with SI likely accounts for the greater inhibitory effect of EtOH on LTP in SI mice. The increase in EtOH sensitivity induced by SI may be important for the changes in the effects of EtOH on anxiety and on learning and memory associated with the prolonged stress attributable to social

  3. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    Science.gov (United States)

    Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H; Farman, Helen H; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

    2014-01-01

    The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  4. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    Full Text Available The gut microbiota (GM modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L strain, L. paracasei DSM13434 (L. para or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  5. Species differences in methanol and formic acid pharmacokinetics in mice, rabbits and primates

    International Nuclear Information System (INIS)

    Sweeting, J. Nicole; Siu, Michelle; McCallum, Gordon P.; Miller, Lutfiya; Wells, Peter G.

    2010-01-01

    Methanol (MeOH) is metabolized primarily by alcohol dehydrogenase in humans, but by catalase in rodents, with species variations in the pharmacokinetics of its formic acid (FA) metabolite. The teratogenic potential of MeOH in humans is unknown, and its teratogenicity in rodents may not accurately reflect human developmental risk due to differential species metabolism, as for some other teratogens. To determine if human MeOH metabolism might be better reflected in rabbits than rodents, the plasma pharmacokinetics of MeOH and FA were compared in male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys over time (24, 48 and 6 h, respectively) following a single intraperitoneal injection of 0.5 or 2 g/kg MeOH or its saline vehicle. Following the high dose, MeOH exhibited saturated elimination kinetics in all 3 species, with similar peak concentrations and a 2.5-fold higher clearance in mice than rabbits. FA accumulation within 6 h in primates was 5-fold and 43-fold higher than in rabbits and mice respectively, with accumulation being 10-fold higher in rabbits than mice. Over 48 h, FA accumulation was nearly 5-fold higher in rabbits than mice. Low-dose MeOH in mice and rabbits resulted in similarly saturated MeOH elimination in both species, but with approximately 2-fold higher clearance rates in mice. FA accumulation was 3.8-fold higher in rabbits than mice. Rabbits more closely than mice reflected primates for in vivo MeOH metabolism, and particularly FA accumulation, suggesting that developmental studies in rabbits may be useful for assessing potential human teratological risk.

  6. Caffeine protects mice against whole-body lethal dose of {gamma}-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    George, K.C.; Hebbar, S.A.; Kale, S.P.; Kesavan, P.C. [Biosciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    1999-06-01

    Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of {gamma}-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the toxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice. (author)

  7. Protective effects of oridonin on the sepsis in mice

    Directory of Open Access Journals (Sweden)

    Yan-Jun Zhao

    2016-09-01

    Full Text Available This study aimed to investigate the protective effects of oridonin (ORI on cecal ligation and puncture (CLP-induced sepsis in mice. Male C57BL/6 mice weighing 22–30 g and aged 8–10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 μg/kg was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin–eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6, and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05. Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05. The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05. Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.

  8. Pregnane X Receptor-Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity.

    Science.gov (United States)

    Spruiell, Krisstonia; Gyamfi, Afua A; Yeyeodu, Susan T; Richardson, Ricardo M; Gonzalez, Frank J; Gyamfi, Maxwell A

    2015-09-01

    Both human and rodent females are more susceptible to developing alcoholic liver disease following chronic ethanol (EtOH) ingestion. However, little is known about the relative effects of acute EtOH exposure on hepatotoxicity in female versus male mice. The nuclear receptor pregnane X receptor (PXR; NR1I2) is a broad-specificity sensor with species-specific responses to toxic agents. To examine the effects of the human PXR on acute EtOH toxicity, the responses of male and female PXR-humanized (hPXR) transgenic mice administered oral binge EtOH (4.5 g/kg) were analyzed. Basal differences were observed between hPXR males and females in which females expressed higher levels of two principal enzymes responsible for EtOH metabolism, alcohol dehydrogenase 1 and aldehyde dehydrogenase 2, and two key mediators of hepatocyte replication and repair, cyclin D1 and proliferating cell nuclear antigen. EtOH ingestion upregulated hepatic estrogen receptor α, cyclin D1, and CYP2E1 in both genders, but differentially altered lipid and EtOH metabolism. Consistent with higher basal levels of EtOH-metabolizing enzymes, blood EtOH was more rapidly cleared in hPXR females. These factors combined to provide greater protection against EtOH-induced liver injury in female hPXR mice, as revealed by markers for liver damage, lipid peroxidation, and endoplasmic reticulum stress. These results indicate that female hPXR mice are less susceptible to acute binge EtOH-induced hepatotoxicity than their male counterparts, due at least in part to the relative suppression of cellular stress and enhanced expression of enzymes involved in both EtOH metabolism and hepatocyte proliferation and repair in hPXR females. U.S. Government work not protected by U.S. copyright.

  9. Characterization, Dissolution, and Solubility of Lead Hydroxypyromorphite [Pb5(PO43OH] at 25–45°C

    Directory of Open Access Journals (Sweden)

    Yinian Zhu

    2015-01-01

    Full Text Available Dissolution of the hydroxypyromorphite [lead hydroxyapatite, Pb5(PO43OH] in HNO3 solution (pH = 2.00, ultrapure water (pH = 5.60, and NaOH solution (pH = 9.00 was experimentally studied at 25°C, 35°C, and 45°C. The XRD, FT-IR, and FE-SEM analyses indicated that the hydroxypyromorphite solids were observed to have indistinguishable change during dissolution. For the hydroxypyromorphite dissolution in aqueous acidic media at initial pH 2.00 and 25°C, the aqueous phosphate concentrations rose quickly and reached the peak values after 1 h dissolution, while the aqueous lead concentrations rose slowly and reached the peak values after 1440 h. The solution Pb/P molar ratio increased constantly from 1.10 to 1.65 near the stoichiometric ratio of 1.67 to 209.85~597.72 and then decreased to 74.76~237.26 for the dissolution at initial pH 2.00 and 25°C~45°C. The average Ksp values for Pb5(PO43OH were determined to be 10−80.77 (10−80.57−10−80.96 at 25°C, 10−80.65 (10−80.38−10−80.99 at 35°C, and 10−79.96 (10−79.38−10−80.71 at 45°C. From the obtained solubility data for the dissolution at initial pH 2.00 and 25°C, the Gibbs free energy of formation [ΔGfo] for Pb5(PO43OH was calculated to be −3796.71 kJ/mol (−3795.55~−3797.78 kJ/mol.

  10. Neuronal erythropoietin overexpression is protective against kanamycin-induced hearing loss in mice.

    Science.gov (United States)

    Bächinger, David; Horvath, Lukas; Eckhard, Andreas; Goosmann, Madeline M; Honegger, Tim; Gassmann, Max; Vogel, Johannes; Naldi, Arianne Monge

    2018-07-01

    Aminoglycosides have detrimental effects on the hair cells of the inner ear, yet these agents indisputably are one of the cornerstones in antibiotic therapy. Hence, there is a demand for strategies to prevent aminoglycoside-induced ototoxicity, which are not available today. In vitro data suggests that the pleiotropic growth factor erythropoietin (EPO) is neuroprotective against aminoglycoside-induced hair cell loss. Here, we use a mouse model with EPO-overexpression in neuronal tissue to evaluate whether EPO could also in vivo protect from aminoglycoside-induced hearing loss. Auditory brainstem response (ABR) thresholds were measured in 12-weeks-old mice before and after treatment with kanamycin for 15 days, which resulted in both C57BL/6 and EPO-transgenic animals in a high-frequency hearing loss. However, ABR threshold shifts in EPO-transgenic mice were significantly lower than in C57BL/6 mice (mean difference in ABR threshold shift 13.6 dB at 32 kHz, 95% CI 3.8-23.4 dB, p = 0.003). Correspondingly, quantification of hair cells and spiral ganglion neurons by immunofluorescence revealed that EPO-transgenic mice had a significantly lower hair cell and spiral ganglion neuron loss than C57BL/6 mice. In conclusion, neuronal overexpression of EPO is protective against aminoglycoside-induce hearing loss, which is in accordance with its known neuroprotective effects in other organs, such as the eye or the brain. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Late biological effects in the lung of C3H inbred mice following exposure to fast neutrons and 60Co-γ-rays

    International Nuclear Information System (INIS)

    Magdon, E.

    1980-01-01

    Histological changes in the lung tissue following local irradiation of the thorax of C 3 H inbred mice were analyzed. The investigation was continued up to 500 d following irradiation with 2 - 8 Gy neutrons and 4 - 30 Gy 60 Co γ-rays, respectively. The study revealed a clear dose dependence and higher effectivity of fast neutrons as to the late effects of the lungs. An increase of the portion of affected connective tissue in the lung was demonstrable already after a dose of 2.5 Gy neutrons and 5 Gy 60 Co γ-rays, respectively. The RBE of fast neutrons for late biological effects on the lung is discussed in connection with previous findings for the RBE of acute effects on tumor and normal tissue. (author)

  12. ST2 Deficiency Ameliorates High Fat Diet-Induced Liver Steatosis In BALB/c Mice

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    Jovicic Nemanja

    2015-03-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is strongly associated with obesity, but the molecular mechanisms of liver steatosis and its progression to non-alcoholic steatohepatitis and fibrosis are incompletely understood. Immune reactivity plays an important role in the pathogenesis of NAFLD. The IL-33/ST2 axis has a protective role in adiposity and atherosclerosis, but its role in obesity-associated metabolic disorders requires further clarification. To investigate the unresolved role of IL-33/ST2 signalling in NAFLD, we used ST2-deficient (ST2-/- and wild type (WT BALB/c mice maintained on a high-fat diet (HFD for 24 weeks. HFD-fed ST2-/- mice exhibited increased weight gain, visceral adipose tissue weight and triglyceridaemia and decreased liver weight compared with diet-matched WT mice. Compared with WT mice on an HFD, ST2 deletion significantly reduced hepatic steatosis, liver inflammation and fibrosis and downregulated the expression of genes related to lipid metabolism in the liver. The frequency of innate immune cells in the liver, including CD68+ macrophages and CD11c+ dendritic cells, was lower in HFD-fed ST2-/- mice, accompanied by lower TNFα serum levels compared with diet-matched WT mice. Less collagen deposition in the livers of ST2-/- mice on an HFD was associated with lower numbers of profibrotic CD11b+Ly6clow monocytes and CD4+IL-17+ T cells in the liver, lower hepatic gene expression of procollagen, IL-33 and IL-13, and lower serum levels of IL-33 and IL-13 compared with diet-matched WT mice.

  13. Uptake of carbon monoxide by C3H mice following X irradiation of lung only or total-body irradiation with 60Co

    International Nuclear Information System (INIS)

    Rappaport, D.S.; Niewoehner, D.E.; Kim, T.H.; Song, C.W.; Levitt, S.H.

    1983-01-01

    Carbon monoxide uptake (V/sub co/) and ventilation rate (VR) of C3H mice were determined at 14 weeks following either X irradiation of lungs only or total-body irradiation with 60 Co at different dose rates. Following localized X irradiation of lung at 97 /sub c/Gy/min there was a reduction in V/sub co/, which was inversely related to radiation dose, with a small reduction below control levels being detected at 7 Gy, the lowest dose tested. An increase in VR could be detected only at doses of 11 Gy, or more. Another group of animals received 11.5 Gy total-body irradiation at either 26.2 or 4.85 /sub c/Gy/min fllowed by transplantation with syngeneic bone marrow. Following total-body irradiation, V/sub co/ was significantly reduced by about 37% at the higher dose rate and 23% at the lower dose rate. In contrast, a trend toward elevated VR was detected only at the higher dose rate.The results indicate that V/sub co/ is a sensitive indicator of radiation-induced lung injury and that under the experimental conditions used V/sub co/ is a more sensitive indicator of radiation-induced lung injury in C3H mice than VR

  14. Protective effect of a mixture of radioprotective substances (AET and mexamine) on the haemopoietic stem cells of mice

    International Nuclear Information System (INIS)

    Vacek, A.; Rotkovska, D.; Sikulova, J.; Dikovenko, E.A.; Barkaja, V.S.; Akademiya Meditsinskikh Nauk SSSR, Sukhumi. Inst. Ehksperimental'noj Patologii i Terapii)

    1978-01-01

    The effect of a combined application of radioprotective substances (AET-i.p., mexamine-s.c.) was studied in mice. The duration of the protective effect on the haematopoietic stem cells and on the survival of mice after a lethal exposure to X-ray irradiation lasted for 5 hours p.i.. The DRF calculated from a change of LD 50/30 reached its maximum (1.53) within 30 min p.i., and was equal to 1.17 within an interval of 5 hrs. The protection of haematopoiesis, as expressed by the DRF calculated from an equieffiective exposure for 2 ESC, reached the maximum within 60 min p.i. (DRF = 3.4). The D 0 calculated from the CFU survival curves of endogenous haemapoietic tissue colonies (ESC) was, within a 120 min interval, almost three times higher (310 R) than in the control group (110 R). After the injection of radioprotective substances a greater number of haemopoietic CFU survives after an exposure to 100-400 R than after mere irradiation. The postirradiation decrease in the weight of small intestine was smaller in protected animals than in the controls. The role of a decrease of the radiation damage to the haemopoietic stem cells in the total protective effect of the radioprotectors used is discussed. (orig./MG) [de

  15. Long-Term Exercise Protects against Cellular Stresses in Aged Mice

    Directory of Open Access Journals (Sweden)

    Irina Belaya

    2018-01-01

    Full Text Available The current study examined the effect of aging and long-term wheel-running on the expression of heat shock protein (HSP, redox regulation, and endoplasmic reticulum (ER stress markers in tibialis anterior (T.A. and soleus muscle of mice. Male mice were divided into young (Y, 3-month-old, old-sedentary (OS, 24-month-old, and old-exercise (OE, 24-month-old groups. The OE group started voluntary wheel-running at 3 months and continued until 24 months of age. Aging was associated with a higher thioredoxin-interacting protein (TxNiP level, lower thioredoxin-1 (TRX-1 to TxNiP ratio—a determinant of redox regulation and increased CHOP, an indicator of ER stress-related apoptosis signaling in both muscles. Notably, GRP78, a key indicator of ER stress, was selectively elevated in T.A. Long-term exercise decreased TxNiP in T.A. and soleus muscles and increased the TRX-1/TxNiP ratio in soleus muscle of aged mice. Inducible HSP70 and constituent HSC70 were upregulated, whereas CHOP was reduced after exercise in soleus muscle. Thus, our data demonstrated that aging induced oxidative stress and activated ER stress-related apoptosis signaling in skeletal muscle, whereas long-term wheel-running improved redox regulation, ER stress adaptation and attenuated ER stress-related apoptosis signaling. These findings suggest that life-long exercise can protect against age-related cellular stress.

  16. Different Molecular/Behavioral Endophenotypes in C57BL/6J Mice Predict the Impact of OX1 Receptor Blockade on Binge-Like Ethanol Intake

    Directory of Open Access Journals (Sweden)

    Manuel Alcaraz-Iborra

    2017-10-01

    Full Text Available Ethanol (EtOH research has focused on stages of dependence. It is of paramount importance to more deeply understand the neurobehavioral factors promoting increased risk for EtOH binge drinking during the early stages of the addiction cycle. The first objective of this study was to evaluate whether C57BL/6J mice showing high drinking in the dark (DID exhibit neurobehavioral traits known to contribute to EtOH binge-drinking disorders. Comparing high vs. low drinkers (HD/LD, we evaluated different types of basal anxiety-like responses, EtOH preference and sensitivity to the reinforcing properties of EtOH, and basal mRNA expression of the OX1/OX2 receptors (OX1r/OX2r within the prefrontal cortex (PFC and the nucleus accumbens (NAcc. Additionally, we tested binge drinking by LD/HD in response to a selective OX1r antagonist following intermittent episodes of DID (iDID. We report that DID consistently segregates two neurobehavioral endophenotypes, HD vs. LD, showing differences in neophobia and/or impulsivity/compulsivity traits. Additionally, HD mice show decreased basal OX1r and OX2r mRNA expression within the NAcc and elevated OX1r within the PFC. Exposure to several intermittent episodes of EtOH DID triggered a rapid increase in EtOH intake over time in LD mice matching that observed in HD mice. Despite HD/LD endophenotypes did not show differences in EtOH intake, they still predicted the response to a pharmacological challenge with a selective OX1r antagonist. The present data underscore the relevance of HD/LD endophenotypes stemming from DID procedures for exploring neurobehavioral processes underlying the early stages of the addiction cycle and EtOH binge-drinking disorders.

  17. Protective and/or recovering effects of various kinds of chemicals and drugs to the hemopoietic injuries caused by the irradiation of 60Co γ-rays in the mice

    International Nuclear Information System (INIS)

    Kagimoto, Akio

    1987-01-01

    We have injected eleven kinds of chemical substances and drugs intraperitoneally in the male ddN mice, and studied the relative protective and/or recovering effects of them to the hemopoietic injuries caused by the whole body irradiation of 600R of 60 Co γ-rays. Good radioprotective activity on bone marrow cells in the irradiated mice was found, when we administered AET (S, 2-aminoethylisothiuronium Br. HBr) before irradiation, 5-HTP (5-hydroxytryptophane) in low dosage before irradiation, Glutathione before irradiation, or Serotonin (5-HT; 5-hydroxytryptamine) in high dosage before irradiation. Good radioprotective or recovering activity was observed on the weight of the spleen, by Serotonin in high and low dosage before irradiation, or DBCC (5,6-dimethyl benzimidazolyl cobamide coenzyme; Vitamin B 12 ) after irradiation. Positive responses of reticulocytes, erythrocytes, hemoglobin, and hematocrit were obtained in the irradiated mice, when we administered Serotonin in high dosage before irradiation, MET (S-Methyl-l-cysteine sulfoxide) before irradiation, a cocktail of Periactin (Cyproheptadine hydrochloride) and Serotonin before irradiation, MET before and after irradiation or Nucleo (a mixture of products made by degrading yeast-RNA) after irradiation respectively. A good response in leukocyte count was observed when Serotonin in high dosage before irradiation was administered, and in granulocyte count by Serotonin in high dosage before or 5-HTP in low dosage before irradiation. Lymphocyte count was protected or recovered by Serotonin in high dosage before or Nucleo after irradiation. Thrombocyte count was protected by Serotonin in high and low dosage before, Glutathione before, or AET before irradiation.(author)

  18. Protection against the clastogenic effect of CIS-PLATINUM by WR-2721, ATP and Vitamin C

    International Nuclear Information System (INIS)

    Rupova, I.; Yagova, A.

    1993-01-01

    The mutagenic effect of antineoplastic drug Cis-Platinum has been assessed by the frequency of micronuclei in polychromatic erythrocytes (PE) in the mouse bone marrow at time intervals of 24, 48 and 73 h. The maximal clastogenic effect of 2 mg/kg of Cis-Platinum has been found at 24 h interval after treatment (3.6%). The protection against mutagenic activity of Cis-Platinum has been studied by pretreatment of the mice with the thiophosphate compound WR-2721, adenosine triphosphate (ATP) and Vitamin C alone or in combinations at the time of maximal response. The radioprotector WR-2721 exerts a high anti-mutagenic activity when applied prior to Cis-Platinum (2.2%; p 0.05). (author)

  19. Immunity to Babesia in mice I. Adoptive transfer of immunity to Babesia rodhaini with immune spleen cells and the effect of irradiation on the protection of immune mice

    NARCIS (Netherlands)

    Kuil, H.; Zivkovic, D.; Seinen, W.; Albers-van Bemmel, C.M.G.; Speksnijder, J.E.

    1984-01-01

    Immunisation of Balb/c mice against Babesia rodhaini by an amicarbalide- controlled infection resulted in a solid immunity which lasted for 216 days. With spleen cells of immune mice protection could be transferred both to naive mice pretreated with cyclophosphamide. Treatment of naive mice with

  20. Vaccination with a Plasmodium chabaudi adami multivalent DNA vaccine cross-protects A/J mice against challenge with P. c. adami DK and virulent Plasmodium chabaudi chabaudi AS parasites.

    Science.gov (United States)

    Scorza, T; Grubb, K; Cambos, M; Santamaria, C; Tshikudi Malu, D; Spithill, T W

    2008-06-01

    A current goal of malaria vaccine research is the development of vaccines that will cross-protect against multiple strains of malaria. In the present study, the breadth of cross-reactivity induced by a 30K multivalent DNA vaccine has been evaluated in susceptible A/J mice (H-2a) against infection with the Plasmodium chabaudi adami DK strain and a virulent parasite subspecies, Plasmodium chabaudi chabaudi AS. Immunized A/J mice were significantly protected against infection with both P. c. adami DK (31-40% reduction in cumulative parasitemia) and P. c. chabaudi AS parasites, where a 30-39% reduction in cumulative parasitemia as well as enhanced survival was observed. The 30K vaccine-induced specific IFN-gamma production by splenocytes in response to native antigens from both P. c. chabaudi AS and P. c. adami DK. Specific antibodies reacting with surface antigens expressed on P. c. adami DS and P. c. chabaudi AS infected red blood cells, and with opsonizing properties, were detected. These results suggest that multivalent vaccines encoding conserved antigens can feasibly induce immune cross-reactivity that span Plasmodium strains and subspecies and can protect hosts of distinct major histocompatibility complex haplotypes.

  1. Total Leishmania antigens with Poly(I:C) induce Th1 protective response.

    Science.gov (United States)

    Sanchez, M V; Eliçabe, R J; Di Genaro, M S; Germanó, M J; Gea, S; García Bustos, M F; Salomón, M C; Scodeller, E A; Cargnelutti, D E

    2017-11-01

    Our proposal was to develop a vaccine based on total Leishmania antigens (TLA) adjuvanted with polyinosinic-polycytidylic acid [Poly(I:C)] able to induce a Th1 response which can provide protection against Leishmania infection. Mice were vaccinated with two doses of TLA-Poly(I:C) administered by subcutaneous route at 3-week interval. Humoral and cellular immune responses induced by the immunization were measured. The protective efficacy of the vaccine was evaluated by challenging mice with infective promastigotes of Leishmania (Leishmania) amazonensis into the footpad. Mice vaccinated with TLA-Poly(I:C) showed a high anti-Leishmania IgG titre, as well as increased IgG1 and IgG2a subclass titres compared with mice vaccinated with the TLA alone. The high IgG2a indicated a Th1 bias response induced by the TLA-Poly(I:C) immunization. Accordingly, the cellular immune response elicited by the formulation was characterized by an increased production of IFN-γ and no significant production of IL-4. The TLA-Poly(I:C) immunization elicited good protection, which was associated with decreased footpad swelling, a lower parasite load and a reduced histopathological alteration in the footpad. Our findings demonstrate a promising vaccine against cutaneous leishmaniasis that is relatively economic and easy to develop and which should be taken into account for preventing leishmaniasis in developing countries. © 2017 John Wiley & Sons Ltd.

  2. Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice

    Science.gov (United States)

    Mifuji Lira, Roque M.; Limón Flores, Alberto Yairh; Salinas Carmona, Mario César

    2016-01-01

    Pulmonary nocardiosis is a granulomatous disease with high mortality that affects both immunosuppressed and immunocompetent patients. The mechanisms leading to the establishment and progression of the infection are currently unknown. An animal model to study these mechanisms is sorely needed. We report the first in vivo model of granulomatous pulmonary nocardiosis that closely resembles human pathology. BALB/c mice infected intranasally with two different doses of GFP-expressing Nocardia brasiliensis ATCC700358 (NbGFP), develop weight loss and pulmonary granulomas. Mice infected with 109 CFUs progressed towards death within a week while mice infected with 108 CFUs died after five to six months. Histological examination of the lungs revealed that both the higher and lower doses of NbGFP induced granulomas with NbGFP clearly identifiable at the center of the lesions. Mice exposed to 108 CFUs and subsequently to 109 CFUs were not protected against disease severity but had less granulomas suggesting some degree of protection. Attempts to identify a cellular target for the infection were unsuccessful but we found that bacterial microcolonies in the suspension used to infect mice were responsible for the establishment of the disease. Small microcolonies of NbGFP, incompatible with nocardial doubling times starting from unicellular organisms, were identified in the lung as early as six hours after infection. Mice infected with highly purified unicellular preparations of NbGFP did not develop granulomas despite showing weight loss. Finally, intranasal delivery of nocardial microcolonies was enough for mice to develop granulomas with minimal weight loss. Taken together these results show that Nocardia brasiliensis microcolonies are both necessary and sufficient for the development of granulomatous pulmonary nocardiosis in mice. PMID:27303806

  3. Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice.

    Directory of Open Access Journals (Sweden)

    Roque M Mifuji Lira

    Full Text Available Pulmonary nocardiosis is a granulomatous disease with high mortality that affects both immunosuppressed and immunocompetent patients. The mechanisms leading to the establishment and progression of the infection are currently unknown. An animal model to study these mechanisms is sorely needed. We report the first in vivo model of granulomatous pulmonary nocardiosis that closely resembles human pathology. BALB/c mice infected intranasally with two different doses of GFP-expressing Nocardia brasiliensis ATCC700358 (NbGFP, develop weight loss and pulmonary granulomas. Mice infected with 109 CFUs progressed towards death within a week while mice infected with 108 CFUs died after five to six months. Histological examination of the lungs revealed that both the higher and lower doses of NbGFP induced granulomas with NbGFP clearly identifiable at the center of the lesions. Mice exposed to 108 CFUs and subsequently to 109 CFUs were not protected against disease severity but had less granulomas suggesting some degree of protection. Attempts to identify a cellular target for the infection were unsuccessful but we found that bacterial microcolonies in the suspension used to infect mice were responsible for the establishment of the disease. Small microcolonies of NbGFP, incompatible with nocardial doubling times starting from unicellular organisms, were identified in the lung as early as six hours after infection. Mice infected with highly purified unicellular preparations of NbGFP did not develop granulomas despite showing weight loss. Finally, intranasal delivery of nocardial microcolonies was enough for mice to develop granulomas with minimal weight loss. Taken together these results show that Nocardia brasiliensis microcolonies are both necessary and sufficient for the development of granulomatous pulmonary nocardiosis in mice.

  4. Toll-like receptor 4-positive macrophages protect mice from Pasteurella pneumotropica-induced pneumonia

    Science.gov (United States)

    Hart, Marcia L.; Mosier, Derek A.; Chapes, Stephen K.

    2003-01-01

    This study investigates Toll-like receptor 4 (TLR4)-positive macrophages in early recognition and clearance of pulmonary bacteria. TLR4 is a trans-membrane receptor that is the primary recognition molecule for lipopolysaccharide of gram-negative bacteria. The TLR4(Lps-del) mouse strains C57BL10/ScN (B10) and STOCK Abb(tm1) TLR4(Lps-del) Slc11a1(s)(B10 x C2D) are susceptible to pulmonary infections and develop pneumonia when naturally or experimentally infected by the opportunistic bacterium Pasteurella pneumotropica. Since these mice have the TLR4(Lps-del) genotype, we hypothesized that reconstitution of mice with TLR4-positive macrophages would provide resistance to this bacterium. A cultured macrophage cell line (C2D macrophages) and bone marrow cells from C2D mice were adoptively transferred to B10 and B10 x C2D mice by intraperitoneal injection. C2D macrophages increased B10 and B10 x C2D mouse resistance to P. pneumotropica. In C2D-recipient mice there was earlier transcription of tumor necrosis factor alpha and chemokines JE and macrophage inflammatory protein 2 (MIP-2) in the lungs of B10 and B10 x C2D mice, and there was earlier transcription of KC and MIP-1alpha in B10 x C2D mice. In addition, the course of inflammation following experimental Pasteurella challenge was altered in C2D recipients. C2D macrophages also protected B10 x C2D mice, which lack CD4(+) T cells. These data indicate that macrophages are critical for pulmonary immunity and can provide host resistance to P. pneumotropica. This study indicates that TLR4-positive macrophages are important for early recognition and clearance of pulmonary bacterial infections.

  5. Generating Chimeric Mice by Using Embryos from Nonsuperovulated BALB/c Mice Compared with Superovulated BALB/c and Albino C57BL/6 Mice.

    Science.gov (United States)

    Esmail, Michael Y; Qi, Peimin; Connor, Aurora Burds; Fox, James G; García, Alexis

    2016-01-01

    The reliable generation of high-percentage chimeras from gene-targeted C57BL/6 embryonic stem cells has proven challenging, despite optimization of cell culture and microinjection techniques. To improve the efficiency of this procedure, we compared the generation of chimeras by using 3 different inbred, albino host, embryo-generating protocols: BALB/cAnNTac (BALB/c) donor mice superovulated at 4 wk of age, 12-wk-old BALB/c donor mice without superovulation, and C57BL/6NTac-Tyr(tm1Arte) (albino B6) mice superovulated at 4 wk of age. Key parameters measured included the average number of injectable embryos per donor, the percentage of live pups born from the total number of embryos transferred to recipients, and the number of chimeric pups with high embryonic-stem-cell contribution by coat color. Although albino B6 donors produced significantly more injectable embryos than did BALB/c donors, 12-wk-old BALB/c donor produced high-percentage (at least 70%) chimeras more than 2.5 times as often as did albino B6 mice and 20 times more efficiently than did 4-wk-old BALB/c donors. These findings clearly suggest that 12-wk-old BALB/c mice be used as blastocyst donors to reduce the number of mice used to generate each chimera, reduce the production of low-percentage chimeras, and maximize the generation of high-percentage chimeras from C57BL/6 embryonic stem cells.

  6. Surface protein Adr2 of Rickettsia rickettsii induced protective immunity against Rocky Mountain spotted fever in C3H/HeN mice.

    Science.gov (United States)

    Gong, Wenping; Xiong, Xiaolu; Qi, Yong; Jiao, Jun; Duan, Changsong; Wen, Bohai

    2014-04-11

    Rickettsia rickettsii is the pathogen of Rocky Mountain spotted fever (RMSF), a life-threatening tick-transmitted infection. Adr2 was a surface-exposed adhesion protein of R. rickettsii and its immunoprotection against RMSF was investigated in mice. Recombinant Adr2 (rAdr2) was used to immunize C3H/HeN mice, and the rickettsial loads in organs of the mice were detected after challenge with R. rickettsii. The levels of specific antibodies of sera from the immunized mice were determined and the sera from immunized mice were applied to neutralize R. rickettsii. Proliferation and cytokine secretion of CD4(+) and CD8(+) T cells isolated from R. rickettsii-infected mice were also assayed after rAdr2 stimulation. After R. rickettsii challenge, the rickettsial loads in spleens, livers, and lungs were significantly lower and the impairment degrees of these organs in rAdr2-immunized mice were markedly slighter, compared with those in negative control mice. The ratio of specific IgG2a/IgG1 of rAdr2-immunized mice kept increasing during the immunization. After treatment with rAdr2-immunized sera, the total number of R. rickettsii organisms adhering and invading host cells was significantly lower than that treated with PBS-immunized sera. Interferon-γ secretion by CD4(+) or CD8(+) T cells and tumor necrosis factor-α secretion by CD4(+) T cells from R. rickettsii-infected mice were respectively significantly greater than those from uninfected mice after rAdr2 stimulation. Adr2 is a protective antigen of R. rickettsii. Protection offered by Adr2 is mainly dependent on antigen-specific cell-mediated immune responses, including efficient activity of CD4(+) and CD8(+) T cells to produce great amount of TNF-α and/or IFN-γ as well as rapid increase of specific IgG2a, which synergistically activate and opsonize host cells to killing intracellular rickettsiae. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.

    Directory of Open Access Journals (Sweden)

    Mayumi Nakahara

    Full Text Available INTRODUCTION: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM. rTM has been approved for the treatment of disseminated intravascular coagulation (DIC in Japan, and is currently undergoing a phase III clinical trial in the United States. METHODS: Histone H3 levels in plasma of healthy volunteers and patients with sepsis and DIC were measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected intravenously with purified histones, and pathological examinations were performed. The protective effects of rTM against histone toxicity were analyzed both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors than in survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding. Platelet depletion protected mice from histone-induced death in the first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might be responsible for death during the early phase. Furthermore, rTM bound to extracellular histones, suppressed histone-induced platelet aggregation, thrombotic occlusion of pulmonary capillaries, and dilatation of the right ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS: Extracellular histones cause massive

  8. Comparison of the protective resistance induced by 60Co-irradiated cercariae and schistosomula of the WFFS and NMRI strains of Schistosoma mansoni

    International Nuclear Information System (INIS)

    James, E.R.; Dobinson, A.R.

    1985-01-01

    Mice, CBA/HT6T6 and C57BL/10, were vaccinated with 1 x 350 or 1 x 500 Schistosoma mansoni cercariae or schistosomula attenuated with 20 or 56 krad 60 Co irradiation and challenged with 200 cercariae. Protective resistance against homologous strain challenge was compared using the Winches Farm Field Station (WFFS) and Naval Medical Research Institute (NMRI) strains of S. mansoni. Maximal resistance to challenge was obtained in both strains of mice with cercariae or schistosomula of either WFFS or NMRI strain attenuated with 20 krad. Protection using organisms attenuated with 56 krad was significantly lower. Since previous studies with the two parasite strains have shown that the biological effects of irradiation are similar, the difference in the immunogenicity of the 56 krad-irradiated NMRI strain in this study from earlier studies must be due either to different local conditions for irradiation or to adaptation of the NMRI strain to a new laboratory environment. This finding may have important implications for vaccination studies and investigations of the mechanisms of immunity where radiation-attenuated parasites are used. (author)

  9. Immunization with 60 kD Ro peptide produces different stages of preclinical autoimmunity in a Sjögren's syndrome model among multiple strains of inbred mice.

    Science.gov (United States)

    Kurien, B T; Dsouza, A; Igoe, A; Lee, Y J; Maier-Moore, J S; Gordon, T; Jackson, M; Scofield, R H

    2013-07-01

    Sjögren's syndrome is a chronic illness manifested characteristically by immune injury to the salivary and lacrimal glands, resulting in dry mouth/eyes. Anti-Ro [Sjögren's syndrome antigen A (SSA)] and anti-La [Sjögren's syndrome antigen B (SSB)] autoantibodies are found frequently in Sjögren's subjects as well as in individuals who will go on to develop the disease. Immunization of BALB/c mice with Ro60 peptides results in epitope spreading with anti-Ro and anti-La along with lymphocyte infiltration of salivary glands similar to human Sjögren's. In addition, these animals have poor salivary function/low saliva volume. In this study, we examined whether Ro-peptide immunization produces a Sjögren's-like illness in other strains of mice. BALB/c, DBA-2, PL/J, SJL/J and C57BL/6 mice were immunized with Ro60 peptide-274. Sera from these mice were studied by immunoblot and enzyme-linked immunosorbent assay for autoantibodies. Timed salivary flow was determined after pharmacological stimulation, and salivary glands were examined pathologically. We found that SJL/J mice had no immune response to the peptide from Ro60, while C57BL/6 mice produced antibodies that bound the peptide but had no epitope spreading. PL/J mice had epitope spreading to other structures of Ro60 as well as to La, but like C57BL/6 and SJL/J had no salivary gland lymphocytic infiltration and no decrement of salivary function. DBA-2 and BALB/c mice had infiltration but only BALB/c had decreased salivary function. The immunological processes leading to a Sjögren's-like illness after Ro-peptide immunization were interrupted in a stepwise fashion in these differing mice strains. These data suggest that this is a model of preclinical disease with genetic control for epitope spreading, lymphocytic infiltration and glandular dysfunction. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  10. Protective and/or recovering effects of various kinds of chemicals and drugs to the hemopoietic injuries caused by the irradiation of /sup 60/Co. gamma. -rays in the mice

    Energy Technology Data Exchange (ETDEWEB)

    Kagimoto, Akio

    1987-01-01

    We have injected eleven kinds of chemical substances and drugs intraperitoneally in the male ddN mice, and studied the relative protective and/or recovering effects of them to the hemopoietic injuries caused by the whole body irradiation of 600R of /sup 60/Co ..gamma..-rays. Good radioprotective activity on bone marrow cells in the irradiated mice was found, when we administered AET (S, 2-aminoethylisothiuronium Br. HBr) before irradiation, 5-HTP (5-hydroxytryptophane) in low dosage before irradiation, Glutathione before irradiation, or Serotonin (5-HT; 5-hydroxytryptamine) in high dosage before irradiation. Good radioprotective or recovering activity was observed on the weight of the spleen, by Serotonin in high and low dosage before irradiation, or DBCC (5,6-dimethyl benzimidazolyl cobamide coenzyme; Vitamin B/sub 12/) after irradiation. Positive responses of reticulocytes, erythrocytes, hemoglobin, and hematocrit were obtained in the irradiated mice, when we administered Serotonin in high dosage before irradiation, MET (S-Methyl-l-cysteine sulfoxide) before irradiation, a cocktail of Periactin (Cyproheptadine hydrochloride) and Serotonin before irradiation, MET before and after irradiation or Nucleo (a mixture of products made by degrading yeast-RNA) after irradiation respectively. A good response in leukocyte count was observed when Serotonin in high dosage before irradiation was administered, and in granulocyte count by Serotonin in high dosage before or 5-HTP in low dosage before irradiation. Lymphocyte count was protected or recovered by Serotonin in high dosage before or Nucleo after irradiation. Thrombocyte count was protected by Serotonin in high and low dosage before, Glutathione before, or AET before irradiation.(author).

  11. 40 CFR 60.35c - Reporting and recordkeeping guidelines.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Reporting and recordkeeping guidelines... PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Municipal Solid Waste Landfills § 60.35c Reporting and recordkeeping guidelines. For approval...

  12. Protection mediated by chemokine CXCL10 in BALB/c mice infected by Leishmania infantum

    Science.gov (United States)

    Figueiredo, Webertty Mayk Eufrásio; Viana, Sayonara de Melo; Alves, Dorotheia Teixeira; Guerra, Priscila Valera; Coêlho, Zirlane Castelo Branco; Barbosa, Helene Santos; Teixeira, Maria Jania

    2017-01-01

    BACKGROUND Visceral leishmaniasis (VL) caused by Leishmania infantum is characterised by the loss of the ability of the host to generate an effective immune response. Chemokines have a direct involvement in the pathogenesis of leishmaniasis, causing a rapid change in the expression of these molecules during infection by Leishmania. OBJECTIVES Herein, it was investigated the role of CXCL10 in controlling infection by L. infantum. METHODS RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/mL). Parasite load, as well as nitric oxide (NO), IL-4 and IL-10 production were assessed at 24 and 48 h after infection. In vivo, BALB/c mice were infected and treated or not with CXCL10 (5 μg/kg) at one, three and seven days of infection. Parasite load, IFN-g, IL-4, TGF-β and IL-10 were evaluated one, seven and 23 days post treatment. FINDINGS In vitro, CXCL10 reduced parasitic load, not dependent on NO, and inhibited IL-10 and IL-4 secretion. In vivo, CXCL10 was able to reduce the parasite load in both liver and spleen, four weeks after infection, representing a higher decrease in the number of parasites in these organs, also induced IFN-γ at day 23 after treatment, correlating with the decrease in parasite load, and reduced IL-10 and TGF-β. MAIN CONCLUSIONS This study suggests a partial protective role of CXCL10 against L. infantum, mediated by IFN-g, not dependent on NO, and with suppression of IL-10 and TGF-β. These data may provide information for the development of new approaches for future therapeutic interventions for VL. PMID:28767981

  13. The complex of PAMAM-OH dendrimer with Angiotensin (1-7) prevented the disuse-induced skeletal muscle atrophy in mice.

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1-7) (Ang-(1-7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues - among them, skeletal muscle - by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1-7) carrier. Bioinformatics analysis showed that the Ang-(1-7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1-7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1-7)/PAMAM-OH complex, but not Ang-(1-7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1-7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1-7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1-7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1-7)/PAMAM-OH complex is an efficient delivery method for Ang-(1-7), since it improves the anti-atrophic activity of this peptide in skeletal muscle.

  14. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

    Science.gov (United States)

    Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

    2016-01-01

    Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

  15. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

    Directory of Open Access Journals (Sweden)

    Sanne Terryn

    2016-08-01

    Full Text Available Post-exposure prophylaxis (PEP against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days and decreased mortality (60% versus 19% survival rate, when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

  16. Protective Effect of Silymarin against Acrolein-Induced Cardiotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    Elahe Taghiabadi

    2012-01-01

    Full Text Available Reactive α,β-unsaturated aldehydes such as acrolein (ACR are major components of environmental pollutants and have been implicated in the neurodegenerative and cardiac diseases. In this study, the protective effect of silymarin (SN against cardiotoxicity induced by ACR in mice was evaluated. Studies were performed on seven groups of six animals each, including vehicle-control (normal saline + 0.5% w/v methylcellulose, ACR (7.5 mg/kg/day, gavage for 3 weeks, SN (25, 50 and 100 mg/kg/day, i.p. plus ACR, vitamin E (Vit E, 100 IU/kg, i.p. plus ACR, and SN (100 mg/kg, i.p. groups. Mice received SN 7 days before ACR and daily thereafter throughout the study. Pretreatment with SN attenuated ACR-induced increased levels of malondialdehyde (MDA, serum cardiac troponin I (cTnI, and creatine kinase-MB (CK-MB, as well as histopathological changes in cardiac tissues. Moreover, SN improved glutathione (GSH content, superoxide dismutase (SOD, and catalase (CAT activities in heart of ACR-treated mice. Western blot analysis showed that SN pretreatment inhibited apoptosis provoked by ACR through decreasing Bax/Bcl-2 ratio, cytosolic cytochrome c content, and cleaved caspase-3 level in heart. In conclusion, SN may have protective effects against cardiotoxicity of ACR by reducing lipid peroxidation, renewing the activities of antioxidant enzymes, and preventing apoptosis.

  17. Lonidamine affects testicular steroid hormones in immature mice

    International Nuclear Information System (INIS)

    Traina, Maria Elsa; Guarino, Maria; Natoli, Alessia; Romeo, Antonella; Urbani, Elisabetta

    2007-01-01

    The effects on the hypothalamus-pituitary-testicular axis of the well-known antispermatogenic drug lonidamine (LND) has not been elucidated so far. In the present study, the possible changes of the testicular steroid hormones were evaluated in immature mice for a better characterization of the LND adverse effects both in its use as antitumoral agent and male contraceptive. Male CD1 mice were orally treated on postnatal day 28 (PND28) with LND single doses (0 or 100 mg/kg b.w.) and euthanized every 24 h from PND29 to PND32, on PND35 and on PND42 (1 and 2 weeks after the administration, respectively). Severe testicular effects were evidenced in the LND treated groups, including: a) significant testis weight increase, 24 h and 48 h after dosing; b) sperm head counts decrease (more than 50% of the control) on PND29-32; c) damage of the tubule morphology primarily on the Sertoli cell structure and germ cell exfoliation. All these reproductive endpoints were recovered on PND42. At the same time, a significant impairment of the testicular steroid balance was observed in the treated mice, as evidenced by the decrease of testosterone (T) and androstenedione (ADIONE) and the increase of 17OH-progesterone (17OH-P4) on the first days after dosing, while the testicular content of 17β-estradiol (E2) was unchanged. The hormonal balance was not completely restored afterwards, as levels of T, ADIONE and 17OH-P4 tended to be higher in the treated mice than in the controls, on PND35 and PND42. These data showed for the first time that LND affects intratesticular steroids in experimental animals. However further data are needed both to elucidate the mechanism responsible for the impairment of these metabolic pathways and to understand if the androgens decrease observed after LND administration could be partially involved in the testicular damage

  18. Use of a crossed high alcohol preferring (cHAP) mouse model with the NIAAA-model of chronic-binge ethanol intake to study liver injury.

    Science.gov (United States)

    Thompson, Kyle J; Nazari, Shayan S; Jacobs, W Carl; Grahame, Nicholas J; McKillop, Iain H

    2017-11-01

    This study sought to compare mice bred to preferentially consume high amounts of alcohol (crossed-high alcohol preferring, cHAP) to c57BL/6 (C57) mice using a chronic-binge ethanol ingestion model to induce alcoholic liver disease (ALD). Male C57 and cHAP mice were randomized to a Lieber-DeCarli control (LDC) diet, Lieber-DeCarli 5% (v/v) ethanol (LDE) diet or free-choice between 10% (v/v) ethanol in drinking water (EtOH-DW) and DW. After 4 weeks mice were gavaged with either 9 g/kg maltose-dextrin (LDC+MD) or 5 g/kg EtOH (LDE+Binge, EtOH-DW+Binge). Nine hours later tissue and serum were collected and analyzed. cHAP mice on EtOH-DW consumed significantly more ethanol than cHAP or C57 mice maintained on LDE. However, cHAP and C57 mice on the LDE+Binge regiment had greater hepatosteatosis and overall degree of liver injury compared to EtOH-DW+Binge. Changes in pro-inflammatory gene expression was more pronounced in cHAP mice than C57 mice. Analysis of liver enzymes revealed a robust induction of CYP2E1 in C57 and cHAP mice maintained on EtOH-DW+Binge or LDE+Binge. However, while C57 mice exhibited higher basal hepatic glutathione than cHAP mice, these mice appeared more susceptible to oxidative stress following LDE+Binge than cHAP counterparts. Despite cHAP mice consuming more total ethanol prior to gavage when maintained on EtOH-DW, LDE followed by gavage created a more severe model of ALD in both C57 and cHAP mice. These data suggest factors other than total amount of alcohol consumed affect degree of ALD development in the chronic-binge model in cHAP mice. cHAP mice voluntarily consume high amounts of ethanol and exhibited hepatic injury when subject to chronic-binge ethanol feeding with the Lieber-DeCarli diet. However, hepatic injury was reduced in cHAP mice in a chronic-binge model following voluntary high ethanol consumption in drinking water. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  19. Experimental toxoplasmosis in Balb/c mice. Prevention of vertical disease transmission by treatment and reproductive failure in chronic infection

    Directory of Open Access Journals (Sweden)

    B Fux

    2000-01-01

    Full Text Available In a study of congenital transmission during acute infection of Toxoplasma gondii, 23 pregnant Balb/c mice were inoculated orally with two cysts each of the P strain. Eight mice were inoculated 6-11 days after becoming pregnant (Group 1. Eight mice inoculated on the 10th-15th day of pregnancy (Group 2 were treated with 100 mg/kg/day of minocycline 48 h after inoculation. Seven mice inoculated on the 10th-15th day of pregnancy were not treated and served as a control (Group 3. Congenital transmission was evaluated through direct examination of the brains of the pups or by bioassay and serologic tests. Congenital transmission was observed in 20 (60.6% of the 33 pups of Group 1, in one (3.6% of the 28 pups of Group 2, and in 13 (54.2% of the 24 pups of Group 3. Forty-nine Balb/c mice were examined in the study of congenital transmission of T. gondii during chronic infection. The females showed reproductive problems during this phase of infection. It was observed accentuated hypertrophy of the endometrium and myometrium. Only two of the females gave birth. Our results demonstrate that Balb/c mice with acute toxoplasmosis can be used as a model for studies of congenital T. gondii infection. Our observations indicate the potential of this model for testing new chemotherapeutic agents against congenital toxoplasmosis.

  20. Hepcidin protects against lethal E. coli sepsis in mice inoculated with isolates from septic patients.

    Science.gov (United States)

    Stefanova, Deborah; Raychev, Antoan; Deville, Jaime; Humphries, Romney; Campeau, Shelley; Ruchala, Piotr; Nemeth, Elizabeta; Ganz, Tomas; Bulut, Yonca

    2018-05-07

    Iron is an essential micronutrient for most microbes and their hosts. Mammalian hosts respond to infection by inducing the iron-regulatory hormone hepcidin, which causes iron sequestration and a rapid decrease in plasma and extracellular iron concentration (hypoferremia). Previous studies showed that hepcidin regulation of iron is essential for protection from infection-associated mortality with the siderophilic pathogens Yersinia enterocolitica and Vibrio vulnificus However, the evolutionary conservation of the hypoferremic response to infection suggests that not only rare siderophilic bacteria but also common pathogens may be targeted by this mechanism. We tested 10 clinical isolates of E. coli from children with sepsis and found that both genetic (hepcidin knockout, HKO) and iatrogenic iron overload (IV iron) potentiated infection with 8 out of 10 studied isolates: after peritoneal injection of E. coli , iron-loaded mice developed sepsis with 60% to 100% mortality within 24h while control wild type mice suffered 0% mortality. Using one strain for more detailed study, we show that iron overload allowed rapid bacterial multiplication and dissemination. We further found that the presence of non-transferrin bound iron (NTBI) in circulation is more important than total plasma or tissue iron in rendering mice susceptible to infection and mortality. Post infection treatment of HKO mice with just two doses of the hepcidin agonist PR73 abolished NTBI and completely prevented sepsis-associated mortality. We demonstrate that siderophilic phenotype extends to clinically common pathogens. The use of hepcidin agonists promises to be an effective early intervention in patients with infections and dysregulated iron metabolism. Copyright © 2018 American Society for Microbiology.

  1. Galectins expressed differently in genetically susceptible C57BL/6 and resistant BALB/c mice during acute ocular Toxoplasma gondii infection.

    Science.gov (United States)

    Chen, S-J; Zhang, Y-X; Huang, S-G; Lu, F-L

    2017-07-01

    Ocular toxoplasmosis (OT) caused by Toxoplasma gondii is a major cause of infectious uveitis, however little is known about its immunopathological mechanism. Susceptible C57BL/6 (B6) and resistant BALB/c mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. B6 mice showed more severe ocular pathology and higher parasite loads in the eyes. The levels of galectin (Gal)-9 and its receptors (Tim-3 and CD137), interferon (IFN)-γ, IL-6 and IL-10 were significantly higher in the eyes of B6 mice than those of BALB/c mice; however, the levels of IFN-α and -β were significantly decreased in the eyes and CLNs of B6 mice but significantly increased in BALB/c mice after infection. After blockage of galectin-receptor interactions by α-lactose, neither ocular immunopathology nor parasite loads were different from those of infected BALB/c mice without α-lactose treatment. Although the expressions of Gal-9/receptor were significantly increased in B6 mice and Gal-1 and -3 were upregulated in both strains of mice upon ocular T. gondii infection, blockage of galectins did not change the ocular pathogenesis of genetic resistant BALB/c mice. However, IFN-α and -β were differently expressed in B6 and BALB/c mice, suggesting that type I IFNs may play a protective role in experimental OT.

  2. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    International Nuclear Information System (INIS)

    Ali, Haytham; Galal, Omima; Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan; Abdelrahim, Eman; Ono, Yusuke; Mostafa, Emtethal; Li, Tao-Sheng

    2014-01-01

    Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit + stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit + stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit + stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms

  3. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Haytham [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Galal, Omima [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Abdelrahim, Eman [Department of Medical Histology, Qena Faculty of Medicine, South Valley University (Egypt); Ono, Yusuke [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Mostafa, Emtethal [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Li, Tao-Sheng, E-mail: litaoshe@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2014-09-26

    Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.

  4. Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis. [X radiation, mice

    Energy Technology Data Exchange (ETDEWEB)

    Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.; Murphy, W.H.

    1978-12-01

    The capacity of immune cells obtained from the major lymphoid compartments to protect C58 mice from transplanted line Ib leukemia, and from an age-dependent autoimmune CNS disease (immune polioencephalomyelitis = IPE) elicited by immunizing old C58 mice with inactivated Ib cells was quantified. Cells used for comparative adoptive protection tests were harvested from the major lymphoid compartments 14 to 15 days after young C58 mice were immunized with inactivated Ib cell preparations. Regression curves were plotted from survival data and the log/sub 10/PD/sub 50/ values were determined. Immune spleen (ISC) and peritoneal cells (IPEC) were significantly more protective against transplanted Ib cells than immune lymph node (ILNC), thymic (ITC), and marrow cells (IMC). In contrast, IPEC and IMC were not protective against IPE and ITC were only marginally protective. ILNC afforded significant protection to transplantable leukemia but were only marginally protective to IPE. When ISC were treated with anti-thy 1.2 serum and complement, protection against transplanted leukemia and IPE was reduced > 99%. When donors of immune lymphoid cells were treated with 12.5 mg of cortisone acetate daily for 2 days before lymphoid cells were harvested, protection against transplanted Ib cells by ISC was reduced by approximately 90% whereas protection against IPE was totally eliminated. Considered together, these results indicate that the protective mechanisms to transplantable leukemia and IPE differ significantly in the same indicator mouse strain.

  5. Distinctive cellular immunity in genetically susceptible BALB/c mice recovered from Leishmania major infection or after subcutaneous immunization with killed parasites

    International Nuclear Information System (INIS)

    Liew, F.Y.; Dhaliwal, J.S.

    1987-01-01

    Genetically susceptible BALB/c mice are refractory to further infection after recovery from Leishmania major infection after a sublethal dose of gamma-irradiation. In contrast, mice immunized with killed promastigotes s.c. develop exacerbated lesions after infection. Both groups of mice produce only a low level of specific antibody and no detectable cytotoxic T cells, but do have a strong antigen-specific DTH, which is adoptively transferable with Lyt-1+2-, L3T4+ T cells. Kinetic and histological studies revealed that mice immunized s.c. developed Jones-Mote hypersensitivity, peaking at 15 hr. with little mononuclear cell infiltration at the site of antigen administration; whereas mice that had recovered from infection developed tuberculin-type of reactivity, peaking at 24 to 48 hr, with intense mononuclear cell infiltration. Splenic T cells from recovered mice, when injected into the footpads of normal recipients together with live promastigotes, were able to retard lesion development; whereas T cells from s.c. immunized mice, when similarly transferred, accelerated disease progression. Antigen-specific culture supernatant of spleen cells from recovered mice also activated normal resident peritoneal macrophages to kill intracellular L. major amastigotes and tumor cells. Culture supernatants of spleen cells from s.c. immunized or normal mice were devoid of such activities. Part of the macrophage-activating potential can be inhibited by antibody specific for IFN-gamma. These results therefore demonstrate that whereas the Jones-Mote reaction is correlated with disease exacerbation, the tuberculin-type of DTH may be protective. Furthermore, in vivo immunity is directly related to the capacity of T cells to produce macrophage-activating factor

  6. Protective specific immunity induced by cyclophosphamide plus tumor necrosis factor alpha combination treatment of EL4-lymphoma-bearing C57BL/6 mice.

    Science.gov (United States)

    Krawczyk, C M; Verstovsek, S; Ujházy, P; Maccubbin, D; Ehrke, M J

    1995-06-01

    A combination treatment protocol initiated 12 days after tumor injection, when the tumor was large, by administering cyclophosphamide (CY, 150 or 250 mg/kg) intraperitoneally followed by intravenous tumor necrosis factor alpha (TNF alpha, 1000 units injection) on days 13, 16, 18, 21, and 23, resulted in about 60% long-term survival (i.e., survival for at least 60 days) in the syngeneic C57BL/6 mouse/EL4 lymphoma model system. The establishment of a specific antitumor immune memory and its possible therapeutic relevance was verified by reinjecting 60-day survivors with EL4 cells; all 60-day survivors that had received the combination treatments rejected the implants and survived for a further 60 days. Thymic cellularity was reduced during treatment and its recovery appeared to correlate with long-term survival and immunity. Thymocytes from mice treated with the combination were found to express significant levels of specific anti-EL4 cytolytic activity following a 4-day stimulation culture with X-irradiated EL4 cells and low concentrations of interleukin-2. This response could not be generated with thymocytes from naive animals. In each case the effect seen with the combination of a moderate CY dose (150 mg/kg) with TNF alpha was better than that seen with either dose of CY alone and equal to or better than that seen with the higher dose of CY combined with TNF alpha. These results indicate that treatment with a single moderate dose of CY in combination with TNF alpha is effective against a large, established tumor in this murine model. Furthermore, all the long-term survivors induced by this treatment developed protective immunity against reimplanted tumor and demonstrated a long-term specific immune memory in the thymus.

  7. Bridging C60 by silicon: Towards non-Van der Waals C60-based materials

    International Nuclear Information System (INIS)

    Tournus, F.; Masenelli, B.; Melinon, P.; Blase, X.; Perez, A.; Pellarin, M.; Broyer, M.; Flank, A.M.; Lagarde, P.

    2002-01-01

    We report the three-dimensional packing of C 60 clusters stabilized by the addition of Si. X-ray absorption spectroscopy reveals that Si atoms are in an unusual environment: between two C 60 , with ten or more carbon neighbors. According to ab initio calculations, the cohesive energy is about 2 eV per Si atom, much higher than the Van der Waals binding energy between two C 60 . Experiment and calculations both indicate a charge transfer from Si to C 60 . Eventually, the film may have a local decahedral symmetry

  8. Metabolite analysis of [11C]Ro15-4513 in mice, rats, monkeys and humans

    International Nuclear Information System (INIS)

    Kida, T.; Noguchi, J.; Zhang, M.-R.; Suhara, T.; Suzuki, K.

    2003-01-01

    We performed in vitro and in vivo assays of the metabolism of [ 11 C]Ro15-4513 over time in the plasma of mice, rats, monkeys and humans, using a radio-HPLC equipped with a sensitive positron detector, in order to compare the metabolic rates of the radiopharmaceutical agent among the different animal species and to establish a highly sensitive analytical method for the radiotracer agent. We also examined the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats. The analytical method used in this study permitted detection of even extremely low levels of radioactivity (approximately 5,000 dpm). In vitro experiments revealed that [ 11 C]Ro15-4513 in the blood was metabolized to hydrolysate [ 11 C]A. The species were classified in descending order of the metabolic rate of the radiotracer in vitro as follows; mice, rats, and monkeys/humans. In the in vitro experiment, the percentage of the unchanged drug in the plasma at 60 minutes postdose was 9% in mice, 70% in rats, 97% in monkeys, and 98% in humans. In vivo metabolite analysis in the blood showed the presence of two radioactive metabolites, consisting of one hydrolysate [ 11 C]A and another unidentified substance. The species were classified in descending order of the metabolic rate of the radiotracer in vivo as follows; mice, rats/humans, and monkeys. The percentage of the unchanged drug in the plasma was 6% in mice, 21% in rats, 26% in humans, and 40% in monkeys. Furthermore, the in vitro and in vivo experiments conducted to analyze the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats revealed that the radiotracer was metabolized to some extent in the brain tissue of these animals. In the in vivo experiment, the percentage of the unchanged drug at 60 min postdose was 86% in the brain tissue of mice and 88% in the brain tissue of rats, while in the in vitro experiment, the corresponding percentage was 93% in mice, and 91% in rats

  9. ON THE ORIGIN OF C_4H AND CH_3OH IN PROTOSTELLAR ENVELOPES

    International Nuclear Information System (INIS)

    Lindberg, Johan E.; Charnley, Steven B.; Cordiner, Martin A.

    2016-01-01

    The formation pathways of different types of organic molecules in protostellar envelopes and other regions of star formation are subjects of intense current interest. We present here observations of C_4H and CH_3OH, tracing two distinct groups of interstellar organic molecules, toward 16 protostars in the Ophiuchus and Corona Australis molecular clouds. Together with observations in the literature, we present C_4H and CH_3OH data from single-dish observations of 40 embedded protostars. We find no correlation between the C_4H and CH_3OH column densities in this large sample. Based on this lack of correlation, a difference in line profiles between C_4H and CH_3OH, and previous interferometric observations of similar sources, we propose that the emission from these two molecules is spatially separated, with the CH_3OH tracing gas that has been transiently heated to high (∼70–100 K) temperatures and the C_4H tracing the cooler large-scale envelope where CH_4 molecules have been liberated from ices. These results provide insight in the differentiation between hot corino and warm carbon-chain chemistry in embedded protostars.

  10. Immunization with a DNA vaccine encoding Toxoplasma gondii Superoxide dismutase (TgSOD) induces partial immune protection against acute toxoplasmosis in BALB/c mice.

    Science.gov (United States)

    Liu, Yuan; Cao, Aiping; Li, Yawen; Li, Xun; Cong, Hua; He, Shenyi; Zhou, Huaiyu

    2017-06-07

    Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects all warm-blooded animals including humans and causes toxoplasmosis. An effective vaccine could be an ideal choice for preventing and controlling toxoplasmosis. T. gondii Superoxide dismutase (TgSOD) might participate in affecting the intracellular growth of both bradyzoite and tachyzoite forms. In the present study, the TgSOD gene was used to construct a DNA vaccine (pEGFP-SOD). TgSOD gene was amplified and inserted into eukaryotic vector pEGFP-C1 and formed the DNA vaccine pEGFP-SOD. Then the BALB/c mice were immunized intramuscularly with the DNA vaccine and those injected with pEGFP-C1, PBS or nothing were treated as controls. Four weeks after the last immunization, all mouse groups followed by challenging intraperitoneally with tachyzoites of T. gondii ME49 strain. Results showed higher levels of total IgG, IgG2α in the sera and interferon gamma (IFN-γ) in the splenocytes from pEGFP-SOD inoculated mice than those unvaccinated, or inoculated with either empty plasmid vector or PBS. The proportions of CD4 + T cells and CD8 + T cells in the spleen from pEGFP-SOD inoculated mice were significantly (p < 0.05) increased compared to control groups. In addition, the survival time of mice immunized with pEGFP-SOD was significantly prolonged as compared to the controls (p < 0.05) although all the mice died. The present study revealed that the DNA vaccine triggered strong humoral and cellular immune responses, and aroused partial protective immunity against acute T. gondii infection in BALB/c mice. The collective data suggests the SOD may be a potential vaccine candidate for further development.

  11. Chronic intermittent ethanol exposure and withdrawal alters (3α,5α)-3-hydroxy-pregnan-20-one immunostaining in cortical and limbic brain regions of C57BL/6J mice.

    Science.gov (United States)

    Maldonado-Devincci, Antoniette M; Cook, Jason B; O'Buckley, Todd K; Morrow, Danielle H; McKinley, Raechel E; Lopez, Marcelo F; Becker, Howard C; Morrow, A Leslie

    2014-10-01

    The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) has been studied during withdrawal from ethanol (EtOH) in humans, rats, and mice. Serum 3α,5α-THP levels decreased, and brain levels were not altered following acute EtOH administration (2 g/kg) in male C57BL/6J mice; however, the effects of chronic intermittent ethanol (CIE) exposure on 3α,5α-THP levels have not been examined. Given that CIE exposure changes subsequent voluntary EtOH drinking in a time-dependent fashion following repeated cycles of EtOH exposure, we conducted a time-course analysis of CIE effects on 3α,5α-THP levels in specific brain regions known to influence drinking behavior. Adult male C57BL/6J mice were exposed to 4 cycles of CIE to induce EtOH dependence. All mice were sacrificed and perfused at 1 of 2 time points, 8 or 72 hours following the final exposure cycle. Free-floating brain sections (40 μm; 3 to 5 sections/region/animal) were immunostained and analyzed to determine relative levels of cellular 3α,5α-THP. Withdrawal from CIE exposure produced time-dependent and region-specific effects on immunohistochemical detection of 3α,5α-THP levels across cortical and limbic brain regions. A transient reduction in 3α,5α-THP immunoreactivity was observed in the central nucleus of the amygdala 8 hours after withdrawal from CIE (-31.4 ± 9.3%). Decreases in 3α,5α-THP immunoreactivity were observed 72 hours following withdrawal in the medial prefrontal cortex (-25.0 ± 9.3%), nucleus accumbens core (-29.9 ± 6.6%), and dorsolateral striatum (-18.5 ± 6.0%), while an increase was observed in the CA3 pyramidal cell layer of the hippocampus (+42.8 ± 19.5%). Sustained reductions in 3α,5α-THP immunoreactivity were observed at both time points in the lateral amygdala (8 hours -28.3 ± 12.8%; 72 hours -27.5 ± 12.4%) and in the ventral tegmental area (8 hours -26.5 ± 9.9%; 72 hours -31.6 ± 13.8%). These data

  12. A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia-reperfusion injury in mice.

    Science.gov (United States)

    Atochin, Dmitriy N; Schepetkin, Igor A; Khlebnikov, Andrei I; Seledtsov, Victor I; Swanson, Helen; Quinn, Mark T; Huang, Paul L

    2016-04-08

    The c-Jun N-terminal kinase (JNK) has been shown to be an important regulator of neuronal cell death. Previously, we synthesized the sodium salt of 11H-indeno[1,2-b]quinoxalin-11-one (IQ-1S) and demonstrated that it was a high-affinity inhibitor of the JNK family. In the present work, we found that IQ-1S could release nitric oxide (NO) during its enzymatic metabolism by liver microsomes. Moreover, serum nitrite/nitrate concentration in mice increased after intraperitoneal injection of IQ-1S. Because of these dual actions as JNK inhibitor and NO-donor, the therapeutic potential of IQ-1S was evaluated in an animal stroke model. We subjected wild-type C57BL6 mice to focal ischemia (30min) with subsequent reperfusion (48h). Mice were treated with IQ-1S (25mg/kg) suspended in 10% solutol or with vehicle alone 30min before and 24h after middle cerebral artery (MCA) occlusion (MCAO). Using laser-Doppler flowmetry, we monitored cerebral blood flow (CBF) above the MCA during 30min of MCAO provoked by a filament and during the first 30min of subsequent reperfusion. In mice treated with IQ-1S, ischemic and reperfusion values of CBF were not different from vehicle-treated mice. However, IQ-1S treated mice demonstrated markedly reduced neurological deficit and infarct volumes as compared with vehicle-treated mice after 48h of reperfusion. Our results indicate that the novel JNK inhibitor releases NO during its oxidoreductive bioconversion and improves stroke outcome in a mouse model of cerebral reperfusion. We conclude that IQ-1S is a promising dual functional agent for the treatment of cerebral ischemia and reperfusion injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. A Novel Dual NO-donating Oxime and c-Jun N-terminal Kinase Inhibitor Protects Against Cerebral Ischemia–Reperfusion Injury in Mice

    Science.gov (United States)

    Atochin, Dmitriy N.; Schepetkin, Igor A.; Khlebnikov, Andrei I.; Seledtsov, Victor I.; Swanson, Helen; Quinn, Mark T.; Huang, Paul L.

    2017-01-01

    The c-Jun N-terminal kinase (JNK) has been shown to be an important regulator of neuronal cell death. Previously, we synthesized the sodium salt of 11H-indeno[1,2-b]quinoxalin-11-one (IQ-1S) and demonstrated that it was a high-affinity inhibitor of the JNK family. In the present work, we found that IQ-1S could release nitric oxide (NO) during its enzymatic metabolism by liver microsomes. Moreover, serum nitrite/nitrate concentration in mice increased after intraperitoneal injection of IQ-1S. Because of these dual actions as JNK inhibitor and NO-donor, the therapeutic potential of IQ-1S was evaluated in an animal stroke model. We subjected wild-type C57BL6 mice to focal ischemia (30 minutes) with subsequent reperfusion (48 hours). Mice were treated with IQ-1S (25 mg/kg) suspended in 10% solutol or with vehicle alone 30 minutes before and 24 hours after middle cerebral artery MCA) occlusion (MCAO). Using laser-Doppler flowmetry, we monitored cerebral blood flow (CBF) above the MCA during 30 minutes of MCAO provoked by a filament and during the first 30 minutes of subsequent reperfusion. In mice treated with IQ-1S, ischemic and reperfusion values of CBF were not different from vehicle-treated mice. However, IQ-1S treated mice demonstrated markedly reduced neurological deficit and infarct volumes as compared with vehicle-treated mice after 48 hours of reperfusion. Our results indicate that the novel JNK inhibitor releases NO during its oxidoreductive bioconversion and improves stroke outcome in a mouse model of cerebral reperfusion. We conclude that IQ-1S is a promising dual functional agent for the treatment of cerebral ischemia and reperfusion injury. PMID:26923672

  14. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice

    Directory of Open Access Journals (Sweden)

    Ladefoged Ole

    2009-01-01

    Full Text Available Abstract Background The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-. We studied the effects instillation or inhalation Printex 90 of carbon black (CB and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL fluid. Results Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60 and single walled carbon nanotubes (SWCNT as well as gold particles and quantum dots (QDs. Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses. Conclusion Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles.

  15. Antibody response is required for protection from Theiler's virus-induced encephalitis in C57BL/6 mice in the absence of CD8+ T cells

    International Nuclear Information System (INIS)

    Kang, B.-S.; Palma, Joann P.; Lyman, Michael A.; Dal Canto, Mauro; Kim, Byung S.

    2005-01-01

    Intracerebral infection of susceptible mice with Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediated demyelinating disease and this system serves as a relevant infectious model for human multiple sclerosis. It was previously shown that β 2 M-deficient C57BL/6 mice lacking functional CD8 + T cells display increased viral persistence and enhanced susceptibility to TMEV-induced demyelination, and yet the majority of mice are free of clinical signs. To understand the mechanisms involved in this general resistance of C57BL/6 mice in the absence of CTL responses, mice (μMT) deficient in the B-cell compartment lacking membrane IgM molecules were treated with anti-CD8 antibody and then infected with TMEV. Although little difference in the proliferative responses of peripheral T cells to UV-inactivated TMEV and the resistance to demyelinating disease was observed between virus-infected μMT and control B6 mice, the levels of CD4 + T cells were higher in the CNS of μMT mice. However, after treatment with anti-CD8 antibody, 100% of the mice displayed clinical gray matter disease and prolonged viral persistence in μMT mice, while only 10% of B6 mice showed clinical symptoms and very low viral persistence. Transfusion of sera from TMEV-infected B6 mice into anti-CD8 antibody-treated μMT mice partially restored resistance to virus-induced encephalitis. These results indicate that the early anti-viral antibody response is also important in the protection from TMEV-induced encephalitis particularly in the absence of CD8 + T cells

  16. Vaccination with a HSV-2 UL24 mutant induces a protective immune response in murine and guinea pig vaginal infection models.

    Science.gov (United States)

    Visalli, Robert J; Natuk, Robert J; Kowalski, Jacek; Guo, Min; Blakeney, Susan; Gangolli, Seema; Cooper, David

    2014-03-10

    The rational design and development of genetically attenuated HSV-2 mutant viruses represent an attractive approach for developing both prophylactic and therapeutic vaccines for genital herpes. Previously, HSV-2 UL24 was shown to be a virulence determinant in both murine and guinea pig vaginal infection models. An UL24-βgluc insertion mutant produced syncytial plaques and replicated to nearly wild type levels in tissue culture, but induced little or no pathological effects in recipient mice or guinea pigs following vaginal infection. Here we report that immunization of mice or guinea pigs with high or low doses of UL24-βgluc elicited a highly protective immune response. UL24-βgluc immunization via the vaginal or intramuscular routes was demonstrated to protect mice from a lethal vaginal challenge with wild type HSV-2. Moreover, antigen re-stimulated splenic lymphocytes harvested from immunized mice exhibited both HSV-2 specific CTL activity and IFN-γ expression. Humoral anti-HSV-2 responses in serum were Th1-polarized (IgG2a>IgG1) and contained high-titer anti-HSV-2 neutralizing activity. Guinea pigs vaccinated subcutaneously with UL24-βgluc or the more virulent parental strain (186) were challenged with a heterologous HSV-2 strain (MS). Acute disease scores were nearly indistinguishable in guinea pigs immunized with either virus. Recurrent disease scores were reduced in UL24-βgluc immunized animals but not to the same extent as those immunized with strain 186. In addition, challenge virus was not detected in 75% of guinea pigs subcutaneously immunized with UL24-βgluc. In conclusion, disruption of the UL24 gene is a prime target for the development of a genetically attenuated live HSV-2 vaccine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Identification of immunodominant Leishmania major antigenic markers of the early C57BL/6 and BALB/c mice infection stages.

    Science.gov (United States)

    Sassi, Atfa; Kaak, Olfa; Elgaaied, Amel Benammar

    2015-08-24

    The C57BL/6 mouse strain is resistant to Leishmania (L.) major infection and, unlike susceptible BALB/c, develops small self healing cutaneous lesions. The specific antibody responses of C57BL/6 and BALB/c mice were previously characterized by the predominance of IgG2a ("resistant" isotype associated with Th1) and IgG1 ("pathogenic" isotype associated with Th2) antibodies, respectively. In this study, we looked for the presence of antigens able to elicit an exclusive or predominant IgG1 production during the early stages of C57BL/6 lesion development and checked whether they are recognized or not by BALB/c mice. We demonstrate first that IgG2a predominance in C57BL/6 sera occurs only late after infection whereas in BALB/c, IgG1 antibodies dominate mostly in the early stages. Interestingly, soon after inoculation of live amastigotes, C57BL/6 displayed an exclusive IgG1 reactivity against particular L. major antigens but with MWs different from those identified in BALB/c. Furthermore, mice immunized with killed amastigotes displayed striking differences in their immunodetection profiles, particularly for the IgG1 isotype. Taken together, the observed differences in the specific antibody repertoires between infected mice resulted, at least in part, from immunological events independent from those triggered by the replicating parasite, and bring new insights into the selection of future vaccine candidates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Experimental Study Of Precipitation Competition Of Ca(OH)2 And Mg(OH)2 On MSF Desalination Condition

    International Nuclear Information System (INIS)

    Sumijanto

    2001-01-01

    Competition study has been carried out by using sea water simulation containing of 142 on deposit ppm of bicarbonate ion, 400 ppm of calcium ion and 1272 ppm of magnesium ion. Experiment was performed by heating sample at temperature 50, 60, 70, 80, and 90 C for 30 minutes. Precipitation competition of Ca(OHh and Mg(OHh was analyzed by reduction of calcium and magnesium ion. Experiment data showed information that at the temperature bellow 800 o C CaCO 3 precipitation was more dominant, meanwhile above than 80 o C precipitation Mg(OH) 2 was more dominant. This competition occurred because at temperature more than 80 o C rate of hydroxyl ion formation and Mg(OH) 2 recipitation was greater than CaCO 3 precipitation and at temperature bellow 80 o C rate of hydrolysis carbonate ion was less than thermal decomposition bicarbonates ion

  19. Protective role of vitamin C against lindane toxicity on the histo ...

    African Journals Online (AJOL)

    We studied the protective effects of vitamin C against the toxic effects of lindane on the epididymis and vas deferens of male mice. There were four treatments: controls (untreated), lindane (20 mg/kg), lindane plus vitamin C (10 mg/kg) and vitamin C only. Lindane induced histopathological alterations in the epididymis and ...

  20. Seeds of Camargue rice (Oryza Sativa L. Var Cigalon) and their responses to exposure to 60-Co gamma radiations. Study of the natural phenomenon of radiation protection

    International Nuclear Information System (INIS)

    Bayonove-Barthelemy, Jacqueline

    1978-01-01

    Within the frame of a project aiming at improving a technique of experimental mutagenesis (seed processing by cobalt-60 gamma rays), this research thesis reports the radiobiological characterization of Cigalon rice seeds, the adjustment of techniques of radiation protection, and the definition of processing and irradiation conditions which could reduce the undesirable physiological effects of cobalt-60 gamma radiation on rice seeds. The author reports the study of variations of physiological radio-sensitivity. Damages are assessed by comparing the growth of irradiated seeds with that of non-irradiated seeds. The mechanism of radiation natural protection is studied by comparing an inhibition in distilled water at two temperatures (5 and 24 C) with that obtained with cysteamine (an efficient radiation protection compound)

  1. Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice.

    Science.gov (United States)

    Griffin, William C; McGovern, Robin W; Bell, Guinevere H; Randall, Patrick K; Middaugh, Lawrence D; Patrick, Kennerly S

    2013-02-01

    Prior research indicates methylphenidate (MPH) and alcohol (ethanol, EtOH) interact to significantly affect responses humans and mice. The present studies tested the hypothesis that MPH and EtOH interact to potentiate ethanol-related behaviors in mice. We used several behavioral tasks including: drug discrimination in MPH-trained and EtOH-trained mice, conditioned place preference (CPP), rota-rod and the parallel rod apparatus. We also used gas chromatographic methods to measure brain tissue levels of EtOH and the D- and L-isomers of MPH and the metabolite, ethylphenidate (EPH). In discrimination, EtOH (1 g/kg) produced a significant leftward shift in the MPH generalization curve (1-2 mg/kg) for MPH-trained mice, but no effects of MPH (0.625-1.25 mg/kg) on EtOH discrimination in EtOH-trained mice (0-2.5 g/kg) were observed. In CPP, the MPH (1.25 mg/kg) and EtOH (1.75 g/kg) combination significantly increased time on the drug paired side compared to vehicle (30.7 %), but this was similar to MPH (28.8 %) and EtOH (33.6 %). Footslip errors measured in a parallel rod apparatus indicated that the drug combination was very ataxic, with footslips increasing 29.5 % compared to EtOH. Finally, brain EtOH concentrations were not altered by 1.75 g/kg EtOH combined with 1.25 mg/kg MPH. However, EtOH significantly increased D-MPH and L-EPH without changing L-MPH brain concentrations. The enhanced behavioral effects when EtOH is combined with MPH are likely due to the selective increase in brain D-MPH concentrations. These studies are consistent with observations in humans of increased interoceptive awareness of the drug combination and provide new clinical perspectives regarding enhanced ataxic effects of this drug combination.

  2. Direct observation of interfacial C60 cluster formation in polystyrene-C60 nanocomposite films

    International Nuclear Information System (INIS)

    Han, Joong Tark; Lee, Geon-Woong; Kim, Sangcheol; Lee, Hae-Jeong; Douglas, Jack F; Karim, Alamgir

    2009-01-01

    Large interfacial C 60 clusters were directly imaged at the supporting film-substrate interface in physically detached polystyrene-C 60 nanocomposite films by atomic force microscopy, confirming the stabilizing mechanism previously hypothesized for thin polymer films. Additionally, we found that the C 60 additive influences basic thermodynamic film properties such as the interfacial energy and the film thermal expansion coefficient.

  3. C{sub 60}{sup 3-} versus C{sub 60}{sup 4-} /C{sub 60}{sup 2-} - synthesis and characterization of five salts containing discrete fullerene anions

    Energy Technology Data Exchange (ETDEWEB)

    Boeddinghaus, M. Bele; Klein, Wilhelm; Wahl, Bernhard; Faessler, Thomas F. [Department of Chemistry, Technische Universitaet Muenchen, Garching (Germany); Jakes, Peter; Eichel, Ruediger A. [Institut fuer Energie- und Klimaforschung (IEK-9), Forschungszentrum Juelich (Germany)

    2014-04-15

    Five new compounds, [Rb(18crown-6)]{sub 3}[C{sub 60}] (1), [Rb(18crown-6)]{sub 6}[C{sub 60}]{sub 2}(C{sub 3}H{sub 7}NO){sub 2}(C{sub 4}H{sub 8}O){sub 2} (2), [Rb(benzo18crown-6)]{sub 6}[C{sub 60}]{sub 2}(C{sub 2}H{sub 8}N{sub 2}){sub 5} (3), [Cs(benzo18crown-6)]{sub 3}C{sub 60}(C{sub 2}H{sub 8}N{sub 2}){sub 2} (4), and [Cs{sub 3}(benzo18crown-6){sub 5}]C{sub 60}(C{sub 2}H{sub 8}N{sub 2}){sub (4.5+x)} (5) were synthesized and characterized by single-crystal X-ray structure determination. All compounds contain discrete C{sub 60} anions, which are ordered in 1, 2, and 4, where direct cation-anion contacts occur. The unit cells of 1 and 2 contain two independent fullerides, which coordinate to the rubidium atoms either of two or of four [Rb(18crown-6)] units. Owing to the presence of differently coordinated fullerene units in compounds 1 and 2, a possible disproportionation of C{sub 60}{sup 3-} into C{sub 60}{sup 2-} and C{sub 60}{sup 4-} anions is discussed. In 3 and 4 the C{sub 60} anions are coordinated by three Rb and Cs atoms, respectively. In all compounds the average charge of the anion is -3. Magnetic data reveal a doublet spin state for 3. The EPR spectra are discussed for compounds 3 and 5. The role of a dynamic Jahn-Teller distortion is discussed, and we report the first IR spectroscopic data of fullerene trianions, which have been obtained in solution. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

    Directory of Open Access Journals (Sweden)

    Ičević Ivana Đ.

    2011-01-01

    Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

  5. Safety, immunogencity, and efficacy of a cold-adapted A/Ann Arbor/6/60 (H2N2) vaccine in mice and ferrets

    International Nuclear Information System (INIS)

    Chen, Grace L.; Lamirande, Elaine W.; Jin Hong; Kemble, George; Subbarao, Kanta

    2010-01-01

    We studied the attenuation, immunogenicity and efficacy of the cold-adapted A/Ann Arbor/6/60 (AA ca) (H2N2) virus in mice and ferrets to evaluate its use in the event of an H2 influenza pandemic. The AA ca virus was restricted in replication in the respiratory tract of mice and ferrets. In mice, 2 doses of vaccine elicited a > 4-fold rise in hemagglutination-inhibition (HAI) titer and resulted in complete inhibition of viral replication following lethal homologous wild-type virus challenge. In ferrets, a single dose of the vaccine elicited a > 4-fold rise in HAI titer and conferred complete protection against homologous wild-type virus challenge in the upper respiratory tract. In both mice and ferrets, the AA ca virus provided significant protection from challenge with heterologous H2 virus challenge in the respiratory tract. The AA ca vaccine is safe, immunogenic, and efficacious against homologous and heterologous challenge in mice and ferrets, supporting the evaluation of this vaccine in clinical trials.

  6. Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

    Science.gov (United States)

    Lilly, Elizabeth A.; Ikeh, Melanie; Nash, Evelyn E.; Fidel, Paul L.

    2018-01-01

    ABSTRACT Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

  7. Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Lilly

    2018-01-01

    Full Text Available Polymicrobial intra-abdominal infections (IAIs are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis. Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge. Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO] survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

  8. Novel Crystal Structure C60 Nanowire

    Science.gov (United States)

    Mickelson, William; Aloni, Shaul; Han, Weiqiang; Cumings, John; Zettl, Alex

    2003-03-01

    We have created insulated C60 nanowire by packing C60 molecules into the interior of insulating boron nitride (BN) nanotubes. For small-diameter BN tubes, the wire consists of a linear chain of C60's. With increasing BN tube inner diameter, novel C60 stacking configurations are obtained (including helical, hollow core, and incommensurate) which are unknown for bulk or thin film forms of C60. C60 in BN nanotubes presents a model system for studying the properties of new dimensionally-constrained "silo" crystal structures.

  9. New baculovirus recombinants expressing Pseudorabies virus (PRV) glycoproteins protect mice against lethal challenge infection.

    Science.gov (United States)

    Grabowska, Agnieszka K; Lipińska, Andrea D; Rohde, Jörg; Szewczyk, Boguslaw; Bienkowska-Szewczyk, Krystyna; Rziha, Hanns-Joachim

    2009-06-02

    The present study demonstrates the protective potential of novel baculovirus recombinants, which express the glycoproteins gB, gC, or gD of Pseudorabies virus (PRV; Alphaherpesvirus of swine) and additionally contain the glycoprotein G of Vesicular Stomatitis Virus (VSV-G) in the virion (Bac-G-PRV). To evaluate the protective capacity, mixtures of equal amounts of the PRV gB-, gC-, and gD-expressing baculoviruses were used for immunization. Three intramuscular immunizations with that Bac-G-PRV mixture could protect mice against a lethal PRV challenge infection. To achieve complete protection high titers of Bac-G-PRV and three immunizations were necessary. This immunization with Bac-G-PRV resulted in the induction of high titers of PRV-specific serum antibodies of the IgG2a subclass and of interferon (IFN)-gamma, indicating a Th1-type immune response. Moreover, splenocytes of immunized mice exhibited natural killer cell activity accompanied by the production of IFN-alpha and IFN-gamma. Collectively, the presented data demonstrate for the first time that co-expression of VSV-G in baculovirus recombinant vaccines can improve the induction of a protective immune response against foreign antigens.

  10. Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice.

    Science.gov (United States)

    Lee, John S; Groebner, Jennifer L; Hadjipanayis, Angela G; Negley, Diane L; Schmaljohn, Alan L; Welkos, Susan L; Smith, Leonard A; Smith, Jonathan F

    2006-11-17

    The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.

  11. Booster vaccination with safe, modified, live-attenuated mutants of Brucella abortus strain RB51 vaccine confers protective immunity against virulent strains of B. abortus and Brucella canis in BALB/c mice.

    Science.gov (United States)

    Truong, Quang Lam; Cho, Youngjae; Kim, Kiju; Park, Bo-Kyoung; Hahn, Tae-Wook

    2015-11-01

    Brucella abortus attenuated strain RB51 vaccine (RB51) is widely used in prevention of bovine brucellosis. Although vaccination with this strain has been shown to be effective in conferring protection against bovine brucellosis, RB51 has several drawbacks, including residual virulence for animals and humans. Therefore, a safe and efficacious vaccine is needed to overcome these disadvantages. In this study, we constructed several gene deletion mutants (ΔcydC, ΔcydD and ΔpurD single mutants, and ΔcydCΔcydD and ΔcydCΔpurD double mutants) of RB51 with the aim of increasing the safety of the possible use of these mutants as vaccine candidates. The RB51ΔcydC, RB51ΔcydD, RB51ΔpurD, RB51ΔcydCΔcydD and RB51ΔcydCΔpurD mutants exhibited significant attenuation of virulence when assayed in murine macrophages in vitro or in BALB/c mice. A single intraperitoneal immunization with RB51ΔcydC, RB51ΔcydD, RB51ΔcydCΔcydD or RB51ΔcydCΔpurD mutants was rapidly cleared from mice within 3 weeks, whereas the RB51ΔpurD mutant and RB51 were detectable in spleens until 4 and 7 weeks, respectively. Vaccination with a single dose of RB51 mutants induced lower protective immunity in mice than did parental RB51. However, a booster dose of these mutants provided significant levels of protection in mice against challenge with either the virulent homologous B. abortus strain 2308 or the heterologous Brucella canis strain 26. In addition, these mutants were found to induce a mixed but T-helper-1-biased humoral and cellular immune response in immunized mice. These data suggest that immunization with a booster dose of attenuated RB51 mutants provides an attractive strategy to protect against either bovine or canine brucellosis.

  12. Protective effect of corticosteroids on radiation pneumonitis in mice

    International Nuclear Information System (INIS)

    Gross, N.J.; Narine, K.R.; Wade, R.

    1988-01-01

    We explored the protective effect of corticosteroids on the mortality of mice that received thoracic irradiation. Methylprednisolone, 100 mg/kg/week, given from 11 weeks after gamma irradiation of the thorax resulted in an increase in the LD50 (11-26 weeks) from 14.3 +/- 0.3 (mean +/- SE) Gy to 17.6 +/- 0.4 Gy, P less than 0.001, a protection factor of 1.2. Withdrawal of steroids at various times during the period of radiation pneumonitis resulted in accelerated mortality in the next 2-4 weeks, so that the cumulative mortality caught up with that of control animals by 4 weeks after steroid withdrawal. However, after the end of the usual period of pneumonitis withdrawal of steroids did not result in accelerated mortality, suggesting that the time when steroids are protective corresponds to the duration of pneumonitis. A smaller dose of steroids, 25 mg/kg/week, was found to be as protective as the larger dose used in the above experiments. The possibility that corticosteroids reduce mortality, even when given many weeks after radiation, may have important practical and theoretical implications

  13. Cytogenetic effects of protracted exposures to alpha-particles from plutonium-239 and to gamma-rays from cobalt-60 compared in male mice

    International Nuclear Information System (INIS)

    Searle, A.G.; Beechey, C.V.; Green, D.; Humphreys, E.R.

    1976-01-01

    Adult C3HX 101 hybrid male mice were injected intravenously with 4 μCi of 239 Pu citrate per kg body weight and examined for evidence of cytogenetic damage to the testis after exposures of 21, 28 and 34 weeks, with average doses from α-particles estimated as 13, 18 and 18 rad respectively (mean dose rate 0.00006 rad/min). Results were compared with those obtained when equivalent males were exposed continuously and concurrently to 1128 rad 60 Co γ-irradiation over 28 weeks (0.004 rad/min) The following estimates of the relative effectiveness of the α-and γ-radiation were made: 24 for reciprocal translocations and for chromosome fragments, 22 for dominant lethal mutations acting after implantation. These values (with mean of 23) are based on average testis doses, with no correction for probable non-homogeneity of α dose distribution. In the mice exposed to γ-irradiation, there were significant reductions in testis mass and epididymal sperm-count

  14. Methamphetamine-induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents.

    Science.gov (United States)

    Albers, D S; Sonsalla, P K

    1995-12-01

    Neurotoxic doses of methamphetamine (METH) can cause hyperthermia in experimental animals. Damage sustained to dopaminergic nerve terminals by this stimulant can be reduced by environmental cooling or by pharmacological manipulation which attenuates the hyperthermia. Many pharmacological agents with very diverse actions protect against METH-induced neuropathology. Several of these compounds, as well as drugs which do not protect, were investigated to determine if there was a relationship between protection and METH-induced hyperthermia. Mice received METH with or without concurrent administration of other drugs and core (i.e., colonic) temperature was monitored during treatment. The animals were sacrificed > or = 5 days later and neostriatal tyrosine hydroxylase activity and dopamine were measured. Core temperature was significantly elevated (> or = 2 degrees C) in mice treated with doses of METH which produced > or = 90% losses in striatal dopamine but not in mice less severally affected (only 50% loss of dopamine). Concurrent treatment of mice with METH and pharmacological agents which protected partially or completely from METH-induced toxicity also prevented the hyperthermic response (i.e., dopamine receptor antagonists, fenfluramine, dizocilpine, alpha-methyl-p-tyrosine, phenytoin, aminooxyacetic acid and propranol). These findings are consistent with the hypothesis that the hyperthermia produced by METH contributes to its neuropathology. However, studies with reserpine, a compound which dramatically lowers core temperature, demonstrated that hyperthermia per se is not a requirement for METH-induced neurotoxicity. Although core temperature was elevated in reserpinized mice treated with METH as compared with reserpinized control mice, their temperatures remained significantly lower than in nonreserpinized control mice. However, the hypothermic state produced in the reserpinized mice did not provide protection from METH-induced toxicity. These data demonstrate

  15. Protective effect of total flavones of Abelmoschus manihot L. Medic against poststroke depression injury in mice and its action mechanism.

    Science.gov (United States)

    Liu, Mei; Jiang, Qiu-Hong; Hao, Ji-Li; Zhou, Lan-Lan

    2009-03-01

    Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic. We investigated the protective effect of TFA against poststroke depression (PSD) injury in mice and its action mechanism. A mouse model of PSD was induced by middle cerebral artery occlusion (MACO) 30 min/reperfusion, followed by isolation feeding and chronic unpredictable mild stress for 2 weeks. Treatment groups received TFA at three different doses (160, 80, and 40 mg/kg, p.o.) or fluoxetine (Flu, 2.5 mg/kg, p.o.) daily for 24 days. Change in behavior, brain tissue malondialdehyde (MDA) levels, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. The expression of brain-derived neurotrophic factor (BDNF) was detected by immunohistochemistry, and mRNA expression of BDNF and cAMP response element-binding protein (CREB) analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Treatment with TFA (160, 80, and 40 mg/kg) significantly ameliorated mice escape-directed behavioral impairment induced by PSD, markedly reduced MDA levels, and increased the activity of SOD, GSH-Px close to normal levels. TFA administration also attenuated PSD-induced neuronal death/losses, upregulated expression of BDNF both at mRNA and protein levels, as well as CREB mRNA levels. TFA had a protective effect against PSD injury in mice. Cardioprotection involves the inhibition of lipid peroxidation and upregulation of BDNF-CREB levels in the hippocampus, which may also be important mechanism of its antidepressants. This potential protection makes TFA a promising therapeutic agent for the PSD. (c) 2009 Wiley-Liss, Inc.

  16. 41 CFR 60-300.24 - Drugs and alcohol.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Drugs and alcohol. 60-300... VETERANS Discrimination Prohibited § 60-300.24 Drugs and alcohol. (a) Specific activities permitted. The contractor: (1) May prohibit the illegal use of drugs and the use of alcohol at the workplace by all...

  17. 41 CFR 60-741.24 - Drugs and alcohol.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Drugs and alcohol. 60-741... INDIVIDUALS WITH DISABILITIES Discrimination Prohibited § 60-741.24 Drugs and alcohol. (a) Specific activities permitted. The contractor: (1) May prohibit the illegal use of drugs and the use of alcohol at the workplace...

  18. 41 CFR 60-250.24 - Drugs and alcohol.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Drugs and alcohol. 60-250... VETERANS Discrimination Prohibited § 60-250.24 Drugs and alcohol. (a) Specific activities permitted. The contractor: (1) May prohibit the illegal use of drugs and the use of alcohol at the workplace by all...

  19. The complex of PAMAM-OH dendrimer with Angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1–7) (Ang-(1–7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1–7) carrier. Bioinformatics analysis showed that the Ang-(1–7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7)/PAMAM-OH complex, but not Ang-(1–7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1–7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1–7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1–7)/PAMAM-OH complex is an efficient delivery method for Ang-(1–7), since it improves the anti-atrophic activity of this peptide in skeletal muscle. PMID:28331320

  20. A chronic toxicity/carcinogenicity study of FD & C Yellow No. 5 (tartrazine) in mice.

    Science.gov (United States)

    Borzelleca, J F; Hallagan, J B

    1988-03-01

    Charles River CD-1 mice were fed FD & C Yellow No. 5 in the diet at levels of 0.0, 0.0, 0.5, 1.5 or 5.0% in a long-term toxicity/carcinogenicity study. Each group consisted of 60 males and 60 females. Maximum exposure was 104 wk for both males and females. No consistent, significant compound-related adverse effects were noted. The no-observed-adverse effect level established in this study was 5.0% (8103 mg/kg/day and 9735 mg/kg/day for male and female mice, respectively.)

  1. MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

    International Nuclear Information System (INIS)

    Kimura, Akihiko; Ishida, Yuko; Wada, Takashi; Yokoyama, Hitoshi; Mukaida, Naofumi; Kondo, Toshikazu

    2005-01-01

    To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs

  2. Nonalcoholic steatohepatitic (NASH) mice are protected from higher hepatotoxicity of acetaminophen upon induction of PPARα with clofibrate

    International Nuclear Information System (INIS)

    Donthamsetty, Shashikiran; Bhave, Vishakha S.; Mitra, Mayurranjan S.; Latendresse, John R.; Mehendale, Harihara M.

    2008-01-01

    The objective was to investigate if the hepatotoxic sensitivity in nonalcoholic steatohepatitic mice to acetaminophen (APAP) is due to downregulation of nuclear receptor PPARα via lower cell division and tissue repair. Male Swiss Webster mice fed methionine and choline deficient diet for 31 days exhibited NASH. On the 32nd day, a marginally toxic dose of APAP (360 mg/kg, ip) yielded 70% mortality in steatohepatitic mice, while all non steatohepatitic mice receiving the same dose survived. 14 C-APAP covalent binding, CYP2E1 protein, and enzyme activity did not differ from the controls, obviating increased APAP bioactivation as the cause of amplified APAP hepatotoxicity. Liver injury progressed only in steatohepatitic livers between 6 and 24 h. Cell division and tissue repair assessed by 3 H-thymidine incorporation and PCNA were inhibited only in the steatohepatitic mice given APAP suggesting that higher sensitivity of NASH liver to APAP-induced hepatotoxicity was due to lower tissue repair. The hypothesis that impeded liver tissue repair in steatohepatitic mice was due to downregulation of PPARα was tested. PPARα was downregulated in NASH. To investigate whether downregulation of PPARα in NASH is the critical mechanism of compromised liver tissue repair, PPARα was induced in steatohepatitic mice with clofibrate (250 mg/kg for 3 days, ip) before injecting APAP. All clofibrate pretreated steatohepatitic mice receiving APAP exhibited lower liver injury, which did not progress and the mice survived. The protection was not due to lower bioactivation of APAP but due to higher liver tissue repair. These findings suggest that inadequate PPARα expression in steatohepatitic mice sensitizes them to APAP hepatotoxicity

  3. Influence of various scavengers of •OH radicals on the radiation sensitivity of yeast and bacteria.

    Science.gov (United States)

    Múčka, Viliam; Bláha, Pavel; Čuba, Václav; Červenák, Jaroslav

    2013-12-01

    To quantitatively investigate the influence of various •OH (hydroxyl radical) scavengers on the radiation sensitivity of yeast and bacteria, particularly to define the relationship between the protective effect of a scavenger and its •OH scavenging efficiency. In order to study the protective effect of •OH scavengers we used various concentrations of four scavengers (methanol, potassium formate, ethanol and ascorbic acid) in isotonic salt solutions. These solutions containing live yeast (Saccharomyces cerevisiae) or bacteria (Escherichia coli) were irradiated with (60)Co isotope γ -radiation using two different doses and dose rates. The number of surviving cells was determined prior to and after irradiation both in suspension with and without scavengers. The surviving fractions after irradiation with and without the scavenger were evaluated. The main results of the paper were: The surviving fraction increased approximately linearly within the measured interval with increasing concentration of the scavenger. The same dependences were found for the protecting effect depending on the scavenging efficiency. The slopes of these dependences (k) were found to be characteristic for each scavenger. The k value determined the degree in which the scavenging of •OH radicals participated in the protection of living cells. The protective effects of scavengers at the same scavenging efficiency were different and unique for each scavenger. No simple relation was found between the efficiency of scavenger k and the rate constant kOH of the reactions between scavengers and •OH radicals. Our results suggest that the studied scavengers effectively protected yeast and bacteria against ionizing radiation. Although the scavenging of •OH radicals seems to be important for protection of living cells, it is clearly not the only process on which the protection is based.

  4. The protective effect of Royal Jelly against the hemopoiesis dysfunction in X-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Emori, Yutaka; Oka, Hideki; Ohya, Osamu; Tamaki, Hajime; Hayashi, Yoshiro [Zeria Pharmaceutical Co., Ltd., Konan, Saitama (Japan). Central Research Laboratories; Nomoto, Kikuo

    1998-02-01

    The protective effect of Royal Jelly (RJ) against the hemopoietic dysfunction in whole body X-irradiated C57BL/6 mice was investigated. When RJ (1.0 g/kg, po or 0.5 g/kg, ip) was administered every day beginning two weeks before X-irradiation (10 Gy), a significant increase in the number of leukocytes and erythrocytes was observed in mice treated with RJ, as compared with X-irradiated control. In addition, the number of colony forming units in culture (CFU-C) of bone marrow cells or splenocytes was significantly increased in mice treated with RJ. Therefore, when granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) in peripheral blood was measured by ELISA kit, a significant increase in the amount of GM-CSF and IL-3 was observed. These results suggest that the protective effect of RJ against hemopoietic dysfunction could be expressed through an increase in the number of hemopoietic stem cells by the induction of hemopoietic factor such as GM-CSF and IL-3. (author)

  5. Aggregation behavior of fullerenes in aqueous solutions: a capillary electrophoresis and asymmetric flow field-flow fractionation study

    NARCIS (Netherlands)

    Astefanei, A.; Núñez, O.; Galceran, M.T.; Kok, W.Th.; Schoenmakers, P.J.

    2015-01-01

    In this work, the electrophoretic behavior of hydrophobic fullerenes [buckminsterfullerene (C-60), C-70, and N-methyl-fulleropyrrolidine (C-60-pyrr)] and water-soluble fullerenes [fullerol (C-60(OH)(24)); polyhydroxy small gap fullerene, hydrated (C-120(OH)(30)); C-60 pyrrolidine tris acid

  6. Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Priscila Marianno

    Full Text Available Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies have shown that environmental enrichment (EE affects ethanol intake and other reinforcing effects. However, different EE protocols may vary in their ability to influence alcohol consumption and stress-induced intake. The present study evaluated whether short (3 h or continuous (24 h EE protocols affect ethanol consumption after periods of withdrawal. Mice were challenged with stressful stimuli (24 h isolation and restraint stress to evaluate the effects of stress on drinking. Male C57BL/6 mice were subjected to a two-bottle choice drinking-in-the-dark paradigm for 15 days (20% ethanol and water, 2 h/day, acquisition phase. Control mice were housed under standard conditions (SC. In the first experiment, one group of mice was housed under EE conditions 24 h/day (EE24h. In the second experiment, the exposure to EE was reduced to 3 h/day (EE3h. After the acquisition phase, the animals were deprived of ethanol for 6 days, followed by 2 h ethanol access once a week. Animals were tested in the elevated plus maze (EPM during ethanol withdrawal. During the last 2 weeks, the mice were exposed to 24 h ethanol access. A 1-h restraint stress test was performed immediately before the last ethanol exposure. EE24h but not EE3h increased anxiety-like behavior during withdrawal compared to controls. Neither EE24h nor EE3h affected ethanol consumption during the 2 h weekly exposure periods. However, EE24h and EE3h mice that were exposed to acute restraint stress consumed less ethanol than controls during a 24 h ethanol access. These results showed that EE reduces alcohol intake after an acute restraint stress.

  7. Raphanus sativus extract protects against Zearalenone induced reproductive toxicity, oxidative stress and mutagenic alterations in male Balb/c mice.

    Science.gov (United States)

    Ben Salah-Abbès, Jalila; Abbès, Samir; Abdel-Wahhab, Mosaad A; Oueslati, Ridha

    2009-04-01

    Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. There is unequivocal evidence of reproductive toxicity of ZEN in male mice although the mechanism of action is unknown. Several reports suggest that exposure to ZEN resulted in oxidative stress, genotoxicity and perturbation of reproductive parameters. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Raphanus sativus growing in Tunisia against ZEN-induced reproductive toxicity and oxidative stress. Fifty male Balb/c mice were divided into five groups and treated for 28 days as follows: the control group, olive oil-treated groups, another treated with ZEN (40 mg/kg b.w), the last one treated with R. sativus extract alone (15 mg/kg b.w) and the other with ZEN + R. sativus extract. Testis samples were collected for the epididymal sperm count, testosterone concentration, and MDA level, GPx, CAT and SOD activities. Blood samples were collected for different biochemical analyses. Also, RAPD-PCR method was performed to assess the antigenotoxic effect of the extract in germ cells. The results indicated that ZEN-induced toxicological effects in accordance to those reported in the literature: decreasing in the sperm number, testosterone level and antioxidant enzyme status. The RAPD-PCR analysis revealed an alteration in the DNA bands patterns between control and ZEN-treated mice. The extract alone, rich in many antioxidant compounds, was safe and succeeded in counteracting the oxidative stress and protect against the toxicity resulting from ZEN.

  8. Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

    Directory of Open Access Journals (Sweden)

    S.Q. Cui

    2015-06-01

    Full Text Available We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each. The model group received 60% (v/v ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N and microglia (by Ib1 were conducted. Glutamic acid (Glu and gamma amino butyric acid (GABA in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC, and tumor necrosis factor (TNF-α and interleukin (IL-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05 by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01, and neurons were reduced only in the hippocampal dentate gyrus (P<0.01 in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05, and Glu/GABA, TNF-α, and IL-1β increased (P<0.01 with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

  9. Characterization Of Mg(OH)2 Precipitation On MSF Desalination Process

    International Nuclear Information System (INIS)

    Sumijanto

    2000-01-01

    The experiment of Mg(OH) sub.2 precipitation has been carry out. Experiment took please by heating sea water simulation with consist of 142 ppm bicarbonate and magnesium ion at temperature 40, 50, 60, 70, 80, 90, 100, 110, and 120 exp.oC respectively by using autoclave. Sampling has been done periodical for 30 minute in interval 300 minute for each temperature. The calculation of Mg(OH) sub.2 precipitation through the decreasing of magnesium concentration with analysis by AAS. From experiment data have the information that Mg(OH) sub.2 precipitation have been formed since 40 exp.oC. From time variable have been the information that the precipitation formed at 30th minute rapidly. Whether at further time the increasing of precipitation are not significant. This phenomena can explained that at each heating step from 40 exp.oC bicarbonate ion be come decomposition with the result carbonate and hydroxide ion and react with magnesium form Mg(OH) sub.2

  10. Radiosensitivity of spermatogenous epithelium stem cells of mice of different strains and age

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.; Konoplyannikov, A.G.

    1988-01-01

    In experiments on CBA and BALB/c male mices (3 months of age) and F 1 (CBAxC57BL/6) hybrides (at the age of 3, 12, and 24 months) a difference was noted in the radiosensitivity of spermatogenous epithelium stem cells displayed by the changes in their colony-forming ability to testicular tubules 42 days following local 60 Co-γ-irradiation. The older the hybrid mice the smaller was the number of spermatogenous epithelium stem cells

  11. [Changes of nitric oxide after trichloroethylene irritation in hairless mice skin and protection of ginkgo biloba extract and vitamin E].

    Science.gov (United States)

    Wang, Liang; Shen, Tong; Zhou, Cheng-fan; Yu, Jun-feng; Zhu, Qi-xing

    2009-04-01

    To study the changes of nitric oxide (NO) in the BALB/c hairless mice skin after trichloroethylene (TCE) irritation and the protection of ginkgo biloba extract (GbE) and vitamin E (VE). 132 BALB/c hairless mice were randomly divided into blank control group, solvent group (olive oil), TCE groups (20%TCE, 40%TCE, 80%TCE and 100%TCE), GbE groups (0.1%GbE, 1%GbE and 10%GbE) and VE groups (5%VE, 10% VE and 20% VE), with 11 animals in each group, 5 for acute irritation test and 6 for the cumulative irritation test. The skin irritation was observed, and the levels of NO in the dorsal skin of BALB/C hairless mice were detected. The kit of NO was used to detect the levels of NO in the dorsal skin of BALB/c hairless mice. (1) The skin presented erythema and edema after TCE irritation both in acute irritation and cumulative irritation test and the skin inflammation showed time-dose effect relationship; the mice skin was protected in GbE or VE groups. (2) In the acute stimulation test, the levels of NO in 80%TCE group (69.895 +/- 9.605 micromol/mg pro) and 100%TCE group (77.273 +/- 9.290 micromol/mg pro) were significantly different compared with blank control group and solvent control group (P skin of BALB/c hairless mice and induce the significant increase of the NO levels. GbE and VE can protect the skin from TCE irritation damage.

  12. Early transcriptional changes in cardiac mitochondria during chronic doxorubicin exposure and mitigation by dexrazoxane in mice

    Energy Technology Data Exchange (ETDEWEB)

    Vijay, Vikrant; Moland, Carrie L.; Han, Tao; Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lee, Taewon [Department of Mathematics, Korea University, Sejong (Korea, Republic of); Herman, Eugene H. [Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850-9734 (United States); Jenkins, G. Ronald [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Cummings, Connie A. [UltraPath Imaging, 2228 Page Road, Durham, NC 27703 (United States); Gao, Yuan; Cao, Zhijun; Yu, Li-Rong [Biomarkers and Alternative Models Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

    2016-03-15

    Identification of early biomarkers of cardiotoxicity could help initiate means to ameliorate the cardiotoxic actions of clinically useful drugs such as doxorubicin (DOX). Since DOX has been shown to target mitochondria, transcriptional levels of mitochondria-related genes were evaluated to identify early candidate biomarkers in hearts of male B6C3F{sub 1} mice given a weekly intravenous dose of 3 mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively). Also, a group of mice was pretreated (intraperitoneally) with the cardio-protectant, dexrazoxane (DXZ; 60 mg/kg) 30 min before each weekly dose of DOX or SAL. At necropsy a week after the last dose, increased plasma concentrations of cardiac troponin T (cTnT) were detected at 18 and 24 mg/kg cumulative DOX doses, whereas myocardial alterations were observed only at the 24 mg/kg dose. Of 1019 genes interrogated, 185, 109, 140, 184, and 451 genes were differentially expressed at 6, 9, 12, 18, and 24 mg/kg cumulative DOX doses, respectively, compared to concurrent SAL-treated controls. Of these, expression of 61 genes associated with energy metabolism and apoptosis was significantly altered before and after occurrence of myocardial injury, suggesting these as early genomics markers of cardiotoxicity. Much of these DOX-induced transcriptional changes were attenuated by pretreatment of mice with DXZ. Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. This information on early transcriptional changes during DOX treatment may be useful in designing cardioprotective strategies targeting mitochondria. - Highlights: • Altered mitochondria-related gene expression before heart injury by doxorubicin • Dexrazoxane mitigated doxorubicin-induced early expression changes in mitochondria. • Dexrazoxane completely ameliorated doxorubicin-induced pathology in mouse heart.

  13. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    Science.gov (United States)

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  14. Fluoxetine protection in decompression sickness in mice is enhanced by blocking TREK-1 potassium channel with the spadin antidepressant.

    Directory of Open Access Journals (Sweden)

    Nicolas eVallée

    2016-02-01

    Full Text Available In mice, disseminated coagulation, inflammation and ischemia induce neurological damages that can lead to the death. These symptoms result from circulating bubbles generated by a pathogenic decompression. An acute fluoxetine treatment or the presence of the TREK-1 potassium channel increased the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50mg/kg in wild-type (WT and TREK-1 deficient mice (Knockout homozygous KO and heterozygous HET. Then, we combined the same fluoxetine treatment with a five-day treatment by spadin, in order to specifically block TREK-1 activity (KO-like mice. KO and KO-like mice could be regarded as antidepressed models.167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux and 4% of mice treated with both spadin and fluoxetine (KO-likeflux died from decompression sickness (DCS symptoms. These values are much lower than those of WT control (62% or KO-like mice (41%. After the decompression protocol, mice showed a significant consumption of their circulating platelets and leukocytes.Spadin antidepressed mice were more likely to declare DCS. Nevertheless, which had both blocked TREK-1 channel and were treated with fluoxetine were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but a concomitant fluoxetine treatment not only decreases DCS severity but increases the survival rate.

  15. Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice.

    Science.gov (United States)

    Martinez, Elisa C; Garg, Ravendra; Shrivastava, Pratima; Gomis, Susantha; van Drunen Littel-van den Hurk, Sylvia

    2016-11-01

    Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in infants and young children. There are no licensed RSV vaccines available, and the few treatment options for high-risk individuals are either extremely costly or cause severe side effects and toxicity. Immunomodulation mediated by a novel formulation consisting of the toll-like receptor 3 agonist poly(I:C), an innate defense regulator peptide and a polyphosphazene (P-I-P) was evaluated in the context of lethal infection with pneumonia virus of mice (PVM). Intranasal delivery of a single dose of P-I-P protected adult mice against PVM when given 24 h prior to challenge. These animals experienced minimal weight loss, no clinical disease, 100% survival, and reduced lung pathology. Similar clinical outcomes were observed in mice treated up to 3 days prior to infection. P-I-P pre-treatment induced early mRNA and protein expression of key chemokine and cytokine genes, reduced the recruitment of neutrophils and eosinophils, decreased virus titers in the lungs, and modulated the delayed exacerbated nature of PVM disease without any short-term side effects. On day 14 post-infection, P-I-P-treated mice were confirmed to be PVM-free. These results demonstrate the capacity of this formulation to prevent PVM and possibly other viral respiratory infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. 24 CFR 3280.306 - Windstorm protection.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Windstorm protection. 3280.306... Requirements § 3280.306 Windstorm protection. (a) Provisions for support and anchoring systems. Each... shall have a vertical tie installed at each diagonal tie location. (e) Protection requirements...

  17. Study of immunogenicity of solid Gardner's lymphosarcoma implanted to C3H/Sumice mice

    International Nuclear Information System (INIS)

    Motycka, K.; Soucek, J.; Potmesilova, I.; Zak, M.; Jandova, A.; Bostik, J.; Pezlarova, A.

    1982-01-01

    Mice of inbred strain C3H/Sumice (H-2sup(k)) were immunized with solid Gardner's lymphosarcoma cells inactivated using a 60 Co source. Immunization once repeated extended average survival after transplantation of proliferation-capable cells of the tumor as against intact controls. After immunization twice repeated, some mice were so resistant that they survived the time of observation without tumor. Significant differences were found in relative numbers of mice in the individual experimental groups which, immunized using the same technique, became little, or totally resistant to the transplantation of viable tumor. Transplantation of spleen cells of the C3H strain mice which survived the time of observation without apparent tumor showed that resistance need not be associated with the disposal of all malignant Gardner's lymphosarcoma cells. Different reasons for immunity to the tumor are disscussed on the basis of the differences in the cytotoxicity of the spleen cells of the C3H (H-2sup(k)) strain mice and those of the C 57B1.B10 (H-2sup(b)) strain, immune to the lymphosarcoma. (author)

  18. Roymillerite, Pb24Mg9(Si9AlO28)(SiO4)(BO3)(CO3)10(OH)14O4, a new mineral: mineralogical characterization and crystal chemistry

    Science.gov (United States)

    Chukanov, Nikita V.; Jonsson, Erik; Aksenov, Sergey M.; Britvin, Sergey N.; Rastsvetaeva, Ramiza K.; Belakovskiy, Dmitriy I.; Van, Konstantin V.

    2017-11-01

    The new mineral roymillerite Pb24Mg9(Si9AlO28)(SiO4)(BO3)(CO3)10(OH)14O4, related to britvinite and molybdophyllite, was discovered in a Pb-rich assemblage from the Kombat Mine, Grootfontein district, Otjozondjupa region, Namibia, which includes also jacobsite, cerussite, hausmannite, sahlinite, rhodochrosite, barite, grootfonteinite, Mn-Fe oxides, and melanotekite. Roymillerite forms platy single-crystal grains up to 1.5 mm across and up to 0.3 mm thick. The new mineral is transparent, colorless to light pink, with a strong vitreous lustre. Cleavage is perfect on (001). Density calculated using the empirical formula is equal to 5.973 g/cm3. Roymillerite is optically biaxial, negative, α = 1.86(1), β ≈ γ = 1.94(1), 2 V (meas.) = 5(5)°. The IR spectrum shows the presence of britvinite-type tetrahedral sheets, {CO}3^{2 - }, {BO}3^{3 - }, and OH- groups. The chemical composition is (wt%; electron microprobe, H2O and CO2 determined by gas chromatography, the content of B2O3 derived from structural data): MgO 4.93, MnO 1.24, FeO 0.95, PbO 75.38, B2O3 0.50, Al2O3 0.74, CO2 5.83, SiO2 7.90, H2O 1.8, total 99.27. The empirical formula based on 83 O atoms pfu (i.e. Z = 1) is Pb24.12Mg8.74Mn1.25Fe0.94B1.03Al1.04C9.46Si9.39H14.27O83. The crystal structure was determined using single-crystal X-ray diffraction data. The new mineral is triclinic, space group P \\bar{1}, with a = 9.315(1), b = 9.316(1), c = 26.463(4) Å, α = 83.295(3)°, β = 83.308(3)°, γ = 60.023(2)°, V = 1971.2(6) Å3. The crystal structure of roymillerite is based built by alternating pyrophyllite-type TOT-modules Mg9(OH)8[(Si,Al)10O28] and I-blocks Pb24(OH)6O4(CO3)10(BO3,SiO4). The strongest lines of the powder X-ray diffraction pattern [ d, Å (I, %) ( hkl)] are: 25.9 (100) (001), 13.1 (11) (002), 3.480 (12) (017, 107, -115, 1-15), 3.378 (14) (126, 216), 3.282 (16) (-2-15, -1-25), 3.185 (12) (-116, 1-16), 2.684 (16) (031, 301, 030, 300, 332, -109, 0-19, 1-18), 2.382 (11) (0.0.-11). Roymillerite is

  19. In contrast to conventional inactivated influenza vaccines, 4xM2e.HSP70c fusion protein fully protected mice against lethal dose of H1, H3 and H9 influenza A isolates circulating in Iran

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahimi, Seyyed Mahmoud, E-mail: smebrahimi@shirazu.ac.ir [Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, P.O. Box 14155-3651,Tehran (Iran, Islamic Republic of); Research Center of Virus and Vaccine, Baqiyatallah University of Medical Science, P.O.Box 14155-3651, Tehran (Iran, Islamic Republic of); Dabaghian, Mehran [Department of Pathobiology, University of Tehran, Faculty of Veterinary Medicine, P.O. Box 14155-6453, Tehran (Iran, Islamic Republic of); Tebianian, Majid [Department of Biotechnology, Razi Vaccine and Serum Research Institute (RVSRI), P.O. Box 31975/148, Karaj, Tehran (Iran, Islamic Republic of); Zabeh Jazi, Mohammad Hossein [Department of Pathobiology, University of Tehran, Faculty of Veterinary Medicine, P.O. Box 14155-6453, Tehran (Iran, Islamic Republic of)

    2012-08-15

    Ideal vaccines against influenza viruses should elicit not only a humoral response, but also a cellular response. Mycobacterium tuberculosis HSP70 (mHSP70) have been found to promote immunogenic APCs function, elicit a strong cytotoxic T lymphocyte (CTL) response, and prevent the induction of tolerance. Moreover, it showed linkage of antigens to the C-terminus of mHSP70 (mHSP70c) can represent them as vaccines resulted in more potent, protective antigen specific responses in the absence of adjuvants or complex formulations. Hence, recombinant fusion protein comprising C-terminus of mHSP70 genetically fused to four tandem repeats of the ectodomain of the conserved influenza matrix protein M2 (M2e) was expressed in Escherichia coli, purified under denaturing condition, refolding, and then confirmed by SDS-PAGE, respectively. The recombinant fusion protein, 4xM2e.HSP70c, retained its immunogenicity and displayed the protective epitope of M2e by ELISA and FITC assays. A prime-boost administration of 4xM2e.HSP70c formulated in F105 buffer by intramuscular route in mice (Balb/C) provided full protection against lethal dose of mouse-adapted H1N1, H3N2, or H9N2 influenza A isolates from Iran compared to 0-33.34% survival rate of challenged unimmunized and immunized mice with the currently in use conventional vaccines designated as control groups. However, protection induced by immunization with 4xM2e.HSP70c failed to prevent weight loss in challenged mice; they experienced significantly lower weight loss, clinical symptoms and higher lung viral clearance in comparison with protective effects of conventional influenza vaccines in challenged mice. These data demonstrate that C-terminal domain of mHSP70 can be a superior candidate to deliver the adjuvant function in M2e-based influenza A vaccine in order to provide significant protection against multiple influenza A virus strains.

  20. In contrast to conventional inactivated influenza vaccines, 4xM2e.HSP70c fusion protein fully protected mice against lethal dose of H1, H3 and H9 influenza A isolates circulating in Iran

    International Nuclear Information System (INIS)

    Ebrahimi, Seyyed Mahmoud; Dabaghian, Mehran; Tebianian, Majid; Zabeh Jazi, Mohammad Hossein

    2012-01-01

    Ideal vaccines against influenza viruses should elicit not only a humoral response, but also a cellular response. Mycobacterium tuberculosis HSP70 (mHSP70) have been found to promote immunogenic APCs function, elicit a strong cytotoxic T lymphocyte (CTL) response, and prevent the induction of tolerance. Moreover, it showed linkage of antigens to the C-terminus of mHSP70 (mHSP70c) can represent them as vaccines resulted in more potent, protective antigen specific responses in the absence of adjuvants or complex formulations. Hence, recombinant fusion protein comprising C-terminus of mHSP70 genetically fused to four tandem repeats of the ectodomain of the conserved influenza matrix protein M2 (M2e) was expressed in Escherichia coli, purified under denaturing condition, refolding, and then confirmed by SDS–PAGE, respectively. The recombinant fusion protein, 4xM2e.HSP70c, retained its immunogenicity and displayed the protective epitope of M2e by ELISA and FITC assays. A prime-boost administration of 4xM2e.HSP70c formulated in F105 buffer by intramuscular route in mice (Balb/C) provided full protection against lethal dose of mouse-adapted H1N1, H3N2, or H9N2 influenza A isolates from Iran compared to 0–33.34% survival rate of challenged unimmunized and immunized mice with the currently in use conventional vaccines designated as control groups. However, protection induced by immunization with 4xM2e.HSP70c failed to prevent weight loss in challenged mice; they experienced significantly lower weight loss, clinical symptoms and higher lung viral clearance in comparison with protective effects of conventional influenza vaccines in challenged mice. These data demonstrate that C-terminal domain of mHSP70 can be a superior candidate to deliver the adjuvant function in M2e-based influenza A vaccine in order to provide significant protection against multiple influenza A virus strains.

  1. CpG oligodeoxyribonucleotides protect mice from Burkholderia pseudomallei but not Francisella tularensis Schu S4 aerosols.

    Science.gov (United States)

    Rozak, David A; Gelhaus, Herbert C; Smith, Mark; Zadeh, Mojgan; Huzella, Louis; Waag, David; Adamovicz, Jeffrey J

    2010-02-05

    Studies have shown that CpG oligodeoxyribonucleotides (ODN) protect mice from various bacterial pathogens, including Burkholderia pseudomallei and Francisella tularensis live vaccine strain (LVS), when administered before parenteral challenge. Given the potential to develop CpG ODN as a pre-treatment for multiple bacterial biological warfare agents, we examined survival, histopathology, and cytokine data from CpG ODN-treated C57BL/6 mice to determine whether previously-reported protection extended to aerosolized B. pseudomallei 1026b and highly virulent F. tularensis Schu S4 infections. We found that, although CpG ODN protected mice from aerosolized B. pseudomallei challenges, the immunostimulant failed to benefit the animals exposed to F. tularensis Schu S4 aerosols. Our results, which contrast with earlier F. tularensis LVS studies, highlight potential differences in Francisella species pathogenesis and underscore the need to evaluate immunotherapies against human pathogenic species.

  2. Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation.

    Science.gov (United States)

    Xiong, Xi; Ren, Yuqian; Cui, Yun; Li, Rui; Wang, Chunxia; Zhang, Yucai

    2017-12-01

    Cholestasis, as a main manifestation, induces liver injury during sepsis. The farnesoid X receptor (FXR) plays an important role in regulating bile acid homeostasis. Whether FXR activation by its agonist obeticholic acid (OCA) is contributed to improve sepsis-induced liver injury remains unknown. The aim of the present study was to investigate the effect of OCA on lipopolysaccharide (LPS)-induced acute liver injury in mice. 8-week old male C57BL/6J mice were randomly divided into control group, LPS group, oral OCA group and LPS plus oral OCA (LPS + OCA) group. The serum and livers were collected for further analysis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin (TBIL) were measured at indicated time after LPS administration. Liver sections were stained with hematoxylin & eosin (H&E). Orally OCA pretreatment stimulated the expression of FXR and BSEP in livers and protected mice from LPS-induced hepatocyte apoptosis and inflammatory infiltration. Consistently, LPS-induced higher serum levels of ALT, AST, TBA and TBIL were significantly reversed by OCA administration. Meanwhile, the mRNA levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) and IL-6 were decreased in livers of mice in LPS + OCA group compared with LPS group. Further investigation indicated that the higher expression of ATF4 and LC3II/I were associated with the protective effect of OCA on LPS-induced liver injury. Orally OCA pretreatment protects mice from LPS-induced liver injury possibly contributed by improved bile acid homeostasis, decreased inflammatory factors and ATF4-mediated autophagy activity in hepatocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Selectively bred crossed high-alcohol-preferring mice drink to intoxication and develop functional tolerance, but not locomotor sensitization during free-choice ethanol access.

    Science.gov (United States)

    Matson, Liana M; Kasten, Chelsea R; Boehm, Stephen L; Grahame, Nicholas J

    2014-01-01

    Crossed high-alcohol-preferring (cHAP) mice were selectively bred from a cross of the HAP1 × HAP2 replicate lines and demonstrate blood ethanol concentrations (BECs) during free-choice drinking reminiscent of those observed in alcohol-dependent humans. In this report, we investigated the relationship between free-choice drinking, intoxication, tolerance, and sensitization in cHAP mice. We hypothesized that initially mice would become ataxic after drinking alcohol, but that increased drinking over days would be accompanied by increasing tolerance to the ataxic effects of ethanol (EtOH). Male and female cHAP mice had free-choice access to 10% EtOH and water (E), while Water mice (W) had access to water alone. In experiment 1, the first drinking experience was monitored during the dark portion of the cycle. Once E mice reached an average intake rate of ≥1.5 g/kg/h, they, along with W mice, were tested for footslips on a balance beam, and BECs were assessed. In experiments 2, 3, and 4, after varying durations of free-choice 10% EtOH access (0, 3, 14, or 21 days), mice were challenged with 20% EtOH and tested for number of footslips on a balance beam or locomotor stimulant response. Blood was sampled for BEC determination. We found that cHAP mice rapidly acquire alcohol intakes that lead to ataxia. Over time, cHAP mice developed behavioral tolerance to the ataxic effects of alcohol, paralleled by escalating alcohol consumption. However, locomotor sensitization did not develop following 14 days of free-choice EtOH access. Overall, we observed increases in free-choice drinking with extended alcohol access paralleled by increases in functional tolerance, but not locomotor sensitization. These data support our hypothesis that escalating free-choice drinking over days in cHAP mice is driven by tolerance to alcohol's behavioral effects. These data are the first to demonstrate that escalating free-choice consumption is accompanied by increasing alcohol tolerance. In

  4. Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice.

    Science.gov (United States)

    Grant, Marianne K O; Seelig, Davis M; Sharkey, Leslie C; Zordoky, Beshay N

    2017-01-01

    There is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known. Therefore, in the present study, we determined the effect of acute DOX exposure on the expression of CYP genes in the hearts of both male and female C57Bl/6 mice. Acute DOX cardiotoxicity was induced by a single intraperitoneal injection of 20 mg/kg DOX in male and female adult C57Bl/6 mice. Cardiac function was assessed 5 days after DOX exposure by trans-thoracic echocardiography. Mice were euthanized 1 day or 6 days after DOX or saline injection. Thereafter, the hearts were harvested and weighed. Heart sections were evaluated for pathological lesions. Total RNA was extracted and expression of natriuretic peptides, inflammatory and apoptotic markers, and CYP genes was measured by real-time PCR. Adult female C57Bl/6 mice were protected from acute DOX-induced cardiotoxicity as they show milder pathological lesions, less inflammation, and faster recovery from DOX-induced apoptosis and DOX-mediated inhibition of beta-type natriuretic peptide. Acute DOX exposure altered the gene expression of multiple CYP genes in a sex-dependent manner. In 24 h, DOX exposure caused male-specific induction of Cyp1b1 and female-specific induction of Cyp2c29 and Cyp2e1. Acute DOX exposure causes sex-dependent alteration of cardiac CYP gene expression. Since cardiac CYP enzymes metabolize several endogenous compounds to biologically active metabolites, sex-dependent alteration of CYP genes may play a role in the sexual dimorphism of acute DOX

  5. Protection from obesity and insulin resistance in mice overexpressing human apolipoprotein C1

    NARCIS (Netherlands)

    Jong, M. C.; Voshol, P. J.; Muurling, M.; Dahlmans, V. E.; Romijn, J. A.; Pijl, H.; Havekes, L. M.

    2001-01-01

    Apolipoprotein (APO) C1 is a 6.6-kDa protein present in plasma and associated with lipoproteins. Using hyperinsulinemic-euglycemic clamp tests, we previously found that in APOC1 transgenic mice, the whole-body insulin-mediated glucose uptake is increased concomitant with a decreased fatty acid

  6. Volume properties and refraction of aqueous solutions of bisadducts of light fullerene C60 and essential amino acids lysine, threonine, and oxyproline (C60(C6H13N2O2)2, C60(C4H8NO3)2, and C60(C5H9NO2)2) at 25°C

    Science.gov (United States)

    Semenov, K. N.; Ivanova, N. M.; Charykov, N. A.; Keskinov, V. A.; Kalacheva, S. S.; Duryagina, N. N.; Garamova, P. V.; Kulenova, N. A.; Nabieva, A.

    2017-02-01

    Concentration dependences of the density of aqueous solutions of bisadducts of light fullerene C60 and essential amino acids are studied by pycnometry. Concentration dependences of the average molar volumes and partial volumes of components (H2O and corresponding bisadducts) are calculated for C60(C6H13N2O2)2-H2O, C60(C4H8NO3)2-H2O, and C60(C5H9NO2)2-H2O binary systems at 25°C. Concentration dependences of the indices of refraction of C60(C6H13N2O2)2-H2O, C60(C4H8NO3)2-H2O, and C60(C5H9NO2)2-H2O binary systems are determined at 25°C. The concentration dependences of specific refraction and molar refraction of bisadducts and aqueous solutions of them are calculated.

  7. Protection of nucleated bone marrow cells of mice against effect of radiation-induced micronucleus formation by using polysaccharides extracted from 'Zi Zhi' (a ganoderma)

    International Nuclear Information System (INIS)

    Chu Fang; Luo Houliang; Luo Gui; Chen Shunle; Liu Zhifang

    1988-01-01

    This paper describes the influence of polysaccharides extracted from 'Zi Zhi' (Ganoderma Sinese Zhao, Xu et Zhang) on the frequency of micronucleated cells induced by 60 Co gamma irradiation at different doses in bone marrow of mice. These polysaccharides of 'Zi Zhi' were shown to be of ability to protect nucleated bone marrow cells from micronucleus formation in irradiated mice. For Swiss mice, a dose reduction factor (DRF) was found to be 1.72 in the range of 0 to 4.728 Gy and for LACA mice, to be 1.73 in the range of 0 to 3.152 Gy. Such findings indicate that these polysaccharides are comparable to L-cysteine in their effeciency of protection

  8. Radioprotection by polyethylene glycol-protein complexes in mice

    International Nuclear Information System (INIS)

    Gray, B.H.; Stull, R.W.

    1983-01-01

    Polyethylene glycol of about 5000 D was activated with cyanuric chloride, and the activated compound was complexed to each of three proteins. Polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase were each radioprotectants when administered prophylactically to female B6CBF1 mice before irradiation. The dose reduction factor for these mice was 1.2 when 5000 units of polyethylene glycol-catalase was administered before 60 Co irradiation. Female B6CBF1 mice administered prophylactic intravenous injections of catalase, polyethylene glycol-albumin, or heat-denatured polyethylene glycol-catalase had survival rates similar to phosphate-buffered saline-injected control mice following 60 Co irradiation. Polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase have radioprotective activity in B6CBF1 mice, which appears to depend in part on enzymatic activities of the complex. However, no radioprotective effect was observed in male C57BL/6 mice injected with each polyethylene glycol-protein complex at either 3 or 24 hr before irradiation. The mechanism for radioprotection by these complexes may depend in part on other factors

  9. Self-Cleaning Photocatalytic Polyurethane Coatings Containing Modified C60 Fullerene Additives

    Directory of Open Access Journals (Sweden)

    Jeffrey G. Lundin

    2014-08-01

    Full Text Available Surfaces are often coated with paint for improved aesthetics and protection; however, additional functionalities that impart continuous self-decontaminating and self-cleaning properties would be extremely advantageous. In this report, photochemical additives based on C60 fullerene were incorporated into polyurethane coatings to investigate their coating compatibility and ability to impart chemical decontaminating capability to the coating surface. C60 exhibits unique photophysical properties, including the capability to generate singlet oxygen upon exposure to visible light; however, C60 fullerene exhibits poor solubility in solvents commonly employed in coating applications. A modified C60 containing a hydrophilic moiety was synthesized to improve polyurethane compatibility and facilitate segregation to the polymer–air interface. Bulk properties of the polyurethane films were analyzed to investigate additive–coating compatibility. Coatings containing photoactive additives were subjected to self-decontamination challenges against representative chemical contaminants and the effects of additive loading concentration, light exposure, and time on chemical decontamination are reported. Covalent attachment of an ethylene glycol tail to C60 improved its solubility and dispersion in a hydrophobic polyurethane matrix. Decomposition products resulting from oxidation were observed in addition to a direct correlation between additive loading concentration and decomposition of surface-residing contaminants. The degradation pathways deduced from contaminant challenge byproduct analyses are detailed.

  10. Toxoplasma gondii vs ionizing radiation: cell and humoral immunity in spleen and gut of isogenic mice immunized with 60Co irradiated tachyzoites

    International Nuclear Information System (INIS)

    Galisteo Junior, Andres Jimenez

    2008-01-01

    We are developing a vaccine for toxoplasmosis, using ionizing radiation as a tool. Here we analyzed the production of systemic and intestinal immunity, with protection studies, in several strains of inbred mice, by oral or parenteral route, using 255 Gy irradiated tachyzoites of T. gondii RH strain, with challenge with cysts of ME- 49 strain. C57Bl/6j, BALB/c and C57Bl/6j IFN-γ -/- mice were immunized with 10 7 irradiated tachyzoites, be parenteral or oral route. Those preparations, both by parenteral or oral routes, induced the production of specific IgG, mainly of the lgG2b subclass, and IgA immunoglobulins in serum, , as determined by ELISA. IgM production was negligible. Parenteral immunized mice showed higher IgG avidity maturation, as compared to oral immunized mice. Fecal excretion of IgG, IgA and IgM was detected in stools of immunized animals, more intense in oral immunized mice. In cellular immunity studies, induced by antigen, with detection of cytokine production by quantitative real-time PCR, there are a great production of IFN-y by spleen cells, with lower levels in Peyer patches cells, where there are a greater IL-2 production. Challenge studies in immunized mice demonstrated protection to infection in all used schedules, greater in BALB/c mice. C57Bl/6j IFN-γ - /- mice, when immunized, showed no signs of disease and produced similar or greater levels of antibodies than wild type mice. They also excreted S-lgA and S-IgM in stools, but with low numbers of brain cysts in parenteral immunized mice, despite similar mortality. Our data points to a fair possibility of use of those irradiated parasites as an oral vaccine, devised to use for veterinary or wild felines vaccination, reducing the production of oocysts by those hosts and interrupting the chain transmission of human toxoplasmosis. (author)

  11. Synthesis of edatrexate (2-13C-glutamate)

    International Nuclear Information System (INIS)

    DeGraw, J.I.; Colwell, W.T.; Jue, Thomas

    1997-01-01

    The experimental antitumor drug Edatrexate, labeled with 99% 13 C at the 2-position of the glutamate acid group was required for 13 C-magnetic resonance spectroscopy studies in biological media. Coupling of 2,4-diamino-4-deoxy-10-ethyl-10-deazapteroic acid with diethyl L-2- 13 C-glutamate as promoted by BOP reagent afforded Edatrexate (2- 13 C-glu) diethyl ester in 60% yield following purification by column chromatography. Saponification by aqueous NaOH in 2-methoxyethanol gave the target molecule in 44% yield or 26% overall. (author)

  12. Early metabolic adaptation in C57BL/6 mice resistant to high fat diet induced weight gain involves an activation of mitochondrial oxidative pathways.

    Science.gov (United States)

    Boulangé, Claire L; Claus, Sandrine P; Chou, Chieh J; Collino, Sebastiano; Montoliu, Ivan; Kochhar, Sunil; Holmes, Elaine; Rezzi, Serge; Nicholson, Jeremy K; Dumas, Marc E; Martin, François-Pierre J

    2013-04-05

    We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The (1)H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of β-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, α-keto-β-methylvalerate and α-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism.

  13. Asymmetric fission and evaporation of C{sup r+}{sub 60} (r = 2-4) fullerene ions in ion-C{sub 60} collisions: III. Universal behaviour of fission

    Energy Technology Data Exchange (ETDEWEB)

    Bordenave-Montesquieu, D; Bordenave-Montesquieu, A; Rentenier, A; Moretto-Capelle, P [LCAR-IRSAMC, UMR 5589 Universite Paul Sabatier-CNRS, 118 rte de Narbonne, 31062 Toulouse Cedex (France)

    2005-04-14

    The behaviour of the asymmetrical fission (AF) scheme (correlated ion distributions) against the collision conditions is investigated using H{sup +}{sub x} (x = 1-3) and He{sup +} projectiles in the 1-130 keV collision energy range. The present work is an extension of our recent publications on this topic using 11 keV protons (Rentenier et al 2004 J. Phys. B: At. Mol. Opt. Phys. 37 2429 and 2455). The threshold for AF is observed at 2 keV proton energy corresponding to a maximum deposited energy equal to about 41 eV. The main result concerns the fragment distributions resulting from AF of C{sup r+}{sub 60} ions, and secondary dissociation of even-n C{sup +}{sub n} fragments, which are both found to remain independent of the projectile species and collision velocity. These findings indicate that they are insensitive to the internal energy distributions of the parent ions. In addition, a contribution of binary collisions between the projectile and individual carbon atoms of the C{sub 60} molecule to AF is identified in the C{sup +}{sub 1} production at the lowest collision velocities, the so-called impulsive fragmentation.

  14. Photoionization of bonding and antibonding-type atom-fullerene hybrid states in Cd@C60 vs Zn@C60

    International Nuclear Information System (INIS)

    Javani, Mohammad H; Manson, Steven T; De, Ruma; Chakraborty, Himadri S; Madjet, Mohamed E

    2014-01-01

    Powerful hybridization of the Cd 4d state with the d-angular momentum state of C 60 π symmetry is found in the local density approximation (LDA) structure of Cd@C 60 ground state. The photoionization of the resulting symmetric and antisymmetric levels are computed using the time dependent LDA method to include electron correlations. Cross sections exhibit effects of the C 60 plasmonic motion coherently coupled to the diffraction-type cavity oscillations induced by local emissions from C 60 . The Cd@C 60 results exhibit a substantial difference from our previous results for Zn@C 60 . (paper)

  15. Therapeutic effects of gingerol on hematopoietic and antioxidative damage of 60Co γ-rays irradiated mice

    International Nuclear Information System (INIS)

    Geng Yanyan; Xie Zhenfei; Zhou Yu; Zeng Xianyin

    2012-01-01

    18 female Kunming mice were chosen and randomly divided into three groups, and the therapeutic effects of gingerol on hemopoietic and antioxidative system in liver of 60 Co γ-rays irradiated mice were developed in this study. Control group was given distilled water intragastrically once a day for five days. Mice in the irradiated group and irradiated + gingerol group were both irradiated at 3 Gy of 60 Co γ-rays and were given distilled water and gingerol intragastrically within 30 min after irradiation respectively, once a day for five days. The mice were sacrificed and sampled in 48 hours after intragastric administration. Compared with control group, the relative spleen index and WBC numbers significantly decreased (P 60 Co γ-rays irradiated mice. (authors)

  16. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice

    International Nuclear Information System (INIS)

    Singh, Vijay K.; Wise, Stephen Y.; Fatanmi, Oluseyi O.; Beattie, Lindsay A.; Ducey, Elizabeth J.; Seed, Thomas M.

    2014-01-01

    The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60 Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans. (author)

  17. Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice.

    Directory of Open Access Journals (Sweden)

    Kazuaki Miyagawa

    Full Text Available Osteocytes express multiple genes involved in mineral metabolism including PHEX, FGF23, DMP1 and FAM20C. In Hyp mice, a murine model for X-linked hypophosphatemia (XLH, Phex deficiency results in the overproduction of FGF23 in osteocytes, which leads to hypophosphatemia and impaired vitamin D metabolism. In this study, to further clarify the abnormality in osteocytes of Hyp mice, we obtained detailed gene expression profiles in osteoblasts and osteocytes isolated from the long bones of 20-week-old Hyp mice and wild-type (WT control mice. The expression of Fgf23, Dmp1, and Fam20c was higher in osteocytic cells than in osteoblastic cells in both genotypes, and was up-regulated in Hyp cells. Interestingly, the up-regulation of these genes in Hyp bones began before birth. On the other hand, the expression of Slc20a1 encoding the sodium/phosphate (Na+/Pi co-transporter Pit1 was increased in osteoblasts and osteocytes from adult Hyp mice, but not in Hyp fetal bones. The direct effects of extracellular Pi and 1,25-dihydroxyvitamin D3 [1,25(OH2D3] on isolated osteoblastic and osteocytic cells were also investigated. Twenty-four-hour treatment with 10-8 M 1,25(OH2D3 increased the expression of Fgf23 in WT osteoblastic cells but not in osteocytic cells. Dmp1 expression in osteocytic cells was increased due to the 24-hour treatment with 10 mM Pi and was suppressed by 10-8 M 1,25(OH2D3 in WT osteocytic cells. We also found the up-regulation of the genes for FGF1, FGF2, their receptors, and Egr-1 which is a target of FGF signaling, in Hyp osteocytic cells, suggesting the activation of FGF/FGFR signaling. These results implicate the complex gene dysregulation in osteoblasts and osteocytes of Hyp mice, which might contribute to the pathogenesis.

  18. Partial Protection of Mice against Trypanosoma cruzi after Immunizing with the TcY 72 Antigenic Preparation

    Directory of Open Access Journals (Sweden)

    Yara M Gomes

    1999-03-01

    Full Text Available A 72 kDa Trypanosoma cruzi glycoprotein recognized by the 164C11 monoclonal antibody (IgM isotype was purified by preparative electrophoresis. The antigenic preparation obtained, named TcY 72, was used to immunize C57Bl/10 mice. The following results were observed after immunization: (1 induction of higher titres of IgG than IgM antibodies, as evaluated by indirect immunofluorescence; (2 significant DTH after injection of epimastigotes in mice footpads; (3 peak parasitemia in immunized mice was significantly reduced and animals were negative by 13 days post-infection, although the mice still succumb to infection; (4 the phenotypic analysis of spleen cell populations showed a decrease in the CD4/CD8 ratio in immunized mice. Taken as a whole, these findings indicate that TcY 72 is immunogenic and potentially important for protective immunity.

  19. Outer Membrane Vesicle Vaccines from Biosafe Surrogates Prevent Acute Lethal Glanders in Mice

    Directory of Open Access Journals (Sweden)

    Michael H. Norris

    2018-01-01

    Full Text Available Burkholderia mallei is a host-adapted Gram-negative mammalian pathogen that causes the severe disease glanders. Glanders can manifest as a rapid acute progression or a chronic debilitating syndrome primarily affecting solipeds and humans in close association with infected animals. In USA, B. mallei is classified as one of the most important bacterial biothreat agents. Presently, there is no licensed glanders vaccine available for humans or animals. In this work, outer membrane vesicles (OMVs were isolated from three attenuated biosafe bacterial strains, Burkholderia pseudomallei Bp82, B. thailandensis E555, and B. thailandensis TxDOH and used to vaccinate mice. B. thailandensis OMVs induced significantly higher antibody responses that were investigated. B. mallei specific serum antibody responses were of higher magnitude in mice vaccinated with B. thailandensis OMVs compared to levels in mice vaccinated with B. pseudomallei OMVs. OMVs derived from biosafe strains protected mice from acute lethal glanders with vesicles from the two B. thailandensis strains affording significant protection (>90% up to 35 days post-infection with some up to 60 days. Organ loads from 35-day survivors indicated bacteria colonization of the lungs, liver, and spleen while those from 60 days had high CFUs in the spleens. The highest antibody producing vaccine (B. thailandensis E555 OMVs also protected C57BL/6 mice from acute inhalational glanders with evidence of full protection.

  20. Packing C60 in Boron Nitride Nanotubes

    Science.gov (United States)

    Mickelson, W.; Aloni, S.; Han, Wei-Qiang; Cumings, John; Zettl, A.

    2003-04-01

    We have created insulated C60 nanowire by packing C60 molecules into the interior of insulating boron nitride nanotubes (BNNTs). For small-diameter BNNTs, the wire consists of a linear chain of C60 molecules. With increasing BNNT inner diameter, unusual C60 stacking configurations are obtained (including helical, hollow core, and incommensurate) that are unknown for bulk or thin-film forms of C60. C60 in BNNTs thus presents a model system for studying the properties of dimensionally constrained ``silo'' crystal structures. For the linear-chain case, we have fused the C60 molecules to form a single-walled carbon nanotube inside the insulating BNNT.

  1. C60H- an intermediate in the photochemical reduction of C60 fullerene with triethylamine

    International Nuclear Information System (INIS)

    Stasko, A.; Brezova, V.; Neudeck, A.; Bartl, A.; Dunsch, L.

    1999-01-01

    The systematic investigations on the photo reduction of C 60 fullerene and its derivatives using triethylamine and TiO 2 donors, and also other techniques, verified the formation of C 60 .- . Formation of the mono-anion a narrow EPR line (pp A = 0.1 mT) was observed. During a continuous irradiation line A is replaced with line B having g B - 2.0006 and pp B = 0.04 mT which also vanished under prolonged irradiation. But lines A and B repeated after stopping irradiation. This unusual behaviour was re-investigated in analogous EPR-NIR experiments using now a rapid NIR spectrometer. The band at 996 nm was assigned to C 60 H - . The mechanism of C 60 H - formation is discussed

  2. The preliminary study in the role of pyrroloquinoline quinine on the γ-ray radiation protection of mice

    International Nuclear Information System (INIS)

    Wu Shiliang; Liu Chunliang; Xu Lan; Zhao Junyu; Qiu Xiuqin

    2009-01-01

    Objective: To study on the role of PQQ (pyrroloquinoline quinone) in the γ-ray radiation protection of mice. Methods: 40 Kunming mice were randomly divided into four groups, namely, non-irradiated group, the simple exposure group, exposure to pre-treatment group, treatment group after irradiation. PQQ mice oral administration was given according to the weight of the daily dose of 2 mg/kg, continuous drug delivery for 7 days. 60 Co γ-ray single irradiation, dose 5 Gy. On the 8th day after irradiation, the mice were killed by cervical dislocation. The collection of serum, liver homogenate was for the determination of biochemical indicators. HE staining of liver slices produced. Results: irradiated mouse serum and liver SOD, T-AOC decreased significantly (P<0.05), MDA was significantly higher (P<0.05). Radiation treatment group serum SOD, T-AOC were significantly higher (P<0.05), MDA was significantly reduced (P<0.05); liver SOD content was significantly higher (P<0.05). All irradiated mice liver plate shows liver disorders, edema of liver cells, degeneration and necrosis. Conclusion: γ-irradiation in mice induced systemic oxidative stress. Liver is one of the radiation-sensitive organs. PQQ for γ-ray irradiation-induced oxidative stress in mice has some protective effect. Its mechanism: PQQ can directly scavenge free radicals, at the same time, mobilize the whole body irradiated mice scavenging system, particularly the activity of SOD and reduce the generation of free radicals and the free radical content. (authors)

  3. Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-CNEN/MG), Belo Horizonte, MG (Brazil)], e-mail: estefaniabio@yahoo.com.br, e-mail: antero@cdtn.br; Resende, Maria Aparecida de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Microbiologia], e-mail: maresend@mono.icb.ufmg.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia], e-mail: goes@mono.icb.ufmg.br, e-mail: brsgarbi@mono.icb.ufmg.br

    2009-07-01

    Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - {gamma}, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-{gamma} production was maintained indicating that a Th1 pattern was

  4. Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

    International Nuclear Information System (INIS)

    Martins, Estefania M.N.; Andrade, Antero S.R.; Resende, Maria Aparecida de; Reis, Bernardo S.; Goes, Alfredo M.

    2009-01-01

    Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - γ, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-γ production was maintained indicating that a Th1 pattern was dominant. For

  5. Synthesis of Hydroxysodalite From Paper Sludge Ash Using NaOH-LiOH Mixtures

    Directory of Open Access Journals (Sweden)

    Takaaki Wajima

    2017-06-01

    Full Text Available Hydroxysodalite zeolite was synthesized at 90 oC from paper sludge ash, which is industrial wastes in paper manufacturing, using NaOH-LiOH mixed solution. Paper sludge ash was discharged from paper making plant as industrial wastes, and the amount is increasing annually. The new utilization of paper sludge ash is desired. Hydroxysodalite can be used to remove HCl gas at high temperature, and there are papers for hydroxysodalite synthesis from various ashes, for example, coal fly ash. In my previous study, hydroxysodalite can be synthesized from paper sludge ash. However, little information can be available on the synthesis of hydroxysodalite from paper sludge ash. Therefore, we attempted to examine the synthesis of hydroxysodalite from paper sludge ash using NaOH-LiOH mixtures. Hydroxysodalite [Na6Al6Si6O24‧8H2O] was obtained in the mixed solution with Li / (Li + Na ratios smaller than 0.25, while katoite [Ca3Al2(SiO4(OH8] was formed in the mixed solutions with the other molar ratios, due to the dissolution of gehlenite [Ca2Al2SiO7]. The observed concentrations of Si and Al in the solution during the reaction explain the synthesis of reaction products, which depends on alkali species.

  6. Decrease of virulence for BALB/c mice produced by continuous subculturing of Nocardia brasiliensis.

    Science.gov (United States)

    Almaguer-Chávez, Janeth A; Welsh, Oliverio; Lozano-Garza, Hector G; Said-Fernández, Salvador; Romero-Díaz, Víktor J; Ocampo-Candiani, Jorge; Vera-Cabrera, Lucio

    2011-10-26

    Subculturing has been extensively used to attenuate human pathogens. In this work we studied the effect of continuous subculturing of Nocardia brasiliensis HUJEG-1 on virulence in a murine model. Nocardia brasiliensis HUJEG-1 was subcultured up to 130 times on brain heart infusion over four years. BALB/c mice were inoculated in the right foot pad with the bacteria subcultured 0, 40, 80, 100 and 130 times (T0, T40, T80 T100 and T130). The induction of resistance was tested by using T130 to inoculate a group of mice followed by challenge with T0 12 weeks later. Biopsies were taken from the newly infected foot-pad and immunostained with antibodies against CD4, CD8 and CD14 in order to analyze the in situ immunological changes. When using T40, T80 T100 and T130 as inoculums we observed lesions in 10, 5, 0 and 0 percent of the animals, respectively, at the end of 12 weeks. In contrast, their controls produced mycetoma in 80, 80, 70 and 60% of the inoculated animals. When studying the protection of T130, we observed a partial resistance to the infection. Immunostaining revealed an intense CD4+ lymphocytic and macrophage infiltrate in healing lesions. After 130 in vitro passages of N. brasiliensis HUJEG-1 a severe decrease in its virulence was observed. Immunization of BALB/c mice, with these attenuated cells, produced a state of partial resistance to infection with the non-subcultured isolate.

  7. Decrease of virulence for BALB/c mice produced by continuous subculturing of Nocardia brasiliensis

    Directory of Open Access Journals (Sweden)

    Ocampo-Candiani Jorge

    2011-10-01

    Full Text Available Abstract Background Subculturing has been extensively used to attenuate human pathogens. In this work we studied the effect of continuous subculturing of Nocardia brasiliensis HUJEG-1 on virulence in a murine model. Methods Nocardia brasiliensis HUJEG-1 was subcultured up to 130 times on brain heart infusion over four years. BALB/c mice were inoculated in the right foot pad with the bacteria subcultured 0, 40, 80, 100 and 130 times (T0, T40, T80 T100 and T130. The induction of resistance was tested by using T130 to inoculate a group of mice followed by challenge with T0 12 weeks later. Biopsies were taken from the newly infected foot-pad and immunostained with antibodies against CD4, CD8 and CD14 in order to analyze the in situ immunological changes. Results When using T40, T80 T100 and T130 as inoculums we observed lesions in 10, 5, 0 and 0 percent of the animals, respectively, at the end of 12 weeks. In contrast, their controls produced mycetoma in 80, 80, 70 and 60% of the inoculated animals. When studying the protection of T130, we observed a partial resistance to the infection. Immunostaining revealed an intense CD4+ lymphocytic and macrophage infiltrate in healing lesions. Conclusions After 130 in vitro passages of N. brasiliensis HUJEG-1 a severe decrease in its virulence was observed. Immunization of BALB/c mice, with these attenuated cells, produced a state of partial resistance to infection with the non-subcultured isolate.

  8. Antidepressants differentially related to 1,25-(OH)₂ vitamin D₃ and 25-(OH) vitamin D₃ in late-life depression.

    Science.gov (United States)

    Oude Voshaar, R C; Derks, W J; Comijs, H C; Schoevers, R A; de Borst, M H; Marijnissen, R M

    2014-04-15

    A low plasma 25-OH vitamin D3 level is a universal risk factor for a wide range of diseases and has also been implicated in late-life depression. It is currently unknown whether the biologically active form of vitamin D, that is, 1,25-(OH)2 vitamin D3, is also decreased in late-life depression, or whether vitamin D levels correlate with specific depression characteristics. We determined plasma 25-OH vitamin D3, 1,25-(OH)2 vitamin D3 and parathormone levels in 355 depressed older persons and 124 non-depressed comparison subjects (age 60 years). Psychopathology was established with the Composite International Diagnostic Interview 2.1, together with potential confounders and depression characteristics (severity, symptom profile, age of onset, recurrence, chronicity and antidepressant drug use). Adjusted for confounders, depressed patients had significantly lower levels of 25-OH vitamin D33 (Cohen's d =0.28 (95% confidence interval: 0.07-0.49), P=0.033) as well as 1,25-(OH)2 vitamin D3 (Cohen's d =0.48 (95% confidence interval: 0.27-0.70), Pdepression characteristics tested, only the use of tricyclic antidepressants (TCAs) was significantly correlated with lower 1,25-(OH)2 vitamin D3 levels (Cohen's d =0.86 (95% confidence interval: 0.53-1.19), Pprecursor 25-OH vitamin D3. As vitamin D levels were significantly lower after adjustment for confounders, vitamin D might have an aetiological role in late-life depression. Differences between depressed and non-depressed subjects were largest for the biologically active form of vitamin D. The differential impact of TCAs on 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 levels suggests modulation of 1-α-hydroxylase and/or 24-hydroxylase, which may in turn have clinical implications for biological ageing mechanisms in late-life depression.

  9. Cold-adapted influenza and recombinant adenovirus vaccines induce cross-protective immunity against pH1N1 challenge in mice.

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    Mark R Soboleski

    Full Text Available The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1 highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus.BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca influenza viruses from 1977 or recombinant adenoviruses (rAd expressing 1934 nucleoprotein (NP and consensus matrix 2 (M2 (NP+M2-rAd. Antibodies against the M2 ectodomain (M2e were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus.Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic.

  10. A CpG oligonucleotide can protect mice from a low aerosol challenge dose of Burkholderia mallei.

    Science.gov (United States)

    Waag, David M; McCluskie, Michael J; Zhang, Ningli; Krieg, Arthur M

    2006-03-01

    Treatment with an oligodeoxynucleotide (ODN) containing CPG motifs (CpG ODN 7909) was found to protect BALB/c mice from lung infection or death after aerosol challenge with Burkholderia mallei. Protection was associated with enhanced levels of gamma interferon (IFN-gamma)-inducible protein 10, interleukin-12 (IL-12), IFN-gamma, and IL-6. Preexposure therapy with CpG ODNs may protect victims of a biological attack from glanders.

  11. Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice

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    Nietfeld Wilfried

    2010-03-01

    Full Text Available Abstract Background The complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia. However, there is little information about the exact contribution of the membrane attack complex (MAC and its inhibitor-protein CD59. Methods Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO in young male and female CD59a knockout and wild-type mice. Two models of MCAO were applied: 60 min MCAO and 48 h reperfusion, as well as 30 min MCAO and 72 h reperfusion. CD59a knockout animals were compared to wild-type animals in terms of infarct size, edema, neurological deficit, and cell death. Results and Discussion CD59a-deficiency in male mice caused significantly increased infarct volumes and brain swelling when compared to wild-type mice at 72 h after 30 min-occlusion time, whereas no significant difference was observed after 1 h-MCAO. Moreover, CD59a-deficient mice had impaired neurological function when compared to wild-type mice after 30 min MCAO. Conclusion We conclude that CD59a protects against ischemic brain damage, but depending on the gender and the stroke model used.

  12. Reactivity improvement of Ca(OH)2 sorbent using diatomaceous earth (DE) from Aceh Province

    Science.gov (United States)

    Mariana, M.; Mahidin, M.; Mulana, F.; Agam, T.; Hafdiansyah, F.

    2018-04-01

    In this study, the diatomaceous earth (DE) from Aceh Province was used to increase the reactivity of Ca(OH)2sorbent. The high silica (SiO2) content of about 97% in the diatomaceous earth allows the increasing reactivity of Ca(OH)2sorbent by forming calcium silicate hydrate (CSH). The CSH improved the porosity characteristic of the sorbent. The improvement process was performed by mixing Ca(OH)2sorbent, diatomaceous earth and water in a beaker glass at the Ca(OH)2/DE weight ratio of 1:10 for 2 hand then dried at 120 °C for 24 h. The dried sorbent was calcined at 500 °C and 800 °C for 2 h. The activated sorbent was characterized using Scanning Electron Microscopy (SEM) for the morphological properties; X- Ray Diffraction (XRD) for the materials characteristics. The adsorption capacity of thesorbent was tested by methylene blue adsorption. The results showed that the Ca(OH)2/DEsorbent had a higher porosity than the Ca(OH)2 adsorbent.The results also showed that Ca(OH)2/DE which was calcined at higher temperature of 800 °C had a higher adsorption capacity compared to Ca(OH)2/DE which was calcined at lower temperature of 500 °C.

  13. Synthesis and properties of A{sub 6}B{sub 2}(OH){sub 16}Cl{sub 2}.4H{sub 2}O (A = Mg, Ni, Zn, Co, Mn and B = Al, Fe) materials for environmental applications

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Anderson, E-mail: anderson_dias@iceb.ufop.br [Departamento de Quimica, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, ICEB II, Sala 67, Ouro Preto-MG, 35400-000 (Brazil); Cunha, Lumena; Vieira, Andiara C. [Departamento de Quimica, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, ICEB II, Sala 67, Ouro Preto-MG, 35400-000 (Brazil)

    2011-09-15

    Highlights: {yields} A{sub 6}B{sub 2}(OH){sub 16}Cl{sub 2}.4H{sub 2}O (A = Mg, Ni, Zn, Co, Mn and B = Al, Fe) materials were synthesized. {yields} Chemical synthesis produced different levels of crystallinity and ordering degree. {yields} Structural investigation by Raman scattering revealed a complex band structure. {yields} A strong correlation between band structure and ionic radius was determined. -- Abstract: Double layered hydroxide materials of composition A{sub 6}B{sub 2}(OH){sub 16}Cl{sub 2}.4H{sub 2}O (A = Mg, Ni, Zn, Co, Mn and B = Al, Fe) were synthesized by chemical precipitation at 60 {sup o}C. Different levels of crystallinity and ordering degree were observed depending upon the chemical environment or the combination between divalent and trivalent cations. The results from high-resolution transmission electron microscopy revealed that nanostructured layered samples were obtained with interplanar spacing compatible with previous literature. Raman scattering was employed to investigate the complex band structure observed, particularly the lattice vibrations at lower frequencies, which is intimately correlated to the cationic radius of both divalent and trivalent ions. The results showed that strongly coordinated water and chloride ions besides highly structured hydroxide layers have a direct influence on the stability of the hydrotalcites. It was observed that transition and decomposition temperatures varied largely for different chemical compositions.

  14. Atom-radical reaction dynamics of O(3P)+C3H5→C3H4+OH: Nascent rovibrational state distributions of product OH

    Science.gov (United States)

    Park, Jong-Ho; Lee, Hohjai; Kwon, Han-Cheol; Kim, Hee-Kyung; Choi, Young-Sang; Choi, Jong-Ho

    2002-08-01

    The reaction dynamics of ground-state atomic oxygen [O(3P)] with allyl radicals (C3H5) has been investigated by applying a combination of crossed beams and laser induced fluorescence techniques. The reactants O(3P) and C3H5 were produced by the photodissociation of NO2 and the supersonic flash pyrolysis of precursor allyl iodide, respectively. A new exothermic channel of O(3P)+C3H5→C3H4+OH was observed and the nascent internal state distributions of the product OH (X 2Π:υ″=0,1) showed substantial bimodal internal excitations of the low- and high-N″ components without Λ-doublet and spin-orbit propensities in the ground and first excited vibrational states. With the aid of the CBS-QB3 level of ab initio theory and Rice-Ramsperger-Kassel-Marcus calculations, it is predicted that on the lowest doublet potential energy surface the major reaction channel of O(3P) with C3H5 is the formation of acrolein (CH2CHCHO)+H, which is consistent with the previous bulk kinetic experiments performed by Gutman et al. [J. Phys. Chem. 94, 3652 (1990)]. The counterpart C3H4 of the probed OH product in the title reaction is calculated to be allene after taking into account the factors of reaction enthalpy, barrier height and the number of intermediates involved along the reaction pathway. On the basis of population analyses and comparison with prior calculations, the statistical picture is not suitable to describe the reactive atom-radical scattering processes, and the dynamics of the title reaction is believed to proceed through two competing dynamical pathways. The major low N″-components with significant vibrational excitation may be described by the direct abstraction process, while the minor but extraordinarily hot rotational distribution of high N″-components implies that some fraction of reactants is sampled to proceed through the indirect short-lived addition-complex forming process.

  15. Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice.

    Directory of Open Access Journals (Sweden)

    Camila Figueiredo Pinzan

    Full Text Available Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6 or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6 to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection.

  16. Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice.

    Science.gov (United States)

    Pinzan, Camila Figueiredo; Sardinha-Silva, Aline; Almeida, Fausto; Lai, Livia; Lopes, Carla Duque; Lourenço, Elaine Vicente; Panunto-Castelo, Ademilson; Matthews, Stephen; Roque-Barreira, Maria Cristina

    2015-01-01

    Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection.

  17. Pathomorphology of spleen lymphocyte apoptosis in large dose 60Co γ-irradiated mice

    International Nuclear Information System (INIS)

    Gao Linlu; Cui Yufang; Yang Hong; Xia Guowei; Peng Ruiyun; Gao Yabing; Wang Dewen

    2000-01-01

    Objective: The aim of the authors was to investigate the pathomorphology changes of spleen lymphocyte apoptosis after 60 Co γ-irradiation. Methods: The mice were irradiated with 6, 9, 12, 15 and 20 Gy of 60 Co γ-rays. At different times after irradiation, the mice were sacrificed and the pathological changes of spleen lymphocyte were observed by light and transmission electron microscopies. Results: Spleen lymphocyte decreased evidently and the peak of apoptosis in spleen lymphocyte was dependent on radiation dose and the time after irradiation. Conclusion: After γ-irradiation with large doses, pathological changes of spleen lymphocyte apoptosis in mice can be divided into obviously different stages. The main causes of death of spleen lymphocytes are different in different dose groups

  18. Evaluation of Protective Immune Responses Induced by Recombinant TrxLp and ENO2 Proteins against Toxoplasma gondii Infection in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Meng Wang

    2016-01-01

    Full Text Available Toxoplasma gondii is an obligate intracellular parasitic protozoan that can infect almost all species of warm-blooded animals. As any chemical-based drugs could not act against the tissue cyst stage of T. gondii, vaccination may be one of the ideal control strategies. In the present study, two new vaccine candidates, named TgENO2 and TgTrxLp, were purified from Escherichia coli with pET-30a(+ expression system and then were injected into BALB/c mice to evaluate the protective efficacy against acute and chronic toxoplasmosis. The results showed that both the recombinant proteins, either alone or in combination, could elicit strong humoral and cellular immune responses with a higher level of IgG antibodies, IFN-γ, IL-2, CD4+, and CD8+ T cells as compared to those in mice from control groups. After acute challenge with tachyzoites of the GJS strain, mice immunized with rTgTrxLp (8±2.77 d, rTgENO2 (7.4±1.81 d, and rTgTrxLp + rTgENO2 (8.38±4.57 d proteins showed significantly longer survival time than those that received Freund’s adjuvant (6.78±2.08 d and PBS (6.38±4.65 d (χ2 = 9.687, df = 4, P=0.046. The protective immunity of rTgTrxLp, rTgENO2, and rTgTrxLp + rTgENO2 proteins against chronic T. gondii infection showed 69.77%, 58.14%, and 20.93% brain cyst reduction as compared to mice that received PBS. The present study suggested that both TgENO2 and TgTrxLp were potential candidates for the development of multicomponent vaccines against toxoplasmosis.

  19. Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection.

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    Magdalena Radwanska

    2007-05-01

    Full Text Available Effector responses induced by polarized CD4+ T helper 2 (Th2 cells drive nonhealing responses in BALB/c mice infected with Leishmania major. Th2 cytokines IL-4 and IL-13 are known susceptibility factors for L. major infection in BALB/c mice and induce their biological functions through a common receptor, the IL-4 receptor alpha chain (IL-4Ralpha. IL-4Ralpha-deficient BALB/c mice, however, remain susceptible to L. major infection, indicating that IL-4/IL-13 may induce protective responses. Therefore, the roles of polarized Th2 CD4+ T cells and IL-4/IL-13 responsiveness of non-CD4+ T cells in inducing non-healer or healer responses have yet to be elucidated. CD4+ T cell-specific IL-4Ralpha (Lck(creIL-4Ralpha(-/lox deficient BALB/c mice were generated and characterized to elucidate the importance of IL-4Ralpha signaling during cutaneous leishmaniasis in the absence of IL-4-responsive CD4+ T cells. Efficient deletion was confirmed by loss of IL-4Ralpha expression on CD4+ T cells and impaired IL-4-induced CD4+ T cell proliferation and Th2 differentiation. CD8+, gammadelta+, and NK-T cells expressed residual IL-4Ralpha, and representative non-T cell populations maintained IL-4/IL-13 responsiveness. In contrast to IL-4Ralpha(-/lox BALB/c mice, which developed ulcerating lesions following infection with L. major, Lck(creIL-4Ralpha(-/lox mice were resistant and showed protection to rechallenge, similar to healer C57BL/6 mice. Resistance to L. major in Lck(creIL-4Ralpha(-/lox mice correlated with reduced numbers of IL-10-secreting cells and early IL-12p35 mRNA induction, leading to increased delayed type hypersensitivity responses, interferon-gamma production, and elevated ratios of inducible nitric oxide synthase mRNA/parasite, similar to C57BL/6 mice. These data demonstrate that abrogation of IL-4 signaling in CD4+ T cells is required to transform non-healer BALB/c mice to a healer phenotype. Furthermore, a beneficial role for IL-4Ralpha signaling in L

  20. Protective effect of diallyl disulfide against the irradiation damage in mice induced by "1"2C"6"+ ion beams

    International Nuclear Information System (INIS)

    Xu Shuai; Ma Xiaofei; Zhang Hong; Liu Yang

    2013-01-01

    The radioprotective effect of Diallyl disulfide (DADS) on "1"2C"6"+ ion irradiation was studied. Pretreated with DADS of different concentration, male Kung-Ming mice were exposed to whole body irradiation with dosage of 4 Gy "1"2C"6"+ ion. The animals were sacrificed after irradiation. Then the bone marrow cells micronucleus rate, malondialdehyde (MDA) levels, content of protein carbonylation, total antioxidant capacity (T-AOC) and alanine aminotransferase (ALT) activity were measured. As compared with those in irradiated group, the ratio of micronucleus cells in marrow and the hepatic ALT activity in the pretreatment group with low dose DADS decreased significantly (p < O.OOl). Similarly, the content of protein carbonylation and the levels of MDA dropped dramatically in the group with middle dose DADS treatment (p < 0.05). On the contrary, the hepatic T-AOC increased markedly in the group of pretreatment with low dose DADS (p < 0.05). The results showed that DADS protect lipoid, protein and genetic material from "1"2C"6"+ ion irradiation by right of resisting oxidative stress. (authors)

  1. Autoradiographic disposition of [1-methyl-14C]- and [2-14C]caffeine in mice

    International Nuclear Information System (INIS)

    Lachance, M.P.; Marlowe, C.; Waddell, W.J.

    1983-01-01

    Male, C57B1/6J mice received either [1-methyl-14C]caffeine or [2-14C]caffeine via the tail vein at a dose of 0.7 or 11 mg/kg, respectively. At 0.1, 0.33, 1, 3, 9, and 24 hr after treatment, the mice were anesthetized with ether and frozen by immersion in dry ice/hexane. The mice were processed for whole-body autoradiography by the Ullberg technique; this procedure does not allow thawing or contact with solvents. All autoradiographs revealed some retention of radioactivity at early time intervals in the lacrimal glands, seminal vesicle fluid, nasal and olfactory epithelium, and retinal melanocytes. The remaining portion of the animal was densitometrically uniform except for the lower levels noted in the CNS and adipose tissues. Excretion of radioactivity by the liver and kidneys seems to be the major routes of elimination. Localization in the liver at late time intervals was confined principally to the centrilobular region. Late sites of retention, observed only after [1-methyl-14C]caffeine administration, included the pancreas, minor and major salivary glands, splenic red pulp, thymal cortex, bone marrow, and gastrointestinal epithelium. Sites of localization present in both studies included the olfactory epithelium, lacrimal glands, hair follicles, and retinal melanocytes. Further studies are needed to determine whether the localization at these various sites is due to metabolic degradation, active transport, or possibly a specific receptor interaction

  2. Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality

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    Ruei-Tang Cheng

    2010-01-01

    Full Text Available When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4∘C±0.3∘C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15 and reduced the hypothermia (core temperature, 37.3∘C. The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediatedαUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality.

  3. Electronically excited C 2 from laser photodissociated C 60

    Science.gov (United States)

    Arepalli, S.; Scott, C. D.; Nikolaev, P.; Smalley, R. E.

    2000-03-01

    Spectral and transient emission measurements are made of radiation from products of laser excitation of buckminsterfullerene (C 60) vapor diluted in argon at 973 K. The principal radiation is from the Swan band system of C 2 and, at early times, also from a black-body continuum. Transient measurements indicate two characteristic periods of decay 2 and 50 μs long, with characteristic decay times of ˜0.3 and 5 μs, respectively. The first period is thought to be associated with decomposition and radiative cooling of C 60 molecules or nano-sized carbon particles and the second period continues with decomposition products of laser excited C 60, C 58, C 56, etc.

  4. Electronic structure and static dipole polarizability of C60-C240

    International Nuclear Information System (INIS)

    Zope, Rajendra R

    2008-01-01

    The electronic structure of C 60 -C 240 and its first-order response to a static electric field is studied by an all-electron density functional theory calculation using large polarized Gaussian basis sets. Our results show that the outer C 240 shell almost completely shields the inner C 60 as inferred from the practically identical values of dipole polarizability of the C 60 -C 240 onion (449 A 3 ) and that of the isolated C 240 fullerene (441 A 3 ). The C 60 -C 240 is thus a near-perfect Faraday cage

  5. Behavioral and neural correlates of acute and scheduled hunger in C57BL/6 mice.

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    Christian M Gallardo

    Full Text Available In rodents, daily feeding schedules induce food anticipatory activity (FAA rhythms with formal properties suggesting mediation by food-entrained circadian oscillators (FEOs. The search for the neuronal substrate of FEOs responsible for FAA is an active area of research, but studies spanning several decades have yet to identify unequivocally a brain region required for FAA. Variability of results across studies leads to questions about underlying biology versus methodology. Here we describe in C57BL/6 male mice the effects of varying the 'dose' of caloric restriction (0%, 60%, 80%, 110% on the expression of FAA as measured by a video-based analysis system, and on the induction of c-Fos in brain regions that have been implicated in FAA. We determined that more severe caloric restriction (60% leads to a faster onset of FAA with increased magnitude. Using the 60% caloric restriction, we found little evidence for unique signatures of neuronal activation in the brains of mice anticipating a daily mealtime compared to mice that were fasted acutely or fed ad-libitum-even in regions such as the dorsomedial and ventrolateral hypothalamus, nucleus accumbens, and cerebellum that have previously been implicated in FAA. These results underscore the importance of feeding schedule parameters in determining quantitative features of FAA in mice, and demonstrate dissociations between behavioral FAA and neural activity in brain areas thought to harbor FEOs or participate in their entrainment or output.

  6. Potencies of vitamin D analogs, 1α-hydroxyvitamin D3 , 1α-hydroxyvitamin D2 and 25-hydroxyvitamin D3 , in lowering cholesterol in hypercholesterolemic mice in vivo.

    Science.gov (United States)

    Quach, Holly P; Dzekic, Tamara; Bukuroshi, Paola; Pang, K Sandy

    2018-04-01

    Vitamin D 3 and the synthetic vitamin D analogs, 1α-hydroxyvitamin D 3 [1α(OH)D 3 ], 1α-hydroxyvitamin D 2 [1α(OH)D 2 ] and 25-hydroxyvitamin D 3 [25(OH)D 3 ] were appraised for their vitamin D receptor (VDR) associated-potencies as cholesterol lowering agents in mice in vivo. These precursors are activated in vivo: 1α(OH)D 3 and 1α(OH)D 2 are transformed by liver CYP2R1 and CYP27A1 to active VDR ligands, 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] and 1α,25-dihydroxyvitamin D 2 [1,25(OH) 2 D 2 ] , respectively. 1α(OH)D 2 may also be activated by CYP24A1 to 1α,24-dihydroxyvitamin D 2 [1,24(OH) 2 D 2 ], another active VDR ligand. 25(OH)D 3 , the metabolite formed via CYP2R1 and or CYP27A1 in liver from vitamin D 3 , is activated by CYP27B1 in the kidney to 1,25(OH) 2 D 3 . In C57BL/6 mice fed the high fat/high cholesterol Western diet for 3 weeks, vitamin D analogs were administered every other day intraperitoneally during the last week of the diet. The rank order for cholesterol lowering, achieved via mouse liver small heterodimer partner (Shp) inhibition and increased cholesterol 7α-hydroxylase (Cyp7a1) expression, was: 1.75 nmol/kg 1α(OH)D 3  > 1248 nmol/kg 25(OH)D 3 (dose ratio of 0.0014) > > 1625 nmol/kg vitamin D 3 . Except for 1.21 nmol/kg 1α(OH)D 2 that failed to lower liver and plasma cholesterol contents, a significant negative correlation was observed between the liver concentration of 1,25(OH) 2 D 3 formed from the precursors and liver cholesterol levels. The composite results show that vitamin D analogs 1α(OH)D 3 and 25(OH)D 3 exhibit cholesterol lowering properties upon activation to 1,25(OH) 2 D 3 : 1α(OH)D 3 is rapidly activated by liver enzymes and 25(OH)D 3 is slowly activated by renal Cyp27b1 in mouse. Copyright © 2018 John Wiley & Sons, Ltd.

  7. Inhibition of the receptor for advanced glycation end-products (RAGE) protects from secondhand smoke (SHS)-induced intrauterine growth restriction IUGR in mice.

    Science.gov (United States)

    Lewis, Joshua B; Mejia, Camilo; Jordan, Clinton; Monson, Troy D; Bodine, Jared S; Dunaway, Todd M; Egbert, Kaleb M; Lewis, Adam L; Wright, Tanner J; Ogden, K Connor; Broberg, Dallin S; Hall, Parker D; Nelson, Shawn M; Hirschi, Kelsey M; Reynolds, Paul R; Arroyo, Juan A

    2017-12-01

    Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with maternal, fetal, or placental abnormalities. Studies investigating the effects of secondhand smoke (SHS) exposure and IUGR are limited. The receptor for advanced glycation end-products (RAGE) is a pro-inflammatory transmembrane receptor increased by SHS in the placenta. We tested the hypothesis that inhibition of RAGE during SHS exposure protects from smoke-induced IUGR. C57BL/6 mice were exposed to SHS or SHS + semi-synthetic glycosaminoglycan ethers (SAGEs) known to inhibit RAGE signaling. Trophoblast cells were treated with cigarette smoke extract (CSE) with or without SAGEs in order to address the effects of RAGE inhibition during trophoblast invasion in vitro. SHS-treated mice demonstrated a significant reduction in fetal weight (7.35-fold, P ≤ 0.0001) and placental weight (1.13-fold, P ≤ 0.0001) compared with controls. Mice co-treated with SHS and SAGEs were protected from SHS-induced fetal weights decreases. SHS treatment of C57BL/6 mice activated placental extracellular signal-regulated kinase (ERK) (3.0-fold, P ≤ 0.05), JNK (2.4-fold, P ≤ 0.05) and p38 (2.1-fold, P ≤ 0.05) and the expression of inflammatory mediators including TNF-α (1.34-fold, P ≤ 0.05) and IL-1β (1.03-fold, P ≤ 0.05). SHS-mediated activation of these molecules was reduced to basal levels when SAGE was co-administered. Invasion of trophoblast cells decreased 92% (P < 0.002) when treated with CSE and CSE-mediated invasion was completely reversed by SAGEs. We conclude that RAGE inhibition protects against fetal weight loss during SHS-induced IUGR. These studies provide insight into tobacco-mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications.

  8. Asymmetric fission and evaporation of Cr+60 (r = 2-4) fullerene ions in ion-C60 collisions: III. Universal behaviour of fission

    International Nuclear Information System (INIS)

    Bordenave-Montesquieu, D; Bordenave-Montesquieu, A; Rentenier, A; Moretto-Capelle, P

    2005-01-01

    The behaviour of the asymmetrical fission (AF) scheme (correlated ion distributions) against the collision conditions is investigated using H + x (x = 1-3) and He + projectiles in the 1-130 keV collision energy range. The present work is an extension of our recent publications on this topic using 11 keV protons (Rentenier et al 2004 J. Phys. B: At. Mol. Opt. Phys. 37 2429 and 2455). The threshold for AF is observed at 2 keV proton energy corresponding to a maximum deposited energy equal to about 41 eV. The main result concerns the fragment distributions resulting from AF of C r+ 60 ions, and secondary dissociation of even-n C + n fragments, which are both found to remain independent of the projectile species and collision velocity. These findings indicate that they are insensitive to the internal energy distributions of the parent ions. In addition, a contribution of binary collisions between the projectile and individual carbon atoms of the C 60 molecule to AF is identified in the C + 1 production at the lowest collision velocities, the so-called impulsive fragmentation

  9. Adjuvant effects of inhaled mono-2-ethylhexyl phthalate in BALB/cJ mice

    DEFF Research Database (Denmark)

    Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.

    2007-01-01

    Phthalates, including di(2-ethylhexyl) phthalate (DEHP), are widely used and have been linked with the development of wheezing and asthma. The main metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP), was investigated for adjuvant effects in a mouse inhalation model. BALB/cJ mice were exposed...... to aerosols of 0.03 or 0.4 mg/m(3) MEHP 5 days/week for 2 weeks and thereafter weekly for 12 weeks together with a low dose of ovalbumin (OVA) as a model allergen. Mice exposed to OVA alone or OVA+Al(OH)(3) served as negative and positive controls, respectively. Finally, all groups were exposed to a nebulized...... as of eosinophils in BAL fluid were observed. OVA-specific IgG1 production in both MEHP groups was significantly increased. OVA-specific IgE and IgG2a were not increased significantly. A dose-dependent increase in inflammatory cells was observed in BAL fluid, leading to significantly higher lymphocyte...

  10. Irreversible binding of 14C-labelled trichloroethylene to mice liver constituents in vivo and in vitro

    International Nuclear Information System (INIS)

    Uehleke, H.; Poplawski-Tabarelli, S.

    1977-01-01

    1) 14 C-labelled trichloroethylene was injected i.p. into male mice (10 μmole/g of b.w.). The radioactivity irreversibly bound to hepatic protein reached highest levels after 6 h : 2 nmole/mg in cytosol protein, 4.4 nmole/mg in mitochondrial protein, and 7.6 nmole/mg in microsomal protein. 2) The commercial trichloroethylene contained radioactive impurities binding to proteins without metabolic activation. Purification by various extraction removed 60-70% of those materials. In aerobic incubates of mice hepatic microsomes and NADPH the covalent binding rate of the purified trichloroethylene was 1.4 nmole/mg protein in 60 min. The activity of rat liver microsomes was approximately 40% less. Covalent binding increased 2-fold with microsomes of mice pretreated with phenobarbital. (orig.) [de

  11. 24 CFR 3280.204 - Kitchen cabinet protection.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Kitchen cabinet protection. 3280... Kitchen cabinet protection. (a) The bottom and sides of combustible kitchen cabinets over cooking ranges... is designed for the future installation of a cooking range, the metal hood and cabinet protection...

  12. Short-term fasting protects mice against γ ray radiation

    International Nuclear Information System (INIS)

    Zhu Shengnan; Gu Xiuling; Song Lian; Tong Jian; Li Jianxiang

    2012-01-01

    Objective: To investigate the antagonistic effects of short-term fasting against 60 Co γ ray radiation. Methods: After fasting ICR mice were irradiated for 3 min at a dose rate of 2.5 Gy/min and then returned to normal diet. General situation, body weight changes, food consumption and toxic status were observed. WBC, organ index and anti-oxidative ability (ROS, SOD, MDA, T-AOC) were analyzed. Results: After 60 Co γ ray radiation, the mice exhibited severe toxic symptoms before death. The survival rates were 0 for control and 12 h group, 12.5% for 48 h group and 50% for 72 h group respectively. ROS production of 72 h group was reduced compared with 0 h group (P<0.05). Conclusion: Short-term fasting may attenuate radiation induced injuries, evidenced by a significant increase in mice survival rate. (authors)

  13. Physical properties of C60 intercalated graphite films

    International Nuclear Information System (INIS)

    Nakahara, T; Hosomi, N; Taniguchi, J; Suzuki, M; Sato, T; Abe, K; Kuwahara, D; Ishikawa, M; Kato, M; Miura, K

    2007-01-01

    Recently, Miura and Tsuda have synthesized C 60 intercalated graphite film (C 60 /Gr) and reported that the C 60 /Gr consists of alternating close-packed C 60 monolayers and graphite layers. They also found that its frictional force is minimal up to the loading force of 100 nN using AFM [Miura K and Tsuda D 2005 e-J. Surf. Sci. Nanotech. 3 21] Thus, we have started to study the physical properties of C 60 /Gr and carried out NMR, Raman scattering and specific heat measurements. These results suggest that C 60 in C 60 /Gr rotates at room temperature

  14. Dietary broccoli protects against fatty liver development but not against progression of liver cancer in mice pretreated with diethylnitrosamine

    Science.gov (United States)

    Chen, Yung-Ju; Myracle, Angela D.; Wallig, Matthew A.; Jeffery, Elizabeth H.

    2016-01-01

    Western-style high fat, high sugar diets are associated with non-alcoholic fatty liver disease (NAFLD) and increased liver cancer risk. Sulforaphane from broccoli may protect against these. Previously we initiated broccoli feeding to mice prior to exposure to the hepatocarcinogen diethylnitrosamine (DEN), and saw protection against NAFLD and liver cancer. Here we administered DEN to unweaned mice, initiating broccoli feeding two weeks later, to determine if broccoli protects against cancer progression. Specifically, male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months. Dietary broccoli decreased hepatic triacylglycerols, NAFLD, liver damage and tumour necrosis factor by month 5 without changing body weight or relative liver weight, but did not slow carcinogenesis, seen in 100% of mice. We conclude that broccoli, a good source of sulforaphane, slows progression of hepatic lipidosis, but not tumourigenesis in this robust model. PMID:27672403

  15. Brucella abortus 2308ΔNodVΔNodW double-mutant is highly attenuated and confers protection against wild-type challenge in BALB/c mice.

    Science.gov (United States)

    Li, Zhiqiang; Wang, Shuli; Zhang, Jinliang; Yang, Guangli; Yuan, Baodong; Huang, Jie; Han, Jincheng; Xi, Li; Xiao, Yanren; Chen, Chuangfu; Zhang, Hui

    2017-05-01

    Brucellosis is an important zoonotic disease of worldwide distribution, which causes animal and human disease. However, the current Brucella abortus (B. abortus) vaccines (S19 and RB51) have several drawbacks, including residual virulence for animals and humans. Moreover, S19 cannot allow serological differentiation between infected and vaccinated animals. We constructed double deletion (ΔNodVΔNodW) mutant from virulent B. abortus 2308 (S2308) by deleting the genes encoding two-component regulatory system (TCS) in chromosome II in S2308.2308ΔNodVΔNodW was significantly reduced survival in murine macrophages (RAW 264.7) and BALB/c mice. Moreover, the inoculated mice showed no splenomegaly. The mutant induced high protective immunity in BALB/c mice against challenge with S2308, and elicited an anti-Brucella-specific immunoglobulin G (IgG) response and induced the secretion of gamma interferon (IFN-γ) and interleukin-4 (IL-4). Moreover, NODV and NODW antigens would allow the serological differentiation between infected and vaccinated animals. These results suggest that 2308ΔNodVΔNodW mutant is a potential live attenuated vaccine candidate and can be used effectively against bovine brucellosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Circumsporozoite Protein-Specific Kd-Restricted CD8+ T Cells Mediate Protective Antimalaria Immunity in Sporozoite-Immunized MHC-I-Kd Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Jing Huang

    2014-01-01

    Full Text Available Although the roles of CD8+ T cells and a major preerythrocytic antigen, the circumsporozoite (CS protein, in contributing protective antimalaria immunity induced by radiation-attenuated sporozoites, have been shown by a number of studies, the extent to which these players contribute to antimalaria immunity is still unknown. To address this question, we have generated C57BL/6 (B6 transgenic (Tg mice, expressing Kd molecules under the MHC-I promoter, called MHC-I-Kd-Tg mice. In this study, we first determined that a single immunizing dose of IrPySpz induced a significant level of antimalaria protective immunity in MHC-I-Kd-Tg mice but not in B6 mice. Then, by depleting various T-cell subsets in vivo, we determined that CD8+ T cells are the main mediator of the protective immunity induced by IrPySpz. Furthermore, when we immunized (MHC-I-Kd-Tg × CS-Tg F1 mice with IrPySpz after crossing MHC-I-Kd-Tg mice with PyCS-transgenic mice (CS-Tg, which are unable to mount PyCS-specific immunity, we found that IrPySpz immunization failed to induce protective antimalaria immunity in (MHC-I-Kd-Tg × CS-Tg F1 mice, thus indicating the absence of PyCS antigen-dependent immunity in these mice. These results indicate that protective antimalaria immunity induced by IrPySpz in MHC-I-Kd-Tg mice is mediated by CS protein-specific, Kd-restricted CD8+ T cells.

  17. Recombinant raccoon pox vaccine protects mice against lethal plague

    Science.gov (United States)

    Osorio, J.E.; Powell, T.D.; Frank, R.S.; Moss, K.; Haanes, E.J.; Smith, S.R.; Rocke, T.E.; Stinchcomb, D.T.

    2003-01-01

    Using a raccoon poxvirus (RCN) expression system, we have developed new recombinant vaccines that can protect mice against lethal plague infection. We tested the effects of a translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen in tissue culture and the induction of antibody responses and protection against Yersinia pestis challenge in mice. The RCN vector successfully expressed the F1 protein of Y. pestis in vitro. In addition, the level of expression was increased by the insertion of the EMCV-IRES and combinations of this and the secretory signal or secretory and anchoring signals. These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis. Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7×104 LD50). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IRES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge. Our studies demonstrate, in vitro and in vivo, the potential importance of the EMCV-IRES and secretory signals in vaccine design. These molecular tools provide a new approach for improving the efficacy of vaccines. In addition, these novel recombinant vaccines could have human, veterinary, and wildlife applications in the prevention of plague.

  18. Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice

    Science.gov (United States)

    Soboleski, Mark R.; Gabbard, Jon D.; Price, Graeme E.; Misplon, Julia A.; Lo, Chia-Yun; Perez, Daniel R.; Ye, Jianqiang; Tompkins, S. Mark; Epstein, Suzanne L.

    2011-01-01

    Background The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus. Methodology/Principal Findings BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus. Conclusion/Significance Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic. PMID:21789196

  19. C60 fullerenes from combustion of common fuels

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, Andrea J., E-mail: ajtiwari@vt.edu [Department of Civil & Environmental Engineering, Virginia Tech, 200 Patton Hall, 750 Drillfield Drive, Blacksburg, VA 24061 (United States); Ashraf-Khorassani, Mehdi, E-mail: mashraf@vt.edu [Department of Chemistry, Virginia Tech, 480 Davidson Hall, 900 West Campus Drive, Virginia Tech, Blacksburg, VA 24061 (United States); Marr, Linsey C., E-mail: lmarr@vt.edu [Department of Civil & Environmental Engineering, Virginia Tech, 200 Patton Hall, 750 Drillfield Drive, Blacksburg, VA 24061 (United States)

    2016-03-15

    Releases of C{sub 60} fullerenes to the environment will increase with the growth of nanotechnology. Assessing the potential risks of manufactured C{sub 60} requires an understanding of how its prevalence in the environment compares to that of natural and incidental C{sub 60}. This work describes the characterization of incidental C{sub 60} present in aerosols generated by combustion of five common fuels: coal, firewood, diesel, gasoline, and propane. C{sub 60} was found in exhaust generated by all five fuels; the highest concentrations in terms of mass of C{sub 60} per mass of particulate matter were associated with diesel and coal. Individual aerosols from these combustion processes were examined by transmission electron microscopy. No relationship was found between C{sub 60} content and either the separation of graphitic layers (lamellae) within the particles, nor the curvature of those lamellae. Estimated global emissions of incidental C{sub 60} to the atmosphere from coal and diesel combustion range from 1.6 to 6.3 t yr{sup −1}, depending upon combustion conditions. These emissions may be similar in magnitude to the total amount of manufactured C{sub 60} produced on an annual basis. Consequent loading of incidental C{sub 60} to the environment may be several orders of magnitude higher than has previously been modeled for manufactured C{sub 60}. - Highlights: • Exhaust of common fuels (coal, diesel, etc.) analyzed via chromatography for C{sub 60.} • All five fuels tested produced C{sub 60} in aerosols in mass fractions up to several ppm. • Emissions of incidental C{sub 60} may be comparable to the total amount manufactured.

  20. Photodetachment of negative C60- ions

    International Nuclear Information System (INIS)

    Amusia, M.Ya.; Baltenkov, A.S.; Krakov, B.G.

    1998-01-01

    A model that describes the electron structure of negative fullerene C 60 - ions is proposed. The model contains only two experimentally observed parameters, namely the fullerene radius and the affinity energy of the electron to neutral C 60 . In the frame of this model, cross sections are calculated of elastic scattering of slow electrons on neutral fullerene, of C 60 - photodetachment near the threshold of this process and of radiative recombination of slow electrons with neutral fullerenes. (orig.)

  1. Trimethyl Chitosan Nanoparticles Encapsulated Protective Antigen Protects the Mice Against Anthrax

    Directory of Open Access Journals (Sweden)

    Anshu Malik

    2018-03-01

    Full Text Available Anthrax is an era old deadly disease against which there are only two currently available licensed vaccines named anthrax vaccine adsorbed and precipitated (AVP. Though they can provide a protective immunity, their multiple side-effects owing to their ill-defined composition and presence of toxic proteins (LF and EF of Bacillus anthracis, the causative organism of anthrax, in the vaccine formulation makes their widespread use objectionable. Hence, an anthrax vaccine that contains well-defined and controlled components would be highly desirable. In this context, we have evaluated the potential of various vaccine formulations comprising of protective antigen (PA encapsulated trimethyl-chitosan nanoparticles (TMC-PA in conjunction with either CpG-C ODN 2395 (CpG or Poly I:C. Each formulation was administered via three different routes, viz., subcutaneous (SC, intramuscular (IM, and intraperitoneal in female BALB/c mice. Irrespective of the route of immunization, CpG or Poly I:C adjuvanted TMC-PA nanoparticles induced a significantly higher humoral response (total serum IgG and its isotypes viz., IgG1, IgG2a, and IgG2b, compared to their CpG or Poly I:C PA counterparts. This clearly demonstrates the synergistic behavior of CpG and Poly I:C with TMC nanoparticles. The adjuvant potential of TMC nanoparticles could be observed in all the three routes as the TMC-PA nanoparticles by themselves induced IgG titers (1–1.5 × 105 significantly higher than both CpG PA and Poly I:C PA groups (2–8 × 104. The effect of formulations on T-helper (Th cell development was assessed by quantifying the Th1-dependant (TNF-α, IFN-γ, and IL-2, Th2-dependant (IL-4, IL-6, and IL-10, and Th17-type (IL-17A cytokines. Adjuvanation with CpG and Poly I:C, the TMC-PA nanoparticles triggered a Th1 skewed immune response, as suggested by an increase in the levels of total IgG2a along with IFN-γ cytokine production. Interestingly, the TMC-PA group showed a Th2-biased

  2. Asymmetric fission and evaporation of C60r+ (r = 2-4) fullerene ions in ion-C60 collisions: II. Dependence on collisional processes?

    International Nuclear Information System (INIS)

    Rentenier, A; Bordenave-Montesquieu, A; Moretto-Capelle, P; Bordenave-Montesquieu, D

    2004-01-01

    In this paper, a quantitative comparison of our experimental data for the asymmetrical fission (AF) and neutral evaporation of the C 60 molecule under proton impact (part I) is made with data published by other authors and often obtained in rather different collisional systems. The comparison with multicharged ions for which more quantitative data are available is focused on. It is demonstrated that size distributions of fragments, averaged fragment sizes, branching ratios between AF and evaporation or between AF channels, are common to all the collisional systems. Differences only appear when the comparison includes the undissociated stable fullerene ion signals

  3. Nonobese Diabetic (NOD Mice Lack a Protective B-Cell Response against the “Nonlethal” Plasmodium yoelii 17XNL Malaria Protozoan

    Directory of Open Access Journals (Sweden)

    Mirian Mendoza

    2016-01-01

    Full Text Available Background. Plasmodium yoelii 17XNL is a nonlethal malaria strain in mice of different genetic backgrounds including the C57BL/6 mice (I-Ab/I-Enull used in this study as a control strain. We have compared the trends of blood stage infection with the nonlethal murine strain of P. yoelii 17XNL malaria protozoan in immunocompetent Nonobese Diabetic (NOD mice prone to type 1 diabetes (T1D and C57BL/6 mice (control mice that are not prone to T1D and self-cure the P. yoelii 17XNL infection. Prediabetic NOD mice could not mount a protective antibody response to the P. yoelii 17XNL-infected red blood cells (iRBCs, and they all succumbed shortly after infection. Our data suggest that the lack of anti-P. yoelii 17XNL-iRBCs protective antibodies in NOD mice is a result of parasite-induced, Foxp3+ T regulatory (Treg cells able to suppress the parasite-specific antibody secretion. Conclusions. The NOD mouse model may help in identifying new mechanisms of B-cell evasion by malaria parasites. It may also serve as a more accurate tool for testing antimalaria therapeutics due to the lack of interference with a preexistent self-curing mechanism present in other mouse strains.

  4. 38 CFR 42.24 - Protective order.

    Science.gov (United States)

    2010-07-01

    ... IMPLEMENTING THE PROGRAM FRAUD CIVIL REMEDIES ACT § 42.24 Protective order. (a) A party or a prospective witness or deponent may file a motion for a protective order with respect to discovery sought by an... more of the following: (1) That the discovery not be had; (2) That the discovery may be had only on...

  5. 31 CFR 16.24 - Protective order.

    Science.gov (United States)

    2010-07-01

    ... FRAUD CIVIL REMEDIES ACT OF 1986 § 16.24 Protective order. (a) A party or a prospective witness or deponent may file a motion for a protective order with respect to discovery sought by an opposing party or... following: (1) That the discovery not be had; (2) That the discovery may be had only on specified terms and...

  6. 20 CFR 355.24 - Protective order.

    Science.gov (United States)

    2010-04-01

    ... REGULATIONS UNDER THE PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 355.24 Protective order. (a) A party or a prospective witness or deponent may file a motion for a protective order with respect to discovery sought by... more of the following: (1) That the discovery not be had; (2) That the discovery may be had only on...

  7. 29 CFR 22.24 - Protective order.

    Science.gov (United States)

    2010-07-01

    ... Secretary of Labor PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 22.24 Protective order. (a) A party or a prospective witness or deponent may file a motion for a protective order with respect to discovery sought by... more of the following: (1) That the discovery not be had; (2) That the discovery may be had only on...

  8. Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice.

    Science.gov (United States)

    Ho, Ada Man-Choi; Qiu, Yanyan; Jia, Yun-Fang; Aguiar, Felipe S; Hinton, David J; Karpyak, Victor M; Weinshilboum, Richard M; Choi, Doo-Sup

    2016-07-01

    Major depression is one of the most prevalent psychiatry comorbidities of alcohol use disorders (AUD). As negative emotions can trigger craving and increase the risk of relapse, treatments that target both conditions simultaneously may augment treatment success. Previous studies showed a potential synergistic effect of Food and Drug Administration approved medication for AUD acamprosate and the antidepressant escitalopram. In this study, we investigated the effects of combining acamprosate and escitalopram on ethanol (EtOH) consumption in stress-induced depressed mice. Forty singly housed C57BL/6J male mice were subjected to chronic unpredictable stress. In parallel, 40 group-housed male mice were subjected to normal husbandry. After 3 weeks, depressive- and anxiety-like behaviors and EtOH consumption were assessed. For the next 7 days, mice were injected with saline, acamprosate (200 mg/kg; twice/d), escitalopram (5 mg/kg; twice/d), or their combination (n = 9 to 11/drug group/stress group). Two-bottle choice limited-access drinking of 15% EtOH and tap water was performed 3 hours into dark phase immediately after the daily dark phase injection. EtOH drinking was monitored for another 7 days without drug administration. Mice subjected to the chronic unpredictable stress paradigm for 3 weeks showed apparent depression- and anxiety-like behaviors compared to their nonstressed counterparts including longer immobility time in the forced swim test and lower sucrose preference. Stressed mice also displayed higher EtOH consumption and preference in a 2-bottle choice drinking test. During the drug administration period, the escitalopram-only and combined drug groups showed significant reduction in EtOH consumption in nonstressed mice, while only the combined drug group showed significantly reduced consumption in stressed mice. However, such reduction did not persist into the postdrug administration period. The combination of acamprosate and escitalopram suppressed

  9. Protective effect of polysaccharides of lentinus edodes on damage in mice induced by ionizing radiation

    International Nuclear Information System (INIS)

    Song Xiuling; Wang Hongfang; Qi Yanfei; Wang Xuerui; Chen Tian; Wang Quan; Li Juan; Li Jing

    2010-01-01

    Objective: To evaluate the protective effect of polysaccharides of lentinus edodes (PLE) on immune and anti-oxidative and hematopoietic function of ionizing irradiated mice, and provide theoretical basis for its clinical application. Methods: Fifty ICR mice were randomly divided into normal control group (NC), irradiating control group (IC), low dose of PLE irradiating group (800 mg · kg -1 ), middle dose of PLE irradiating group (1600 mg · kg -1 ), and high dose of PLE irradiating group (2400 mg · kg -1 ) (n=10). The mice in PLE groups were gaster-poured by PLE for 7 d, the mice in NC group and IC group were gaster-poured by 0.9% sodium chloride solution. The mice in all groups except NC group were irradiated with 2 Gy X-ray on the eighth day. The spleen index, thymus index, the activity of SOD and content of MDA, the number of WBC, the micronucleus rate of bone marrow polychromalic erythrocytes (PCE)were detected at the 24th hour after radiation. Results: Compared with IC group,the spleen index, thymus index and activity of SOD in high dose of PLE irradiating group were increased markedly (P<0.05); the contents of MDA in middle and high dose of PLE irradiating groups were increased significantly (P<0.05). The number of WBC in PLE groups was increased significantly (P<0.05); the micronucleus rates of bone marrow PCE in middle and high dose of PLE irradiating groups were decreased significantly (P<0.05). Conclusion: PLE has an obvious protective effect on damage in X-ray irradiated mice. (authors)

  10. Structure of C60: Partial orientational order in the room-temperature modification of C60

    International Nuclear Information System (INIS)

    Buergi, H.B.; Restori, R.; Schwarzenbach, D.

    1993-01-01

    Using published synchrotron X-ray data, the room-temperature scattering density distribution of pure C 60 has been parametrized in terms of a combination of eight oriented symmetry-related images of the molecule, and of a freely spinning molecule. Corresponding populations are 61 and 39%. The oriented part of the model is obtained, in good approximation, by imposing m anti 3m symmetry on the energetically more favourable major orientation in the low-temperature structure of C 60 . The model was refined using angle restraints to impose the icosahedral molecular symmetry and displacement-factor restraints to restrict thermal movements to rigid-body translations and librations. Translational displacement factors are in the range 0.017-0.023 A 2 . The orientational probability density distribution obtained from the model shows maxima for C 60 orientations possessing anti 3m crystallographic site symmetry. It is also relatively large for the C 60 orientations with cubic site symmetry m anti 3. The smallest energy barrier for reorientation between different anti 3m orientations via an m anti 3 orientation appears to be less than 2 kJ mol -1 . On average, 75% of the intermolecular contacts of the oriented molecules are longer than those observed in the low-temperature structure, the other 25% are less favourable. The second orientation of C 60 found in the low-temperature structure could not be identified at room temperature. (orig.)

  11. Rapid outer-surface protein C DNA tattoo vaccination protects against Borrelia afzelii infection.

    Science.gov (United States)

    Wagemakers, A; Mason, L M K; Oei, A; de Wever, B; van der Poll, T; Bins, A D; Hovius, J W R

    2014-12-01

    Borrelia afzelii is the predominant Borrelia species causing Lyme borreliosis in Europe. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines against Borrelia burgdorferi sensu stricto. DNA tattooing is a novel vaccination method that can be applied in a rapid vaccination schedule. We vaccinated C3H/HeN mice with B. afzelii strain PKo OspC (outer-surface protein C) using a codon-optimized DNA vaccine tattoo and compared this with recombinant protein vaccination in a 0-2-4 week vaccination schedule. We also assessed protection by DNA tattoo in a 0-3-6 day schedule. DNA tattoo and recombinant OspC vaccination induced comparable total IgG responses, with a lower IgG1/IgG2a ratio after DNA tattoo. Two weeks after syringe-challenge with 5 × 10(5) B. afzelii spirochetes most vaccinated mice had negative B. afzelii tissue DNA loads and all were culture negative. Furthermore, DNA tattoo vaccination in a 0-3-6 day regimen also resulted in negative Borrelia loads and cultures after challenge. To conclude, DNA vaccination by tattoo was fully protective against B. afzelii challenge in mice in a rapid vaccination protocol, and induces a favorable humoral immunity compared to recombinant protein vaccination. Rapid DNA tattoo is a promising vaccination strategy against spirochetes.

  12. Vaccination with Recombinant Cryptococcus Proteins in Glucan Particles Protects Mice against Cryptococcosis in a Manner Dependent upon Mouse Strain and Cryptococcal Species

    Directory of Open Access Journals (Sweden)

    Charles A. Specht

    2017-11-01

    Full Text Available Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus-derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii. The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1 were selected, recombinantly expressed in Escherichia coli, purified, and loaded into GPs. Three mouse strains (C57BL/6, BALB/c, and DR4 were then vaccinated with the antigen-laden GPs, following which they received a pulmonary challenge with virulent C. neoformans and C. gattii strains. Four candidate vaccines (GP-Cda1, GP-Cda2, GP-Cda3, and GP-Sod1 afforded a significant survival advantage in at least one mouse model; some vaccine combinations provided added protection over that seen with either antigen alone. Vaccine-mediated protection against C. neoformans did not necessarily predict protection against C. gattii. Vaccinated mice developed pulmonary inflammatory responses that effectively contained the infection; many surviving mice developed sterilizing immunity. Predicted T helper cell epitopes differed between mouse strains and in the degree to which they matched epitopes predicted in humans. Thus, we have discovered cryptococcal proteins that make promising candidate vaccine antigens. Protection varied depending on the mouse strain and cryptococcal species, suggesting that a successful human subunit vaccine will need to contain multiple antigens, including ones that are species specific.

  13. Protective Effect of Anthocyanins Extract from Blueberry on TNBS-Induced IBD Model of Mice

    Directory of Open Access Journals (Sweden)

    Lin-Hua Wu

    2011-01-01

    Full Text Available This study was carried out to evaluate the protective effect of anthocyanins extract of blueberry on trinitrobenzene sulfonic acid (TNBS-induced inflammatory bowel disease (IBD model of mice. The study employed female C57BL/6 mice (n = 50, and colitis was induced by intracolonic injection of 0.5 mg of TNBS dissolved in 50% ethanol–phosphate buffered solution. The mice were divided into five groups (n = 10: vehicle, TNBS control and anthocyanins groups that received different doses of anthocyanins extract (10, 20 and 40 mg kg-1 daily for 6 days. Both increase in body weight and diarrhea symptoms were monitored each day. After 6 days, the animals were killed, and the following parameters were assessed: colon length, morphological score, histological score and biochemical assay (NO, myeloperoxidase (MPO, interleukin (IL-12, IL-10, tumor necrosis factor (TNF-α and interferon (IFN-γ. The results showed that the anthocyanins extract of blueberry rendered strong protection against TNBS-induced colonic damage at a dosage of 40 mg kg-1. When compared with the control, anthocyanins extract significantly prevented loss of body weight and ameliorated the scores of diarrhea, morphology and histology. Treatment with anthocyanins extract restored IL-10 excretion, as well as caused reduction in the levels of NO, MPO, IL-12, TNF-α and IFN-γ. Our research revealed the protective effect of anthocyanins extract from blueberry on TNBS-induced experimental colitis in mice, as well as examined whether high levels of dietary blueberries would lower the risk or have protective effects on human IBD, which may require further investigation.

  14. Brucella lipopolysaccharide reinforced Salmonella delivering Brucella immunogens protects mice against virulent challenge.

    Science.gov (United States)

    Lalsiamthara, Jonathan; Lee, John Hwa

    2017-06-01

    Intracellular pathogen Salmonella exhibits natural infection broadly analogous to Brucella, this phenomenon makes Salmonella a pragmatic choice for an anti-Brucella vaccine delivery platform. In this study we developed and formulated a combination of four attenuated Salmonella Typhimurium live vector strains delivering heterologous Brucella antigens (rBs), namely lumazine synthase, proline racemase subunit A, lipoprotein outer membrane protein-19, and Cu-Zn superoxide dismutase. With an aim to develop a cross-protecting vaccine, Brucella pan-species conserved rBs were selected. The present study compared the efficacy of smooth and rough variants of Salmonella delivery vector and also evaluated the inclusion of purified Brucella lipopolysaccharide (LPS) in the formulation. Immunization of SPF-BALB/c mice with the vaccine combinations significantly (P≤0.05) reduced splenic wild-type Brucella abortus 544 colonization as compared to non-immunized mice as well as Salmonella only immunized mice. Increased induction of Brucella specific-IgG, sIgA production, and antigen-specific splenocyte proliferative responses were observed in the mice immunized with the formulations as compared to naïve or vector only immunized mice. Modulatory effects of rB and LPS on production of interleukin (IL)-4, IL-12, and interferon-γ were detected in splenocytes of mice immunized with the formulation. Rough Salmonella variant in combination with LPS could further enhance the efficacy of the delivery when applied intraperitoneally. Taken together, it is compelling that Brucella LPS-augmented Salmonella vector delivering immunogenic Brucella proteins may be more suitable than the current non-ideal live Brucella abortus vaccine. The vaccine system also provides a basis for the development of cross-protecting vaccine capable of preventing multispecies brucellosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Distribution and binding of [14C]acrylamide to macromolecules in SENCAR and BALB/c mice following oral and topical administration

    International Nuclear Information System (INIS)

    Carlson, G.P.; Weaver, P.M.

    1985-01-01

    To determine if differences in acrylamide distribution or its binding to DNA could be responsible for the reported higher incidence of skin papillomas observed after oral administration compared to topical application, [ 14 C]acrylamide was administered by topical application and oral intubation to male SENCAR and BALB/mice. Portions of lung, liver, stomach, testes, and skin were removed, and 14 C was measured at 15 min, 30 min, 1, 6, 12, 24, and 48 hr. Binding to DNA, RNA, and protein was measured at 6 and 48 hr. Following oral administration, few strain differences in distribution or binding were noted. After topical application, SENCAR mice generally showed higher tissue concentrations than did the BALB/c mice at the early time periods but not at the later ones. Comparing the two routes, comparable concentrations were observed in all tissues except the skin where the amount of [ 14 C]acrylamide after topical application was approximately 100 times that observed after oral administration. At 48 hr, binding to DNA was sevenfold higher after topical than after oral administration. The effect of route on papilloma formation cannot be explained, therefore, on the basis of either a difference in distribution or binding to DNA in the target organ. The binding of acrylamide to DNA in skin was similar in both SENCAR and BALB/c mice indicating that the much greater susceptibility of the SENCAR mice to tumorigenesis cannot be explained simply on the basis of distribution or macromolecular binding

  16. Enhancement of ambipolar characteristics in single-walled carbon nanotubes using C{sub 60} and fabrication of logic gates

    Energy Technology Data Exchange (ETDEWEB)

    Park, Steve [Department of Materials Science and Engineering, Stanford University, Durand Building, 496 Lomita Mall, Stanford, California 94305-4034 (United States); Nam, Ji Hyun [Department of Electrical Engineering, Stanford University, David Packard Building, 350 Serra Mall, Mail Code: 9505, Stanford, California 94305-9505 (United States); Koo, Ja Hoon; Lei, Ting; Bao, Zhenan, E-mail: zbao@stanford.edu [Department of Chemical Engineering, Stanford University, Shriram Center, 443 Via Ortega, Room 307, Stanford, California 94305-4145 (United States)

    2015-03-09

    We demonstrate a technique to convert p-type single-walled carbon nanotube (SWNT) network transistor into ambipolar transistor by thermally evaporating C{sub 60} on top. The addition of C{sub 60} was observed to have two effects in enhancing ambipolar characteristics. First, C{sub 60} served as an encapsulating layer that enhanced the ambipolar characteristics of SWNTs. Second, C{sub 60} itself served as an electron transporting layer that contributed to the n-type conduction. Such a dual effect enables effective conversion of p-type into ambipolar characteristics. We have fabricated inverters using our SWNT/C{sub 60} ambipolar transistors with gain as high as 24, along with adaptive NAND and NOR logic gates.

  17. Interleukin-18 protects mice from Enterovirus 71 infection.

    Science.gov (United States)

    Li, Zheng; Wang, Hongbin; Chen, Yihui; Niu, Junling; Guo, Qiuhong; Leng, Qibin; Huang, Zhong; Deng, Zhirui; Meng, Guangxun

    2017-08-01

    Previous study has demonstrated that the NLRP3 inflammasome is essential for protecting murine host against Enterovirus 71 (EV71) infection. However, the underlying mechanism remained unknown. Here we discovered that the pleiotropic cytokine interleukin-18 (IL-18), an NLRP3 inflammasome-dependent effector protein, exhibits a protective capability against EV71 challenge. Deficiency of IL-18 in mice exacerbated EV71 infection, which was reflected by increased viral replication, elevated production of interferons (IFN-β, IFN-γ), proinflammatory cytokines (TNF-α, IL-6) and chemokine CCL2,as well as decreased survival of experimental animals. Conversely, administration of recombinant IL-18 considerably restrained EV71 infection in IL-18 deficient mice. Thus, our results revealed a protective role for IL-18 against EV71 challenge, and indicated a novel therapeutic application for IL-18 in EV71 associated hand, foot, and mouth disease (HFMD). Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Chemical potential pinning due to equilibrium electron transfer at metal/C60-doped polymer interfaces

    Science.gov (United States)

    Heller, C. M.; Campbell, I. H.; Smith, D. L.; Barashkov, N. N.; Ferraris, J. P.

    1997-04-01

    We report electroabsorption measurements of the built-in electrostatic potential in metal/C60-doped polymer/metal structures to investigate chemical potential pinning due to equilibrium electron transfer from a metal contact to the electron acceptor energy level of C60 molecules in the polymer film. The built-in potentials of a series of structures employing thin films of both undoped and C60-doped poly[2-methoxy, 5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) were measured. For undoped MEH-PPV, which has an energy gap of about 2.4 eV, the maximum built-in potential is about 2.1 eV, whereas for C60-doped MEH-PPV the maximum built-in potential decreases to 1.5 eV. Electron transfer to the C60 molecules close to the metal interface pins the chemical potential of the metal contact near the electron acceptor energy level of C60 and decreases the built-in potential of the structure. From the systematic dependence of the built-in potential on the metal work function we find that the electron acceptor energy level of C60 in MEH-PPV is about 1.7 eV above the hole polaron energy level of MEH-PPV.

  19. Excess electron is trapped in a large single molecular cage C60F60.

    Science.gov (United States)

    Wang, Yin-Feng; Li, Zhi-Ru; Wu, Di; Sun, Chia-Chung; Gu, Feng-Long

    2010-01-15

    A new kind of solvated electron systems, sphere-shaped e(-)@C60F60 (I(h)) and capsule-shaped e(-)@C60F60 (D6h), in contrast to the endohedral complex M@C60, is represented at the B3LYP/6-31G(d) + dBF (diffusive basis functions) density functional theory. It is proven, by examining the singly occupied molecular orbital (SOMO) and the spin density map of e(-)@C60F60, that the excess electron is indeed encapsulated inside the C60F60 cage. The shape of the electron cloud in SOMO matches with the shape of C60F60 cage. These cage-like single molecular solvated electrons have considerably large vertical electron detachment energies VDE of 4.95 (I(h)) and 4.67 eV (D6h) at B3LYP/6-31+G(3df) + dBF level compared to the VDE of 3.2 eV for an electron in bulk water (Coe et al., Int Rev Phys Chem 2001, 20, 33) and that of 3.66 eV for e(-)@C20F20 (Irikura, J Phys Chem A 2008, 112, 983), which shows their higher stability. The VDE of the sphere-shaped e(-)@C60F60 (I(h)) is greater than that of the capsule-shaped e(-)@C60F60 (D6h), indicating that the excess electron prefers to reside in the cage with the higher symmetry to form the more stable solvated electron. It is also noticed that the cage size [7.994 (I(h)), 5.714 and 9.978 A (D6h) in diameter] is much larger than that (2.826 A) of (H2O)20- dodecahedral cluster (Khan, Chem Phys Lett 2005, 401, 85). Copyright 2009 Wiley Periodicals, Inc.

  20. Ca (OH)2Nanoparticles Based on Acrylic Copolymers for the consolidation and protection of Ancient Egypt Calcareous Stone Monuments

    Science.gov (United States)

    Al-Dosari, Mohammad A.; Darwish, Sawsan S.; Adam, Mahmoud A.; Elmarzugi, Nagib A.; Al-Mouallimi, Nadia; Ahmed, Sayed M.

    2017-04-01

    The deterioration of calcareous stones materials used in artistic/architectural field is one of the most serious problems facing conservation today. The aim of this study was to evaluate the effectiveness of nanosized particles of calcium hydroxide (slaked lime) as a consolidation and protection material dispersed in acrylic copolymer, poly ethylmethacrylate/methylacrylate (70:30) (Poly (EMA/MA), for calcareous stone monuments and painted surfaces affected by different kinds of decay. The synthesis process of Ca (OH)2 nanoparticles/polymer nanocomposites have been prepared by in situ emulsion polymerization system. The prepared nanocomposite containing 5% of Ca (OH)2 nanoparticles showed obvious transparency features and represent nanocomposites coating technology with hydrophobic, consolidating and well protection properties.

  1. Ca (OH)2Nanoparticles Based on Acrylic Copolymers for the consolidation and protection of Ancient Egypt Calcareous Stone Monuments

    International Nuclear Information System (INIS)

    Al-Dosari, Mohammad A.; Ahmed, Sayed M.; Darwish, Sawsan S.; Adam, Mahmoud A.; Elmarzugi, Nagib A.; Al-Mouallimi, Nadia

    2017-01-01

    The deterioration of calcareous stones materials used in artistic/architectural field is one of the most serious problems facing conservation today. The aim of this study was to evaluate the effectiveness of nanosized particles of calcium hydroxide (slaked lime) as a consolidation and protection material dispersed in acrylic copolymer, poly ethylmethacrylate/methylacrylate (70:30) (Poly (EMA/MA), for calcareous stone monuments and painted surfaces affected by different kinds of decay. The synthesis process of Ca (OH) 2 nanoparticles/polymer nanocomposites have been prepared by in situ emulsion polymerization system. The prepared nanocomposite containing 5% of Ca (OH) 2 nanoparticles showed obvious transparency features and represent nanocomposites coating technology with hydrophobic, consolidating and well protection properties. (paper)

  2. A shock tube study of C4–C6 straight chain alkenes + OH reactions

    KAUST Repository

    Khaled, Fathi

    2016-06-28

    Alkenes are known to be good octane boosters and they are major components of commercial fuels. Detailed theoretical calculations and direct kinetic measurements of elementary reactions of alkenes with combustion radicals are scarce for C4 alkenes and they are practically absent for C5 and larger alkenes. The overall rate coefficients for the reaction of OH radical with 1-butene (CH CHCH CH, k ), 1-pentene (CH CHCH CH-CH, k ), cis/trans 2-pentene (CH CHCHCH CH, k and k ), 1-hexene (CH CHCH CH CH CH, k ) and cis/trans 2-hexene (CH CHCHCH CH CH, k and k ) were measured behind reflected shock waves over the temperature range of 833-1377K and pressures near 1.5atm. The reaction progress was followed by measuring mole fraction of OH radicals near 306.7nm using UV laser absorption technique. It is found that the rate coefficients of OH+trans-2-alkenes are larger than those of OH+cis-2-alkenes, followed by OH+1-alkenes. The derived Arrhenius expressions for the overall rate coefficients (in cm.mol.s) are:. kI=(4.83±0.03)104.T2.72±0.01.exp(940.8±2.9cal/molRT)(946K-1256K) + kII=(5.66±0.54)10-1.T4.14±0.80.exp(4334±227cal/molRT)(875K-1379K) + kIII=(3.25±0.12)104.T2.76±0.5.exp(1962±83cal/molRT)(877K-1336K) + kIV=(3.42±0.09)104.T2.76±0.5.exp(1995±59cal/molRT)(833K-1265K) + kV=(7.65±0.58)10-4.T5±1.exp(5840±175cal/molRT)(836K-1387K) + kVI=(2.58±0.06)106.T2.17±0.37.exp(1461±55cal/molRT)(891K-1357K) + kVII=(3.08±0.05)106.T2.18±0.37.exp(1317±38cal/molRT)(881K-1377K) +

  3. A shock tube study of C4–C6 straight chain alkenes + OH reactions

    KAUST Repository

    Khaled, Fathi; Badra, Jihad; Farooq, Aamir

    2016-01-01

    Alkenes are known to be good octane boosters and they are major components of commercial fuels. Detailed theoretical calculations and direct kinetic measurements of elementary reactions of alkenes with combustion radicals are scarce for C4 alkenes and they are practically absent for C5 and larger alkenes. The overall rate coefficients for the reaction of OH radical with 1-butene (CH CHCH CH, k ), 1-pentene (CH CHCH CH-CH, k ), cis/trans 2-pentene (CH CHCHCH CH, k and k ), 1-hexene (CH CHCH CH CH CH, k ) and cis/trans 2-hexene (CH CHCHCH CH CH, k and k ) were measured behind reflected shock waves over the temperature range of 833-1377K and pressures near 1.5atm. The reaction progress was followed by measuring mole fraction of OH radicals near 306.7nm using UV laser absorption technique. It is found that the rate coefficients of OH+trans-2-alkenes are larger than those of OH+cis-2-alkenes, followed by OH+1-alkenes. The derived Arrhenius expressions for the overall rate coefficients (in cm.mol.s) are:. kI=(4.83±0.03)104.T2.72±0.01.exp(940.8±2.9cal/molRT)(946K-1256K) + kII=(5.66±0.54)10-1.T4.14±0.80.exp(4334±227cal/molRT)(875K-1379K) + kIII=(3.25±0.12)104.T2.76±0.5.exp(1962±83cal/molRT)(877K-1336K) + kIV=(3.42±0.09)104.T2.76±0.5.exp(1995±59cal/molRT)(833K-1265K) + kV=(7.65±0.58)10-4.T5±1.exp(5840±175cal/molRT)(836K-1387K) + kVI=(2.58±0.06)106.T2.17±0.37.exp(1461±55cal/molRT)(891K-1357K) + kVII=(3.08±0.05)106.T2.18±0.37.exp(1317±38cal/molRT)(881K-1377K) +

  4. Fibroblast Growth Factor-23 and Vitamin D Metabolism in Subjects with eGFR ≥60 ml/min/1.73 m².

    Science.gov (United States)

    Nakatani, Shinya; Nakatani, Ayumi; Tsugawa, Naoko; Yamada, Shinsuke; Mori, Katsuhito; Imanishi, Yasuo; Ishimura, Eiji; Okano, Toshio; Inaba, Masaaki

    2015-01-01

    Fibroblast growth factor (FGF)-23 and parathyroid hormone (PTH) are both potent phosphaturic hormones. Since they exert opposite effects on vitamin D metabolism, the measurement of 3 vitamin D metabolites; 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D), allows the distinction of the effects of FGF-23 from those of PTH. The aim of this study was to elucidate which factor, FGF-23 or PTH, plays a more important role in the regulation of vitamin D metabolites in subjects with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m(2). Subjects with eGFR ≥60 ml/min/1.73 m(2) (n = 20) were enrolled and their serum levels of FGF-23, intact PTH, and vitamin D metabolites were determined. Serum FGF-23 correlated inversely with 1,25(OH)2D (r = -0.717, p = 0.0004) and the 1,25(OH)2D/25-OH-D ratio (r = -0.518, p = 0.019), compared with a significant positive correlation between serum intact PTH and the 1,25(OH)2D/25-OH-D ratio (r = 0.562, p = 0.010). Multiple regression analyses revealed serum FGF-23 as a significant factor that was associated with serum 1,25(OH)2D (β = -0.593, p = 0.018), 1,25(OH)2D/25-OH-D ratio (β = -0.521, p = 0.025), and the 24,25(OH)2D/1,25(OH)2D ratio (β = 0.632, p = 0.008), and intact PTH as a significant factor associated with the 1,25(OH)2D/25-OH-D ratio (β = 0.445, p = 0.028). This study demonstrated that, even in subjects with eGFR ≥60 ml/min/1.73 m(2), FGF-23 might play an important role in the regulation of vitamin D metabolism. In addition to the established role of PTH, the association between FGF-23 and indices of vitamin D metabolism suggested the potential role of FGF-23 on phosphate metabolism in such patients. © 2015 S. Karger AG, Basel.

  5. The purification of coal tar by the addition of quinoline and Zn(oh)/sub 2/

    International Nuclear Information System (INIS)

    Zhou, P.; Chen, Q.L.; Ao, X.Q.; Kang, C

    2017-01-01

    The coal tar was purified by the addition of quinoline and Zn(OH)2, in order to decrease the content of carbon and inorganic oxide particles. The effect on the viscosity and ash content of the coal tar were investigated by altering temperature, time, and the amount of quinolone and Zn(OH)2 . When the volume ratio between quinolone and coal tar was 20:1 and the static time was 24 h. The viscosity of three layers decreased with rising temperature. When the static temperature and time was 45 °C and 24 h, respectively. The viscosity of three layers decreased with the arising amount of quinoline. And when the volume ratio between quinolone and coal tar was 20:1 and the temperature was 45 °C. The viscosity of three layers decreased first and then increased with the prolonging of static time. And when the static time of coal tar was 24 h, the viscosity of coal tar is the lowest. Because of the lower viscosity of coal tar, decreasing the content of carbon and ash particles in upper and middle layer, the ash content decreased from 0.168% to 0.092%. The addition of Zn(OH)2 can lead ash content in middle layer decrease to 0.058%. Zn2SiO4 and ZnAl2O4 may be produced due to the reaction between Zn (OH) 2 and SiO2 or Al2O3, which can settle down easily. The results show that the content of carbon and inorganic oxide particles in upper-middle-class (the middle 4/5 of the whole volume) decreased with the addition of quinolone and Zn(OH)2 . When the volume ratio between quinolone and coal tar was 50:2, quality ratio between coal tar and Zn(OH)2 was 20000:1, the mixture were heated up to 45 °C at atmospheric pressure and keeping this constant temperature for 24 h, the ash content in upper-middle-class can decreased to 0.058%. (author)

  6. Isoflurane produces sustained cardiac protection after ischemia-reperfusion injury in mice.

    Science.gov (United States)

    Tsutsumi, Yasuo M; Patel, Hemal H; Lai, N Chin; Takahashi, Toshiyuki; Head, Brian P; Roth, David M

    2006-03-01

    Isoflurane reduces myocardial ischemia-reperfusion injury within hours to days of reperfusion. Whether isoflurane produces sustained cardiac protection has never been examined. The authors studied isoflurane-induced cardiac protection in the intact mouse after 2 h and 2 weeks of reperfusion and determined the dependence of this protection on adenosine triphosphate-dependent potassium channels and the relevance of this protection to myocardial function and apoptosis. Mice were randomly assigned to receive oxygen or isoflurane for 30 min with 15 min of washout. Some mice received mitochondrial (5-hydroxydecanoic acid) or sarcolemmal (HMR-1098) adenosine triphosphate-dependent potassium channel blockers with or without isoflurane. Mice were then subjected to a 30-min coronary artery occlusion followed by 2 h or 2 weeks of reperfusion. Infarct size was determined at 2 h and 2 weeks of reperfusion. Cardiac function and apoptosis were determined 2 weeks after reperfusion. Isoflurane did not change hemodynamics. Isoflurane reduced infarct size after reperfusion when compared with the control groups (27.7 +/- 6.3 vs. 41.7 +/- 6.4% at 2 h and 19.6 +/- 5.9 vs. 28.8 +/- 9.0% at 2 weeks). Previous administration of 5-hydroxydecanoic acid, but not HMR-1098, abolished isoflurane-induced cardiac protection. At 2 weeks, left ventricular end-diastolic diameter was decreased significantly and end-systolic pressure and maximum and minimum dP/dt were improved by isoflurane. Isoflurane-treated mice subjected to ischemia and 2 weeks of reperfusion showed less expression of proapoptotic genes, significantly decreased expression of cleaved caspase-3, and significantly decreased deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive nuclei compared with the control group. Cardiac protection induced by isoflurane against necrotic and apoptotic cell death is associated with an acute memory period that is sustained and functionally relevant 2 weeks after

  7. Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization.

    Science.gov (United States)

    Chu, Hannah X; Broughton, Brad R S; Kim, Hyun Ah; Lee, Seyoung; Drummond, Grant R; Sobey, Christopher G

    2015-07-01

    Ly6C(hi) monocytes are generally thought to exert a proinflammatory role in acute tissue injury, although their impact after injuries to the central nervous system is poorly defined. CC chemokine receptor 2 is expressed on Ly6C(hi) monocytes and plays an essential role in their extravasation and transmigration into the brain after cerebral ischemia. We used a selective CC chemokine receptor 2 antagonist, INCB3344, to assess the effect of Ly6C(hi) monocytes recruited into the brain early after ischemic stroke. Male C57Bl/6J mice underwent occlusion of the middle cerebral artery for 1 hour followed by 23 hours of reperfusion. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (10, 30 or 100 mg/kg IP) 1 hour before ischemia and at 2 and 6 hours after ischemia. At 24 hours, we assessed functional outcomes, infarct volume, and quantified the immune cells in blood and brain by flow cytometry or immunofluorescence. Gene expression of selected inflammatory markers was assessed by quantitative polymerase chain reaction. Ly6C(hi) monocytes were increased 3-fold in the blood and 10-fold in the brain after stroke, and these increases were selectively prevented by INCB3344 in a dose-dependent manner. Mice treated with INCB3344 exhibited markedly worse functional outcomes and larger infarct volumes, in association with reduced M2 polarization and increased peroxynitrite production in macrophages, compared with vehicle-treated mice. Our data suggest that Ly6C(hi) monocytes exert an acute protective effect after ischemic stroke to limit brain injury and functional deficit that involves promotion of M2 macrophage polarization. © 2015 American Heart Association, Inc.

  8. Protective role of vitamin C and E against sodium arsenate induced changes in developing kidney of albino mice

    International Nuclear Information System (INIS)

    Qureshi, F.; Tahir, M.; Sami, W.

    2009-01-01

    Background: Arsenic is a teratogenic agent present in the environment as oxides and arsenate and humans are exposed to it through contaminated drinking water, food, soil and air. This investigation was undertaken to evaluate protective role of Vitamin C and E against teratogenic injury produced by sodium arsenate in developing kidney of the mouse. Methods: Twenty-four pregnant albino mice of BALB/c strain, were randomly divided into 4 groups of 6 each: A1, A2, A3 and A4. Group A1 served as the control and received weight related distilled water by intra-peritoneal (I/P) injection, group A2 was given a single doses of 35 mg/kg on 8 GD whereas groups A3 and A4 were treated with Vitamin C and E by IP injection, 9 mg/kg/day and 15 mg/kg/day respectively, starting from 8 day and continued for the rest of the pregnancy period. The foetal kidneys were weighed and histological studies carried out including micrometry on different components of nephron. Results: Sodium arsenate toxicity manifested as an increase in weight of the kidneys, wider nephrogenic zone and significant reduction in the mean of number of mature renal corpuscles as compared to the control group (p<0.000). There were moderate to severe necrotic and degenerative changes in proximal and distal convoluted tubules; glomeruli were hyper cellular, the Bowman's spaces were obliterated. There was a statistically significant difference in mean diameter of renal corpuscles of group A2 when compared with groups A1, A3 and A4, (p<0.000). Conclusions: The findings implied that groups receiving Vitamin C and E along with sodium arsenate showed an overall improvement in all parameters, indicating the protective role of Vitamin C and E against arsenic induced teratogenicity in developing kidney and are safe to use during pregnancy without deleterious effect on human conspectuses in arsenic exposed areas. (author)

  9. The Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Protects against Dyslipidemia-Related Kidney Injury in Apolipoprotein E Knockout Mice

    Directory of Open Access Journals (Sweden)

    Jingjing Li

    2014-06-01

    Full Text Available The goal of this study was to investigate the possible protective effects of sitagliptin against dyslipidemia-related kidney injury in apolipoprotein E knockout (apoE−/− mice. Eight-week-old male apoE−/− mice were randomized to receive either a high fat diet (HFD, apoE−/− group or HFD mixed with sitagliptin (sita + apoE−/− group for 16 weeks. A control group of age- and gender-matched C57BL/6J mice were fed a HFD. The apoE−/− group exhibited increases in body weight and serum lipid levels in addition to high-density lipoprotein, and increases in 24-h urinary 8-hydroxy-2-deoxyguanosine and albuminuria excretion. Decreased insulin sensitivity was also observed in the apoE−/− group. These mice additionally contained enlargements of the glomerular mesangial matrix area, lipid deposition area, and renal interstitium collagen area. The apoE−/− group also demonstrated down-regulation of phosphorylated AMP-activated protein kinase (AMPK, increases in renal mRNA expression of transforming growth factor-beta 1 (TGF-β1 and fibronectin (FN, and increased protein expression of Akt, TGF-β1, FN and p38/ERK mitogen-activated protein kinase (MAPK. Sitagliptin treatment successfully ameliorated all the deleterious effects of dyslipidemia tested. To our knowledge, this is the first time that sitagliptin has been shown to reverse the renal dysfunction and structural damage induced by dyslipidemia in apoE−/− mice. Our results suggest that the renoprotective mechanism of sitagliptin may be due to a reduction in Akt levels, a restoration of AMPK activity, and inhibition of TGF-β1, FN, and p38/ERK MAPK signaling pathways.

  10. Changes of natural killer activity following local 60Co irradiation in intracranial tumor-bearing mice

    International Nuclear Information System (INIS)

    Otsuka, Shin-ichi; Suda, Kinya; Yamashita, Junkoh; Takeuchi, Juji; Handa, Hajime

    1982-01-01

    Changes of natural killer activity (NK activity) by local 60 Co irradiation in intracranial tumor-bearing mice were studied by the method of 51 Cr release assay. Local irradiation was administered 10 days after intracranial transplantation of 203-Glioma which had been originally induced by 20-methylcholanthrene in C57BL mice. Irradiation suppressed the growth of tumor and prolonged the mean survival time. The 50% survival time of untreated mice was about 2.5 weeks but that of mice treated by a single dose of 1000 rad and 1500 rad of irradiation was about 4.5 weeks and 6.5 weeks respectively. NK activity of spleen cells in these mice was serially examined. NK activity was gradually increased in mice treated by local irradiation, while it was gradually decreased in mice without treatment. On the other hand, NK activity remained unchanged in non-tumor-bearing control mice. Mice treated with 1000 rad and 1500 rad of irradiation showed 44.0% and 47.6% of % specific 51 Cr release respectively 11 days after irradiation while normal mice showed 18.0%. The increased NK activity after local irradiation suggested that local irradiation might have enhanced the immunological defence mechanisms against the tumor in the tumor-bearing hosts. Some characteristics of effector cells in this assay system were examined. The cytotoxicity of spleen cells was removed by the treatment of anti-BAT serum and complement but was not removed by the treatment of anti-Thy-1.2 serum and complement. Since NK activity reflects the immunological resistance to tumors to some extent, it is felt important to clarify the significance of changes of NK activity in patients with brain tumors in relation to various treatments including surgery, radiotherapy, chemotherapy and immunotherapy in the next step. (author)

  11. Adoptive transfer of dendritic cells expressing CD11c reduces the immunological response associated with experimental colitis in BALB/c mice.

    Science.gov (United States)

    Paiatto, Lisiery N; Silva, Fernanda G D; Yamada, Áureo T; Tamashiro, Wirla M S C; Simioni, Patricia U

    2018-01-01

    In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms. To induce oral tolerance, BALB/c mice were fed 4mg/mL OVA solution for seven consecutive days. Spleen DCs were isolated from tolerant (tDC) and naïve (nDC) mice, and then adoptively transferred to syngeneic mice. Three days later, colitis was induced in DC treated mice by intrarectal instillation of 100μg2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Control subjects received only intrarectal instillation of either TNBS solution or a vehicle. Five days later, mice from all groups were euthanized and examined for physiological and immunological parameters. Regarding the phenotype, we observed that the frequencies of CD11+ MHC II+ and CD11+ MHCII+ CD86+ cells were significantly lower in DCs isolated from tolerant mice than in those from naive mice. However, pretreatment with both types of DCs was able to significantly reduce clinical signs of colitis such as diarrhea, rectal prolapse, bleeding, and cachexia, although only treatment with tDCs was able to prevent weight loss from instillation of TNBS. In vitro proliferation of spleen cells from mice treated with either type of DCs was significantly lower than that observed in splenic cell cultures of naïve mice. Although no significant difference was observed in the frequencies of Treg cells in the experimental groups, the frequency of Th17+CD4+cellsand the secretion of IL-17 were more reduced in the cultures of spleen cells from mice treated with either type of DCs. The levels of IL-9 and IFN

  12. A comparative study of the progression of radiation pulmonary injury in C57BL/6J and C3H/HeN mice

    International Nuclear Information System (INIS)

    Liu Ying; Li Yang; Peng Ruiyun; Wang Shuming; Gao Yabing; Ma Junjie; Song Liangwen

    2007-01-01

    Objective: To compare the course of radiation pulmonary injury in C57BL/6J and C3H/HeN mice. Methods: C57BL/6J and C3H/HeN mice irradiated with 20 Gy 60 Co gamma rays were used as animal models. Sirius red staining and hydroxyproline measurement were used to detect the distribution of type I and III collagens and the content of pulmonary hydroxyproline. Immunohistochemistry was used to observe the changes of the expressions of fibronectin (FN) and laminin (LN) and alpha-smooth muscle actin (α-SMA) in the lung. Results: The changes in the lungs in C57BL/6J mice were as follows: the pathological changes undergone interstitial pneumonia, proliferation and fibrosis; significant increase of collagen deposition; FN increased rapidly to a significantly higher level at 1 and 3 months after irradiation than that in the control (P<0.01), and then decreased gradually to a normal level at 6 month after irradiation; LN elevated gradually after irradiation; the expressions of α-SMA were more intense than that in C3H/HeN mice. The changes in the lungs in C3H/HeN mice were as follows: the pathological changes mainly developed institial pneumonitis; no significant changes of FN expression was observed after irradiation compared to that in the control; LN increased significantly at 1 and 3 months after irradiation, and then decreased gradually. Conclusions: The models of radiation pulmonary fibrosis-sensitive and-resistant were established by irradiation with gamma rays, C57BL/6J mice developed late radiation pulmonary fibrosis, and were characterized by the significant accumulation of collagen. C3H/HeN mice did not develop radiation pulmonary fibrosis. (authors)

  13. Gaseous hydrogen sulfide protects against myocardial ischemia-reperfusion injury in mice partially independent from hypometabolism.

    Directory of Open Access Journals (Sweden)

    Pauline M Snijder

    Full Text Available BACKGROUND: Ischemia-reperfusion injury (IRI is a major cause of cardiac damage following various pathological processes. Gaseous hydrogen sulfide (H2S is protective during IRI by inducing a hypometabolic state in mice which is associated with anti-apoptotic, anti-inflammatory and antioxidant properties. We investigated whether gaseous H2S administration is protective in cardiac IRI and whether non-hypometabolic concentrations of H2S have similar protective properties. METHODS: Male C57BL/6 mice received a 0, 10, or 100 ppm H2S-N2 mixture starting 30 minutes prior to ischemia until 5 minutes pre-reperfusion. IRI was inflicted by temporary ligation of the left coronary artery for 30 minutes. High-resolution respirometry equipment was used to assess CO2-production and blood pressure was measured using internal transmitters. The effects of H2S were assessed by histological and molecular analysis. RESULTS: Treatment with 100 ppm H2S decreased CO2-production by 72%, blood pressure by 14% and heart rate by 25%, while treatment with 10 ppm H2S had no effects. At day 1 of reperfusion 10 ppm H2S showed no effect on necrosis, while treatment with 100 ppm H2S reduced necrosis by 62% (p<0.05. Seven days post-reperfusion, both 10 ppm (p<0.01 and 100 ppm (p<0.05 H2S showed a reduction in fibrosis compared to IRI animals. Both 10 ppm and 100 ppm H2S reduced granulocyte-influx by 43% (p<0.05 and 60% (p<0.001, respectively. At 7 days post-reperfusion both 10 and 100 ppm H2S reduced expression of fibronectin by 63% (p<0.05 and 67% (p<0.01 and ANP by 84% and 63% (p<0.05, respectively. CONCLUSIONS: Gaseous administration of H2S is protective when administered during a cardiac ischemic insult. Although hypometabolism is restricted to small animals, we now showed that low non-hypometabolic concentrations of H2S also have protective properties in IRI. Since IRI is a frequent cause of myocardial damage during percutaneous coronary intervention and cardiac

  14. TLR2 signal influences the iNOS/NO responses and worm development in C57BL/6J mice infected with Clonorchis sinensis.

    Science.gov (United States)

    Yang, Qing-Li; Shen, Ji-Qing; Jiang, Zhi-Hua; Shi, Yun-Liang; Wan, Xiao-Ling; Yang, Yi-Chao

    2017-08-07

    Although the responses of inducible nitric oxide synthase (iNOS) and associated cytokine after Clonorchis sinensis infection have been studied recently, their mechanisms remain incompletely understood. In this study, we investigated the effects of toll-like receptor 2 (TLR2) signals on iNOS/nitric oxide (NO) responses after C. sinensis infection. We also evaluated the correlations between iNOS responses and worm development, which are possibly regulated by TLR2 signal. TLR2 wild-type and mutant C57BL/6 J mice were infected with 60 C. sinensis metacercariae, and the samples were collected at 30, 60, 90 and 120 days post-infection (dpi). The total serum NO levels were detected using Griess reagent after nitrate was reduced to nitrite. Hepatic tissue samples from the infected mice were sliced and stained with hematoxylin and eosin (HE) to observe worm development in the intrahepatic bile ducts. The iNOS mRNA transcripts in the splenocytes were examined by real time reverse transcriptase polymerase chain reaction (qRT-PCR), and iNOS expression was detected by immunohistochemistry. Developing C. sinensis juvenile worms were more abundant in the intrahepatic bile ducts of TLR2 mutant mice than those of TLR2 wild-type mice. However, no eggs were found in the faeces of both mice samples. The serum levels of total NO significantly increased in TLR2 mutant mice infected with C. sinensis at 30 (t (5)  = 2.595, P = 0.049), 60 (t (5)  = 7.838, P = 0.001) and 90 dpi (t (5)  = 3.032, P = 0.029). Meanwhile, no changes occurred in TLR2 wild-type mice compared with uninfected controls during the experiment. The iNOS expression in splenocytes showed unexpected higher background levels in TLR2 mutant mice than those in TLR2 wild-type mice. Furthermore, the iNOS mRNA transcripts in splenocytes were significantly increased in the TLR2 wild-type mice infected with C. sinensis at 30 (t (5)  = 5.139, P = 0.004), 60 (t (5)  = 6.138, P = 0.002) and 90 dpi (t (5)  = 6

  15. Characterization and protective property of Brucella abortus cydC and looP mutants.

    Science.gov (United States)

    Truong, Quang Lam; Cho, Youngjae; Barate, Abhijit Kashinath; Kim, Suk; Hahn, Tae-Wook

    2014-11-01

    Brucella abortus readily multiplies in professional or nonprofessional phagocytes in vitro and is highly virulent in mice. Isogenic mutants of B. abortus biovar 1 strain IVKB9007 lacking the ATP/GDP-binding protein motif A (P-loop) (named looP; designated here the IVKB9007 looP::Tn5 mutant) and the ATP-binding/permease protein (cydC; designated here the IVKB9007 cydC::Tn5 mutant) were identified and characterized by transposon mutagenesis using the mini-Tn5Km2 transposon. Both mutants were found to be virtually incapable of intracellular replication in both murine macrophages (RAW264.7) and the HeLa cell line, and their virulence was significantly impaired in BALB/c mice. Respective complementation of the IVKB9007 looP::Tn5 and IVKB9007 cydC::Tn5 mutants restored their ability to survive in vitro and in vivo to a level comparable with that of the wild type. These findings indicate that the cydC and looP genes play important roles in the virulence of B. abortus. In addition, intraperitoneal immunization of mice with a dose of the live IVKB9007 looP::Tn5 and IVKB9007 cydC::Tn5 mutants provided a high degree of protection against challenge with pathogenic B. abortus strain 544. Both mutants should be evaluated further as a live attenuated vaccine against bovine brucellosis for their ability to stimulate a protective immune response. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. Evaluation the protective effect of diphenhydramine against acute toxicity induced by levamisole in male mice

    Directory of Open Access Journals (Sweden)

    M.Y. Matti

    2015-06-01

    Full Text Available The aim of this study was to evaluate the protective effect of different doses of diphenhydramine against acute toxicosis with Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramine against Levamisole toxicosis also examined on the level of cholinesterase (ChE activity. Subcutanous injection of 100mg/kg levamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was not related to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin 2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantly decreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramine at low dose alone or with acute dose of levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisole was not related to inhibition of ChE. The low dose of diphenhydramine protected mice from Levamisole toxicity. The antidoatal effect of diphenhydramine not at the level of protection from ChE inhibition. There was no adverse interaction between two drugs.

  17. The complex of PAMAM-OH dendrimer with Angiotensin (1–7 prevented the disuse-induced skeletal muscle atrophy in mice

    Directory of Open Access Journals (Sweden)

    Márquez-Miranda V

    2017-03-01

    Full Text Available Valeria Márquez-Miranda,1,2,* Johanna Abrigo,3,4,* Juan Carlos Rivera,3,4 Ingrid Araya-Durán,1 Javier Aravena,3,4 Felipe Simon,3,4 Nicolás Pacheco,1 Fernando Danilo González-Nilo,1,2,5 Claudio Cabello-Verrugio3,4 1Center for Bioinformatics and Integrative Biology (CBIB, Facultad de Ciencias Biologicas, Universidad Andres Bello, Santiago, 2Fundación Fraunhofer Chile Research, Las Condes, 3Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas & Facultad de Medicina, Universidad Andres Bello, 4Millennium Institute on Immunology and Immunotherapy, Santiago, 5Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile *These authors contributed equally to this work Abstract: Angiotensin (1–7 (Ang-(1–7 is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine (PAMAM-OH dendrimer as an Ang-(1–7 carrier. Bioinformatics analysis showed that the Ang-(1–7-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7 and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7/PAMAM-OH complex, but not Ang-(1–7 alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7/PAMAM-OH complex being intraperitoneally

  18. Crystal structures of Th(OH)PO4, U(OH)PO4 and Th2O(PO4)2. Condensation mechanism of M(IV)(OH)PO4 (M= Th, U) into M2O(PO4)2

    International Nuclear Information System (INIS)

    Dacheux, N.; Clavier, N.; Wallez, G.; Quarton, M.

    2007-01-01

    Three new crystal structures, isotypic with β-Zr 2 O(PO 4 ) 2 , have been resolved by the Rietveld method. All crystallize with an orthorhombic cell (S.G.: Cmca) with a = 7.1393(2) Angstroms, b = 9.2641(2) Angstroms, c 12.5262(4) Angstroms, V = 828.46(4) (Angstroms) 3 and Z = 8 for Th(OH)PO 4 ; a = 7.0100(2) Angstroms, b = 9.1200(2) Angstroms, c = 12.3665(3) Angstroms, V 790.60(4) (Angstroms) 3 and Z = 8 for U(OH)PO 4 ; a 7.1691(3) Angstroms, b 9.2388(4) Angstroms, c = 12.8204(7) Angstroms, V 849.15(7) (Angstroms) 3 and Z = 4 for Th 2 O(PO 4 ) 2 . By heating, the M(OH)PO 4 (M Th, U) compounds condense topotactically into M 2 O(PO 4 ) 2 , with a change of the environment of the tetravalent cation that lowers from 8 to 7 oxygen atoms. The lower stability of Th 2 O(PO 4 ) 2 compared to that of U 2 O(PO 4 ) 2 seems to result from this unusual environment for tetravalent thorium. (authors)

  19. The use of CH3OH additive to NaOH for etching alpha particle tracks in a CR-39 plastic nuclear track detector

    International Nuclear Information System (INIS)

    Ashry, A.H.; Abdalla, A.M.; Rammah, Y.S.; Eisa, M.; Ashraf, O.

    2014-01-01

    Fast detection of alpha particles in CR-39 detectors was investigated using a new chemical etchant. 252 Cf and 241 Am sources were used for irradiating samples of CR-39 SSNTDs with fission fragments and alpha particles in air at normal temperature and pressure. A series of experimental chemical etching are carried out using new etching solution (8 ml of 10N NaOH+1 ml CH 3 OH) at 60 °C to detect alpha particle in short time in CR-39 detectors. Suitable analyzing software has been used to analyze experimental data. From fission and alpha track diameters, the value of bulk etching rate is equal to 2.73 μm/h. Both the sensitivity and etching efficiency were found to vary with the amount of methanol in the etching solution. Pure NaOH was used as a control to compare with the result from etching in NaOH with different concentrations of CH 3 OH. The etching efficiency is determined and compared with conventional aqueous solution of 6.25N NaOH at 70 °C for etching time equals 5 h. In this study, the obtained etching efficiency shows a considerable agreement with the previous work. - Highlights: • The value of bulk etching rate is equal to 2.73 μm/h. • Fast detection of alpha particles in CR-39 detectors. • Samples of CR-39 have been irradiated with fission fragments. • Etching efficiency was determined

  20. Reducing HAuCl4 by the C60 dianion: C60-directed self-assembly of gold nanoparticles into novel fullerene bound gold nanoassemblies

    International Nuclear Information System (INIS)

    Liu Wei; Gao Xiang

    2008-01-01

    The C 60 dianion is used to reduce tetrachloroauric acid (HAuCl 4 ) for the first time; three-dimensional C 60 bound gold (Au-C 60 ) nanoclusters are obtained from C 60 -directed self-assembly of gold nanoparticles due to the strong affinities of Au-C 60 and C 60 -C 60 . The process was monitored in situ by UV-vis-NIR spectroscopy. The resulting Au-C 60 nanoclusters were characterized using transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy-dispersive spectroscopy (EDS), x-ray powder diffraction (XRD), x-ray photoelectron spectroscopy (XPS), and FT-IR and Raman spectroscopies. TEM demonstrates the formation of 3D nanonetwork aggregates, which are composed of discrete gold nanocores covered with a C 60 monolayer. The SAED and XRD patterns indicate that the gold nanocores inside the capped C 60 molecules belong to the face-centred cubic crystal structure, while the C 60 molecules are amorphous. The EDS and XPS measurements validate that the Au-C 60 nanoclusters contain only Au and C elements and Au 3+ is reduced to Au 0 . FT-IR spectroscopy shows the chemiadsorption of C 60 to the gold nanocores, while Raman spectroscopy demonstrates the electron transfer from the gold nanocores to the chemiadsorbed C 60 molecules. Au-C 60 nanoclusters embedded in tetraoctyl-n-ammonium bromide (TOAB) on glassy carbon electrodes (GCEs) have been fabricated and have shown stable and well-defined electrochemical responses in aqueous solution

  1. Augmentation of DHCR24 expression by hepatitis C virus infection facilitates viral replication in hepatocytes.

    Science.gov (United States)

    Takano, Takashi; Tsukiyama-Kohara, Kyoko; Hayashi, Masahiro; Hirata, Yuichi; Satoh, Masaaki; Tokunaga, Yuko; Tateno, Chise; Hayashi, Yukiko; Hishima, Tsunekazu; Funata, Nobuaki; Sudoh, Masayuki; Kohara, Michinori

    2011-09-01

    We characterized the role of 24-dehydrocholesterol reductase (DHCR24) in hepatitis C virus infection (HCV). DHCR24 is a cholesterol biosynthetic enzyme and cholesterol is a major component of lipid rafts, which is reported to play an important role in HCV replication. Therefore, we examined the potential of DHCR24 as a target for novel HCV therapeutic agents. We examined DHCR24 expression in human hepatocytes in both the livers of HCV-infected patients and those of chimeric mice with human hepatocytes. We targeted DHCR24 with siRNA and U18666A which is an inhibitor of both DHCR24 and cholesterol synthesis. We measured the level of HCV replication in these HCV replicon cell lines and HCV infected cells. U18666A was administrated into chimeric mice with humanized liver, and anti-viral effects were assessed. Expression of DHCR24 was induced by HCV infection in human hepatocytes in vitro, and in human hepatocytes of chimeric mouse liver. Silencing of DHCR24 by siRNA decreased HCV replication in replicon cell lines and HCV JFH-1 strain-infected cells. Treatment with U18666A suppressed HCV replication in the replicon cell lines. Moreover, to evaluate the anti-viral effect of U18666A in vivo, we administrated U18666A with or without pegylated interferon to chimeric mice and observed an inhibitory effect of U18666A on HCV infection and a synergistic effect with interferon. DHCR24 is an essential host factor which augmented its expression by HCV infection, and plays a significant role in HCV replication. DHCR24 may serve as a novel anti-HCV drug target. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. Toxoplasma gondii vs ionizing radiation: intestinal immunity induced in C57bl/6j mice by irradiated tachyzoites

    International Nuclear Information System (INIS)

    Galisteo Junior, Andres Jimenez.

    2004-01-01

    We study the oral route for the development of a vaccine for toxoplasmosis, using parasites irradiated with 60 Cobalt, as an alternative for vaccine development to this worldwide parasitic infection. We evaluated the development of immunity at serum or mucosal levels, and their efficiency in protect the mice against challenge with oral cysts of the Me-49 strain. C57Bl/6j isogenic mice were immunized by oral route with 107 255 Gy irradiated tachyzoites from RH strain, at several protocols using milk as anti-peptic adjuvant and alum hydroxide as antacid. The preparations of irradiated tachyzoites induced production of serum IgG and IgA in immunized mice, as determined by ELISA, with IgG2a as the dominant subclass, similar to chronic infection. Their use with adjuvant allowed the excretion of significant amounts of IgA in stools also IgG, despite a lesser extent. There are suggestion of tolerance induction at mucosal level, with lower antigen induced proliferation and lower in vitro antibody production by spleen and gut lymphocytes, with the latter doses, specially when milk was used as adjuvant. All oral preparations induced some quantitative protection against challenge, which was similar to the parenteral route only isolated alum hydroxide was used as adjuvant. All these data support the possibility of the development of an oral vaccine against toxoplasmosis, using irradiated tachyzoites, which would be possible tool in near future for use in field baits, for immunizing either domestic or wild felines. (author)

  3. STM topographical images of C60

    International Nuclear Information System (INIS)

    Wang, Z.; Zhang, P.; Moskovits, M.

    1991-01-01

    In this paper STM topographical images of C 60 are reported. The images are consistent with a molecule approximately 9 Angstrom in diameter possessing the now-famous soccer ball structure. With the molecule deposited on gold, its atomic structure is not resolved. On graphite the structure of the within the borders of the C 60 molecule is dominated by that of the graphite forming a moire-like pattern. Some evidence of atomic structure is seen in multilayers of C 60 where some five- and six-membered rings are visible. These may, however, be features of fragments of the fullerene rather than whole molecules

  4. Impact of OH Heterogenous Oxidation on the Evolution of Brown Carbon Aerosol Optical Properties

    Science.gov (United States)

    Schnitzler, E.; Abbatt, J.

    2017-12-01

    The effects of varying relative humidity (RH) on the evolution of brown carbon (BrC) optical properties induced by heterogeneous OH oxidation were investigated in a series of photooxidation chamber experiments. A BrC surrogate was generated from aqueous 1,3-dihydroxybenzene (10 mM) and H2O2 (10 mM) exposed to >300 nm radiation, atomized, passed through a series of trace gas denuders, and injected into the chamber, which was conditioned to about 10 or 60% RH. Following aerosol injection, H2O2 was continuously bubbled into the chamber; an hour later, the chamber was irradiated with black-lights (UV-B) to produce OH. Before irradiation, aerosol absorption and scattering at 405 nm, measured using a photoacoustic spectrometer, decreased due only to deposition and dilution, and single scattering albedo (SSA) was relatively steady. In the presence of gas-phase OH, absorption first increased, despite continued particle losses, and SSA decreased. Subsequently, absorption decreased faster than scattering, and SSA increased uniformly. At 60% RH, colour enhancement, likely associated with functionalization, was greatest after only minutes of reaction. In contrast, at 10% RH, peak colour enhancement occurred after about two hours of reaction, indicating that the decrease in RH and the attendant increase in particle viscosity significantly impeded heterogeneous OH oxidation of the BrC surrogate.

  5. Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding C3H/HeN mice

    DEFF Research Database (Denmark)

    Moser, C; Johansen, H K; Song, Z

    1997-01-01

    model of this infection was established in two strains of mice: C3H/HeN and BALB/c, generally known as Th1 and Th2 responders, respectively, which were challenged with alginate-embedded P. aeruginosa. Mortality was significantly lower in C3H/HeN compared to BALB/c mice (p ... was cleared more efficiently in C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology (p BALB/c mice (p ... from the two strains of mice, the interferon-(IFN-) gamma levels were higher, whereas IL-4 levels were lower in C3H/HeN mice than in BALB/c mice. The implications of these findings for CF patients with chronic P. aeruginosa lung infection are discussed....

  6. Fusion of a viral antigen to invariant chain leads to augmented T-cell immunity and improved protection in gene-gun DNA-vaccinated mice

    DEFF Research Database (Denmark)

    Grujic, Mirjana; Holst, Peter J; Christensen, Jan P

    2009-01-01

    It has recently been demonstrated that a recombinant replication-deficient human adenovirus 5 (Ad5) vector expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) fused to the p31 invariant (Ii) chain confers broad, long-lasting T-cell immunity that completely protects C57BL/6 mice...... with the unlinked construct. In contrast, substantial protection against peripheral challenge was not observed. Additional experiments with T-cell subset-depleted or perforin-deficient mice revealed that virus control in vaccinated mice depends critically on cytotoxic CD8(+) T cells. Finally, priming with the naked...

  7. A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

    Directory of Open Access Journals (Sweden)

    Douglas S. Kernodle

    2013-01-01

    Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  8. Characterization of SeseC_01411 as a surface protective antigen of Streptococcus equi ssp. zooepidemicus.

    Science.gov (United States)

    Xie, Honglin; Wei, Zigong; Ma, Chunquan; Li, Shun; Liu, Xiaohong; Fu, Qiang

    2018-06-01

    Streptococcus equi ssp. zooepidemicus (Streptococcus zooepidemicus, SEZ) is a commensal bacterium related to opportunistic infections of many species, including humans, dogs, cats, and pigs. SeseC_01411 has been proven to be immunogenic. However, its protective efficacy remained to be evaluated. In the present study, the purified recombinant SeseC_01411 could elicit a strong humoral antibody response and protect against lethal challenge with virulent SEZ in mice. Our finding confirmed that SeseC_01411 distributes on the surface of SEZ. In addition, the hyperimmune sera against SeseC_01411 could efficiently kill the bacteria in the phagocytosis test. The present study identified the immunogenic protein, SeseC_01411, as a novel surface protective antigen of SEZ. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Preparation and biodistribution of radiolabeled fullerene C60 nanocrystals

    International Nuclear Information System (INIS)

    Nikolic, Nadezda; Vranjes-Duric, Sanja; Jankovic, Drina; Dokic, Divna; Mirkovic, Marija; Bibic, Natasa; Trajkovic, Vladimir

    2009-01-01

    The present study describes for the first time a procedure for the radiolabeling of fullerene (C 60 ) nanocrystals (nanoC 60 ) with Na 125 I, as well as the biodistribution of radiolabeled nanoC 60 ( 125 I-nanoC 60 ). The solvent exchange method with tetrahydrofuran was used to make colloidal water suspensions of radiolabeled nanoC 60 particles. The radiolabeling procedure with the addition of Na 125 I to tetrahydrofuran during dissolution of C 60 gave a higher radiochemical yield of radiolabeled nanoC 60 particles in comparison to the second option, in which Na 125 I was added after C 60 was dissolved. Using photon correlation spectroscopy and transmission electron microscopy, 125 I-nanoC 60 particles were found to have a crystalline structure and a mean diameter of 200-250 nm. The 125 I-nanoC 60 had a particularly high affinity for human serum albumin, displaying 95% binding efficiency after 1 h. Biodistribution studies of 125 I-nanoC 60 in rats indicated significant differences in tissue accumulation of 125 I-nanoC 60 and the radioactive tracer Na 125 I. The higher accumulation of radiolabeled nanoC 60 was observed in liver and spleen, while accumulation in thyroid, stomach, lungs and intestines was significantly lower in comparison to Na 125 I. In addition to being useful for testing the biological distribution of nanoC 60 , the described radiolabeling procedure might have possible applications in cancer radiotherapy.

  10. Combined effects of diethylpropion and alcohol on locomotor activity of mice: participation of the dopaminergic and opioid systems

    Directory of Open Access Journals (Sweden)

    Gevaerd M.S.

    1999-01-01

    Full Text Available The widespread consumption of anorectics and combined anorectic + alcohol misuse are problems in Brazil. In order to better understand the interactive effects of ethanol (EtOH and diethylpropion (DEP we examined the locomotion-activating effects of these drugs given alone or in combination in mice. We also determined whether this response was affected by dopamine (DA or opioid receptor antagonists. A total of 160 male Swiss mice weighing approximately 30 g were divided into groups of 8 animals per group. The animals were treated daily for 7 consecutive days with combined EtOH + DEP (1.2 g/kg and 5.0 mg/kg, ip, EtOH (1.2 g/kg, ip, DEP (5.0 mg/kg, ip or the control solution coadministered with the DA antagonist haloperidol (HAL, 0.075 mg/kg, ip, the opioid antagonist naloxone (NAL, 1.0 mg/kg, ip, or vehicle. On days 1, 7 and 10 after the injections, mice were assessed in activity cages at different times (15, 30, 45 and 60 min for 5 min. The acute combination of EtOH plus DEP induced a significantly higher increase in locomotor activity (day 1: 369.5 ± 34.41 when compared to either drug alone (day 1: EtOH = 232.5 ± 23.79 and DEP = 276.0 ± 12.85 and to control solution (day 1: 153.12 ± 7.64. However, the repeated administration of EtOH (day 7: 314.63 ± 26.79 and day 10: 257.62 ± 29.91 or DEP (day 7: 309.5 ± 31.65 and day 10: 321.12 ± 39.24 alone or in combination (day 7: 459.75 ± 41.28 and day 10: 427.87 ± 33.0 failed to induce a progressive increase in the locomotor response. These data demonstrate greater locomotion-activating effects of the EtOH + DEP combination, probably involving DA and/or opioid receptor stimulation, since the daily pretreatment with HAL (day 1: EtOH + DEP = 395.62 ± 11.92 and EtOH + DEP + HAL = 371.5 ± 6.76; day 7: EtOH + DEP = 502.5 ± 42.27 and EtOH + DEP + HAL = 281.12 ± 16.08; day 10: EtOH + DEP = 445.75 ± 16.64 and EtOH + DEP + HAL = 376.75 ± 16.4 and NAL (day 1: EtOH + DEP = 553.62 ± 38.15 and EtOH

  11. Protective effect of Hongxue tea mixture against radiation injury in mice

    International Nuclear Information System (INIS)

    Zhao Chun; Zhang Xuehui; Wang Qi

    2005-01-01

    Objective: To develop health food of anti-radiation among biological source in Yunnan. Methods: Screening test was done of the health food of biological source of anti-radiation injury in mice. It is indicated that Hong-Xue Tea Mixture among the biological source has the effect against radiation injury, observing experiment of dose-effect of Hong-Xue Tea Mixture was done. Micronuclei in the bone marrow polychromatophilic erythrocytes in each dose group of mice were examined, leucocytes number and 30 day survival rate of mice following whole-body 5.0 Gy γ irradiation were also determined. Results: Research showed that Hong-Xue Tea Mixture and Spirulina Platensis Mixture among the biological source have protective effect against radiation injury in mice. Observing experiment of dose-effect of Hong-Xue Tea Mixture show that low, medium and high dose of Hong-Xue Tea Mixture can significantly decrease bone marrow PECMN rate of mice, increase leucocytes number and 30 day survival rate. Conclusion: Hong-Xue Tea Mixture has potent protective effects against radiation injury in mice. (authors)

  12. Disintegration of C60 by Xe ion irradiation

    International Nuclear Information System (INIS)

    Kalish, R.; Samoiloff, A.; Hoffman, A.; Uzan-Saguy, C.

    1993-01-01

    The Changes in resistivity of fullerene (C 60 ) films subject to 320 keV Xe ion irradiation are investigated as a function of ion dose. From a comparison of this dependence with similar data on other Xe irradiated C containing insulating materials and with data on C implanted fused quartz, it is concluded that upon ion impact C 60 clusters completely disintegrate. This disintegration releases about 60 C atoms which disperse amongst the remaining intact C 60 spheres giving rise to hopping conductivity between isolated C atoms. 16 refs., 3 figs

  13. Electronic Structure of Eu6C60

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-Xiong; LI Hong-Nian; XU Ya-Bo; WANG Peng; ZHANG Wen-Hua; XU Fa-Qiang

    2009-01-01

    We study the valence band of Eu-intercalated C60 by synchrotron radiation photoelectron spectroscopy to un-derstand the ferromagnetism (FM) and the giant magnetoresistance (GMR) of Eu6C60. The results reveal the semiconducting property and the remarkable 5d6s-π hybridization. Eu-C60 bonding has both ionic and covalent contributions. No more than half the 5d6s electrons transfer from Eu to the LUMO derived band of C60, and the LUMO+1 derived band is not filled. The remaining valence electrons of Eu, together with some π (LUMO, HOMO and HOMO-1) electrons, constitute the covalent bond. The electronic structure implies that the magnetic coupling in Eu6C60 should be through the intra-atomic f-sd exchange and the medium of the π electrons. The possibility of the GMR being tunnelling magnetoresistance is ruled out.

  14. Relativistic electronic structure calculations on endohedral Gd rate at C60, La rate at C60, Gd rate at C74, and La rate at C74

    International Nuclear Information System (INIS)

    Lu, J.; Zhang, X.; Zhao, X.

    2000-01-01

    Relativistic discrete-variational local density functional calculations on endohedral Gd rate at C 60 , La rate at C 60 ,Gd rate at C 74 , and La rate at C 74 are performed. All the C 60 - and C 74 -derived levels are lowered upon endohedral Gd and La doping. Both the Gd (4f 7 5d 1 6s 2 ) and La (5d 1 6s 2 ) atoms only donate their two 6s valence electrons to the cages, leaving behind their 5d electrons when they are placed at the cage centers. Compared with large-band-gap C 60 , small-band-gap C 74 and Gd (La)-metallofullerenes have strong both electron-donating and electron-accepting characters, and the calculated ionization potentials and electron affinities for them agree well with the available experimental data. (orig.)

  15. Doped Sc2C(OH)2 MXene: new type s-pd band inversion topological insulator.

    Science.gov (United States)

    Balcı, Erdem; Akkuş, Ünal Özden; Berber, Savas

    2018-04-18

    The electronic structures of Si and Ge substitutionally doped Sc 2 C(OH) 2 MXene monolayers are investigated in density functional theory. The doped systems exhibit band inversion, and are found to be topological invariants in Z 2 theory. The inclusion of spin orbit coupling results in band gap openings. Our results point out that the Si and Ge doped Sc 2 C(OH) 2 MXene monolayers are topological insulators. The band inversion is observed to have a new mechanism that involves s and pd states.

  16. Doped Sc2C(OH)2 MXene: new type s-pd band inversion topological insulator

    Science.gov (United States)

    Balcı, Erdem; Özden Akkuş, Ünal; Berber, Savas

    2018-04-01

    The electronic structures of Si and Ge substitutionally doped Sc2C(OH)2 MXene monolayers are investigated in density functional theory. The doped systems exhibit band inversion, and are found to be topological invariants in Z 2 theory. The inclusion of spin orbit coupling results in band gap openings. Our results point out that the Si and Ge doped Sc2C(OH)2 MXene monolayers are topological insulators. The band inversion is observed to have a new mechanism that involves s and pd states.

  17. CETP Expression Protects Female Mice from Obesity-Induced Decline in Exercise Capacity.

    Science.gov (United States)

    Cappel, David A; Lantier, Louise; Palmisano, Brian T; Wasserman, David H; Stafford, John M

    2015-01-01

    Pharmacological approaches to reduce obesity have not resulted in dramatic reductions in the risk of coronary heart disease (CHD). Exercise, in contrast, reduces CHD risk even in the setting of obesity. Cholesteryl Ester Transfer Protein (CETP) is a lipid transfer protein that shuttles lipids between serum lipoproteins and tissues. There are sexual-dimorphisms in the effects of CETP in humans. Mice naturally lack CETP, but we previously reported that transgenic expression of CETP increases muscle glycolysis in fasting and protects against insulin resistance with high-fat diet (HFD) feeding in female but not male mice. Since glycolysis provides an important energy source for working muscle, we aimed to define if CETP expression protects against the decline in exercise capacity associated with obesity. We measured exercise capacity in female mice that were fed a chow diet and then switched to a HFD. There was no difference in exercise capacity between lean, chow-fed CETP female mice and their non-transgenic littermates. Female CETP transgenic mice were relatively protected against the decline in exercise capacity caused by obesity compared to WT. Despite gaining similar fat mass after 6 weeks of HFD-feeding, female CETP mice showed a nearly two-fold increase in run distance compared to WT. After an additional 6 weeks of HFD-feeding, mice were subjected to a final exercise bout and muscle mitochondria were isolated. We found that improved exercise capacity in CETP mice corresponded with increased muscle mitochondrial oxidative capacity, and increased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). These results suggest that CETP can protect against the obesity-induced impairment in exercise capacity and may be a target to improve exercise capacity in the context of obesity.

  18. CETP Expression Protects Female Mice from Obesity-Induced Decline in Exercise Capacity.

    Directory of Open Access Journals (Sweden)

    David A Cappel

    Full Text Available Pharmacological approaches to reduce obesity have not resulted in dramatic reductions in the risk of coronary heart disease (CHD. Exercise, in contrast, reduces CHD risk even in the setting of obesity. Cholesteryl Ester Transfer Protein (CETP is a lipid transfer protein that shuttles lipids between serum lipoproteins and tissues. There are sexual-dimorphisms in the effects of CETP in humans. Mice naturally lack CETP, but we previously reported that transgenic expression of CETP increases muscle glycolysis in fasting and protects against insulin resistance with high-fat diet (HFD feeding in female but not male mice. Since glycolysis provides an important energy source for working muscle, we aimed to define if CETP expression protects against the decline in exercise capacity associated with obesity. We measured exercise capacity in female mice that were fed a chow diet and then switched to a HFD. There was no difference in exercise capacity between lean, chow-fed CETP female mice and their non-transgenic littermates. Female CETP transgenic mice were relatively protected against the decline in exercise capacity caused by obesity compared to WT. Despite gaining similar fat mass after 6 weeks of HFD-feeding, female CETP mice showed a nearly two-fold increase in run distance compared to WT. After an additional 6 weeks of HFD-feeding, mice were subjected to a final exercise bout and muscle mitochondria were isolated. We found that improved exercise capacity in CETP mice corresponded with increased muscle mitochondrial oxidative capacity, and increased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α. These results suggest that CETP can protect against the obesity-induced impairment in exercise capacity and may be a target to improve exercise capacity in the context of obesity.

  19. Curiosities at c=24

    International Nuclear Information System (INIS)

    Schellekens, A.N.; Yankielowicz, S.

    1989-01-01

    Two examples of c=24 holomorphic conformal field theories are given that do not correspond to Niemeier lattices or Z 2 twists of Niemeier lattices. One of these examples clarifies a recently discovered modular invariant of F 4 at level 6, which can be interpreted as the 'complement' of SU(3) level 2 within a new c=24 theory. (orig.)

  20. UV photolysis of 4-iodo-, 4-bromo-, and 4-chlorophenol: Competition between C-Y (Y = halogen) and O-H bond fission

    Science.gov (United States)

    Sage, Alan G.; Oliver, Thomas A. A.; King, Graeme A.; Murdock, Daniel; Harvey, Jeremy N.; Ashfold, Michael N. R.

    2013-04-01

    The wavelength dependences of C-Y and O-H bond fission following ultraviolet photoexcitation of 4-halophenols (4-YPhOH) have been investigated using a combination of velocity map imaging, H Rydberg atom photofragment translational spectroscopy, and high level spin-orbit resolved electronic structure calculations, revealing a systematic evolution in fragmentation behaviour across the series Y = I, Br, Cl (and F). All undergo O-H bond fission following excitation at wavelengths λ ≲ 240 nm, on repulsive ((n/π)σ*) potential energy surfaces (PESs), yielding fast H atoms with mean kinetic energies ˜11 000 cm-1. For Y = I and Br, this process occurs in competition with prompt C-I and C-Br bond cleavage on another (n/π)σ* PES, but no Cl/Cl* products unambiguously attributable to one photon induced C-Cl bond fission are observed from 4-ClPhOH. Differences in fragmentation behaviour at longer excitation wavelengths are more marked. Prompt C-I bond fission is observed following excitation of 4-IPhOH at all λ ≤ 330 nm; the wavelength dependent trends in I/I* product branching ratio, kinetic energy release, and recoil anisotropy suggest that (with regard to C-I bond fission) 4-IPhOH behaves like a mildly perturbed iodobenzene. Br atoms are observed when exciting 4-BrPhOH at long wavelengths also, but their velocity distributions suggest that dissociation occurs after internal conversion to the ground state. O-H bond fission, by tunnelling (as in phenol), is observed only in the cases of 4-FPhOH and, more weakly, 4-ClPhOH. These observed differences in behaviour can be understood given due recognition of (i) the differences in the vertical excitation energies of the C-Y centred (n/π)σ* potentials across the series Y = I increased spin-orbit coupling in, particularly, 4-IPhOH. The present results provide (another) reminder of the risks inherent in extrapolating photochemical behaviour measured for one molecule at one wavelength to other (related) molecules and to

  1. Femtosecond Dynamics of Photoexcited C60 Films.

    Science.gov (United States)

    Causa', Martina; Ramirez, Ivan; Martinez Hardigree, Josue F; Riede, Moritz; Banerji, Natalie

    2018-04-19

    The well known organic semiconductor C 60 is attracting renewed attention due to its centimeter-long electron diffusion length and high performance of solar cells containing 95% fullerene, yet its photophysical properties remain poorly understood. We elucidate the dynamics of Frenkel and intermolecular (inter-C 60 ) charge-transfer (CT) excitons in neat and diluted C 60 films from high-quality femtosecond transient absorption (TA) measurements performed at low fluences and free from oxygen or pump-induced photodimerization. We find from preferential excitation of either species that the CT excitons give rise to a strong electro-absorption (EA) signal but are extremely short-lived. The Frenkel exciton relaxation and triplet yield strongly depend on the C 60 aggregation. Finally, TA measurements on full devices with applied electric field allow us to optically monitor the dissociation of CT excitons into free charges for the first time and to demonstrate the influence of cluster size on the spectral signature of the C 60 anion.

  2. Electronic structure of single crystal C60

    International Nuclear Information System (INIS)

    Wu, J.; Shen, Z.X.; Dessau, D.S.; Cao, R.; Marshall, D.S.; Pianetta, P.; Lindau, I.; Yang, X.; Terry, J.; King, D.M.; Wells, B.O.; Elloway, D.; Wendt, H.R.; Brown, C.A.; Hunziker, H.; Vries, M.S. de

    1992-01-01

    We report angle-resolved photoemission data from single crystals of C 60 cleaved in UHV. Unlike the other forms of pure carbon, the valence band spectrum of C 60 consists of many sharp features that can be essentially accounted for by the quantum chemical calculations describing individual molecules. This suggests that the electronic structure of solid C 60 is mainly determined by the bonding interactions within the individual molecules. We also observe remarkable intensity modulations of the photoemission features as a function of photon energy, suggesting strong final state effects. Finally, we address the issue of the band width of the HOMO state of C 60 . We assert that the width of the photoemission peak of C 60 does not reflect the intrinsic band width because it is broadened by the non 0-0 transitions via the Franck-Condon principle. Our view point provides a possible reconciliation between these photoemission data and those measured by other techniques. (orig.)

  3. Interaction between poly(vinyl pyrrolidone) PVP and fullerene C60 at the interface in PVP-C60 nanofluids–A spectroscopic study

    Science.gov (United States)

    Behera, M.; Ram, S.

    2018-03-01

    Fourier transform infrared and Raman bands shows a discernible enhancement in band intensity of C–H stretching, C=O stretching, C–N stretching, C–H2 bending, and C–H2 in-plane bending in PVP molecules in the presence of C60 molecules. Amplification in intensity is ascribed to microscopic interactions results when a donation of nonbonding electron (n) occurs from a “>N–C=O” entity of PVP into a lowest unoccupied molecular orbital of the C60 molecule in PVP-C60 charge transfer (CT) complex. The C=O stretching band intensity (integrated) Vs C60 content plot exhibits a peak near a critical 13.9 μM C60 value owing to percolation effect. Light emission spectra show that even a small addition of 4.63 μM C60 able to suppress the band intensity by ~23% as a result of an energy loss. The integrated band intensity also decreases through a peak near 13.9 μM when plotted against the C60-content. In correlation to the vibration spectra, the maximum effect observed both in light emission and excitation spectra suggests a percolation effect in the CT complex. Exhibition of percolation threshold in C60-PVP donor-acceptor complex will be helpful in optimizing the photovoltaic properties vital for solar cell applications.

  4. Photochemical reactivity of aqueous fullerene clusters: C{sub 60} versus C{sub 70}

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Wen-Che, E-mail: whou@mail.ncku.edu.tw; Huang, Shih-Hong

    2017-01-15

    Highlights: • Aqueous C{sub 60} and C{sub 70} clusters (nC{sub 60} and nC{sub 70}) formed through direct mixing with water adopted a face-centered cubic crystal structure. • The AQYs of nC{sub 60} were greater than those of nC{sub 70}. • Both nC{sub 60} and nC{sub 70} lost considerable organic carbon contents (>80%) after ∼8 months of outdoor sunlight irradiation. • The intermediate photoproducts of nC{sub 60} and nC{sub 70} exhibited an increased content of oxygen-containing functionalities. - Abstract: Over the past few years, there has been a strong interest in exploring the potential impact of fullerenes in the environment. Despite that both C{sub 60} and C{sub 70} have been detected in environmental matrices, the research on the impact of higher fullerenes, such as C{sub 70,} has been largely missing. This study evaluated and compared the phototransformation of aqueous C{sub 60} and C{sub 70} clusters (nC{sub 60} and nC{sub 70}) and their {sup 1}O{sub 2} production under sunlight and lamp light irradiation (315 nm, 360 nm and 420 nm). The nC{sub 60} and nC{sub 70} samples formed by direct mixing with water adopted a face-centered cubic (FCC) crystal structure. The apparent quantum yields (AQYs) of fullerene phototransformed were relatively constant over the examined wavelengths, while {sup 1}O{sub 2} production AQYs decreased with increased wavelengths. The long-term fate studies with outdoor sunlight indicated that both nC{sub 60} and nC{sub 70} lost considerable organic carbon contents (>80%) in water after ∼8 months of irradiation and that the intermediate photoproducts of nC{sub 60} and nC{sub 70} exhibited a progressively increased level of oxygen-containing functionalities. Overall, the study indicates that nC{sub 70} can be photochemically removed under sunlight conditions and that the photoreactivity of nC{sub 60} based on AQYs is greater than that of nC{sub 70}.

  5. Coordinate cis-[Cr(C2O4(pm(OH22]+ Cation as Molecular Biosensor of Pyruvate’s Protective Activity Against Hydrogen Peroxide Mediated Cytotoxity

    Directory of Open Access Journals (Sweden)

    Lech Chmurzyński

    2008-08-01

    Full Text Available In this paper instrumental methods of carbon dioxide (CO2 detection in biological material were compared. Using cis-[Cr(C2O4(pm(OH22]+ cation as a specific molecular biosensor and the stopped-flow technique the concentrations of CO2 released from the cell culture medium as one of final products of pyruvate decomposition caused by hydrogen peroxide were determined. To prove the usefulness of our method of CO2 assessment in the case of biological samples we investigated protective properties of exogenous pyruvate in cultured osteosarcoma 143B cells exposed to 1 mM hydrogen peroxide (H2O2 added directly to culture medium. Pyruvic acid is well known scavenger of H2O2 and, moreover, a molecule which is recognized as one of the major mediator of oxidative stress detected in many diseases and pathological situations like ischemiareperfusion states. The pyruvate's antioxidant activity is described as its rapid reaction with H2O2,which causes nonenzymatic decarboxylation of pyruvate and releases of CO2, water and acetate as final products. In this work for the first time we have correlated the concentration of CO2 dissolved in culture medium with pyruvate's oxidant-scavenging abilities. Moreover, the kinetics of the reaction between aqueous solution of CO2 and coordinate ion, cis-[Cr(C2O4(pm(OH22]+ was analysed. The results obtained enabled determination of the number of steps of the reaction studied. Based on the kinetic equations, rate constants were determined for each step.

  6. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, Jennifer E [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Raymond, Angela M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Winn, Louise M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada)

    2006-03-01

    In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

  7. A Lactobacillus plantarum strain isolated from kefir protects against intestinal infection with Yersinia enterocolitica O9 and modulates immunity in mice.

    Science.gov (United States)

    De Montijo-Prieto, Soumi; Moreno, Encarnación; Bergillos-Meca, Triana; Lasserrot, Agustín; Ruiz-López, María-Dolores; Ruiz-Bravo, Alfonso; Jiménez-Valera, María

    2015-10-01

    Lactobacillus plantarum C4, previously isolated from kefir and characterized as a potential probiotic strain, was tested for its protective and immunomodulatory capacity in a murine model of yersiniosis. The inoculation of BALB/c mice with a low pathogenicity serotype O9 strain of Yersinia enterocolitica results in a prolonged intestinal infection with colonization of Peyer's patches. Pretreatment with C4 was without effect on fecal excretion of yersiniae, but shortened the colonization of Peyer's patches. This protective effect was associated with pro-inflammatory status in the intestinal mucosa (TNF-α production in infected mice was increased by C4) and an increase in total IgA secretion. At a systemic level, C4 did not promote a pro-inflammatory response, although production of the immunoregulatory cytokine IFN-γ was enhanced. These findings suggest that L. plantarum C4 can increase resistance to intestinal infections through its immunomodulatory activity. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  8. 13C, 18O, and D Fractionation Effects in the Reactions of CH3OH Isotopologues with Cl andOH Radicals

    DEFF Research Database (Denmark)

    Feilberg, Karen; Gruber-Stadler, Margaret; Johnson, Matthew Stanley

    2008-01-01

    A relative rate experiment is carried out for six isotopologues of methanol and their reactions with OH and Cl radicals. The reaction rates of CH2DOH, CHD2OH, CD3OH, 13CH3OH, and CH3 18OH with Cl and OH radicals are measured by long-path FTIR spectroscopy relative to CH3OH at 298 ( 2 K and 1013...... with measured high-resolution infrared spectra as references. The relative reaction rates defined as R ) klight/kheavy are determined to be: kOH + CH3OH/kOH + 13CH3OH ) 1.031 ( 0.020, kOH + CH3OH/kOH + CH3 18OH ) 1.017 ( 0.012, kOH + CH3OH/kOH + CH2DOH ) 1.119 ( 0.045, kOH + CH3OH/kOH + CHD2OH ) 1.326 ( 0...... reactions with CH3OH were further investigated using canonical variational transition state theory with small curvature tunneling and compared to experimental measurements as well as to those observed in CH4 and several other substituted methane species. Udgivelsesdato: 16 August 2008...

  9. UV photolysis of 4-iodo-, 4-bromo-, and 4-chlorophenol: competition between C-Y (Y = halogen) and O-H bond fission.

    Science.gov (United States)

    Sage, Alan G; Oliver, Thomas A A; King, Graeme A; Murdock, Daniel; Harvey, Jeremy N; Ashfold, Michael N R

    2013-04-28

    The wavelength dependences of C-Y and O-H bond fission following ultraviolet photoexcitation of 4-halophenols (4-YPhOH) have been investigated using a combination of velocity map imaging, H Rydberg atom photofragment translational spectroscopy, and high level spin-orbit resolved electronic structure calculations, revealing a systematic evolution in fragmentation behaviour across the series Y = I, Br, Cl (and F). All undergo O-H bond fission following excitation at wavelengths λ ≲ 240 nm, on repulsive ((n∕π)σ∗) potential energy surfaces (PESs), yielding fast H atoms with mean kinetic energies ∼11,000 cm(-1). For Y = I and Br, this process occurs in competition with prompt C-I and C-Br bond cleavage on another (n∕π)σ∗ PES, but no Cl∕Cl∗ products unambiguously attributable to one photon induced C-Cl bond fission are observed from 4-ClPhOH. Differences in fragmentation behaviour at longer excitation wavelengths are more marked. Prompt C-I bond fission is observed following excitation of 4-IPhOH at all λ ≤ 330 nm; the wavelength dependent trends in I∕I∗ product branching ratio, kinetic energy release, and recoil anisotropy suggest that (with regard to C-I bond fission) 4-IPhOH behaves like a mildly perturbed iodobenzene. Br atoms are observed when exciting 4-BrPhOH at long wavelengths also, but their velocity distributions suggest that dissociation occurs after internal conversion to the ground state. O-H bond fission, by tunnelling (as in phenol), is observed only in the cases of 4-FPhOH and, more weakly, 4-ClPhOH. These observed differences in behaviour can be understood given due recognition of (i) the differences in the vertical excitation energies of the C-Y centred (n∕π)σ∗ potentials across the series Y = I bond strength, cf. that of the rival O-H bond, and (ii) the much increased spin-orbit coupling in, particularly, 4-IPhOH. The present results provide (another) reminder of the risks inherent in extrapolating photochemical

  10. Slow positron beam study of corrosion behavior of AM60B magnesium alloy in NaCl solution

    International Nuclear Information System (INIS)

    Yang, W.; Zhu, Z.J.; Wang, J.J.; Wu, Y.C.; Zhai, T.; Song, G.-L.

    2016-01-01

    Highlights: • Positron annihilation is a sensitive tool to characterize the corrosion layer. • The interfacial voids promoted the formation of Mg(OH) 2 corrosion layer. • Mg(OH) 2 precipitated during early corrosion stage provided a temporary protection. - Abstract: The corrosion behavior of super vacuum die-cast AM60B magnesium alloys immersed in a 5 wt% NaCl solution was investigated by slow positron beam technique, XRD, XPS, SEM and potentiodynamic polarization tests. The XRD and XPS results indicated that Mg(OH) 2 was main corrosion product in the salt solution. With prolonging the immersion time, a significant decrease of Doppler-broadened annihilation line-width parameter near the surface after corrosion was observed and interpreted that the pre-existing interfacial voids between oxide film and matrix might promote the formation of Mg(OH) 2 corrosion layer. Polarization tests found that Mg(OH) 2 could provide a temporary protection.

  11. PrPC displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrPC knockout mice

    International Nuclear Information System (INIS)

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

    2012-01-01

    Highlights: ► PrP C in solution acts as a radical scavenger. ► PrP C reduces hydrogen peroxide toxicity in astrocytes. ► Increase in ROS disrupted the cell cycle in the PrP C -knockout astrocytes. ► PrP C prevents the cell death independently of an SOD-like activity. -- Abstract: The PrP 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 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 C decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu 2+ /ascorbate/H 2 O 2 ), which was demonstrated by approximately 70% less DMPO/OH · . In cultured PrP C -knockout astrocytes from mice, the absence of PrP C caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3 h of H 2 O 2 treatment. This rapid increase in ROS disrupted the cell cycle in the PrP 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 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.

  12. Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice.

    Science.gov (United States)

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Park, Hae-Ran; Jung, Uhee; Jang, Jong Sik; Jo, Sung Kee

    2009-12-01

    The protective properties of an herbal preparation (HemoHIM) against intestinal damage were examined by evaluating its effects on jejunal crypt survival, morphological changes, and apoptosis in gamma-irradiated mice. The mice were whole-body irradiated with 12 Gy for the examination of jejunal crypt survival and any morphological changes and with 2 Gy for the detection of apoptosis and Ki-67 labeling. Irradiation was conducted using (60)Co gamma-rays. HemoHIM treatment was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hours pre-irradiation and 30 minutes post-irradiation or orally at a dosage of 250 mg/kg of body weight/day for 7 or 11 days before necropsy. The HemoHIM-treated group displayed a significant increase in survival of jejunal crypts, when compared to the irradiation controls. HemoHIM treatment decreased intestinal morphological changes such as crypt depth, villus height, mucosal length, and basal lamina length of 10 enterocytes after irradiation. Furthermore, the administration of HemoHIM protected intestinal cells from irradiation-induced apoptosis. These results suggested that HemoHIM may be therapeutically useful to reduce intestinal injury following irradiation.

  13. Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.

    Directory of Open Access Journals (Sweden)

    Danny Gauvreau

    Full Text Available BACKGROUND: Obesity is considered as a systemic chronic low grade inflammation characterized by increased serum pro-inflammatory proteins and accumulation of macrophages within white adipose tissue (WAT of obese patients. C5L2, a 7-transmembrane receptor, serves a dual function, binding the lipogenic hormone acylation stimulating protein (ASP, and C5a, involved in innate immunity. AIM: We evaluated the impact of C5L2 on macrophage infiltration in WAT of wildtype (Ctl and C5L2 knock-out (C5L2(-/- mice over 6, 12 and 24 weeks on a chow diet and moderate diet-induced obesity (DIO conditions. RESULTS: In Ctl mice, WAT C5L2 and C5a receptor mRNA increased (up to 10-fold both over time and with DIO. By contrast, in C5L2(-/-, there was no change in C5aR in WAT. C5L2(-/- mice displayed higher macrophage content in WAT, varying by time, fat depot and diet, associated with altered systemic and WAT cytokine patterns compared to Ctl mice. However, in all cases, the M1 (pro- vs M2 (anti-inflammatory macrophage proportion was unchanged but C5L2(-/- adipose tissue secretome appeared to be more chemoattractant. Moreover, C5L2(-/- mice have increased food intake, increased WAT, and altered WAT lipid gene expression, which is reflected systemically. Furthermore, C5L2(-/- mice have altered glucose/insulin metabolism, adiponectin and insulin signalling gene expression in WAT, which could contribute to development of insulin resistance. CONCLUSION: Disruption of C5L2 increases macrophage presence in WAT, contributing to obesity-associated pathologies, and further supports a dual role of complement in WAT. Understanding this effect of the complement system pathway could contribute to targeting treatment of obesity and its comorbidities.

  14. Modulation of macrophage activation state protects tissue from necrosis during critical limb ischemia in thrombospondin-1-deficient mice.

    Directory of Open Access Journals (Sweden)

    Nicolas Bréchot

    Full Text Available BACKGROUND: Macrophages, key regulators of healing/regeneration processes, strongly infiltrate ischemic tissues from patients suffering from critical limb ischemia (CLI. However pro-inflammatory markers correlate with disease progression and risk of amputation, suggesting that modulating macrophage activation state might be beneficial. We previously reported that thrombospondin-1 (TSP-1 is highly expressed in ischemic tissues during CLI in humans. TSP-1 is a matricellular protein that displays well-known angiostatic properties in cancer, and regulates inflammation in vivo and macrophages properties in vitro. We therefore sought to investigate its function in a mouse model of CLI. METHODS AND FINDINGS: Using a genetic model of tsp-1(-/- mice subjected to femoral artery excision, we report that tsp-1(-/- mice were clinically and histologically protected from necrosis compared to controls. Tissue protection was associated with increased postischemic angiogenesis and muscle regeneration. We next showed that macrophages present in ischemic tissues exhibited distinct phenotypes in tsp-1(-/- and wt mice. A strong reduction of necrotic myofibers phagocytosis was observed in tsp-1(-/- mice. We next demonstrated that phagocytosis of muscle cell debris is a potent pro-inflammatory signal for macrophages in vitro. Consistently with these findings, macrophages that infiltrated ischemic tissues exhibited a reduced postischemic pro-inflammatory activation state in tsp-1(-/- mice, characterized by a reduced Ly-6C expression and a less pro-inflammatory cytokine expression profile. Finally, we showed that monocyte depletion reversed clinical and histological protection from necrosis observed in tsp-1(-/- mice, thereby demonstrating that macrophages mediated tissue protection in these mice. CONCLUSION: This study defines targeting postischemic macrophage activation state as a new potential therapeutic approach to protect tissues from necrosis and promote tissue

  15. Protective effect of porphyran isolated from discolored nori (Porphyra yezoensis) on lipopolysaccharide-induced endotoxin shock in mice.

    Science.gov (United States)

    Nishiguchi, Tomoki; Cho, Kichul; Isaka, Shogo; Ueno, Mikinori; Jin, Jun-O; Yamaguchi, Kenichi; Kim, Daekyung; Oda, Tatsuya

    2016-12-01

    Porphyran, a sulfated polysaccharide, isolated from discolored nori (Porphyra yezoensis) (dc-porphyran) and one fraction (F1) purified from dc-porphyran by DEAE-chromatography showed the protective effects on LPS-induced endotoxin shock in mice. Intraperitoneal (i.p.) treatment with dc-porphyran or F1 (100mg/kg) 60min prior to i.p. injection of LPS (30mg/kg) completely protected mice from LPS lethality. At 10mg/kg concentration, F1 demonstrated more protection than dc-porphyran. Intravenous (i.v.) challenge of LPS, even at 20mg/kg, was more lethal than i.p. administration; i.v. injection of F1 (100mg/kg) with LPS significantly improved the survival rate. However, i.v. dc-porphyran (100mg/kg) produced an even lower survival rate than that of LPS alone. We examined pro-inflammatory mediators such as NO and TNF-α in serum. F1 significantly reduced the levels of these markers. Additionally, F1 significantly decreased the malondialdehyde level in the liver, a marker of oxidative stress, while dc-porphyran had almost no effect. Furthermore, F1 significantly decreased the production of TNF-α and NO in peritoneal exudate cells harvested from LPS-challenged mice, while dc-porphyran treatment showed a lesser decrease. Our results suggest that porphyran isolated from discolored nori, especially F1, is capable of suppressing LPS-induced endotoxin shock in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice.

    Directory of Open Access Journals (Sweden)

    Kim M Gerecke

    Full Text Available Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF, have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is dependent upon BDNF, we compared the neuroprotective effects of voluntary exercise in mice heterozygous for the BDNF gene (BDNF+/- with strain-matched wild-type (WT mice. Stereological estimates of SNpc DA neurons from WT mice allowed 90 days exercise via unrestricted running demonstrated complete protection against the MPTP-induced neurotoxicity. However, BDNF+/- mice allowed 90 days of unrestricted exercise were not protected from MPTP-induced SNpc DA neuron loss. Proteomic analysis comparing SN and striatum from 90 day exercised WT and BDNF+/- mice showed differential expression of proteins related to energy regulation, intracellular signaling and trafficking. These results suggest that a full genetic complement of BDNF is critical for the exercise-induced neuroprotection of SNpc DA neurons.

  17. Chimeric vaccine composed of viral peptide and mammalian heat-shock protein 60 peptide protects against West Nile virus challenge.

    Science.gov (United States)

    Gershoni-Yahalom, Orly; Landes, Shimon; Kleiman-Shoval, Smadar; Ben-Nathan, David; Kam, Michal; Lachmi, Bat-El; Khinich, Yevgeny; Simanov, Michael; Samina, Itzhak; Eitan, Anat; Cohen, Irun R; Rager-Zisman, Bracha; Porgador, Angel

    2010-08-01

    The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat-shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458-Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431-Ep15, a control conjugate, were not protected. The chimeric p458-Ep15 peptide induced WNV-specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon-gammain vitro. Challenge of chimeric peptide-immunized mice considerably enhanced WNV-specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV.

  18. Impurity and particle recycling reduction by boronization in JT-60U

    International Nuclear Information System (INIS)

    Higashijima, S.; Sugie, T.; Kubo, H.; Tsuji, S.; Shimada, M.; Asakura, N.; Hosogane, N.; Kawano, Y.; Nakamura, H.; Itami, K.; Sakasai, A.; Shimizu, K.; Ando, T.; Saidoh, M.

    1995-01-01

    In JT-60U boronization using decaborane was carried out. Boronization reduced the oxygen impurity in OH discharges and shortened the wall conditioning after the vacuum vessel vent and consequently enabled JT-60U to produce clean plasmas easily except for NB heated plasmas. After boronization, particle recycling was reduced drastically in OH and NB discharges. High confinement plasmas were obtained including high β p mode and H-mode discharges. In the latest boronization part of divertor plates were replaced with B 4 C coated tiles with a B 4 C thickness similar 300 μm. After introducing B 4 C divertor tiles, an explosive generation of boron particles from the tiles was observed. By the combined effects of boronization with decaborane and boron generation from B 4 C tiles, oxygen impurity was so low that oxygen line signals were reduced to noise levels after the latest boronization. On the other hand, boron burst from the B 4 C tiles restricted the operation of JT-60U. ((orig.))

  19. Mitochondrial Targeted Endonuclease III DNA Repair Enzyme Protects against Ventilator Induced Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Masahiro Hashizume

    2014-08-01

    Full Text Available The mitochondrial targeted DNA repair enzyme, 8-oxoguanine DNA glycosylase 1, was previously reported to protect against mitochondrial DNA (mtDNA damage and ventilator induced lung injury (VILI. In the present study we determined whether mitochondrial targeted endonuclease III (EndoIII which cleaves oxidized pyrimidines rather than purines from damaged DNA would also protect the lung. Minimal injury from 1 h ventilation at 40 cmH2O peak inflation pressure (PIP was reversed by EndoIII pretreatment. Moderate lung injury due to ventilation for 2 h at 40 cmH2O PIP produced a 25-fold increase in total extravascular albumin space, a 60% increase in W/D weight ratio, and marked increases in MIP-2 and IL-6. Oxidative mtDNA damage and decreases in the total tissue glutathione (GSH and the GSH/GSSH ratio also occurred. All of these indices of injury were attenuated by mitochondrial targeted EndoIII. Massive lung injury caused by 2 h ventilation at 50 cmH2O PIP was not attenuated by EndoIII pretreatment, but all untreated mice died prior to completing the two hour ventilation protocol, whereas all EndoIII-treated mice lived for the duration of ventilation. Thus, mitochondrial targeted DNA repair enzymes were protective against mild and moderate lung damage and they enhanced survival in the most severely injured group.

  20. Immunity to sporozoite-induced malaria infection in mice. I. The effect of immunization of T and B cell-deficient mice

    International Nuclear Information System (INIS)

    Chen, D.H.; Tigelaar, R.E.; Weinbaum, F.I.

    1977-01-01

    The cellular basis of immunity to sporozoites was investigated by examining the effect of immunization of T and B cell-deficient C57BL/6N x BALB/c AnN F 1 (BLCF 1 ) mice compared to immunocompetent controls. Immunization of T cell-deficient (ATX-BM-ATS) BLCF 1 mice with x-irradiated sporozoites did not result in the generation of protective immunity. The same immunization protocols protected all immunocompetent controls. In contrast, B cell-deficient (μ-suppressed) BLCF 1 mice were protected by immunization in the majority of cases. The absence of detectable serum circumsporozoite precipitins or sporozoite neutralizing activity in the μ-suppressed mice that resisted a sporozoite challenge suggests a minor role for these humoral factors in protection. These data demonstrate a preeminent role for T cells in the induction of protective immunity in BLCF 1 mice against a P. berghei sporozoite infection

  1. Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag.

    Science.gov (United States)

    Garrod, Tamsin J; Gargett, Tessa; Yu, Wenbo; Major, Lee; Burrell, Christopher J; Wesselingh, Steven; Suhrbier, Andreas; Grubor-Bauk, Branka; Gowans, Eric J

    2014-11-04

    Traditional vaccine strategies that induce antibody responses have failed to protect against HIV infection in clinical trials, and thus cell-mediated immunity is now an additional criterion. Recent clinical trials that aimed to induce strong T cell responses failed to do so. Therefore, to enhance induction of protective T cell responses, it is crucial that the optimum antigen combination is chosen. Limited research has been performed into the number of antigens selected for an HIV vaccine. This study aimed to compare DNA vaccines encoding either a single HIV antigen or a combination of two antigens, using intradermal vaccination of C57BL/6 mice. Immune assays were performed on splenocytes, and in vivo protection was examined by challenge with a chimeric virus, EcoHIV, able to infect mouse but not human leukocytes, at 10 days (short term) and 60 days (long term) post final vaccination. At 60 days there was significantly lower frequency of induced antigen-specific CD8(+) T cells in the spleens of pCMVgag-pol-vaccinated mice compared with mice which received pCMVgag only. Most importantly, short term viral control of EcoHIV was similar for pCMVgag and pCMVgag-pol-vaccinated mice at day 10, but only the pCMVgag-vaccinated significantly controlled EcoHIV at day 60 compared with pCMV-vaccinated mice, showing that control was reduced with the inclusion of the HIV pol gene. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Physical properties of CO-dark molecular gas with C+ and OH observations

    Science.gov (United States)

    Tang, Ningyu; Li, Di; Heiles, Carl E.; ISM Group in National Astronomical Observatories, CAS

    2017-01-01

    The lifecycle of interstellar medium (ISM) is critical for understanding galaxy evolution. The transition between atomic neutral medium and dense molecular gas, however, cannot be traced adequately by either HI or CO emission. Results from dust observations of Planck all-sky mission and gamma-ray observations of Energetic Gamma Ray Experiment Telescope (EGRET) have revealed the existence of “CO dark molecular gas” (DMG) - molecular gas without CO emission. The physical conditions of DMG including density, temperature, and molecular composition are basis of understanding the ISM evolution. We analyzed physical properties of DMG with HI-self absorption and C+ fine line emission at 158 um toward the lines of sight of Galactic Observations of Terahertz C+ (GOTC+). DMG clouds have a median excitation temperature of 56 K and median volume density of 230 cm2, showing intermediate physical properties between atomic and molecular gas. Sixteen DMG clouds with high visual extinction (AV>=2.7 mag) were found. CO abundance compared to H2 in these clouds is two orders magnitude smaller than the cannonical value in the Milky Way and cannot be explained by the chemical evolutionary model. They may be formed through the agglomeration of pre-existing molecular gas in the Milky Way. We have finished a follow up survey of OH 18 cm lines toward 51 sightlines of GOTC+ including sightlines with DMG clouds through Arecibo telescope. DMG may result in the absence of correlation between CO and OH column density. A possible correlation was found between C+ and OH column density in tracing DMG.

  3. Characteristics of infrared point sources associated with OH masers

    International Nuclear Information System (INIS)

    Mu Jimang; Esimbek, Jarken; Zhou Jianjun; Zhang Haijuan

    2010-01-01

    We collect 3249 OH maser sources from the literature published up to April 2007, and compile a new catalog of OH masers. We look for the exciting sources of these masers and their infrared properties from IRAS and MSX data, and make a statistical study. MSX sources associated with stellar 1612 MHz OH masers are located mainly above the blackbody line; this is caused by the dust absorption of stellar envelopes, especially in the MSX A band. The mid-IR sources associated with stellar OH masers are concentrated in a small region in an [A]-[D] vs. [A]-[E] diagram with a small fraction of contamination; this gives us a new criterion to search for new stellar OH masers and distinguish stellar masers from unknown types of OH masers. IR sources associated with 1612 MHz stellar OH masers show an expected result: the average flux of sources with F60 > F25 increases with increasing wavelength, while those with F60 F25.

  4. OH vibrational activation and decay dynamics of CH4-OH entrance channel complexes

    International Nuclear Information System (INIS)

    Wheeler, Martyn D.; Tsiouris, Maria; Lester, Marsha I.; Lendvay, Gyoergy

    2000-01-01

    Infrared spectroscopy has been utilized to examine the structure and vibrational decay dynamics of CH 4 -OH complexes that have been stabilized in the entrance channel to the CH 4 +OH hydrogen abstraction reaction. Rotationally resolved infrared spectra of the CH 4 -OH complexes have been obtained in the OH fundamental and overtone regions using an IR-UV (infrared-ultraviolet) double-resonance technique. Pure OH stretching bands have been identified at 3563.45(5) and 6961.98(4) cm-1 (origins), along with combination bands involving the simultaneous excitation of OH stretching and intermolecular bending motions. The infrared spectra exhibit extensive homogeneous broadening arising from the rapid decay of vibrationally activated CH 4 -OH complexes due to vibrational relaxation and/or reaction. Lifetimes of 38(5) and 25(3) ps for CH 4 -OH prepared with one and two quanta of OH excitation, respectively, have been extracted from the infrared spectra. The nascent distribution of the OH products from vibrational predissociation has been evaluated by ultraviolet probe laser-induced fluorescence measurements. The dominant inelastic decay channel involves the transfer of one quantum of OH stretch to the pentad of CH 4 vibrational states with energies near 3000 cm-1. The experimental findings are compared with full collision studies of vibrationally excited OH with CH 4 . In addition, ab initio electronic structure calculations have been carried out to elucidate the minimum energy configuration of the CH 4 -OH complex. The calculations predict a C 3v geometry with the hydrogen of OH pointing toward one of four equivalent faces of the CH 4 tetrahedron, consistent with the analysis of the experimental infrared spectra. (c) 2000 American Institute of Physics

  5. Withdrawal from Chronic Nicotine Administration Impairs Contextual Fear Conditioning in C57BL/6 Mice

    OpenAIRE

    Davis, Jennifer A.; James, John R.; Siegel, Steven J.; Gould, Thomas J.

    2005-01-01

    The effects of acute nicotine administration (0.09 mg/kg nicotine), chronic nicotine administration (6.3 mg/kg/d nicotine for 14 d), and withdrawal from chronic nicotine administration on fear conditioning in C57BL/6 mice were examined. Mice were trained using two coterminating conditioned stimulus (30 s; 85 dB white noise)– unconditioned stimulus (2 s; 0.57 mA foot shock) pairings and tested 24 h later for contextual and cued fear conditioning. Acute nicotine administration enhanced contextu...

  6. Protective effect of Hippophae rhamnoides leaf extract on gamma irradiation induced clastogenecity in mice

    International Nuclear Information System (INIS)

    Tyagi, Anuradha; Prasad, Jagdish; Bala, Madhu

    2012-01-01

    Hippophae rhamnoides (sea buckthorn) is a plant belonging to Elaeagnaceae family and is distributed worldwide. It has variety of uses from nutritional food to pharmacological application. The study was aimed to analyse the extract from Hippophae rhamnoides leaves for their possible protective effects against the whole body 60 Co-a-irradiation. The study was performed on six groups of male mice i.e. untreated group, H. rhamnoides extract group, irradiated (2Gy), irradiated (3Gy), H. rhamnoides and irradiated (2Gy) and H. rhamnoides and irradiated (3Gy). In each group micronucleus test was performed utilising bone marrow and peripheral blood. The mice were sacrificed 30 hrs after treatment and analysed for the presence of micronuclei. In the present study, there was no significant increase in the frequency of either micronucleated polychromatic erythrocytes (MNPCEs) or normochromatic erythrocytes (NCE) in H. rhamnoides extract treated group over the negative control group of animals, indicating its non-clastogenic and non-toxic activity in the erythropoietic system. H. rhamnoides extract showed good anti-clastogenic activity against the a-irradiation induced clastogenecity in both the tissues i.e. bone marrow and peripheral blood by reducing the frequency of micronuclei. Also the administration of H. rhamnoides extract along with irradiation was slightly able to increase the frequency of PCE in bone marrow as well as in peripheral blood in comparison to the irradiated group (2Gy and 3Gy) indicating its ability to reduce the toxicity caused by irradiation in the erythropoietic system. Thus the results indicate the non-clastogenic effect of H. rhamnoides leaf extract and significant protective activity against 60 Co-a-irradiation suggesting its pharmacological significance for development of radioprotector. (author)

  7. 羟基多溴联苯醚(3'-OH-BDE-7)的大鼠体外肝代谢研究%IN VITRO METABOLISM STUDY OF 3'-OH-2,4-diBDE-7 IN RAT LIVER S9 FRACTION

    Institute of Scientific and Technical Information of China (English)

    赖永权; 陈学国; 蔡宗苇

    2011-01-01

    本文利用液相色谱-质谱联用技术,建立了羟基多溴联苯醚3'-OH-BDE-7在S.D.大鼠肝匀浆中的体外代谢研究方法.实验结果表明,3'-OH-BDE-7的主要代谢产物为2,4-二溴苯酚和二羟基多溴联苯醚(diOHPBDEs),并且其在温孵30min,时代谢转化率为90%.3'-OH-BDE-7的代谢研究为其它羟基多溴联苯醚的相应研究提供了信息,其代谢行为也对更好地理解PBDEs和OH-PBDEs的毒理和动力学具有一定意义.%Polybrominated diphenyl ethers (PBDEs) are an important class of brominated flame retardants that have been widely used in industrial and consumer products. PBDEs have become worldwide environmental pollutants because of the bioaccumulation, long-distance transportation and potential biological toxicities.Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are a relatively new group of phenolic compounds that have attracted particular interest due to their endocrine disrupting potency. OH-PBDEs are similar to PBDEs in chemical structure, but were reported to show stronger biological effects. In this study, we investigated in vitro metabolic behaviors of selected 3'-OH-BDE-7 in rat liver S9 fraction. The obtained results indicated that 2,4-dibromophenol and diOH-PBDEs were the major metabolites of OH-PBDEs. It's worth noting that the hydroquinone like metabolites might pose a potential health risk to human and wild animals.

  8. First insights into the protective effects of a recombinant swinepox virus expressing truncated MRP of Streptococcus suis type 2 in mice.

    Science.gov (United States)

    Huang, Dongyan; Zhu, Haodan; Lin, Huixing; Xu, Jiarong; Lu, Chengping

    2012-01-01

    To explore the potential of the swinepox virus (SPV) as vector for Streptococcus suis vaccines, a vector system was developed for the construction of a recombinant SPV carrying bacterial genes. Using this system, a recombinant virus expressing truncated muramidase-released protein (MRP) of S. suis type 2 (SS2), designated rSPV-MRP, was produced and identified by PCR, western blotting and immunofluorescence assays. The rSPV-MRP was found to be only slightly attenuated in PK-15 cells, when compared with the wild-type virus. After immunization intramuscularly with rSPV-MRP, SS2 inactive vaccine (positive control), wild-type SPV (negative control) and PBS (blank control) respectively, all CD1 mice were challenged with a lethal dose or a sublethal dose of SS2 highly virulent strain ZY05719. While SS2 inactive vaccine protected all mice, immunization with rSPV-MRP resulted in 60% survival and protected mice against a lethal dose of the highly virulent SS2 strain, compared with the negative control (P MRP had a significantly reduced bacterial burden in all organs examined, compared to negative controls and blank controls (P MRP-vaccinated group were significantly higher (P MRP provided mice with protection from systemic SS2 infection. If SPV recombinants have the potential as S. suis vaccines for the use in pigs has to be evaluated in further studies.

  9. Protective effects of pseudoginsenoside-F11 on methamphetamine-induced neurotoxicity in mice.

    Science.gov (United States)

    Wu, Chun Fu; Liu, Yan Li; Song, Ming; Liu, Wen; Wang, Jin Hui; Li, Xian; Yang, Jing Yu

    2003-08-01

    In the present study, pseudoginsenoside-F(11) (PF(11)), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10 mg/kg four times at 2-h intervals, and PF(11) was orally administered at the doses of 4 and 8 mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF(11) did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light-dark box task. In the forced swimming task, PF(11) significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF(11) greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF(11) significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3,4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF(11) could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF(11) is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.

  10. Radioprotective properties of tocopherol succinate against ionizing radiation in mice

    International Nuclear Information System (INIS)

    Singh, V.K.; Singh, P.K.; Wise, S.Y.; Posarac, A.; Fatanmi, O.O.

    2013-01-01

    Threats of nuclear and other radiologic exposures have been increasing but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. In prior publications we have demonstrated the efficacy of tocopherol succinate (TS) as a promising radiation countermeasure with the potential to protect against lethal doses of ionizing radiation exposure. The aim of this study was to gain further insight regarding how TS protects mice against a lethal dose of radiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of TS, and 24 h later exposed to 60 Co γ-radiation. Intestinal tissues or spleen/thymus were harvested after irradiation and analyzed for CD68-positive inflammatory cells and apoptotic cells by immunostaining of jejunal cross-sections. Comet assay was used to analyze DNA damage in various tissues. Phospho-histone H3 (pH3) and the proliferating cell nuclear antigen (PCNA) were used as mitotic markers for immunostaining jejunal cross-sections. We observed that injecting TS significantly decreased the number of CD68-positive cells, DNA damage and apoptotic cells (bcl-associated X protein (BAX), caspase 3 and cleaved poly (ADP-ribose) polymerase-positive cells) as judged by various apoptotic pathway markers. TS treatment also increased proliferating cells in irradiated mice. Results of this study further support our contention that TS protects mice against lethal doses of ionizing radiation by inhibiting radiation-induced apoptosis and DNA damage while enhancing cell proliferation. (author)

  11. Degradability of aged aquatic suspensions of C60 nanoparticles

    DEFF Research Database (Denmark)

    Hartmann, B.; Buendia, Inmaculada M.; Baun, Anders

    2011-01-01

    While studies of the potential human and environmental effects of C60 and its derivatives are emerging in the scientific literature, the environmental fate of C60 is still largely unknown. In this study, aged aqueous suspensions of C60 (nC60) were investigated in the respirometric OECD test...... for ready biodegradability. Two suspensions of nC60 were prepared by stirring and aged under indirect exposure to sunlight for 36 months, which resulted in relatively stable suspensions with a dark-brown colour. The suspended nC60 could not be extracted into toluene and indicating that the particles were...... no longer present as underivatised nC60 but had undergone a transformation. TEM images and particle tracking analysis showed that the suspension consisted of particle aggregates with a size of 156 nm (SD=54nm) and 139nm (Sd=49), respectively, but also contained smaller aggregates. Samples of the nC60...

  12. Immune cells from SR/CR mice induce the regression of established tumors in BALB/c and C57BL/6 mice

    DEFF Research Database (Denmark)

    Koch, Janne; Hau, Jann; Pravsgaard Christensen, Jan

    2013-01-01

    of resistance to EL-4 lymphoma cells and J774A.1 monocyte-macrophage cancer cells. The cancer resistance against S180 sarcoma cells could be transferred to susceptible non-resistant BALB/c mice as well as C57BL/6 mice after depletion of both CD4+/CD8+ leukocytes and B-cells from SR/CR mice. In the responding...

  13. Investigation on the Effect of Green Inhibitors for Corrosion Protection of Mild Steel in 1 M NaOH Solution

    Directory of Open Access Journals (Sweden)

    Premjith Jayakumar Ramakrishnan

    2014-01-01

    Full Text Available Alkaline corrosion is one of the main issues faced by the industries. The main chemicals abundantly used in industries are NaOH, H3PO4, HCl, and H2SO4. Corrosion control of metals has technical, economical, environmental, and aesthetical importance. The use of inhibitors is one of the best options to protect metals and alloys against corrosion. The corrosion protection of mild steel in 1 M NaOH solution by mix of Henna/Zeolite powder was studied at different temperatures by weight loss technique. Adsorption, activation, and statistical studies were addressed in this work. Adsorption studies showed that inhibitor adsorbed on metal surface according to Langmuir isotherm. Surface studies were performed by using UV-spectra and SEM. The adsorption of inhibitor on the steel surface was found to obey Langmuir’s adsorption isotherm. The inhibition efficiency increased with increasing concentration of the inhibitor in NaOH medium. Inhibition mechanism is deduced from the concentration and temperature dependence of the inhibition efficiency, Langmuir’s adsorption isotherm, SEM, and UV spectroscopic results.

  14. Moderate beer consumption does not change early or mature atherosclerosis in mice

    Directory of Open Access Journals (Sweden)

    Blanco-Vaca Francisco

    2004-01-01

    Full Text Available Abstract Background Although the consumption of wine in particular has been associated with a lower risk of atherothrombotic cardiovascular disease, systematic reviews differ as to the relative protective effect of beer, wine and spirits. Two previous studies showed that red wine reduces fatty streak formation (early atherosclerosis but not mature atherosclerosis in apolipoprotein (apo E-deficient (apoE-/- mice. Aim of the study To determine whether a moderate beer intake would affect early and mature atherosclerotic lesion formation using control C57BL/6 and apoE-/- mice, respectively, as models. Methods Control C57BL/6 and apoE-/- mice were randomized to receive either water, ethanol, mild beer, dark beer or ethanol-free beer. The level of beer was designed to approximate the alcohol intake currently believed to be beneficial in reducing human vascular risk. Control C57BL/6 mice were fed a Western diet for 24 weeks, and apoE-/- mice a chow diet for 12 weeks. At the end of the trial period, mice were euthanized and atherosclerotic lesions quantified. Plasma lipid concentrations were also measured. Results The amount of atherosclerosis and average number of lesions in the proximal aortic region did not differ among groups in control C57BL/6 mice (p = 0.32 and p = 0.29, respectively and apoE-/- mice (p = 0.19 and p = 0.59, respectively. No consistent differences were observed in plasma lipid and lipoprotein concentrations among water, ethanol and beer groups. Conclusions Moderate beer consumption does not change the development of early or mature atherosclerosis in mice. Our findings do not support the hypothesis of an anti-atherogenic effect of beer. Other potential protective actions of moderate beer consumption such as plaque stabilization, a reduction in plaque intrinsic thrombogenicity, or a reduction in the systemic propensity to thrombosis, remain to be studied.

  15. Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice.

    Science.gov (United States)

    Benneyworth, Michael A; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine

    2005-06-01

    The drug discrimination procedure is the most frequently used in vivo model of hallucinogen activity. Historically, most drug discrimination studies have been conducted in the rat. With the development of genetically modified mice, a powerful new tool has become available for investigating the mechanisms of drug-induced behavior. The current paper is part of an ongoing effort to determine the utility of the drug discrimination technique for evaluating hallucinogenic drugs in mice. To establish the training procedures and characterize the stimulus properties of (+)lysergic acid diethylamide (LSD) in mice. Using a two-lever drug discrimination procedure, C57Bl/6J mice were trained to discriminate 0.45 mg/kg LSD vs saline on a VI30 sec schedule of reinforcement, with vanilla-flavored Ensure serving as the reinforcer. As in rats, acquisition was orderly, but the training dose was nearly five-fold higher for mice than rats. LSD lever selection was dose-dependent. Time-course studies revealed a rapid loss of the LSD stimulus effects. The 5-HT(2A/2C) receptor agonist, 2,5-dimethoxy-4-bromoamphetamine [(-)DOB] (1.0 mg/kg), substituted fully for LSD and the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) (1.6 mg/kg), substituted partially for LSD. Pretreatment with the 5-HT(2A) receptor-selective antagonist, MDL 100907, or the 5-HT(1A)-selective antagonist WAY 100635, showed that each antagonist only partially blocked LSD discrimination. Substitution of 1.0 mg/kg (-)DOB for LSD was fully blocked by pretreatment with MDL 100907 but unaltered by WAY 100635 pretreatment. These data suggest that in mice the stimulus effects of LSD have both a 5-HT(2A) receptor and a 5-HT(1A) receptor component.

  16. 40 CFR 60.73 - Emission monitoring.

    Science.gov (United States)

    2010-07-01

    ... (NO2). The span value shall be 500 ppm of NO2. Method 7 shall be used for the performance evaluations... performance test under § 60.8 or any continuous monitoring system performance evaluation under § 60.13(c). (c....73 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED...

  17. 10 CFR 73.60 - Additional requirements for physical protection at nonpower reactors.

    Science.gov (United States)

    2010-01-01

    ... nonpower reactors. 73.60 Section 73.60 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION... requirements for physical protection at nonpower reactors. Each nonpower reactor licensee who, pursuant to the... perform their duties. (6) Prior to entry into a material access area, packages shall be searched for...

  18. Dicty_cDB: FC-BS24 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BS24 (Link to dictyBase) - - - Contig-U16209-1 FC-BS24Z (Li...nk to Original site) - - FC-BS24Z 721 - - - - Show FC-BS24 Library FC (Link to library) Clone ID FC-BS24 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16209-1 Original site URL http://dict...nce. 52 9e-12 4 BQ096846 |BQ096846.1 IfHdk00487 Ictalurus furcatus head kidney cDNA library Ict...N SA ;, mRNA sequence. 44 1e-10 4 BM438323 |BM438323.1 IpLvr01076 Liver cDNA library Ictalurus punctatus cDN

  19. The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice.

    Science.gov (United States)

    Al Mansouri, Shamma; Ojha, Shreesh; Al Maamari, Elyazia; Al Ameri, Mouza; Nurulain, Syed M; Bahi, Amine

    2014-09-01

    Several recent studies have suggested that brain CB2 cannabinoid receptors play a major role in alcohol reward. In fact, the implication of cannabinoid neurotransmission in the reinforcing effects of ethanol (EtOH) is becoming increasingly evident. The CB2 receptor agonist, β-caryophyllene (BCP) was used to investigate the role of the CB2 receptors in mediating alcohol intake and ethanol-induced conditioned place preference (EtOH-CPP) and sensitivity in mice. The effect of BCP on alcohol intake was evaluated using the standard two-bottle choice drinking method. The mice were presented with increasing EtOH concentrations and its consumption was measured daily. Consumption of saccharin and quinine solutions was measured following the EtOH preference tests. Finally, the effect of BCP on alcohol reward and sensitivity was tested using an unbiased EtOH-CPP and loss of righting-reflex (LORR) procedures, respectively. BCP dose-dependently decreased alcohol consumption and preference. Additionally, BCP-injected mice did not show any difference from vehicle mice in total fluid intake in a 24-hour paradigm nor in their intake of graded concentrations of saccharin or quinine, suggesting that the CB2 receptor activation did not alter taste function. More importantly, BCP inhibited EtOH-CPP acquisition and exacerbated LORR duration. Interestingly, these effects were abrogated when mice were pre-injected with a selective CB2 receptor antagonist, AM630. Overall, the CB2 receptor system appears to be involved in alcohol dependence and sensitivity and may represent a potential pharmacological target for the treatment of alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Degradability of aged aquatic suspensions of C60 nanoparticles

    DEFF Research Database (Denmark)

    Hartmann, Nanna Isabella Bloch; Buendia, Inmaculada M.; Bak, Jimmy

    2011-01-01

    In this study, aged aqueous suspensions of C(60) (nC(60)) were investigated in the respirometric OECD test for ready biodegradability. Two suspensions of nC(60) were prepared by stirring and aged under indirect exposure to sunlight for 36 months. ATR-FTIR analyses confirmed the presence of C(60)-...

  1. Critical role of IFN-gamma in CFA-mediated protection of NOD mice from diabetes development.

    Science.gov (United States)

    Mori, Yoshiko; Kodaka, Tetsuro; Kato, Takako; Kanagawa, Edith M; Kanagawa, Osami

    2009-11-01

    IFN-gamma signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN-gamma signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN-gamma receptor-deficient (IFN-gammaR(-/-)) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN-gamma is necessary for the CFA-mediated protection of NOD mice from diabetes. There is no difference in the T(h)1/T(h)17 balance between IFN-gammaR(-/-) NOD and wild-type NOD mice. There is also no difference in the total numbers and percentages of regulatory T (Treg) cells in the lymph node CD4(+) T-cell populations between IFN-gammaR(-/-) NOD and wild-type NOD mice. However, pathogenic T cells lacking IFN-gammaR are resistant to the suppressive effect of Treg cells, both in vivo and in vitro. Therefore, it is likely that CFA-mediated protection against diabetes development depends on a change in the balance between Treg cells and pathogenic T cells, and IFN-gamma signaling seems to control the susceptibility of pathogenic T cells to the inhibitory activity of Treg cells.

  2. Diffraction symmetry in crystalline, close-packed C60

    International Nuclear Information System (INIS)

    Fleming, R.M.; Siegrist, T.; Marsh, P.M.; Hessen, B.; Kortan, A.R.; Murphy, D.W.; Haddon, R.C.; Tycko, R.; Dabbagh, G.; Mujsce, A.M.

    1991-01-01

    The authors have grown crystals of the carbon structure C 60 by sublimation. In contrast to solution-grown crystals, the sublimed crystals have long range order with no evidence of solvent inclusions. Sublimed C 60 forms three dimensional, faceted crystals with a close-packed, face centered cubic unit cell. The authors have refined a crystal structure using the soccer ball model of the C 60 molecule. The results from this paper indicate that the C 60 molecule has the expected spherical shape, however the data are not sufficiently accurate to unambiguously determine atomic positions

  3. Direct measurements of OH and other product yields from the HO2  + CH3C(OO2 reaction

    Directory of Open Access Journals (Sweden)

    F. A. F. Winiberg

    2016-03-01

    Full Text Available The reaction CH3C(OO2 + HO2  →  CH3C(OOOH + O2 (Reaction R5a, CH3C(OOH + O3 (Reaction R5b, CH3 + CO2 + OH + O2 (Reaction R5c was studied in a series of experiments conducted at 1000 mbar and (293 ± 2 K in the HIRAC simulation chamber. For the first time, products, (CH3C(OOOH, CH3C(OOH, O3 and OH from all three branching pathways of the reaction have been detected directly and simultaneously. Measurements of radical precursors (CH3OH, CH3CHO, HO2 and some secondary products HCHO and HCOOH further constrained the system. Fitting a comprehensive model to the experimental data, obtained over a range of conditions, determined the branching ratios α(R5a  =  0.37 ± 0.10, α(R5b =  0.12 ± 0.04 and α(R5c =  0.51 ± 0.12 (errors at 2σ level. Improved measurement/model agreement was achieved using k(R5  =  (2.4 ± 0.4  ×  10−11 cm3 molecule−1 s−1, which is within the large uncertainty of the current IUPAC and JPL recommended rate coefficients for the title reaction. The rate coefficient and branching ratios are in good agreement with a recent study performed by Groß et al. (2014b; taken together, these two studies show that the rate of OH regeneration through Reaction (R5 is more rapid than previously thought. GEOS-Chem has been used to assess the implications of the revised rate coefficients and branching ratios; the modelling shows an enhancement of up to 5 % in OH concentrations in tropical rainforest areas and increases of up to 10 % at altitudes of 6–8 km above the equator, compared to calculations based on the IUPAC recommended rate coefficient and yield. The enhanced rate of acetylperoxy consumption significantly reduces PAN in remote regions (up to 30 % with commensurate reductions in background NOx.

  4. Brucella abortus mutants lacking ATP-binding cassette transporter proteins are highly attenuated in virulence and confer protective immunity against virulent B. abortus challenge in BALB/c mice.

    Science.gov (United States)

    Truong, Quang Lam; Cho, Youngjae; Park, Soyeon; Park, Bo-Kyoung; Hahn, Tae-Wook

    2016-06-01

    Brucella abortus RB51 is an attenuated vaccine strain that has been most frequently used for bovine brucellosis. Although it is known to provide good protection in cattle, it still has some drawbacks including resistance to rifampicin, residual virulence and pathogenicity in humans. Thus, there has been a continuous interest on new safe and effective bovine vaccine candidates. In the present study, we have constructed unmarked mutants by deleting singly cydD and cydC genes, which encode ATP-binding cassette transporter proteins, from the chromosome of the virulent Brucella abortus isolate from Korean cow (referred to as IVK15). Both IVK15ΔcydD and ΔcydC mutants showed increased sensitivity to metal ions, hydrogen peroxide and acidic pH, which are mimic to intracellular environment during host infection. Additionally, the mutants exhibited a significant growth defect in RAW264.7 cells and greatly attenuated in mice. Vaccination of mice with either IVK15ΔcydC or IVK15ΔcydD mutant could elicit an anti-Brucella specific immunoglobulin G (IgG) and IgG subclass responses as well as enhance the secretion of interferon-gamma, and provided better protection against challenge with B. abortus strain 2308 than with the commercial B. abortus strain RB51 vaccine. Collectively, these results suggest that both IVK15ΔcydC and IVK15ΔcydD mutants could be an attenuated vaccine candidate against B. abortus. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Two related lithium calixarene complexes, [p-tert-butylcalix[4]arene(OMe)(OH)2(OLi)](2).4MeCN and {p-tert-butylcalix[4]arene(OH)2(OLi)[OLi(NCMe)2]}(2).8MeCN, determined using synchrotron radiation.

    Science.gov (United States)

    Lee, Darren S; Elsegood, Mark R J; Redshaw, Carl; Zhan, Shuzhong

    2009-08-01

    The crystal structures of acetonitrile solvates of two related lithium calixarene complexes have been determined by low-temperature single-crystal X-ray diffraction using synchrotron radiation. Bis(mu-5,11,17,23-tetra-tert-butyl-26,28-dihydroxy-25-methoxy-27-oxidocalix[4]arene)dilithium(I) acetonitrile tetrasolvate, [Li2(C45H57O4)2].4C2H3N or [p-tert-butylcalix[4]arene(OMe)(OH)2(OLi)](2).4MeCN, (I), crystallizes with the complex across a centre of symmetry and with four molecules of unbound acetonitrile of crystallization per complex. Tetraacetonitrilebis(mu-5,11,17,23-tetra-tert-butyl-26,28-dihydroxy-25,27-dioxidocalix[4]arene)tetralithium(I) acetonitrile octasolvate, [Li4(C44H54O4)2(C2H3N)4].8C2H3N or {p-tert-butylcalix[4]arene(OH)2(OLi)[OLi(NCMe)2]}(2).8MeCN, (II), also crystallizes with the complex lying across a centre of symmetry and contains eight molecules of unbound acetonitrile per complex plus four more directly bound to two of the lithium ions, two on each ion. The cores of both complexes are partially supported by O-H...O hydrogen bonds. The methoxy methyl groups in (I) prevent the binding of any more than two Li+ ions, while the corresponding two O-atom sites in (II) bind an extra Li(+) ion each, making four in total. The calixarene cone adopts an undistorted cone conformation in (I), but an elliptical one in (II).

  6. Chemical potential pinning due to equilibrium electron transfer at metal/C{sub 60}-doped polymer interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Heller, C.M.; Campbell, I.H.; Smith, D.L. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Barashkov, N.N.; Ferraris, J.P. [The University of Texas at Dallas, Richardson, Texas 75080 (United States)

    1997-04-01

    We report electroabsorption measurements of the built-in electrostatic potential in metal/C{sub 60}-doped polymer/metal structures to investigate chemical potential pinning due to equilibrium electron transfer from a metal contact to the electron acceptor energy level of C{sub 60} molecules in the polymer film. The built-in potentials of a series of structures employing thin films of both undoped and C{sub 60}-doped poly[2-methoxy, 5-(2{sup {prime}}-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) were measured. For undoped MEH-PPV, which has an energy gap of about 2.4 eV, the maximum built-in potential is about 2.1 eV, whereas for C{sub 60}-doped MEH-PPV the maximum built-in potential decreases to 1.5 eV. Electron transfer to the C{sub 60} molecules close to the metal interface pins the chemical potential of the metal contact near the electron acceptor energy level of C{sub 60} and decreases the built-in potential of the structure. From the systematic dependence of the built-in potential on the metal work function we find that the electron acceptor energy level of C{sub 60} in MEH-PPV is about 1.7 eV above the hole polaron energy level of MEH-PPV. {copyright} {ital 1997 American Institute of Physics.}

  7. Electronic structure and static dipole polarizability of C{sub 60}-C{sub 240}

    Energy Technology Data Exchange (ETDEWEB)

    Zope, Rajendra R [Department of Physics, University of Texas at El Paso, El Paso, TX 79958 (United States)

    2008-04-28

    The electronic structure of C{sub 60}-C{sub 240} and its first-order response to a static electric field is studied by an all-electron density functional theory calculation using large polarized Gaussian basis sets. Our results show that the outer C{sub 240} shell almost completely shields the inner C{sub 60} as inferred from the practically identical values of dipole polarizability of the C{sub 60}-C{sub 240} onion (449 A{sup 3}) and that of the isolated C{sub 240} fullerene (441 A{sup 3}). The C{sub 60}-C{sub 240} is thus a near-perfect Faraday cage.

  8. Design of Highly Sensitive C2H5OH Sensors Using Self-Assembled ZnO Nanostructures

    Directory of Open Access Journals (Sweden)

    Jong-Heun Lee

    2011-10-01

    Full Text Available Various ZnO nanostructures such as porous nanorods and two hierarchical structures consisting of porous nanosheets or crystalline nanorods were prepared by the reaction of mixtures of oleic-acid-dissolved ethanol solutions and aqueous dissolved Zn-precursor solutions in the presence of NaOH. All three ZnO nanostructures showed sensitive and selective detection of C2H5OH. In particular, ultra-high responses (Ra/Rg = ~1,200, Ra: resistance in air, Rg: resistance in gas to 100 ppm C2H5OH was attained using porous nanorods and hierarchical structures assembled from porous nanosheets, which is one of the highest values reported in the literature. The gas response and linearity of gas sensors were discussed in relation to the size, surface area, and porosity of the nanostructures.

  9. Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation.

    Science.gov (United States)

    Imai, Rika; Asai, Kanae; Hanai, Jun-ichi; Takenaka, Masaru

    2015-07-01

    Glia Maturation Factor-β (GMF), a brain specific protein, is induced by proteinuria in renal tubules. Ectopic GMF overexpression causes apoptosisin vitro via cellular vulnerability to oxidative stress. In order to examine the roles of GMF in non-brain tissue, we constructed transgenic mice overexpressing GMF (GMF-TG). The GMF-TG mice exhibited appearance phenotypes associated with premature aging. The GMF-TG mice also demonstrated short lifespans and reduced hair regrowth, suggesting an accelerated aging process. The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies. Importantly, we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice. The GMF-TG mice showed accelerated aging in the kidney, compared with wild-type mice, showing increased TGF-β1, CTGF gene and serum creatinine. The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks. In conclusion, we propose that GMF-TG mice might be a novel mouse model of accelerated aging, due to the abnormal lamin A.

  10. Experimental measurements of U24Py nanocluster behavior in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Flynn, Shannon L.; Szymanowski, Jennifer E.S.; Fein, Jeremy B. [Univ. of Notre Dame, IN (United States). Department of Civil and Environmental Engineering and Earth Sciences; Dembowski, Mateusz [Univ. of Notre Dame, IN (United States). Department of Chemistry and Biochemistry; Burns, Peter C. [Univ. of Notre Dame, IN (United States). Department of Civil and Environmental Engineering and Earth Sciences; Univ. of Notre Dame, IN (United States). Department of Chemistry and Biochemistry

    2016-07-01

    Uranyl peroxide nanoclusters may impact the mobility and partitioning of uranium at contaminated sites and could be used in the isolation of uranium during the reprocessing of nuclear waste. Their behavior in aqueous systems must be better understood to predict the environmental fate of uranyl peroxide nanoclusters and for their use in engineered systems. The aqueous stability of only one uranyl peroxide nanocluster, U60 (K{sub 16}Li{sub 44}[UO{sub 2}(O{sub 2})OH]{sub 60}), has been studied to date [Flynn, S. L., Szymanowski, J. E. S., Gao, Y., Liu, T., Burns, P. C., Fein, J. B.: Experimental measurements of U60 nanocluster stability in aqueous solution. Geochemica et Cosmochimica Acta 156, 94-105 (2015)]. In this study, we measured the aqueous stability of a second uranyl peroxide nanocluster, U24Py (Na{sub 30}[(UO{sub 2}){sub 24}(O{sub 2}){sub 24}(HP{sub 2}O{sub 7}){sub 6}(H{sub 2}P{sub 2}O{sub 7}){sub 6}]), in batch systems as a function of time, pH, and nanocluster concentration, and then compared the aqueous behavior of U24Py to U60 to determine whether the size and morphology differences result in differences in their aqueous behaviors. Systems containing U24Py nanoclusters took over 30 days to achieve steady-state concentrations of monomeric U, Na, and P, illustrating slower reaction kinetics than parallel U60 systems. Furthermore, U24Py exhibited lower stability in solution than U60, with an average of 72% of the total mass in each nanocluster suspension being associated with the U24Py nanocluster, whereas 97% was associated with the U60 nanocluster in parallel experiments [Flynn, S. L., Szymanowski, J. E. S., Gao, Y., Liu, T., Burns, P. C., Fein, J. B.: Experimental measurements of U60 nanocluster stability in aqueous solution. Geochemica et Cosmochimica Acta 156, 94-105 (2015)]. The measurements from the batch experiments were used to calculate ion activity product (IAP) values for the reaction between the U24Py nanocluster and its constituent monomeric

  11. Corticosterone facilitates extinction of fear memory in BALB/c mice but strengthens cue related fear in C57BL/6 mice.

    Science.gov (United States)

    Brinks, V; de Kloet, E R; Oitzl, M S

    2009-04-01

    Corticosterone, the naturally occurring glucocorticoid of rodents is secreted in response to stressors and is known for its facilitating and detrimental effects on emotional learning and memory. The large variability in the action of corticosterone on processing of emotional memories is postulated to depend on genetic background and the spatio-temporal domain in which the hormone operates. To address this hypothesis, mice of two strains with distinct corticosterone secretory patterns and behavioural phenotype (BALB/c and C57BL/6J) were treated with corticosterone (250 microg/kg, i.p.), either 5 min before or directly after acquisition in a fear conditioning task. As the paradigm allowed assessing in one experimental procedure both context- and cue-related fear behaviour, we were able to detect generalization and specificity of fear. BALB/c showed generalized strong fear memory, while C57BL/6J mice discriminated between freezing during context- and cue episodes. Corticosterone had opposite effects on fear memory depending on the strain and time of injection. Corticosterone after acquisition did not affect C57BL/6J mice, but destabilized consolidation and facilitated extinction in BALB/c. Corticosterone 5 min before acquisition strengthened stress-associated signals: BALB/c no longer showed lower fear memory, while C57BL/6J mice displayed increased fear memory and impaired extinction in cue episodes. We propose that corticosterone-induced facilitation of fear memory in C57BL/6J mice can be used to study the development of fear memories, corticosterone administration in BALB/c mice presents a model to examine treatment. We conclude that genetic background and time of corticosterone action are modifiers of fear memory with interesting translational implications for anxiety-related diseases.

  12. Mechanism of the protective effects of long chain n-alkyl glucopyranosides against ultrasound-induced cytolysis of HL-60 cells.

    Science.gov (United States)

    Cheng, Jason Y; Riesz, Peter

    2007-07-01

    Recently it has been shown that long chain (C5-C8) n-alkyl glucopyranosides completely inhibit ultrasound-induced cytolysis [J.Z. Sostaric, N. Miyoshi, P. Riesz, W.G. DeGraff, and J.B. Mitchell, Free Radical Biol. Med., 39 (2005) 1539]. This protective effect has possible applications in HIFU (high intensity focused ultrasound) for tumor treatment, and in ultrasound assisted drug delivery and gene therapy. n-Alkyl glucopyranosides with hexyl (5mM), heptyl (3mM), octyl (2mM) n-alkyl chains protected 100% of HL-60 cells in vitro from 1.057 MHz ultrasound-induced cytolysis under a range of conditions that resulted in 35-100% cytolysis in the absence of glucopyranosides. However the hydrophilic methyl-beta-d-glucopyranoside did not protect cells. The surface active n-alkyl glucopyranosides accumulate at the gas-liquid interface of cavitation bubbles. The OH radicals and H atoms formed in collapsing cavitation bubbles react by H-atom abstraction from either the n-alkyl chain or the glucose moiety of the n-alkyl glucopyranosides. Owing to the high concentration of the long chain surfactants at the gas-liquid interface of cavitation bubbles, the initially formed carbon radicals on the alkyl chains are transferred to the glucose moieties to yield radicals which react with oxygen leading to the formation of hydrogen peroxide. In this work, we find that the sonochemically produced hydrogen peroxide yields from oxygen-saturated solutions of long chain (hexyl, octyl) n-alkyl glucopyranosides at 614 kHz and 1.057 MHz ultrasound increase with increasing n-alkyl glucopyranoside concentration but are independent of concentration for methyl-beta-D-glucopyranoside. These results are consistent with the previously proposed mechanism of sonoprotection [J.Z. Sostaric, N. Miyoshi, P. Riesz, W.G. DeGraff, and J.B. Mitchell, Free Radical Biol. Med., 39 (2005) 1539]. This sequence of events prevents sonodynamic cell killing by initiation of lipid peroxidation chain reactions in cellular

  13. Reaction OH + OH studied over the 298-834 K temperature and 1-100 bar pressure ranges.

    Science.gov (United States)

    Sangwan, Manuvesh; Chesnokov, Evgeni N; Krasnoperov, Lev N

    2012-06-21

    Self-reaction of hydroxyl radicals, OH + OH → H(2)O + O (1a) and OH + OH → H(2)O(2) (1b), was studied using pulsed laser photolysis coupled to transient UV-vis absorption spectroscopy over the 298-834 K temperature and 1-100 bar pressure ranges (bath gas He). A heatable high-pressure flow reactor was employed. Hydroxyl radicals were prepared using reaction of electronically excited oxygen atoms, O((1)D), produced in photolysis of N(2)O at 193 nm, with H(2)O. The temporal behavior of OH radicals was monitored via transient absorption of light from a dc discharge in H(2)O/Ar low-pressure resonance lamp at ca. 308 nm. The absolute intensity of the photolysis light was determined by accurate in situ actinometry based on the ozone formation in the presence of molecular oxygen. The results of this study combined with the literature data indicate that the rate constant of reaction 1a, associated with the pressure independent component, decreases with temperature within the temperature range 298-414 K and increases above 555 K. The pressure dependent rate constant for (1b) was parametrized using the Troe expression as k(1b,inf) = (2.4 ± 0.6) × 10(-11)(T/300)(-0.5) cm(3) molecule(-1) s(-1), k(1b,0) = [He] (9.0 ± 2.2) × 10(-31)(T/300)(-3.5±0.5) cm(3) molecule(-1) s(-1), F(c) = 0.37.

  14. The radiation protection environmental assesment for 60Co irradiation room

    International Nuclear Information System (INIS)

    Zheng Meiyang; Jin Guohua; Shen Genfang

    2010-01-01

    60 Co source is applied in the process such as sterilizing agricultural products in irradiation room of some Academy of Agricultural Sciences, which is very effective in agricultural applications. However, 60 Co is highly toxic, once the leak, the consequences would be disastrous. So it is necessary to summarize the radiation protection and safety evaluation of the irradiation room indoor and outdoor, to ensure the health and lives of the staff and the surrounding population. The radiation detectors monitor six points around the irradiation room. Results show that design of irradiation room of Academy of Agricultural Sciences are mostly safe and reliable, regardless of the source in working condition. And consequences also show 60 Co source in the normal operating will not put adverse effects on the surrounding environment. In addition, the outer radiation protective measures are also outlined, in view of 60 Co own identity. (authors)

  15. Protective efficacy of Emblica against radiation and lead induced biochemical changes in the kidney of Swiss albino mice

    International Nuclear Information System (INIS)

    Chakrawarti, Aruna; Dev, Rahul; Rathore, Narendra Singh; Khatri, Anand

    2012-01-01

    Ionizing radiation kills cells in the area being treated (the target tissue) as well as other surrounding healthy cells. The damaging effects of ionizing radiation on healthy tissue create a major barrier in effective treatment of common human cancers. Thus there is a need to find a safe and highly effective avenue to reduce normal cell damage during cancer therapy, plants have been used in the traditional healthcare system from time immemorial, and phyto products continue to play an essential role in medicine. Emblica, is reported to have an excellent radio protective activity, antioxidant and a free radical scavenger. In light of above, the present study was aimed to evaluate the protective effect of Emblica against radiation and lead induced biochemical alterations in the kidney of Swiss albino mice. The animals were exposed to 6.0 Gy of gamma rays with or without Lead acetate treatment. The Emblica was administered seven days prior to irradiation or Lead Acetate treatment. The animals from all experimental groups were sacrificed by cervical dislocation at each post treatment intervals of 1, 2, 4, 7, 14 and 28 days. After sacrificing the animals, pieces of the kidney were taken out and kept at - 20 deg C for different biochemical parameters. For the study the animals were exposed to 6.0 Gy of gamma rays with or without Lead acetate treatments. In the experimental groups the Emblica juice was given seven days prior to the radiation or lead acetate treatment. The various biochemical parameters viz, total proteins, glycogen, cholesterol, acid phosphatase and alkaline phosphatase activities, DNA and RNA were estimated. The values were observed in the form of increase or decrease. After combined treatment of radiation and lead acetate the changes were more severe showing synergistic effect of both the agent. An early and fast recovery was also noticed in Emblica pre-treated animals. Thus it appears that Emblica is potent enough to check Lead and Radiation induced

  16. Quench Protection and Magnet Powe Supply Requirements for the MICE Focusing and Coupling Magnets

    International Nuclear Information System (INIS)

    Green, Michael A.; Witte, Holger

    2005-01-01

    This report discusses the quench protection and power supply requirements of the MICE superconducting magnets. A section of the report discusses the quench process and how to calculate the peak voltages and hotspot temperature that result from a magnet quench. A section of the report discusses conventional quench protection methods. Thermal quench back from the magnet mandrel is also discussed. Selected quench protection methods that result in safe quenching of the MICE focusing and coupling magnets are discussed. The coupling of the MICE magnets with the other magnets in the MICE is described. The consequences of this coupling on magnet charging and quenching are discussed. Calculations of the quenching of a magnet due quench back from circulating currents induced in the magnet mandrel due to quenching of an adjacent magnet are discussed. The conclusion of this report describes how the MICE magnet channel will react when one or magnets in that channel are quenched

  17. Junctional Adhesion Molecule (JAM)-C Deficient C57BL/6 Mice Develop a Severe Hydrocephalus

    Science.gov (United States)

    Liebner, Stefan; Mittelbronn, Michel; Deutsch, Urban; Enzmann, Gaby; Adams, Ralf H.; Aurrand-Lions, Michel; Plate, Karl H.; Imhof, Beat A.; Engelhardt, Britta

    2012-01-01

    The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C−/− mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C−/− mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C−/− C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C−/− mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3rd ventricle in JAM-C−/− C57BL/6 mice. Taken together, our study suggests that JAM-C−/− C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C. PMID:23029139

  18. Recombinant canine adenovirus type-2 expressing TgROP16 provides partial protection against acute Toxoplasma gondii infection in mice.

    Science.gov (United States)

    Li, Xiu-Zhen; Lv, Lin; Zhang, Xu; Anchang, Kenneth Yongabi; Abdullahi, Auwalu Yusuf; Tu, Liqing; Wang, Xiaohu; Xia, Lijun; Zhang, Xiu-Xiang; Feng, Weili; Lu, Chunxia; Li, Shoujun; Yuan, Zi-Guo

    2016-11-01

    We previously demonstrated that the survival time of BALB/c mice challenged with Toxoplasma gondii RH strain was prolonged by immunising the mice with a eukaryotic vector expressing the protein ROP16 of T. gondii. Building upon previous findings, we are exploring improved vaccination strategies to enhance protection. In this work, a novel recombinant canine adenovirus type 2 expressing ROP16 (CAV-2-ROP16) of T. gondii was constructed and identified to express ROP16 in Madin-Darby canine kidney cells (MDCK) cells by western blot (WB) and indirect immunofluorescence (IFA) assays. Intramuscular immunisation of BALB/c mice with CAV-2-ROP16 was performed to evaluate the humoral and cellular immune responses. This vaccination triggered significant humoral and cellular responses, including ROP16-stimulated lymphoproliferation (P0.05), revealing that a predominant Th1-type response had developed. The cell-mediated cytotoxic activity with high levels of IFN-γ and TNF-α was significantly increased in both CD4 + and CD8 + T-cell compartments in the mice immunised with CAV-2-ROP16 (Pdays post infection compared with control mice that all died within seven days (Pvaccination until now. Our work presents the successful use of recombinant virus CAV-2-ROP16 in vaccination protocols to protect against intraperitoneal challenge with the virulent RH strain of T. gondii. This system was shown to be extremely efficient in eliciting humoral and cellular immune responses that led to a significant improvement in survival time in mice. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

    Science.gov (United States)

    Jain, Nidhi; Oswal, Neelam; Chawla, Amanpreet Singh; Agrawal, Tanvi; Biswas, Moanaro; Vrati, Sudhanshu; Rath, Satyajit; George, Anna; Bal, Vineeta; Medigeshi, Guruprasad R

    2017-02-01

    Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null) are highly susceptible and die over 10-18 day period as compared to the wild-type (WT) mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB). Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

  20. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

    Directory of Open Access Journals (Sweden)

    Nidhi Jain

    2017-02-01

    Full Text Available Following Japanese encephalitis virus (JEV infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null are highly susceptible and die over 10-18 day period as compared to the wild-type (WT mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB. Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

  1. Crystal structure, equation of state, and elasticity of hydrous aluminosilicate phase, topaz-OH (Al2SiO4(OH)2) at high pressures

    Science.gov (United States)

    Mookherjee, Mainak; Tsuchiya, Jun; Hariharan, Anant

    2016-02-01

    We examined the equation of state and high-pressure elasticity of the hydrous aluminosilicate mineral topaz-OH (Al2SiO4(OH)2) using first principles simulation. Topaz-OH is a hydrous phase in the Al2O3-SiO2-H2O (ASH) ternary system, which is relevant for the mineral phase relations in the hydrated sedimentary layer of subducting slabs. Based on recent neutron diffraction experiments, it is known that the protons in the topaz-OH exhibit positional disorder with half occupancy over two distinct crystallographic sites. In order to adequately depict the proton environment in the topaz-OH, we examined five crystal structure models with distinct configuration for the protons in topaz-OH. Upon full geometry optimization we find two distinct space group, an orthorhombic Pbnm and a monoclinic P21/c for topaz-OH. The topaz-OH with the monoclinic P21/c space group has a lower energy compared to the orthorhombic Pbmn space group symmetry. The pressure-volume results for the monoclinic topaz-OH is well represented by a third order Birch-Murnaghan formulation, with V0mon = 348.63 (±0.04) Å3, K0mon = 164.7 (±0.04) GPa, and K0mon = 4.24 (±0.05). The pressure-volume results for the orthorhombic topaz-OH is well represented by a third order Birch-Murnaghan formulation, with V0orth = 352.47 (±0.04) Å3, K0orth = 166.4 (±0.06) GPa, and K0orth = 4.03 (±0.04). While the bulk moduli are very similar for both the monoclinic and orthorhombic topaz-OH, the shear elastic constants and the shear moduli are very sensitive to the position of the proton, orientation of the O-H dipole, and the space group symmetry. The S-wave anisotropy for the orthorhombic and monoclinic topaz-OH are also quite distinct. In the hydrated sedimentary layer of subducting slabs, transformation of a mineral assemblage consisting of coesite (SiO2) and diaspore (AlOOH) to topaz-OH (Al2SiO4(OH)2) is likely to be accompanied by an increase in density, compressional velocity, and shear wave velocity. However

  2. Evidence that radio-sensitive cells are central to skin-phase protective immunity in CBA/Ca mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni as well as in naive mice protected with vaccine serum

    International Nuclear Information System (INIS)

    Delgado, V.S.; McLaren, D.J.

    1990-01-01

    Naive CBA/Ca mice and CBA/ca mice vaccinated 4 weeks previously with radiation-attenuated cercariae of Schistosoma mansoni were subjected to 550 rad of whole body (gamma) irradiation and then challenged 3 days later with normal cercariae. The perfusion recovery data showed that this procedure reduced the primary worm burden in naive mice by 22% and the challence worm burden in vaccinated mice by 82%. Irradiation also ablated the peripheral blood leucocytes of both mouse groups by 90-100% at the time of challenge. Histological data revealed that such treatment caused a dramatic change in number, size and leucocyte composition of cutaneous inflammatory skin reactions that characterize challenged vacccinated mice and are known to entrap invading larvae; cutaneous eosinophils were preferentially abolished by this treatment. Polyvaccine mouse serum that conferred protection passively upon naive recipient mice, failed to protect naive/irradiated mice when administered by the same protocol. Distraction of macrophages by treatment of mice with silica did not affect the establishment of a primary worm burden and reduced the protection exhibited by vaccinated mice by only 16%. These data indicade that radio-sensitive cells are important to both innate and specific acquired resistance in this mouse model and that macrophages contribute only marginally to the expression of vaccine immunity. (author)

  3. The Effect of Sun Radiation on the Course of Cutaneous Leishmaniasis in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Amir Abas Azarian

    2011-03-01

    Full Text Available Objective(sStudies have described immunomedulatory effects of sun exposure and ultraviolet radiation on infectious and neoplastic diseases. Here the effect of exposure to low potency radiation of sun on the course of leishmaniasis in mice was studied. Materials and MethodsFifteen BALB/c mice were exposed to suberythemogenic doses of sun (mean 180 mJ/cm2/day of UVB 2 months before and 4 months after Leishmania major inoculation to food pad. Control group was kept in the sun protected environment. From 2nd to 17th week after inoculation, size of the lesion was recorded in each group weekly and at last week the parasite burden in spleen was detected. Results were compared between two groups. ResultsSeven mice from case group and 9 mice from control group survived up to last week. The mean lesion size was 0.90±0.59 cm in exposed and 4.01±3.59 cm in unexposed mice (P= 0.037. Parasite burden in spleen of case and control groups were 5.5±4.61 and 106.94±279.76 respectively (P= 0.006.ConclusionChronic exposure of BALB/c mice to suberythemogenic doses of sun suppressed skin lesion and decreased the extension of L. major to spleen.

  4. Protection of mice against Giardia muris infection.

    Science.gov (United States)

    Roberts-Thomson, I C; Mitchell, G F

    1979-01-01

    Strains of mice showing relatively rapid (BALB/c) and defective (C3H/He) spontaneous elimination of Giardia muris displayed marked differences in the degree of resistance to infection induced by prior injection of trophozoites in Freund complete adjuvant. PMID:468385

  5. Effects of 60Co γ-radiation on brain hippocampal tissue of adult mice

    International Nuclear Information System (INIS)

    Liu Yongbao; Rao Yongqing; Xu Luxi

    2000-01-01

    Objective: To study neuro-pathological changes of hippocampus tissue in adult mice following a series of irradiation with 60 Co γ-rays. Methods: Male mice of Kunming strain in experimental group (n = 8) were exposed total-bodily to 60 Co γ-rays at 2.0 Gy once every two days. A histopathological imaging analysis of the mouse brain tissue was carried out after paraffin embedding and a series of sections were made and stained with Nissl and Weil staining methods. Results: In the irradiation group (the cumulative dose = 26 Gy) loss of pyramidal cells in hippocampus was significant when compared with the control group. Neuro-pathological changes were characterised by reduced neuron size, nuclear pyknosis and karyolysis. The neurofibrillar density of the pyramidal layer in the irradiation group was much lower than that of the control group (P CA2>CA3>CA4 in the hippocampus. Conclusion: The neuronal damage in hippocampus after 60 Co irradiation could form a pathological basis in reduction of memorial and learning ability

  6. Photophysics of C60 Colloids

    Science.gov (United States)

    2012-11-28

    nonlinear-optical properties and excited-state dynamics of pristine, oxygen- doped , and photopolymerized C-60 in the solid-state," Physical Review B...C45 (2009). 139. E. A. Brujan, "Numerical investigation on the dynamics of cavitation nanobubbles," Microfluidics and Nanofluidics 11(5), 511-517

  7. Effect of allyl alcohol on hepatic transporter expression: Zonal patterns of expression and role of Kupffer cell function

    International Nuclear Information System (INIS)

    Campion, Sarah N.; Tatis-Rios, Cristina; Augustine, Lisa M.; Goedken, Michael J.; Rooijen, Nico van; Cherrington, Nathan J.; Manautou, Jose E.

    2009-01-01

    During APAP toxicity, activation of Kupffer cells is critical for protection from hepatotoxicity and up-regulation of multidrug resistance-associated protein 4 (Mrp4) in centrilobular hepatocytes. The present study was performed to determine the expression profile of uptake and efflux transporters in mouse liver following treatment with allyl alcohol (AlOH), a periportal hepatotoxicant. This study also investigated the role of Kupffer cells in AlOH hepatotoxicity, and whether changes in transport protein expression by AlOH are dependent on the presence of Kupffer cells. C57BL/6J mice received 0.1 ml clodronate liposomes to deplete Kupffer cells or empty liposomes 48 h prior to dosing with 60 mg/kg AlOH, i.p. Hepatotoxicity was assessed by plasma ALT and histopathology. Hepatic transporter mRNA and protein expression were determined by branched DNA signal amplification assay and Western blotting, respectively. Depletion of Kupffer cells by liposomal clodronate treatment resulted in heightened susceptibility to AlOH toxicity. Exposure to AlOH increased mRNA levels of several Mrp genes, while decreasing organic anion transporting polypeptides (Oatps) mRNA expression. Protein analysis mirrored many of these mRNA changes. The presence of Kupffer cells was not required for the observed changes in uptake and efflux transporters induced by AlOH. Immunofluorescent analysis revealed enhanced Mrp4 staining exclusively in centrilobular hepatocytes of AlOH treated mice. These findings demonstrate that Kupffer cells are protective from AlOH toxicity and that induction of Mrp4 occurs in liver regions away from areas of AlOH damage independent of Kupffer cell function. These results suggest that Kupffer cell mediators do not play a role in mediating centrilobular Mrp4 induction in response to periportal damage by AlOH

  8. Down-Regulation of Homer1b/c Protects Against Chemically Induced Seizures Through Inhibition of mTOR Signaling

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    Lei Cao

    2015-03-01

    Full Text Available Background: Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. Reducing Homer1b/c expression has been shown in previous studies to be protective against excitotoxic insults, implicating Homer1b/c in the physiological regulation of aberrant neuronal excitability. Methods: To test the efficacy of a Homer1b/c reducing therapy for disorders with a detrimental hyperexcitability profile in mice, we used small interfere RNA (siRNA to decrease endogenous Homer1b/c expression in mouse hippocampus. The baseline motor and cognitive behavior was measured by sensorimotor tests, Morris water maze and elevated plus maze tasks. The anti-epileptic effects of Homer1b/c knockdown were determined in two chemically induced seizure models induced by Picrotoxin (PTX or pentylenetetrazole (PTZ administration. Results: The results of sensorimotor tests, Morris water maze and elevated plus maze tasks showed that Homer1b/c reduction had no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced Homerb/c protein had less severe seizures than control mice. Total Homer1b/c protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of Homer1b/c. In addition, the phosphorylation of mammalian target of rapamycin (mTOR and its target protein S6 was significantly inhibited in Homer1b/c down-regulated mice. Homer1b/c knockdown-induced inhibition of mTOR pathway was partially ablated by the metabotropic glutamate receptor 5 (mGluR5 agonist CHPG. Conclusion: Our results demonstrate that endogenous Homer1b/c is integral for regulating neuronal hyperexcitability in adult animals and suggest that reduction of Homer1b/c could protect against chemically induced seizures through inhibition mTOR pathway.

  9. Protective effects of Astragalus-Lilygranules on intestinal mucosal barrier of mice in high altitude hypoxia

    Directory of Open Access Journals (Sweden)

    Ling LI

    2016-10-01

    Full Text Available Objective  To investigate the protective effect of Astragalus-Lily Granules on intestinal mucosa and intestinal flora homeostasis in mice under high altitude hypoxia condition. Methods  We put mice into high altitude hypoxia cabin to establish high altitude hypoxia model mice. Sixty Kunming mice were randomly divided into control group, model group, Astragalus-Lily particles (ALP low, medium and high dose groups [1.75, 3.5, 7g/(kg•d] respectively. After three days of routine feeding, the ALP mice received drug by intragastric administration, once a day for continuous 17 days,control group and model group were given double distilled water in same volume. From the 15th day, all the mice but control group were exposed to simulated high altitude hypoxia condition for 3 days in a high altitude hypoxia cabin after they were gavaged for half an hour daily. By the 18th day, the fresh mouse feces were collected and smeared to observe the changes of microflora. The pathological changes of intestinal tissues were observed by HE staining and the expression of HIF-1αprotein in intestines was detected by immunohistochemistry. Results  The enterococci and gram negative bacteria showed a higher proportion (65.2%±2.4% and 56.7%±3.3%, respectively in the model group compared with the control group (24.7%±1.2%, 23.2%±1.5%, respectively, P<0.05. The pathological score of intestinal mucosal necrosis and edema (3.10±0.99, 3.30±0.67 respectively and inflammatory cell count (15.93±3.30, 16.40±3.97/ HP respectively was higher compared with the model group (0.70±0.67, 0.80±0.78; 4.07±2.12, 4.28±2.16/HP respectively; P<0.05. HIF-1αexpression increased significantly compared with the model group (P<0.05. The enterococci (46.7%±2.0%, 32.0%±2.6% respectively and gram negative bacteria rate (34.2%±1.6%, 38.0%±2.8% respectively in the ALP medium and high dose groups were lower compared with the model group (24.7%±1.2%, 23.2%±1.5% respectively, P<0

  10. LncRNA: a new player in 1α, 25(OH)(2) vitamin D(3) /VDR protection against skin cancer formation.

    Science.gov (United States)

    Jiang, Yan J; Bikle, Daniel D

    2014-03-01

    Sunlight, vitamin D and skin cancer form a controversial brew. While too much sunlight exposure causes skin cancer, it is the major source of vitamin D from skin. We propose that these processes can be balanced. Vitamin D signalling (VDS) protects against skin cancer as demonstrated by the susceptibility of the skin to tumor formation in VDR null mice and protection from UVB-induced mutations when VDR agonists are administered. The question is how is protection afforded. Previously, we have focused on the Wnt/β-catenin/hedgehog and DNA damage repair (DDR) pathways. As VDR regulates hundreds of genes with thousands of VDR response elements (VDRE) throughout the genome, and many VDREs are in non-coding regions, we decided to explore long non-coding RNAs (lncRNA). LncRNAs are mRNA-like transcripts ranging from 200 bases ~100 kb lacking significant open reading frames. They are aberrantly expressed in human cancers and involved in a spectrum of tumorigenic/metastatic processes (cell proliferation/apoptosis/angiogenesis). We discovered that VDS regulated the expression of certain lncRNAs in a manner consistent with VDS protection against skin cancer. Given the huge variation in genes actively regulated by 1,25(OH)2 D from different cell types, it is conceivable that our results could apply to personalized medicine based on the distinctive lncRNA profiles. These lncRNAs could also serve as skin cancer biomarkers secreted into the blood or urine via exosomes as demonstrated in other cancer types (breast, prostate). Modulation of lncRNA profile by VDS may also provide insight into regulating pathways such as Wnt/ß-catenin and hedgehog. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Protective effects of the fermented milk Kefir on X-ray irradiation-induced intestinal damage in B6C3F1 mice

    International Nuclear Information System (INIS)

    Teruya, Kiichiro; Nakamichi, Noboru; Shirahata, Sanetaka; Myojin-Maekawa, Yuki; Shimamoto, Fumio; Watanabe, Hiromitsu; Tokumaru, Koichiro; Tokumaru, Sennosuke

    2013-01-01

    Gastrointestinal damage associated with radiation therapy is currently an inevitable outcome. The protective effect of Kefir was assessed for its usefulness against radiation-induced gastrointestinal damage. A Kefir supernatant was diluted by 2- or 10-fold and administered for 1 week prior to 8 Gray (Gy) X-ray irradiation at a dose rate of 2 Gy/min, with an additional 15d of administration post-irradiation. The survival rate of control mice with normal drinking water dropped to 70% on days 4 through 9 post-irradiation. On the other hand, 100% of mice in the 10- and 2-fold-diluted Kefir groups survived up to day 9 post-irradiation (p<0.05 and p<0.01, respectively). Examinations for crypt regeneration against 8, 10 and 12 Gy irradiation at a dose rate of 4 Gy/min revealed that the crypt number was significantly increased in the mice administered both diluted Kefir solutions (p<0.01 for each). Histological and immunohistochemical examinations revealed that the diluted Kefir solutions protected the crypts from radiation, and promoted crypt regeneration. In addition, lyophilized Kefir powder was found to significantly recover the testis weights (p<0.05), but had no effects on the body and spleen weights, after 8 Gy irradiation. These findings suggest that Kefir could be a promising candidate as a radiation-protective agent. (author)

  12. Estimation of the parameters of cytotoxicity of fullerene C60 and C60-containing composites in vitro

    International Nuclear Information System (INIS)

    Priluts'ka, S.V.; Grinyuk, Yi.Yi.; Golub, O.A.; Matishevs'ka, O.P.

    2006-01-01

    The influence of fullerene C 60 and C 60 -containing composites (on the basis of aminopropylaerosyl (ApA)) on the stability of erythrocytes to acid haemolysis and the viability of thymocytes, ascite forms of Erlich and leucosis L1210 cells is studied. The obtained results indicate the possibility to use ApA as a matrix for conjugation with other elements and for the further biological studies of composites photosensitizing the effect

  13. Cardiovascular changes in atherosclerotic ApoE-deficient mice exposed to Co60 (γ radiation.

    Directory of Open Access Journals (Sweden)

    Prem Kumarathasan

    Full Text Available BACKGROUND: There is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation. METHODS AND RESULTS: B6.129P2-ApoE tmlUnc mice on a low-fat diet were acutely exposed (whole body to Co60 (γ (single dose 0, 0.5, and 2 Gy at a dose rate of 36.32 cGy/min, or repeatedly (cumulative dose 0 and 2 Gy at a dose-rate of 0.1 cGy/min for 5 d/wk, over a period of 4 weeks. Biological endpoints were investigated after 3-6 months of recovery post-radiation. The nitrative stress marker 3-nitrotyrosine and the vasoregulator peptides endothelin-1 and endothelin-3 in plasma were increased (p<0.05 in a dose-dependent manner 3-6 months after acute or chronic exposure to radiation. The oxidative stress marker 8-isoprostane was not affected by radiation, while plasma 8-hydroxydeoxyguanosine and L-3,4-dihydroxyphenylalanine decreased (p<0.05 after treatment. At 2Gy radiation dose, serum cholesterol was increased (p = 0.008 relative to controls. Percent lesion area increased (p = 0.005 with age of animal, but not with radiation treatment. CONCLUSIONS: Our observations are consistent with persistent nitrative stress and activation of the endothelinergic system in ApoE-/- mice after low-level ionizing radiation exposures. These mechanisms are known factors in the progression of atherosclerosis and other cardiovascular diseases.

  14. Fulereno[C60]: química e aplicações Fullerene C60: chemistry and applications

    Directory of Open Access Journals (Sweden)

    Leandro José dos Santos

    2010-01-01

    Full Text Available Fullerene chemistry has become a very active research field in the two last decades, largely because of the exceptional properties of the C60 molecule and the variety of fullerene derivatives that appear to be possible. In this review, a general analysis of fullerene C60 reactivity is performed. The principal methods for the covalent modification of this fascinating carbon cage are presented. The prospects of using fullerene derivatives as medicinal drugs and photoactive materials in light converting devices are demonstrated.

  15. Protective effects of acemannan against radiation induced damage in Swiss albino mice

    International Nuclear Information System (INIS)

    Kumar, Sumit; Tiku, Ashu Bhan

    2013-01-01

    Aloe vera is one of the well known medicinal plant and posses a large no. of beneficial bioactive components like Anthraquinone, C-glycosides, anthrones, emodin, acemannan etc. Acemannan (poly-acetylated mannose) is one of the active component present in aloe vera gel and has anticancerous and antimicrobial properties. It has also been reported to have wound healing properties and has role as immunomodulator. The objective of the present study was to evaluate protective efficacy of acemannan against radiation induced damage in in-vitro and in in-vivo using murine splenocytes and Swiss albino mice as a model system. In vitro studies were done using primary mouse splenocytes cultures and effect of radiation on cell proliferation, viability, ROS, DNA damage and apoptosis were studies using MTT, trypan blue, DCFDA, single cell gel electrophoresis and ladder assay respectively. For in-vivo studies mice were pretreated with different doses of drug for 7 days followed by irradiation (5 Gy). Twenty four hours post-irradiation mice was sacrificed to observe the activity of antioxidant enzymes and level of protein expression. Acemannan showed a significant induction of proliferation of splenocytes in radiation treated groups both in in-vitro and in in-vivo. Beside a decrease in radiation induced ROS and DNA damage was observed in in-vitro system. Acemannan treatment was able to reduce the radiation induced apoptosis by about 50% both in in-vitro and in in-vivo. In in-vivo acemannan helps in the restoration of the antioxidant enzyme level (catalase, SOD, DTD and GST) besides maintaining the proper redox status via GSH, in irradiated mice. In our studies a dose of 50 mg/kg body wt of acemannan showed the best protective effects. On the basis of the above results it could be concluded that acemannan may have radioprotective potential. (author)

  16. Modulation of cisplatin-induced reactive oxygen species production by fullerene C(60 in normal and transformed lymphoid cells

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    D. V. Franskevych

    2016-02-01

    Full Text Available The early response of normal (Wistar rat thymocytes and transformed (mice lymphoid leukemia L1210 cells to treatment with anticancer drug cisplatin or to combined treatment with cisplatin and carbon nanostructure fullerene C60 was studied. We demonstrated with fluorescent probes DCFH-DA and TMRE that cisplatin at concentration 1 μg/ml induced reactive oxygen species (ROS production and decreased the value of mitochondrial membrane potential in both cell types. The combined treatment with cisplatin (1 μg/ml and fullerene C60 (7.2 μg/ml was shown to be followed by oppositely directed modulation of ROS production in thymocytes and L1210 cells. Cisplatin-induced ROS production was intensified in L1210 cells, while in thymocytes it was decreased. It is supposed that the different effects of combined treatment are associated with peculiarities of fullerene C60 accumulation and localization in normal and cancer cells.

  17. Effect of Fluosol-DA 20% and oxygen on response of C57BL/6 mice to whole-body irradiation

    International Nuclear Information System (INIS)

    Waldow, S.M.; Lustig, R.A.; Brass-Marlow, E.L.; Nunno, M.P.; Holst, R.J.; Wallner, P.E.

    1990-01-01

    Normal tissue effects in mice due to combinations of a perfluorochemical emulsion, Fluosol-DA 20%, 100% oxygen, and whole-body irradiation were investigated. Eight-to-10-week-old C57BL/6 male mice were injected via the tail vein with 10 ml/kg of Fluosol-DA with and without subsequent exposure to oxygen for 60 minutes. Animals then received graded doses of whole-body radiation (4 MV photons) at a dose rate of 2.85 +/- .015 Gy/minute. Using linear regression analysis, the lethal doses of radiation to 50% and 10% of the animals within 30 days in the absence of Fluosol-DA and oxygen were 8.35 Gy (95% c.l.:7.77-8.93 Gy) and 6.73 Gy (95% cl.:6.21-7.25 Gy), respectively, and were unaffected by Fluosol-DA and/or oxygen pre-treatment. However, Fluosol-DA given alone or in combination with oxygen produced increased balding and decreased graying incidence in mice within 60 days, and resulted in depressed weight gain 15 to 60 days post-treatment. Normal tissue effects due to administration of Fluosol-DA and oxygen in combination with whole-body irradiation have been demonstrated but appear minimal compared to other anti-tumor modalities currently under investigation

  18. A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is highly immunogenic and protects mice in active and passive immunizations.

    Directory of Open Access Journals (Sweden)

    Annett Hessel

    Full Text Available BACKGROUND: The development of novel influenza vaccines inducing a broad immune response is an important objective. The aim of this study was to evaluate live vaccines which induce both strong humoral and cell-mediated immune responses against the novel human pandemic H1N1 influenza virus, and to show protection in a lethal animal challenge model. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, the hemagglutinin (HA and neuraminidase (NA genes of the influenza A/California/07/2009 (H1N1 strain (CA/07 were inserted into the replication-deficient modified vaccinia Ankara (MVA virus--a safe poxviral live vector--resulting in MVA-H1-Ca and MVA-N1-Ca vectors. These live vaccines, together with an inactivated whole virus vaccine, were assessed in a lung infection model using immune competent Balb/c mice, and in a lethal challenge model using severe combined immunodeficient (SCID mice after passive serum transfer from immunized mice. Balb/c mice vaccinated with the MVA-H1-Ca virus or the inactivated vaccine were fully protected from lung infection after challenge with the influenza H1N1 wild-type strain, while the neuraminidase virus MVA-N1-Ca induced only partial protection. The live vaccines were already protective after a single dose and induced substantial amounts of neutralizing antibodies and of interferon-gamma-secreting (IFN-gamma CD4- and CD8 T-cells in lungs and spleens. In the lungs, a rapid increase of HA-specific CD4- and CD8 T cells was observed in vaccinated mice shortly after challenge with influenza swine flu virus, which probably contributes to the strong inhibition of pulmonary viral replication observed. In addition, passive transfer of antisera raised in MVA-H1-Ca vaccinated immune-competent mice protected SCID mice from lethal challenge with the CA/07 wild-type virus. CONCLUSIONS/SIGNIFICANCE: The non-replicating MVA-based H1N1 live vaccines induce a broad protective immune response and are promising vaccine candidates for

  19. Late inflammatory and thrombotic changes in irradiated hearts of C57BL/6 wild-type and atherosclerosis-prone ApoE-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Patties, I.; Glasow, A. [University of Leipzig, Department of Radiation Therapy, Leipzig (Germany); Haagen, J. [University of Technology, Department of Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden (Germany); Doerr, W. [University of Technology, Department of Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden (Germany); CCC, Medical University/AKH, Department of Radiation Oncology and Christian Doppler Laboratory for Medical Radiation Research for Radiooncology, Vienna (Austria); Hildebrandt, G. [University of Rostock, Department of Radiotherapy and Radiation Oncology, Rostock (Germany)

    2014-09-09

    Radiation-induced heart disease represents a late complication of thoracic radiotherapy. We investigated the inflammatory and thrombotic response after local heart irradiation in wild-type and atherosclerosis-prone mice. Atherosclerosis-prone ApoE{sup -/-} and C57BL/6 wild-type mice were sacrificed 20, 40, and 60 weeks after irradiation with 0.2, 2, 8, or 16 Gy. The expression of CD31, vascular cell adhesion molecule-1 (VCAM-1), thrombomodulin (TM), and CD45 were quantified by immunofluorescence staining of heart tissue sections. Microvascular density decreased at 40 weeks after 16 Gy in C57BL/6 but not in ApoE{sup -/-} mice. CD31 expression declined in C57BL/6 mice at 40 weeks (8 Gy), but increased in ApoE{sup -/-} mice at 20 (2/8/16 Gy) and 60 weeks (16 Gy). Capillary area decreased in C57BL/6 at 40 weeks (8/16 Gy) but increased in ApoE{sup -/-} mice at 20 weeks (16 Gy). Endocardial VCAM-1 expression remained unchanged. TM-positive capillaries decreased at 40 weeks (8/16 Gy) in C57BL/6 and at 60 weeks (2/16 Gy) in ApoE{sup -/-} mice. Leukocyte infiltration transiently rose 40 weeks after 8 Gy (only ApoE{sup -/-}) and 16 Gy. After receiving a low irradiation dose of 0.2 Gy, no significant changes were observed in any of the mouse models. This study demonstrated that local heart irradiation affects microvascular structure and induces inflammatory/thrombotic responses in mice in a dose- and time-dependent manner. Thereby, significant prothrombotic changes were found in both strains, although they were progressive in ApoE{sup -/-} mice only. Proinflammatory responses, like the increase of adhesion molecules and leukocyte infiltration, were more pronounced and occurred at lower doses in ApoE{sup -/-} vs. C57BL/6 mice. These findings indicate that metabolic risk factors, such as decreased ApoE lipoproteins, may lead to an enhanced proinflammatory and prothrombotic late response in locally irradiated hearts. (orig.) [German] Strahlungsinduzierte kardiovaskulaere

  20. Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections.

    Science.gov (United States)

    Lilly, Elizabeth A; Ikeh, Melanie; Nash, Evelyn E; Fidel, Paul L; Noverr, Mairi C

    2018-01-16

    Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non- albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans / S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis / S. aureus -mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis -induced protection. C. dubliniensis / S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1 hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1 + cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans / S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

  1. Black tattoos protect against UVR-induced skin cancer in mice.

    Science.gov (United States)

    Lerche, Catharina M; Sepehri, Mitra; Serup, Jørgen; Poulsen, Thomas; Wulf, Hans Christian

    2015-09-01

    Black tattoos may involve risk of cancer owing to polycyclic aromatic hydrocarbons including benzo(a)pyrene (BaP) in inks. Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and black tattoo may therefore potentially be very problematic, but has not been previously studied. Immunocompetent C3.Cg/TifBomTac mice (n = 99) were tattooed on the back with Starbrite Tribal Black(™) . This ink has a high content of the carcinogen BaP. Half of the mice were irradiated with three standard erythema doses UVR thrice weekly. Time to induction of first, second and third squamous cell carcinoma (SCC) was measured. Controls were 'tattooed' without ink. All irradiated mice developed SCCs while no malignant tumours were found in the nonirradiated group. In the tattooed and irradiated group, the development of the first, second and third SCC was significantly delayed in comparison with the irradiated controls without black tattoos (212, 232, 247 days vs. 163, 183, 191 days, P tattoos, remarkably, the development of UVR-induced skin cancer was delayed by the tattoos. Skin reflectance measurement indicated that the protective effect of black pigment in the dermis might be attributed to UVR absorption by black pigment below the epidermis and thereby reduction of backscattered radiation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Toxoplasma gondii vs ionizing radiation: cell and humoral immunity in spleen and gut of isogenic mice immunized with {sup 60}Co irradiated tachyzoites; Toxoplasma gondii vs radiacao ionizante: imunidade humoral e celular em baco e intestino de camundongos isogenicos imunizados com taquizoitos irradiados por cobalto 60

    Energy Technology Data Exchange (ETDEWEB)

    Galisteo, Junior, Andres Jimenez

    2008-07-01

    We are developing a vaccine for toxoplasmosis, using ionizing radiation as a tool. Here we analyzed the production of systemic and intestinal immunity, with protection studies, in several strains of inbred mice, by oral or parenteral route, using 255 Gy irradiated tachyzoites of T. gondii RH strain, with challenge with cysts of ME- 49 strain. C57Bl/6j, BALB/c and C57Bl/6j IFN-{gamma}{sup -/-} mice were immunized with 10{sup 7} irradiated tachyzoites, be parenteral or oral route. Those preparations, both by parenteral or oral routes, induced the production of specific IgG, mainly of the lgG2b subclass, and IgA immunoglobulins in serum, , as determined by ELISA. IgM production was negligible. Parenteral immunized mice showed higher IgG avidity maturation, as compared to oral immunized mice. Fecal excretion of IgG, IgA and IgM was detected in stools of immunized animals, more intense in oral immunized mice. In cellular immunity studies, induced by antigen, with detection of cytokine production by quantitative real-time PCR, there are a great production of IFN-y by spleen cells, with lower levels in Peyer patches cells, where there are a greater IL-2 production. Challenge studies in immunized mice demonstrated protection to infection in all used schedules, greater in BALB/c mice. C57Bl/6j IFN-{gamma} -{sup /-} mice, when immunized, showed no signs of disease and produced similar or greater levels of antibodies than wild type mice. They also excreted S-lgA and S-IgM in stools, but with low numbers of brain cysts in parenteral immunized mice, despite similar mortality. Our data points to a fair possibility of use of those irradiated parasites as an oral vaccine, devised to use for veterinary or wild felines vaccination, reducing the production of oocysts by those hosts and interrupting the chain transmission of human toxoplasmosis. (author)

  3. Detection of fullerenes (C60 and C70) in commercial cosmetics

    International Nuclear Information System (INIS)

    Benn, Troy M.; Westerhoff, Paul; Herckes, Pierre

    2011-01-01

    Detection methods are necessary to quantify fullerenes in commercial applications to provide potential exposure levels for future risk assessments of fullerene technologies. The fullerene concentrations of five cosmetic products were evaluated using liquid chromatography with mass spectrometry to separate and specifically detect C 60 and C 70 from interfering cosmetic substances (e.g., castor oil). A cosmetic formulation was characterized with transmission electron microscopy, which confirmed that polyvinylpyrrolidone encapsulated C 60 . Liquid-liquid extraction of fullerenes from control samples approached 100% while solid-phase and sonication in toluene extractions yielded recoveries of 27-42%. C 60 was detected in four commercial cosmetics ranging from 0.04 to 1.1 μg/g, and C 70 was qualitatively detected in two samples. A single-use quantity of cosmetic (0.5 g) may contain up to 0.6 μg of C 60 , demonstrating a pathway for human exposure. Steady-state modeling of fullerene adsorption to biosolids is used to discuss potential environmental releases from wastewater treatment systems. - Highlights: → Fullerenes were detected in cosmetics up to 1.1 μg/g. → Liquid-liquid extraction efficiently recovers fullerenes in cosmetic matrices. → Solid-phase extraction reduces LC-MS detection interferences for C60. → Cosmetics can increase human and environmental fullerene exposures. - Fullerenes were detected in cosmetics with liquid chromatography-mass spectrometry up to 1.1 μg/g, demonstrating a source for human/environmental exposure.

  4. Influence of 24-Nor-Ursodeoxycholic Acid on Hepatic Disposition of [(18)F]Ciprofloxacin, a Positron Emission Tomography Study in Mice.

    Science.gov (United States)

    Wanek, Thomas; Halilbasic, Emina; Visentin, Michele; Mairinger, Severin; Römermann, Kerstin; Stieger, Bruno; Kuntner, Claudia; Müller, Markus; Langer, Oliver; Trauner, Michael

    2016-01-01

    24-nor-ursodeoxycholic acid (norUDCA) is a novel therapeutic approach to cholestatic liver diseases. In mouse models of cholestasis, norUDCA induces basolateral multidrug resistance-associated proteins 4 (Mrp4) and 3 in hepatocytes, which provide alternative escape routes for bile acids accumulating during cholestasis but could also result in altered hepatic disposition of concomitantly administered substrate drugs. We used positron emission tomography imaging to study the influence of norUDCA on hepatic disposition of the model Mrp4 substrate [(18)F]ciprofloxacin in wild-type and Mdr2((-/-)) mice, a model of cholestasis. Animals underwent [(18)F]ciprofloxacin positron emission tomography at baseline and after norUDCA treatment. After norUDCA treatment, liver-to-blood area under the curve ratio of [(18)F]ciprofloxacin was significantly decreased compared to baseline, both in wild-type (-34.0 ± 2.1%) and Mdr2((-/-)) mice (-20.5 ± 6.0%). [(18)F]Ciprofloxacin uptake clearance from blood into liver was reduced by -17.1 ± 9.0% in wild-type and by -20.1 ± 7.3% in Mdr2((-/-)) mice. Real-time PCR analysis showed significant increases in hepatic Mrp4 and multidrug resistance-associated protein 3 mRNA after norUDCA. Transport experiments in organic anion transporting polypeptide (OATP)1B1-, OATP1B3-, and OATP2B1-transfected cells revealed weak transport of [(14)C]ciprofloxacin by OATP1B3 and OATP2B1 and no inhibition by norUDCA. In conclusion, our data suggest that changes in hepatic [(18)F]ciprofloxacin disposition in mice after norUDCA treatment were caused by induction of basolateral Mrp4 in hepatocytes. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Suppressing effects of glucan on micronuclei induced by Co60 in mice

    International Nuclear Information System (INIS)

    Chorvatovicova, D.

    1991-01-01

    The effects of glucan on the frequency of micronuclei in polychromatic erythrocytes of A/Ph mouse bone marrow induced by Co 60 irradiation were examined. Suppressing effect of three glucan derivatives was statistically significant (P 3 substituent (DS 0.89). Intraperitoneal application of glucan has to be done earlier than one hour after irradiation. The suppressive effects of glucans can be explained by their ability to trap OH radicals and so decrease the clastogenic effect of irradiation. The results may be useful for therapeutic application of glucan with radiation therapy. (orig.) [de

  6. Glucagon receptor knockout mice are protected against acute olanzapine-induced hyperglycemia.

    Science.gov (United States)

    Castellani, Laura N; Peppler, Willem T; Sutton, Charles D; Whitfield, Jamie; Charron, Maureen J; Wright, David C

    2017-08-01

    To determine if glucagon is involved in mediating the increase in blood glucose levels caused by the second-generation antipsychotic drug olanzapine. Whole body glucagon receptor deficient mice (Gcgr -/- ) or WT littermate controls were injected with olanzapine (5mg/kg BW IP) and changes in blood glucose measured over the following 120min. Separate cohorts of mice were treated with olanzapine and changes in pyruvate tolerance, insulin tolerance and whole body substrate oxidation were determined. Olanzapine treatment increased serum glucagon and lead to rapid increases in blood glucose concentrations in WT mice. Gcgr -/- mice were protected against olanzapine-induced increases in blood glucose but this was not explained by differences in terminal serum insulin concentrations, enhanced AKT phosphorylation in skeletal muscle, adipose tissue or liver or differences in RER. In both genotypes olanzapine induced an equivalent degree of insulin resistance as measured using an insulin tolerance test. Olanzapine treatment led to an exaggerated glucose response to a pyruvate challenge in WT but not Gcgr -/- mice and this was paralleled by reductions in the protein content of PEPCK and G6Pase in livers from Gcgr -/- mice. Gcgr -/- mice are protected against olanzapine-induced increases in blood glucose. This is likely a result of reductions in liver glucose output, perhaps secondary to decreases in PEPCK and G6Pase protein content. Our findings highlight the central role of the liver in mediating olanzapine-induced disturbances in glucose homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Partial protective effect of intranasal immunization with recombinant Toxoplasma gondii rhoptry protein 17 against toxoplasmosis in mice.

    Directory of Open Access Journals (Sweden)

    Hai-Long Wang

    Full Text Available Toxoplasma gondii (T. gondii is an obligate intracellular protozoan parasite that infects a variety of mammals, including humans. An effective vaccine for this parasite is therefore needed. In this study, RH strain T. gondii rhoptry protein 17 was expressed in bacteria as a fusion with glutathione S-transferase (GST and the recombinant proteins (rTgROP17 were purified via GST-affinity chromatography. BALB/c mice were nasally immunised with rTgROP17, and induction of immune responses and protection against chronic and lethal T. gondii infections were investigated. The results revealed that mice immunised with rTgROP17 produced high levels of specific anti-rTgROP17 IgGs and a mixed IgG1/IgG2a response of IgG2a predominance. The systemic immune response was associated with increased production of Th1 (IFN-γand IL-2 and Th2 (IL-4 cytokines, and enhanced lymphoproliferation (stimulation index, SI in the mice immunised with rTgROP17. Strong mucosal immune responses with increased secretion of TgROP17-specific secretory IgA (SIgA in nasal, vaginal and intestinal washes were also observed in these mice. The vaccinated mice displayed apparent protection against chronic RH strain infection as evidenced by their lower liver and brain parasite burdens (59.17% and 49.08%, respectively than those of the controls. The vaccinated mice also exhibited significant protection against lethal infection of the virulent RH strain (survival increased by 50% compared to the controls. Our data demonstrate that rTgROP17 can trigger strong systemic and mucosal immune responses against T. gondii and that ROP17 is a promising candidate vaccine for toxoplasmosis.

  8. Fabrication of C60/amorphous carbon superlattice structures

    International Nuclear Information System (INIS)

    Kojima, Nobuaki; Ohshita, Yoshio; Yamaguchi, Masafumi

    2001-01-01

    The nitrogen doping effects in C 60 films by RF plasma source was investigated, and it was found that the nitrogen ion bombardment broke up C 60 molecules and changed them into amorphous carbon. Based on these results, formation of C 60 /amorphous carbon superlattice structure was proposed. The periodic structure of the resulted films was confirmed by XRD measurements, as the preliminary results of fabrication of the superlattice structure

  9. Order-disorder transitions in C60 and C70

    International Nuclear Information System (INIS)

    Ramasesha, S.K.

    1995-01-01

    In recent years enormous effort has been put in understanding the chemical and physical properties of C 60 and C 70 . Order-disorder transition in C 60 occurs around 250 K at ambient pressure. At the transition freely rotating molecules get orientationally ordered in a simple cubic lattice. Application of pressure increases the transition temperature at a rate of ≅ 10 K kbar -1 , indicating that pressure favours the ordered state. The DSC and x-ray studies on C 70 indicate two phase transitions, one around 270 K and the other around 340 K at room pressure. These transitions also occur at higher temperatures at higher pressures. Application of pressure is found to lift the degeneracy of the energetically equivalent rotational configurations. The high pressure studies are reviewed in the light of existing literature. (author)

  10. C60-based ebselen derivative: synthesis by bingel cyclopropanation and enhanced antioxidative and neuroprotective activity

    International Nuclear Information System (INIS)

    Xufeng Liu; Wenchao Guan; Wengshan Ke

    2007-01-01

    C 60 -based ebselen derivative 3 was synthesized through Bingel cyclopropanation of C 60 with the ebselen malonate 2. Compound 3 was obtained in 42% yield (based on consumed C 60 ) in a three-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2aminoethoxy)ethanol. Its structure was confirmed by 1H NMR, 13 C NMR, IR, UV and FAB-MS spectroscopy analyses. In order to verify the enhanced antioxidative and neuroprotective activity of 3, a C 60 derivative (4), an ebselen derivative (2), and their mixture (4 plus 2 in equimolar ratio) were employed to treat cortical neuronal cells, following the same procedure used with 3 and at the same final concentration (30 μmol L -1 ). Cell viabilities of the four treated groups were estimated by LDH (lactic dehydrogenase) leakage and MTT (3-(4, 5-dimethylthiazole-2yl)-2,5-diphenyl-tetrazolium bromide) assays. Results showed that the antioxidative and protective activities of C 60 -based ebselen derivative 3 against H 2 O 2 -mediated neuronal injury (MTT(OD) 0.364 ± 0.028; LDH release (UL -1 ) 4.66 ± 0.28) were significantly higher than those of C 6 )0 derivative 4 (MTT(OD) 0.324 ± 0.025; LDH release (UL -1 ) 5.39 ± 0.17), ebselen derivative 2 (MTT(OD) 0.294 ± 0.021; LDH release (UL -1 ) 5.71 ± 0.27), and the mixture of 4 and 2 (MTT(OD) 0.310 ± 0.018; LDH release (UL -1 ) 5.54 ±0.39). These findings demonstrated that the combination of two molecular units with similar biological activities (C 60 and ebselen) may be a desirable way of obtaining new and more biologically effective C 60 -based compounds. (author)

  11. Protective effect of intermittent fasting on the mortality of gamma-irradiated mice

    International Nuclear Information System (INIS)

    Kozubik, A.; Pospisil, M.

    1982-01-01

    The effect of 1 to 6 weeks' adaptation to intermittent fasting (alternating periods of 24 h fasting and subsequent 24 h feeding) on the manifestations of radioresistance of mice subjected to whole-body gamma-irradiation was studied. A favourable effect of this feeding regimen on the survival of irradiated animals was observed. The optimal redioprotective effect was achieved in mice adapted to intermittent fasting for 2 to 3 weeks and irradiated after 24 h of food intake. Furthermore, it was shown that the radioresistance of the adapted organism depends on the momentary state of food intake. After renewal of the normal ad libitum feeding the adaptively induced radioresistance decreases. (orig.) [de

  12. Protective effect of intermittent fasting on the mortality of gamma-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Kozubik, A.; Pospisil, M.

    1982-12-01

    The effect of 1 to 6 weeks' adaptation to intermittent fasting (alternating periods of 24 h fasting and subsequent 24 h feeding) on the manifestations of radioresistance of mice subjected to whole-body gamma-irradiation was studied. A favourable effect of this feeding regimen on the survival of irradiated animals was observed. The optimal redioprotective effect was achieved in mice adapted to intermittent fasting for 2 to 3 weeks and irradiated after 24 h of food intake. Furthermore, it was shown that the radioresistance of the adapted organism depends on the momentary state of food intake. After renewal of the normal ad libitum feeding the adaptively induced radioresistance decreases.

  13. Protective effect of intermittent fasting on the mortality of gamma-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Kozubik, A; Pospisil, M

    1982-12-01

    The effect of 1 to 6 weeks' adaptation to intermittent fasting (alternating periods of 24 h fasting and subsequent 24 h feeding) on the manifestations of radioresistance of mice subjected to whole-body gamma-irradiation was studied. A favourable effect of this feeding regimen on the survival of irradiated animals was observed. The optimal redioprotective effect was achieved in mice adapted to intermittent fasting for 2 to 3 weeks and irradiated after 24 h of food intake. Furthermore, it was shown that the radioresistance of the adapted organism depends on the momentary state of food intake. After renewal of the normal ad libitum feeding the adaptively induced radioresistance decreases.

  14. Use of a recombinant Salmonella enterica serovar Typhimurium strain expressing C-Raf for protection against C-Raf induced lung adenoma in mice

    International Nuclear Information System (INIS)

    Gentschev, Ivaylo; Fensterle, Joachim; Schmidt, Andreas; Potapenko, Tamara; Troppmair, Jakob; Goebel, Werner; Rapp, Ulf R

    2005-01-01

    Serine-threonine kinases of the Raf family (A-Raf, B-Raf, C-Raf) are central players in cellular signal transduction, and thus often causally involved in the development of cancer when mutated or over-expressed. Therefore these proteins are potential targets for immunotherapy and a possible basis for vaccine development against tumors. In this study we analyzed the functionality of a new live C-Raf vaccine based on an attenuated Salmonella enterica serovar Typhimurium aroA strain in two Raf dependent lung tumor mouse models. The antigen C-Raf has been fused to the C-terminal secretion signal of Escherichia coli α-hemolysin and expressed in secreted form by an attenuated aroA Salmonella enterica serovar Typhimurium strain via the α-hemolysin secretion pathway. The effect of the immunization with this recombinant C-Raf strain on wild-type C57BL/6 or lung tumor bearing transgenic BxB mice was analyzed using western blot and FACS analysis as well as specific tumor growth assays. C-Raf antigen was successfully expressed in secreted form by an attenuated Salmonella enterica serovar Typhimurium aroA strain using the E. coli hemolysin secretion system. Immunization of wild-type C57BL/6 or tumor bearing mice provoked specific C-Raf antibody and T-cell responses. Most importantly, the vaccine strain significantly reduced tumor growth in two transgenic mouse models of Raf oncogene-induced lung adenomas. The combination of the C-Raf antigen, hemolysin secretion system and Salmonella enterica serovar Typhimurium could form the basis for a new generation of live bacterial vaccines for the treatment of Raf dependent human malignancies

  15. Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice.

    Science.gov (United States)

    Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Sharma, Yogita; Saroha, Babita; Datusalia, Ashok Kumar; Bezbaruah, Babul Kumar

    2016-06-01

    The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.

  16. Vaccination with recombinant L7/L12-truncated Omp31 protein induces protection against Brucella infection in BALB/c mice.

    Science.gov (United States)

    Golshani, Maryam; Rafati, Sima; Dashti, Amir; Gholami, Elham; Siadat, Seyed Davar; Oloomi, Mana; Jafari, Anis; Bouzari, Saeid

    2015-06-01

    Brucellosis is the most common bacterial zoonotic disease worldwide and no vaccine is available for the prevention of human brucellosis. In humans, brucellosis is mostly caused by Brucella melitensis and Brucella abortus. The Outer membrane protein 31 (Omp31) and L7/L12 are immunodominant and protective antigens conserved in human Brucella pathogens. In the present study, we evaluated the humoral and cellular immune responses induced by a fusion protein designed based on the Truncated form of Omp31 (TOmp31) and L7-L12 antigens. Vaccination of BALB/c mice with the recombinant fusion protein (rL7/L12-TOmp31) provided the significant protection level against B. melitensis and B. abortus challenge. Moreover, rL7/L12-TOmp31 elicited a strong specific IgG response (higher IgG2a titers) and significant IFN-γ/IL2 production and T-cell proliferation was also observed. The T helper1 (Th1) oriented response persisted for 12 weeks after the first immunization. The rL7/L12-TOmp31 could be a new potential antigen candidate for the development of a subunit vaccine against B. melitensis and B. abortus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Protective immunity induced by 67 K outer membrane protein of phase I Coxiella burnetii in mice and guinea pigs

    International Nuclear Information System (INIS)

    Zhang, Y.X.; Zhi, N.; Yu, S.R.; Li, Q.J.; Yu, G.Q.; Zhang, X.

    1994-01-01

    A 67 K outer membrane protein (OMP) isolated from phase I Coxiella burnetii QiYi strain was purified with monoclonal antibodies (MoAb) coupled to CNBr-Sepharose 4B. Chemical analyses of the 67 K protein showed that it contained seventeen kids of amino acids and no lipopolysaccharides. The immunogenicity and protectivity of the 67 K protein against C. burnetii was evaluated in mice and guinea pigs bi in vitro lymphocyte proliferation assay, delayed-type skin test, antibody conversion rate, and immunization and challenge tests. Intraperitoneal injection of the 67 K protein resulted in antibody production against phase I and II whole cell antigens. The anti-67 K antibody conversion rate was found to be 100% in mice and guinea pigs as well. Lymphocytes were responses in vitro to specific antigen. In addition, delayed-type hypersensitivity appeared two weeks after immunization with the 67 K protein. Moreover, 199% of mice and guinea pigs inoculated with the 67 K protein were protected against a challenge with 10 3 ID 50 virulent C. burnetii. In conclusion, these results demonstrate that the 67 K OMP elicits in vivo and in vitro both B cell-mediated and T cell-mediated immunity in mice and guinea pigs. Thus the 67 K protein is a candidate for an effective subunit vaccine against Q fever. (author)

  18. Effects of social isolation, re-socialization and age on cognitive and aggressive behaviors of Kunming mice and BALB/c mice.

    Science.gov (United States)

    An, Dong; Chen, Wei; Yu, De-Qin; Wang, Shi-Wei; Yu, Wei-Zhi; Xu, Hong; Wang, Dong-Mei; Zhao, Dan; Sun, Yi-Ping; Wu, Jun-Cheng; Tang, Yi-Yuan; Yin, Sheng-Ming

    2017-05-01

    Both Kunming (KM) mice and BALB/c mice have been widely used as rodent models to investigate stress-associated mental diseases. However, little is known about the different behaviors of KM mice and BALB/c mice after social isolation, particularly cognitive and aggressive behaviors. In this study, the behaviors of KM and BALB/c mice isolated for 2, 4 and 8 weeks and age-matched controls were evaluated using object recognition, object location and resident-intruder tests. The recovery of behavioral deficits by re-socialization was also examined for the isolated mice in adolescence. Our study showed that isolation for 2, 4 and 8 weeks led to cognitive deficits and increased aggressiveness for both KM and BALB/c mice. An important finding is that re-socialization could completely recover spatial/non-spatial cognitive deficits resulted from social isolation for both KM and BALB/c mice. In addition, age only impacted aggressiveness of KM mice. Moreover, isolation duration showed different impacts on cognitive and aggressive behaviors for both KM and BALB/c mice. Furthermore, BALB/c mice showed weak spatial/non-spatial memory and low aggressiveness when they were at the same age and isolation duration, compared to KM mice. In conclusion, KM mice and BALB/c mice behaved characteristically under physiology and isolation conditions. © 2016 Japanese Society of Animal Science.

  19. Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics.

    Science.gov (United States)

    Saitta, Kyle S; Zhang, Carmen; Lee, Kang Kwang; Fujimoto, Kazunori; Redinbo, Matthew R; Boelsterli, Urs A

    2014-01-01

    1.  We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip). 2.  Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation. 3.  Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t1/2 of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole. 4.  Using the fluorescent probe 5 (and 6)-carboxy-2',7'-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice. 5.  These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones.

  20. HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice

    DEFF Research Database (Denmark)

    Boucherma, Rachid; Kridane-Miledi, Hédia; Bouziat, Romain

    2013-01-01

    We have generated a panel of transgenic mice expressing HLA-A*01:03, -A*24:02, -B*08:01, -B*27:05, -B*35:01, -B*44:02, or -C*07:01 as chimeric monochain molecules (i.e., appropriate HLA α1α2 H chain domains fused with a mouse α3 domain and covalently linked to human β2-microglobulin). Whereas...... a quantitative and qualitative restoration of the peripheral CD8(+) T cell repertoire, which exhibited a TCR diversity comparable with C57BL/6 WT mice. Potent epitope-specific, HLA-restricted, IFN-γ-producing CD8(+) T cell responses were generated against known reference T cell epitopes after either peptide...

  1. Asymmetric fission and evaporation of C{sub 60}{sup r+} (r = 2-4) fullerene ions in ion-C{sub 60} collisions: II. Dependence on collisional processes?

    Energy Technology Data Exchange (ETDEWEB)

    Rentenier, A; Bordenave-Montesquieu, A; Moretto-Capelle, P; Bordenave-Montesquieu, D [LCAR-IRSAMC, UMR 5589 Universite Paul Sabatier-CNRS, 118 rte de Narbonne, 31062 Toulouse Cedex (France)

    2004-06-28

    In this paper, a quantitative comparison of our experimental data for the asymmetrical fission (AF) and neutral evaporation of the C{sub 60} molecule under proton impact (part I) is made with data published by other authors and often obtained in rather different collisional systems. The comparison with multicharged ions for which more quantitative data are available is focused on. It is demonstrated that size distributions of fragments, averaged fragment sizes, branching ratios between AF and evaporation or between AF channels, are common to all the collisional systems. Differences only appear when the comparison includes the undissociated stable fullerene ion signals.

  2. Effect of cyanide on the distribution of 60Co in mice

    International Nuclear Information System (INIS)

    Frankenberg, L.

    1982-01-01

    The effect of cyanide on the distribution of cobalt was studied by injecting mice i.p. with potassium cyanide 61.4 μmoles/kg, followed 1 min later by 60 CoCl 2 38.5 μmoles/kg i.v. Blood and tissue concentrations of 60 Co were then determined up to 48 h after injection and the results were compared with those obtained from control animals receiving 60 CoCl 2 only. In animals treated with cobalt plus cyanide, considerably higher concentrations of 60 Co were found in the spleen in comparison with controls during the whole observation period, whereas the 60 Co concentration in the pancreas was lower than that of controls during the first 4 h. In other tissues no significant differences between cyanide-treated animals and controls were noticed. Determination of complex-bound cyanide demonstrated that the increased uptake of cobalt in the spleen observed in cyanide-treated animals was due to cobalt-cyanide complex(es). Cyanide did not affect the plasma protein binding of cobalt. (orig.)

  3. Mass loss from OH/IR stars - Models for the infrared emission of circumstellar dust shells

    Science.gov (United States)

    Justtanont, K.; Tielens, A. G. G. M.

    1992-01-01

    The IR emission of a sample of 24 OH/IR stars is modeled, and the properties of circumstellar dust and mass-loss rate of the central star are derived. It is shown that for some sources the observations of the far-IR emission is well fitted with a lambda exp -1 law, while some have a steeper index of 1.5. For a few sources, the presence of circumstellar ice grains is inferred from detailed studies of the observed 10-micron feature. Dust mass-loss rates are determined from detailed studies for all the stars in this sample. They range from 6.0 x 10 exp -10 solar mass/yr for an optically visible Mira to 2.2 x 10 exp -6 solar mass/yr for a heavily obscured OH/IR star. These dust mass-loss rates are compared to those calculated from IRAS photometry using 12-, 25-, and 60-micron fluxes. The dust mass-loss rates are also compared to gas mass-loss rates determined from OH and CO observations. For stars with tenuous shells, a dust-to-gas ratio of 0.001 is obtained.

  4. Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

    Directory of Open Access Journals (Sweden)

    Chise Tateno

    Full Text Available We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID. We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and

  5. Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

    Science.gov (United States)

    Tateno, Chise; Kawase, Yosuke; Tobita, Yoshimi; Hamamura, Satoko; Ohshita, Hiroki; Yokomichi, Hiroshi; Sanada, Harumi; Kakuni, Masakazu; Shiota, Akira; Kojima, Yuha; Ishida, Yuji; Shitara, Hiroshi; Wada, Naoko A; Tateishi, Hiromi; Sudoh, Masayuki; Nagatsuka, Shin-Ichiro; Jishage, Kou-Ichi; Kohara, Michinori

    2015-01-01

    We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID) mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps) replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID). We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb) levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and useful hosts for

  6. Outbred CD1 mice are as suitable as inbred C57BL/6J mice in performing social tasks.

    Science.gov (United States)

    Hsieh, Lawrence S; Wen, John H; Miyares, Laura; Lombroso, Paul J; Bordey, Angélique

    2017-01-10

    Inbred mouse strains have been used preferentially for behavioral testing over outbred counterparts, even though outbred mice reflect the genetic diversity in the human population better. Here, we compare the sociability of widely available outbred CD1 mice with the commonly used inbred C57BL/6J (C57) mice in the one-chamber social interaction test and the three-chamber sociability test. In the one-chamber task, intra-strain pairs of juvenile, non-littermate, male CD1 or C57 mice display a series of social and aggressive behaviors. While CD1 and C57 pairs spend equal amount of time socializing, CD1 pairs spend significantly more time engaged in aggressive behaviors than C57 mice. In the three-chamber task, sociability of C57 mice was less dependent on acclimation paradigms than CD1 mice. Following acclimation to all three chambers, both groups of age-matched male mice spent more time in the chamber containing a stranger mouse than in the empty chamber, suggesting that CD1 mice are sociable like C57 mice. However, the observed power suggests that it is easier to achieve statistical significance with C57 than CD1 mice. Because the stranger mouse could be considered as a novel object, we assessed for a novelty effect by adding an object. CD1 mice spend more time in the chamber with a stranger mouse than that a novel object, suggesting that their preference is social in nature. Thus, outbred CD1 mice are as appropriate as inbred C57 mice for studying social behavior using either the single or the three-chamber test using a specific acclimation paradigm. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Affine Fullerene C60 in a GS-Quasigroup

    Directory of Open Access Journals (Sweden)

    Vladimir Volenec

    2014-01-01

    Full Text Available It will be shown that the affine fullerene C60, which is defined as an affine image of buckminsterfullerene C60, can be obtained only by means of the golden section. The concept of the affine fullerene C60 will be constructed in a general GS-quasigroup using the statements about the relationships between affine regular pentagons and affine regular hexagons. The geometrical interpretation of all discovered relations in a general GS-quasigroup will be given in the GS-quasigroup C(1/2(1+5.

  8. a.c. conductance study of polycrystal C60

    International Nuclear Information System (INIS)

    Yan Feng; Wang Yening; Huang Yineng; Gu Min; Zhang Qingming; Shen Huimin

    1995-01-01

    The a.c. (1 60 polycrystal (grain size 30 nm) has been studied from 100 to 350 K. Below 150 K, the a.c. conductance is nearly proportional to the temperature and frequency. This is proposed to be due to the hopping of localized states around the Fermi level. Above 200 K, the a.c. conductance exhibits a rapid increase with temperature, and shows a thermally activated behaviour with an activation energy of 0.389 eV below a certain temperature and 0.104 eV above it. A frequency dependent conductance at a fixed temperature is also obtained with a power law σ similar ω s (s∼0.8). For a sample of normal grain size, we have measured a peak near 250 K and a much smaller conductance. These results indicate that the defective na ture of our sample (small grain size, disorder or impurities) plays an important role for the transport properties. The existence of nanocrystals in the sample may give rise to localized states and improve its a.c. conductance. The two activation energies can be attributed to the coexistence of the crystalline and amorphous phases of C 60 . ((orig.))

  9. Concerted effects of heterogeneous nuclear ribonucleoprotein C1/C2 to control vitamin D-directed gene transcription and RNA splicing in human bone cells.

    Science.gov (United States)

    Zhou, Rui; Park, Juw Won; Chun, Rene F; Lisse, Thomas S; Garcia, Alejandro J; Zavala, Kathryn; Sea, Jessica L; Lu, Zhi-Xiang; Xu, Jianzhong; Adams, John S; Xing, Yi; Hewison, Martin

    2017-01-25

    Traditionally recognized as an RNA splicing regulator, heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2) can also bind to double-stranded DNA and function in trans as a vitamin D response element (VDRE)-binding protein. As such, hnRNPC1/C2 may couple transcription induced by the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH) 2 D) with subsequent RNA splicing. In MG63 osteoblastic cells, increased expression of the 1,25(OH) 2 D target gene CYP24A1 involved immunoprecipitation of hnRNPC1/C2 with CYP24A1 chromatin and RNA. Knockdown of hnRNPC1/C2 suppressed expression of CYP24A1, but also increased expression of an exon 10-skipped CYP24A1 splice variant; in a minigene model the latter was attenuated by a functional VDRE in the CYP24A1 promoter. In genome-wide analyses, knockdown of hnRNPC1/C2 resulted in 3500 differentially expressed genes and 2232 differentially spliced genes, with significant commonality between groups. 1,25(OH) 2 D induced 324 differentially expressed genes, with 187 also observed following hnRNPC1/C2 knockdown, and a further 168 unique to hnRNPC1/C2 knockdown. However, 1,25(OH) 2 D induced only 10 differentially spliced genes, with no overlap with differentially expressed genes. These data indicate that hnRNPC1/C2 binds to both DNA and RNA and influences both gene expression and RNA splicing, but these actions do not appear to be linked through 1,25(OH) 2 D-mediated induction of transcription. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Stress-induced NQO1 controls stability of C/EBPα against 20S proteasomal degradation to regulate p63 expression with implications in protection against chemical-induced skin cancer.

    Science.gov (United States)

    Patrick, B A; Jaiswal, A K

    2012-10-04

    Previously, we have shown a role of cytosolic NAD(P)H:quinone oxidoreductase 1 (NQO1) in the stabilization of p63 against 20S proteasomal degradation resulting in thinning of the epithelium and chemical-induced skin cancer (Oncogene (2011) 30, 1098-1107). Current studies have demonstrated that NQO1 control of CCAAT-enhancer binding protein (C/EBPα) against 20S proteasomal degradation also contributes to the upregulation of p63 expression and protection. Western and immunohistochemistry analysis revealed that disruption of the NQO1 gene in mice and mouse keratinocytes led to degradation of C/EBPα and loss of p63 gene expression. p63 promoter mutagenesis, transfection and chromatin immunoprecipitation assays identified a C/EBPα-binding site between nucleotide position -185 and -174 that bound to C/EBPα and upregulated p63 gene expression. Co-immunoprecipitation and immunoblot analysis demonstrated that 20S proteasomes directly interacted and degraded C/EBPα. NQO1 direct interaction with C/EBPα led to stabilization of C/EBPα against 20S proteasomal degradation. NQO1 protection of C/EBPα required binding of NADH with NQO1. Exposure of skin and keratinocytes to the chemical stress agent benzo(a)pyrene led to induction of NQO1 and stabilization of C/EBPα protein, resulting in an increase in p63 RNA and protein in wild-type but not in NQO1-/- mice. Collectively, the current data combined with previous data suggest that stress induction of NQO1 through both stabilization of C/EBPα and increase in p63 and direct stabilization of p63 controls keratinocyte differentiation, leading to protection against chemical-induced skin carcinogenesis. The studies are significant as 2-4% human individuals are homozygous and 23% are heterozygous for the NQO1P187S mutation and might be susceptible to stress-induced skin diseases.

  11. Complement activation and liver impairment in trichloroethylene-sensitized BALB/c mice.

    Science.gov (United States)

    Zhang, Jiaxiang; Zha, Wansheng; Wang, Feng; Jiang, Tao; Xu, Shuhai; Yu, Junfeng; Zhou, Chengfan; Shen, Tong; Wu, Changhao; Zhu, Qixing

    2013-01-01

    Our recent studies have shown that trichloroethylene (TCE) was able to induce multisystem injuries in the form of occupational medicamentosa-like dermatitis, including skin, kidney, and liver damages. However, the role of complement activation in the immune-mediated liver injury is not known. This study examined the role of complement activation in the liver injury in a mouse model of TCE-induced sensitization. Treatment of female BALB/c mice with TCE under specific dosing protocols resulted in skin inflammation and sensitization. Skin edema and erythema occurred in TCE-sensitized groups. Trichloroethylene sensitization produced liver histopathological lesions, increased serum alanine aminotransferase, aspartate transaminase activities, and the relative liver weight. The concentrations of serum complement components C3a-desArg, C5a-desArg, and C5b-9 were significantly increased in 24-hour, 48-hour, and 72-hour sensitization-positive groups treated with TCE and peaked in the 72-hour sensitization-positive group. Depositions of C3a, C5a, and C5b-9 into the liver tissue were also revealed by immunohistochemistry. Immunofluorescence further verified high C5b-9 expression in 24-hour, 48-hour, and 72-hour sensitization-positive groups in response to TCE treatment. Reverse transcription-polymerase chain reaction detected C3 messenger RNA expression in the liver, and this was significantly increased in 24-hour and 48-hour sensitization-positive groups with a transient reduction at 72 hours. These results provide the first experimental evidence that complement activation may play a key role in the generation and progression of immune-mediated hepatic injury by exposure to TCE.

  12. Induction of apoptosis through ER stress and TP53 in MCF-7 cells by the nanoparticle [Gd@C82(OH)22]n: A systems biology study.

    Science.gov (United States)

    Wang, Lin; Meng, Jie; Cao, Weipeng; Li, Qizhai; Qiu, Yuqing; Sun, Baoyun; Li, Lei M

    2014-06-01

    those of HEK293T and MCF-7 cells induced by the miR-23a∼27a∼24-2 cluster. Furthermore, one of the inferred regulatory mechanisms comprises the apoptosis network centered around TP53, whose effective regulation of apoptosis is somehow reestablished after [Gd@C82(OH)22]n treatment. These results elucidate the application and development of [Gd@C82(OH)22]n and other fullerene derivates. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Serotonin-mediated central fatigue underlies increased endurance capacity in mice from lines selectively bred for high voluntary wheel running.

    Science.gov (United States)

    Claghorn, Gerald C; Fonseca, Ivana A T; Thompson, Zoe; Barber, Curtis; Garland, Theodore

    2016-07-01

    Serotonin (5-hydroxytryptamine; 5-HT) is implicated in central fatigue, and 5-HT1A pharmaceuticals are known to influence locomotor endurance in both rodents and humans. We studied the effects of a 5-HT1A agonist and antagonist on both forced and voluntary exercise in the same set of mice. This cohort of mice was taken from 4 replicate lines of mice that have been selectively bred for high levels of voluntary wheel running (HR) as compared with 4 non-selected control (C) lines. HR mice run voluntarily on wheels about 3× as many revolutions per day as compared with C, and have greater endurance during forced treadmill exercise. We hypothesized that drugs targeting serotonin receptors would have differential effects on locomotor behavior of HR and C mice. Subcutaneous injections of a 5-HT1A antagonist (WAY-100,635), a combination of 5-HT1A agonist and a 5-HT1A/1B partial agonist (8-OH-DPAT+pindolol), or physiological saline were given to separate groups of male mice before the start of each of three treadmill trials. The same manipulations were used later during voluntary wheel running on three separate nights. WAY-100,635 decreased treadmill endurance in HR but not C mice (dose by linetype interaction, P=0.0014). 8-OH-DPAT+pindolol affected treadmill endurance (PWheel running was reduced in HR but not C mice at the highest dose of 8-OH-DPAT+pindolol (dose by linetype, P=0.0221), but was not affected by WAY-100,635 treatment. These results provide further evidence that serotonin signaling is an important determinant of performance during both forced and voluntary exercise. Although the elevated wheel running of HR mice does not appear related to alterations in serotonin signaling, their enhanced endurance capacity does. More generally, our results indicate that both forced and voluntary exercise can be affected by an intervention that acts (primarily) centrally. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The electronic structure of C60 and its derivatives

    International Nuclear Information System (INIS)

    Lichtenberger, D.L.; Rempe, M.E.; Gruhn, N.E.; Wright, L.L.

    1993-01-01

    Molecular orbital calculations are used to examine the electronic structure of C 60 and its interaction with metals and some other atoms. The bonding capabilities of the η 5 , η 6 , and the two possible η 2 sites of C 60 to metals are probed with Fenske-Hall calculations of a silver cation bound in those positions. These results are compared to the bonding capabilities of cyclopentadiene, benzene and ethylene, respectively. It is found that the silver cation bonding to C 60 is favored at the η 2 that is shared between five-membered rings, but that the silver cation bonds more favorably to ethylene than to the η 2 site of C 60 . The electronic structure of the known platinum compound, C 60 Pt(phosphine) 2 , where the bonding is also to this η 2 site, is investigated and compared to the electronic structure of the corresponding ethylene complex. In this more electron-rich metal case, the bonding of the C 60 and ethylene are very similar. A calculation on C 60 OsO 4 (NH 3 ) 2 , where C 60 is bound to two oxygens, shows that the orbital composition correlates with the observed NMR shifts of the carbon atoms. The calculations are used to clarify the interpretations of experimental data obtained from STM, NMR, PES and reactivity. The latest results of these electronic studies will be presented

  15. Sm29, but not Sm22.6 retains its ability to induce a protective immune response in mice previously exposed to a Schistosoma mansoni infection.

    Directory of Open Access Journals (Sweden)

    Clarice Carvalho Alves

    2015-02-01

    Full Text Available BACKGROUND: A vaccine against schistosomiasis would have a great impact in disease elimination. Sm29 and Sm22.6 are two parasite tegument proteins which represent promising antigens to compose a vaccine. These antigens have been associated with resistance to infection and reinfection in individuals living in endemic area for the disease and induced partial protection when evaluated in immunization trials using naïve mice. METHODOLOGY/PRINCIPALS FINDINGS: In this study we evaluated rSm29 and rSm22.6 ability to induce protection in Balb/c mice that had been previously infected with S. mansoni and further treated with Praziquantel. Our results demonstrate that three doses of the vaccine containing rSm29 were necessary to elicit significant protection (26%-48%. Immunization of mice with rSm29 induced a significant production of IL-2, IFN-γ, IL-17, IL-4; significant production of specific antibodies; increased percentage of CD4+ central memory cells in comparison with infected and treated saline group and increased percentage of CD4+ effector memory cells in comparison with naïve Balb/c mice immunized with rSm29. On the other hand, although immunization with Sm22.6 induced a robust immune response, it failed to induce protection. CONCLUSION/SIGNIFICANCE: Our results demonstrate that rSm29 retains its ability to induce protection in previously infected animals, reinforcing its potential as a vaccine candidate.

  16. High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

    Science.gov (United States)

    Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

    2017-09-30

    Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

  17. Effect of He pressure on the superconducting transition temperatures of Na2CsC60 and (NH3)4Na2CsC60

    International Nuclear Information System (INIS)

    Schirber, J.E.; Bayless, W.R.; Rosseinsky, M.J.; Zhou, O.; Fleming, R.M.; Murphy, D.; Fischer, J.E.

    1994-01-01

    The Na based mixed alkali doped C 60 superconductors show anomalous behavior with respect to the ''universal'' superconducting transition temperature T c vs lattice constant a 0 relation followed by most of the fcc A 3 C 60 superconductors. We have measured dt c /dP for Na 2 CsC 60 and (NH 3 ) 4 Na 2 CsC 60 using solid He as the pressure medium to ∼ 6 kbar finding dT c /dP equal to -0.8±(0.01) K/kbar and -1.0(±0.1)K/kbar for Na 2 CsC 60 and Na 2 (NH 3 ) 4 C 60 respectively. Our value for Na 2 CsC 60 differs markedly from that obtained by Mizuki et al of about -1.3 K/kbar. However, using N 2 or Ar, we obtain values for dT c /dP in substantial agreement with Mizuki et al who used fluorinert to generate their pressure. This work emphasizes the need for compressibility measurements with the same pressure medium in the appropriate temperature range so that meaningful comparisons can be made between various pressure measurements and models which are based on lattic spacing

  18. Contribution of non-immune phagocytes to protection of mice against Vibrio cholerae

    International Nuclear Information System (INIS)

    Tsuru, Sumiaki; Seno, Masao; Tsuchiya, Choji; Noritake, Masayuki; Wasada, Kazunori

    1980-01-01

    Bacterial kinetics of Vibrio cholerae 569B in the local infection of mice was examined after the γ-ray-irradiation or the treatment with carrageenan. In the control mice, bacterial number decreased exponentially. In the mice treated with carrageenan gave similar tendency. In the irradiated mice, however, decrease in bacterial number was not as significant and the clearance was never observed. From these results, it is concluded that the protection against V. cholerae local infection depends mainly on polymorphonuclear cells in the early phase. (author)

  19. Electron Impact Ionization of C60

    International Nuclear Information System (INIS)

    Duenser, B.; Lezius, M.; Scheier, P.; Deutsch, H.; Maerk, T.D.

    1995-01-01

    Absolute partial and total cross sections for the electron impact ionization of C 60 have been measured using a novel approach for the absolute calibration. The results obtained reveal not only an anomalous large parent ion cross section (as compared to the other ionization channels), but also anomalies for the production of multiply charged parent and fragment ions. This special behavior has its origin in the specific electronic and geometric structure of C 60 . Semiclassical calculations for singly charged ions support the measured data

  20. Vibrational spectroscopic study of poldervaartite CaCa[SiO3(OH)(OH)

    Science.gov (United States)

    Frost, Ray L.; López, Andrés; Scholz, Ricardo; Lima, Rosa Malena Fernandes

    2015-02-01

    We have studied the mineral poldervaartite CaCa[SiO3(OH)(OH)] which forms a series with its manganese analogue olmiite CaMn[SiO3(OH)](OH) using a range of techniques including scanning electron microscopy, thermogravimetric analysis, Raman and infrared spectroscopy. Chemical analysis shows the mineral is reasonably pure and contains only calcium and manganese with low amounts of Al and F. Thermogravimetric analysis proves the mineral decomposes at 485 °C with a mass loss of 7.6% compared with the theoretical mass loss of 7.7%. A strong Raman band at 852 cm-1 is assigned to the SiO stretching vibration of the SiO3(OH) units. Two Raman bands at 914 and 953 cm-1 are attributed to the antisymmetric vibrations. Intense prominent peaks observed at 3487, 3502, 3509, 3521 and 3547 cm-1 are assigned to the OH stretching vibration of the SiO3(OH) units. The observation of multiple OH bands supports the concept of the non-equivalence of the OH units. Vibrational spectroscopy enables a detailed assessment of the molecular structure of poldervaartite.

  1. DMA mitigates ionizing radiation induced damage in Balb/c mice through Akt/NFκB/PTEN pathway

    International Nuclear Information System (INIS)

    Tiwari, Vinod; Ranjan, Atul; Tandon, Vibha

    2014-01-01

    Ionizing radiation is associated with massive apoptosis in tumor as well as in radiosensitive organs. DMA, (5-(4-methylpiperazin-1-yl)-2-(2'-(3,4-dimethoxy-phenyl)-5'-benzimidazolyl) a cytoprotective radiomodulator, work in dual mode of action as free radical quencher and modifier of genomic instability caused by radiation. We observed 34% radioprotection with 50 mg/Kg bw intravenous dose of DMA in Balb/c mice at 8 Gy. DMA treatment before irradiation restored the normal crypts and villi architecture in Balb/c mice. The villi height was restored equivalent to control group in DMA treated animals, whereas, it was degenerated in irradiated animals. IR-induced apoptosis was reduced in spleen in presence of DMA as a result of preservation of splenic lymphocytes from radiation. This clearly exhibits the radioprotective ability of DMA to mitigate radiation induced tissue damage. IR-induced S phase check point was overcome by DMA. DMA promoted activation and phosphorylation of GSK3β through the activation of Akt in Balb/c mice. There was reduction in PTEN level in DMA pretreated mice where as it was upregulated in irradiated mice. Relative enhanced kinase activity of Akt was observed in DMA treated Balb/c mice and irradiated A549, MRC5 cell lines. There was no significant radioprotection in DMA treated Akt siRNA transfected cells in comparison to only Akt siRNA transfected cells with increasing dose of radiation. Akt activation was found in a dose-dependent manner by DMA through Luciferase reporter assay. We observed that DMA treated HEK cells transfected with control siRNA, resulted in less early apoptotic cells within 24h, but radiation (5 Gy) treated cells showed 20% early apoptotic cells within 3 h which were reduced to 12% at 3 h, 9% at 6 h and 8% at 24 h in DMA+radiation treated cells determined by Annexin V binding assay. Further molecular mRNA expression analysis of key regulatory genes unveil that DMA inhibited p21 and augmented Akt and Gadd45 in

  2. Mechanism of the protective effects of long chain n-alkyl glucopyranosides against ultrasound-induced cytolysis of HL-60 cells

    OpenAIRE

    Cheng, Jason Y.; Riesz, Peter

    2007-01-01

    Recently it has been shown that long chain (C5 to C8) n-alkyl glucopyranosides completely inhibit ultrasound-induced cytolysis [1]. This protective effect has possible applications in HIFU (high intensity focused ultrasound) for tumor treatment, and in ultrasound assisted drug delivery and gene therapy. n-Alkyl glucopyranosides with hexyl (5mM), heptyl (3mM), octyl (2mM) n-alkyl chains protected 100% of HL-60 cells in-vitro from 1.057 MHz ultrasound induced cytolysis under a range of conditio...

  3. Administration of kefir-fermented milk protects mice against Giardia intestinalis infection.

    Science.gov (United States)

    Franco, Mariana Correa; Golowczyc, Marina A; De Antoni, Graciela L; Pérez, Pablo F; Humen, Martín; Serradell, María de los Angeles

    2013-12-01

    Giardiasis, caused by the protozoan Giardia intestinalis, is one of the most common intestinal diseases worldwide and constitutes an important problem for the public health systems of various countries. Kefir is a probiotic drink obtained by fermenting milk with 'kefir grains', which consist mainly of bacteria and yeasts that coexist in a complex symbiotic association. In this work, we studied the ability of kefir to protect mice from G. intestinalis infection, and characterized the host immune response to this probiotic in the context of the intestinal infection. Six- to 8-week-old C75BL/6 mice were separated into four groups: controls, kefir mice (receiving 1 : 100 dilution of kefir in drinking water for 14 days), Giardia mice (infected orally with 4×10(7) trophozoites of G. intestinalis at day 7) and Giardia-kefir mice (kefir-treated G. intestinalis-infected mice), and killed at 2 or 7 days post-infection. Kefir administration was able to significantly reduce the intensity of Giardia infection at 7 days post-infection. An increase in the percentage of CD4(+) T cells at 2 days post-infection was observed in the Peyer's patches (PP) of mice belonging to the Giardia group compared with the control and kefir groups, while the percentage of CD4(+) T cells in PP in the Giardia-kefir group was similar to that of controls. At 2 days post-infection, a reduction in the percentage of B220-positive major histocompatibility complex class II medium cells in PP was observed in infected mice compared with the other groups. At 7 days post-infection, Giardia-infected mice showed a reduction in RcFcε-positive cells compared with the control group, suggesting a downregulation of the inflammatory response. However, the percentages of RcFcε-positive cells did not differ from controls in the kefir and Giardia-kefir groups. An increase in IgA-positive cells was observed in the lamina propria of the kefir group compared with controls at 2 days post-infection. Interestingly, the

  4. Protective effect study of polysaccharides from tremella fuciformis on hematopoietic function in radiation-injured mice

    International Nuclear Information System (INIS)

    Xu, Wen-qing; Yang, Fu-jun; Shen, Xiu; Wang, Yue-ying; Liu, Pei-xun

    2008-01-01

    A kind of water-soluble homogeneous polysaccharide named as TFB was isolated and purified from Tremella Fuciformis by DEAE-Sephadex A-25 and Sephadex G-150. Its chemical and physical characteristics was determined by chemical methods, gas chromatography, mass spectrum and size exclusion chromatography. Colony-forming unit of spleen(CFU-S), number of nucleated cells in bone marrow (BMNC) and spleen index were adopted to investigate the effect on hematopoietic function of TFB at 6 mg/kg, 12 mg/kg, 24 mg/kg in mice irradiated with 7.5 Gy 137 Cs γ-rays. The results indicated that TFB is composed of glucose, mannose and serine in closely molar ratios of 8:2:0.1. Its relative molecular weight is estimated to be 68,000 by HPGPC. Its main chain is comprised of 1,4 linked glucose and 1,2,3,4,6 linked mannose, the branch point is at the site of mannose. Side chain is comprised of terminal glucose, Serine, H 2 N-1,4,6 linked mannose. Glucose uronic acid may be in main chain because of its 32.88 % content. The numbers of nucleated cells in bone marrow, colony-forming unit of spleen and spleen index increased markedly compared with the negative control group in mice treated with WTF-B administered 6 mg/kg ip. for three days prior to 137 Cs-γray irradiation, and the number of nucleated cells in bone marrow increased markedly but the CFU-S manifested no difference in mice treated with WTF-B administered 12 mg/kg and 24 mg/kg ip. compared with the negative control group. We can make conclusion that Polysaccharides of Tremella fuciformis has protective effects on hematopoietic function in radiation-injured mice, its optimal dose is 6 mg/kg. (author)

  5. C{sub 60}-based ebselen derivative: synthesis by bingel cyclopropanation and enhanced antioxidative and neuroprotective activity

    Energy Technology Data Exchange (ETDEWEB)

    Xufeng Liu [HuaZhong University of Science and Technology, Wuhan (China). Dept. of Chemistry; Wenchao Guan [Ministry of Education, Wuhan, (China). Hubei University. Key Lab. for the Synthesis and Application of Organic Functional Molecules]. E-mail: wcguan04@yahoo.com.cn; Wengshan Ke [Hubei University, Wuhan (China). College of Life Science

    2007-07-01

    C{sub 60}-based ebselen derivative 3 was synthesized through Bingel cyclopropanation of C{sub 60} with the ebselen malonate 2. Compound 3 was obtained in 42% yield (based on consumed C{sub 60}) in a three-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2aminoethoxy)ethanol. Its structure was confirmed by {sup 1H} NMR, {sup 13}C NMR, IR, UV and FAB-MS spectroscopy analyses. In order to verify the enhanced antioxidative and neuroprotective activity of 3, a C{sub 60} derivative (4), an ebselen derivative (2), and their mixture (4 plus 2 in equimolar ratio) were employed to treat cortical neuronal cells, following the same procedure used with 3 and at the same final concentration (30 {mu}mol L{sup -1}). Cell viabilities of the four treated groups were estimated by LDH (lactic dehydrogenase) leakage and MTT (3-(4, 5-dimethylthiazole-2yl)-2,5-diphenyl-tetrazolium bromide) assays. Results showed that the antioxidative and protective activities of C{sub 60}-based ebselen derivative 3 against H{sub 2}O{sub 2}-mediated neuronal injury (MTT(OD) 0.364 {+-} 0.028; LDH release (UL{sup -1}) 4.66 {+-} 0.28) were significantly higher than those of C{sub 6})0 derivative 4 (MTT(OD) 0.324 {+-} 0.025; LDH release (UL{sup -1}) 5.39 {+-} 0.17), ebselen derivative 2 (MTT(OD) 0.294 {+-} 0.021; LDH release (UL{sup -1}) 5.71 {+-} 0.27), and the mixture of 4 and 2 (MTT(OD) 0.310 {+-} 0.018; LDH release (UL{sup -1}) 5.54 {+-}0.39). These findings demonstrated that the combination of two molecular units with similar biological activities (C{sub 60} and ebselen) may be a desirable way of obtaining new and more biologically effective C{sub 60}-based compounds. (author)

  6. A recombinant novirhabdovirus presenting at the surface the E Glycoprotein from West Nile Virus (WNV is immunogenic and provides partial protection against lethal WNV challenge in BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Angella Nzonza

    Full Text Available West Nile Virus (WNV is a zoonotic mosquito-transmitted flavivirus that can infect and cause disease in mammals including humans. Our study aimed at developing a WNV vectored vaccine based on a fish Novirhabdovirus, the Viral Hemorrhagic Septicemia virus (VHSV. VHSV replicates at temperatures lower than 20°C and is naturally inactivated at higher temperatures. A reverse genetics system has recently been developed in our laboratory for VHSV allowing the addition of genes in the viral genome and the recovery of the respective recombinant viruses (rVHSV. In this study, we have generated rVHSV vectors bearing the complete WNV envelope gene (EWNV (rVHSV-EWNV or fragments encoding E subdomains (either domain III alone or domain III fused to domain II (rVHSV-DIIIWNV and rVHSV-DII-DIIIWNV, respectively in the VHSV genome between the N and P cistrons. With the objective to enhance the targeting of the EWNV protein or EWNV-derived domains to the surface of VHSV virions, Novirhadovirus G-derived signal peptide and transmembrane domain (SPG and TMG were fused to EWNV at its amino and carboxy termini, respectively. By Western-blot analysis, electron microscopy observations or inoculation experiments in mice, we demonstrated that both the EWNV and the DIIIWNV could be expressed at the viral surface of rVHSV upon addition of SPG. Every constructs expressing EWNV fused to SPG protected 40 to 50% of BALB/cJ mice against WNV lethal challenge and specifically rVHSV-SPGEWNV induced a neutralizing antibody response that correlated with protection. Surprisingly, rVHSV expressing EWNV-derived domain III or II and III were unable to protect mice against WNV challenge, although these domains were highly incorporated in the virion and expressed at the viral surface. In this study we demonstrated that a heterologous glycoprotein and non membrane-anchored protein, can be efficiently expressed at the surface of rVHSV making this approach attractive to develop new vaccines

  7. Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice

    Directory of Open Access Journals (Sweden)

    Fatemeh Sheikhbahaei

    2016-12-01

    Full Text Available Background: Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ as a fraction of Nigella sativa on methotrexate (MTX- induced germ cell apoptosis in male mice. Materials and Methods: In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6. A single dose of MTX (20 mg/kg and different concentrations of TQ were administrated for 4 consecutive days. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay was performed on paraffin embedded tissue sections to analysis the occurrence of apoptosis in the testis. Reverse transcription polymerase chain reaction (RT-PCR of apoptosis-related genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. Results: In the MTX group, there was a significant increase in morphologic sign of germ cell degeneration of tubules (48 ± 0.6%, apoptotic index (AI; 2.3 ± 0.6%, as well as mRNA expression of p53 (P=0.008, caspase 8 (P=0.002, caspase 3 (P=0.005, caspase 9 (P=0.000, bax (P=0.004 and the ratio of bax/bcl-2 (P=0.000, whereas there was an decrease in the expression of bcl-2 (P=0.003, as compared to control group. In MTX+TQ groups, the data showed that different concentrations of TQ could improve the harmful effects caused by the MTX. The best protective effects were achieved in MTX+TQ (10 mg/kg. Conclusion: TQ protects testicular germ cell against MTX-induced apoptosis by affecting related genes regulation.

  8. Bovine α-Lactalbumin Hydrolysates (α-LAH Ameliorate Adipose Insulin Resistance and Inflammation in High-Fat Diet-Fed C57BL/6J Mice

    Directory of Open Access Journals (Sweden)

    Jing Gao

    2018-02-01

    Full Text Available Obesity-induced adipose inflammation has been demonstrated to be a key cause of insulin resistance. Peptides derived from bovine α-lactalbumin have been shown to inhibit the activities of dipeptidyl peptidase IV (DPP-IV and angiotensin converting enzyme (ACE, scavenge 2,2′-azinobis [3-ethylbenzothiazoline-6-sulfonate] (ABTS+ radical and stimulate glucagon-like peptide-2 secretion. In the present study, the effects of bovine α-lactalbumin hydrolysates (α-LAH on adipose insulin resistance and inflammation induced by high-fat diet (HFD were investigated. The insulin resistance model was established by feeding C57BL/6J mice with HFD (60% kcal from fat for eight weeks. Then, the mice were fed with HFD and bovine α-LAH of different doses (100 mg/kg b.w., 200 mg/kg b.w. and 400 mg/kg b.w. for another 12 weeks to evaluate its protective effects against HFD-induced insulin resistance. The oral glucose tolerance test (OGTT and intraperitoneal insulin tolerance test (ipITT were conducted after intervention with α-LAH for 10 weeks and 11 weeks, respectively. Results showed that bovine α-LAH significantly reduced body weight, blood glucose, serum insulin, and HOMA-IR (homeostatic model assessment of insulin resistance levels, lowered the area-under-the-curve (AUC during OGTT and ipITT, and downregulated inflammation-related gene [tumor necrosis factor (TNF-α, interleukin (IL-6, monocyte chemoattractant protein (MCP-1] expression in adipose tissues of HFD-fed C57BL/6J mice. Furthermore, bovine α-LAH also suppressed insulin receptor substrate 1 (IRS-1 serine phosphorylation (Ser307, Ser612, enhanced protein kinase B (known as Akt phosphorylation, and inhibited the activation of inhibitor of kappaB kinase (IKK and mitogen activated protein kinase (MAPK signaling pathways in adipose tissues of HFD-fed C57BL/6J mice. These results suggested that bovine α-LAH could ameliorate adipose insulin resistance and inflammation through IKK and MAPK signaling

  9. Total Flavonoids from Mimosa Pudica Protects Carbon Tetrachloride -Induced Acute Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Zhen-qin QIU

    2015-03-01

    Full Text Available Objective: To observe the protective effect of total flavonoids from Mimosa pudica on carbon tetrachloride (CCl4-induced acute liver injury in mice. Methods: CCl4-induced acute liver injury model in mice was established. The activity of ALT and AST, the content of serum albumin (Alb and total antioxidant capacity (T-AOC were determined. The content of malondiadehyde (MDA was measured and the activity of superoxide dismutase (SOD was determined. The histopathological changes of liver were observed.Results: Compared with CCl4 modle group, each dose group of total flavonouida from Mimosa pudica couldreduced the activity of ALT and AST in mice obviously (P<0.01, indicating they had remarkably protective effect on CCl4-induced acute liver injury in mice. high and middle dose groups of total flavonouida from Mimosa pudica couldincrease the content of Alb in mice (P<0.01. Each dose group of total flavonouida from Mimosa pudica could enhance the level of T-AOC (P<0.01. each dose group of total flavonouida from Mimosa pudica could lower the content of liver homogenate MDA but enhance the activity of SOD in a dose-depended manner (P<0.01. Conclusion: Total flavones from Mimosa Pudica have obvious protective effect on CCl4-induced acute liver injury in mice.

  10. Zika Virus: Protecting Pregnant Women and Babies PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the April 2017 CDC Vital Signs report. Zika virus infection during pregnancy can cause serious birth defects. Learn how to protect babies from Zika-related health conditions.

  11. Development of sensitisation or tolerance following repeated OVA inhalation in BALB/cJ mice. Dose-dependency and modulation by the Al(OH)3 adjuvant

    DEFF Research Database (Denmark)

    Clausen, Susanne Knoth; Bergqvist, Mette; Poulsen, Lars K.

    2003-01-01

    Anthropogenically induced exposures may, due to their adjuvant effect, promote development of sensitisation to commonly occurring aeroallergens. No generally accepted model exists for determination of adjuvant effect of airborne substances. Therefore, BALB/cJ mice were exposed for 10 consecutive...

  12. Characterization of the CD8+ T cell responses directed against respiratory syncytial virus during primary and secondary infection in C57BL/6 mice

    International Nuclear Information System (INIS)

    Lukens, Michael V.; Claassen, Erwin A.W.; Graaff, Patricia M.A. de; Dijk, Mariska E.A. van; Hoogerhout, Peter; Toebes, Mireille; Schumacher, Ton N.; Most, Robbert G. van der; Kimpen, Jan L.L.; Bleek, Grada M. van

    2006-01-01

    The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4 + and CD8 + T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse strains and allow dissection of immune mechanisms by using transgenic and knockout mice that are mostly available on a C57BL/6 background, we characterized the specificity, level and functional capabilities of CD8 + T cells during primary and secondary responses in lung parenchyma, airways and spleens of C57BL/6 mice. During the primary response, epitopes were recognized originating from the matrix, fusion, nucleo- and attachment proteins, whereas the secondary response focused predominantly on the matrix epitope. C57BL/6 mice are less permissive for hRSV infection than BALB/c mice, yet we found CD8 + T cell responses in the lungs and bronchoalveolar lavage, comparable to the responses described for BALB/c mice

  13. Attenuated lung fibrosis in interleukin 6 knock-out mice after C-ion irradiation to lung

    International Nuclear Information System (INIS)

    Saito-Fujita, Tomoko; Iwakawa, Mayumi; Nakamura, Etsuko; Nakawatari, Miyako; Fujita, Hidetoshi; Moritake, Takashi; Imai, Takashi

    2011-01-01

    There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice. The mice underwent thoracic irradiation with 10 Gy of C-ion beam or sham-irradiation and were examined by histology. Immunoreactivity for IL-6 was induced at the site of bronchiolar epithelium, in pneumocytes and in monocytes by C-ion irradiation. At 24 weeks after irradiation, the infiltration of macrophages, detected by positive immunohistological staining with Mac3 antibody, was observed in alveolar spaces both in WT and IL-6 KO mice. The thickening of bronchiolar and alveolar walls exhibited in WT mice, but not KO mice, and fibrotic changes detected by Masson-Trichrome staining, were observed only in the lungs of WT mice, while it was attenuated in IL-6 KO mice. These results indicated that IL-6 might not be essential for activating macrophages in the late phase, but plays an important role for fibrotic changes of the alveolar wall after irradiation. (author)

  14. Fast heavy ion collisions with C60: Collective excitation

    International Nuclear Information System (INIS)

    Kadhane, Umesh; Kelkar, A.H.; Misra, D.; Kumar, Ajay; Tribedi, L.C.

    2006-01-01

    Ionization and fragmentation of C 60 in collision with 5 MeV/μm O 6+ ions are studied using recoil ion ToF method. Relative ionization cross sections up to C 60 4+ are determined. The qualitative trend for different C 60 charge states was compared against simple plasmon excitation model

  15. Podocyte specific knock out of selenoproteins does not enhance nephropathy in streptozotocin diabetic C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Carlson Bradley A

    2008-07-01

    Full Text Available Abstract Background Selenoproteins contain selenocysteine (Sec, commonly considered the 21st genetically encoded amino acid. Many selenoproteins, such as the glutathione peroxidases and thioredoxin reductases, protect cells against oxidative stress by functioning as antioxidants and/or through their roles in the maintenance of intracellular redox balance. Since oxidative stress has been implicated in the pathogenesis of diabetic nephropathy, we hypothesized that selenoproteins protect against this complication of diabetes. Methods C57BL/6 mice that have a podocyte-specific inability to incorporate Sec into proteins (denoted in this paper as PodoTrsp-/- and control mice were made diabetic by intraperitoneal injection of streptozotocin, or were injected with vehicle. Blood glucose, body weight, microalbuminuria, glomerular mesangial matrix expansion, and immunohistochemical markers of oxidative stress were assessed. Results After 3 and 6 months of diabetes, control and PodoTrsp-/- mice had similar levels of blood glucose. There were no differences in urinary albumin/creatinine ratios. Periodic acid-Schiff staining to examine mesangial matrix expansion also demonstrated no difference between control and PodoTrsp-/- mice after 6 months of diabetes, and there were no differences in immunohistochemical stainings for nitrotyrosine or NAD(PH dehydrogenase, quinone 1. Conclusion Loss of podocyte selenoproteins in streptozotocin diabetic C57BL/6 mice does not lead to increased oxidative stress as assessed by nitrotyrosine and NAD(PH dehydrogenase, quinone 1 immunostaining, nor does it lead to worsening nephropathy.

  16. The protective effect of Sambucus ebulus against lung toxicity induced by gamma irradiation in mice

    Directory of Open Access Journals (Sweden)

    Mohammad Karami

    2015-01-01

    Full Text Available The aim of present study was to investigate the potential antioxidant and lung protective activities of Sambucus ebulus (SE against toxicity induced by gamma irradiation. Hydroalcoholic extract of SE (20, 50 and 100 mg/kg was studied for its lung protective activity. Phenol and flavonoid contents of SE were determined. Male C57 mice were divided into ten groups with five mice per group. Only the first and second groups (as negative control received intraperitoneally normal saline fluid. Groups 3 to 5 received only SE extract at doses of 20 mg/kg, 50 mg/kg and 100 mg/kg intraperitoneally; three groups were repeatedly injected for 15 days as chronic group. Groups 6 to 8 received a single-dose of gamma irradiation just 2 hours before irradiation as acute group. The ninth and tenth groups (as positive control received only gamma rays. Animal was exposed whole-body to 6 Gy gamma radiation. After irradiation, tissue sections of lung parenchyma were examined by light microscope for any histopathologic changes. SE at doses 50 and 100 mg/kg improved markedly histopathological changes induced by gamma irradiation in lung. Lung protective effect of SE could be due to attention of lipid peroxidation. Our study demonstrated that SE as a natural product has a protective effect against lung toxicity induced by   gamma irradiation in animal.

  17. Comparison of the acute ultraviolet photoresponse in congenic albino hairless C57BL/6J mice relative to outbred SKH1 hairless mice

    Science.gov (United States)

    Konger, Raymond L.; Derr-Yellin, Ethel; Hojati, Delaram; Lutz, Cathleen; Sundberg, John P.

    2016-01-01

    Hairless albino Crl:SKH1-Hrhr mice are commonly utilized for studies in which hair or pigmentation would introduce an impediment to observational studies. Being an outbred strain, the SKH1 model suffers from key limitations that are not seen with congenic mouse strains. Inbred and congenic C57BL/6J mice are commonly utilized for modified genetic mouse models. We compare the acute UV-induced photoresponse between outbred SKH1 mice and an immune competent, hairless, albino C57BL/6J congenic mouse line [B6.Cg-Tyrc-2J Hrhr/J]. Histologically, B6.Cg-Tyrc-2J Hrhr/J skin is indistinguishable from that of SKH1 mice. The skin of both SKH1 and B6.Cg-Tyrc-2J Hrhr/J mice exhibited a reduction in hypodermal adipose tissue, the presence of utricles and dermal cystic structures, the presence of dermal granulomas, and epidermal thickening. In response to a single 1500 J/m2 UVB dose, the edema and apoptotic response was equivalent in both mouse strains. However, B6.Cg-Tyrc-2J Hrhr/J mice exhibited a more robust delayed sunburn reaction, with an increase in epidermal erosion, scab formation, and myeloperoxidase activity relative to SKH1 mice. Compared with SKH1 mice, B6.Cg-Tyrc-2J Hrhr/J also exhibited an aberrant proliferative response to this single UV exposure. Epidermal Ki67 immunopositivity was significantly suppressed in B6.Cg-Tyrc-2J Hrhr/J mice at 24 hours post-UV. A smaller non-significant reduction in Ki67 labeling was observed in SKH1 mice. Finally, at 72 hours post-UV, SKH1 mice, but not B6.Cg-Tyrc-2J Hrhr/J mice, exhibited a significant increase in Ki67 immunolabeling relative to non-irradiated controls. Thus, B6.Cg-Tyrc-2J Hrhr/J mice are suitable for photobiology experiments. PMID:27095432

  18. Photodetachment of negative C{sub 60}{sup -} ions

    Energy Technology Data Exchange (ETDEWEB)

    Amusia, M.Ya.; Baltenkov, A.S.; Krakov, B.G. [Ioffe Physico-Technical Inst., St. Petersburg (Russian Federation)]|[U.A. Arifov Institute of Electronics, Tashkent, 700143 (Uzbekistan)

    1998-06-15

    A model that describes the electron structure of negative fullerene C{sub 60}{sup -} ions is proposed. The model contains only two experimentally observed parameters, namely the fullerene radius and the affinity energy of the electron to neutral C{sub 60}. In the frame of this model, cross sections are calculated of elastic scattering of slow electrons on neutral fullerene, of C{sub 60}{sup -} photodetachment near the threshold of this process and of radiative recombination of slow electrons with neutral fullerenes. (orig.) 21 refs.

  19. L-citrulline protects from kidney damage in type 1 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Maritza J Romero

    2013-12-01

    Full Text Available Rationale. Diabetic nephropathy is a major cause of end-stage renal disease, associated with endothelial dysfunction. Chronic supplementation of L-arginine (L-arg, the substrate for endothelial nitric oxide synthase (eNOS, failed to improve vascular function. L-citrulline (L-cit supplementation not only increases L-arg synthesis, but also inhibits cytosolic arginase I (Arg I, a competitor of eNOS for the use of L-arg, in the vasculature. Aims. To investigate whether L-cit treatment reduces diabetic nephropathy in streptozotocin (STZ-induced type 1 diabetes in mice and rats and to study its effects on arginase II (ArgII function, the main renal isoform. Methods. STZ-C57BL6 mice received L-cit or vehicle supplemented in the drinking water. For comparative analysis, diabetic ArgII knock out mice and L-cit-treated STZ-rats were evaluated. Results. L-cit exerted protective effects in kidneys of STZ-rats, and markedly reduced urinary albumin excretion, tubulo-interstitial fibrosis and kidney hypertrophy, observed in untreated diabetic mice. Intriguingly, L-cit treatment was accompanied by a sustained elevation of tubular ArgII at 16 wks and significantly enhanced plasma levels of the anti-inflammatory cytokine IL-10. Diabetic ArgII knock out mice showed greater BUN levels, hypertrophy, and dilated tubules than diabetic wild type mice. Despite a marked reduction in collagen deposition in ArgII knock out mice, their albuminuria was not significantly different from diabetic wild type animals. L-cit also restored NO/ROS balance and barrier function in high glucose-treated monolayers of human glomerular endothelial cells. Moreover, L-cit also has the ability to establish an anti-inflammatory profile, characterized by increased IL-10 and reduced IL-1beta and IL-12(p70 generation in the human proximal tubular cells. Conclusions. L-cit supplementation established an anti-inflammatory profile and significantly preserved the nephron function during type 1

  20. Protective immune responses with trickle infections of third-stage filarial larvae of Wuchereria bancrofti in mice.

    Science.gov (United States)

    Rajasekariah, G R; Monteiro, Y M; Netto, A; Deshpande, L; Subrahmanyam, D

    1989-01-01

    Groups of inbred BALB/c mice were immunized with trickle doses of 20 live third-stage larvae (L3) of Wuchereria bancrofti each subcutaneously or with 150 microg of sonicated microfilarial antigens emulsified in Freund's adjuvant intramuscularly. An antibody response was distinctly seen after seven trickle doses of L3 and following with the sonicated microfilarial immunization. Due to the non-permissive nature of inbred mice to W. bancrofti infections, a novel immunization approach was adopted using appropriate age- and sex-matched controls. The anti-L3 response in terms of antibody-dependent cell-mediated adhesion and killing was assessed in the immunized animals by implanting live L3 in micropore chambers subcutaneously. About 75% L3 W. bancrofti were affected in animals sensitized with seven trickle doses of L3. When sensitizations were continued, as high as 92% of L3 were seen affected with ten trickle doses compared with 27% in age-matched controls. Immunization with sonicated microfilarial antigen affected about 70% of L3 as opposed to only 12% in controls. A positive correlation was observed in the antibody response with protectivity. This method of induction and assessment of the anti-L3 response involving a small set of animals has not only allowed quantification of affected L3 but has also enabled us to visualize larval conditions in immunologically activated animals. The micropore chamber system, would be useful in monitoring the induction of protective immune response against W. bancrofti in inbred mice. Experimentation on large numbers of animals is required to elucidate further the response of mice towards L3 and also to pinpoint the putative protective antigens. PMID:12412764